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Sample records for compounds pharmaceutical drugs

  1. Biotechnology, nanotechnology, and pharmacogenomics and pharmaceutical compounding, Part 1.

    Science.gov (United States)

    Allen, Loyd V

    2015-01-01

    The world of pharmaceuticals is changing rapidly as biotechnology continues to grow and nanotechnology appears on the horizon. Biotechnology is gaining in importance in extemporaneous pharmaceutical compounding, and nanotechnology and pharmacogenomics could drastically change the practice of pharmacy. This article discusses biotechnology and the factors to consider when compounding biotechnology drugs.

  2. Contamination levels of human pharmaceutical compounds in French surface and drinking water.

    Science.gov (United States)

    Mompelat, S; Thomas, O; Le Bot, B

    2011-10-01

    The occurrence of 20 human pharmaceutical compounds and metabolites from 10 representative therapeutic classes was analysed from resource and drinking water in two catchment basins located in north-west France. 98 samples were analysed from 63 stations (surface water and drinking water produced from surface water). Of the 20 human pharmaceutical compounds selected, 16 were quantified in both the surface water and drinking water, with 22% of the values above the limit of quantification for surface water and 14% for drinking water). Psychostimulants, non-steroidal anti-inflammatory drugs, iodinated contrast media and anxiolytic drugs were the main therapeutic classes of human pharmaceutical compounds detected in the surface water and drinking water. The results for surface water were close to results from previous studies in spite of differences in prescription rates of human pharmaceutical compounds in different countries. The removal rate of human pharmaceutical compounds at 11 water treatment units was also determined. Only caffeine proved to be resistant to drinking water treatment processes (with a minimum rate of 5%). Other human pharmaceutical compounds seemed to be removed more efficiently (average elimination rate of over 50%) by adsorption onto activated carbon and oxidation/disinfection with ozone or chlorine (not taking account of the disinfection by-products). These results add to the increasing evidence of the occurrence of human pharmaceutical compounds in drinking water that may represent a threat to human beings exposed to a cocktail of human pharmaceutical compounds and related metabolites and by-products in drinking water.

  3. Conversion of pharmaceuticals and other drugs by fungal peroxygenases

    OpenAIRE

    Poraj-Kobielska, Marzena

    2013-01-01

    Over the recent years, increasing scientific attention has been paid to pharmaceuticals, other drugs and their metabolites. These substances are of particular interest because of their physiological, toxicological and ecotoxicological effects in the human body and respectively in the environment. Cytochrome P450 enzymes (P450s) play a key role in the conversion and detoxification of bioactive compounds including many pharmaceuticals and drugs. Most of these enzymes belong to the monooxygenase...

  4. Impact of pharmaceutical cocrystals: the effects on drug pharmacokinetics.

    Science.gov (United States)

    Shan, Ning; Perry, Miranda L; Weyna, David R; Zaworotko, Michael J

    2014-09-01

    Pharmaceutical cocrystallization has emerged in the past decade as a new strategy to enhance the clinical performance of orally administered drugs. A pharmaceutical cocrystal is a multi-component crystalline material in which the active pharmaceutical ingredient is in a stoichiometric ratio with a second compound that is generally a solid under ambient conditions. The resulting cocrystal exhibits different solid-state thermodynamics, leading to changes in physicochemical properties that offer the potential to significantly modify drug pharmacokinetics. The impact of cocrystallization upon drug pharmacokinetics has not yet been well delineated. Herein, we compile previously published data to address two salient questions: what effect does cocrystallization impart upon physicochemical properties of a drug substance and to what degree can those effects impact its pharmacokinetics. Cocrystals can impact various aspects of drug pharmacokinetics, including, but not limited to, drug absorption. The diversity of solid forms offered through cocrystallization can facilitate drastic changes in solubility and pharmacokinetics. Therefore, it is unsurprising that cocrystal screening is now a routine step in early-stage drug development. With the increasing recognition of pharmaceutical cocrystals from clinical, regulatory and legal perspectives, the systematic commercialization of cocrystal containing drug products is just a matter of time.

  5. Impact of Sterile Compounding Batch Frequency on Pharmaceutical Waste.

    Science.gov (United States)

    Abbasi, Ghalib; Gay, Evan

    2017-01-01

    Purpose: To measure the impact of increasing sterile compounding batch frequency on pharmaceutical waste as it relates to cost and quantity. Methods: Pharmaceutical IV waste at a tertiary care hospital was observed and recorded for 7 days. The batching frequency of compounded sterile products (CSPs) was then increased from twice daily to 4 times daily. After a washout period, pharmaceutical IV waste was then recorded for another 7 days. The quantity of units wasted and the cost were compared between both phases to determine the impact that batching frequency has on IV waste, specifically among high- and low-cost drugs. Results: Patient days increased from 2,459 during phase 1 to 2,617 during phase 2. The total number of CSPs wasted decreased from 3.6 to 2.7 doses per 100 patient days. Overall cost was reduced from $4,585.36 in phase 1 to $4,453.88 in phase 2. The value of wasted high-cost drugs per 100 patient days increased from $146 in phase 1 to $149 in phase 2 ( p > .05). The value of wasted low cost drugs per 100 patient days decreased from $41 in phase 1 to $21 in phase 2 ( p waste quantity and cost. The highest impact of the intervention was observed among low-cost CSPs.

  6. Amorphization of Molecular Liquids of Pharmaceutical Drugs by Acoustic Levitation

    Directory of Open Access Journals (Sweden)

    C. J. Benmore

    2011-08-01

    Full Text Available It is demonstrated that acoustic levitation is able to produce amorphous forms from a variety of organic molecular compounds with different glass forming abilities. This can lead to enhanced solubility for pharmaceutical applications. High-energy x-ray experiments show that several viscous gels form from saturated pharmaceutical drug solutions after 10–20 min of levitation at room temperature, most of which can be frozen in solid form. Laser heating of ultrasonically levitated drugs can also result in the vitrification of molecular liquids, which is not attainable using conventional amorphization methods.

  7. Radiopharmaceuticals using radioactive compounds in pharmaceutics and medicine

    International Nuclear Information System (INIS)

    Theobald, A.

    1989-01-01

    This review of the latest techniques and developments indicates the importance of radiopharmaceutical techniques in the development of drug compounds. It presents practical demonstrations, offers practical exercises, as well as the underlying theoretical considerations: it will supplement existing (mostly American) texts in this subject, since most industrial pharmaceutical companies have a keen interest in the area and most pharmaceutical courses include the subject at degree level. The authors emphasize the pharmaceutical applications throughout. They review targeting aspects, including cell and protein labelling: and discuss radiotracers in testing dosage forms and formulation studies. Safety and legislation are considered, with reviews of the handling techniques, radiation monitoring, radiochromatography and the use of computer techniques. The latter part of the work discusses standards for radiopharmaceuticals, sterility and pyrogen testing, as well as both radiochromatographic and electrophoretic methods and their importance to quality control. (author)

  8. Pharmaceutical drugs, WWTP, and hydric bodies

    Directory of Open Access Journals (Sweden)

    Quezia Bezerra Cass

    2007-12-01

    Full Text Available In the last decade, special attention has been given to the presence of pharmaceutical compounds in the aquatic environment; once that the continuous supply and persistence of these substances can be severally prejudicial to the biota. Thus, the development and application of new technologies that allows the removal or diminishes these contaminants has been the focus of the environment sanitation area. However, the absence of specific monitoring programs at the waste water treatment plant (WWTP, unfeasibly the behaviour evaluation of pharmaceutical drugs in the installed plants. The aim work, based on the factors involved in the input of these contaminants in the environment, and take attention to the pathway in the implementation of adequate treatment systems to minimize the deterioration of the aquatic ecosystems.

  9. Behaviour of pharmaceuticals and psychotic drugs in conventional and advanced wastewater treatments

    International Nuclear Information System (INIS)

    Cortacans Torre, J. A.; Castillo Gonzalez, I. del; Hernandez Lehmann, A.; Hernandez Munoz, A.; Rodriguez Barrera, X.

    2009-01-01

    The occurrence of various pharmaceuticals and psychotic drugs in wastewater and their removal rates in a conventional wastewater treatment plant has been investigated. The psychoactive drugs are poorly removed in the biological step. However, most pharmaceuticals except of carbamazepine, are significantly biodegraded depending the removal degree on the type of compound and on the sludge retention time of the biological treatment. Also, the removal efficiency of conventional tertiary treatments and ultrafiltration and nano filtration membranes using two pilot plants was examined. the effects of retaining pharmaceuticals with ultrafiltration and nano filtration membranes do not greatly differ despite the difference in their pore size. (Author) 25 refs.

  10. Cyclodextrins as drug carriers in Pharmaceutical Technology: The state of the art.

    Science.gov (United States)

    Conceição, Jaime; Adeoye, Oluwatomide; Cabral-Marques, Helena Maria; Lobo, Jose Manuel Sousa

    2017-12-18

    Cyclodextrins (CDs) are versatile excipients with an essential role in drug delivery, as they can form non-covalently bonded inclusion complexes (host-guest complexes) with several drugs either in solution or in the solid state. The main purpose of this publication was to carry out a state of the art of CDs as complexing agents in drug carrier systems. In this way, the history, properties and pharmaceutical applications of the CDs were highlighted with typical examples. The methods to enhance the complexation efficiency (CE) and the CDs applications in solid dosage forms were emphasized in more detail. The main advantages of using these cyclic oligosaccharides are as follows: (1) to enhance solubility/dissolution/ bioavailability of poorly soluble drugs; (2) to enhance drug stability; (3) to modify the drug release site and/or time profile; and (4) to reduce drug side effects (for example, gastric or ocular irritation). These compounds present favorable toxicological profile for human use and therefore there are various medicines containing CDs approved by regulatory authorities worldwide. On the other hand, the major drawback of CDs is the increase in formulation bulk, once the CE is, in general, very low. This aspect is particularly relevant in solid dosage forms and limits the use of CDs to potent drugs. CDs have great potential as drug carriers in Pharmaceutical Technology and can be used by the formulator in order to improve the drug properties such as solubility, bioavailability and stability. Additionally, recent studies have shown that these compounds can be applied as active pharmaceutical ingredients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Corrosion inhibition of aluminum 6063 using some pharmaceutical compounds

    International Nuclear Information System (INIS)

    Fouda, A.S.; Al-Sarawy, A.A.; Ahmed, F.Sh.; El-Abbasy, H.M.

    2009-01-01

    The corrosion inhibition characteristics of some pharmaceutical compounds on aluminum 6063 in 0.5 mol l -1 H 3 PO 4 has been studied using weight loss and galvanostatic polarization techniques. Results showed that the inhibition occurs through adsorption of the inhibitor molecules on the metal surface. The inhibition efficiency increased with increasing inhibitor concentration, but decreased with increasing temperature. The adsorption of first group pharmaceutical compounds on the metal surface is found to obey Frumkin's adsorption isotherm, but the adsorption of second group pharmaceutical compounds is found to obey Temkin's adsorption isotherm. Thermodynamic parameters for adsorption process were determined. Galvanostatic polarization studies showed that first and second groups' pharmaceutical compounds are mixed-type inhibitors and the results obtained from the two techniques are in good agreement

  12. Photoredox-catalyzed deuteration and tritiation of pharmaceutical compounds.

    Science.gov (United States)

    Loh, Yong Yao; Nagao, Kazunori; Hoover, Andrew J; Hesk, David; Rivera, Nelo R; Colletti, Steven L; Davies, Ian W; MacMillan, David W C

    2017-12-01

    Deuterium- and tritium-labeled pharmaceutical compounds are pivotal diagnostic tools in drug discovery research, providing vital information about the biological fate of drugs and drug metabolites. Herein we demonstrate that a photoredox-mediated hydrogen atom transfer protocol can efficiently and selectively install deuterium (D) and tritium (T) at α-amino sp 3 carbon-hydrogen bonds in a single step, using isotopically labeled water (D 2 O or T 2 O) as the source of hydrogen isotope. In this context, we also report a convenient synthesis of T 2 O from T 2 , providing access to high-specific-activity T 2 O. This protocol has been successfully applied to the high incorporation of deuterium and tritium in 18 drug molecules, which meet the requirements for use in ligand-binding assays and absorption, distribution, metabolism, and excretion studies. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  13. Assessment of MEKC suitability for residue drug monitoring on pharmaceutical manufacturing equipment

    CSIR Research Space (South Africa)

    Boca, MB

    2008-03-01

    Full Text Available obtained for all compounds. The method could be used as part of a cleaning validation study when assaying trace levels of co-trimoxazole drug, some of its decomposition products and detergent in the swab samples collected from pharmaceutical manufacturing...

  14. Pharmaceutical Compounds in Wastewater: Wetland Treatment as a Potential Solution

    Directory of Open Access Journals (Sweden)

    John R. White

    2006-01-01

    Full Text Available Pharmaceutical compounds are being released into the aquatic environment through wastewater discharge around the globe. While there is limited removal of these compounds within wastewater treatment plants, wetland treatment might prove to be an effective means to reduce the discharge of the compounds into the environment. Wetlands can promote removal of these pharmaceutical compounds through a number of mechanisms including photolysis, plant uptake, microbial degradation, and sorption to the soil. We review relevant laboratory research on these various mechanisms and provide data on the few studies that have examined wetland removal. There is a need to document the degree to which various pharmaceutical compounds are removed in full-scale treatment wetlands, as there is a paucity of data on overall pharmaceutical removal rates.

  15. Quantitative determination of solid-state forms of a pharmaceutical development compound in drug substance and tablets.

    Science.gov (United States)

    Xie, Yong; Tao, Wenle; Morrison, Henry; Chiu, Rick; Jona, Janan; Fang, Jan; Cauchon, Nina

    2008-10-01

    Common analytical techniques including Raman, NIR, and XRD were evaluated for quantitative determination of three solid-state forms (amorphous, Form B and Form C) of a development compound. Raman spectroscopy was selected as the primary analytical technique with sufficient sensitivity to monitor and quantify the neat drug substance alone and in the drug product. A reliable multivariate curve resolution (MCR) method based on the second derivative Raman measurements of the three pure physical forms was developed and validated with 3.5% root mean square error of prediction (RMSEP) for Form B, which was selected as the preferred form for further development. A partial least squares (PLS) algorithm was also used for the multivariate calibration of both the NIR and Raman measurements. The long-term stability of Form B as a neat active pharmaceutical ingredient (API) and in a tablet formulation was quantitatively monitored under various stress conditions of temperature and moisture. Moisture, temperature, excipients and compression were found to have significant effects on the phase transition behavior of Form B.

  16. Pharmaceutical compounds in drinking water

    Directory of Open Access Journals (Sweden)

    Vikas Chander

    2016-06-01

    Full Text Available Pharmaceutical products and their wastes play a major role in the degradation of environment. These drugs have positive as well as negative consequences on different environmental components including biota in different ways. Many types of pharmaceutical substances have been detected with significant concentrations through various advanced instrumental techniques in surface water, subsurface water, ground water, domestic waste water, municipal waste water and industrial effluents. The central as well as state governments in India are providing supports by creating excise duty free zones to promote the pharmaceutical manufacturers for their production. As a result, pharmaceutical companies are producing different types of pharmaceutical products at large scale and also producing complex non-biodegradable toxic wastes byproducts and releasing untreated or partially treated wastes in the environment in absence of strong regulations. These waste pollutants are contaminating all types of drinking water sources. The present paper focuses on water quality pollution by pharmaceutical pollutants, their occurrences, nature, metabolites and their fate in the environment.

  17. Effects of halogenated aromatics/aliphatics and nitrogen(N)-heterocyclic aromatics on estimating the persistence of future pharmaceutical compounds using a modified QSAR model.

    Science.gov (United States)

    Lim, Seung Joo; Fox, Peter

    2014-02-01

    The effects of halogenated aromatics/aliphatics and nitrogen(N)-heterocyclic aromatics on estimating the persistence of future pharmaceutical compounds were investigated using a modified half life equation. The potential future pharmaceutical compounds investigated were approximately 2000 pharmaceutical drugs currently undergoing the United States Food and Drug Administration (US FDA) testing. EPI Suite (BIOWIN) model estimates the fates of compounds based on the biodegradability under aerobic conditions. While BIOWIN considered the biodegradability of a compound only, the half life equation used in this study was modified by biodegradability, sorption and cometabolic oxidation. It was possible that the potential future pharmaceutical compounds were more accurately estimated using the modified half life equation. The modified half life equation considered sorption and cometabolic oxidation of halogenated aromatic/aliphatics and nitrogen(N)-heterocyclic aromatics in the sub-surface, while EPI Suite (BIOWIN) did not. Halogenated aliphatics in chemicals were more persistent than halogenated aromatics in the sub-surface. In addition, in the sub-surface environment, the fates of organic chemicals were much more affected by halogenation in chemicals than by nitrogen(N)-heterocyclic aromatics. © 2013.

  18. Behavior of pharmaceuticals and drugs of abuse in a drinking water treatment plant (DWTP) using combined conventional and ultrafiltration and reverse osmosis (UF/RO) treatments

    Energy Technology Data Exchange (ETDEWEB)

    Boleda, Ma Rosa [AGBAR-Aiguees de Barcelona, Gral Batet 5-7, 08028 Barcelona (Spain); Galceran, Ma Teresa [University of Barcelona, Department Analytical Chemistry, Av. Diagonal 647, 08028 Barcelona (Spain); Ventura, Francesc, E-mail: fventura@agbar.es [AGBAR-Aiguees de Barcelona, Gral Batet 5-7, 08028 Barcelona (Spain)

    2011-06-15

    The behavior along the potabilization process of 29 pharmaceuticals and 12 drugs of abuse identified from a total of 81 compounds at the intake of a drinking water treatment plant (DWTP) has been studied. The DWTP has a common treatment consisting of dioxychlorination, coagulation/flocculation and sand filtration and then water is splitted in two parallel treatment lines: conventional (ozonation and carbon filtration) and advanced (ultrafiltration and reverse osmosis) to be further blended, chlorinated and distributed. Full removals were reached for most of the compounds. Iopromide (up to 17.2 ng/L), nicotine (13.7 ng/L), benzoylecgonine (1.9 ng/L), cotinine (3.6 ng/L), acetaminophen (15.6 ng/L), erythromycin (2.0 ng/L) and caffeine (6.0 ng/L) with elimination efficiencies {>=}94%, were the sole compounds found in the treated water. The advanced treatment process showed a slightly better efficiency than the conventional treatment to eliminate pharmaceuticals and drugs of abuse. - Highlights: > The presence of pharmaceuticals and drugs of abuse in surface water was demonstrated. > Elimination in both potabilization processes reached levels >99% for most compounds. > Four pharmaceuticals and three drugs of abuse survived the potabilization process. - The efficiency of potabilization processes to eliminate or transform pharmaceuticals and illicit drugs is evaluated.

  19. Behavior of pharmaceuticals and drugs of abuse in a drinking water treatment plant (DWTP) using combined conventional and ultrafiltration and reverse osmosis (UF/RO) treatments

    International Nuclear Information System (INIS)

    Boleda, Ma Rosa; Galceran, Ma Teresa; Ventura, Francesc

    2011-01-01

    The behavior along the potabilization process of 29 pharmaceuticals and 12 drugs of abuse identified from a total of 81 compounds at the intake of a drinking water treatment plant (DWTP) has been studied. The DWTP has a common treatment consisting of dioxychlorination, coagulation/flocculation and sand filtration and then water is splitted in two parallel treatment lines: conventional (ozonation and carbon filtration) and advanced (ultrafiltration and reverse osmosis) to be further blended, chlorinated and distributed. Full removals were reached for most of the compounds. Iopromide (up to 17.2 ng/L), nicotine (13.7 ng/L), benzoylecgonine (1.9 ng/L), cotinine (3.6 ng/L), acetaminophen (15.6 ng/L), erythromycin (2.0 ng/L) and caffeine (6.0 ng/L) with elimination efficiencies ≥94%, were the sole compounds found in the treated water. The advanced treatment process showed a slightly better efficiency than the conventional treatment to eliminate pharmaceuticals and drugs of abuse. - Highlights: → The presence of pharmaceuticals and drugs of abuse in surface water was demonstrated. → Elimination in both potabilization processes reached levels >99% for most compounds. → Four pharmaceuticals and three drugs of abuse survived the potabilization process. - The efficiency of potabilization processes to eliminate or transform pharmaceuticals and illicit drugs is evaluated.

  20. Pharmaceutical Compounds in Wastewater: Wetland Treatment as a Potential Solution

    OpenAIRE

    White, John R.; Belmont, Marco A.; Metcalfe, Chris D.

    2006-01-01

    Pharmaceutical compounds are being released into the aquatic environment through wastewater discharge around the globe. While there is limited removal of these compounds within wastewater treatment plants, wetland treatment might prove to be an effective means to reduce the discharge of the compounds into the environment. Wetlands can promote removal of these pharmaceutical compounds through a number of mechanisms including photolysis, plant uptake, microbial degradation, and sorption to the ...

  1. A Simple and Direct LC-MS Method for Determination of Genotoxic Impurity Hydroxylamine in Pharmaceutical compounds.

    Science.gov (United States)

    Kumar, Thangarathinam; Ramya, Mohandass; Srinivasan, Viswanathan; Xavier, N

    2017-08-01

    Hydroxylamine is a known genotoxic impurity compound that needs to be controlled down to ppm level in pharmaceutical processes. It is difficult to detect using conventional analytical techniques due to its physio-chemical properties like lack of chromophore, low molecular weight, absence of carbon atom and high polarity. In addition to that, analysis of the pharmaceutical samples encounters considerable obstruction from matrix components that greatly overshadow the response of hydroxylamine. This study describes a simple, sensitive and direct Liquid Chromatographic-Mass Spectrometric method (LC-MS) for detection of hydroxylamine in pharmaceutical compounds. The LC-MS method was detected up to 0.008 ppm of hydroxylamine with S/N > 3.0 and quantified up to 0.025 ppm of hydroxylamine with S/N ratio >10.0. This validated method can be applied as a generic method to detect the hydroxylamine for pharmaceutical process control and drug substance release. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Pharmaceuticals and illicit drugs in wastewater samples in north-eastern Tunisia.

    Science.gov (United States)

    Moslah, Bilel; Hapeshi, Evroula; Jrad, Amel; Fatta-Kassinos, Despo; Hedhili, Abderrazek

    2017-04-07

    Pharmaceutically active substances (PhACs) and drugs of abuse (DAs) are two classes of contaminants of emerging concern that have attracted great concern and interest by the scientific community during the last two decades. Numerous studies have revealed their presence in treated urban wastewaters. This is mainly due to the fact that some compounds are not efficiently removed during wastewater treatment processes, and are thus able to reach the aquatic environment through wastewater discharge and reuse practices. The application of an optimized multi-residue method for the simultaneous confirmation and quantification of licit and illicit drugs has been investigated in influent and effluent wastewater samples from seven wastewater treatment plants (WWTPs) located in north-eastern Tunisia. Analysis was performed through ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Out of 12 pharmaceutical compounds analyzed, 11 of them were detected mainly in effluent wastewaters. In both matrices, antibiotics and β-blockers were the most detected groups. This suggests that these compounds show noticeable resistance against biological treatment in WWTPs. The estimated concentrations of antibiotics in effluents ranged from ca. 35 ng/L to 1.2 μg/L. However, all five studied illicit drugs were detected, mainly in influent wastewaters. Forensic investigation performed on people suspected to be drug abusers covering all Tunisian cities was conducted by monitoring an epidemiological study of human urine samples surveying rate of consumption for illicit drugs. Hence, these preliminary results confirmed the presence of illicit drugs in the influent wastewater samples. For example, quantification ranges for cocaine were found to be 25-450 ng/L in influent wastewater samples. Significant differences for cocaine consumption across the two sampling methods were observed. Consequently, we conclude that the analyses in wastewater are more reflective of the

  3. Pharmaceutical drug detailing in primary care: extent and methods

    DEFF Research Database (Denmark)

    Schramm, Jesper

    The dimension and methods of pharmaceutical marketing towards 47 danish general practitioners is described. Conclusions: Pharmaceutical drug detailing possesses a huge potential to influence the prescription pattern of GP's.......The dimension and methods of pharmaceutical marketing towards 47 danish general practitioners is described. Conclusions: Pharmaceutical drug detailing possesses a huge potential to influence the prescription pattern of GP's....

  4. Assessment of Non-Sterile Pharmaceutical Compounding Practices ...

    African Journals Online (AJOL)

    A descriptive cross-sectional survey was conducted to assess the practices of non-sterile pharmaceutical compounding in selected 42 community and 3 hospital pharmacies in Addis Ababa, Ethiopia from 01 April, 2016 to 15 May, 2016. The study revealed that the most commonly prescribed and compounded non-sterile ...

  5. [Pharmaceutical chemistry of drug-initiated photosensitivity].

    Science.gov (United States)

    Rácz, Ákos; Tóth, Lívia

    2015-01-01

    The photosensitivity originated from drugs is a common problem in medical and pharmaceutical practice. It is of prominent importance in drug development and in regulatory issues. The photosensitizer effect of drug substances is determined by their chemical structures, and it mainly originates from aromatic chromophore systems and photo-dissociable bonds forming free radicals. The photodegradation may happen in many different types of chemical reaction pathways. Our aim is to demonstrate in this review the interrelations between structure and photodegradation. We show examples for the different reaction types, with drugs from different pharmacologic therapeutic classes. The in vivo chemical reactivity of photodegradates of pharmaceutical substances, the in vitro methods of investigation for testing photoreactivity and phototoxicity, and briefly the clinical tests for photosensitivity disorders are also discussed.

  6. Multi-residue screening of prioritised human pharmaceuticals, illicit drugs and bactericides in sediments and sludge.

    Science.gov (United States)

    Langford, Katherine H; Reid, Malcolm; Thomas, Kevin V

    2011-08-01

    A robust multi-residue method was developed for the analysis of a selection of pharmaceutical compounds, illicit drugs and personal care product bactericides in sediments and sludges. Human pharmaceuticals were selected for analysis in Scottish sewage sludge and freshwater sediments based on prescription, physico-chemical and occurrence data. The method was suitable for the analysis of the selected illicit drugs amphetamine, benzoylecgonine, cocaine, and methamphetamine, the pharmaceuticals atenolol, bendroflumethiazide, carbamazepine, citalopram, diclofenac, fluoxetine, ibuprofen, and salbutamol, and the bactericides triclosan and triclocarban in sewage sludge and freshwater sediment. The method provided an overall recovery of between 56 and 128%, RSDs of between 2 and 19% and LODs of between 1 and 50 ng g(-1). Using the methodology the human pharmaceuticals atenolol, carbamazepine and citalopram and the bactericides triclosan and triclocarban were detected in Scottish sewage sludge. The illicit drugs cocaine, its metabolite benzoylecgonine, amphetamine and methamphetamine were not detected in any of the samples analysed. Triclosan and triclocarban were present at the highest concentrations with triclocarban detected in all but one sample and showing a pattern of co-occurrence in both sludge and sediment samples.

  7. [New drug development by innovative drug administration--"change" in pharmaceutical field].

    Science.gov (United States)

    Nagai, T

    1997-11-01

    New drug development can be made by providing products of higher "selectivity for the drug" for medical treatment. There are two ways for the approach to get higher "selectivity of drug": 1) discovery of new compounds with high selectivity of drug; 2) innovation of new drug administration, that is new formulation and/or method with high selectivity of drug by integration and harmonization of various hard/soft technologies. An extensive increase of biological information and advancement of surrounding science and technology may modify the situation as the latter overcomes the former in the 21 century. As the science and technology in the 21 century is said to be formed on "3H", that is, 1. hybrid; 2. hi-quality; 3. husbandry, the new drug development by innovative drug administration is exactly based on the science and technology of 3H. Its characteristic points are interdisciplinary/interfusion, international, of philosophy/ethics, and systems of hard/hard/heart. From these points of view, not only the advance of unit technology but also a revolution in thinking way should be "must" subjects. To organize this type of research well, a total research activity such as ROR (research on research) might take an important and efficient role. Here the key words are the "Optimization technology" and "Change in Pharmaceutical Fields." As some examples of new drug innovation, our trials on several topical mucosal adhesive dosage forms and parenteral administration of peptide drugs such as insulin and erythropoietin will be described.

  8. Liquid separation techniques coupled with mass spectrometry for chiral analysis of pharmaceuticals compounds and their metabolites in biological fluids.

    Science.gov (United States)

    Erny, G L; Cifuentes, A

    2006-02-24

    Determination of the chiral composition of drugs is nowadays a key step in order to determine purity, activity, bioavailability, biodegradation, etc., of pharmaceuticals. In this article, works published for the last 5 years on the analysis of chiral drugs by liquid separation techniques coupled with mass spectrometry are reviewed. Namely, chiral analysis of pharmaceuticals including, e.g., antiinflammatories, antihypertensives, relaxants, etc., by liquid chromatography-mass spectrometry and capillary electrophoresis-mass spectrometry are included. The importance and interest of the analysis of the enantiomers of the active compound and its metabolites in different biological fluids (plasma, urine, cerebrospinal fluid, etc.) are also discussed.

  9. [Moderation-integrated-balance presupposition of Chinese medicine compound and pharmacological problems in traditional Chinese drug research].

    Science.gov (United States)

    Zhao, Jun-Ning

    2017-03-01

    The moderation-integrated-balance presupposition (MIBP) of Chinese medicine compound was first proposed in this paper based on the review of function characteristics and action principles of Chinese medicine compound. Furthermore, the pharmacological problems of traditional Chinese drug research were discussed in details. The results were of important value in accelerating the transformation of traditional Chinese medicine compound, and constructing the new drug innovation and review system for traditional Chinese medicine. Copyright© by the Chinese Pharmaceutical Association.

  10. Drug metabolism and pharmacokinetic diversity of ranunculaceae medicinal compounds.

    Science.gov (United States)

    Hao, Da-Cheng; Ge, Guang-Bo; Xiao, Pei-Gen; Wang, Ping; Yang, Ling

    2015-01-01

    The wide-reaching distributed angiosperm family Ranunculaceae has approximately 2200 species in around 60 genera. Chemical components of this family include several representative groups: benzylisoquinoline alkaloid (BIA), ranunculin, triterpenoid saponin and diterpene alkaloid, etc. Their extensive clinical utility has been validated by traditional uses of thousands of years and current evidence-based medicine studies. Drug metabolism and pharmacokinetic (DMPK) studies of plant-based natural products are an indispensable part of comprehensive medicinal plant exploration, which could facilitate conservation and sustainable utilization of Ranunculaceae pharmaceutical resources, as well as new chemical entity development with improved DMPK parameters. However, DMPK characteristics of Ranunculaceaederived medicinal compounds have not been summarized. Black cohosh (Cimicifuga) and goldenseal (Hydrastis) raise concerns of herbdrug interaction. DMPK studies of other Ranunculaceae genera, e.g., Nigella, Delphinium, Aconitum, Trollius, and Coptis, are also rapidly increasing and becoming more and more clinically relevant. In this contribution, we highlight the up-to-date awareness, as well as the challenges around the DMPK-related issues in optimization of drug development and clinical practice of Ranunculaceae compounds. Herb-herb interaction of Ranunculaceae herb-containing traditional Chinese medicine (TCM) formula could significantly influence the in vivo pharmacokinetic behavior of compounds thereof, which may partially explain the complicated therapeutic mechanism of TCM formula. Although progress has been made on revealing the absorption, distribution, metabolism, excretion and toxicity (ADME/T) of Ranunculaceae compounds, there is a lack of DMPK studies of traditional medicinal genera Aquilegia, Thalictrum and Clematis. Fluorescent probe compounds could be promising substrate, inhibitor and/or inducer in future DMPK studies of Ranunculaceae compounds. A better

  11. Pharmaceutical penetration of new drug and pharmaceutical market structure in Taiwan: hospital-level prescription of thiazolidinediones for diabetes.

    Science.gov (United States)

    Tsai, Yi-Wen; Wen, Yu-Wen; Huang, Weng-Foung; Kuo, Ken N; Chen, Pei-Fen; Shih, Hsin-Wei; Lee, Yue-Chune

    2010-06-01

    This study used Taiwan's National Health Insurance claim database (years 2000-2005) to examine how thiazolidinediones (TZD), a new class of drugs for diabetes, penetrated into Taiwan's hospitals, and its association with the concentration of all diabetes drugs at the hospital level. We collected 72 monthly summaries of diabetes prescriptions from all hospitals in Taiwan. Hospital-level pharmaceutical concentration was measured by penetration of TZD, defined as monthly market share of TZD in each hospital. Concentration of diabetes drugs was measured by Herfindahl-Hirschman indices. We found a negative association (coefficient = -0.3610) between TZD penetration and concentration of diabetes drug but a positive association between penetration of TZD and the volume of prescribed diabetes drugs (coefficient = 0.4088). In conclusion, hospital characteristics and volume of services determined the concentration of pharmaceuticals at the institution level, reflecting the heterogeneous competition between pharmaceutical companies within each hospital. Institution-level pharmaceutical concentration influences the adoption and penetration of new drugs.

  12. Microcap pharmaceutical firms: linking drug pipelines to market value.

    Science.gov (United States)

    Beach, Robert

    2012-01-01

    This article examines predictors of the future market value of microcap pharmaceutical companies. This is problematic since the large majority of these firms seldom report positive net income. Their value comes from the potential of a liquidity event such as occurs when a key drug is approved by the FDA. The typical scenario is one in which the company is either acquired by a larger pharmaceutical firm or enters into a joint venture with another pharmaceutical firm. Binary logistic regression is used to determine the impact of the firm's drug treatment pipeline and its investment in research and development on the firm's market cap. Using annual financial data from 2007 through 2010, this study finds that the status of the firm's drug treatment pipeline and its research and development expenses are significant predictors of the firm's future stock value relative to other microcap pharmaceutical firms.

  13. Defining Patient Centric Pharmaceutical Drug Product Design.

    Science.gov (United States)

    Stegemann, Sven; Ternik, Robert L; Onder, Graziano; Khan, Mansoor A; van Riet-Nales, Diana A

    2016-09-01

    The term "patient centered," "patient centric," or "patient centricity" is increasingly used in the scientific literature in a wide variety of contexts. Generally, patient centric medicines are recognized as an essential contributor to healthy aging and the overall patient's quality of life and life expectancy. Besides the selection of the appropriate type of drug substance and strength for a particular indication in a particular patient, due attention must be paid that the pharmaceutical drug product design is also adequately addressing the particular patient's needs, i.e., assuring adequate patient adherence and the anticipate drug safety and effectiveness. Relevant pharmaceutical design aspects may e.g., involve the selection of the route of administration, the tablet size and shape, the ease of opening the package, the ability to read the user instruction, or the ability to follow the recommended (in-use) storage conditions. Currently, a harmonized definition on patient centric drug development/design has not yet been established. To stimulate scientific research and discussions and the consistent interpretation of test results, it is essential that such a definition is established. We have developed a first draft definition through various rounds of discussions within an interdisciplinary AAPS focus group of experts. This publication summarizes the outcomes and is intended to stimulate further discussions with all stakeholders towards a common definition of patient centric pharmaceutical drug product design that is useable across all disciplines involved.

  14. Chiral separation of pharmaceutical compounds using electrochemically modulated liquid chromatography (EMLC)

    Energy Technology Data Exchange (ETDEWEB)

    Wang, S. [Iowa State Univ., Ames, IA (United States)

    1999-02-12

    This research explores the application of a new technique, termed electrochemically modulated liquid chromatography (EMLC), to the chiral separations of pharmaceutical compounds. The introduction section provides a literature review of the technique and its applications, as well as brief overview of the research described in each of the next two chapters. Chapter 2 investigates the EMLC-based enantiomeric separation of a group of chiral benzodiazepines with β-cyclodextrin as a chiral mobile phase additive. Chapter 3 demonstrates the effects of several experimental parameters on the separation efficiency of drug enantiomers. The author concludes with a general summary and possible directions for future studies. Chapters 2 and 3 are processed separately.

  15. Reconsidering Japan's underperformance in pharmaceuticals: evidence from Japan's anticancer drug sector.

    Science.gov (United States)

    Umemura, Maki

    2010-01-01

    Unlike its automobile or electronics industries, Japan's pharmaceutical industry did not become a global leader. Japan remains a net importer of pharmaceuticals and has introduced few global blockbuster drugs. Alfred Chandler argued that Japan's pharmaceutical firms remained relatively weak because Western firms enjoyed an insurmountable first first-mover advantage. However, this case study of the anticancer drug sector illustrates that Chandler's explanation is incomplete. Japanese medical culture, government policy, and research environment also played a substantial role in shaping the industry. In the 1970s and 1980s, these factors encouraged firms to develop little few effective drugs with low side effects, and profit from Japan's domestic market. But, these drugs were unsuitable to foreign markets with more demanding efficacy standards. As a result, Japan not only lost more than a decade in developing ineffective drugs, but also neglected to create the infrastructure necessary to develop innovative drugs and build a stronger pharmaceutical industry.

  16. The effects of radiation treatment on drugs and pharmaceutical additives. Pt. 5

    International Nuclear Information System (INIS)

    Schnell, R.; Boegl, W.

    1982-01-01

    The sterilization of medical instruments (e.g. catheters, one-way syringes) with ionizing radiation is successfully practiced in many countries. Simultaneously, the results of many experiments involving the sterilization of pharmaceuticals and aiding substances with radiation have been published during the past years. Experiences have shown that radiation treatment in many cases has brought about aberrations in the irradiated substances. In this bibliographic study (Part I-V), the results of 275 radiation tested pharmaceuticals are discussed and evaluated. The substances were treated with ionizing radiation in their pure form (solid substance or liquid), as aqueous or alcohol solution, as emulsion or in compound form, almost exclusively with gamma radiation from cobalt-60 sources. The radiation doses applied amounted from some krd to about 100 Mrd. The results of the original papers analyzed in this Part V are not summarized separately since the final Part VII of the study on the effects of irradiation of drugs and drug additives will contain a survey for all essential data discussed in Parts I to VI. (orig.) [de

  17. [Pharmaceutical application of cyclodextrins as multi-functional drug carriers].

    Science.gov (United States)

    Uekama, Kaneto

    2004-12-01

    Owing to the increasingly globalized nature of the cyclodextrin (CyD)-related science and technology, development of the CyD-based pharmaceutical formulation is rapidly progressing. The pharmaceutically useful CyDs are classified into hydrophilic, hydrophobic, and ionic derivatives. Because of the multi-functional characteristics and bioadaptability, these CyDs are capable of alleviating the undesirable properties of drug molecules through the formation of inclusion complexes or the form of CyD/drug conjugates. This review outlines the current application of CyDs in drug delivery and pharmaceutical formulation, focusing on the following evidences. 1) The hydrophilic CyDs enhance the rate and extent of bioavailability of poorly water-soluble drugs. 2) The amorphous CyDs such as 2-hydroxypropyl-beta-CyD are useful for inhibition of polymorphic transition and crystallization rates of drugs during storage. 3) The delayed release formulation can be obtained by the use of enteric type CyDs such as O-carboxymethyl-O-ethyl-beta-CyD. 4) The hydrophobic CyDs are useful for modification of the release site and/or time profile of water-soluble drugs with prolonged therapeutic effects. 5) The branched CyDs are particularly effective in inhibiting the adsorption to hydrophobic surface of containers and aggregation of polypeptide and protein drugs. 6) The combined use of different CyDs and/or pharmaceutical additives can serve as more functional drug carriers, improving efficacy and reducing side effects. 7) The CyD/drug conjugates may provide a versatile means for the constructions of not only colonic delivery system but also site-specific drug release system, including gene delivery. On the basis of the above-mentioned knowledge, the advantages and limitations of CyDs in the design of advanced dosage forms will be discussed.

  18. Antibiotic, Pharmaceutical, and Wastewater-Compound Data for Michigan, 1998-2005

    Science.gov (United States)

    Haack, Sheridan Kidd

    2010-01-01

    Beginning in the late 1990's, the U.S. Geological Survey began to develop analytical methods to detect, at concentrations less than 1 microgram per liter (ug/L), emerging water contaminants such as pharmaceuticals, personal-care chemicals, and a variety of other chemicals associated with various human and animal sources. During 1998-2005, the U.S. Geological Survey analyzed the following Michigan water samples: 41 samples for antibiotic compounds, 28 samples for pharmaceutical compounds, 46 unfiltered samples for wastewater compounds (dissolved and suspended compounds), and 113 filtered samples for wastewater compounds (dissolved constituents only). The purpose of this report is to summarize the status of emerging contaminants in Michigan waters based on data from several different project-specific sample-collection efforts in Michigan during an 8-year period. During the course of the 8-year sampling effort, antibiotics were determined at 20 surface-water sites and 2 groundwater sites, pharmaceuticals were determined at 11 surface-water sites, wastewater compounds in unfiltered water were determined at 31 surface-water sites, and wastewater compounds in filtered water were determined at 40 surface-water and 4 groundwater sites. Some sites were visited only once, but others were visited multiple times. A variety of quality-assurance samples also were collected. This report describes the analytical methods used, describes the variations in analytical methods and reporting levels during the 8-year period, and summarizes all data using current (2009) reporting criteria. Very few chemicals were detected at concentrations greater than current laboratory reporting levels, which currently vary from a low of 0.005 ug/L for some antibiotics to 5 ug/L for some wastewater compounds. Nevertheless, 10 of 51 chemicals in the antibiotics analysis, 9 of 14 chemicals in the pharmaceuticals analysis, 34 of 67 chemicals in the unfiltered-wastewater analysis, and 56 of 62 chemicals in

  19. Characterization of pharmaceutically active compounds in Dongting Lake, China: Occurrence, chiral profiling and environmental risk.

    Science.gov (United States)

    Ma, Ruixue; Wang, Bin; Lu, Shaoyong; Zhang, Yizhe; Yin, Lina; Huang, Jun; Deng, Shubo; Wang, Yujue; Yu, Gang

    2016-07-01

    Twenty commonly used pharmaceuticals including eight chiral drugs were investigated in Dongting Lake, China. The contamination level was relatively low on a global scale. Twelve pharmaceuticals were identified. The most abundant compound was caffeine followed by diclofenac, DEET, mefenamic acid, fluoxetine, ibuprofen and carbamazepine with mean concentrations from 2.0 to 80.8ngL(-1). Concentrations between East and West Dongting Lake showed spatial difference, with the West Dongting Lake less polluted. The relatively high ratio of caffeine versus carbamazepine (over 50) may indicate there was possible direct discharge of domestic wastewater into the lake. This is the first study presenting a survey allowing for comprehensive analysis of multiclass achiral and chiral pharmaceuticals including beta-blockers, antidepressants and anti-inflammatory drugs in freshwater lake. The enantiomeric compositions presented racemic to weakly enantioselective, with the highest enantiomeric fraction (EF) of 0.63 for fluoxetine. Meanwhile, venlafaxine was identified and evaluated the environment risk in surface water in China for the first time. The results of risk assessment suggested that fluoxetine, venlafaxine and diclofenac acid might pose a significant risk to aquatic organisms in Dongting Lake. The resulting data will be useful to enrich the research of emerging pollutants in freshwater lake and stereochemistry for environment investigations. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Fate and removal of pharmaceuticals and illicit drugs in conventional and membrane bioreactor wastewater treatment plants and by riverbank filtration.

    Science.gov (United States)

    Petrovic, Mira; de Alda, Maria Jose Lopez; Diaz-Cruz, Silvia; Postigo, Cristina; Radjenovic, Jelena; Gros, Meritxell; Barcelo, Damià

    2009-10-13

    Pharmaceutically active compounds (PhACs) and drugs of abuse (DAs) are two important groups of emerging environmental contaminants that have raised an increasing interest in the scientific community. A number of studies revealed their presence in the environment. This is mainly due to the fact that some compounds are not efficiently removed during wastewater treatment processes, being able to reach surface and groundwater and subsequently, drinking waters. This paper reviews the data regarding the levels of pharmaceuticals and illicit drugs detected in wastewaters and gives an overview of their removal by conventional treatment technologies (applying activated sludge) as well as advanced treatments such as membrane bioreactor. The paper also gives an overview of bank filtration practices at managed aquifer recharge sites and discusses the potential of this approach to mitigate the contamination by PhACs and DAs.

  1. Pharmaceutical companies and their drugs on social media: a content analysis of drug information on popular social media sites.

    Science.gov (United States)

    Tyrawski, Jennifer; DeAndrea, David C

    2015-06-01

    Many concerns have been raised about pharmaceutical companies marketing their drugs directly to consumers on social media. This form of direct-to-consumer advertising (DTCA) can be interactive and, because it is largely unmonitored, the benefits of pharmaceutical treatment could easily be overemphasized compared to the risks. Additionally, nonexpert consumers can share their own drug product testimonials on social media and illegal online pharmacies can market their services on popular social media sites. There is great potential for the public to be exposed to misleading or dangerous information about pharmaceutical drugs on social media. Our central aim was to examine how pharmaceutical companies use social media to interact with the general public and market their drugs. We also sought to analyze the nature of information that appears in search results for widely used pharmaceutical drugs in the United States on Facebook, Twitter, and YouTube with a particular emphasis on the presence of illegal pharmacies. Content analyses were performed on (1) social media content on the Facebook, Twitter, and YouTube accounts of the top 15 pharmaceutical companies in the world and (2) the content that appears when searching on Facebook, Twitter, and YouTube for the top 20 pharmaceutical drugs purchased in the United States. Notably, for the company-specific analysis, we examined the presence of information similar to various forms of DTCA, the audience reach of company postings, and the quantity and quality of company-consumer interaction. For the drug-specific analysis, we documented the presence of illegal pharmacies, personal testimonials, and drug efficacy claims. From the company-specific analysis, we found information similar to help-seeking DTCA in 40.7% (301/740) of pharmaceutical companies' social media posts. Drug product claims were present in only 1.6% (12/740) of posts. Overall, there was a substantial amount of consumers who interacted with pharmaceutical

  2. Pharmaceutical Companies and Their Drugs on Social Media: A Content Analysis of Drug Information on Popular Social Media Sites

    Science.gov (United States)

    2015-01-01

    Background Many concerns have been raised about pharmaceutical companies marketing their drugs directly to consumers on social media. This form of direct-to-consumer advertising (DTCA) can be interactive and, because it is largely unmonitored, the benefits of pharmaceutical treatment could easily be overemphasized compared to the risks. Additionally, nonexpert consumers can share their own drug product testimonials on social media and illegal online pharmacies can market their services on popular social media sites. There is great potential for the public to be exposed to misleading or dangerous information about pharmaceutical drugs on social media. Objective Our central aim was to examine how pharmaceutical companies use social media to interact with the general public and market their drugs. We also sought to analyze the nature of information that appears in search results for widely used pharmaceutical drugs in the United States on Facebook, Twitter, and YouTube with a particular emphasis on the presence of illegal pharmacies. Methods Content analyses were performed on (1) social media content on the Facebook, Twitter, and YouTube accounts of the top 15 pharmaceutical companies in the world and (2) the content that appears when searching on Facebook, Twitter, and YouTube for the top 20 pharmaceutical drugs purchased in the United States. Notably, for the company-specific analysis, we examined the presence of information similar to various forms of DTCA, the audience reach of company postings, and the quantity and quality of company-consumer interaction. For the drug-specific analysis, we documented the presence of illegal pharmacies, personal testimonials, and drug efficacy claims. Results From the company-specific analysis, we found information similar to help-seeking DTCA in 40.7% (301/740) of pharmaceutical companies’ social media posts. Drug product claims were present in only 1.6% (12/740) of posts. Overall, there was a substantial amount of consumers

  3. SOME ASPECTS OF THE MARKETING STUDIES FOR THE PHARMACEUTICAL MARKET OF ANTIVIRAL DRUGS

    Directory of Open Access Journals (Sweden)

    A. G. Salnikova

    2015-01-01

    Full Text Available Antiviral drugs are widely used in medicinal practice. They suppress the originator and stimulate the protection of an organism. The drugs are used for the treatment of flu and ARVI, herpetic infections, virus hepatitis, HIV-infection. Contemporary pharmaceutical market is represented by a wide range of antiviral drugs. Marketing studies are conducted to develop strategies, used for the enhancement of pharmacy organization activity efficiency. Conduction of the marketing researches of pharmaceutical market is the purpose of this study. We have used State Registry of Drugs, State Record of Drugs, List of vital drugs, questionnaires of pharmaceutical workers during our work. Historical, sociological, mathematical methods, and a method of expert evaluation were used in the paper. As the result of the study we have made the following conclusions. We have studied and generalized the literature data about classification and application of antiviral drugs, marketing, competition. The assortment of antiviral drugs on the pharmaceutical market of the Russian Federation was also studied. We have conducted an analysis for the obtainment of the information about antiviral drugs by pharmaceutical workers. We have determined the competitiveness of antiviral drugs, and on the basis of the research conducted we have submitted an offer for pharmaceutical organizations to form the range of antiviral drugs.

  4. Pharmaceutical cocrystals: the coming wave of new drug substances.

    Science.gov (United States)

    Brittain, Harry G

    2013-02-01

    Solid crystalline phases containing two cocrystallized components offer a new development pathway whereby one can potentially improve the physical characteristics (i.e., equilibrium solubility, dissolution rate, solid-state stability, etc.) of a drug substance that exhibits a profile that is less than desirable. In this commentary, the topic of pharmaceutical cocrystals will be briefly explored, and a short exposition of the solubility and dissolution rate advantages that have been realized in various systems will be provided. The Guidance for Industry document recently proposed by United States Food and Drug Administration will be outlined, and its requirements explained. Finally, the subset of pharmaceutical cocrystals that consist of a drug substance and a salt of that substance (termed a salt cocrystal) will be examined to illustrate this additional class of pharmaceutical cocrystals that may offer significant scientific and regulatory advantages. Copyright © 2012 Wiley Periodicals, Inc.

  5. The occurrence and removal of selected pharmaceutical compounds in a sewage treatment works utilising activated sludge treatment

    Energy Technology Data Exchange (ETDEWEB)

    Jones, O.A.H. [Institute of Environmental Policy, Imperial College, London SW7 2AZ (United Kingdom); Voulvoulis, N. [Institute of Environmental Policy, Imperial College, London SW7 2AZ (United Kingdom); Lester, J.N. [School of Water Sciences, Cranfield University, Cranfield, Bedfordshire MK43 0AL (United Kingdom)]. E-mail: j.lester@cranfield.ac.uk

    2007-02-15

    Pharmaceutical substances have been detected in sewage effluents as well as receiving waters in many parts of the world. In this study, the occurrence and removal of a number of drug compounds were studied within a large sewage treatment plant in the south of England. Samples were processed using solid phase extraction and analysed using gas chromatography-mass spectrometry (GC-MS). The results demonstrate that ibuprofen, paracetamol, salbutamol and mefenamic acid were present in both the influent and effluent of the works while propranolol-HCl was not found above the limit of quantification in any sample. Elimination rates were circa 90% for each compound but several hundred nanograms per litre were still present in the final effluent. - This report looks at the occurrence and removal rates of drugs in English wastewater.

  6. The occurrence and removal of selected pharmaceutical compounds in a sewage treatment works utilising activated sludge treatment

    International Nuclear Information System (INIS)

    Jones, O.A.H.; Voulvoulis, N.; Lester, J.N.

    2007-01-01

    Pharmaceutical substances have been detected in sewage effluents as well as receiving waters in many parts of the world. In this study, the occurrence and removal of a number of drug compounds were studied within a large sewage treatment plant in the south of England. Samples were processed using solid phase extraction and analysed using gas chromatography-mass spectrometry (GC-MS). The results demonstrate that ibuprofen, paracetamol, salbutamol and mefenamic acid were present in both the influent and effluent of the works while propranolol-HCl was not found above the limit of quantification in any sample. Elimination rates were circa 90% for each compound but several hundred nanograms per litre were still present in the final effluent. - This report looks at the occurrence and removal rates of drugs in English wastewater

  7. Behaviour of pharmaceuticals and psychotic drugs in conventional and advanced wastewater treatments; Comportamiento de medicamentos y psicofarmacos en tratamaientos de depuracion convencionales y terciarios

    Energy Technology Data Exchange (ETDEWEB)

    Cortacans Torre, J. A.; Castillo Gonzalez, I. del; Hernandez Lehmann, A.; Hernandez Munoz, A.; Rodriguez Barrera, X.

    2009-07-01

    The occurrence of various pharmaceuticals and psychotic drugs in wastewater and their removal rates in a conventional wastewater treatment plant has been investigated. The psychoactive drugs are poorly removed in the biological step. However, most pharmaceuticals except of carbamazepine, are significantly biodegraded depending the removal degree on the type of compound and on the sludge retention time of the biological treatment. Also, the removal efficiency of conventional tertiary treatments and ultrafiltration and nano filtration membranes using two pilot plants was examined. the effects of retaining pharmaceuticals with ultrafiltration and nano filtration membranes do not greatly differ despite the difference in their pore size. (Author) 25 refs.

  8. Fate of pharmaceutical compounds in hydroponic mesocosms planted with Scirpus validus

    International Nuclear Information System (INIS)

    Zhang, Dong Qing; Gersberg, Richard M.; Hua, Tao; Zhu, Junfei; Goyal, Manish Kumar; Ng, Wun Jern; Tan, Soon Keat

    2013-01-01

    A systematic approach to assess the fate of selected pharmaceuticals (carbamazepine, naproxen, diclofenac, clofibric acid and caffeine) in hydroponic mesocosms is described. The overall objective was to determine the kinetics of depletion (from solution) and plant uptake for these compounds in mesocosms planted with S. validus growing hydroponically. The potential for translocation of these pharmaceuticals from the roots to the shoots was also assessed. After 21 days of incubation, nearly all of the caffeine, naproxen and diclofenac were eliminated from solution, whereas carbamazepine and clofibric acid were recalcitrant to both photodegradation and biodegradation. The fact that the BAFs for roots for carbamazepine and clofibric acid were greater than 5, while the BAFs for naproxen, diclofenac and caffeine were less than 5, implied that the latter two compounds although recalcitrant to biodegradation, still had relatively high potential for plant uptake. Naproxen was sensitive to both photodegradation (30–42%) and biodegradation (>50%), while diclofenac was particularly sensitive (>70%) to photodegradation alone. No significant correlations (p > 0.05) were found between the rate constants of depletion or plant tissue levels of the pharmaceuticals and either log K ow or log D ow . -- Highlights: •All of pharmaceuticals were removed from solution efficiently after 21 d of incubation. •Effects of photodegradation and biodegradation on pharmaceutical removal were studied. •The pharmaceutical concentrations in the plant tissues were detected. •No correlation was found between pharmaceutical levels in plant tissues and log K ow or log D ow . •Log K ow is the most significant parameter for predicting pharmaceutical levels. -- All the tested pharmaceuticals (carbamazepine, naproxen, diclofenac, clofibric acid and caffeine) were efficiently removed from nutrient solution

  9. Occurrence and concentrations of pharmaceutical compounds in groundwater used for public drinking-water supply in California

    Energy Technology Data Exchange (ETDEWEB)

    Fram, Miranda S., E-mail: mfram@usgs.gov [U.S. Geological Survey California Water Science Center, 6000 J Street, Placer Hall, Sacramento, CA 95819-6129 (United States); Belitz, Kenneth, E-mail: kbelitz@usgs.gov [U.S. Geological Survey California Water Science Center, 4165 Spruance Road, Suite 200, San Diego, CA 95101-0812 (United States)

    2011-08-15

    Pharmaceutical compounds were detected at low concentrations in 2.3% of 1231 samples of groundwater (median depth to top of screened interval in wells = 61 m) used for public drinking-water supply in California. Samples were collected statewide for the California State Water Resources Control Board's Groundwater Ambient Monitoring and Assessment (GAMA) Program. Of 14 pharmaceutical compounds analyzed, 7 were detected at concentrations greater than or equal to method detection limits: acetaminophen (used as an analgesic, detection frequency 0.32%, maximum concentration 1.89 {mu}g/L), caffeine (stimulant, 0.24%, 0.29 {mu}g/L), carbamazepine (mood stabilizer, 1.5%, 0.42 {mu}g/L), codeine (opioid analgesic, 0.16%, 0.214 {mu}g/L), p-xanthine (caffeine metabolite, 0.08%, 0.12 {mu}g/L), sulfamethoxazole (antibiotic, 0.41%, 0.17 {mu}g/L), and trimethoprim (antibiotic, 0.08%, 0.018 {mu}g/L). Detection frequencies of pesticides (33%), volatile organic compounds not including trihalomethanes (23%), and trihalomethanes (28%) in the same 1231 samples were significantly higher. Median detected concentration of pharmaceutical compounds was similar to those of volatile organic compounds, and higher than that of pesticides. Pharmaceutical compounds were detected in 3.3% of the 855 samples containing modern groundwater (tritium activity > 0.2 TU). Pharmaceutical detections were significantly positively correlated with detections of urban-use herbicides and insecticides, detections of volatile organic compounds, and percentage of urban land use around wells. Groundwater from the Los Angeles metropolitan area had higher detection frequencies of pharmaceuticals and other anthropogenic compounds than groundwater from other areas of State with similar proportions of urban land use. The higher detection frequencies may reflect that groundwater flow systems in Los Angeles area basins are dominated by engineered recharge and intensive groundwater pumping. - Highlights: {yields

  10. Occurrence and concentrations of pharmaceutical compounds in groundwater used for public drinking-water supply in California

    International Nuclear Information System (INIS)

    Fram, Miranda S.; Belitz, Kenneth

    2011-01-01

    Pharmaceutical compounds were detected at low concentrations in 2.3% of 1231 samples of groundwater (median depth to top of screened interval in wells = 61 m) used for public drinking-water supply in California. Samples were collected statewide for the California State Water Resources Control Board's Groundwater Ambient Monitoring and Assessment (GAMA) Program. Of 14 pharmaceutical compounds analyzed, 7 were detected at concentrations greater than or equal to method detection limits: acetaminophen (used as an analgesic, detection frequency 0.32%, maximum concentration 1.89 μg/L), caffeine (stimulant, 0.24%, 0.29 μg/L), carbamazepine (mood stabilizer, 1.5%, 0.42 μg/L), codeine (opioid analgesic, 0.16%, 0.214 μg/L), p-xanthine (caffeine metabolite, 0.08%, 0.12 μg/L), sulfamethoxazole (antibiotic, 0.41%, 0.17 μg/L), and trimethoprim (antibiotic, 0.08%, 0.018 μg/L). Detection frequencies of pesticides (33%), volatile organic compounds not including trihalomethanes (23%), and trihalomethanes (28%) in the same 1231 samples were significantly higher. Median detected concentration of pharmaceutical compounds was similar to those of volatile organic compounds, and higher than that of pesticides. Pharmaceutical compounds were detected in 3.3% of the 855 samples containing modern groundwater (tritium activity > 0.2 TU). Pharmaceutical detections were significantly positively correlated with detections of urban-use herbicides and insecticides, detections of volatile organic compounds, and percentage of urban land use around wells. Groundwater from the Los Angeles metropolitan area had higher detection frequencies of pharmaceuticals and other anthropogenic compounds than groundwater from other areas of State with similar proportions of urban land use. The higher detection frequencies may reflect that groundwater flow systems in Los Angeles area basins are dominated by engineered recharge and intensive groundwater pumping. - Highlights: → Pharmaceuticals analyzed in

  11. Why trash don't pass? pharmaceutical licensing and safety performance of drugs.

    Science.gov (United States)

    Banerjee, Tannista; Nayak, Arnab

    2017-01-01

    This paper examines how asymmetric information in pharmaceutical licensing affects the safety standards of licensed drugs. Pharmaceutical companies often license potential drug molecules at different stages of drug development from other pharmaceutical or biotechnology companies and complete the remaining of research stages before submitting the new drug application(NDA) to the food and drug administration. The asymmetric information associated with the quality of licensed molecules might result in the molecules which are less likely to succeed to be licensed out, while those with greater potential of success being held internally for development. We identify the NDAs submitted between 1993 and 2004 where new molecular entities were acquired through licensing. Controlling for other drug area specific and applicant firm specific factors, we investigate whether drugs developed with licensed molecules face higher probability of safety based recall and ultimate withdrawal from the market than drugs developed internally. Results suggest the opposite of Akerlof's (Q J Econ 84:488-500, 1970) lemons problem. Licensed molecules rather have less probability of facing safety based recalls and ultimate withdrawal from the market comparing to internally developed drug molecules. This suggests that biotechnology and small pharmaceutical firms specializing in pharmaceutical research are more efficient in developing good potential molecules because of their concentrated research. Biotechnology firms license out good potential molecules because it increases their market value and reputation. In addition, results suggest that both the number of previous approved drugs in the disease area, and also the applicant firms' total number of previous approvals in all disease areas reduce the probability that an additional approved drug in the same drug area will potentially be harmful.

  12. Biodegradability of pharmaceutical compounds in agricultural soils irrigated with treated wastewater

    International Nuclear Information System (INIS)

    Grossberger, Amnon; Hadar, Yitzhak; Borch, Thomas; Chefetz, Benny

    2014-01-01

    Pharmaceutical compounds (PCs) are introduced into agricultural soils via irrigation with treated wastewater (TWW). Our data show that carbamazepine, lamotrigine, caffeine, metoprolol, sulfamethoxazole and sildenafil are persistent in soils when introduced via TWW. However, other PCs, namely diclofenac, ibuprofen, bezafibrate, gemfibrozil and naproxen were not detected in soils when introduced via TWW. This is likely due to rapid degradation as confirmed in our microcosm studies where they exhibited half-lives (t 1/2 ) between 0.2–9.5 days when soils were spiked at 50 ng/g soil and between 3 and 68 days when soils were spiked at 5000 ng/g soil. The degradation rate and extent of PCs observed in microcosm studies were similar in soils that had been previously irrigated with TWW or fresh water. This suggests that pre-exposure of the soils to PCs via irrigation with TWW does not enhance their biodegradation. This suggests that PCs are probably degraded in soils via co-metabolism. Highlights: • Some pharmaceuticals are highly persistent in arable soils. • Weak acid pharmaceuticals are readily degradable in agricultural soils. • Irrigation with treated wastewater does not enhance degradation of pharmaceuticals. • Degradation of pharmaceuticals in soil is probably occurred via co-metabolism. -- Some pharmaceutical compounds are persistent in arable soils when introduced via irrigation with treated wastewater

  13. Homochiral drugs: a demanding tendency of the pharmaceutical industry.

    Science.gov (United States)

    Núñez, María C; García-Rubiño, M Eugenia; Conejo-García, Ana; Cruz-López, Olga; Kimatrai, María; Gallo, Miguel A; Espinosa, Antonio; Campos, Joaquín M

    2009-01-01

    The issue of drug chirality is now a major theme in the design and development of new drugs, underpinned by a new understanding of the role of molecular recognition in many pharmacologically relevant events. In general, three methods are utilized for the production of a chiral drug: the chiral pool, separation of racemates, and asymmetric synthesis. Although the use of chiral drugs predates modern medicine, only since the 1980's has there been a significant increase in the development of chiral pharmaceutical drugs. An important commercial reason is that as patents on racemic drugs expire, pharmaceutical companies have the opportunity to extend patent coverage through development of the chiral switch enantiomers with desired bioactivity. Stimulated by the new policy statements issued by the regulatory agencies, the pharmaceutical industry has systematically begun to develop chiral drugs in enantiometrically enriched pure forms. This new trend has caused a tremendous change in the industrial small- and large-scale production to enantiomerically pure drugs, leading to the revisiting and updating of old technologies, and to the development of new methodologies of their large-scale preparation (as the use of stereoselective syntheses and biocatalyzed reactions). The final decision whether a given chiral drug will be marketed in an enantiomerically pure form, or as a racemic mixture of both enantiomers, will be made weighing all the medical, financial and social proficiencies of one or other form. The kinetic, pharmacological and toxicological properties of individual enantiomers need to be characterized, independently of a final decision.

  14. Sex, gender, and pharmaceutical politics: From drug development to marketing.

    Science.gov (United States)

    Fisher, Jill A; Ronald, Lorna M

    2010-08-01

    Biological sex differences and sociocultural gender norms affect the provision of health care products and services, but there has been little explicit analysis of the impact of sex differences and gender norms on the regulation of pharmaceutical development and marketing. This article provides an overview of the regulation of pharmaceuticals and examines the ways that regulatory agencies account for sex and gender in their review of scientific data and marketing materials. The primary focus is on the US context, but information is also included about regulatory models in Europe, Canada, and Japan for comparative purposes. Specific examples show how sex differences and gender norms influence scientific and policy decisions about pharmaceuticals. The United States and Canada were found to be the only countries that have explicit requirements to include women in clinical trials and to perform sex-based subgroup analysis on study results. The potential influence of politics on regulatory decisions may have led to an uneven application of standards, as seen through the examples of mifepristone (for abortion) and sildenafil citrate (for erectile dysfunction). Three detailed case studies illustrate the importance of considering sex and gender in pharmaceutical development and marketing: Phase I clinical trials; human papillomavirus quadrivalent vaccine; and tegaserod, a drug for irritable bowel syndrome. Sex and gender play important roles in pharmaceutical regulation, from the design of clinical trials and the approval of new drugs to advertising and postmarketing surveillance. However, regulatory agencies pay insufficient attention to both biological sex differences and sociocultural gender norms. This disregard perpetuates inequalities by ignoring drug safety problems that predominate in women and by allowing misleading drug marketing that reinforces gender stereotypes. Recommendations have been made to improve the regulation of pharmaceuticals in regard to sex and

  15. Pharmaceuticals: pharmaceutical cost controls--2005. End of Year Issue Brief.

    Science.gov (United States)

    Seay, Melicia; Varma, Priya

    2005-12-31

    The enactment of the Omnibus Budget Reconciliation Act of 1990 (OBRA '90) gave states the option of offering pharmaceutical benefits within their Medicaid programs. But the law placed restrictions on states' flexibility to control what prescriptions they would cover and required the states to reimburse outpatient prescription drugs from manufacturers that signed rebate agreements with the U.S. Department of Health and Human Services. Forty-nine states--Arizona is excluded, based on its program structure--and the District of Columbia currently offer prescription drug coverage under the Medicaid Drug Rebate Program. During the past four years, states all over the country have been plagued with revenue shortfalls in their state Medicaid budgets. While the fiscal situation improved for most states in the 2004 legislative session, many states still face budget pressures in 2005. Compounding existing budget pressures are threats from the Bush Administration to shift increased costs of the Medicaid program on to the states. All things considered, the economic pressure of funding Medicaid is at the top of legislative agendas in 2005. As in previous years, states are attempting to reduce costs to their Medicaid programs by seeking savings in their pharmaceutical programs. Prescription drug costs are highly attributed as a contributing factor to the fiscal climate of state Medicaid programs. Currently, prescription drug spending outpaces that of every other category of health care and drug prices are rising faster than inflation. In response, states are instituting a variety of pharmaceutical cost control measures such as creating preferred drug lists (PDLs), negotiating supplemental rebates, forming bulk purchasing pools, promoting generic drug substitution and implementing price controls. As prescription drug cost containment tools have gained acceptance and momentum, they continue to be controversial. This issue brief explores the debate, history, methodology, utilization

  16. Automated Solid Phase Extraction (SPE) LC/NMR Applied to the Structural Analysis of Extractable Compounds from a Pharmaceutical Packaging Material of Construction.

    Science.gov (United States)

    Norwood, Daniel L; Mullis, James O; Davis, Mark; Pennino, Scott; Egert, Thomas; Gonnella, Nina C

    2013-01-01

    The structural analysis (i.e., identification) of organic chemical entities leached into drug product formulations has traditionally been accomplished with techniques involving the combination of chromatography with mass spectrometry. These include gas chromatography/mass spectrometry (GC/MS) for volatile and semi-volatile compounds, and various forms of liquid chromatography/mass spectrometry (LC/MS or HPLC/MS) for semi-volatile and relatively non-volatile compounds. GC/MS and LC/MS techniques are complementary for structural analysis of leachables and potentially leachable organic compounds produced via laboratory extraction of pharmaceutical container closure/delivery system components and corresponding materials of construction. Both hyphenated analytical techniques possess the separating capability, compound specific detection attributes, and sensitivity required to effectively analyze complex mixtures of trace level organic compounds. However, hyphenated techniques based on mass spectrometry are limited by the inability to determine complete bond connectivity, the inability to distinguish between many types of structural isomers, and the inability to unambiguously determine aromatic substitution patterns. Nuclear magnetic resonance spectroscopy (NMR) does not have these limitations; hence it can serve as a complement to mass spectrometry. However, NMR technology is inherently insensitive and its ability to interface with chromatography has been historically challenging. This article describes the application of NMR coupled with liquid chromatography and automated solid phase extraction (SPE-LC/NMR) to the structural analysis of extractable organic compounds from a pharmaceutical packaging material of construction. The SPE-LC/NMR technology combined with micro-cryoprobe technology afforded the sensitivity and sample mass required for full structure elucidation. Optimization of the SPE-LC/NMR analytical method was achieved using a series of model compounds

  17. Occurrence and concentrations of pharmaceutical compounds in groundwater used for public drinking-water supply in California.

    Science.gov (United States)

    Fram, Miranda S; Belitz, Kenneth

    2011-08-15

    Pharmaceutical compounds were detected at low concentrations in 2.3% of 1231 samples of groundwater (median depth to top of screened interval in wells=61 m) used for public drinking-water supply in California. Samples were collected statewide for the California State Water Resources Control Board's Groundwater Ambient Monitoring and Assessment (GAMA) Program. Of 14 pharmaceutical compounds analyzed, 7 were detected at concentrations greater than or equal to method detection limits: acetaminophen (used as an analgesic, detection frequency 0.32%, maximum concentration 1.89 μg/L), caffeine (stimulant, 0.24%, 0.29 μg/L), carbamazepine (mood stabilizer, 1.5%, 0.42 μg/L), codeine (opioid analgesic, 0.16%, 0.214 μg/L), p-xanthine (caffeine metabolite, 0.08%, 0.12 μg/L), sulfamethoxazole (antibiotic, 0.41%, 0.17 μg/L), and trimethoprim (antibiotic, 0.08%, 0.018 μg/L). Detection frequencies of pesticides (33%), volatile organic compounds not including trihalomethanes (23%), and trihalomethanes (28%) in the same 1231 samples were significantly higher. Median detected concentration of pharmaceutical compounds was similar to those of volatile organic compounds, and higher than that of pesticides. Pharmaceutical compounds were detected in 3.3% of the 855 samples containing modern groundwater (tritium activity>0.2 TU). Pharmaceutical detections were significantly positively correlated with detections of urban-use herbicides and insecticides, detections of volatile organic compounds, and percentage of urban land use around wells. Groundwater from the Los Angeles metropolitan area had higher detection frequencies of pharmaceuticals and other anthropogenic compounds than groundwater from other areas of the state with similar proportions of urban land use. The higher detection frequencies may reflect that groundwater flow systems in Los Angeles area basins are dominated by engineered recharge and intensive groundwater pumping. Published by Elsevier B.V.

  18. Pharmaceutical Cocrystals: Regulatory and Strategic Aspects, Design and Development

    Directory of Open Access Journals (Sweden)

    Dipak Dilip Gadade

    2016-12-01

    Full Text Available Cocrystal is a concept of the supramolecular chemistry which is gaining the extensive interest of researchers from pharmaceutical and chemical sciences and of drug regulatory agencies. The prominent reason of which is its ability to modify physicochemical properties of active pharmaceutical ingredients. During the development of the pharmaceutical product, formulators have to optimize the physicochemical properties of active pharmaceutical ingredients. Pharmaceutical cocrystals can be employed to improve vital physicochemical characteristics of a drug, including solubility, dissolution, bioavailability and stability of pharmaceutical compounds while maintaining its therapeutic activity. It is advantageous being a green synthesis approach for production of pharmaceutical compounds. The formation polymorphic forms, solvates, hydrates and salts of cocrystals during the synthesis reported in the literature which can be a potential issue in the development of pharmaceutical cocrystals. The approaches like hydrogen bonding rules, solubility parameters, screening through the CSD database or thermodynamic characteristics can be utilized for the rational design of cocrystals and selection of coformers for synthesis multi-component cocrystals. Considering the significance of pharmaceutical cocrystals pharmaceutical regulatory authorities in the United States and Europe issued guidance documents which may be helpful for pharmaceutical product registration in these regions. In this article, we deal with the design, synthesis, strategic aspects and characteristics of cocrystals along perspectives on its regulatory and intellectual property considerations.

  19. Pharmaceutical Cocrystals: Regulatory and Strategic Aspects, Design and Development.

    Science.gov (United States)

    Gadade, Dipak Dilip; Pekamwar, Sanjay Sudhakar

    2016-12-01

    Cocrystal is a concept of the supramolecular chemistry which is gaining the extensive interest of researchers from pharmaceutical and chemical sciences and of drug regulatory agencies. The prominent reason of which is its ability to modify physicochemical properties of active pharmaceutical ingredients. During the development of the pharmaceutical product, formulators have to optimize the physicochemical properties of active pharmaceutical ingredients. Pharmaceutical cocrystals can be employed to improve vital physicochemical characteristics of a drug, including solubility, dissolution, bioavailability and stability of pharmaceutical compounds while maintaining its therapeutic activity. It is advantageous being a green synthesis approach for production of pharmaceutical compounds. The formation polymorphic forms, solvates, hydrates and salts of cocrystals during the synthesis reported in the literature which can be a potential issue in the development of pharmaceutical cocrystals. The approaches like hydrogen bonding rules, solubility parameters, screening through the CSD database or thermodynamic characteristics can be utilized for the rational design of cocrystals and selection of coformers for synthesis multi-component cocrystals. Considering the significance of pharmaceutical cocrystals pharmaceutical regulatory authorities in the United States and Europe issued guidance documents which may be helpful for pharmaceutical product registration in these regions. In this article, we deal with the design, synthesis, strategic aspects and characteristics of cocrystals along perspectives on its regulatory and intellectual property considerations.

  20. The possibility of obtaining marketing authorization of orphan pharmaceutical compounding preparations: 3,4-DAP for Lambert-Eaton Myasthenic Syndrome.

    Science.gov (United States)

    de Wilde, Sofieke; de Jong, Maria G H; Lipka, Alexander F; Guchelaar, Henk-Jan; Schimmel, Kirsten J M

    2018-03-01

    Pharmaceutical compounding preparations, produced by (hospital) pharmacies, usually do not have marketing authorization. As a consequence, some of these pharmaceutical compounding preparations can be picked-up by a pharmaceutical company to obtain marketing authorization, often leading to price increases. An example is the 3,4-diaminopyridine slow release (3,4-DAP SR) tablets for Lambert-Eaton Myasthenic Syndrome (LEMS). In 2009 marketing authorization was given for the commercial immediate release phosphate salt of the drug, including a fifty-fold price increase compared to the pharmaceutical compounding preparation. Obtaining marketing authorization for 3,4-DAP SR by academia might have been a solution to prevent this price increase. To determine whether the available data of a pharmaceutical compounding preparation with long-term experience in regular care are adequate to obtain marketing authorization, 3,4-DAP SR is used as a case study. A retrospective qualitative case-study was performed. Initially, document analysis was executed by collecting the required data for marketing authorization in general and whether data of Firdapse® and 3,4-DAP SR met these requirements. Secondly, the (non-) available data of the two formulations were compared with each other to determine the differences in availability. At the time of approval, almost all data were available for both Firdapse® and 3,4-DAP SR. Conversely, much of the data used for the approval of Firdapse® originated from the 3,4-DAP immediate release (3,4-DAP IR) formulation. Only two bioequivalence studies and one pharmacology safety study was performed with Firdapse® before marketing authorization application. In conclusion, at time Firdapse® obtained approval, the data available did not differ substantially from 3,4-DAP SR, indicating that approval with 3,4-DAP SR would have been possible. We make a plea for approval of orphan medicinal products developed and manufactured by academic institutions as to

  1. Behavior of pharmaceuticals and drugs of abuse in a drinking water treatment plant (DWTP) using combined conventional and ultrafiltration and reverse osmosis (UF/RO) treatments.

    Science.gov (United States)

    Boleda, M A Rosa; Galceran, M A Teresa; Ventura, Francesc

    2011-06-01

    The behavior along the potabilization process of 29 pharmaceuticals and 12 drugs of abuse identified from a total of 81 compounds at the intake of a drinking water treatment plant (DWTP) has been studied. The DWTP has a common treatment consisting of dioxychlorination, coagulation/flocculation and sand filtration and then water is splitted in two parallel treatment lines: conventional (ozonation and carbon filtration) and advanced (ultrafiltration and reverse osmosis) to be further blended, chlorinated and distributed. Full removals were reached for most of the compounds. Iopromide (up to 17.2 ng/L), nicotine (13.7 ng/L), benzoylecgonine (1.9 ng/L), cotinine (3.6 ng/L), acetaminophen (15.6 ng/L), erythromycin (2.0 ng/L) and caffeine (6.0 ng/L) with elimination efficiencies ≥ 94%, were the sole compounds found in the treated water. The advanced treatment process showed a slightly better efficiency than the conventional treatment to eliminate pharmaceuticals and drugs of abuse. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. The interaction of encapsulated pharmaceutical drugs with a silica matrix.

    Science.gov (United States)

    Morais, Everton C; Correa, Gabriel G; Brambilla, Rodrigo; Radtke, Claudio; Baibich, Ione Maluf; dos Santos, João Henrique Z

    2013-03-01

    A series of seven drugs, namely, fluoxetine, gentamicin, lidocaine, morphine, nifedipine, paracetamol and tetracycline, were encapsulated. The encapsulated systems were characterized using a series of complementary techniques: Fourier-transform infrared spectroscopy (FT-IR), diffusive reflectance spectroscopy in the UV-vis region (DRS) and X-ray photoelectron spectroscopy (XPS). According to the DRS spectra, most of the encapsulated systems showed a band shift of the maximum absorption when compared with the corresponding bare pharmaceutical. Additionally, after encapsulation, the drugs exhibited infrared band shifts toward higher wavenumbers, which in turn provided insight into potential sites for interaction with the silica framework. The amine group showed a band shift in the spectra of almost all the drugs (except nifedipine and tetracycline). This finding indicates the possibility of a hydrogen bonding interaction between the drug and the silica via electron donation from the amine group to the silica framework. XPS confirmed this interaction between the pharmaceuticals and the silica through the amine group. A correlation was observed between the textural characteristics of the solids and the spectroscopic data, suggesting that the amine groups from the pharmaceuticals were more perturbed upon encapsulation. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Core competencies for pharmaceutical physicians and drug development scientists

    Science.gov (United States)

    Silva, Honorio; Stonier, Peter; Buhler, Fritz; Deslypere, Jean-Paul; Criscuolo, Domenico; Nell, Gerfried; Massud, Joao; Geary, Stewart; Schenk, Johanna; Kerpel-Fronius, Sandor; Koski, Greg; Clemens, Norbert; Klingmann, Ingrid; Kesselring, Gustavo; van Olden, Rudolf; Dubois, Dominique

    2013-01-01

    Professional groups, such as IFAPP (International Federation of Pharmaceutical Physicians and Pharmaceutical Medicine), are expected to produce the defined core competencies to orient the discipline and the academic programs for the development of future competent professionals and to advance the profession. On the other hand, PharmaTrain, an Innovative Medicines Initiative project, has become the largest public-private partnership in biomedicine in the European Continent and aims to provide postgraduate courses that are designed to meet the needs of professionals working in medicines development. A working group was formed within IFAPP including representatives from PharmaTrain, academic institutions and national member associations, with special interest and experience on Quality Improvement through education. The objectives were: to define a set of core competencies for pharmaceutical physicians and drug development scientists, to be summarized in a Statement of Competence and to benchmark and align these identified core competencies with the Learning Outcomes (LO) of the PharmaTrain Base Course. The objectives were successfully achieved. Seven domains and 60 core competencies were identified and aligned accordingly. The effective implementation of training programs using the competencies or the PharmaTrain LO anywhere in the world may transform the drug development process to an efficient and integrated process for better and safer medicines. The PharmaTrain Base Course might provide the cognitive framework to achieve the desired Statement of Competence for Pharmaceutical Physicians and Drug Development Scientists worldwide. PMID:23986704

  4. Core Competencies for Pharmaceutical Physicians and Drug Development Scientists

    Directory of Open Access Journals (Sweden)

    Honorio eSilva

    2013-08-01

    Full Text Available Professional groups, such as IFAPP (International Federation of Pharmaceutical Physicians and Pharmaceutical Medicine, are expected to produce the defined core competencies to orient the discipline and the academic programs for the development of future competent professionals and to advance the profession. On the other hand, PharmaTrain, an Innovative Medicines Initiative project, has become the largest public-private partnership in biomedicine in the European Continent and aims to provide postgraduate courses that are designed to meet the needs of professionals working in medicines development. A working group was formed within IFAPP including representatives from PharmaTrain, academic institutions and national member associations, with special interest and experience on Quality Improvement through education. The objectives were: to define a set of core competencies for pharmaceutical physicians and drug development scientists, to be summarized in a Statement of Competence and to benchmark and align these identified core competencies with the Learning Outcomes of the PharmaTrain Base Course. The objectives were successfully achieved. Seven domains and 60 core competencies were identified and aligned accordingly. The effective implementation of training programs using the competencies or the PharmaTrain Learning Outcomes anywhere in the world may transform the drug development process to an efficient and integrated process for better and safer medicines. The PharmaTrain Base Course might provide the cognitive framework to achieve the desired Statement of Competence for Pharmaceutical Physicians and Drug Development Scientists worldwide.

  5. A cross-sectional study of the availability and pharmacist's knowledge of nano-pharmaceutical drugs in Palestinian hospitals.

    Science.gov (United States)

    Assali, Mohyeddin; Shakaa, Ali; Abu-Hejleh, Sabaa; Abu-Omar, Reham; Karajeh, Nareman; Ajory, Nawal; Zyoud, Saed; Sweileh, Waleed

    2018-04-05

    Nanomedicine is the medical application of nanomaterials that may have an infinite size with the range less than 100 nm. This science has provided solutions to many of the current limitations in the diagnosis and treatment of diseases. Therefore, the pharmacist's knowledge and awareness of nano-pharmaceutical drugs will increase their availability in the market, and will improve the patient's compliance to their drug therapy. This study aimed to determine the availability of nano-pharmaceutical drugs in Palestinian hospitals and evaluate the extent of pharmacist's knowledge about them. A cross-sectional study design questionnaire was used to determine the availability of nano-pharmaceutical drugs based on the database of the ministry of health in the Palestinian hospitals (governmental, private and non- governmental organizations). Moreover, the knowledge of these nano-pharmaceutical drugs among pharmacists working in Palestinian hospitals was assessed based on developed questionnaire from the literature of the pharmaceutical formulations and nano-formulations. The variables were analyzed using Statistical Package for Social Sciences (SPSS 22). Fifty six pharmacists from 27 hospitals in the West bank completed the survey. The results regarding the availability of nano-pharmaceutical drugs indicated only eight available in hospitals with a frequency range 0-39.3%. Moreover, pharmacist's knowledge in the pharmaceutical formulations was better than that in nano-formulations. The availability of nano-pharmaceutical drugs in Palestinian hospitals was not adequate due to the lack of various nano-pharmaceutical drugs. The knowledge among pharmacists regarding nano-pharmaceutical drugs should be improved by providing courses in nanomedicine during the undergraduate pharmacy programs.

  6. Tropical Journal of Pharmaceutical Research: Submissions

    African Journals Online (AJOL)

    The Tropical Journal of Pharmaceutical Research is an international Open Access ... drug events, medical and other life sciences, and related engineering fields). ... Studies on synthesis of new compounds should only be considered if they ...

  7. Pharmaceutical compounds in shallow groundwater in non-agricultural areas of Minnesota: study design, methods, and data, 2013

    Science.gov (United States)

    Elliott, Sarah M.; Erickson, Melinda L.

    2014-01-01

    The U.S. Geological Survey, in cooperation with the Minnesota Pollution Control Agency, completed a study on the occurrence of pharmaceutical compounds and other contaminants of emerging concern in shallow groundwater in non-agricultural areas of Minnesota during 2013. This report describes the study design and methods for the study on the occurrence of pharmaceuticals and other contaminants of emerging concern, and presents the data collected on pharmaceutical compounds. Samples were analyzed by the U.S. Geological Survey National Water Quality Laboratory for 110 pharmaceutical compounds using research method 9017. Samples from 21 of 45 wells had detectable concentrations of at least one of the 110 compounds analyzed. One sample contained detectable concentrations of nine compounds, which was the most detected in a single sample. Fewer than five compounds were detected in most samples. Among all samples, 27 of the 110 compounds were detected in groundwater from at least one well. Desmethyldiltiazem and nicotine were the most frequently detected compounds, each detected in 5 of 46 environmental samples (one well was sampled twice so a total of 46 environmental samples were collected from 45 wells). Caffeine had the highest detectable concentration of all the compounds at 2,060 nanograms per liter.

  8. Dynamics and sources of pharmaceutically active compounds in a coastal Mediterranean river during heavy rains.

    Science.gov (United States)

    Reoyo-Prats, Brice; Aubert, Dominique; Sellier, Amélie; Roig, Benoit; Palacios, Carmen

    2018-03-01

    Concentrations of pharmaceutically active compounds (PACs) in freshwater systems depend on numerous factors such as land use and hydrometeorological conditions. In the Mediterranean, heavy rain events are of particular importance as they highly influence the concentration of micropollutants found in freshwater and are a source of recurrent first foul flushes due to combined sewer overflows (CSOs). In this study, we seek to assess the dynamics of pharmaceuticals during storm events in coastal Mediterranean rivers at a fine scale and to determine their contribution to multicontamination phenomena owing to CSOs. Our results showed that, while dissolved PACs followed the same trend as other contaminants, i.e., they increased significantly during CSOs, PACs in the total fraction did not peak yet maintained their already high concentrations for slightly longer due to their release via CSOs. Pharmaceutical concentrations for both the dissolved and the total fraction were dramatically diluted during the peak river flow. A fine-scale follow-up of PACs dynamics in the total fraction, including the differentiation of sewer overflows from both the right and left river banks, as well as the analyses of a large amount of PACs molecules, allowed us to clearly identify their major sources. While domestic inputs were dominated by nicotine and caffeine, the use of gadolinium (an MRI contrast agent) as a marker, attributed the main source of medical drugs such as tramadol, ibuprofen, and diclofenac to the major public hospital of the region. Thus, identifying major sources of PACs and implementing adapted water treatments directly at those sources would be the most cost-efficient alternative to cope with pharmaceutical drugs in coastal Mediterranean aquatic environments. Moreover, PACs behavior differed depending on the molecules considered and the source of these molecules, but we could not establish a direct link between their behavior and their chemical or physical properties. Our

  9. Pharmaceutical drugs, WWTP, and hydric bodies

    OpenAIRE

    Quezia Bezerra Cass; Eny Maria Vieira; Juliana Cristina Barreiro; Ricardo Wagner Reis Filho

    2007-01-01

    In the last decade, special attention has been given to the presence of pharmaceutical compounds in the aquatic environment; once that the continuous supply and persistence of these substances can be severally prejudicial to the biota. Thus, the development and application of new technologies that allows the removal or diminishes these contaminants has been the focus of the environment sanitation area. However, the absence of specific monitoring programs at the waste water treatment plant (WW...

  10. Fingerprinting analysis of non-crystalline pharmaceutical compounds using high energy X-rays and the total scattering pair distribution function

    Science.gov (United States)

    Davis, Timur D.

    2011-12-01

    In the development of new medicinal products, poor oral bioavailability, due to the low solubilities of many active pharmaceutical ingredients (APIs), is increasingly a barrier for treatments to be administered using tablet or capsule formulations and one of the main challenges facing the pharmaceutical industry. Non-crystalline phases such as the amorphous and nanostructured states can confer increased solubility to a drug, and therefore, have recently garnered a lot of interest from pharmaceutical researchers. However, little is known about local ordering in non-crystalline pharmaceuticals due to the lack of reliable experimental probes, hindering the clinical application of these compounds. The powerful tools of crystallography begin to lose their potency for structures on the nanoscale; conventional X-ray powder diffraction (XRPD) patterns become broad and featureless in these cases and are not useful for differentiating between different local molecular packing arrangements. In this thesis, we introduce the use of high energy X-rays coupled with total scattering pair distribution function (TSPDF) and fingerprinting analysis to investigate the local structures of non-crystalline pharmaceutical compounds. The high energy X-rays allow us to experimentally collect diffuse scattering intensities, which contain information about a sample's local ordering, in addition to the Bragg scattering available in conventional XRPD experiments, while the TSPDF allows us to view the intra- and inter-molecular correlations in real space. The goal of this study was to address some fundamental problems involving fingerprinting non-crystalline APIs using TSPDF in order to lay the groundwork for the proper use of the technique by the pharmaceutical community. We achieved this by developing the methodology as well as the exploring the scientific implications. On the methodology side, we introduced PDFGetX3, a new software program for calculating TSPDFs that simplifies the procedure

  11. Occurrence and concentrations of pharmaceutical compounds in deep groundwater used for public drinking-water supply in California

    Science.gov (United States)

    Fram, Miranda S.; Belitz, Kenneth

    2011-01-01

    Pharmaceutical compounds were detected at low concentrations in 2.3% of 1231 samples of groundwater (median depth to top of screened interval in wells = 61 m) used for public drinking-water supply in California. Samples were collected statewide for the California State Water Resources Control Board's Groundwater Ambient Monitoring and Assessment (GAMA) Program. Of 14 pharmaceutical compounds analyzed, 7 were detected at concentrations greater than or equal to method detection limits: acetaminophen (used as an analgesic, detection frequency 0.32%, maximum concentration 1.89 μg/L), caffeine (stimulant, 0.24%, 0.29 μg/L), carbamazepine (mood stabilizer, 1.5%, 0.42 μg/L), codeine (opioid analgesic, 0.16%, 0.214 μg/L), p-xanthine (caffeine metabolite, 0.08%, 0.12 μg/L), sulfamethoxazole (antibiotic, 0.41%, 0.17 μg/L), and trimethoprim (antibiotic, 0.08%, 0.018 μg/L). Detection frequencies of pesticides (33%), volatile organic compounds not including trihalomethanes (23%), and trihalomethanes (28%) in the same 1231 samples were significantly higher. Median detected concentration of pharmaceutical compounds was similar to those of volatile organic compounds, and higher than that of pesticides. Pharmaceutical compounds were detected in 3.3% of the 855 samples containing modern groundwater (tritium activity > 0.2 TU). Pharmaceutical detections were significantly positively correlated with detections of urban-use herbicides and insecticides, detections of volatile organic compounds, and percentage of urban land use around wells. Groundwater from the Los Angeles metropolitan area had higher detection frequencies of pharmaceuticals and other anthropogenic compounds than groundwater from other areas of the state with similar proportions of urban land use. The higher detection frequencies may reflect that groundwater flow systems in Los Angeles area basins are dominated by engineered recharge and intensive groundwater pumping.

  12. [The role of biotechnology in pharmaceutical drug design].

    Science.gov (United States)

    Gaisser, Sibylle; Nusser, Michael

    2010-01-01

    Biotechnological methods have become an important tool in pharmaceutical drug research and development. Today approximately 15 % of drug revenues are derived from biopharmaceuticals. The most relevant indications are oncology, metabolic disorders and disorders of the musculoskeletal system. For the future it can be expected that the relevance of biopharmaceuticals will further increase. Currently, the share of substances in preclinical testing that rely on biotechnology is more than 25 % of all substances in preclinical testing. Products for the treatment of cancer, metabolic disorders and infectious diseases are most important. New therapeutic approaches such as RNA interference only play a minor role in current commercial drug research and development with 1.5 % of all biological preclinical substances. Investments in sustainable high technology such as biotechnology are of vital importance for a highly developed country like Germany because of its lack of raw materials. Biotechnology helps the pharmaceutical industry to develop new products, new processes, methods and services and to improve existing ones. Thus, international competitiveness can be strengthened, new jobs can be created and existing jobs preserved.

  13. Marketing pharmaceutical drugs to women in magazines: a content analysis.

    Science.gov (United States)

    Sokol, Jennifer; Wackowski, Olivia; Lewis, M J

    2010-01-01

    To examine the prevalence and content of pharmaceutical ads in demographically different women's magazines. A content analysis was conducted using one year's worth of 5 different women's magazines of varying age demographics. Magazines differed in the proportion of drug ads for different health conditions (eg, cardiovascular) and target audience by age demographic. Use of persuasive elements (types of appeals, evidence) varied by condition promoted (eg, mental-health drug ads more frequently used emotional appeals). Ads placed greater emphasis on direction to industry information resources than on physician discussions. Prevalence of pharmaceutical advertising in women's magazines is high; continued surveillance is recommended.

  14. Waste-indicator and pharmaceutical compounds in landfill-leachate-affected ground water near Elkhart, Indiana, 2000-2002.

    Science.gov (United States)

    Buszka, P M; Yeskis, D J; Kolpin, D W; Furlong, E T; Zaugg, S D; Meyer, M T

    2009-06-01

    Four wells downgradient from a landfill near Elkhart, Indiana were sampled during 2000-2002 to evaluate the presence of waste-indicator and pharmaceutical compounds in landfill-leachate-affected ground water. Compounds detected in leachate-affected ground water included detergent metabolites (p-nonylphenol, nonylphenol monoethoxylate, nonylphenol diethoxylate, and octylphenol monoethoxylate), plasticizers (ethanol-2-butoxy-phosphate and diethylphthalate), a plastic monomer (bisphenol A), disinfectants (1,4-dichlorobenzene and triclosan), an antioxidant (5-methyl-1H-benzotriazole), three fire-retardant compounds (tributylphosphate and tri(2-chloroethyl)phosphate, and tri(dichlorisopropyl)phosphate), and several pharmaceuticals and metabolites (acetaminophen, caffeine, cotinine, 1,7-dimethylxanthine, fluoxetine, and ibuprofen). Acetaminophen, caffeine, and cotinine detections confirm prior indications of pharmaceutical and nicotinate disposal in the landfill.

  15. Preliminary risk assessment database and risk ranking of pharmaceuticals in the environment

    International Nuclear Information System (INIS)

    Cooper, Emily R.; Siewicki, Thomas C.; Phillips, Karl

    2008-01-01

    There is increasing concern about pharmaceuticals entering surface waters and the impacts these compounds may have on aquatic organisms. Many contaminants, including pharmaceuticals, are not completely removed by wastewater treatment. Discharge of effluent into surface waters results in chronic low-concentration exposure of aquatic organisms to these compounds, with unknown impacts. Exposure of virulent bacteria in wastewater to antibiotic residues may also induce resistance, which could threaten human health. The purpose of this study was to provide information on pharmaceutical threats to the environment. A preliminary risk assessment database for common pharmaceuticals was created and put into a web-accessible database named 'Pharmaceuticals in the Environment, Information for Assessing Risk' (PEIAR) to help others evaluate potential risks of pharmaceutical contaminants in the environment. Information from PEIAR was used to prioritize compounds that may threaten the environment, with a focus on marine and estuarine environments. The pharmaceuticals were ranked using five different combinations of physical-chemical and toxicological data, which emphasized different risks. The results of the ranking methods differed in the compounds identified as high risk; however, drugs from the central nervous system, cardiovascular, and anti-infective classes were heavily represented within the top 100 drugs in all rankings. Anti-infectives may pose the greatest overall risk based upon our results using a combination of factors that measure environmental transport, fate, and aquatic toxicity. The dataset is also useful for highlighting information that is still needed to assuredly assess risk

  16. Incorporating Natural Products, Pharmaceutical Drugs, Self-Care and Digital/Mobile Health Technologies into Molecular-Behavioral Combination Therapies for Chronic Diseases

    Science.gov (United States)

    Bulaj, Grzegorz; Ahern, Margaret M.; Kuhn, Alexis; Judkins, Zachary S.; Bowen, Randy C.; Chen, Yizhe

    2016-01-01

    Merging pharmaceutical and digital (mobile health, mHealth) ingredients to create new therapies for chronic diseases offers unique opportunities for natural products such as omega-3 polyunsaturated fatty acids (n-3 PUFA), curcumin, resveratrol, theanine, or α-lipoic acid. These compounds, when combined with pharmaceutical drugs, show improved efficacy and safety in preclinical and clinical studies of epilepsy, neuropathic pain, osteoarthritis, depression, schizophrenia, diabetes and cancer. Their additional clinical benefits include reducing levels of TNFα and other inflammatory cytokines. We describe how pleiotropic natural products can be developed as bioactive incentives within the network pharmacology together with pharmaceutical drugs and self-care interventions. Since approximately 50% of chronically-ill patients do not take pharmaceutical drugs as prescribed, psychobehavioral incentives may appeal to patients at risk for medication non-adherence. For epilepsy, the incentive-based network therapy comprises anticonvulsant drugs, antiseizure natural products (n-3 PUFA, curcumin or/and resveratrol) coupled with disease-specific behavioral interventions delivered by mobile medical apps. The add-on combination of antiseizure natural products and mHealth supports patient empowerment and intrinsic motivation by having a choice in self-care behaviors. The incentivized therapies offer opportunities: (1) to improve clinical efficacy and safety of existing drugs, (2) to catalyze patient-centered, disease self-management and behavior-changing habits, also improving health-related quality-of-life after reaching remission, and (3) merging copyrighted mHealth software with natural products, thus establishing an intellectual property protection of medical treatments comprising the natural products existing in public domain and currently promoted as dietary supplements. Taken together, clinical research on synergies between existing drugs and pleiotropic natural products

  17. Fate of pharmaceutical compounds in hydroponic mesocosms planted with Scirpus validus.

    Science.gov (United States)

    Zhang, Dong Qing; Gersberg, Richard M; Hua, Tao; Zhu, Junfei; Goyal, Manish Kumar; Ng, Wun Jern; Tan, Soon Keat

    2013-10-01

    A systematic approach to assess the fate of selected pharmaceuticals (carbamazepine, naproxen, diclofenac, clofibric acid and caffeine) in hydroponic mesocosms is described. The overall objective was to determine the kinetics of depletion (from solution) and plant uptake for these compounds in mesocosms planted with S. validus growing hydroponically. The potential for translocation of these pharmaceuticals from the roots to the shoots was also assessed. After 21 days of incubation, nearly all of the caffeine, naproxen and diclofenac were eliminated from solution, whereas carbamazepine and clofibric acid were recalcitrant to both photodegradation and biodegradation. The fact that the BAFs for roots for carbamazepine and clofibric acid were greater than 5, while the BAFs for naproxen, diclofenac and caffeine were less than 5, implied that the latter two compounds although recalcitrant to biodegradation, still had relatively high potential for plant uptake. Naproxen was sensitive to both photodegradation (30-42%) and biodegradation (>50%), while diclofenac was particularly sensitive (>70%) to photodegradation alone. No significant correlations (p > 0.05) were found between the rate constants of depletion or plant tissue levels of the pharmaceuticals and either log Kow or log Dow. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Occurrence of pharmaceutical compounds in urban wastewater: Removal, mass load and environmental risk after a secondary treatment—A review

    International Nuclear Information System (INIS)

    Verlicchi, P.; Al Aukidy, M.; Zambello, E.

    2012-01-01

    This review focuses on 118 pharmaceuticals, belonging to seventeen different therapeutic classes, detected in raw urban wastewater and effluent from an activated sludge system, a usual treatment adopted for urban wastewaters worldwide prior to final discharge into surface water bodies. Data pertaining to 244 conventional activated sludge systems and 20 membrane biological reactors are analysed and the observed ranges of variability of each selected compound in their influent and effluent reported, with particular reference to the substances detected most frequently and in higher concentrations. A snapshot of the ability of these systems to remove such compounds is provided by comparing their global removal efficiencies for each substance. Where possible, the study then evaluates the average daily mass load of the majority of detected pharmaceuticals exiting the secondary treatment step. The final part of the review provides an assessment of the environmental risk posed by their presence in the secondary effluent by means of the risk quotient that is the ratio between the average pharmaceutical concentration measured in the secondary effluent and the predicted no-effect concentration. Finally, mass load rankings of the compounds under review are compared with those based on their risk level. This analysis shows that the highest amounts discharged through secondary effluent pertain to one antihypertensive, and several beta-blockers and analgesics/anti-inflammatories, while the highest risk is posed by antibiotics and several psychiatric drugs and analgesics/anti-inflammatories. These results are reported with a view to aiding scientists and administrators in planning measures aiming to reduce the impact of treated urban wastewater discharge into surface water bodies. - Highlights: ► The review refers to 118 pharmaceuticals occurring in raw and treated wastewaters. ► Data from 264 municipal WWTPs with a CAS or an MBR were analysed. ► The removal rates achieved

  19. Occurrence of pharmaceutical compounds in urban wastewater: Removal, mass load and environmental risk after a secondary treatment-A review

    Energy Technology Data Exchange (ETDEWEB)

    Verlicchi, P., E-mail: paola.verlicchi@unife.it [Dept. of Engineering, University of Ferrara, Via Saragat 1, I-44122 Ferrara (Italy); Terra and AcquaTech Technopoles, Via Borsari 46, I-44121 Ferrara (Italy); Al Aukidy, M., E-mail: mustafakether.alaukidi@unife.it [Dept. of Engineering, University of Ferrara, Via Saragat 1, I-44122 Ferrara (Italy); Zambello, E., E-mail: elena.zambello@unife.it [Dept. of Engineering, University of Ferrara, Via Saragat 1, I-44122 Ferrara (Italy); Terra and AcquaTech Technopoles, Via Borsari 46, I-44121 Ferrara (Italy)

    2012-07-01

    This review focuses on 118 pharmaceuticals, belonging to seventeen different therapeutic classes, detected in raw urban wastewater and effluent from an activated sludge system, a usual treatment adopted for urban wastewaters worldwide prior to final discharge into surface water bodies. Data pertaining to 244 conventional activated sludge systems and 20 membrane biological reactors are analysed and the observed ranges of variability of each selected compound in their influent and effluent reported, with particular reference to the substances detected most frequently and in higher concentrations. A snapshot of the ability of these systems to remove such compounds is provided by comparing their global removal efficiencies for each substance. Where possible, the study then evaluates the average daily mass load of the majority of detected pharmaceuticals exiting the secondary treatment step. The final part of the review provides an assessment of the environmental risk posed by their presence in the secondary effluent by means of the risk quotient that is the ratio between the average pharmaceutical concentration measured in the secondary effluent and the predicted no-effect concentration. Finally, mass load rankings of the compounds under review are compared with those based on their risk level. This analysis shows that the highest amounts discharged through secondary effluent pertain to one antihypertensive, and several beta-blockers and analgesics/anti-inflammatories, while the highest risk is posed by antibiotics and several psychiatric drugs and analgesics/anti-inflammatories. These results are reported with a view to aiding scientists and administrators in planning measures aiming to reduce the impact of treated urban wastewater discharge into surface water bodies. - Highlights: Black-Right-Pointing-Pointer The review refers to 118 pharmaceuticals occurring in raw and treated wastewaters. Black-Right-Pointing-Pointer Data from 264 municipal WWTPs with a CAS or an

  20. Pharmaceutical cocrystals: a novel approach for oral bioavailability enhancement of drugs.

    Science.gov (United States)

    Chadha, Renu; Saini, Anupam; Arora, Poonam; Bhandari, Swati

    2012-01-01

    Solid dosage forms are by far the preferred drug delivery systems. However, these often face the problem of poor and erratic bioavailability during the drug development process. Numerous formulation strategies for drug delivery are currently under development, among which the solid forms such as polymorphs, solvates, salts, and cocrystals have been considered to be the most important for improving dissolution rate and bioavailability. Cocrystallization is a fairly new approach in pharmaceutical industry that can improve the solubility and, consequently, the bioactivity of the active pharmaceutical ingredient (API) without compromising its structural integrity. Pharmaceutical cocrystals have found their place in drug delivery, primarily due to their ability to produce alternative, viable solid forms when a more standard approach of salt and polymorph formation fails to deliver the desired objectives. Over the past few years, a number of papers have been published focusing on a broad range of subjects, from traditional crystal engineering to structure-property relationships of cocrystals. The present review, however, illustrates how the cocrystalline forms of APIs have improved their in vitro dissolution rate and in vivo bioavailability, often correlating well with their improved solubility as well.

  1. Occurrence of pharmaceutical compounds in wastewater process streams in Dublin, Ireland.

    Science.gov (United States)

    Lacey, Clair; Basha, Shaik; Morrissey, Anne; Tobin, John M

    2012-01-01

    The aim of this work is to establish baseline levels of pharmaceuticals in three wastewater treatment plant (WWTP) streams in the greater Dublin region to assess the removal efficiency of the selected WWTPs and to investigate the existence of any seasonal variability. Twenty compounds including several classes of antibiotics, acidic and basic pharmaceuticals, and prescribed medications were selected for investigation using a combination of membrane filtration, solid phase extraction (SPE) cleanup, and liquid chromatography-electrospray ionization tandem mass spectrometry. Fourteen of the selected compounds were found in the samples. Increased effluent concentrations, compared to influent concentrations, for a number of compounds (carbamazepine, clotrimazole, propranolol, nimesulide, furosemide, mefenamic acid, diclofenac, metoprolol, and gemfibrozil) were observed. The detected concentrations were generally below toxicity levels and based on current knowledge are unlikely to pose any threat to aquatic species. Mefenamic acid concentrations detected in both Leixlip and Swords effluents may potentially exert ecotoxicological effects with maximum risk quotients (i.e., ratio of predicted exposure concentration to predicted no effect concentration) of 4.04 and 1.33, respectively.

  2. Pharmaceutical products as emerging contaminant in water: relevance for developing nations and identification of critical compounds for Indian environment.

    Science.gov (United States)

    Chinnaiyan, Prakash; Thampi, Santosh G; Kumar, Mathava; Mini, K M

    2018-04-17

    Pharmaceuticals and personal care products (PPCPs) are contaminants of emerging concern and have been detected worldwide in water bodies in trace concentrations. Most of these emerging contaminants are not regulated in water quality standards except a few in the developed countries. In the case of developing countries, research in this direction is at a nascent stage. For the effective management of Pharmaceutical contaminants (PC) in developing countries, the relevance of PCs as an emerging contaminant has to be analyzed followed by regular monitoring of the environment. Considering the resource constraints, this could be accomplished by identifying the priority compounds which is again region specific and dependent on consumption behavior and pattern. In this work, relevance of pharmaceutical compound as emerging contaminant in water for a developing country like India is examined by considering the data pertaining to pharmaceutical consumption data. To identify the critical Pharmaceutical Contaminants to be monitored in the Indian environment, priority compounds from selected prioritization methods were screened with the compounds listed in National List of Essential Medicine (NLEM), India. Further, information on the number of publications on the compound as an emerging contaminant, data on monitoring studies in India and the number of brands marketing the compound in India were also analyzed. It is found that out of 195 compounds from different prioritization techniques, only 77 compounds were found relevant to India based on NLEM sorting.

  3. 78 FR 26375 - Food and Drug Administration/International Society for Pharmaceutical Engineering Co-Sponsorship...

    Science.gov (United States)

    2013-05-06

    ...] Food and Drug Administration/International Society for Pharmaceutical Engineering Co-Sponsorship... Society of Pharmaceutical Engineering (ISPE), is announcing a conference entitled ``Redefining the `C' in CGMP: Creating, Implementing and Sustaining a Culture of Quality'' Pharmaceutical Quality System (ICH...

  4. Impurities in Drug Products and Active Pharmaceutical Ingredients.

    Science.gov (United States)

    Kątny, M; Frankowski, M

    2017-05-04

    Analytical methods should be selective and fast. In modern times, scientists strive to meet the criteria of green chemistry, so they choose analytical procedures that are as short as possible and use the least toxic solvents. It is quite obvious that the products intended for human consumption should be characterized as completely as possible. The safety of a drug is dependent mainly on the impurities that it contains. High pressure liquid chromatography and ultra-high pressure liquid chromatography have been proposed as the main techniques for forced degradation and impurity profiling. The aim of this article was to characterize the relevant classification of drug impurities and to review the methods of impurities determination for atorvastatin (ATV) and duloxetine (DLX) (both in active pharmaceutical ingredients and in different dosage forms). These drugs have an impact on two systems of the human body: cardiac and nervous. Simple characteristics of ATV and DLX, their properties and specificity of action on the human body, are also included in this review. The analyzed pharmaceuticals-ATV (brand name Lipiron) and DLX (brand name Cymbalta)-were selected for this study based on annual rankings prepared by Information Medical Statistics.

  5. Occurrence of pharmaceuticals in Taiwan's surface waters: impact of waste streams from hospitals and pharmaceutical production facilities.

    Science.gov (United States)

    Lin, Angela Yu-Chen; Tsai, Yu-Ting

    2009-06-01

    We investigated the occurrence and distribution of pharmaceuticals (including antibiotics, estrogens, non-steroidal anti-inflammatory drugs (NSAIDs), beta-blockers, and lipid regulators) in three rivers and in the waste streams of six hospitals and four pharmaceutical production facilities in Taiwan. The most frequently detected pharmaceuticals were acetaminophen, erythromycin-H(2)O, sulfamethoxazole, and gemfibrozil. NSAIDs were the next most-often detected compounds, with a detection frequency >60%. The other analytes were not detected or were seen in only a few samples at trace concentrations. The present study demonstrates a significant discharge of human medications from hospital and drug production facilities into surface waters in the Taipei district. The high concentrations of pharmaceuticals found in the Sindian and Dahan rivers demonstrate the alarming degree to which they have been impacted by urban drainage (waste effluents from hospitals, households, and pharmaceutical production facilities). The ubiquitous occurrence at extremely high concentrations of acetaminophen and erythromycin-H(2)O in both rivers (up to 15.7 and 75.5 microg/L) and in wastewater from hospitals and pharmaceutical production facilities (up to 417.5 and 7.84 microg/L) was unique. This finding, in combination with acetaminophen's status as the drug most often prescribed by Taiwan's dominant clinical institute, suggests the potential use of acetaminophen as a molecular indicator of contamination of Taiwan's aqueous environments with untreated urban drainage.

  6. Analysis of pharmaceutical market of nootropic drugs in Ukraine

    Directory of Open Access Journals (Sweden)

    Олена Валеріївна Савельєва

    2015-11-01

    Full Text Available Diseases of the nervous system takes one of the key place in disease distribution and mortality all over the world. According to the data of WHO near 30 % of population takes nootropic drugs regularly. For older people this specific part in modern society increases inexorably. This parameter reaches approximately 50 %. Although it should be noted that incidence of nervous system diseases rises in young people too. These facts prove about actuality and much need for medicinal drugs of abovementioned class, particularly, nootropic drugs which are most commonly used for neurotherapy.Aim. The aim of this research was carrying-out of analytical review of pharmaceutical market of nootropic drugs in Ukraine.Methods. Statistical and marketing methods of investigation of electronic and paper sources of information. Object of research is an information about nootropic drugs registered in Ukraine.Results. It has been found that Ukrainian pharmaceuticals compose 57 % of nootropics’ market. There are 16 producing countries of nootropic drugs on Ukrainian market. Investigation of nootropics’ market showed that these drugs present in different dosage forms (tablets, capsules, syrups, pills, suspensions, solutions for injection, solutions for infusion, oral solutions, sachets, among which tablets prevail.Conclusions. Synthetic nootropic drugs prevail and compose 87 % of Ukrainian market, fraction of herbal drugs is 13 %, and they are characterized with monotonic content and represented with medicinal products of Ginkgo Biloba. Results concerning dosage forms’ ratio prove that herbal medicinal products having nootropic action are mostly presented in the form of tablets (67 %

  7. Markers of anthropogenic contamination: A validated method for quantification of pharmaceuticals, illicit drug metabolites, perfluorinated compounds, and plasticisers in sewage treatment effluent and rain runoff.

    Science.gov (United States)

    Wilkinson, John L; Swinden, Julian; Hooda, Peter S; Barker, James; Barton, Stephen

    2016-09-01

    An effective, specific and accurate method is presented for the quantification of 13 markers of anthropogenic contaminants in water using solid phase extraction (SPE) followed by high performance liquid chromatography (HPLC) tandem mass spectrometry (MS/MS). Validation was conducted according to the International Conference on Harmonisation (ICH) guidelines. Method recoveries ranged from 77 to 114% and limits of quantification between 0.75 and 4.91 ng/L. A study was undertaken to quantify the concentrations and loadings of the selected contaminants in 6 sewage treatment works (STW) effluent discharges as well as concentrations in 5 rain-driven street runoffs and field drainages. Detection frequencies in STW effluent ranged from 25% (ethinylestradiol) to 100% (benzoylecgonine, bisphenol-A (BPA), bisphenol-S (BPS) and diclofenac). Average concentrations of detected compounds in STW effluents ranged from 3.62 ng/L (ethinylestradiol) to 210 ng/L (BPA). Levels of perfluorinated compounds (PFCs) perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA) as well as the plasticiser BPA were found in street runoff at maximum levels of 1160 ng/L, 647 ng/L and 2405 ng/L respectively (8.52, 3.09 and 2.7 times more concentrated than maximum levels in STW effluents respectively). Rain-driven street runoff may have an effect on levels of PFCs and plasticisers in receiving rivers and should be further investigated. Together, this method with the 13 selected contaminants enables the quantification of various markers of anthropogenic pollutants: inter alia pharmaceuticals, illicit drugs and their metabolites from humans and improper disposal of drugs, while the plasticisers and perfluorinated compounds may also indicate contamination from industrial and transport activity (street runoff). Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Removal of Pharmaceutical Compounds from Hospital Wastewaters Using Nanomaterials: A Review

    Directory of Open Access Journals (Sweden)

    Hasan Bagheri

    2016-06-01

    Full Text Available Over the past few years, residual pharmaceuticals (antibiotics, anticonvulsants, antipyretics drugs, hormones have begun to be considered as emerging environmental pollutants due to their continuous input and persistence to aquatic ecosystem even at low concentrations. Therefore, the development of efficient, cost-effective, and stable methods and materials for the wastewaters treatment have gained more recognition in recent years. In the path of meeting these developments, nanomaterials have attracted much attention as economical, convenient and ecofriendly tools for removing of pharmaceuticals from the hospital wastewaters because of their unique properties. The present review deals with recent advances in removal and/or destruction of residual pharmaceutical in wastewater samples using nanomaterials including metal nanoparticles, carbon nanotubes and nanofilters. In spite of using a variety of nanomaterials to remove the residual of pharmaceuticals, there is still a dearth of successful applicability of them in industrial processes. Therefore, some defects of nanomaterials to be used for the removal of pharmaceutical contaminate in environmental samples and their impacts on human health and environment is briefly discussed.

  9. 42 CFR 423.132 - Public disclosure of pharmaceutical prices for equivalent drugs.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Public disclosure of pharmaceutical prices for equivalent drugs. 423.132 Section 423.132 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT... BENEFIT Benefits and Beneficiary Protections § 423.132 Public disclosure of pharmaceutical prices for...

  10. Using containerless methods to develop amorphous pharmaceuticals.

    Science.gov (United States)

    Weber, J K R; Benmore, C J; Suthar, K J; Tamalonis, A J; Alderman, O L G; Sendelbach, S; Kondev, V; Yarger, J; Rey, C A; Byrn, S R

    2017-01-01

    Many pipeline drugs have low solubility in their crystalline state and require compounding in special dosage forms to increase bioavailability for oral administration. The use of amorphous formulations increases solubility and uptake of active pharmaceutical ingredients. These forms are rapidly gaining commercial importance for both pre-clinical and clinical use. Synthesis of amorphous drugs was performed using an acoustic levitation containerless processing method and spray drying. The structure of the products was investigated using in-situ high energy X-ray diffraction. Selected solvents for processing drugs were investigated using acoustic levitation. The stability of amorphous samples was measured using X-ray diffraction. Samples processed using both spray drying and containerless synthesis were compared. We review methods for making amorphous pharmaceuticals and present data on materials made by containerless processing and spray drying. It was shown that containerless processing using acoustic levitation can be used to make phase-pure forms of drugs that are known to be difficult to amorphize. The stability and structure of the materials was investigated in the context of developing and making clinically useful formulations. Amorphous compounds are emerging as an important component of drug development and for the oral delivery of drugs with low solubility. Containerless techniques can be used to efficiently synthesize small quantities of pure amorphous forms that are potentially useful in pre-clinical trials and for use in the optimization of clinical products. Developing new pharmaceutical products is an essential enterprise to improve patient outcomes. The development and application of amorphous pharmaceuticals to increase absorption is rapidly gaining importance and it provides opportunities for breakthrough research on new drugs. There is an urgent need to solve problems associated with making formulations that are both stable and that provide high

  11. When 'drugs' become 'drugs': issues of pharmaceutical abuse in France from the 1960s to the 1990s.

    Science.gov (United States)

    Marchant, Alexandre

    2014-01-01

    Since the 1970s, media frenzies about drug addiction have focused mainly on illicit drugs taken by rebellious or marginalised addicts, relegating iatrogenic drug abuse, and policies and problems linked to psychotropic pharmaceuticals available by prescription or over-the-counter to the shadows. In this article I go beyond the division between illicit drugs and medicines still configuring both public representations and historiography: using archival materials from the 1960s-1990s in France, I highlight some blind spots in drug history. Firstly I demonstrate the role of pharmaceutical abuse in the career of addicts, and then examine regulation policies, which are the dark side, however complementary, of drug policies and prohibition. Finally, I analyse the role of physicians and pharmacists in this control, and discuss the various professional debates relating to the legal supply of psychoactive drugs. In all these issues, the frame of the Cold War context will also be highlighted.

  12. Old Yet New--Pharmaceuticals from Plants

    Science.gov (United States)

    Houghton, Peter J.

    2001-02-01

    Plants or their crude extracts have been used since prehistory to treat human ailments. Plants are still used in this way in many parts of the world, but Western scientific medicine has tended to isolate active compounds, or make derivatives of them, for use as drugs. Compounds produced by the plant have been important pharmaceuticals since the isolation of morphine almost two hundred years ago and new naturally occurring compounds such as paclitaxel are continually being introduced commercially. Bioactive molecules may also be produced from chemicals found in plants by chemical modification using synthetic chemistry or microorganisms (as in the production of steroids). A third major contribution of plant chemicals to drugs is their utilization as templates for the design of new compounds made by synthesis (e.g. the discovery of aspirin and related compounds from substances in willow bark). New pharmaceuticals from plants are being discovered by examining traditional medicines and by large-scale bioassay screening processes. In addition, the chemical survival systems of plants that exist in hostile environments are receiving increasing attention as leads to discover active compounds. The knowledge of botanical relationships helps find new sources of known compounds of interest and novel compounds with similar structures from related species. Future prospects for the discovery of new compounds from plants are broadened by the new technologies of gene manipulation, tissue culture, and combinatorial chemistry, so it is very likely that natural products from plants will continue to play an important role in the fight against disease.

  13. Occurrence of illicit drugs and selected pharmaceuticals in Slovak municipal wastewater.

    Science.gov (United States)

    Bodík, Igor; Mackuľak, Tomáš; Fáberová, Milota; Ivanová, Lucia

    2016-10-01

    We analyzed illicit drugs and their metabolites and pharmaceuticals in wastewater from 15 selected wastewater treatment plants (WWTPs) in Slovakia. Our results indicate that methamphetamine is one of the most commonly used illegal drugs in all the regions of Slovakia monitored in this study. Compared with the international results, the Slovak cities of Dunajská Streda (479 mg/day/1000inh) and Trnava (354 mg/day/1000inh) are among the cities with the largest numbers of methamphetamine users in Europe. These results indicate an increase in the incidence of drugs in big cities and in the satellite cities (Trnava and Dunajská Streda) near Bratislava. These results also confirm the police statistics about production and use of illicit drugs in Slovakia. The highest specific loads of cocaine were found in Bratislava (112 mg/day/1000inh), followed by Petržalka (74 mg/day/1000inh). Compared with other European cities, Bratislava and the other Slovak cities in this study have a relatively low number of COC consumers. The ecstasy load in wastewater from larger cities also significantly increased over the weekend and during music festivals. The highest 2-year mean concentrations of THC-COOH, a cannabis biomarker, were observed in the sewage from BA-Petržalka and BA-Central (191 and 171 ng/L, respectively). A first complex monitoring of pharmaceuticals in all therapeutic groups was also realized in selected Slovak WWTPs. Occurrence of wide spectrum of pharmaceuticals with very high concentrations as well as consumptions were observed mainly in small Slovak cities. Considering all 120 monitored pharmaceuticals, Valsartan had the highest concentrations: 6000 ng/L, on average.

  14. Occurrence of pharmaceuticals, hormones, and organic wastewater compounds in Pennsylvania waters, 2006-09

    Science.gov (United States)

    Reif, Andrew G.; Crawford, J. Kent; Loper, Connie A.; Proctor, Arianne; Manning, Rhonda; Titler, Robert

    2012-01-01

    Concern over the presence of contaminants of emerging concern, such as pharmaceutical compounds, hormones, and organic wastewater compounds (OWCs), in waters of the United States and elsewhere is growing. Laboratory techniques developed within the last decade or new techniques currently under development within the U.S. Geological Survey now allow these compounds to be measured at concentrations in nanograms per liter. These new laboratory techniques were used in a reconnaissance study conducted by the U.S. Geological Survey, in cooperation with the Pennsylvania Department of Environmental Protection, to determine the occurrence of contaminants of emerging concern in streams, streambed sediment, and groundwater of Pennsylvania. Compounds analyzed for in the study are pharmaceuticals (human and veterinary drugs), hormones (natural and synthetic), and OWCs (detergents, fragrances, pesticides, industrial compounds, disinfectants, polycyclic aromatic hydrocarbons, fire retardants and plasticizers). Reconnaissance sampling was conducted from 2006 to 2009 to identify contaminants of emerging concern in (1) groundwater from wells used to supply livestock, (2) streamwater upstream and downstream from animal feeding operations, (3) streamwater upstream from and streamwater and streambed sediment downstream from municipal wastewater effluent discharges, (4) streamwater from sites within 5 miles of drinking-water intakes, and (5) streamwater and streambed sediment where fish health assessments were conducted. Of the 44 pharmaceutical compounds analyzed in groundwater samples collected in 2006 from six wells used to supply livestock, only cotinine (a nicotine metabolite) and the antibiotics tylosin and sulfamethoxazole were detected. The maximum concentration of any contaminant of emerging concern was 24 nanograms per liter (ng/L) for cotinine, and was detected in a groundwater sample from a Lebanon County, Pa., well. Seven pharmaceutical compounds including acetaminophen

  15. Development of a common priority list of pharmaceuticals relevant for the water cycle

    NARCIS (Netherlands)

    de Voogt, P.; Janex-Habibi, M.-L.; Sacher, F.; Puijker, L.; Mons, M.

    2009-01-01

    Pharmaceutically active compounds (PhACs), including prescription drugs, over-the-counter medications, drugs used in hospitals and veterinary drugs, have been found throughout the water cycle. A desk study was initiated by the Global Water Research Coalition to consolidate a uniform selection of

  16. Continuous flow technology vs. the batch-by-batch approach to produce pharmaceutical compounds.

    Science.gov (United States)

    Cole, Kevin P; Johnson, Martin D

    2018-01-01

    For the manufacture of small molecule drugs, many pharmaceutical innovator companies have recently invested in continuous processing, which can offer significant technical and economic advantages over traditional batch methodology. This Expert Review will describe the reasons for this interest as well as many considerations and challenges that exist today concerning continuous manufacturing. Areas covered: Continuous processing is defined and many reasons for its adoption are described. The current state of continuous drug substance manufacturing within the pharmaceutical industry is summarized. Current key challenges to implementation of continuous manufacturing are highlighted, and an outlook provided regarding the prospects for continuous within the industry. Expert commentary: Continuous processing at Lilly has been a journey that started with the need for increased safety and capability. Over twelve years the original small, dedicated group has grown to more than 100 Lilly employees in discovery, development, quality, manufacturing, and regulatory designing in continuous drug substance processing. Recently we have focused on linked continuous unit operations for the purpose of all-at-once pharmaceutical manufacturing, but the technical and business drivers that existed in the very beginning for stand-alone continuous unit operations in hybrid processes have persisted, which merits investment in both approaches.

  17. RFID in the pharmaceutical industry: addressing counterfeits with technology.

    Science.gov (United States)

    Taylor, Douglas

    2014-11-01

    The use of Radio Frequency Identification (RFID) in the pharmaceutical industry has grown in recent years. The technology has matured from its specialized tracking and retail uses to a systemic part of supply chain management in international pharmaceutical production and distribution. Counterfeit drugs, however, remain a significant challenge for governments, pharmaceutical companies, clinicians, and patients and the use of RFID to track these compounds represents an opportunity for development. This paper discusses the medical, technological, and economic factors that support widespread adoption of RFID technology in the pharmaceutical industry in an effort to prevent counterfeit medicines from harming patients and brand equity.

  18. Pharmaceutical assistance in the enteral administration of drugs: choosing the appropriate pharmaceutical formulation

    Directory of Open Access Journals (Sweden)

    Gisele de Lima

    2009-03-01

    Full Text Available Objective: To study solid medications for oral delivery on the formulary of Hospital Israelita Albert Einstein (HIAE, investigating the  possibility of using these drugs through enteral feeding tubes, and recommending appropriate administration. Methods: Study carried out through survey of solid medications for oral delivery included on the formulary of HIAE, literature review, and analysis of medication monographs, manufacturer information and pharmacotechnical data of active ingredients and excipients. It was observed the factors that might hinder or complicate the administration of these drugs though enteral tubes, and was drawn an information chart with recommendations about drug administration in this context. Rresults: The study evaluated 234 medications; and the main problems of administering these drugs through enteral feeding tubes were as follows: changes in drug pharmacokinetics (38; gastrointestinal damage (9; risk of obstruction (40, drug-nutrient interactions (7; biological hazards (5 and no information (33. Cconclusions: Compiling this information helps the healthcare team to choose the appropriate pharmaceutical formulation for medications administered through enteral tubes, and may help identify adverse events related to this technique.

  19. From crystal to compound: structure-based antimalarial drug discovery.

    Science.gov (United States)

    Drinkwater, Nyssa; McGowan, Sheena

    2014-08-01

    Despite a century of control and eradication campaigns, malaria remains one of the world's most devastating diseases. Our once-powerful therapeutic weapons are losing the war against the Plasmodium parasite, whose ability to rapidly develop and spread drug resistance hamper past and present malaria-control efforts. Finding new and effective treatments for malaria is now a top global health priority, fuelling an increase in funding and promoting open-source collaborations between researchers and pharmaceutical consortia around the world. The result of this is rapid advances in drug discovery approaches and technologies, with three major methods for antimalarial drug development emerging: (i) chemistry-based, (ii) target-based, and (iii) cell-based. Common to all three of these approaches is the unique ability of structural biology to inform and accelerate drug development. Where possible, SBDD (structure-based drug discovery) is a foundation for antimalarial drug development programmes, and has been invaluable to the development of a number of current pre-clinical and clinical candidates. However, as we expand our understanding of the malarial life cycle and mechanisms of resistance development, SBDD as a field must continue to evolve in order to develop compounds that adhere to the ideal characteristics for novel antimalarial therapeutics and to avoid high attrition rates pre- and post-clinic. In the present review, we aim to examine the contribution that SBDD has made to current antimalarial drug development efforts, covering hit discovery to lead optimization and prevention of parasite resistance. Finally, the potential for structural biology, particularly high-throughput structural genomics programmes, to identify future targets for drug discovery are discussed.

  20. Application of Incoherent Inelastic Neutron Scattering in Pharmaceutical Analysis

    DEFF Research Database (Denmark)

    Bordallo, Heloisa N.; A. Zakharov, Boris; Boidyreva, E.V.

    2012-01-01

    This study centers on the use of inelastic neutron scattering as an alternative tool for physical characterization of solid pharmaceutical drugs. On the basis of such approach, relaxation processes in the pharmaceutical compound phenacetin (p-ethoxyacetanilide, C(10)H(13)NO(2)) were evidenced...... contributes to understanding the relationships between intermolecular hydrogen bonds, intramolecular dynamics, and conformational flexibility in pharmaceuticals on a molecular level, which can help in evaluating phase stability with respect to temperature variations on processing or on storage, and is related...

  1. Electrosprayed nanoparticles for drug delivery and pharmaceutical applications

    Science.gov (United States)

    Sridhar, Radhakrishnan; Ramakrishna, Seeram

    2013-01-01

    Nanotechnology based Pharma has emerged significantly and has influenced the Pharma industry up to a considerable extent. Nanoparticles technology holds a good share of the nanotech Pharma and is significant in comparison with the other domains. Electrospraying technology answers the potential needs of nanoparticle production such as scalability, reproducibility, effective encapsulation etc. Many drugs have been electrosprayed with and without polymer carriers. Drug release characteristics are improved with the incorporation of biodegradable polymer carriers which sustain the release of encapsulated drug. Electrospraying is acknowledged as an important technique for the preparation of nanoparticles with respect to pharmaceutical applications. Herein we attempted to consolidate the reports pertaining to electrospraying and their corresponding therapeutic application area. PMID:23512013

  2. Drug-likeness analysis of traditional Chinese medicines: 2. Characterization of scaffold architectures for drug-like compounds, non-drug-like compounds, and natural compounds from traditional Chinese medicines.

    Science.gov (United States)

    Tian, Sheng; Li, Youyong; Wang, Junmei; Xu, Xiaojie; Xu, Lei; Wang, Xiaohong; Chen, Lei; Hou, Tingjun

    2013-01-21

    In order to better understand the structural features of natural compounds from traditional Chinese medicines, the scaffold architectures of drug-like compounds in MACCS-II Drug Data Report (MDDR), non-drug-like compounds in Available Chemical Directory (ACD), and natural compounds in Traditional Chinese Medicine Compound Database (TCMCD) were explored and compared. First, the different scaffolds were extracted from ACD, MDDR and TCMCD by using three scaffold representations, including Murcko frameworks, Scaffold Tree, and ring systems with different complexity and side chains. Then, by examining the accumulative frequency of the scaffolds in each dataset, we observed that the Level 1 scaffolds of the Scaffold Tree offer advantages over the other scaffold architectures to represent the scaffold diversity of the compound libraries. By comparing the similarity of the scaffold architectures presented in MDDR, ACD and TCMCD, structural overlaps were observed not only between MDDR and TCMCD but also between MDDR and ACD. Finally, Tree Maps were used to cluster the Level 1 scaffolds of the Scaffold Tree and visualize the scaffold space of the three datasets. The analysis of the scaffold architectures of MDDR, ACD and TCMCD shows that, on average, drug-like molecules in MDDR have the highest diversity while natural compounds in TCMCD have the highest complexity. According to the Tree Maps, it can be observed that the Level 1 scaffolds present in MDDR have higher diversity than those presented in TCMCD and ACD. However, some representative scaffolds in MDDR with high frequency show structural similarities to those in TCMCD and ACD, suggesting that some scaffolds in TCMCD and ACD may be potentially drug-like fragments for fragment-based and de novo drug design.

  3. Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation.

    Science.gov (United States)

    Patil, Hemlata; Tiwari, Roshan V; Repka, Michael A

    2016-02-01

    Hot-melt extrusion (HME) is a promising technology for the production of new chemical entities in the developmental pipeline and for improving products already on the market. In drug discovery and development, industry estimates that more than 50% of active pharmaceutical ingredients currently used belong to the biopharmaceutical classification system II (BCS class II), which are characterized as poorly water-soluble compounds and result in formulations with low bioavailability. Therefore, there is a critical need for the pharmaceutical industry to develop formulations that will enhance the solubility and ultimately the bioavailability of these compounds. HME technology also offers an opportunity to earn intellectual property, which is evident from an increasing number of patents and publications that have included it as a novel pharmaceutical formulation technology over the past decades. This review had a threefold objective. First, it sought to provide an overview of HME principles and present detailed engineered extrusion equipment designs. Second, it included a number of published reports on the application of HME techniques that covered the fields of solid dispersions, microencapsulation, taste masking, targeted drug delivery systems, sustained release, films, nanotechnology, floating drug delivery systems, implants, and continuous manufacturing using the wet granulation process. Lastly, this review discussed the importance of using the quality by design approach in drug development, evaluated the process analytical technology used in pharmaceutical HME monitoring and control, discussed techniques used in HME, and emphasized the potential for monitoring and controlling hot-melt technology.

  4. Synthetic biology approaches in drug discovery and pharmaceutical biotechnology.

    Science.gov (United States)

    Neumann, Heinz; Neumann-Staubitz, Petra

    2010-06-01

    Synthetic biology is the attempt to apply the concepts of engineering to biological systems with the aim to create organisms with new emergent properties. These organisms might have desirable novel biosynthetic capabilities, act as biosensors or help us to understand the intricacies of living systems. This approach has the potential to assist the discovery and production of pharmaceutical compounds at various stages. New sources of bioactive compounds can be created in the form of genetically encoded small molecule libraries. The recombination of individual parts has been employed to design proteins that act as biosensors, which could be used to identify and quantify molecules of interest. New biosynthetic pathways may be designed by stitching together enzymes with desired activities, and genetic code expansion can be used to introduce new functionalities into peptides and proteins to increase their chemical scope and biological stability. This review aims to give an insight into recently developed individual components and modules that might serve as parts in a synthetic biology approach to pharmaceutical biotechnology.

  5. Stacking-cyclodextrin-microchip electrokinetic chromatographic determination of gabapentinoid drugs in pharmaceutical and biological matrices.

    Science.gov (United States)

    Zeid, Abdallah M; Kaji, Noritada; Nasr, Jenny Jeehan M; Belal, Fathalla F; Baba, Yoshinobu; Walash, Mohamed I

    2017-06-23

    A facile, rapid, and highly sensitive microchip-based electrokinetic chromatographic method was developed for the simultaneous analysis of two gabapentinoid drugs, gabapentin (GPN) and pregabalin (PGN). Both drugs were first reacted with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F) via nucleophilic substitution reactions to yield highly fluorescent products with λ ex/em 470/540nm. Analyses of both fluorescently labeled compounds were achieved within 200s in a poly(methyl methacrylate) (PMMA) microchip with a 30mm separation channel. Optimum separation was achieved using a borate buffer (pH 9.0) solution containing methylcellulose and β-cyclodextrin (β-CD) as buffer additives. Methylcellulose acted as a dynamic coating to prevent adsorption of the studied compounds on the inner surfaces of the microchannels, while β-CD acted as a pseudo-stationary phase to improve the separation efficiency between the labeled drugs with high resolution (Rs>7). The fluorescence intensities of the labeled drugs were measured using a light emitting diode-induced fluorescence detector at 540nm after excitation at 470nm. The sensitivity of the method was enhanced 14- and 17-fold for PGN and GPN, respectively by field-amplified stacking relative to traditional pinched injection so that it could quantify 10ngmL -1 for both analytes, with a detection limit lower than 3ngmL -1 . The developed method was efficiently applied to analyze PGN and GPN in their pharmaceutical dosage forms and in biological fluids. The extraction recoveries of the studied drugs from plasma and urine samples were more than 89% with%RSD values lower than 6.2. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. RESEARCH OF CONDITION OF PUBLIC DRUG ASSISTANCE DURING INDEPENDENCE YEARS OF UKRAINE - FORMATION OF PHARMACEUTICAL MARKET

    Directory of Open Access Journals (Sweden)

    V. O. Boryshchuk

    2015-10-01

    Full Text Available The aim of the research was to study the correspondence of existing legislative and regulatory requirements of the pharmaceutical industry development, the analysis of the formation of the Ukrainian pharmaceutical market, the condition of drug assistance according to European requirements and recommendations of the WHO. For the study archival materials, publications in scientific journals, and mass media were used, laws and provisions regulating pharmaceutical activity were studied and a survey among citizens was conducted. Systematic and logical methods, analytical and comparative analysis were applied, and own researches were performed. For 22 years of Ukrainian statehood formation the following institutes were created: Pharmacological College, Pharmacopoeia Committee and State Service for Quality Control of Drugs which were transported to other institutes. Important laws were adopted: the Law of Ukraine «On Medicines», the Law of Ukraine «On small-scale privatization», the Law of Ukraine «On large-scale privatization» and others, which contributed to the formation and development of the pharmaceutical market. In comparison with 1990 the amount of drugstore chains increased two and a half times and in 2013 in the country already worked 15 566 drugstores, including 3 025 in villages. Specific peculiarity of pharmaceutical market formation in Ukraine was the creation of powerful own regional and all-Ukrainian drugstore chains, that is greatly different from such situation in EU countries, where the legislation allows to have only one or two drugstores. As the result of pharmaceutical market formation the drugs nomenclature increased eight times and now makes up more than 20 000 names, including 92.4 % generic drugs. According to publications, Ukraine lacks about 40 % of drug molecules needed for medical treatment, and 30 % of studied drugs are not proved. There is the problem of uncontrollable turnover and drugs consumption in Ukraine

  7. Fenton-like reaction: a possible way to efficiently remove illicit drugs and pharmaceuticals from wastewater.

    Science.gov (United States)

    Mackuľak, Tomáš; Mosný, Michal; Grabic, Roman; Golovko, Oksana; Koba, Olga; Birošová, Lucia

    2015-03-01

    We analyzed 13 psychoactive pharmaceuticals, illicit drugs and their metabolites in wastewater treatment plant influent and effluent and the possibility of their degradation by biological and chemical processes. Tramadol (413-853 ng/L) and methamphetamine (460-682 ng/L) were the most concentrated compounds in the wastewater in winter and summer, respectively. A significant decrease in the concentration of tramadol in wastewater was measured during the summer. The lowest efficiency was observed for tramadol, venlafaxine, citalopram and oxazepam (∼ 10%) and the highest efficiency was observed for amphetamine and THC-COOH (∼ 80%). The efficiency of compound degradation via the Fenton reaction, a modified Fenton reaction and different degradation (by algae, wood-rotting fungi and enzymes at influent versus effluent) was determined. The Fenton reaction and its modification were efficient at eliminating these substances in comparison with the tested biological processes. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Occurrence of pharmaceuticals, hormones, and perfluorinated compounds in groundwater in Taiwan.

    Science.gov (United States)

    Lin, Yen-Ching; Lai, Webber Wei-Po; Tung, Hsin-hsin; Lin, Angela Yu-Chen

    2015-05-01

    In this work, we investigated the emerging pollutants in Taiwanese groundwater for the first time and correlated their presence with possible contamination sources. Fifty target pharmaceuticals and perfluorinated chemicals in groundwater were mostly present at ng L(-1) concentrations, except for 17α-ethynylestradiol, sulfamethoxazole, and acetaminophen (maximums of 1822, 1820, and 1036 ng L(-1), respectively). Perfluorinated compounds were detected with the highest frequencies in groundwater at almost all of the sample sites, especially short-chained perfluorinated carboxylates, which were easily transferred to the groundwater. The results indicate that the compounds found to have high detection frequencies and concentrations in groundwater are similar to those found in other countries around the world. Most common pharmaceuticals that contain hydrophilic groups, such as sulfonamide antibiotics and caffeine, are easily transported through surface waters to groundwater. The results also indicated that the persistent natures of emerging contaminants with high detection frequencies in surface water and groundwater, such as perfluorooctanesulfonate (risk quotient >1), caffeine, and carbamazepine, should be further studied and evaluated.

  9. Radiation chemistry of salicylic and methyl substituted salicylic acids: Models for the radiation chemistry of pharmaceutical compounds

    International Nuclear Information System (INIS)

    Ayatollahi, Shakiba; Kalnina, Daina; Song, Weihua; Turks, Maris; Cooper, William J.

    2013-01-01

    Salicylic acid and its derivatives are components of many medications and moieties found in numerous pharmaceutical compounds. They have been used as models for various pharmaceutical compounds in pharmacological studies, for the treatment of pharmaceuticals and personal care products (PPCPs), and, reactions with natural organic matter (NOM). In this study, the radiation chemistry of benzoic acid, salicylic acid and four methyl substituted salicylic acids (MSA) is reported. The absolute bimolecular reaction rate constants for hydroxyl radical reaction with benzoic and salicylic acids as well as 3-methyl-, 4-methyl-, 5-methyl-, and 6-methyl-salicylic acid were determined (5.86±0.54)×10 9 , (1.07±0.07)×10 10 , (7.48±0.17)×10 9 , (7.31±0.29)×10 9 , (5.47±0.25)×10 9 , (6.94±0.10)×10 9 (M −1 s −1 ), respectively. The hydrated electron reaction rate constants were measured (3.02±0.10)×10 9 , (8.98±0.27)×10 9 , (5.39±0.21)×10 9 , (4.33±0.17)×10 9 , (4.72±0.15)×10 9 , (1.42±0.02)×10 9 (M −1 s −1 ), respectively. The transient absorption spectra for the six model compounds were examined and their role as model compounds for the radiation chemistry of pharmaceuticals investigated. - Highlights: • Free radical chemistry of salicylic and 4 methyl salicylic acids is investigated. • The transient absorptions spectra for model compounds are measured. • Absolute bimolecular reaction rate constants for hydroxyl radical are determined. • Solvated electron reaction rate constants are calculated. • The use of salicylic acids as models for pharmaceuticals is explored

  10. Neuromarketing techniques in pharmaceutical drugs advertising. A discussion and agenda for future research.

    Science.gov (United States)

    Orzan, G; Zara, I A; Purcarea, V L

    2012-12-15

    Recent years have seen an "explosion" in the abilities of scientists to use neuroscience in new domains. Unfortunately, it is little known and reported on how advertising companies make more effective pharmaceutical drugs commercials. The purpose of this paper is to analyze how neuromarketing techniques may impact the consumer response to pharmaceutical advertising campaigns. The result shows that using neuromarketing methods a pharmaceutical company can better understand the conscious and unconscious consumer's thoughts and tailor specific marketing messages.

  11. [Me-too pharmaceuticals -- marketing-strategies of drug producers and drug purchasers. Example: non-ionic contrast media].

    Science.gov (United States)

    Wild, C; Puig, S

    2004-11-01

    In the context of increasing economic pressure upon on hospital budgets, it is inevitable that central and standardized purchasing of pharmaceuticals must be considered. It was the aim of this assessment to analyse the many different non-ionic contrast media/CM products on the actual "clinical relevance of the differences" in order to give advice for a more concerted purchasing of CM. The assessment was commissioned by a large scale Austrian hospital cooperation; it can be regarded as the beginning of a broad strategy against the many new, only rarely innovative, but nevertheless patent-protected pharmaceuticals. Eight different non-ionic contrast media - used in routine care - were compared for their physico-chemical characteristics: osmolality, nephrotoxicity, viscosity, hydrophilicity and electric charge. In a systematic review 193 publications were analysed. The examined CM show similar pharmacokinetic and -dynamic attributes, and no differences of clinical relevance. An optimisation of purchasing pharmaceuticals by standardisation of the range of products takes place in the context of common strategies of producers and buying agents in marketing-economies. The strategies of the pharmaceutical industry (patent protection of me-too drugs, high-price-policy, extensive marketing of up to 40 % of revenue) and the counter-strategies of the central hospital purchasers (market concentration, drug commissions, institutional measures to disentangle interests) are presented - exemplified by contrast media - in this article.

  12. Synthetic biology for pharmaceutical drug discovery

    Directory of Open Access Journals (Sweden)

    Trosset JY

    2015-12-01

    Full Text Available Jean-Yves Trosset,1 Pablo Carbonell2,3 1Bioinformation Research Laboratory, Sup’Biotech, Villejuif, France; 2Faculty of Life Sciences, SYNBIOCHEM Centre, Manchester Institute of Biotechnology, University of Manchester, Manchester, UK; 3Department of Experimental and Health Sciences (DCEXS, Research Programme on Biomedical Informatics (GRIB, Hospital del Mar Medical Research Institute (IMIM, Universitat Pompeu Fabra (UPF, Barcelona, Spain Abstract: Synthetic biology (SB is an emerging discipline, which is slowly reorienting the field of drug discovery. For thousands of years, living organisms such as plants were the major source of human medicines. The difficulty in resynthesizing natural products, however, often turned pharmaceutical industries away from this rich source for human medicine. More recently, progress on transformation through genetic manipulation of biosynthetic units in microorganisms has opened the possibility of in-depth exploration of the large chemical space of natural products derivatives. Success of SB in drug synthesis culminated with the bioproduction of artemisinin by microorganisms, a tour de force in protein and metabolic engineering. Today, synthetic cells are not only used as biofactories but also used as cell-based screening platforms for both target-based and phenotypic-based approaches. Engineered genetic circuits in synthetic cells are also used to decipher disease mechanisms or drug mechanism of actions and to study cell–cell communication within bacteria consortia. This review presents latest developments of SB in the field of drug discovery, including some challenging issues such as drug resistance and drug toxicity. Keywords: metabolic engineering, plant synthetic biology, natural products, synthetic quorum sensing, drug resistance

  13. Correlation between octanol/water and liposome/water distribution coefficients and drug absorption of a set of pharmacologically active compounds.

    Science.gov (United States)

    Esteves, Freddy; Moutinho, Carla; Matos, Carla

    2013-06-01

    Absorption and consequent therapeutic action are key issues in the development of new drugs by the pharmaceutical industry. In this sense, different models can be used to simulate biological membranes to predict the absorption of a drug. This work compared the octanol/water and the liposome/water models. The parameters used to relate the two models were the distribution coefficients between liposomes and water and octanol and water and the fraction of drug orally absorbed. For this study, 66 drugs were collected from literature sources and divided into four groups according to charge and ionization degree: neutral; positively charged; negatively charged; and partially ionized/zwitterionic. The results show a satisfactory linear correlation between the octanol and liposome systems for the neutral (R²= 0.9324) and partially ionized compounds (R²= 0.9367), contrary to the positive (R²= 0.4684) and negatively charged compounds (R²= 0.1487). In the case of neutral drugs, results were similar in both models because of the high fraction orally absorbed. However, for the charged drugs (positively, negatively, and partially ionized/zwitterionic), the liposomal model has a more-appropriate correlation with absorption than the octanol model. These results show that the neutral compounds only interact with membranes through hydrophobic bonds, whereas charged drugs favor electrostatic interactions established with the liposomes. With this work, we concluded that liposomes may be a more-appropriate biomembrane model than octanol for charged compounds.

  14. Attitudes and beliefs regarding direct-to-consumer advertising of pharmaceutical drugs: an exploratory comparison of physicians and pharmaceutical sales representatives.

    Science.gov (United States)

    Schulz, Steven A; Broekemier, Gregory M; Burkink, Tim J

    2014-01-01

    Even with many changes in regulation in recent years, direct-to-consumer advertising (DTCA) of pharmaceutical drugs remains a complicated and contentious issue. Many in our society argue for increased legislation of DTCA while others believe that DTCA serves a useful purpose and should not be overregulated. This study was designed to compare attitudes and beliefs regarding DTCA held by two key stakeholder groups, physicians and pharmaceutical sales representatives. A questionnaire was created, pretested, and administered to 30 physicians and 30 pharmaceutical sales representatives to investigate these issues. Significant differences between these two groups were found and implications for DTCA are discussed.

  15. Pharmaceuticals as Groundwater Tracers - Applications and Limitations

    Science.gov (United States)

    Scheytt, T. J.; Mersmann, P.; Heberer, T.

    2003-12-01

    Pharmaceutically active substances and metabolites are found at concentrations up to the microgram/L-level in groundwater samples from the Berlin (Germany) area and from several other places world wide. Among the compounds detected in groundwater are clofibric acid, propyphenazone, diclofenac, ibuprofen, and carbamazepine. Clofibric acid, the active metabolite of clofibrate and etofibrate (blood lipid regulators) is detected in groundwater at maximum concentrations of 7300 ng/L. Among the most important input paths of drugs are excretion and disposal into the sewage system. Groundwater contamination is likely to be due to leaky sewage systems, influent streams, bank filtration, and irrigation with effluent water from sewage treatment plants. There are no known natural sources of the above mentioned pharmaceuticals. The use of pharmaceuticals as tracers may include: (a) Quantification of infiltration from underground septic tanks (b) Detection of leaky sewage systems / leaky sewage pipes (c) Estimation of the effectiveness of sewage treatment plants (d) Identification of transport pathways of other organic compounds (e) Quantification of surface water / groundwater interaction (f) Characterization of the biodegradation potential. The use of pharmaceuticals as tracers is limited by variations in input. These variations depend on the amount of drugs prescribed and used in the study area, the social structure of the community, the amount of hospital discharge, and temporal concentration variations. Furthermore, the analysis of trace amounts of pharmaceuticals is sophisticated and expensive and may therefore limit the applicability of pharmaceuticals as tracers. Finally, the transport and degradation behavior of pharmaceuticals is not fully understood. Preliminary experiments in the laboratory were conducted using sediment material and groundwater from the Berlin area to evaluate the transport and sorption behavior of selected drugs. Results of the column experiments

  16. Risk screening of pharmaceutical compounds in Romanian aquatic environment.

    Science.gov (United States)

    Gheorghe, Stefania; Petre, Jana; Lucaciu, Irina; Stoica, Catalina; Nita-Lazar, Mihai

    2016-06-01

    The aquatic environment is under increased pressure by pharmaceutically active compounds (PhACs) due to anthropogenic activities. In spite of being found at very low concentrations (ng/L to μg/L) in the environment, PhACs represent a real danger to aquatic ecosystems due to their bioaccumulation and long-term effects. In this study, the presence in the aquatic environment of six non-steroidal anti-inflammatory drugs (ibuprofen, diclofenac, acetaminophen, naproxen, indomethacin, and ketoprofen), caffeine, and carbamazepine were monitored. Moreover, their aquatic risk and ecotoxicity by three biological models were evaluated. The monitoring studies performed in Romania showed that all studied PhACs were naturally present at concentrations >0.01 μg/L, pointing out the necessity to perform further toxicity tests for environmental risk assessment. The toxicity studies were carried out on aquatic organisms or bacteria and they indicated, for most of the tested PhACs, an insignificant or low toxicity effects: lethal concentrations (LC50) on fish Cyprinus carpio ranged from 42.60 mg/L to more than 100 mg/L; effective concentrations (EC50) on planktonic crustacean Daphnia magna ranged from 11.02 mg/L to more than 100 mg/L; inhibitory concentrations (IC50)/microbial toxic concentrations (MTC) on Vibrio fischeri and other bacterial strains ranged from 7.02 mg/L to more than 100 mg/L. The PhAC aquatic risk was assessed by using the ratio between measured environmental concentration (MEC) and predicted no effect concentration (PNEC) calculated for each type of organism. The average of quotient risks (RQs) revealed that the presence of these compounds in Romania's aquatic environment induced a lower or moderate aquatic risk.

  17. Neuromarketing techniques in pharmaceutical drugs advertising. A discussion and agenda for future research

    Science.gov (United States)

    Orzan, G; Zara, IA; Purcarea, VL

    2012-01-01

    Recent years have seen an “explosion" in the abilities of scientists to use neuroscience in new domains. Unfortunately, it is little known and reported on how advertising companies make more effective pharmaceutical drugs commercials. The purpose of this paper is to analyze how neuromarketing techniques may impact the consumer response to pharmaceutical advertising campaigns. The result shows that using neuromarketing methods a pharmaceutical company can better understand the conscious and unconscious consumer’s thoughts and tailor specific marketing messages. PMID:23346245

  18. Pharmaceutical structure montages as catalysts for design and discovery.

    Science.gov (United States)

    Njarðarson, Jon T

    2012-05-01

    Majority of pharmaceuticals are small molecule organic compounds. Their structures are most effectively described and communicated using the graphical language of organic chemistry. A few years ago we decided to harness this powerful language to create new educational tools that could serve well for data mining and as catalysts for discovery. The results were the Top 200 drug posters, which we have posted online for everyone to enjoy and update yearly. This article details the origin and motivation for our design and highlights the value of this graphical format by presenting and analyzing a new pharmaceutical structure montage (poster) focused on US FDA approved drugs in 2011.

  19. Adequacy of pharmacological information provided in pharmaceutical drug advertisements in African medical journals.

    Directory of Open Access Journals (Sweden)

    Oshikoya KA

    2009-06-01

    Full Text Available Pharmaceutical advertisement of drugs is a means of advocating drug use and their selling but not a substitute for drug formulary to guide physicians in safe prescribing. Objectives: To evaluate drug advertisements in Nigerian and other African medical journals for their adequacy of pharmacological information. Methods: Twenty four issues from each of West African Journal of Medicine (WAJM, East African Medical Journal (EAMJ, South African Medical Journal (SAMJ, Nigerian Medical Practitioner (NMP, Nigerian Quarterly Journal of Hospital Medicine (NQJHM and Nigerian Postgraduate Medical Journal (NPMJ were reviewed. While EAMJ, SAMJ and NMP are published monthly, the WAJM, NQJHM and NPMJ are published quarterly. The monthly journals were reviewed between January 2005 and December 2006, and the quarterly journals between January 2001 and December 2006. The drug information with regards to brand/non-proprietary name, pharmacological data, clinical information, pharmaceutical information and legal aspects was evaluated as per World Health Organisation (WHO criteria. Counts in all categories were collated for each advertiser.Results: Forty one pharmaceutical companies made 192 advertisements. 112 (58.3% of these advertisements were made in the African medical journals. Pfizer (20.3% and Swipha (12.5% topped the list of the advertising companies. Four (2.1% adverts mentioned generic names only, 157 (81.8% mentioned clinical indications. Adults and children dosage (39.6%, use in special situations such as pregnancy and renal or liver problems (36.5%, adverse effects (30.2%, average duration of treatment (26.0%, and potential for interaction with other drugs (18.7% were less discussed. Pharmaceutical information such as available dosage forms and product and package information {summary of the generic and proprietary names, the formulation strength, active ingredient, route of administration, batch number, manufactured and expiry dates, and the

  20. How do pharmaceutical companies handle consumer adverse drug reaction reports? An overview based on a survey of French drug safety managers and officers.

    Science.gov (United States)

    Fleuranceau-Morel, P

    2002-01-01

    It is surprising to see how consumer Adverse Drug Reaction (ADR) reports have been continuously increasing for the last few years in Europe. This probably results from the influence of United States (US) market where the patients feels justified in telephoning the pharmaceutical companies directly with queries regarding their treatment. The growing number of alternative sources of information (e.g. health and popular magazines, spots on radio and TV etc.) to which a consumer is exposed has added to this growth too. The changing relationship between patients and doctors may also contribute to this phenomenon. It is then interesting to evaluate the way pharmaceutical companies currently deal with consumer ADR reports. The management of consumer ADR reporting was investigated by means of a questionnaire sent to 46 French drug safety managers and drug safety officers (DSOs) of multinational pharmaceutical companies. The analysis of the survey stressed the fact that pharmaceutical companies should be prepared to face up to an increase in the number of consumer ADR reports. It clearly appears that the consumers who telephone to register side-effects should be forwarded to a trained DSO with medical or pharmaceutical background and the communication skills acquired through specific training. This person should also be able to release adequate product information validated by his/her own company. The influence of the US market seems to be changing the way pharmaceutical companies deal with consumer ADR reports. Nowadays, these reports are entered into a drug safety database by most of the companies without previously having contacted the patient's general practitioner (GP) or specialist for medical confirmation. Lastly, the drug safety managers and DSOs consulted have divided opinions about the usefulness of call centres and e-mails as tools for ADR reporting. But both tools are globally rejected by the pharmaceutical companies as a reliable means of reporting. As stated

  1. Drug Design, Development, and Delivery: An Interdisciplinary Course on Pharmaceuticals

    Science.gov (United States)

    Prausnitz, Mark R.; Bommarius, Andreas S.

    2011-01-01

    We developed a new interdisciplinary course on pharmaceuticals to address needs of undergraduate and graduate students in chemical engineering and other departments. This course introduces drug design, development, and delivery in an integrated fashion that provides scientific depth in context with broader impacts in business, policy, and ethics.…

  2. Influence of Inorganic Ions and Organic Substances on the Degradation of Pharmaceutical Compound in Water Matrix

    Directory of Open Access Journals (Sweden)

    Edyta Kudlek

    2016-11-01

    Full Text Available The paper determined the influence of inorganic substances and high-molecular organic compounds on the decomposition of diclofenac, ibuprofen, and carbamazepine in the process of photocatalysis conducted with the presence of Titanium dioxide (TiO2. It was determined that the presence of such ions as CO 3 2 − , HCO 3 − , HPO 4 2 − as well as SO 4 2 − inhibited the decomposition of carbamazepine, whereas the efficiency of diclofenac degradation was decreased only by the presence of CO 3 2 − and HCO 3 − anions. In case of ibuprofen sodium salt (IBU, all investigated anions influenced the increase in its decomposition rate. The process of pharmaceutical photooxidation conducted in suspensions with Al3+ and Fe3+ cations was characterized by a significantly decreased efficiency when compared to the solution deprived of inorganic compounds. The addition of Ca2+, Mg2+ and NH4+ affected the increase of reaction rate constant value of diclofenac and ibuprofen decomposition. On the other hand, high molecular organic compounds present in the model effluent additionally catalysed the degradation process of pharmaceutical compounds and constituted an additional sorbent that enabled to decrease their concentration. Toxicological analysis conducted in deionized water with pharmaceutical compounds’ patterns proved the production of by-products from oxidation and/or reduction of micropollutants, which was not observed for model effluent irradiation.

  3. [Access to drugs and the situation of the pharmaceutical market in Ecuador].

    Science.gov (United States)

    Ortiz-Prado, Esteban; Galarza, Claudio; León, Fernando Cornejo; Ponce, Jorge

    2014-07-01

    In the area of public health, it is fundamental to understand the structure and dynamics of the Ecuadorian pharmaceutical market, its segmentation between the public and private sectors, and its relationship with supply and demand, both for generic and brand-name drugs. To achieve this, an observational descriptive study was conducted with information obtained from the available scientific, institutional, technical-administrative, and economic databases. Furthermore, the scientific information concerning the Ecuadorian and regional pharmaceutical market was reviewed through the PubMed and Ovid search engines. In Ecuador, 69.6% of dispensed drugs are brand-name and 30.4% are generics. Of all registered drugs in the country, 1,829 (13.6%) are considered over-the-counter and 11,622 (86.4%) are for sale under medical prescription. In terms of sales, 93.15% correspond to brand-name drugs and only 6.85% to generics. Ninety percent of the pharmacies are located in urban areas and only 10% in rural areas. In the last five years, prices have increased by 12.5% for brand-name drugs and 0.86% for generics. Brand-name drugs are dispensed and consumed 2.3 times more than generics. The majority of pharmacies are located in urban areas, showing that there is a relationship between purchasing power and access to drugs. Although the regulatory authority stipulates that 13% of drugs should be over-the-counter, approximately 60% of the population acquires drugs without a medical prescription.

  4. Comparative studies on drug binding to the purified and pharmaceutical-grade human serum albumins: Bridging between basic research and clinical applications of albumin.

    Science.gov (United States)

    Ashrafi-Kooshk, Mohammad Reza; Ebrahimi, Farangis; Ranjbar, Samira; Ghobadi, Sirous; Moradi, Nastaran; Khodarahmi, Reza

    2015-09-01

    Human serum albumin (HSA), the most abundant protein in blood plasma, is a monomeric multidomain protein that possesses an extraordinary capacity for binding, so that serves as a circulating depot for endogenous and exogenous compounds. During the heat sterilization process, the structure of pharmaceutical-grade HSA may change and some of its activities may be lost. In this study, to provide deeper insight on this issue, we investigated drug-binding and some physicochemical properties of purified albumin (PA) and pharmaceutical-grade albumin (PGA) using two known drugs (indomethacin and ibuprofen). PGA displayed significantly lower drug binding capacity compared to PA. Analysis of the quenching and thermodynamic parameters indicated that intermolecular interactions between the drugs and the proteins are different from each other. Surface hydrophobicity as well as the stability of PGA decreased compared to PA, also surface hydrophobicity of PA and PGA increased upon drugs binding. Also, kinetic analysis of pseudo-esterase activities indicated that Km and Vmax parameters for PGA enzymatic activity are more and less than those of PA, respectively. This in vitro study demonstrates that the specific drug binding of PGA is significantly reduced. Such studies can act as connecting bridge between basic research discoveries and clinical applications. Copyright © 2015 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  5. Membrane-Based Technologies in the Pharmaceutical Industry and Continuous Production of Polymer-Coated Crystals/Particles.

    Science.gov (United States)

    Chen, Dengyue; Sirkar, Kamalesh K; Jin, Chi; Singh, Dhananjay; Pfeffer, Robert

    2017-01-01

    Membrane technologies are of increasing importance in a variety of separation and purification applications involving liquid phases and gaseous mixtures. Although the most widely used applications at this time are in water treatment including desalination, there are many applications in chemical, food, healthcare, paper and petrochemical industries. This brief review is concerned with existing and emerging applications of various membrane technologies in the pharmaceutical and biopharmaceutical industry. The goal of this review article is to identify important membrane processes and techniques which are being used or proposed to be used in the pharmaceutical and biopharmaceutical operations. How novel membrane processes can be useful for delivery of crystalline/particulate drugs is also of interest. Membrane separation technologies are extensively used in downstream processes for bio-pharmaceutical separation and purification operations via microfiltration, ultrafiltration and diafiltration. Also the new technique of membrane chromatography allows efficient purification of monoclonal antibodies. Membrane filtration techniques of reverse osmosis and nanofiltration are being combined with bioreactors and advanced oxidation processes to treat wastewaters from pharmaceutical plants. Nanofiltration with organic solvent-stable membranes can implement solvent exchange and catalyst recovery during organic solvent-based drug synthesis of pharmaceutical compounds/intermediates. Membranes in the form of hollow fibers can be conveniently used to implement crystallization of pharmaceutical compounds. The novel crystallization methods of solid hollow fiber cooling crystallizer (SHFCC) and porous hollow fiber anti-solvent crystallization (PHFAC) are being developed to provide efficient methods for continuous production of polymer-coated drug crystals in the area of drug delivery. This brief review provides a general introduction to various applications of membrane technologies in

  6. Tracing pharmaceuticals in a municipal plant for integrated wastewater and organic solid waste treatment

    Energy Technology Data Exchange (ETDEWEB)

    Jelic, Aleksandra [Department of Environmental Chemistry, Institute of Environmental Assessment and Water Research (IDAEA), Spanish Council for Scientific Research (CSIC), Jordi Girona 18-26, 08034 Barcelona (Spain); Fatone, Francesco; Di Fabio, Silvia [Department of Biotechnology, University of Verona, Strada Le Grazie 15, I-37134, Verona (Italy); Interuniversity Consortium ' Chemistry for the Environment' (INCA), Via delle Industrie, I-30135, Marghera-Venice (Italy); Petrovic, Mira, E-mail: mpetrovic@icra.cat [Catalan Institution for Research and Advanced Studies (ICREA), Passeig Lluis Companys 23, 80010 Barcelona (Spain); Catalan Institute for Water Research (ICRA), H2O Building, Scientific and Technological Park of the University of Girona, 101-E-17003 Girona (Spain); Cecchi, Franco [Department of Biotechnology, University of Verona, Strada Le Grazie 15, I-37134, Verona (Italy); Interuniversity Consortium ' Chemistry for the Environment' (INCA), Via delle Industrie, I-30135, Marghera-Venice (Italy); Barcelo, Damia [Department of Environmental Chemistry, Institute of Environmental Assessment and Water Research (IDAEA), Spanish Council for Scientific Research (CSIC), Jordi Girona 18-26, 08034 Barcelona (Spain); Catalan Institute for Water Research (ICRA), H2O Building, Scientific and Technological Park of the University of Girona, 101-E-17003 Girona (Spain)

    2012-09-01

    The occurrence and removal of 42 pharmaceuticals, belonging to different therapeutic groups (analgesics and anti-inflammatory drugs, anti-ulcer agent, psychiatric drugs, antiepileptic drug, antibiotics, ss-blockers, diuretics, lipid regulator and cholesterol lowering statin drugs and anti-histamines), were studied in the wastewater and sewage sludge trains of a full scale integrated treatment plant. The plant employs a biological nutrient removal (BNR) process for the treatment of municipal wastewater, and a single-stage mesophilic anaerobic co-digestion for the treatment of wasted activated sludge mixed with the organic fraction of municipal solid waste (OFMSW), followed by a short-cut nitrification-denitrification of the anaerobic supernatant in a sequential batch reactor. Influent and effluent wastewater, as well as thickened, digested and treated sludge were sampled and analyzed for the selected pharmaceuticals in order to study their presence and fate during the treatment. Twenty three compounds were detected in influent and effluent wastewater and eleven in sludge. Infiltration of groundwater in the sewer system led to a dilution of raw sewage, resulting in lower concentrations in wastewater (up to 0.7 {mu}g/L in influent) and sludge (70 ng/g d.w.). Due to the dilution, overall risk quotient for the mixture of pharmaceuticals detected in effluent wastewater was less than one, indicating no direct risk for the aquatic environment. A wide range of removal efficiencies during the treatment was observed, i.e. < 20% to 90%. The influent concentrations of the target pharmaceuticals, as polar compounds, were undoubtedly mostly affected by BNR process in the wastewater train, and less by anaerobic-co-digestion. Mass balance calculations showed that less than 2% of the total mass load of the studied pharmaceuticals was removed by sorption. Experimentally estimated distribution coefficients (< 500 L/kg) also indicated that the selected pharmaceuticals preferably remain

  7. Tracing pharmaceuticals in a municipal plant for integrated wastewater and organic solid waste treatment

    International Nuclear Information System (INIS)

    Jelic, Aleksandra; Fatone, Francesco; Di Fabio, Silvia; Petrovic, Mira; Cecchi, Franco; Barcelo, Damia

    2012-01-01

    The occurrence and removal of 42 pharmaceuticals, belonging to different therapeutic groups (analgesics and anti-inflammatory drugs, anti-ulcer agent, psychiatric drugs, antiepileptic drug, antibiotics, ß-blockers, diuretics, lipid regulator and cholesterol lowering statin drugs and anti-histamines), were studied in the wastewater and sewage sludge trains of a full scale integrated treatment plant. The plant employs a biological nutrient removal (BNR) process for the treatment of municipal wastewater, and a single-stage mesophilic anaerobic co-digestion for the treatment of wasted activated sludge mixed with the organic fraction of municipal solid waste (OFMSW), followed by a short-cut nitrification–denitrification of the anaerobic supernatant in a sequential batch reactor. Influent and effluent wastewater, as well as thickened, digested and treated sludge were sampled and analyzed for the selected pharmaceuticals in order to study their presence and fate during the treatment. Twenty three compounds were detected in influent and effluent wastewater and eleven in sludge. Infiltration of groundwater in the sewer system led to a dilution of raw sewage, resulting in lower concentrations in wastewater (up to 0.7 μg/L in influent) and sludge (70 ng/g d.w.). Due to the dilution, overall risk quotient for the mixture of pharmaceuticals detected in effluent wastewater was less than one, indicating no direct risk for the aquatic environment. A wide range of removal efficiencies during the treatment was observed, i.e. < 20% to 90%. The influent concentrations of the target pharmaceuticals, as polar compounds, were undoubtedly mostly affected by BNR process in the wastewater train, and less by anaerobic-co-digestion. Mass balance calculations showed that less than 2% of the total mass load of the studied pharmaceuticals was removed by sorption. Experimentally estimated distribution coefficients (< 500 L/kg) also indicated that the selected pharmaceuticals preferably remain

  8. Temporal trends of select pharmaceutical compounds entering an estuary from a small, urban river

    Science.gov (United States)

    The fate and effects of pharmaceutical compounds have been widely studied in freshwater systems; however, less is known about their behavior in marine ecosystems. In many coastal watersheds, there are river systems that are receiving waters for domestic wastewater treatment effl...

  9. Carbon Nanomaterials Based Electrochemical Sensors/Biosensors for the Sensitive Detection of Pharmaceutical and Biological Compounds

    Directory of Open Access Journals (Sweden)

    Bal-Ram Adhikari

    2015-09-01

    Full Text Available Electrochemical sensors and biosensors have attracted considerable attention for the sensitive detection of a variety of biological and pharmaceutical compounds. Since the discovery of carbon-based nanomaterials, including carbon nanotubes, C60 and graphene, they have garnered tremendous interest for their potential in the design of high-performance electrochemical sensor platforms due to their exceptional thermal, mechanical, electronic, and catalytic properties. Carbon nanomaterial-based electrochemical sensors have been employed for the detection of various analytes with rapid electron transfer kinetics. This feature article focuses on the recent design and use of carbon nanomaterials, primarily single-walled carbon nanotubes (SWCNTs, reduced graphene oxide (rGO, SWCNTs-rGO, Au nanoparticle-rGO nanocomposites, and buckypaper as sensing materials for the electrochemical detection of some representative biological and pharmaceutical compounds such as methylglyoxal, acetaminophen, valacyclovir, β-nicotinamide adenine dinucleotide hydrate (NADH, and glucose. Furthermore, the electrochemical performance of SWCNTs, rGO, and SWCNT-rGO for the detection of acetaminophen and valacyclovir was comparatively studied, revealing that SWCNT-rGO nanocomposites possess excellent electrocatalytic activity in comparison to individual SWCNT and rGO platforms. The sensitive, reliable and rapid analysis of critical disease biomarkers and globally emerging pharmaceutical compounds at carbon nanomaterials based electrochemical sensor platforms may enable an extensive range of applications in preemptive medical diagnostics.

  10. Information on the quality of substance for the preparation of pharmaceutical drugs in terms of hospital pharmacy

    Directory of Open Access Journals (Sweden)

    Jovović Marija Đ.

    2015-01-01

    Full Text Available Explanation the topic The pharmaceutical activity is the activity of public or social and special interest, because it is a direct function of health care. Topic positioning and discussion The aim of this paper is to highlight the importance of ensuring the quality of pharmaceutical substances that supplies hospitals, which are used for production of galenic and magistral drugs. Conclusion Compliance with national legislation, as well as establishing compliance prescribed by the European legislation in the field of drug development is binding. Therefore, all manufacturers of drugs and/or active pharmaceutical ingredients must apply quality standards prescribed by the European Pharmacopoeia in order to develop, manufacture and sales of medicines. When it comes to the quality of pharmaceutical ingredients for the production of drugs in the pharmacy, pharmacies especially in residential institutions in our country is permanently done by harmonizing national legislation in order to improve conditions for the preparation and production of galenic drugs in terms of inpatient health institutions performed in a manner that is prescribed by international regulations. This requires the adaptation of institutions, including fundamental changes in competence as national professional and administrative and regulatory rules that apply to state- and private sectors.

  11. 'Pro et contra' ionic liquid drugs - Challenges and opportunities for pharmaceutical translation.

    Science.gov (United States)

    Balk, Anja; Holzgrabe, Ulrike; Meinel, Lorenz

    2015-08-01

    Ionic liquids (ILs) are organic salts with a melting point below 100°C. Active pharmaceutical ingredients (APIs) are transformed into ILs by combining them with typically large yet charged counterions. ILs hold promise to build a large design space for relevant pharmaceutical parameters, particularly for poorly water soluble drugs. It is for this wide design space that ILs may be the entry into the fascinating vision of modifying physico-chemical properties without the need to structurally modify the active pharmaceutical ingredient itself. This extremely intriguing pharmaceutical option is critically discussed including its potential and limitations. The review is starting off with an introduction to the metathesis and characterization of ILs, and leads over to examples for pharmaceutical application, including enhancement of dissolution rate and kinetic solubility and hygroscopicity adaptation, respectively. Tuning biopharmaceutics and toxicology by proper IL design is another focus. The review connects the interrelated chemical, physical, pharmaceutical, and toxicological outcome of API-ILs, serving as guidance for the formulation scientist who aims at expanding ones armamentarium for poorly water soluble APIs while avoiding structural modification, thereof. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Enantiomeric profiling of a chemically diverse mixture of chiral pharmaceuticals in urban water

    International Nuclear Information System (INIS)

    Evans, S.; Bagnall, J.; Kasprzyk-Hordern, B.

    2017-01-01

    Due to concerns regarding the release of pharmaceuticals into the environment and the understudied impact of stereochemistry of pharmaceuticals on their fate and biological potency, we focussed in this paper on stereoselective transformation pathways of selected chiral pharmaceuticals (16 pairs) at both microcosm (receiving waters and activated sludge wastewater treatment simulating microcosms) and macrocosm (wastewater treatment plant (WWTP) utilising activated sludge technology and receiving waters) scales in order to test the hypothesis that biodegradation of chiral drugs is stereoselective. Our monitoring programme of a full scale activated sludge WWTP and receiving environment revealed that several chiral drugs, those being marketed mostly as racemates, are present in wastewater and receiving waters enriched with one enantiomeric form (e.g. fluoxetine, mirtazapine, salbutamol, MDMA). This is most likely due to biological metabolic processes occurring in humans and other organisms. Both activated sludge and receiving waters simulating microcosms confirmed our hypothesis that chiral drugs are subject to stereoselective microbial degradation. It led, in this research, to preferential degradation of S-(+)-enantiomers of amphetamines, R-(+)-enantiomers of beta-blockers and S-(+)-enantiomers of antidepressants. In the case of three parent compound – metabolite pairs (venlafaxine – desmethylvenlafaxine, citalopram – desmethylcitalopram and MDMA - MDA), while parent compounds showed higher resistance to both microbial metabolism and photodegradation, their desmethyl metabolites showed much higher degradation rate both in terms of stereoselective metabolic and non-stereoselective photochemical processes. It is also worth noting that metabolites tend to be, as expected, enriched with enantiomers of opposite configuration to their parent compounds, which might have significant toxicological consequences when evaluating the metabolic residues of chiral pollutants

  13. Determination of pharmaceutical compounds in surface- and ground-water samples by solid-phase extraction and high-performance liquid chromatography-electrospray ionization mass spectrometry

    Science.gov (United States)

    Cahill, J.D.; Furlong, E.T.; Burkhardt, M.R.; Kolpin, D.; Anderson, L.G.

    2004-01-01

    Commonly used prescription and over-the-counter pharmaceuticals are possibly present in surface- and ground-water samples at ambient concentrations less than 1 μg/L. In this report, the performance characteristics of a combined solid-phase extraction isolation and high-performance liquid chromatography–electrospray ionization mass spectrometry (HPLC–ESI-MS) analytical procedure for routine determination of the presence and concentration of human-health pharmaceuticals are described. This method was developed and used in a recent national reconnaissance of pharmaceuticals in USA surface waters. The selection of pharmaceuticals evaluated for this method was based on usage estimates, resulting in a method that contains compounds from diverse chemical classes, which presents challenges and compromises when applied as a single routine analysis. The method performed well for the majority of the 22 pharmaceuticals evaluated, with recoveries greater than 60% for 12 pharmaceuticals. The recoveries of angiotensin-converting enzyme inhibitors, a histamine (H2) receptor antagonist, and antihypoglycemic compound classes were less than 50%, but were retained in the method to provide information describing the potential presence of these compounds in environmental samples and to indicate evidence of possible matrix enhancing effects. Long-term recoveries, evaluated from reagent-water fortifications processed over 2 years, were similar to initial method performance. Method detection limits averaged 0.022 μg/L, sufficient for expected ambient concentrations. Compound-dependent matrix effects on HPLC/ESI-MS analysis, including enhancement and suppression of ionization, were observed as a 20–30% increase in measured concentrations for three compounds and greater than 50% increase for two compounds. Changing internal standard and more frequent ESI source maintenance minimized matrix effects. Application of the method in the national survey demonstrates that several

  14. Occurrence and fate of bulk organic matter and pharmaceutically active compounds in managed aquifer recharge: A review

    KAUST Repository

    Maeng, Sungkyu

    2011-05-01

    Managed aquifer recharge (MAR) is a natural water treatment process that induces surface water to flow in response to a hydraulic gradient through soil/sediment and into a vertical or horizontal well. It is a relatively cost-effective, robust and sustainable technology. Detailed characteristics of bulk organic matter and the occurrence and fate of pharmaceutically active compounds (PhACs) during MAR processes such as bank filtration (BF) and artificial recharge (AR) were reviewed. Understanding the fate of bulk organic matter during BF and AR is an essential step in determining pre- and/or post-treatment requirements. Analysis of organic matter characteristics using a suite of analytical tools suggests that there is a preferential removal of non-humic substances during MAR. Different classes of PhACs were found to behave differently during BF and AR. Antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), beta blockers, and steroid hormones generally exhibited good removal efficiencies, especially for compounds having hydrophobic-neutral characteristics. However, anticonvulsants showed a persistent behavior during soil passage. There were also some redox-dependent PhACs. For example, X-ray contrast agents measured, as adsorbable organic iodine (AOI), and sulfamethoxazole (an antibiotic) degraded more favorably under anoxic conditions compared to oxic conditions. Phenazone-type pharmaceuticals (NSAIDs) exhibited better removal under oxic conditions. The redox transition from oxic to anoxic conditions during soil passage can enhance the removal of PhACs that are sensitive to redox conditions. In general, BF and AR can be included in a multi-barrier treatment system for the removal of PhACs. © 2011.

  15. Occurrence and fate of bulk organic matter and pharmaceutically active compounds in managed aquifer recharge: a review.

    Science.gov (United States)

    Maeng, Sung Kyu; Sharma, Saroj K; Lekkerkerker-Teunissen, Karin; Amy, Gary L

    2011-05-01

    Managed aquifer recharge (MAR) is a natural water treatment process that induces surface water to flow in response to a hydraulic gradient through soil/sediment and into a vertical or horizontal well. It is a relatively cost-effective, robust and sustainable technology. Detailed characteristics of bulk organic matter and the occurrence and fate of pharmaceutically active compounds (PhACs) during MAR processes such as bank filtration (BF) and artificial recharge (AR) were reviewed. Understanding the fate of bulk organic matter during BF and AR is an essential step in determining pre- and/or post-treatment requirements. Analysis of organic matter characteristics using a suite of analytical tools suggests that there is a preferential removal of non-humic substances during MAR. Different classes of PhACs were found to behave differently during BF and AR. Antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), beta blockers, and steroid hormones generally exhibited good removal efficiencies, especially for compounds having hydrophobic-neutral characteristics. However, anticonvulsants showed a persistent behavior during soil passage. There were also some redox-dependent PhACs. For example, X-ray contrast agents measured, as adsorbable organic iodine (AOI), and sulfamethoxazole (an antibiotic) degraded more favorably under anoxic conditions compared to oxic conditions. Phenazone-type pharmaceuticals (NSAIDs) exhibited better removal under oxic conditions. The redox transition from oxic to anoxic conditions during soil passage can enhance the removal of PhACs that are sensitive to redox conditions. In general, BF and AR can be included in a multi-barrier treatment system for the removal of PhACs. Copyright © 2011. Published by Elsevier Ltd.

  16. Liquid separation techniques coupled with mass spectrometry for chiral analysis of pharmaceuticals compounds and their metabolites in biological fluids.

    OpenAIRE

    Erny, Guillaume L.; Cifuentes, Alejandro

    2006-01-01

    Determination of the chiral composition of drugs is nowadays a key step in order to determine purity, activity, bioavailability, biodegradation, etc, of pharmaceuticals. In this manuscript, works published for the last 5 years on the analysis of chiral drugs by liquid separation techniques coupled with mass spectrometry are reviewed. Namely, chiral analysis of pharmaceuticals including e.g., antiinflammatories, antihypertensives, relaxants, etc, by liquid chromatography-mass spectrometry and ...

  17. Analytical Validation of Accelerator Mass Spectrometry for Pharmaceutical Development: the Measurement of Carbon-14 Isotope Ratio

    International Nuclear Information System (INIS)

    Keck, B.D.; Ognibene, T.; Vogel, J.S.

    2010-01-01

    Accelerator mass spectrometry (AMS) is an isotope based measurement technology that utilizes carbon-14 labeled compounds in the pharmaceutical development process to measure compounds at very low concentrations, empowers microdosing as an investigational tool, and extends the utility of 14 C labeled compounds to dramatically lower levels. It is a form of isotope ratio mass spectrometry that can provide either measurements of total compound equivalents or, when coupled to separation technology such as chromatography, quantitation of specific compounds. The properties of AMS as a measurement technique are investigated here, and the parameters of method validation are shown. AMS, independent of any separation technique to which it may be coupled, is shown to be accurate, linear, precise, and robust. As the sensitivity and universality of AMS is constantly being explored and expanded, this work underpins many areas of pharmaceutical development including drug metabolism as well as absorption, distribution and excretion of pharmaceutical compounds as a fundamental step in drug development. The validation parameters for pharmaceutical analyses were examined for the accelerator mass spectrometry measurement of 14 C/C ratio, independent of chemical separation procedures. The isotope ratio measurement was specific (owing to the 14 C label), stable across samples storage conditions for at least one year, linear over 4 orders of magnitude with an analytical range from one tenth Modern to at least 2000 Modern (instrument specific). Further, accuracy was excellent between 1 and 3 percent while precision expressed as coefficient of variation is between 1 and 6% determined primarily by radiocarbon content and the time spent analyzing a sample. Sensitivity, expressed as LOD and LLOQ was 1 and 10 attomoles of carbon-14 (which can be expressed as compound equivalents) and for a typical small molecule labeled at 10% incorporated with 14 C corresponds to 30 fg equivalents. AMS

  18. Analytical Validation of Accelerator Mass Spectrometry for Pharmaceutical Development: the Measurement of Carbon-14 Isotope Ratio.

    Energy Technology Data Exchange (ETDEWEB)

    Keck, B D; Ognibene, T; Vogel, J S

    2010-02-05

    Accelerator mass spectrometry (AMS) is an isotope based measurement technology that utilizes carbon-14 labeled compounds in the pharmaceutical development process to measure compounds at very low concentrations, empowers microdosing as an investigational tool, and extends the utility of {sup 14}C labeled compounds to dramatically lower levels. It is a form of isotope ratio mass spectrometry that can provide either measurements of total compound equivalents or, when coupled to separation technology such as chromatography, quantitation of specific compounds. The properties of AMS as a measurement technique are investigated here, and the parameters of method validation are shown. AMS, independent of any separation technique to which it may be coupled, is shown to be accurate, linear, precise, and robust. As the sensitivity and universality of AMS is constantly being explored and expanded, this work underpins many areas of pharmaceutical development including drug metabolism as well as absorption, distribution and excretion of pharmaceutical compounds as a fundamental step in drug development. The validation parameters for pharmaceutical analyses were examined for the accelerator mass spectrometry measurement of {sup 14}C/C ratio, independent of chemical separation procedures. The isotope ratio measurement was specific (owing to the {sup 14}C label), stable across samples storage conditions for at least one year, linear over 4 orders of magnitude with an analytical range from one tenth Modern to at least 2000 Modern (instrument specific). Further, accuracy was excellent between 1 and 3 percent while precision expressed as coefficient of variation is between 1 and 6% determined primarily by radiocarbon content and the time spent analyzing a sample. Sensitivity, expressed as LOD and LLOQ was 1 and 10 attomoles of carbon-14 (which can be expressed as compound equivalents) and for a typical small molecule labeled at 10% incorporated with {sup 14}C corresponds to 30 fg

  19. Pharmaceutical cocrystals as an opportunity to modify drug properties: From the idea to application. A review.

    Science.gov (United States)

    Sokal, Agnieszka; Pindelska, Edyta

    2017-12-26

    The properties of many drugs which have been available on the pharmaceutical market for a long time still need to be improved. Cocrystals are the solid state drug modification which can improve such properties as low solubility, stability and mechanical properties (e.g. compressibility). In this paper examples how to use cocrystals to modify properties of API (Active Pharmaceutical Ingredient) will be reported. Additionally, in this review the way from an idea of the new cocrystal to drug dosage form registration will be shortly described. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Scanning ion images; analysis of pharmaceutical drugs at organelle levels

    Science.gov (United States)

    Larras-Regard, E.; Mony, M.-C.

    1995-05-01

    With the ion analyser IMS 4F used in microprobe mode, it is possible to obtain images of fields of 10 × 10 [mu]m2, corresponding to an effective magnification of 7000 with lateral resolution of 250 nm, technical characteristics that are appropriate for the size of cell organelles. It is possible to characterize organelles by their relative CN-, P- and S- intensities when the tissues are prepared by freeze fixation and freeze substitution. The recognition of organelles enables correlation of the tissue distribution of ebselen, a pharmaceutical drug containing selenium. The various metabolites characterized in plasma, bile and urine during biotransformation of ebselen all contain selenium, so the presence of the drug and its metabolites can be followed by images of Se. We were also able to detect the endogenous content of Se in tissue, due to the increased sensitivity of ion analysis in microprobe mode. Our results show a natural occurrence of Se in the border corresponding to the basal lamina of cells of proximal but not distal tubules of the kidney. After treatment of rats with ebselen, an additional site of Se is found in the lysosomes. We suggest that in addition to direct elimination of ebselen and its metabolites by glomerular filtration and urinary elimination, a second process of elimination may occur: Se compounds reaching the epithelial cells via the basal lamina accumulate in lysosomes prior to excretion into the tubular fluid. The technical developments of using the IMS 4F instrument in the microprobe mode and the improvement in preparation of samples by freeze fixation and substitution further extend the limit of ion analysis in biology. Direct imaging of trace elements and molecules marked with a tracer make it possible to determine their targets by comparison with images of subcellular structures. This is a promising advance in the study of pathways of compounds within tissues, cells and the whole organism.

  1. Between pharmaceutical patents and European patients: is a compromise still possible?

    Science.gov (United States)

    Garattini, Livio; Padula, Anna

    2017-10-01

    Pharmaceutical regulation has always attempted to balance the public health objective to make safe and effective drugs available for patients while providing commercial incentives through patents. Here we discuss whether it is still possible to find a balance between the incentives on the supply side and the regulatory framework on the demand side. Areas covered: The current regulatory framework on pharmaceutical exclusivity has been harshly criticized by many experts, arguing about whether it is still fit for public purposes and needs. Here we envisage a different scenario without 'revolutionizing' the whole present system. The main radical change should concern the present management of pharmaceutical patents by introducing a specific agency dedicated to them. Secondly, specific pharmaceutical patents could be restricted to compounds for one (or more) declared indication(s). Thirdly, pharmaceutical patents should be kept only for compounds that start a first clinical trial within five years from the granting date. Expert opinion: We think it is time to reconsider the regulation of pharmaceutical patents in the light of their relevance in terms of public health. New models of enhancing research investments are required for long-term sustainability of public pharmaceutical expenditure and the EU can still play a leading role.

  2. Study of split-ring resonators for use on a pharmaceutical drug capsule for microwave activated drug release

    DEFF Research Database (Denmark)

    Jónasson, Sævar Þór; Jensen, Brian Sveistrup; Johansen, Tom Keinicke

    2012-01-01

    In this paper, a novel method for externally activating a pharmaceutical drug capsule by use of split-ring resonators (SRR) is introduced. To this end, the effect of the orientation of the SRRs on the ability to activate the capsules is examined. A coplanar waveguide is used to excite an identical...... pair of SRRs fabricated on a substrate, representing an enlarged lid for a pharmaceutical drug capsule. Orientations where the electric field component of a quasi-TEM wave lies across the gap of the SRRs provides the largest response. The optimal case is when the electric field component lies across...... the gap simultaneously with the magnetic field component normal to the SRRs. Furthermore, an analysis of the optimal conductivity and relative permittivity for enhanced temperature rise in the lid is performed. Conductivity of 0.09 S/m and relative permittivity of 12 shows the highest temperature rise....

  3. Transparency in the pharmaceutical industry - A cost accounting approach to the prices of drugs

    NARCIS (Netherlands)

    Broekhof, Martijn

    2002-01-01

    The WTO TRIPS agreement grants pharmaceutical companies patent rights on new innovative drugs. Patents give these companies the opportunity to charge higher prices for their drugs in order to recover their R&D expenses. For developing countries this is one of the reasons why people in developing

  4. [Drugs and pharmaceutical episodes in "Sazae-San": Japanese comic strips in 1940s-1970s].

    Science.gov (United States)

    Goino, Masahiko

    2009-01-01

    This is a report on episodes with references to drugs and pharmaceuticals in one of the most famous Japanese comic strips, "Sazae-san", in the period from 1945 to 1974. There were 111 episodes of "Sazae-san" including references to drugs and pharmaceuticals in this period. In the period from 1945 to 1954, there were some references to pharmacists and pharmacies but only a small number of references in the period from 1965 to 1974. In the period from 1945 to 1954, there were references to disinfectants and insecticides in the hygienic chemistry field. However, in the period from 1965 to 1974, there were references to environmental problems, food additives and agricultural chemicals. As drug development has progressed, the number of references to practical drugs in "Sazae-san" has decreased over the period from 1945-1974.

  5. Studies of the impact of occupational exposure of pharmaceutical workers on the development of antimicrobial drug resistance.

    Science.gov (United States)

    Sarker, Md Moklesur Rahman; Islam, Kamrun Nahar; Huri, Hasniza Zaman; Rahman, Monzur; Imam, Hasan; Hosen, Md Biplob; Mohammad, Nur; Sarker, Md Zaidul Islam

    2014-01-01

    Pharmaceutical workers involved with the production of antimicrobial drugs are exposed to various antimicrobial chemicals in different steps of manufacturing such as grinding, sieving, compression, granulation, mixing and filling. These exposures may lead to the development of multidrug resistance (MDR) in bacteria. Scientific reports on the occupational health hazard of pharmaceutical workers involved in manufacturing antibiotics are scarce. The present study aimed to compare the degree of bacterial resistance in pharmaceutical workers in Bangladesh to that of individuals not involved in the pharmaceutical field. Twenty male workers from five local pharmaceutical companies and twenty male subjects not involved in the pharmaceutical field (non-pharmaceutical subjects) were randomly selected. Nasal fluid, mucus/cough and stool specimens were collected from each subject and were cultured separately at 37°C for 24 hours to obtain bacterial growth. The cultured species were then identified, isolated and subjected to microbial sensitivity testing against 18 different antibiotics from eight different groups by the disk diffusion method. Staphylococcus spp., Pseudomonas spp. and Escherichia coli were identified and isolated from the culture of nasal fluids, mucuses and stools, respectively. All the isolated species of bacteria exhibited significant enhancement of the degree of MDR in pharmaceutical workers compared with non-pharmaceutical subjects. Workers with a longer working history had greater degree of antibiotic resistance and vice versa. It can be certainly considered that the exposure of pharmaceutical workers to antibiotic agents resulted in a high incidence of multidrug resistance. Effective steps should be taken to minimize inherent exposure of pharmaceutical workers to antibiotics during work to prevent antimicrobial drug resistance.

  6. Using data from drug discovery and development to aid the aquatic environmental risk assessment of human pharmaceuticals: concepts, considerations, and challenges.

    Science.gov (United States)

    Winter, Matthew J; Owen, Stewart F; Murray-Smith, Richard; Panter, Grace H; Hetheridge, Malcolm J; Kinter, Lewis B

    2010-01-01

    Over recent years, human pharmaceuticals have been detected in the aquatic environment. This, combined with the fact that many are (by design) biologically active compounds, has raised concern about potential impacts in wildlife species. This concern was realized with two high-profile cases of unforeseen environmental impact (i.e., estrogens and diclofenac), which have led to a flurry of work addressing how best to predict such effects in the future. One area in which considerable research effort has been made, partially in response to regulatory requirements, has been on the potential use of preclinical and clinical pharmacological and toxicological data (generated during drug development from nonhuman mammals and humans) to predict possible effects in nontarget, environmentally relevant species: so-called read across. This approach is strengthened by the fact that many physiological systems are conserved between mammals and certain environmentally relevant species. Consequently, knowledge of how a pharmaceutical works (the “mode-of-action,” or MoA) in nonclinical species and humans could assist in the selection of appropriate test species, study designs, and endpoints, in an approach referred to as “intelligent testing.” Here we outline the data available from the human drug development process and suggest how this might be used to design a testing strategy best suited to the specific characteristics of the drug in question. In addition, we review published data that support this type of approach, discuss the potential pitfalls associated with read across, and identify knowledge gaps that require filling to ensure accuracy in the extrapolation of data from preclinical and clinical studies, for use in the environmental risk assessment of human pharmaceuticals.

  7. Drugs for cardiovascular disease in India: perspectives of pharmaceutical executives and government officials on access and development-a qualitative analysis.

    Science.gov (United States)

    Newman, Charles; Ajay, Vamadevan S; Srinivas, Ravi; Bhalla, Sandeep; Prabhakaran, Dorairaj; Banerjee, Amitava

    2016-01-01

    India shoulders the greatest global burden of cardiovascular diseases (CVDs), which are the leading cause of mortality worldwide. Drugs are the bedrock of treatment and prevention of CVD. India's pharmaceutical industry is the third largest, by volume, globally, but access to CVD drugs in India is poor. There is a lack of qualitative data from government and pharmaceutical sectors regarding CVD drug development and access in India. By purposive sampling, we recruited either Indian government officials, or pharmaceutical company executives. We conducted a stakeholder analysis via semi-structured, face-to-face interviews in India. Topic guides allow for the exploration of key issues across multiple interviews, along with affording the interviewer the flexibility to examine matters arising from the discussions themselves. After transcription, interviews underwent inductive thematic analysis. Ten participants were interviewed (Government Officials: n = 5, and Pharmaceutical Executives: n = 5). Two themes emerged: i) 'Policy-derived Factors'; ii) 'Patient- derived Factors' with three findings. First, both government and pharmaceutical participants felt that the focus of Indian pharma is shifting to more complex, high-quality generics and to new drug development, but production of generic drugs rather than new molecular entities will remain a major activity. Second, current trial regulations in India may restrict India's potential role in the future development of CVD drugs. Third, it is likely that the Indian government will tighten its intellectual property regime in future, with potentially far-reaching implications on CVD drug development and access. Our stakeholder analysis provides some support for present patent regulations, whilst suggesting areas for further research in order to inform future policy decisions regarding CVD drug development and availability. Whilst interviewees suggested government policy plays an important role in shaping the industry, a

  8. The Development of a Parenteral Pharmaceutical Formulation of a New Class of Compounds of Nitrosourea.

    Science.gov (United States)

    Nikolaeva, Ludmila; Oborotova, Natalia; Bunyatyan, Natalia; Zhang, Xi; Sanarova, Ekaterina; Lantsova, Anna; Orlova, Olga; Polozkova, Alevtina

    2016-11-01

    Despite the rapid development of medical technologies, chemotherapy treatment still occupies an important place in clinical oncology. In this regard, the current research in this area focuses on the synthesis of new highly effective antitumor substances that have minimal side effects and the development of stable pharmaceutical formulations (PF) on their basis. In order to solve this problem, the I. Ya. Postovsky Institute of Organic Synthesis of the Ural Branch of the Russian Academy of Sciences actively sought for original substances, namely, nitrosourea (NU) derivatives, one of the most promising classes of anticancer drugs. As a result of this research, a novel NU derivative was synthesized, namely ormustine, which showed high antitumor activity in preliminary preclinical trials. It is now crucial to develop an ormustine pharmaceutical formulation. Conducted technological studies showed that the most suitable solvent for the drug substance is 0.1 M hydrochloric acid, which ensures its rapid dissolution by ultrasonic treatment. A significant reduction in the concentration of the active ingredient during the storage of the solution required the development of a technique of its lyophilization and the selection of a shaper such as a Kollidon 17 PF. Upon completion of the development of a pharmaceutical formulation of ormustine, its stability after lyophilization was demonstrated, and a sufficient amount of the drug has been acquired for preclinical research.

  9. Drug repurposing from the perspective of pharmaceutical companies.

    Science.gov (United States)

    Cha, Y; Erez, T; Reynolds, I J; Kumar, D; Ross, J; Koytiger, G; Kusko, R; Zeskind, B; Risso, S; Kagan, E; Papapetropoulos, S; Grossman, I; Laifenfeld, D

    2018-01-01

    Drug repurposing holds the potential to bring medications with known safety profiles to new patient populations. Numerous examples exist for the identification of new indications for existing molecules, most stemming from serendipitous findings or focused recent efforts specifically limited to the mode of action of a specific drug. In recent years, the need for new approaches to drug research and development, combined with the advent of big data repositories and associated analytical methods, has generated interest in developing systematic approaches to drug repurposing. A variety of innovative computational methods to enable systematic repurposing screens, experimental as well as through in silico approaches, have emerged. An efficient drug repurposing pipeline requires the combination of access to molecular data, appropriate analytical expertise to enable robust insights, expertise and experimental set-up for validation and clinical development know-how. In this review, we describe some of the main approaches to systematic repurposing and discuss the various players in this field and the need for strategic collaborations to increase the likelihood of success in bringing existing molecules to new indications, as well as the current advantages, considerations and challenges in repurposing as a drug development strategy pursued by pharmaceutical companies. This article is part of a themed section on Inventing New Therapies Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc. © 2017 The British Pharmacological Society.

  10. General public knowledge, perceptions and practice towards pharmaceutical drug advertisements in the Western region of KSA.

    Science.gov (United States)

    Al-Haddad, Mahmoud S; Hamam, Fayez; Al-Shakhshir, Sami M

    2014-04-01

    This study aims to examine general public knowledge and behavior toward pharmaceutical advertisements in the Western part of KSA. A cross sectional convenience sampling technique was used in this study. A total of 1445 valid questionnaires were received and analyzed using SPSS version 16 at alpha value of 0.05. Majority of respondents were aware of different types of drugs to be advertised and drug advertisements should seek approval from the health authorities. Television and Internet showed the highest effect on consumers. Almost half of the participants preferred an advertised drug over non-advertised one. Most of the respondents indicated that the quality of frequently advertised drugs is not better than those prescribed by the doctors. Majority of participants had positive beliefs toward advertised drugs concerning their role in education and spreading of awareness among the public. Pharmaceutical advertisements harm the doctor-patient relationship as evidenced by one-third of the investigated sample. Moreover, majority of the participants mentioned that they would consult another doctor or even change the current doctor if he/she refused to prescribe an advertised medication. Results of this study could be used to develop awareness programs for the general public and try to enforce the regulations and policies to protect the general public and patients from the business oriented pharmaceutical companies and drug suppliers.

  11. The teaching of drug development to medical students: collaboration between the pharmaceutical industry and medical school.

    Science.gov (United States)

    Stanley, A G; Jackson, D; Barnett, D B

    2005-04-01

    Collaboration between the medical school at Leicester and a local pharmaceutical company, AstraZeneca, led to the design and implementation of an optional third year special science skills module teaching medical students about drug discovery and development. The module includes didactic teaching about the complexities of the drug discovery process leading to development of candidate drugs for clinical investigation as well as practical experience of the processes involved in drug evaluation preclinically and clinically. It highlights the major ethical and regulatory issues concerned with the production and testing of novel therapies in industry and the NHS. In addition it helps to reinforce other areas of the medical school curriculum, particularly the understanding of clinical study design and critical appraisal. The module is assessed on the basis of a written dissertation and the critical appraisal of a drug advertisement. This paper describes the objectives of the module and its content. In addition we outline the results of an initial student evaluation of the module and an assessment of its impact on student knowledge and the opinion of the pharmaceutical industry partner. This module has proven to be popular with medical students, who acquire a greater understanding of the work required for drug development and therefore reflect more favourably on the role of pharmaceutical companies in the UK.

  12. Can open-source drug R&D repower pharmaceutical innovation?

    Science.gov (United States)

    Munos, B

    2010-05-01

    Open-source R&D initiatives are multiplying across biomedical research. Some of them-such as public-private partnerships-have achieved notable success in bringing new drugs to market economically, whereas others reflect the pharmaceutical industry's efforts to retool its R&D model. Is open innovation the answer to the innovation crisis? This Commentary argues that although it may likely be part of the solution, significant cultural, scientific, and regulatory barriers can prevent it from delivering on its promise.

  13. Drug recall: An incubus for pharmaceutical companies and most serious drug recall of history.

    Science.gov (United States)

    Nagaich, Upendra; Sadhna, Divya

    2015-01-01

    There has been an increasing trend in the number of prescribed and over-the-counter drug recall over the last few years. The recall is usually due to company's discovery, customer's complaint or Food and Drug Administration (FDA) observation. The process of recall involves a planned specific course of action, which addresses the depth of recall, need for public warning, and the extent of effectiveness checks for the recall. The FDA review and/or recommend changes to the firm's recall strategy, as appropriate. The critical recall information list includes the identity of the product; summary of the failure; amount of product produced in the distribution chain and direct account. Product recalls clashes thousands of companies every year affecting: sales, testing customer relationships and disrupting supply chains. Drug recall is incubus for pharmaceutical companies. It effects the reputation of the company. The reason for the recall can be divided into two categories: manufacturing affined and safety/efficacy affined. It is essential to follow all the guidelines related to drug development and manufacturing procedure so as to minimize drug recall.

  14. [Pharmaceutical drugs containing lactose can as a rule be used by persons with lactose intolerance].

    Science.gov (United States)

    Vinther, Siri; Rumessen, Jöri Johannes; Christensen, Mikkel

    2015-03-09

    Lactose is often used as an excipient in pharmaceutical drugs. Current evidence indicates that the amount of lactose in most drugs is not sufficient to cause symptoms in persons with lactose intolerance, although interindividual differences in sensitivity probably exist. Patient preferences and/or suboptimal treatment adherence could be reasons for considering lactose-free drug alternatives.

  15. Analysis of Pharmaceutical and Personal Care Compounds in Wastewater Sludge and Aqueous Samples using GC-MS/MS

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, Lirong [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Mitroshkov, Alexandre V. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Gilmore, Tyler J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-03-15

    The Bioenergy Program at Pacific Northwest National Laboratory (PNNL) is evaluating the feasibility of converting wastewater sludge materials to fuels. Wastewater sludge from various municipalities will be used in the evaluation process and as with any municipal waste, there is the potential for residual contaminates to remain in the sludge following wastewater treatment. Many surveys and studies have confirmed the presence of pharmaceuticals in municipal wastewater and effluents (World Health Organization, 2011). Determination of the presence and concentrations of the contaminants is required to define the proper handling of this sludge. A list of targeted compounds was acquired from the literature and an analytical method was developed for the pharmaceutical and personal care compounds. The presence of organics complicated the analytical techniques and, in some cases, the precision of the results. However, residual concentrations of a range of compounds were detected in the wastewater sludge and the presence and concentrations of these compounds will be considered in identifying the appropriate handling of this material in conduct of research.

  16. Interactions and incompatibilities of pharmaceutical excipients with active pharmaceutical ingredients: a comprehensive review

    Directory of Open Access Journals (Sweden)

    Sonali S. Bharate

    2010-09-01

    Full Text Available Studies of active drug/excipient compatibility represent an important phase in the preformulation stage of the development of all dosage forms. The potential physical and chemical interactions between drugs and excipients can affect the chemical nature, the stability and bioavailability of drugs and, consequently, their therapeutic efficacy and safety. The present review covers the literature reports of interaction and incompatibilities of commonly used pharmaceutical excipients with different active pharmaceutical ingredients in solid dosage forms. Examples of active drug/excipient interactions, such as transacylation, the Maillard browning reaction, acid base reactions and physical changes are discussed for different active pharmaceutical ingredients belonging to different therapeutic categories viz antiviral, anti-inflammatory, antidiabetic, antihypertensive, anti-convulsant, antibiotic, bronchodialator, antimalarial, antiemetic, antiamoebic, antipsychotic, antidepressant, anticancer, anticoagulant and sedative/hypnotic drugs and vitamins. Once the solid-state reactions of a pharmaceutical system are understood, the necessary steps can be taken to avoid reactivity and improve the stability of drug substances and products.

  17. The exploitation of "sicko-chatting" by the pharmaceutical industry : a strategy for the normalization of drug use

    OpenAIRE

    Niquette , Manon

    2012-01-01

    International audience; The Exploitation of 'sicko-chatting' by the Pharmaceutical industry: a strategy for the Normalization of drug use Pharmaceutical drugs are consumer goods. As such, they inscribe the transition from normality to pathology within the ambit of health marketing (Duclos, 2008, p. 109). It is now widely acknowledged that this pathology is not just a mere quantitative modification of the normal state, but that it also implies the patient's qualitative assessment of his or her...

  18. Synthesis and applications of radiolabelled drugs in pharmaceutical development

    International Nuclear Information System (INIS)

    Landvatter, S.W.; Heys, J.R.; Garner, K.T.; Mack, J.F.; Senderoff, S.G.; Shu, A.Y.; Villani, A.J.; Saunders, D.

    1994-01-01

    Radiolabelled drugs play a vital role in the development of new pharmaceuticals including application in drug discovery, pre-clinical development and clinical development. The synthesis of these pharmaceuticals in tritium or carbon-14 labelled form poses many challenges for the synthetic organic chemist. The actual choice of synthetic route must take into account the small scale, limited choice and high cost of labelled precursors, and the positioning of the label into a metabolically stable position. There are, however, a number of synthetic strategies available for overcoming these constraints. Although in some C-14 syntheses the requisite labelled raw material can be purchased and the existing synthesis adapted for labelling, frequently the synthetic challenge is the synthesis of a structurally simple, yet commercially unavailable, labelled precursor (e.g., γ-butyrolactone-[2- 14 C], cyclohexanone-[ 3 H], CuCN-[ 14 C], 2-furancarboxaldehyde-[ 14 C]). Another useful strategy in C-14 synthesis is the conversion of an advanced intermediate, or perhaps the unlabelled product itself, into a precursor which can then be reconverted into the labelled version of the intermediate. Occasionally, a new total synthesis must be developed. In addition to these strategies, tritium labelling can uniquely take advantage of exchange labelling techniques, synthesis and reduction of unsaturated precursors, or tritium-halogen replacement reactions. Examples of these strategies and use of the labelled products are discussed

  19. Basic pharmaceutical technology

    OpenAIRE

    Angelovska, Bistra; Drakalska, Elena

    2017-01-01

    The lecture deals with basics of pharmaceutical technology as applied discipline of pharmaceutical science, whose main subject of study is formulation and manufacture of drugs. In a broad sense, pharmaceutical technology is science of formulation, preparation, stabilization and determination of the quality of medicines prepared in the pharmacy or in pharmaceutical industry

  20. [Hospital pharmaceutical practice in prison].

    Science.gov (United States)

    Harcouët, L

    2010-09-01

    Since 1994, hospital pharmaceutical teams have been in charge of pharmaceutical tasks in "unités de consultation et de soins ambulatoires" (UCSA), which are hospital consulting care units in French prisons. In 2008, pharmaceutical team in Parisian prisons received 6500 prescriptions and prepared 85,000 nominative bags containing drugs. Prisoners were 1.3% to receive treatments against HIV, 8.2% cardiovascular drugs, 7.2% opioid substitution treatments, and 52.9% psychoactive drugs, including 39.3% hypnotics, 40.5% anxiolytics, 11.3% antidepressants and 12.2% neuroleptics. In prison, the dichotomy between somatic and mental care is marked, attitudes of prisoners about their medicines are complex (important claims, embezzlement, etc.) and it is difficult for law defendants to maintain treatment confidentiality and to prepare prison outing in terms of health. To attenuate the heterogeneity of drug distribution systems in French prisons, we propose pharmaceutical analysis of prescriptions and nominative dispensation, computerization in UCSA in coordination with hospitals, a better contribution of prison medical and pharmaceutical staff in hospital "drug committees" and the redaction of pharmaceutical guidelines. Acting in concert with multidisciplinary medical staff in UCSA, pharmaceutical teams have to develop epidemiological studies to improve knowledge in prisoner's health and also prevention and health care in prison. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  1. [Drug management of prisoners: Role of the pharmaceutical staff to ensure patient safety].

    Science.gov (United States)

    Lalande, L; Bertin, C; Rioufol, C; Boleor, P; Cabelguenne, D

    2016-03-01

    In the prisons of Lyon, drug management of inmates implies cooperation between general practitioners, psychiatrists and pharmacists. All the medical prescriptions are reviewed by the pharmacists of the medical unit. The aim of this work was to synthesize the pharmaceutical interventions performed and show the implication of the pharmaceutical staff in detecting and handling prescribing errors. Pharmaceutical interventions performed between the 1st of June 2012 and the 31st December 2014 and entered in the Act-IP(®) database (SFPC) were retrospectively analyzed. Among the 18,205 prescriptions reviewed, 4064 (22.3%) had a prescription error. The main problems encountered were by decreasing order of frequency: missing monitoring (15% of the interventions), lack of compliance (13%), over dosage (10%), lack of conformity with recommendations or consensus (8%). Interventions were accepted in 78% cases. Most prescribing errors implied medications of the central nervous system. Among the interventions, 8% were initiated by pharmacy technicians, mainly lack of compliance. The pharmaceutical interventions reported reflected actions of securisation initiated by the pharmacists in cooperation with physicians: monitoring of patients taking antipsychotic medications or benzodiazepines maximal dosages. Besides, in this population with a high prevalence of psychiatric comorbidities and important suicide rate, detection of patients with default of compliance is one of the keys for drug optimization among these patients as it is an explanation for therapeutic failure. Copyright © 2015 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

  2. Assessment of chimeric mice with humanized livers in new drug development: generation of pharmacokinetics, metabolism and toxicity data for selecting the final candidate compound.

    Science.gov (United States)

    Kamimura, Hidetaka; Ito, Satoshi

    2016-01-01

    1. Chimeric mice with humanized livers are expected to be a novel tool for new drug development. This review discusses four applications where these animals can be used efficiently to collect supportive data for selecting the best compound in the final stage of drug discovery. 2. The first application is selection of the final compound based on estimated pharmacokinetic parameters in humans. Since chimeric mouse livers are highly repopulated with human hepatocytes, hepatic clearance values in vivo could be used preferentially to estimate pharmacokinetic profiles for humans. 3. The second is prediction of human-specific or disproportionate metabolites. Chimeric mice reproduce human-specific metabolites of drugs under development to conform to ICH guidance M3(R2), except for compounds that were extensively eliminated by co-existing mouse hepatocytes. 4. The third is identifying metabolites with distinct pharmacokinetic profiles in humans. Slow metabolite elimination specifically in humans increases its exposure level, but if its elimination is faster in laboratory animals, the animal exposure level might not satisfy ICH guidance M3(R2). 5. Finally, two examples of reproducing acute liver toxicity in chimeric mice are introduced. Integrated pharmacokinetics, metabolism and toxicity information are expected to assist pharmaceutical scientists in selecting the best candidate compound in new drug development.

  3. Analysis of the domestic pharmaceutical market drugs for the treatment of urolithiasis

    Directory of Open Access Journals (Sweden)

    V. L. Shevina

    2014-12-01

    Full Text Available Urolithiasis is a metabolic disease caused by various endogenous and (or exogenous factors, often is hereditary and is defined by the stone presence in the urinary system. Antibacterial therapies, herbal medicine, dietary restrictions, mineral water are used in the complex treatment of patients with urolithiasis after removal of concrement by different methods. The search for new and improvement of already known methods of treatment of urolithiasis remains relevant to date. Along with the use of synthetic drugs the use of herbal remedies that have diuretic, antispasmodic, bacteriostatic and many other effects is appropriate. An extremely valuable feature of herbal products is their ability to enhance excretion of urea and other nitrogenous waste products of metabolism, which is especially important in cases of severe renal failure of different aetiology. Note, however, that the range of herbal medicines used for the treatment of urolithiasis with symptoms of azotaemia is rather limited. The aim of our study was to investigate the range of medicines used to treat urolithiasis presented in the domestic pharmaceutical market by different countries, as well as to determine whether the Ukrainian medicines are available in the domestic market. Materials and Methods The analysis of products’ range was performed according to the State Register of Medicines of Ukraine and АТС classification system. The object of the study was the medicinal products, which are used for treatment of urolithiasis. Results The products were analysed according to three АТС groups: products that inhibit uric acid synthesis; other urologicals; solvents of urinary concrement. The study has shown that 21 products are registered in Ukraine (June 2014. It has been established that the market is distributed almost equally between domestic and foreign manufacturers i.e. 8 foreign and 7 domestic manufacturers are present in the pharmaceutical market. The next stage of research

  4. The route from problem to solution in multistep continuous flow synthesis of pharmaceutical compounds.

    Science.gov (United States)

    Bana, Péter; Örkényi, Róbert; Lövei, Klára; Lakó, Ágnes; Túrós, György István; Éles, János; Faigl, Ferenc; Greiner, István

    2017-12-01

    Recent advances in the field of continuous flow chemistry allow the multistep preparation of complex molecules such as APIs (Active Pharmaceutical Ingredients) in a telescoped manner. Numerous examples of laboratory-scale applications are described, which are pointing towards novel manufacturing processes of pharmaceutical compounds, in accordance with recent regulatory, economical and quality guidances. The chemical and technical knowledge gained during these studies is considerable; nevertheless, connecting several individual chemical transformations and the attached analytics and purification holds hidden traps. In this review, we summarize innovative solutions for these challenges, in order to benefit chemists aiming to exploit flow chemistry systems for the synthesis of biologically active molecules. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Overview on zein protein: a promising pharmaceutical excipient in drug delivery systems and tissue engineering.

    Science.gov (United States)

    Labib, Gihan

    2018-01-01

    Natural pharmaceutical excipients have been applied extensively in the past decades owing to their safety and biocompatibility. Zein, a natural protein of plant origin offers great benefit over other synthetic polymers used in controlled drug and biomedical delivery systems. It was used in a variety of medical fields including pharmaceutical and biomedical drug targeting, vaccine, tissue engineering, and gene delivery. Being biodegradable and biocompatible, the current review focuses on the history and the medical application of zein as an attractive still promising biopolymer. Areas covered: The current review gives a broadscope on zein as a still promising protein excipient in different fields. Zein- based drug and biomedical delivery systems are discussed with special focus on current and potential application in controlled drug delivery systems, and tissue engineering. Expert opinion: Zein as a protein of natural origin can still be considered a promising polymer in the field of drug delivery systems as well as in tissue engineering. Although different researchers spotted light on zein application in different industrial fields extensively, the feasibility of its use in the field of drug delivery replenished by investigators in recent years has not yet been fully approached.

  6. Human-health pharmaceutical compounds in Lake Mead, Nevada and Arizona, and Las Vegas Wash, Nevada, October 2000-August 2001

    Science.gov (United States)

    Boyd, Robert A.; Furlong, Edward T.

    2002-01-01

    The U.S. Geological Survey and the National Park Service conducted a reconnaissance study to investigate the occurrence of selected human-health pharmaceutical compounds in water samples collected from Lake Mead on the Colorado River and Las Vegas Wash, a waterway used to transport treated wastewater from the Las Vegas metropolitan area to Lake Mead. Current research indicates many of these compounds can bioaccumulate and may adversely affect aquatic organisms by disrupting physiological processes, impairing reproductive functions, increasing cancer rates, contributing to the development of antibiotic-resistant strains of bacteria, and acting in undesirable ways when mixed with other substances. These compounds may be present in effluent because a high percentage of prescription and non-prescription drugs used for human-health purposes are excreted from the body as a mixture of parent compounds and degraded metabolite compounds; also, they can be released to the environment when unused products are discarded by way of toilets, sinks, and trash in landfills. Thirteen of 33 targeted compounds were detected in at least one water sample collected between October 2000 and August 2001. All concentrations were less than or equal to 0.20 micrograms per liter. The most frequently detected compounds in samples from Las Vegas Wash were caffeine, carbamazepine (used to treat epilepsy), cotinine (a metabolite of nicotine), and dehydronifedipine (a metabolite of the antianginal Procardia). Less frequently detected compounds in samples collected from Las Vegas Wash were antibiotics (clarithromycin, erythromycin, sulfamethoxazole, and trimethoprim), acetaminophen (an analgesic and anti-inflammatory), cimetidine (used to treat ulcers), codeine (a narcotic and analgesic), diltiazem (an antihypertensive), and 1,7-dimethylxanthine (a metabolite of caffeine). Fewer compounds were detected in samples collected from Lake Mead than from Las Vegas Wash. Caffeine was detected in all samples

  7. Kitchen chemistry: A scoping review of the diversionary use of pharmaceuticals for non-medicinal use and home production of drug solutions.

    Science.gov (United States)

    Van Hout, Marie Claire

    2014-01-01

    Misuse of pharmaceuticals is of increasing drug policy and public health concern. A scoping review was conducted on the diversionary use of pharmaceuticals for non-medicinal use and home production of drug solutions. The research question was broad: What is known from the existing literature about the diversion of pharmaceuticals for non-medicinal use and for home production of drug solutions? The scoping process centred on the systematic selection, collection, and summarization of extant knowledge within this broad thematic remit. One hundred and thirty-four records were grouped into discrete thematic categories namely: non medicinal use and tampering with pharmaceuticals, oral misuse of codeine cough syrups, homemade drug solutions, and home-produced drug-related harms in the narrative review design. Forms of abuse of codeine cough syrup include mixtures with alcohol or soft drinks ('Purple Drank'), with kratom leaves ('Kratom cocktails'), or chemically altered to extract dextromorphan ('Lemon Drop'). Production of homemade opiates ('Cheornaya', 'Kolyosa', Himiya', 'Braun', 'Krokodil'), methamphetamine ('Vint', 'Pervitin'), methcathinone ('Jeff'), and cathinone ('Boltushka') are described. Displacement patterns between the non-medical use of pharmaceuticals, commercial, and homemade drugs appear dependent on availability of opiates, prescribing practices, supervision of substitution drug dosing, availability of cheap ingredients, policing, and awareness of harms. Adverse health and social consequences relate to the use of unknown and contaminated (end) substances, injecting practices, redosing, medical complications, and death. The review highlights a public health imperative requiring a multidisciplinary approach to quantify potential impact and required integrated policy responses incorporating international regulation, enforcement, health surveillance and service delivery. Copyright © 2014 John Wiley & Sons, Ltd.

  8. Small molecule compound logistics outsourcing--going beyond the "thought experiment".

    Science.gov (United States)

    Ramsay, Devon L; Kwasnoski, Joseph D; Caldwell, Gary W

    2012-01-01

    Increasing pressure on the pharmaceutical industry to reduce cost and focus internal resources on "high value" activities is driving a trend to outsource traditionally "in-house" drug discovery activities. Compound collections are typically viewed as drug discovery's "crown jewels"; however, in late 2007, Johnson & Johnson Pharmaceutical Research & Development (J PRD) took a bold step to move their entire North American compound inventory and processing capability to an external third party vendor. The authors discuss the combination model implemented, that of local compound logistics site support with an outsourced centralized processing center. Some of the lessons learned over the past five years were predictable while others were unexpected. The substantial cost savings, improved local service response and flexible platform to adjust to changing business needs resulted. Continued sustainable success relies heavily upon maintaining internal headcount dedicated to vendor management, an open collaboration approach and a solid information technology infrastructure with complete transparency and visibility.

  9. Incorporation of in silico biodegradability screening in early drug development--a feasible approach?

    Science.gov (United States)

    Steger-Hartmann, Thomas; Länge, Reinhard; Heuck, Klaus

    2011-05-01

    The concentration of a pharmaceutical found in the environment is determined by the amount used by the patient, the excretion and metabolism pattern, and eventually by its persistence. Biological degradation or persistence of a pharmaceutical is experimentally tested rather late in the development of a pharmaceutical, often shortly before submission of the dossier to regulatory authorities. To investigate whether the aspect of persistence of a compound could be assessed early during drug development, we investigated whether biodegradation of pharmaceuticals could be predicted with the help of in silico tools. To assess the value of in silico prediction, we collected results for the OECD 301 degradation test ("ready biodegradability") of 42 drugs or drug synthesis intermediates and compared them to the prediction of the in silico tool BIOWIN. Of these compounds, 38 were predictable with BIOWIN, which is a module of the Estimation Programs Interface (EPI) Suite™ provided by the US EPA. The program failed to predict the two drugs which proved to be readily biodegradable in the degradation tests. On the other hand, BIOWIN predicted two compounds to be readily biodegradable which, however, proved to be persistent in the test setting. The comparison of experimental data with the predicted one resulted in a specificity of 94% and a sensitivity of 0%. The results of this study do not indicate that application of the biodegradation prediction tool BIOWIN is a feasible approach to assess the ready biodegradability during early drug development.

  10. Analysis of pharmaceutical and other organic wastewater compounds in filtered and unfiltered water samples by gas chromatography/mass spectrometry

    Science.gov (United States)

    Zaugg, Steven D.; Phillips, Patrick J.; Smith, Steven G.

    2014-01-01

    Research on the effects of exposure of stream biota to complex mixtures of pharmaceuticals and other organic compounds associated with wastewater requires the development of additional analytical capabilities for these compounds in water samples. Two gas chromatography/mass spectrometry (GC/MS) analytical methods used at the U.S. Geological Survey National Water Quality Laboratory (NWQL) to analyze organic compounds associated with wastewater were adapted to include additional pharmaceutical and other organic compounds beginning in 2009. This report includes a description of method performance for 42 additional compounds for the filtered-water method (hereafter referred to as the filtered method) and 46 additional compounds for the unfiltered-water method (hereafter referred to as the unfiltered method). The method performance for the filtered method described in this report has been published for seven of these compounds; however, the addition of several other compounds to the filtered method and the addition of the compounds to the unfiltered method resulted in the need to document method performance for both of the modified methods. Most of these added compounds are pharmaceuticals or pharmaceutical degradates, although two nonpharmaceutical compounds are included in each method. The main pharmaceutical compound classes added to the two modified methods include muscle relaxants, opiates, analgesics, and sedatives. These types of compounds were added to the original filtered and unfiltered methods largely in response to the tentative identification of a wide range of pharmaceutical and other organic compounds in samples collected from wastewater-treatment plants. Filtered water samples are extracted by vacuum through disposable solid-phase cartridges that contain modified polystyrene-divinylbenzene resin. Unfiltered samples are extracted by using continuous liquid-liquid extraction with dichloromethane. The compounds of interest for filtered and unfiltered sample

  11. Microemulsion utility in pharmaceuticals: Implications for multi-drug delivery.

    Science.gov (United States)

    Callender, Shannon P; Mathews, Jessica A; Kobernyk, Katherine; Wettig, Shawn D

    2017-06-30

    Emulsion technology has been utilized extensively in the pharmaceutical industry. This article presents a comprehensive review of the literature on an important subcategory of emulsions, microemulsions. Microemulsions are optically transparent, thermodynamically stable colloidal systems, 10-100nm diameter, that form spontaneously upon mixing of oil, water and emulsifier. This review is the first to address advantages and disadvantages, as well as considerations and challenges in multi-drug delivery. For the period 1 January 2011-30 April 2016, 431 publications related to microemulsion drug delivery were identified and screened according to microemulsion, drug classification, and surfactant types. Results indicate the use of microemulsions predominantly in lipophilic drug delivery (79.4%) via oil-in-water microemulsions and non-ionic surfactants (90%) for oral or topical administration. Cancer is the disease state most targeted followed by inflammatory diseases, microbial infections and cardiovascular disease. Key generalizations from this analysis include: 1) microemulsion formulation is largely based on trial-and-error despite over 1200 publications related to microemulsion drug delivery since their discovery in 1943; 2) characterization using methods including interfacial tension, droplet size, electrical conductivity, turbidity and viscosity may provide additional information for greater predictability; 3) microemulsion drug delivery publications arise primarily from China (27%) and India (21%) suggesting additional research opportunities elsewhere. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. An automated synthesis-purification-sample-management platform for the accelerated generation of pharmaceutical candidates.

    Science.gov (United States)

    Sutherland, J David; Tu, Noah P; Nemcek, Thomas A; Searle, Philip A; Hochlowski, Jill E; Djuric, Stevan W; Pan, Jeffrey Y

    2014-04-01

    A flexible and integrated flow-chemistry-synthesis-purification compound-generation and sample-management platform has been developed to accelerate the production of small-molecule organic-compound drug candidates in pharmaceutical research. Central to the integrated system is a Mitsubishi robot, which hands off samples throughout the process to the next station, including synthesis and purification, sample dispensing for purity and quantification analysis, dry-down, and aliquot generation.

  13. Aerosol-Assisted Fast Formulating Uniform Pharmaceutical Polymer Microparticles with Variable Properties toward pH-Sensitive Controlled Drug Release

    Directory of Open Access Journals (Sweden)

    Hong Lei

    2016-05-01

    Full Text Available Microencapsulation is highly attractive for oral drug delivery. Microparticles are a common form of drug carrier for this purpose. There is still a high demand on efficient methods to fabricate microparticles with uniform sizes and well-controlled particle properties. In this paper, uniform hydroxypropyl methylcellulose phthalate (HPMCP-based pharmaceutical microparticles loaded with either hydrophobic or hydrophilic model drugs have been directly formulated by using a unique aerosol technique, i.e., the microfluidic spray drying technology. A series of microparticles of controllable particle sizes, shapes, and structures are fabricated by tuning the solvent composition and drying temperature. It is found that a more volatile solvent and a higher drying temperature can result in fast evaporation rates to form microparticles of larger lateral size, more irregular shape, and denser matrix. The nature of the model drugs also plays an important role in determining particle properties. The drug release behaviors of the pharmaceutical microparticles are dependent on their structural properties and the nature of a specific drug, as well as sensitive to the pH value of the release medium. Most importantly, drugs in the microparticles obtained by using a more volatile solvent or a higher drying temperature can be well protected from degradation in harsh simulated gastric fluids due to the dense structures of the microparticles, while they can be fast-released in simulated intestinal fluids through particle dissolution. These pharmaceutical microparticles are potentially useful for site-specific (enteric delivery of orally-administered drugs.

  14. Organically functionalized mesoporous SBA-15 as sorbents for removal of selected pharmaceuticals from water

    Energy Technology Data Exchange (ETDEWEB)

    Bui, Tung Xuan [School of Environmental Science and Engineering, Gwangju Institute of Science and Technology (GIST), 261 Cheomdan-gwagiro, Buk-gu, Gwangju 500-712 (Korea, Republic of); Kang, Seo-Young [International Environmental Research Center (IERC), Gwangju Institute of Science and Technology (GIST), 261 Cheomdan-gwagiro, Buk-gu, Gwangju 500-712 (Korea, Republic of); Lee, Sang-Hyup [Water Environment Center, Korea Institute of Science and Technology, Cheongryang, Seoul 130-650 (Korea, Republic of); Choi, Heechul, E-mail: hcchoi@gist.ac.kr [School of Environmental Science and Engineering, Gwangju Institute of Science and Technology (GIST), 261 Cheomdan-gwagiro, Buk-gu, Gwangju 500-712 (Korea, Republic of)

    2011-10-15

    Highlights: {yields} SBA-15 grafted with aminopropyl, hydroxymethyl, and trimethylsilyl groups as sorbents. {yields} Sorbents for removal of a mixture of 12 pharmaceuticals from water. {yields} Hydroxymethyl-SBA-15 shows similar adsorption efficiency like SBA-15. {yields} Aminopropyl-SBA-15 makes increase for clofibric acid, diclofenac, decrease for atenolol, estrone, trimethoprim. {yields} Trimethylsilyl-SBA-15 makes increase for 9 compounds; 7 compounds from 70.6% to 98.9%. - Abstract: Mesoporous silica SBA-15 and its postfunctionalized counterparts with hydroxymethyl (HM-SBA-15), aminopropyl (AP-SBA-15), and trimethylsilyl (TMS-SBA-15) were prepared and characterized by powder X-ray diffraction, N{sub 2} adsorption-desorption measurement, Fourier-transform infrared spectroscopy, and elemental analysis. The removal of a mixture of 12 selected pharmaceuticals was investigated by batch adsorption experiments onto SBA-15 and the grafted materials. SBA-15 showed to have moderate adsorption affinity with amino-containing (atenolol, trimethoprim) and hydrophobic pharmaceuticals, but it displayed minimal adsorption affinity toward hydrophilic compounds. HM-SBA-15 was analogous with SBA-15 in terms of the adsorption efficiency toward all pharmaceuticals. AP-SBA-15 exhibited an increase in the adsorption of two acidic compounds (clofibric acid, diclofenac) but a decrease in the adsorption of estrone and the two amino-containing compounds. Among the grafted materials, TMS-SBA-15 had the highest adsorption affinity toward most pharmaceuticals. Moreover, the adsorption of nine pharmaceuticals to TMS-SBA-15 was significantly higher than that to SBA-15; seven of which showed the removal percentages from 70.6% to 98.9% onto TMS-SBA-15. The number of pharmaceuticals showing high adsorption efficiency onto TMS-SBA-15 did not alter significantly as the pH changed in the range of 5.5-7.6. The results suggest that TMS-SBA-15 is a promising material for the removal of pharmaceuticals

  15. Organically functionalized mesoporous SBA-15 as sorbents for removal of selected pharmaceuticals from water

    International Nuclear Information System (INIS)

    Bui, Tung Xuan; Kang, Seo-Young; Lee, Sang-Hyup; Choi, Heechul

    2011-01-01

    Highlights: → SBA-15 grafted with aminopropyl, hydroxymethyl, and trimethylsilyl groups as sorbents. → Sorbents for removal of a mixture of 12 pharmaceuticals from water. → Hydroxymethyl-SBA-15 shows similar adsorption efficiency like SBA-15. → Aminopropyl-SBA-15 makes increase for clofibric acid, diclofenac, decrease for atenolol, estrone, trimethoprim. → Trimethylsilyl-SBA-15 makes increase for 9 compounds; 7 compounds from 70.6% to 98.9%. - Abstract: Mesoporous silica SBA-15 and its postfunctionalized counterparts with hydroxymethyl (HM-SBA-15), aminopropyl (AP-SBA-15), and trimethylsilyl (TMS-SBA-15) were prepared and characterized by powder X-ray diffraction, N 2 adsorption-desorption measurement, Fourier-transform infrared spectroscopy, and elemental analysis. The removal of a mixture of 12 selected pharmaceuticals was investigated by batch adsorption experiments onto SBA-15 and the grafted materials. SBA-15 showed to have moderate adsorption affinity with amino-containing (atenolol, trimethoprim) and hydrophobic pharmaceuticals, but it displayed minimal adsorption affinity toward hydrophilic compounds. HM-SBA-15 was analogous with SBA-15 in terms of the adsorption efficiency toward all pharmaceuticals. AP-SBA-15 exhibited an increase in the adsorption of two acidic compounds (clofibric acid, diclofenac) but a decrease in the adsorption of estrone and the two amino-containing compounds. Among the grafted materials, TMS-SBA-15 had the highest adsorption affinity toward most pharmaceuticals. Moreover, the adsorption of nine pharmaceuticals to TMS-SBA-15 was significantly higher than that to SBA-15; seven of which showed the removal percentages from 70.6% to 98.9% onto TMS-SBA-15. The number of pharmaceuticals showing high adsorption efficiency onto TMS-SBA-15 did not alter significantly as the pH changed in the range of 5.5-7.6. The results suggest that TMS-SBA-15 is a promising material for the removal of pharmaceuticals from aqueous phase

  16. Microtitrimetric determination of a drug content of pharmaceuticals containing olanzapine in non-aqueous medium

    Directory of Open Access Journals (Sweden)

    KANAKAPURA BASAVAIAH

    2009-05-01

    Full Text Available Two simple, rapid, reliable and cost-effective methods based on titrimetry in non-aqueous medium are described for the determination of olanzapine in pharmaceuticals. In these methods, the drug dissolved in the glacial acetic acid was titrated with the acetous perchloric acid with visual and potentiometric end point detection, crystal violet being used as the indicator for visual titration. The methods are applicable over 1-15 mg range of olanzapine. The procedures were applied to determine olanzapine in pharmaceutical products and the results were found to be in a good agreement with those obtained by the reference method. Associated pharmaceutical materials did not interfere. The precision results, expressed by inter-day and intra-day relative standard deviation values, were satisfactory, higher than 2%. The accuracy was satisfactory as well. The methods proved to be suitable for the analysis of olanzapine in bulk drug and in tablets. The accuracy and reliability of the methods were further ascertained by recovery studies via a standard addition technique with percent recoveries in the range 97.51-103.7% with a standard deviation of less than 2%.

  17. Illicit drugs and pharmaceuticals in the environment--forensic applications of environmental data, Part 2: Pharmaceuticals as chemical markers of faecal water contamination.

    Science.gov (United States)

    Kasprzyk-Hordern, Barbara; Dinsdale, Richard M; Guwy, Alan J

    2009-06-01

    This manuscript is part two of a two-part study aiming to provide a better understanding and application of environmental data not only for environmental aims but also to meet forensic objectives. In this paper pharmaceuticals were investigated as potential chemical indicators of water contamination with sewage. The monitoring program carried out in Wales revealed that some pharmaceuticals are particularly persistent and/or ubiquitous in contaminated river water and therefore might be considered as potential conservative or labile wastewater indicators. In particular, these include some anti-inflammatory/analgesics, antiepileptics, beta-blockers, some H2-receptor antagonists and antibacterial drugs.

  18. Determination of drug, excipients and coating distribution in pharmaceutical tablets using NIR-CI

    Directory of Open Access Journals (Sweden)

    Anna Palou

    2012-04-01

    Full Text Available The growing interest of the pharmaceutical industry in Near Infrared-Chemical Imaging (NIR-CI is a result of its high usefulness for quality control analyses of drugs throughout their production process (particularly of its non-destructive nature and expeditious data acquisition. In this work, the concentration and distribution of the major and minor components of pharmaceutical tablets are determined and the spatial distribution from the internal and external sides has been obtained. In addition, the same NIR-CI allowed the coating thickness and its surface distribution to be quantified. Images were processed to extract the target data and calibration models constructed using the Partial Least Squares (PLS algorithms. The concentrations of Active Pharmaceutical Ingredient (API and excipients obtained for uncoated cores were essentially identical to the nominal values of the pharmaceutical formulation. But the predictive ability of the calibration models applied to the coated tablets decreased as the coating thickness increased. Keywords: Near infrared Chemical Imaging (NIR-CI, Hyperspectral imaging, Component distribution, Tablet coating distribution, Partial Least Squares (PLS regression

  19. Clarke's Isolation and identification of drugs in pharmaceuticals, body fluids, and post-mortem material

    National Research Council Canada - National Science Library

    Clarke, E. G. C; Moffat, A. C; Jackson, J. V

    1986-01-01

    This book is intended for scientists faced with the difficult problem of identifying an unknown drug in a pharmaceutical product, in a sample of tissue or body fluid from a living patient, or in post-mortem material...

  20. Co-binding of pharmaceutical compounds at mineral surfaces: Molecular investigations of dimer formation at goethite/water interfaces

    OpenAIRE

    Xu , Jing; Marsac , Rémi; Costa , Dominique; Cheng , Wei; Wu , Feng; Boily , Jean-François; Hanna , Khalil

    2017-01-01

    International audience; The emergence of antibiotic and anti-inflammatory agents in aquatic and terrestrial systems is becoming a serious threat to human and animal health worldwide. Because pharmaceutical compounds rarely exist individually in nature, interactions between various compounds can have unforeseen effects on their binding to mineral surfaces. This work demonstrates this important possibility for the case of two typical antibiotic and anti-inflammatory agents (nalidixic acid (NA) ...

  1. The lay user perspective on the quality of pharmaceuticals, drug therapy and pharmacy services--results of focus group discussions

    DEFF Research Database (Denmark)

    Traulsen, Janine Marie; Almarsdóttir, Anna Birna; Björnsdóttir, Ingunn

    2002-01-01

    This article presents the results of a study on quality of pharmacy services and perceived risk of pharmaceuticals. The results presented here are part of a multi-study evaluation of major changes in drug distribution in Iceland.......This article presents the results of a study on quality of pharmacy services and perceived risk of pharmaceuticals. The results presented here are part of a multi-study evaluation of major changes in drug distribution in Iceland....

  2. Chromatographic and Spectral Analysis of Two Main Extractable Compounds Present in Aqueous Extracts of Laminated Aluminum Foil Used for Protecting LDPE-Filled Drug Vials

    Science.gov (United States)

    Akapo, Samuel O.; Syed, Sajid; Mamangun, Anicia; Skinner, Wayne

    2009-01-01

    Laminated aluminum foils are increasingly being used to protect drug products packaged in semipermeable containers (e.g., low-density polyethylene (LDPE)) from degradation and/or evaporation. The direct contact of such materials with primary packaging containers may potentially lead to adulteration of the drug product by extractable or leachable compounds present in the closure system. In this paper, we described a simple and reliable HPLC method for analysis of an aqueous extract of laminated aluminum foil overwrap used for packaging LDPE vials filled with aqueous pharmaceutical formulations. By means of combined HPLC-UV, GC/MS, LC/MS/MS, and NMR spectroscopy, the two major compounds detected in the aqueous extracts of the representative commercial overwraps were identified as cyclic oligomers with molecular weights of 452 and 472 and are possibly formed from poly-condensation of the adhesive components, namely, isophthalic acid, adipic acid, and diethylene glycol. Lower molecular weight compounds that might be associated with the “building blocks” of these compounds were not detected in the aqueous extracts. PMID:20140083

  3. Occurrence of pharmaceuticals and perfluorinated compounds and evaluation of the availability of reclaimed water in Kinmen

    Directory of Open Access Journals (Sweden)

    Webber Wei-Po Lai

    2016-09-01

    Full Text Available Emerging contaminants have commonly been observed in environmental waters but have not been included in water quality assessments at many locations around the world. To evaluate the availability of reclaimed water in Kinmen, Taiwan, this study provides the first survey of the distribution of thirty-three pharmaceuticals and five perfluorinated chemicals in lake waters and water from local wastewater treatment plants (WWTPs. The results showed that the target emerging contaminants in Kinmen lakes were at trace ng/L concentrations. In addition, most of the target compounds were present in the Jincheng and Taihu WWTP influents at ng/L concentrations levels, of which 5 compounds (erythromycin-H2O (1340 ng/L, ibuprofen (1763 ng/L, atenolol (1634 ng/L, acetaminophen (2143 ng/L, and caffeine (3113 ng/L reached μg/L concentrations. The overall treatment efficiencies of the Jincheng and Taihu WWTPs with respect to these pharmaceuticals and perfluorinated chemicals were poor; half of the compounds were less than 50% removed. Five compounds (sulfamethoxazole, erythromycin-H2O, clarithromycin, ciprofloxacin and ofloxacin with risk quotient (RQ values > 1 in the effluent should be further investigated to understand their effects on the aquatic environment. Additional and advanced treatment units are found necessary to provide high-quality recycled water and sustainable water resources.

  4. Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond

    Science.gov (United States)

    Van Voorhis, Wesley C.; Adams, John H.; Adelfio, Roberto; Ahyong, Vida; Akabas, Myles H.; Alano, Pietro; Alday, Aintzane; Alemán Resto, Yesmalie; Alsibaee, Aishah; Alzualde, Ainhoa; Andrews, Katherine T.; Avery, Simon V.; Avery, Vicky M.; Ayong, Lawrence; Baker, Mark; Baker, Stephen; Ben Mamoun, Choukri; Bhatia, Sangeeta; Bickle, Quentin; Bounaadja, Lotfi; Bowling, Tana; Bosch, Jürgen; Boucher, Lauren E.; Boyom, Fabrice F.; Brea, Jose; Brennan, Marian; Burton, Audrey; Caffrey, Conor R.; Camarda, Grazia; Carrasquilla, Manuela; Carter, Dee; Belen Cassera, Maria; Chih-Chien Cheng, Ken; Chindaudomsate, Worathad; Chubb, Anthony; Colon, Beatrice L.; Colón-López, Daisy D.; Corbett, Yolanda; Crowther, Gregory J.; Cowan, Noemi; D’Alessandro, Sarah; Le Dang, Na; Delves, Michael; Du, Alan Y.; Duffy, Sandra; Abd El-Salam El-Sayed, Shimaa; Ferdig, Michael T.; Fernández Robledo, José A.; Fidock, David A.; Florent, Isabelle; Fokou, Patrick V. T.; Galstian, Ani; Gamo, Francisco Javier; Gold, Ben; Golub, Todd; Goldgof, Gregory M.; Guha, Rajarshi; Guiguemde, W. Armand; Gural, Nil; Guy, R. Kiplin; Hansen, Michael A. E.; Hanson, Kirsten K.; Hemphill, Andrew; Hooft van Huijsduijnen, Rob; Horii, Takaaki; Horrocks, Paul; Hughes, Tyler B.; Huston, Christopher; Igarashi, Ikuo; Ingram-Sieber, Katrin; Itoe, Maurice A.; Jadhav, Ajit; Naranuntarat Jensen, Amornrat; Jensen, Laran T.; Jiang, Rays H. Y.; Kaiser, Annette; Keiser, Jennifer; Ketas, Thomas; Kicka, Sebastien; Kim, Sunyoung; Kirk, Kiaran; Kumar, Vidya P.; Kyle, Dennis E.; Lafuente, Maria Jose; Landfear, Scott; Lee, Nathan; Lee, Sukjun; Lehane, Adele M.; Li, Fengwu; Little, David; Liu, Liqiong; Llinás, Manuel; Loza, Maria I.; Lubar, Aristea; Lucantoni, Leonardo; Lucet, Isabelle; Maes, Louis; Mancama, Dalu; Mansour, Nuha R.; March, Sandra; McGowan, Sheena; Medina Vera, Iset; Meister, Stephan; Mercer, Luke; Mestres, Jordi; Mfopa, Alvine N.; Misra, Raj N.; Moon, Seunghyun; Moore, John P.; Morais Rodrigues da Costa, Francielly; Müller, Joachim; Muriana, Arantza; Nakazawa Hewitt, Stephen; Nare, Bakela; Nathan, Carl; Narraidoo, Nathalie; Nawaratna, Sujeevi; Ojo, Kayode K.; Ortiz, Diana; Panic, Gordana; Papadatos, George; Parapini, Silvia; Patra, Kailash; Pham, Ngoc; Prats, Sarah; Plouffe, David M.; Poulsen, Sally-Ann; Pradhan, Anupam; Quevedo, Celia; Quinn, Ronald J.; Rice, Christopher A.; Abdo Rizk, Mohamed; Ruecker, Andrea; St. Onge, Robert; Salgado Ferreira, Rafaela; Samra, Jasmeet; Robinett, Natalie G.; Schlecht, Ulrich; Schmitt, Marjorie; Silva Villela, Filipe; Silvestrini, Francesco; Sinden, Robert; Smith, Dennis A.; Soldati, Thierry; Spitzmüller, Andreas; Stamm, Serge Maximilian; Sullivan, David J.; Sullivan, William; Suresh, Sundari; Suzuki, Brian M.; Suzuki, Yo; Swamidass, S. Joshua; Taramelli, Donatella; Tchokouaha, Lauve R. Y.; Theron, Anjo; Thomas, David; Tonissen, Kathryn F.; Townson, Simon; Tripathi, Abhai K.; Trofimov, Valentin; Udenze, Kenneth O.; Ullah, Imran; Vallieres, Cindy; Vigil, Edgar; Vinetz, Joseph M.; Voong Vinh, Phat; Vu, Hoan; Watanabe, Nao-aki; Weatherby, Kate; White, Pamela M.; Wilks, Andrew F.; Winzeler, Elizabeth A.; Wojcik, Edward; Wree, Melanie; Wu, Wesley; Yokoyama, Naoaki; Zollo, Paul H. A.; Abla, Nada; Blasco, Benjamin; Burrows, Jeremy; Laleu, Benoît; Leroy, Didier; Spangenberg, Thomas; Wells, Timothy; Willis, Paul A.

    2016-01-01

    A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery. The Medicines for Malaria Venture Malaria Box is a collection of over 400 compounds representing families of structures identified in phenotypic screens of pharmaceutical and academic libraries against the Plasmodium falciparum malaria parasite. The set has now been distributed to almost 200 research groups globally in the last two years, with the only stipulation that information from the screens is deposited in the public domain. This paper reports for the first time on 236 screens that have been carried out against the Malaria Box and compares these results with 55 assays that were previously published, in a format that allows a meta-analysis of the combined dataset. The combined biochemical and cellular assays presented here suggest mechanisms of action for 135 (34%) of the compounds active in killing multiple life-cycle stages of the malaria parasite, including asexual blood, liver, gametocyte, gametes and insect ookinete stages. In addition, many compounds demonstrated activity against other pathogens, showing hits in assays with 16 protozoa, 7 helminths, 9 bacterial and mycobacterial species, the dengue fever mosquito vector, and the NCI60 human cancer cell line panel of 60 human tumor cell lines. Toxicological, pharmacokinetic and metabolic properties were collected on all the compounds, assisting in the selection of the most promising candidates for murine proof-of-concept experiments and medicinal

  5. Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond.

    Directory of Open Access Journals (Sweden)

    Wesley C Van Voorhis

    2016-07-01

    Full Text Available A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery. The Medicines for Malaria Venture Malaria Box is a collection of over 400 compounds representing families of structures identified in phenotypic screens of pharmaceutical and academic libraries against the Plasmodium falciparum malaria parasite. The set has now been distributed to almost 200 research groups globally in the last two years, with the only stipulation that information from the screens is deposited in the public domain. This paper reports for the first time on 236 screens that have been carried out against the Malaria Box and compares these results with 55 assays that were previously published, in a format that allows a meta-analysis of the combined dataset. The combined biochemical and cellular assays presented here suggest mechanisms of action for 135 (34% of the compounds active in killing multiple life-cycle stages of the malaria parasite, including asexual blood, liver, gametocyte, gametes and insect ookinete stages. In addition, many compounds demonstrated activity against other pathogens, showing hits in assays with 16 protozoa, 7 helminths, 9 bacterial and mycobacterial species, the dengue fever mosquito vector, and the NCI60 human cancer cell line panel of 60 human tumor cell lines. Toxicological, pharmacokinetic and metabolic properties were collected on all the compounds, assisting in the selection of the most promising candidates for murine proof-of-concept experiments

  6. The contribution of pharmaceutically active compounds from healthcare facilities to a receiving sewage treatment plant in Canada.

    Science.gov (United States)

    Kleywegt, Sonya; Pileggi, Vince; Lam, Yuet Ming; Elises, Alan; Puddicomb, Aaron; Purba, Gurminder; Di Caro, Joanne; Fletcher, Tim

    2016-04-01

    Concentrations and percent loadings of pharmaceutically active compounds (PhACs) and other emerging contaminants released from healthcare facilities (2 hospitals and a long-term care facility) to a sewage treatment plant (STP) in a large urban sewershed were evaluated. An additional hospital outside the sewershed was also monitored. Fourteen of the 24 steroids/hormones and 88 of the 117 PhACs and emerging contaminants were detected at least once. Commonly used substances, including cotinine, caffeine and its metabolite 1,7-dimethylxanthine, ibuprofen and naproxen (analgesics), venlafaxine (antidepressant), and N,N-diethyl-meta-toluamide (insect repellant), were detected in all samples at all sites. Concentrations detected in the large specialty hospital outside the sewershed were similar to those within the sewershed. Cytotoxic drugs (tamoxifen and cyclophosphamide) and x-ray contrast media (iopamidol and diatrizoic acid) were infrequently detected in hospital effluents. Analysis for antibiotics indicated that azithromycin, clarithromycin, ciprofloxacin, erythromycin, ofloxacin, and sulfamethoxazole were consistently detected in hospital wastewaters, as was triclosan (antibacterial agent). Fifteen compounds individually contributed greater than 1% to the total PhAC and emerging contaminant load to the STP from the 2 hospitals in the sewershed, and 9 compounds in the STP effluent exceeded ecotoxicological criteria. The present survey demonstrates that point source discharges from healthcare facilities in this sewershed make a small contribution to the overall PhAC and emerging contaminant loading compared with the total concentrations entering the receiving STP. © 2015 SETAC.

  7. Pharmaceutical Additive Manufacturing: a Novel Tool for Complex and Personalized Drug Delivery Systems.

    Science.gov (United States)

    Zhang, Jiaxiang; Vo, Anh Q; Feng, Xin; Bandari, Suresh; Repka, Michael A

    2018-06-25

    Inter-individual variability is always an issue when treating patients of different races, genders, ages, pharmacogenetics, and pharmacokinetic characteristics. However, the development of novel dosage forms is limited by the huge investments required for production line modifications and dosages diversity. Additive manufacturing (AM) or 3D printing can be a novel alternative solution for the development of controlled release dosages because it can produce personalized or unique dosage forms and more complex drug-release profiles. The primary objective of this manuscript is to review the 3D printing processes that have been used in the pharmaceutical area, including their general aspects, materials, and the operation of each AM technique. Advantages and shortcomings of the technologies are discussed with respect to practice and practical applications. Thus, this review will provide an overview and discussion on advanced pharmaceutical AM technologies, which can be used to produce unique controlled drug delivery systems and personalized dosages for the future of personalized medicine.

  8. Fluency of pharmaceutical drug names predicts perceived hazardousness, assumed side effects and willingness to buy.

    Science.gov (United States)

    Dohle, Simone; Siegrist, Michael

    2014-10-01

    The impact of pharmaceutical drug names on people's evaluations and behavioural intentions is still uncertain. According to the representativeness heuristic, evaluations should be more positive for complex drug names; in contrast, fluency theory suggests that evaluations should be more positive for simple drug names. Results of three experimental studies showed that complex drug names were perceived as more hazardous than simple drug names and negatively influenced willingness to buy. The results are of particular importance given the fact that there is a worldwide trend to make more drugs available for self-medication. © The Author(s) 2013.

  9. Determination of prilocaine HCl in bulk drug and pharmaceutical formulation by GC-NPD method

    Directory of Open Access Journals (Sweden)

    Atila Alptug

    2013-01-01

    Full Text Available The novel analytical method was developed and validated for determination of prilocaine HCl in bulk drug and pharmaceutical formulation by gas chromatography-nitrogen phosphorus detection (GC-NPD. The chromatographic separation was performed using a HP-5MS column. The calibration curve was linear over the concentration range of 40-1000 ng ml-1 with a correlation coefficient of 0.9998. The limits of detection (LOD and quantification (LOQ of method were 10 ng ml-1 and 35 ng ml-1, respectively. The within-day and between-day precision, expressed as the percent relative standard deviation (RSD% was less than 5.0%, and accuracy (percent relative error was better than 4.0%. The developed method can be directly and easily applied for determination of prilocaine HCl in bulk drug and pharmaceutical formulation using internal standard methodology.

  10. Nanocrystals Technology for Pharmaceutical Science.

    Science.gov (United States)

    Cheng, Zhongyao; Lian, Yumei; Kamal, Zul; Ma, Xin; Chen, Jianjun; Zhou, Xinbo; Su, Jing; Qiu, Mingfeng

    2018-05-17

    Nanocrystals technology is a promising method for improving the dissolution rate and enhancing the bioavailability of poorly soluble drugs. In recent years, it has been developing rapidly and applied to drug research and engineering. Nanocrystal drugs can be formulated into various dosage forms. This review mainly focused on the nanocrystals technology and its application in pharmaceutical science. Firstly, different preparation methods of nanocrystal technology and the characterization of nanocrystal drugs are briefly described. Secondly, the application of nanocrystals technology in pharmaceutical science is mainly discussed followed by the introduction of sustained release formulations. Then, the scaling up process, marketed nanocrystal drug products and regulatory aspects about nanodrugs are summarized. Finally, the specific challenges and opportunities of nanocrystals technology for pharmaceutical science are summarized and discussed. This review will provide a comprehensive guide for scientists and engineers in the field of pharmaceutical science and biochemical engineering. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Occurrence of pharmaceutically active and non-steroidal estrogenic compounds in three different wastewater recycling schemes in Australia.

    Science.gov (United States)

    Al-Rifai, Jawad H; Gabelish, Candace L; Schäfer, Andrea I

    2007-10-01

    The discovery that natural and synthetic chemicals, in the form of excreted hormones and pharmaceuticals, as well as a vast array of compounds with domestic and industrial applications, can enter the environment via wastewater treatment plants and cause a wide variety of environmental and health problems even at very low concentrations, suggests the need for improvement of water recycling. Three Australian wastewater recycling schemes, two of which employ reverse osmosis (RO) technology, the other applying ozonation and biological activated carbon filtration, have been studied for their ability to remove trace organic contaminants including 11 pharmaceutically active compounds and two non-steroidal estrogenic compounds. Contaminant concentrations were determined using a sensitive analytical method comprising solid phase extraction, derivatization and GC with MS using selected ion monitoring. In raw wastewater, concentrations of analgesics and non-steroidal anti-inflammatory medications were comparable to those found in wastewaters around the world. Remarkably, removal efficiencies for the three schemes were superior to literature values and RO was responsible for the greatest proportion of contaminant removal. The ability of RO membranes to concentrate many of the compounds was demonstrated and highlights the need for continued research into monitoring wastewater treatment, concentrate disposal, improved water recycling schemes and ultimately, safer water and a cleaner environment.

  12. Exotic multifaceted medicinal plants of drugs and pharmaceutical ...

    African Journals Online (AJOL)

    They are sources of drugs and are used in herbal medicine to treat measles, malaria, asthma, eczema, cough, hepatitis, ringworm, ulcer and scabies. These plants are continuously screened and evaluated for their pharmacological properties. Bioactive compounds comprising flavanoids, alkaloids, steroids, terpenoids and ...

  13. Strategies to reduce the risk of drug-induced QT interval prolongation: a pharmaceutical company perspective.

    Science.gov (United States)

    Pollard, C E; Valentin, J-P; Hammond, T G

    2008-08-01

    Drug-induced prolongation of the QT interval is having a significant impact on the ability of the pharmaceutical industry to develop new drugs. The development implications for a compound causing a significant effect in the 'Thorough QT/QTc Study' -- as defined in the clinical regulatory guidance (ICH E14) -- are substantial. In view of this, and the fact that QT interval prolongation is linked to direct inhibition of the hERG channel, in the early stages of drug discovery the focus is on testing for and screening out hERG activity. This has led to understanding of how to produce low potency hERG blockers whilst retaining desirable properties. Despite this, a number of factors mean that when an integrated risk assessment is generated towards the end of the discovery phase (by conducting at least an in vivo QT assessment) a QT interval prolongation risk is still often apparent; inhibition of hERG channel trafficking and partitioning into cardiac tissue are just two confounding factors. However, emerging information suggests that hERG safety margins have high predictive value and that when hERG and in vivo non-clinical data are combined, their predictive value to man, whilst not perfect, is >80%. Although understanding the anomalies is important and is being addressed, of greater importance is developing a better understanding of TdP, with the aim of being able to predict TdP rather than using an imperfect surrogate marker (QT interval prolongation). Without an understanding of how to predict TdP risk, high-benefit drugs for serious indications may never be marketed.

  14. Do pharmaceuticals, pathogens, and other organic waste water compounds persist when waste water is used for recharge?

    Science.gov (United States)

    Cordy, Gail E.; Duran, Norma L.; Bouwer, Herman; Rice, Robert C.; Furlong, Edward T.; Zaugg, Steven D.; Meyer, Michael T.; Barber, Larry B.; Kolpin, Dana W.

    2004-01-01

    A proof-of-concept experiment was devised to determine if pharmaceuticals and other organic waste water compounds (OWCs), as well as pathogens, found in treated effluent could be transported through a 2.4 m soil column and, thus, potentially reach ground water under recharge conditions similar to those in arid or semiarid climates. Treated effluent was applied at the top of the 2.4 m long, 32.5 cm diameter soil column over 23 days, Samples of the column inflow were collected from the effluent storage tank at the beginning (Tbegin) and end (Tend) of the experiment, and a sample of the soil column drainage at the base of the column (Bend) was collected at the end of the experiment. Samples were analyzed for 131 OWCs including veterinary and human antibiotics, other prescription and nonprescription drugs, widely used household and industrial chemicals, and steroids and reproductive hormones, as well as the pathogens Salmonella and Legionella. Analytical results for the two effluent samples taken at the beginning (Tbegin) and end (Tend) of the experiment indicate that the number of OWCs detected in the column inflow decreased by 25% (eight compounds) and the total concentration of OWCs decreased by 46% while the effluent was in the storage tank during the 23-day experiment. After percolating through the soil column, an additional 18 compounds detected in Tend (67% of OWCs) were no longer detected in the effluent (Bend) and the total concentration of OWCs decreased by more than 70%. These compounds may have been subject to transformation (biotic and abiotic), adsorption, and (or) volatilization in the storage tank and during travel through the soil column. Eight compounds—carbamazapine; sulfamethoxazole; benzophenone; 5-methyl-1H-benzotriazole; N,N-diethyltoluamide; tributylphosphate; tri(2-chloroethyl) phosphate; and cholesterol—were detected in all three samples indicating they have the potential to reach ground water under recharge conditions similar to those in

  15. Anticancer drug discovery and pharmaceutical chemistry: a history.

    Science.gov (United States)

    Braña, Miguel F; Sánchez-Migallón, Ana

    2006-10-01

    There are several procedures for the chemical discovery and design of new drugs from the point of view of the pharmaceutical or medicinal chemistry. They range from classical methods to the very new ones, such as molecular modeling or high throughput screening. In this review, we will consider some historical approaches based on the screening of natural products, the chances for luck, the systematic screening of new chemical entities and serendipity. Another group comprises rational design, as in the case of metabolic pathways, conformation versus configuration and, finally, a brief description on available new targets to be carried out. In each approach, the structure of some examples of clinical interest will be shown.

  16. Plant Bioactive Metabolites and Drugs Produced by Endophytic Fungi of Spermatophyta

    Directory of Open Access Journals (Sweden)

    Rosario Nicoletti

    2015-09-01

    Full Text Available It is known that plant-based ethnomedicine represented the foundation of modern pharmacology and that many pharmaceuticals are derived from compounds occurring in plant extracts. This track still stimulates a worldwide investigational activity aimed at identifying novel bioactive products of plant origin. However, the discovery that endophytic fungi are able to produce many plant-derived drugs has disclosed new horizons for their availability and production on a large scale by the pharmaceutical industry. In fact, following the path traced by the blockbuster drug taxol, an increasing number of valuable compounds originally characterized as secondary metabolites of plant species belonging to the Spermatophyta have been reported as fermentation products of endophytic fungal strains. Aspects concerning sources and bioactive properties of these compounds are reviewed in this paper.

  17. Emerging trends in the stabilization of amorphous drugs

    DEFF Research Database (Denmark)

    Laitinen, Riikka; Löbmann, Korbinian; Strachan, Clare J.

    2013-01-01

    The number of active pharmaceutical substances having high therapeutic potential but low water solubility is constantly increasing, making it difficult to formulate these compounds as oral dosage forms. The solubility and dissolution rate, and thus potentially the bioavailability, of these poorly...... water-soluble drugs can be increased by the formation of stabilized amorphous forms. Currently, formulation as solid polymer dispersions is the preferred method to enhance drug dissolution and to stabilize the amorphous form of a drug. The purpose of this review is to highlight emerging alternative...... of mesoporous silicon and silica-based carriers are presented as potential means to increase the stability of amorphous pharmaceuticals....

  18. Recognizing misleading pharmaceutical marketing online.

    Science.gov (United States)

    De Freitas, Julian; Falls, Brian A; Haque, Omar S; Bursztajn, Harold J

    2014-01-01

    In light of decision-making psychology, this article details how drug marketing operates across established and novel web domains and identifies some common misleading trends and influences on prescribing and patient-initiated medication requests. The Internet has allowed pharmaceutical marketing to become more salient than ever before. Although the Internet's growth has improved the dissemination of pharmaceutical information, it has also led to the increased influence of misleading pharmaceutical marketing. Such mismarketing is of concern, especially in psychiatry, since psychotropics generate considerable revenue for drug companies. In a climate of resource-limited drug regulation and time-strapped physicians, we recommend improving both independent monitoring and consumer awareness of Internet-enabled, potentially misleading, pharmaceutical marketing influences. © 2014 American Academy of Psychiatry and the Law.

  19. Human-Health Pharmaceutical Compounds in Lake Mead, Nevada and Arizona, and Las Vegas Wash, Nevada, October 2000-August 2001

    National Research Council Canada - National Science Library

    Boyd, Robert A; Furlong, Edward T

    2002-01-01

    The U.S. Geological Survey and the National Park Service conducted a reconnaissance study to investigate the occurrence of selected human-health pharmaceutical compounds in water samples collected from Lake...

  20. Rapid analysis of pharmaceutical drugs using LIBS coupled with multivariate analysis.

    Science.gov (United States)

    Tiwari, P K; Awasthi, S; Kumar, R; Anand, R K; Rai, P K; Rai, A K

    2018-02-01

    Type 2 diabetes drug tablets containing voglibose having dose strengths of 0.2 and 0.3 mg of various brands have been examined, using laser-induced breakdown spectroscopy (LIBS) technique. The statistical methods such as the principal component analysis (PCA) and the partial least square regression analysis (PLSR) have been employed on LIBS spectral data for classifying and developing the calibration models of drug samples. We have developed the ratio-based calibration model applying PLSR in which relative spectral intensity ratios H/C, H/N and O/N are used. Further, the developed model has been employed to predict the relative concentration of element in unknown drug samples. The experiment has been performed in air and argon atmosphere, respectively, and the obtained results have been compared. The present model provides rapid spectroscopic method for drug analysis with high statistical significance for online control and measurement process in a wide variety of pharmaceutical industrial applications.

  1. Medicinal gold compounds

    International Nuclear Information System (INIS)

    Parish, R.V.; Cottrill, S.M.

    1987-01-01

    A major use of gold compounds in the pharmaceutical industry is for anti-arthritic agents. The disease itself is not understood and little is known about the way in which the drugs act, but detailed pictures of the distribution of gold in the body are available, and some of the relevant biochemistry is beginning to emerge. The purpose of this article is to give a survey of the types of compounds presently employed in medicine, of the distribution of gold in the body which results from their use, and of some relevant chemistry. Emphasis is placed on results obtained in the last few years

  2. Biological Activity of Ionic Liquids and Their Application in Pharmaceutics and Medicine.

    Science.gov (United States)

    Egorova, Ksenia S; Gordeev, Evgeniy G; Ananikov, Valentine P

    2017-05-24

    Ionic liquids are remarkable chemical compounds, which find applications in many areas of modern science. Because of their highly tunable nature and exceptional properties, ionic liquids have become essential players in the fields of synthesis and catalysis, extraction, electrochemistry, analytics, biotechnology, etc. Apart from physical and chemical features of ionic liquids, their high biological activity has been attracting significant attention from biochemists, ecologists, and medical scientists. This Review is dedicated to biological activities of ionic liquids, with a special emphasis on their potential employment in pharmaceutics and medicine. The accumulated data on the biological activity of ionic liquids, including their antimicrobial and cytotoxic properties, are discussed in view of possible applications in drug synthesis and drug delivery systems. Dedicated attention is given to a novel active pharmaceutical ingredient-ionic liquid (API-IL) concept, which suggests using traditional drugs in the form of ionic liquid species. The main aim of this Review is to attract a broad audience of chemical, biological, and medical scientists to study advantages of ionic liquid pharmaceutics. Overall, the discussed data highlight the importance of the research direction defined as "Ioliomics", studies of ions in liquids in modern chemistry, biology, and medicine.

  3. Potential physiological effects of pharmaceutical compounds in Atlantic salmon (Salmo salar) implied by transcriptomic analysis.

    Science.gov (United States)

    Hampel, Miriam; Alonso, Esteban; Aparicio, Irene; Bron, James E; Santos, Juan Luis; Taggart, John B; Leaver, Michael J

    2010-05-01

    Pharmaceuticals are emerging pollutants widely used in everyday urban activities which can be detected in surface, ground, and drinking waters. Their presence is derived from consumption of medicines, disposal of expired medications, release of treated and untreated urban effluents, and from the pharmaceutical industry. Their growing use has become an alarming environmental problem which potentially will become dangerous in the future. However, there is still a lack of knowledge about long-term effects in non-target organisms as well as for human health. Toxicity testing has indicated a relatively low acute toxicity to fish species, but no information is available on possible sublethal effects. This study provides data on the physiological pathways involved in the exposure of Atlantic salmon as representative test species to three pharmaceutical compounds found in ground, surface, and drinking waters based on the evaluation of the xenobiotic-induced impairment resulting in the activation and silencing of specific genes. Individuals of Atlantic salmon (Salmo salar) parr were exposed during 5 days to environmentally relevant concentrations of three representative pharmaceutical compounds with high consumption rates: the analgesic acetaminophen (54.77+/-34.67 microg L(-1)), the anticonvulsant carbamazepine (7.85+/-0.13 microg L(-1)), and the beta-blocker atenolol (11.08+/-7.98 microg L(-1)). Five immature males were selected for transcriptome analysis in brain tissues by means of a 17k salmon cDNA microarray. For this purpose, mRNA was isolated and reverse-transcribed into cDNA which was labeled with fluorescent dyes and hybridized against a common pool to the arrays. Lists of significantly up- and down-regulated candidate genes were submitted to KEGG (Kyoto Encyclopedia of Genes and Genomes) in order to analyze for induced pathways and to evaluate the usefulness of this method in cases of not completely annotated test organisms. Exposure during 5 days to

  4. Patent indicators: a window to pharmaceutical market success.

    Science.gov (United States)

    Guo, Yang; Hu, Yuanjia; Zheng, Mingli; Wang, Yitao

    2013-07-01

    Pharmaceutical success in the market is the best reward for pharmaceutical investors undergoing the lengthy, costly and risky process of pharmaceutical Research and Development (R&D). Drugs with high market revenues trigger fierce competition between pharmaceutical enterprises, as is demonstrated by the increasing Mergers & Acquisitions (M&A) cases focusing on seizing the best-selling products. On the other hand, patents, as the best shield for innovative drugs against generic drugs, become a powerful weapon for pharmaceutical enterprises to win the substantial returns generated by market exclusivity. Patents seem to be directly responsible for the commercial success of new medicines. In this context, it is of great significance to find out the empirical associations between pharmaceutical commercial success and patents. By comprehensively analysing 127 drugs marketed in the USA and their 621 American patents, this article identifies the evidence to link various patent indicators with pharmaceutical sales in actual market.

  5. Thermodynamics of water-solid interactions in crystalline and amorphous pharmaceutical materials.

    Science.gov (United States)

    Sacchetti, Mark

    2014-09-01

    Pharmaceutical materials, crystalline and amorphous, sorb water from the atmosphere, which affects critical factors in the development of drugs, such as the selection of drug substance crystal form, compatibility with excipients, dosage form selection, packaging, and product shelf-life. It is common practice to quantify the amount of water that a material sorbs at a given relative humidity (RH), but the results alone provide minimal to no physicochemical insight into water-solid interactions, without which pharmaceutical scientists cannot develop an understanding of their materials, so as to anticipate and circumvent potential problems. This research was conducted to advance the science of pharmaceutical materials by examining the thermodynamics of solids with sorbed water. The compounds studied include nonhygroscopic drugs, a channel hydrate drug, a stoichiometric hydrate excipient, and an amorphous excipient. The water sorption isotherms were measured over a range of temperature to extract the partial molar enthalpy and entropy of sorbed water as well as the same quantities for some of the solids. It was found that water-solid interactions spanned a range of energy and entropy as a function of RH, which was unique to the solid, and which could be valuable in identifying batch-to-batch differences and effects of processing in material performance. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  6. The international pharmaceutical market as a source of low-cost prescription drugs for U.S. patients.

    Science.gov (United States)

    Kesselheim, Aaron S; Choudhry, Niteesh K

    2008-04-15

    In response to increasing prescription drug costs, more U.S. patients and policymakers are importing less-expensive pharmaceutical products from other countries. Large-scale prescription drug importation is currently illegal, but the U.S. Food and Drug Administration permits individuals to bring in 90-day supplies of drugs for personal use. As patient use of foreign-bought drugs has increased, federal legislators have continued to debate the full legalization of importation. Three factors help guide whether U.S. patients and policymakers can rely on other countries as sources of imported prescription drugs: whether the safety of the product can be ensured, how the import price compares with domestic prices, and how importation might affect the exporting country's pharmaceutical market. In wealthier countries with active regulatory systems, drug safety can be adequately ensured, and brand-name products are usually less expensive than in the United States (although generic drugs may be more expensive). However, implementing large-scale importation can negatively impact the originating country's market and can diminish the long-term cost savings for U.S. consumers. In low- and middle-income countries, prices may be reduced for both brand-name and generic drugs, but the prevalence of unauthorized products on the market makes ensuring drug safety more difficult. It may be reasonable for individual U.S. consumers to purchase essential medicines from certain international markets, but the most effective way to decrease drug costs overall is the appropriate use of domestic generic drugs, which are available for almost every major therapeutic class.

  7. Compounding and Extralabel Use of Drugs in Exotic Animal Medicine.

    Science.gov (United States)

    Powers, Lauren V; Davidson, Gigi

    2018-05-01

    Extralabel drug use is the use of a Food and Drug Administration (FDA)-approved drug in a manner different from what is stipulated on the approved label. Compounding is the process of preparing a medication in a manner not indicated on the label to create a formulation specifically tailored to the needs of an individual patient. Extralabel drug use and compounding are vital aspects of safe and effective drug delivery to patients in exotic animal practice. There are few FDA-approved drugs for exotic animal species, and many approved drugs for other species are not available in suitable formulations for use in exotic animals. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Native fluorescence detection of biomolecular and pharmaceutical compounds in capillary electrophoresis: detector designs, performance and applications: A review

    NARCIS (Netherlands)

    de Kort, B.J.; de Jong, G.J.; Somsen, G.W.

    2013-01-01

    This review treats the coupling of capillary electrophoresis (CE) with fluorescence detection (Flu) for the analysis of natively fluorescent biomolecular and pharmaceutical compounds. CE-Flu combines the excellent separation efficiency of CE with the high selectivity and sensitivity of Flu. In

  9. Compliance revisited: pharmaceutical drug trials in the era of the contract research organization.

    Science.gov (United States)

    Jonvallen, Petra

    2009-12-01

    Over the past decade, the management of clinical trials of pharmaceuticals has become a veritable industry, as evidenced by the emergence and proliferation of contract research organizations (CROs) that co-ordinate and monitor trials. This article focuses on work performed by one CRO involved in the introduction of new software, modelled on industrial production processes, into clinical trial practices. It investigates how this new management technique relates to the work performed in the clinic to ensure that trial participants comply with the protocol. Using an analytical distinction between 'classical' management work and invisible work, the article contextualizes the meaning of compliance in the clinic and suggests that the work involved in producing compliance should be taken into consideration by those concerned with validity of trials, as clinical trials are put under private industrial management. The article builds on participant observation at a Swedish university hospital and interviews the nurses, dieticians, doctors and a software engineer, all part of a team involved in pharmaceutical drug trials on a potential obesity drug.

  10. Polymorphs and prodrugs and salts (oh my!: an empirical analysis of "secondary" pharmaceutical patents.

    Directory of Open Access Journals (Sweden)

    Amy Kapczynski

    Full Text Available BACKGROUND: While there has been much discussion by policymakers and stakeholders about the effects of "secondary patents" on the pharmaceutical industry, there is no empirical evidence on their prevalence or determinants. Characterizing the landscape of secondary patents is important in light of recent court decisions in the U.S. that may make them more difficult to obtain, and for developing countries considering restrictions on secondary patents. METHODOLOGY/PRINCIPAL FINDINGS: We read the claims of the 1304 Orange Book listed patents on all new molecular entities approved in the U.S. between 1988 and 2005, and coded the patents as including chemical compound claims (claims covering the active molecule itself and/or one of several types of secondary claims. We distinguish between patents with any secondary claims, and those with only secondary claims and no chemical compound claims ("independent" secondary patents. We find that secondary claims are common in the pharmaceutical industry. We also show that independent secondary patents tend to be filed and issued later than chemical compound patents, and are also more likely to be filed after the drug is approved. When present, independent formulation patents add an average of 6.5 years of patent life (95% C.I.: 5.9 to 7.3 years, independent method of use patents add 7.4 years (95% C.I.: 6.4 to 8.4 years, and independent patents on polymorphs, isomers, prodrug, ester, and/or salt claims add 6.3 years (95% C.I.: 5.3 to 7.3 years. We also provide evidence that late-filed independent secondary patents are more common for higher sales drugs. CONCLUSIONS/SIGNIFICANCE: Policies and court decisions affecting secondary patenting are likely to have a significant impact on the pharmaceutical industry. Secondary patents provide substantial additional patent life in the pharmaceutical industry, at least nominally. Evidence that they are also more common for best-selling drugs is consistent with accounts of

  11. Stability-indicating HPLC determination of pramipexole dihydrochloride in bulk drug and pharmaceutical dosage form

    OpenAIRE

    Panditrao, Vedavati M; Sarkate, Aniket P; Sangshetti, Jaiprakash N; Wakte, Pravin S; Shinde, Devanand B

    2011-01-01

    A novel stability-indicating high-performance liquid chromatographic assay method was developed and validated for quantitative determination of pramipexole dihydrochloride in bulk drugs and in pharmaceutical dosage form in the presence of degradation products. An isocratic, reversed phase HPLC method was developed to separate the drug from the degradation products, using an Ace5-C18 (250×4.6 mm, 5 µm) advance chromatography column, and 10 mmol L-1 ammonium acetate and acetonitrile (75:25 v/v)...

  12. Selective micellar electrokinetic chromatographic method for simultaneous determination of some pharmaceutical binary mixtures containing non-steroidal anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    Michael E. El-Kommos

    2013-02-01

    Full Text Available A simple and selective micellar electrokinetic chromatographic (MEKC method has been developed for the analysis of five pharmaceutical binary mixtures containing three non-steroidal anti-inflammatory drugs (NSAIDs. The investigated mixtures were Ibuprofen (IP–Paracetamol (PC, Ibuprofen (IP–Chlorzoxazone (CZ, Ibuprofen (IP–Methocarbamol (MC, Ketoprofen (KP–Chlorzoxazone (CZ and Diclofenac sodium (DS–Lidocaine hydrochloride (LC. The separation was run for all mixtures using borate buffer (20 mM, pH 9 containing 15% (v/v methanol and 100 mM sodium dodecyl sulphate (SDS at 15 kV and the components were detected at 214 nm. Different factors affecting the electrophoretic mobility of the seven investigated drugs were studied and optimized. The method was validated according to international conference of harmonization (ICH guidelines and United States pharmacopoeia (USP. The method was applied to the analysis of five pharmaceutical binary mixtures in their dosage forms. The results were compared with other reported high performance liquid chromatographic methods and no significant differences were observed. Keywords: Capillary electrophoresis, Micellar electrokinetic chromatographic method, Non-steroidal anti-inflammatory drugs, Pharmaceutical binary mixtures, Pharmaceutical analysis

  13. Emerging Pollutant of Concern: Occurrence of Pharmaceutical Compounds in Asia with Particular Preference to Southeast Asia Countries

    Directory of Open Access Journals (Sweden)

    Hashim Nor Haslina

    2016-01-01

    Full Text Available Southeast Asia countries were developing countries, with the rapid development for a better living condition leads to longer life expectancy, which increased total population. It may result in increased the demand of pharmaceutical in domestic use and or in hospital. Although most wastewater treatment plants (WWTPs met the local authority’s regulatory requirement, there are still many pharmaceutical compound incompletely removed and discharge to the water stream and enter the environment. Recently many studies and researches have published on the occurrence and source as well as the fate of pharmaceuticals all over the world including Asia. As part of Asia region, Southeast Asia countries (Malaysia, Philippines, Singapore, Thailand, Vietnam, Brunei, Cambodia, and Lao PDR seem has lack of research knowledge and information regarding this emerging pollutant issues compared to developed Asia country as China, Korea and Hong Kong. In this paper, it will review recent studies occurrences (surface and wastewater on most common pharmaceuticals with several recommendations to overcome and thus summarise the actual situation in Southeast Asia.

  14. [Drug advertising as communication between the pharmaceutical industry and the physician: advertisements for psychotropic drugs in the Dutch medical journal, Nederlands Tijdschrift voor Geneeskunde, 1900-1940].

    Science.gov (United States)

    van der Hoogte, Arjo Roersch; Pieters, Toine

    2010-01-01

    In this article we explore the historical development of drug advertisements for psychotropic drugs in the leading Dutch medical journal from 1900 to 1940. The advertisements for hypnotics and sedatives, in The Nederlands Tijdschrift voor Geneeskunde (Dutch medical journal) reflected the changes in the vocabulary and image promoted by the pharmaceutical companies. In the first two decades, the advertisements were sober and to the point, and included the trademark, company name, molecular formula and therapeutic properties of the medication. The emphasis was on creating a scientific image of reliable symptom control for the therapeutic drug. In doing so, the ethical drug companies tried (successfully) to distinguish themselves from the producers of patent medicines. Once scientific credibility was established, the form and content of the advertisements changed significantly. In the late 1920s and 1930s drug companies embraced modern advertising techniques, developing a figurative language to address the changing beliefs and practices of Dutch physicians. Instead of promoting therapeutic drugs as safe and scientific, the emphasis was on their effectiveness in comparison to similar drugs. In the process, scientific information was reduced to an indispensable standardized minimum, whereby therapeutic drugs were advertised according to the latest pharmacological taxonomy rather than molecular formulas. The image-making of 'ethical marketing' began during the interwar years when marketers applied modern advertising techniques and infotainment strategies. The scanty black and white informational bulletins transitioned into colourful advertisements. The pharmaceutical companies employed the same medical language as used by physicians, so that one word or image in an advertisement would suffice for the physician to recognize a drug and its therapeutic properties. These developments show the changing relationship between the modern ethical pharmaceutical industry and Dutch

  15. Illicit drugs and pharmaceuticals in the environment - Forensic applications of environmental data, Part 2: Pharmaceuticals as chemical markers of faecal water contamination

    International Nuclear Information System (INIS)

    Kasprzyk-Hordern, Barbara; Dinsdale, Richard M.; Guwy, Alan J.

    2009-01-01

    This manuscript is part two of a two-part study aiming to provide a better understanding and application of environmental data not only for environmental aims but also to meet forensic objectives. In this paper pharmaceuticals were investigated as potential chemical indicators of water contamination with sewage. The monitoring program carried out in Wales revealed that some pharmaceuticals are particularly persistent and/or ubiquitous in contaminated river water and therefore might be considered as potential conservative or labile wastewater indicators. In particular, these include some anti-inflammatory/analgesics, antiepileptics, beta-blockers, some H2-receptor antagonists and antibacterial drugs. - Wastewater as an indicative source of information can be used in forensic applications.

  16. Illicit drugs and pharmaceuticals in the environment - Forensic applications of environmental data, Part 2: Pharmaceuticals as chemical markers of faecal water contamination

    Energy Technology Data Exchange (ETDEWEB)

    Kasprzyk-Hordern, Barbara, E-mail: B.Kasprzyk-Hordern@hud.ac.u [University of Huddersfield, Department of Chemical and Biological Sciences, Queensgate, Huddersfield HD1 3DH (United Kingdom); University of Glamorgan, Sustainable Environment Research Centre, Faculty of Health, Sport and Science, Pontypridd CF37 1DL (United Kingdom); Dinsdale, Richard M.; Guwy, Alan J. [University of Glamorgan, Sustainable Environment Research Centre, Faculty of Health, Sport and Science, Pontypridd CF37 1DL (United Kingdom)

    2009-06-15

    This manuscript is part two of a two-part study aiming to provide a better understanding and application of environmental data not only for environmental aims but also to meet forensic objectives. In this paper pharmaceuticals were investigated as potential chemical indicators of water contamination with sewage. The monitoring program carried out in Wales revealed that some pharmaceuticals are particularly persistent and/or ubiquitous in contaminated river water and therefore might be considered as potential conservative or labile wastewater indicators. In particular, these include some anti-inflammatory/analgesics, antiepileptics, beta-blockers, some H2-receptor antagonists and antibacterial drugs. - Wastewater as an indicative source of information can be used in forensic applications.

  17. Sorption of structurally different ionized pharmaceutical and illicit drugs to a mixed-mode coated microsampler.

    Science.gov (United States)

    Peltenburg, Hester; Timmer, Niels; Bosman, Ingrid J; Hermens, Joop L M; Droge, Steven T J

    2016-05-20

    The mixed-mode (C18/strong cation exchange-SCX) solid-phase microextraction (SPME) fiber has recently been shown to have increased sensitivity for ionic compounds compared to more conventional sampler coatings such as polyacrylate and polydimethylsiloxane (PDMS). However, data for structurally diverse compounds to this (prototype) sampler coating are too limited to define its structural limitations. We determined C18/SCX fiber partitioning coefficients of nineteen cationic structures without hydrogen bonding capacity besides the charged group, stretching over a wide hydrophobicity range (including amphetamine, amitriptyline, promazine, chlorpromazine, triflupromazine, difenzoquat), and eight basic pharmaceutical and illicit drugs (pKa>8.86) with additional hydrogen bonding moieties (MDMA, atenolol, alprenolol, metoprolol, morphine, nicotine, tramadol, verapamil). In addition, sorption data for three neutral benzodiazepines (diazepam, temazepam, and oxazepam) and the anionic NSAID diclofenac were collected to determine the efficiency to sample non-basic drugs. All tested compounds showed nonlinear isotherms above 1mmol/L coating, and linear isotherms below 1mmol/L. The affinity for C18/SCX-SPME for tested organic cations without Hbond capacities increased with longer alkyl chains, ranging from logarithmic fiber-water distribution coefficients (log Dfw) of 1.8 (benzylamine) to 5.8 (triflupromazine). Amines smaller than benzylamine may thus have limited detection levels, while cationic surfactants with alkyl chain lengths >12 carbon atoms may sorb too strong to the C18/SCX sampler which hampers calibration of the fiber-water relationship in the linear range. The log Dfw for these simple cation structures closely correlates with the octanol-water partition coefficient of the neutral form (Kow,N), and decreases with increased branching and presence of multiple aromatic rings. Oxygen moieties in organic cations decreased the affinity for C18/SCX-SPME. Log Dfw values of

  18. Integrating systems Approaches into Pharmaceutical Sciences

    DEFF Research Database (Denmark)

    Westerhoff, H.V.; Mosekilde, Erik; Noe, C. R.

    2008-01-01

    During the first week of December 2007, the European Federation for Pharmaceutical Sciences (EUFEPS) and BioSim, the major European Network of Excellence on Systems Biology, held a challenging conference on the use of mathematical models in the drug development process. More precisely, the purpose...... of the conference was to promote the ‘Integration of Systems Approaches into Pharmaceutical Sciences’ in view of optimising the development of new effective drugs. And a challenge this is, considering both the high attrition rates in the pharmaceutical industry and the failure of finding definitive drug solutions...... for many of the diseases that plague mankind today. The conference was co-sponsored by the American College of Clinical Pharmacology, the European Center for Pharmaceutical Medicine, and the Swiss Society of Pharmaceutical Sciences and, besides representatives from the European Regulatory Agencies and FDA...

  19. Environmental risk management for pharmaceutical compounds

    Energy Technology Data Exchange (ETDEWEB)

    Voulvoulis, N [Imperial College London (United Kingdom)

    2004-09-15

    Pharmaceuticals are a highly variable group of organic compounds with the potential to cause harm to aquatic ecosystems and human health. Thousands of tones of pharmacologically active substances are used annually but surprisingly little is known about their ultimate fate in the environment. The data collected to date, rarely provide information on the processes that determine their environmental fate and although they receive considerable pharmacological and clinical testing during development, knowledge of their ecotoxicity is poor. One major concern is that antibiotics found in sewage effluent may cause increased resistance amongst natural bacterial populations. The debate over risks associated with chemicals in the environment represents more than just another disagreement in the scientific community. It has opened the door to a new way of thinking about the onset of uninherited diseases, the nature of scientific investigation, and the role of scientific knowledge in the policymaking process. For example, research evidence on endocrine disruption collected over the last few years has changed dramatically the way we think about chemical risks. In part, this change has also been attributed to the precautionary principle, as a new approach to environmental policy forged in Europe. The term ''precautionary approach'' declares an obligation to control the dangerous substances even before a definitive causal link had been established between the chemicals and health or environmental effects, and represents a radical departure from traditional approaches to risk assessment and particularly risk management, which includes an integration of the assessment, communication and mitigation of risks.

  20. Marketing orientation in pharmaceutical industry

    Directory of Open Access Journals (Sweden)

    Prošić Danica

    2006-01-01

    Full Text Available Pharmaceutical companies are major stakeholders in the global health agenda Virtually all drugs used by patients in Europe reach markets through the promotion tactics of a small number of corporations with a tremendous impact on global health. The sector is both fast growing and highly profitable. Effective marketing strategies are a crucial ingredient in making sure pharmaceutical products and profits flow in a virtuous cycle. At first glance, the relationship between doctors and drug companies, as well as advertising practices for over-the-counter medication, appears tightly regulated. According to many consumer organizations, drug promotion in Europe today can be characterized as nice and friendly marketing. This refers to the creation of a false sense of trust that consumers associate with branded pharmaceutical products, as a result of pharmaceutical marketing efforts disguised as genuine corporate responsibility.

  1. The application of structure-based assessment to support safety and chemistry diligence to manage genotoxic impurities in active pharmaceutical ingredients during drug development.

    Science.gov (United States)

    Dobo, Krista L; Greene, Nigel; Cyr, Michelle O; Caron, Stéphane; Ku, Warren W

    2006-04-01

    Starting materials and intermediates used to synthesize pharmaceuticals are reactive in nature and may be present as impurities in the active pharmaceutical ingredient (API) used for preclinical safety studies and clinical trials. Furthermore, starting materials and intermediates may be known or suspected mutagens and/or carcinogens. Therefore, during drug development due diligence need be applied from two perspectives (1) to understand potential mutagenic and carcinogenic risks associated with compounds used for synthesis and (2) to understand the capability of synthetic processes to control genotoxic impurities in the API. Recently, a task force comprised of experts from pharmaceutical industry proposed guidance, with recommendations for classification, testing, qualification and assessing risk of genotoxic impurities. In our experience the proposed structure-based classification, has differentiated 75% of starting materials and intermediates as mutagenic and non-mutagenic with high concordance (92%) when compared with Ames results. Structure-based assessment has been used to identify genotoxic hazards, and prompted evaluation of fate of genotoxic impurities in API. These two assessments (safety and chemistry) culminate in identification of genotoxic impurities known or suspected to exceed acceptable levels in API, thereby triggering actions needed to assure appropriate control and measurement methods are in place. Hypothetical case studies are presented demonstrating this multi-disciplinary approach.

  2. Adverse-drug-event data provided by pharmaceutical companies.

    Science.gov (United States)

    Cudny, Magdalena E; Graham, Angie S

    2008-06-01

    Pharmaceutical company drug information center (PCDIC) responses to queries about adverse drug events (ADEs) were studied to determine whether PCDICs search sources other than the prescribing information on the package insert (PI) and whether the PCDICs' approach differs according to whether an ADE is listed in the PI (labeled) or not (unlabeled). Companies were selected from a list of PCDICs in the Physicians' Desk Reference. One oral or injectable prescription drug from each company was selected. For each drug, a labeled ADE and an unlabeled ADE about which to query the PCDICs were randomly selected from the index of an annual publication on ADEs. The investigators telephoned the PCDICs with an open-ended inquiry about the incidence, timing, and management of the ADE as reported in the literature and the company's internal data; they clarified that the request did not concern a specific patient. Whether or not information was provided, the source searched was recorded (PI, literature, internal database), and the percentages of PCDICs that used each source for labeled and for unlabeled ADEs were analyzed. Results were obtained from 100 companies to questions about 100 drugs (200 ADEs). For ADEs overall, 80% used the PI, 50% the medical literature, and 38% internal data. For labeled versus unlabeled ADEs, respectively, the PI was used by 84% and 76%; literature, both 50%; and internal data, 35% and 41%. The PCDIC specialists referencing the PI did not always provide accurate or up-to-date information. Some specialists, when asked to query internal databases, said that was not an option. For both labeled and unlabeled ADEs, the PI was the primary source used by PCDICs to answer safety questions about their products, and internal data were the least-used source. Most resources used by PCDICs are readily available to practicing pharmacists.

  3. Bitterness prediction in-silico: A step towards better drugs.

    Science.gov (United States)

    Bahia, Malkeet Singh; Nissim, Ido; Niv, Masha Y

    2018-02-05

    Bitter taste is innately aversive and thought to protect against consuming poisons. Bitter taste receptors (Tas2Rs) are G-protein coupled receptors, expressed both orally and extra-orally and proposed as novel targets for several indications, including asthma. Many clinical drugs elicit bitter taste, suggesting the possibility of drugs re-purposing. On the other hand, the bitter taste of medicine presents a major compliance problem for pediatric drugs. Thus, efficient tools for predicting, measuring and masking bitterness of active pharmaceutical ingredients (APIs) are required by the pharmaceutical industry. Here we highlight the BitterDB database of bitter compounds and survey the main computational approaches to prediction of bitter taste based on compound's chemical structure. Current in silico bitterness prediction methods provide encouraging results, can be constantly improved using growing experimental data, and present a reliable and efficient addition to the APIs development toolbox. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Application of the threshold of toxicological concern concept to pharmaceutical manufacturing operations.

    Science.gov (United States)

    Dolan, David G; Naumann, Bruce D; Sargent, Edward V; Maier, Andrew; Dourson, Michael

    2005-10-01

    A scientific rationale is provided for estimating acceptable daily intake values (ADIs) for compounds with limited or no toxicity information to support pharmaceutical manufacturing operations. These ADIs are based on application of the "thresholds of toxicological concern" (TTC) principle, in which levels of human exposure are estimated that pose no appreciable risk to human health. The same concept has been used by the US Food and Drug Administration (FDA) to establish "thresholds of regulation" for indirect food additives and adopted by the Joint FAO/WHO Expert Committee on Food Additives for flavoring substances. In practice, these values are used as a statement of safety and indicate when no actions need to be taken in a given exposure situation. Pharmaceutical manufacturing relies on ADIs for cleaning validation of process equipment and atypical extraneous matter investigations. To provide practical guidance for handling situations where relatively unstudied compounds with limited or no toxicity data are encountered, recommendations are provided on ADI values that correspond to three categories of compounds: (1) compounds that are likely to be carcinogenic, (2) compounds that are likely to be potent or highly toxic, and (3) compounds that are not likely to be potent, highly toxic or carcinogenic. Corresponding ADIs for these categories of materials are 1, 10, and 100 microg/day, respectively.

  5. Critical evaluation of methodology commonly used in sample collection, storage and preparation for the analysis of pharmaceuticals and illicit drugs in surface water and wastewater by solid phase extraction and liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Baker, David R; Kasprzyk-Hordern, Barbara

    2011-11-04

    The main aim of this manuscript is to provide a comprehensive and critical verification of methodology commonly used for sample collection, storage and preparation in studies concerning the analysis of pharmaceuticals and illicit drugs in aqueous environmental samples with the usage of SPE-LC/MS techniques. This manuscript reports the results of investigations into several sample preparation parameters that to the authors' knowledge have not been reported or have received very little attention. This includes: (i) effect of evaporation temperature and (ii) solvent with regards to solid phase extraction (SPE) extracts; (iii) effect of silanising glassware; (iv) recovery of analytes during vacuum filtration through glass fibre filters and (v) pre LC-MS filter membranes. All of these parameters are vital to develop efficient and reliable extraction techniques; an essential factor given that target drug residues are often present in the aqueous environment at ng L(-1) levels. Presented is also the first comprehensive review of the stability of illicit drugs and pharmaceuticals in wastewater. Among the parameters studied are: time of storage, temperature and pH. Over 60 analytes were targeted including stimulants, opioid and morphine derivatives, benzodiazepines, antidepressants, dissociative anaesthetics, drug precursors, human urine indicators and their metabolites. The lack of stability of analytes in raw wastewater was found to be significant for many compounds. For instance, 34% of compounds studied reported a stability change >15% after only 12 h in raw wastewater stored at 2 °C; a very important finding given that wastewater is typically collected with the use of 24 h composite samplers. The stability of these compounds is also critical given the recent development of so-called 'sewage forensics' or 'sewage epidemiology' in which concentrations of target drug residues in wastewater are used to back-calculate drug consumption. Without an understanding of stability

  6. Occurrence and fate of pharmaceutically active compounds in the environment, a case study: Hoeje River in Sweden

    Energy Technology Data Exchange (ETDEWEB)

    Bendz, David [Swedish Geotechnical Institute, Department of Environmental Technology, Hospitalsgatan 16A, S-211 33 Malmoe (Sweden); Paxeus, Nicklas A [Gryaab, Karl IX:s vaeg, S-418 34 Gothenburg (Sweden); Ginn, Timothy R [University of California, Department of Civil and Environmental Engineering, 1 Shields Avenue, 2001 Engineering III, Davis, CA 95616 (United States); Loge, Frank J [University of California, Department of Civil and Environmental Engineering, 1 Shields Avenue, 2001 Engineering III, Davis, CA 95616 (United States)

    2005-07-15

    Pharmaceutically active compounds (PhACs) in the environment lately have been acknowledged to constitute a health risk for humans and terrestrial and aquatic ecosystems. Human and veterinary applications are the main sources of PhACs in the environment and the major pathways are excretion and discharge to the environment through sewage treatment plants (STPs). In this study, the occurrence and fate of selected human PhACs belonging to different therapeutic classes (non-steroidal anti-inflammatory drugs, lipid regulators, anti-epileptics, antibiotics and {beta}-blockers) were investigated in a small river in the very south of Sweden. The objectives of the study were to evaluate the impact of a high and rather constant load in sewage influent on downstream concentrations and whether substances that are metabolized to a high degree in humans also show a low persistency in a natural aquatic environment. Water samples were collected from the influent and effluent of the STP, in a series of dammed reservoirs leading to discharge into the Hoeje River in Sweden, and at several locations in the river downstream of the outfall. After enrichment by solid-phase extraction, the compounds were analyzed using GC-MS (methylated derivatives) or LC-MS/MS. In addition to the targeted pharmaceuticals, GC-MS analysis of the samples revealed the presence of other sewage-related pollutants (triclosan, caffeine, flame-retardants, antioxidants) and these results where included for comparison. Removal efficiencies were calculated in the STP and found to display a wide range with numerous species surviving treatment at greater than half their influent concentrations, including diclofenac, the anti-epileptic carbamazepine, a {beta}-blocker (propanolol), and antibiotics trimetoprim and sulfamethoxazole. Low removals were also observed for Tris(2-chloroisopropyl)phosphate (flame retardant), BHT-aldehyde (oxidation product of BHT) and synthetic musk (HHCB). The concentrations of chloride (Cl

  7. Occurrence and fate of pharmaceutically active compounds in the environment, a case study: Hoeje River in Sweden

    International Nuclear Information System (INIS)

    Bendz, David; Paxeus, Nicklas A.; Ginn, Timothy R.; Loge, Frank J.

    2005-01-01

    Pharmaceutically active compounds (PhACs) in the environment lately have been acknowledged to constitute a health risk for humans and terrestrial and aquatic ecosystems. Human and veterinary applications are the main sources of PhACs in the environment and the major pathways are excretion and discharge to the environment through sewage treatment plants (STPs). In this study, the occurrence and fate of selected human PhACs belonging to different therapeutic classes (non-steroidal anti-inflammatory drugs, lipid regulators, anti-epileptics, antibiotics and β-blockers) were investigated in a small river in the very south of Sweden. The objectives of the study were to evaluate the impact of a high and rather constant load in sewage influent on downstream concentrations and whether substances that are metabolized to a high degree in humans also show a low persistency in a natural aquatic environment. Water samples were collected from the influent and effluent of the STP, in a series of dammed reservoirs leading to discharge into the Hoeje River in Sweden, and at several locations in the river downstream of the outfall. After enrichment by solid-phase extraction, the compounds were analyzed using GC-MS (methylated derivatives) or LC-MS/MS. In addition to the targeted pharmaceuticals, GC-MS analysis of the samples revealed the presence of other sewage-related pollutants (triclosan, caffeine, flame-retardants, antioxidants) and these results where included for comparison. Removal efficiencies were calculated in the STP and found to display a wide range with numerous species surviving treatment at greater than half their influent concentrations, including diclofenac, the anti-epileptic carbamazepine, a β-blocker (propanolol), and antibiotics trimetoprim and sulfamethoxazole. Low removals were also observed for Tris(2-chloroisopropyl)phosphate (flame retardant), BHT-aldehyde (oxidation product of BHT) and synthetic musk (HHCB). The concentrations of chloride (Cl - ) and

  8. Pharmaceutical cocrystals: walking the talk.

    Science.gov (United States)

    Bolla, Geetha; Nangia, Ashwini

    2016-06-28

    Pharmaceutical cocrystals belong to a sub-class of cocrystals wherein one of the components is a drug molecule (or an active pharmaceutical ingredient, API) and the second is a benign food or drug grade additive (generally regarded as safe, GRAS). The two components are hydrogen-bonded in a fixed stoichiometric ratio in the crystal lattice. In the past decade, pharmaceutical cocrystals have demonstrated significant promise in their ability to modify the physicochemical and pharmacokinetic properties of drug substances, such as the solubility and dissolution rate, bioavailability, particle morphology and size, tableting and compaction, melting point, physical form, biochemical and hydration stability, and permeability. In this feature review, we highlight some prominent examples of drug cocrystals which exhibit variable hardness/softness and elasticity/plasticity depending on coformer selection, improvement of solubility and permeability in the same cocrystal, increase of the melting point for solid formulation, enhanced color performance, photostability and hydration stability, and a longer half-life. Cocrystals of flavanoids and polyphenols can make improved pharmaceuticals and also extend to the larger class of nutraceuticals. The application of crystal engineering to assemble ternary cocrystals expands this field to drug-drug cocrystals which may be useful in multi-drug resistance, mitigating side effects of drugs, or attenuating/enhancing drug action synergistically by rational selection. The advent of new techniques for structural characterization beyond the standard X-ray diffraction will provide a better understanding of drug phases which are at the borderline of crystalline-amorphous nature and even newer opportunities in the future.

  9. Using transcriptomics to guide lead optimization in drug discovery projects: Lessons learned from the QSTAR project.

    Science.gov (United States)

    Verbist, Bie; Klambauer, Günter; Vervoort, Liesbet; Talloen, Willem; Shkedy, Ziv; Thas, Olivier; Bender, Andreas; Göhlmann, Hinrich W H; Hochreiter, Sepp

    2015-05-01

    The pharmaceutical industry is faced with steadily declining R&D efficiency which results in fewer drugs reaching the market despite increased investment. A major cause for this low efficiency is the failure of drug candidates in late-stage development owing to safety issues or previously undiscovered side-effects. We analyzed to what extent gene expression data can help to de-risk drug development in early phases by detecting the biological effects of compounds across disease areas, targets and scaffolds. For eight drug discovery projects within a global pharmaceutical company, gene expression data were informative and able to support go/no-go decisions. Our studies show that gene expression profiling can detect adverse effects of compounds, and is a valuable tool in early-stage drug discovery decision making. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Small-Molecule Compounds Exhibiting Target-Mediated Drug Disposition (TMDD): A Minireview.

    Science.gov (United States)

    An, Guohua

    2017-02-01

    Nonlinearities are commonplace in pharmacokinetics, and 1 special source is the saturable binding of the drug to a high-affinity, low-capacity target, a phenomenon known as target-mediated drug disposition (TMDD). Compared with large-molecule compounds undergoing TMDD, which has been well recognized due to its high prevalence, TMDD in small-molecule compounds is more counterintuitive and has not been well appreciated. With more and more potent small-molecule drugs acting on highly specific targets being developed as well as increasingly sensitive analytical techniques becoming available, many small-molecule compounds have recently been reported to have nonlinear pharmacokinetics imparted by TMDD. To expand our current knowledge of TMDD in small-molecule compounds and increase the awareness of this clinically important phenomenon, this minireview provides an overview of the small-molecule compounds that demonstrate nonlinear pharmacokinetics imparted by TMDD. The present review also summarizes the general features of TMDD in small-molecule compounds and highlights the differences between TMDD in small-molecule compounds and large-molecule compounds. © 2016, The American College of Clinical Pharmacology.

  11. How to revive breakthrough innovation in the pharmaceutical industry.

    Science.gov (United States)

    Munos, Bernard H; Chin, William W

    2011-06-29

    Over the past 20 years, pharmaceutical companies have implemented conservative management practices to improve the predictability of therapeutics discovery and success rates of drug candidates. This approach has often yielded compounds that are only marginally better than existing therapies, yet require larger, longer, and more complex trials. To fund them, companies have shifted resources away from drug discovery to late clinical development; this has hurt innovation and amplified the crisis brought by the expiration of patents on many best-selling drugs. Here, we argue that more breakthrough therapeutics will reach patients only if the industry ceases to pursue "safe" incremental innovation, re-engages in high-risk discovery research, and adopts collaborative innovation models that allow sharing of knowledge and costs among collaborators.

  12. The Impact of Biotechnology on Pharmaceutics.

    Science.gov (United States)

    Block, Lawrence H.

    1990-01-01

    The emergence of bioactive peptides and proteins as new drug species poses formidable problems for the pharmaceutical scientist. Implications for revision or change in undergraduate and graduate pharmaceutics curricula derive from the biopharmaceutical, pharmacokinetic, and physiochemical aspects of the new drug species, which differ from…

  13. Interaction between pharmaceutical companies and physicians who prescribe antiretroviral drugs for treating AIDS

    Directory of Open Access Journals (Sweden)

    Mario Cesar Scheffer

    Full Text Available CONTEXT AND OBJECTIVE: Given that Brazil has a universal public policy for supplying medications to treat HIV and AIDS, the aim here was to describe the forms of relationship between physicians and the pharmaceutical companies that produce antiretrovirals (ARVs. DESIGN AND SETTING: Cross-sectional epidemiological study conducted in the state of São Paulo. METHODS : Secondary database linkage was used, with structured interviews conducted by telephone among a sample group of 300 physicians representing 2,361 professionals who care for patients with HIV and AIDS. RESULTS : Around two thirds (64% of the physicians prescribing ARVs for HIV and AIDS treatment in the state of São Paulo who were interviewed declared that they had some form of relationship with pharmaceutical companies, of which the most frequent were receipt of publications (54%, visits by sales promoters (51% and receipt of small-value objects (47%. CONCLUSIONS: Two forms of relationship between the pharmaceutical industry and physicians who deal with HIV and AIDS can be highlighted: facilitation of professionals' access to continuing education; and antiretroviral drug brand name promotion.

  14. Application of the near-infrared spectroscopy in the pharmaceutical technology.

    Science.gov (United States)

    Jamrógiewicz, Marzena

    2012-07-01

    Near-infrared (NIR) spectroscopy is currently the fastest-growing and the most versatile analytical method not only in the pharmaceutical sciences but also in the industry. This review focuses on recent NIR applications in the pharmaceutical technology. This article covers monitoring, by NIR, of many manufacturing processes, such as granulation, mixing or drying, in order to determine the end-point of these processes. In this paper, apart from basic theoretical information concerning the NIR spectra, there are included determinations of the quality and quantity of pharmaceutical compounds. Some examples of measurements and control of physicochemical parameters of the final medicinal products, such as hardness, porosity, thickness size, compression strength, disintegration time and potential counterfeit are included. Biotechnology and plant drug analysis using NIR is also described. Moreover, some disadvantages of this method are stressed and future perspectives are anticipated. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Occurrence of pharmaceuticals and cocaine in a Brazilian coastal zone.

    Science.gov (United States)

    Pereira, Camilo D Seabra; Maranho, Luciane A; Cortez, Fernando S; Pusceddu, Fabio H; Santos, Aldo R; Ribeiro, Daniel A; Cesar, Augusto; Guimarães, Luciana L

    2016-04-01

    The present study determined environmental concentrations of pharmaceuticals, cocaine, and the main human metabolite of cocaine in seawater sampled from a subtropical coastal zone (Santos, Brazil). The Santos Bay is located in a metropolitan region and receives over 7367m(3) of wastewater per day. Five sample points under strong influence of the submarine sewage outfall were chosen. Through quantitative analysis by LC-MS/MS, 33 compounds were investigated. Seven pharmaceuticals (atenolol, acetaminophen, caffeine, losartan, valsartan, diclofenac, and ibuprofen), an illicit drug (cocaine), and its main human metabolite (benzoylecgonine) were detected at least once in seawater sampled from Santos Bay at concentrations that ranged from ng·L(-1) to μg·L(-1). In light of the possibility of bioaccumulation and harmful effects, the high concentrations of pharmaceuticals and cocaine found in this marine subtropical ecosystem are of environmental concern. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Tracking 20 years of compound-to-target output from literature and patents.

    Directory of Open Access Journals (Sweden)

    Christopher Southan

    Full Text Available The statistics of drug development output and declining yield of approved medicines has been the subject of many recent reviews. However, assessing research productivity that feeds development is more difficult. Here we utilise an extensive database of structure-activity relationships extracted from papers and patents. We have used this database to analyse published compounds cumulatively linked to nearly 4000 protein target identifiers from multiple species over the last 20 years. The compound output increases up to 2005 followed by a decline that parallels a fall in pharmaceutical patenting. Counts of protein targets have plateaued but not fallen. We extended these results by exploring compounds and targets for one large pharmaceutical company. In addition, we examined collective time course data for six individual protease targets, including average molecular weight of the compounds. We also tracked the PubMed profile of these targets to detect signals related to changes in compound output. Our results show that research compound output had decreased 35% by 2012. The major causative factor is likely to be a contraction in the global research base due to mergers and acquisitions across the pharmaceutical industry. However, this does not rule out an increasing stringency of compound quality filtration and/or patenting cost control. The number of proteins mapped to compounds on a yearly basis shows less decline, indicating the cumulative published target capacity of global research is being sustained in the region of 300 proteins for large companies. The tracking of six individual targets shows uniquely detailed patterns not discernible from cumulative snapshots. These are interpretable in terms of events related to validation and de-risking of targets that produce detectable follow-on surges in patenting. Further analysis of the type we present here can provide unique insights into the process of drug discovery based on the data it actually

  17. Measuring clinical trial transparency: an empirical analysis of newly approved drugs and large pharmaceutical companies.

    Science.gov (United States)

    Miller, Jennifer E; Wilenzick, Marc; Ritcey, Nolan; Ross, Joseph S; Mello, Michelle M

    2017-12-05

    To define a series of clinical trial transparency measures and apply them to large pharmaceutical and biotechnology companies and their 2014 FDA-approved drugs. Cross-sectional descriptive analysis of all clinical trials supporting 2014 Food and Drugs Administration (FDA)-approved new drug applications (NDAs) for novel drugs sponsored by large companies. Data from over 45 sources, including Drugs@FDA.gov, ClinicalTrials.gov, corporate and international registries; PubMed, Google Scholar, EMBASE, corporate press releases, Securities and Exchange Commission (SEC) filings and personal communications with drug manufacturers. Trial registration, results reporting, clinical study report (CSR) synopsis sharing, biomedical journal publication, and FDA Amendments Acts (FDAAA) compliance, analysed on the drug level. The FDA approved 19 novel new drugs, sponsored by 11 large companies, involving 553 trials, in 2014. We analysed 505 relevant trials. Per drug, a median of 100% (IQR 86%-100%) of trials in patients were registered, 71% (IQR 57%-100%) reported results or shared a CSR synopsis, 80% (70%-100%) were published and 96% (80%-100%) were publicly available in some form by 13 months after FDA approval. Disclosure rates were lower at FDA approval (65%) and improved significantly by 6 months post FDA approval. Per drug, a median of 100% (IQR 75%-100%) of FDAAA-applicable trials were compliant. Half of reviewed drugs had publicly disclosed results for all trials in patients in our sample. One trial was uniquely registered in a corporate registry, and not ClinicalTrials.gov; 0 trials were uniquely registered in international registries. Among large pharmaceutical companies and new drugs, clinical trial transparency is high based on several standards, although opportunities for improvement remain. Transparency is markedly higher for trials in patients than among all trials supporting drug approval, including trials in healthy volunteers. Ongoing efforts to publicly track

  18. Antiviral lead compounds from marine sponges

    KAUST Repository

    Sagar, Sunil

    2010-10-11

    Marine sponges are currently one of the richest sources of pharmacologically active compounds found in the marine environment. These bioactive molecules are often secondary metabolites, whose main function is to enable and/or modulate cellular communication and defense. They are usually produced by functional enzyme clusters in sponges and/or their associated symbiotic microorganisms. Natural product lead compounds from sponges have often been found to be promising pharmaceutical agents. Several of them have successfully been approved as antiviral agents for clinical use or have been advanced to the late stages of clinical trials. Most of these drugs are used for the treatment of human immunodeficiency virus (HIV) and herpes simplex virus (HSV). The most important antiviral lead of marine origin reported thus far is nucleoside Ara-A (vidarabine) isolated from sponge Tethya crypta. It inhibits viral DNA polymerase and DNA synthesis of herpes, vaccinica and varicella zoster viruses. However due to the discovery of new types of viruses and emergence of drug resistant strains, it is necessary to develop new antiviral lead compounds continuously. Several sponge derived antiviral lead compounds which are hopedto be developed as future drugs are discussed in this review. Supply problems are usually the major bottleneck to the development of these compounds as drugs during clinical trials. However advances in the field of metagenomics and high throughput microbial cultivation has raised the possibility that these techniques could lead to the cost-effective large scale production of such compounds. Perspectives on biotechnological methods with respect to marine drug development are also discussed. 2010 by the authors; licensee MDPI.

  19. Simultaneous achiral-chiral analysis of pharmaceutical compounds using two-dimensional reversed phase liquid chromatography-supercritical fluid chromatography.

    Science.gov (United States)

    Venkatramani, C J; Al-Sayah, Mohammad; Li, Guannan; Goel, Meenakshi; Girotti, James; Zang, Lisa; Wigman, Larry; Yehl, Peter; Chetwyn, Nik

    2016-02-01

    A new interface was designed to enable the coupling of reversed phase liquid chromatography (RPLC) and supercritical fluid chromatography (SFC). This online two-dimensional chromatographic system utilizing RPLC in the first dimension and SFC in the second was developed to achieve simultaneous achiral and chiral analysis of pharmaceutical compounds. The interface consists of an eight-port, dual-position switching valve with small volume C-18 trapping columns. The peaks of interest eluting from the first RPLC dimension column were effectively focused as sharp concentration pulses on small volume C-18 trapping column/s and then injected onto the second dimension SFC column. The first dimension RPLC separation provides the achiral purity result, and the second dimension SFC separation provides the chiral purity result (enantiomeric excess). The results are quantitative enabling simultaneous achiral, chiral analysis of compounds. The interface design and proof of concept demonstration are presented. Additionally, comparative studies to conventional SFC and case studies of the applications of 2D LC-SFC in pharmaceutical analysis is presented. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Environmental risk management for pharmaceutical compounds

    Energy Technology Data Exchange (ETDEWEB)

    Voulvoulis, N. [Imperial College London (United Kingdom)

    2004-09-15

    Pharmaceuticals are a highly variable group of organic compounds with the potential to cause harm to aquatic ecosystems and human health. Thousands of tones of pharmacologically active substances are used annually but surprisingly little is known about their ultimate fate in the environment. The data collected to date, rarely provide information on the processes that determine their environmental fate and although they receive considerable pharmacological and clinical testing during development, knowledge of their ecotoxicity is poor. One major concern is that antibiotics found in sewage effluent may cause increased resistance amongst natural bacterial populations. The debate over risks associated with chemicals in the environment represents more than just another disagreement in the scientific community. It has opened the door to a new way of thinking about the onset of uninherited diseases, the nature of scientific investigation, and the role of scientific knowledge in the policymaking process. For example, research evidence on endocrine disruption collected over the last few years has changed dramatically the way we think about chemical risks. In part, this change has also been attributed to the precautionary principle, as a new approach to environmental policy forged in Europe. The term ''precautionary approach'' declares an obligation to control the dangerous substances even before a definitive causal link had been established between the chemicals and health or environmental effects, and represents a radical departure from traditional approaches to risk assessment and particularly risk management, which includes an integration of the assessment, communication and mitigation of risks.

  1. Macrolide Hybrid Compounds: Drug Discovery Opportunities in Anti- Infective and Anti-inflammatory Area.

    Science.gov (United States)

    Paljetak, Hana Cipcic; Tomaskovic, Linda; Matijasic, Mario; Bukvic, Mirjana; Fajdetic, Andrea; Verbanac, Donatella; Peric, Mihaela

    2017-01-01

    Macrolides, polyketide natural products, and their 15-membered semi-synthetic derivatives are composed of substituted macrocyclic lactone ring and used primarily as potent antibiotics. Recently their usefulness was extended to antimalarial and anti-inflammatory area. Hybrid macrolides presented in this article are the next generation semi-synthetic compounds that combine pharmacophores from antibacterial, antimalarial and anti-inflammatory area with 14- and 15-membered azalide scaffolds. Antibacterial azalide hybrids with sulphonamides showed improved activity against resistant streptococci while quinolone conjugates demonstrated full coverage of respiratory pathogens including macrolide resistant strains and their efficacy was confirmed in mouse pneumonia model. Antimalarial macrolide hybrids, mainly involving (chloro)quinoline pharmacophores, showed outstanding activity against chloroquine resistant strains, favourable pharmacokinetics, promising in vivo efficacy as well as encouraging developmental potential. Anti-inflammatory hybrids were obtained by combining macrolides with corticosteroid and non-steroidal anti-inflammatory drugs. They were found active in in vivo animal models of locally induced inflammation, asthma, inflammatory bowel disease and rheumatoid arthritis and demonstrated improved safety over parent steroid drugs. Overall, macrolide hybrids possess significant potential to be developed as potent novel medicines in therapeutic areas of utmost pharmaceutical interest. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. NMR imaging and pharmaceutical sciences

    International Nuclear Information System (INIS)

    Beall, P.T.; Good, W.R.

    1986-01-01

    Described is the technique of NMR-imaging in diagnostic medicine. Proton and phosphorus NMR in diagnosis of abnormal tissue pathology. Discussed is the value of NMR to the pharmaceutical sciences. NMR may play an important role in monitoring the response of tissues to drugs, determining the localization of drugs, performing real time pharmacokinetics and testing the use of NMR contrast pharmaceuticals

  3. Neotropics and natural ingredients for pharmaceuticals: why isn't South American biodiversity on the crest of the wave?

    Science.gov (United States)

    Desmarchelier, Cristian

    2010-06-01

    Despite the advent of biotechnology and modern methods of combinatorial chemistry and rational drug design, nature still plays a surprisingly important role as a source of new pharmaceutical compounds. These are marketed either as herbal drugs or as single active ingredients. South American tropical ecosystems (or the Neotropics) encompass one-third of the botanical biodiversity of the planet. For centuries, indigenous peoples have been using plants for healing purposes, and scientists are making considerable efforts in order to validate these uses from a pharmacological/phytochemical point of view. However, and despite the unique plant diversity in the region, very few natural pharmaceutical ingredients from this part of the world have reached the markets in industrialized countries. The present review addresses the importance of single active ingredients and herbal drugs from South American flora as natural ingredients for pharmaceuticals; it highlights the most relevant cases in terms of species of interest; and discusses the key entry barriers for these products in industrialized countries. It explores the reasons why, in spite of the region's competitive advantages, South American biodiversity has been a poor source of natural ingredients for the pharmaceutical industry. (c) 2010 John Wiley & Sons, Ltd.

  4. Innovation in the pharmaceutical industry: New estimates of R&D costs.

    Science.gov (United States)

    DiMasi, Joseph A; Grabowski, Henry G; Hansen, Ronald W

    2016-05-01

    The research and development costs of 106 randomly selected new drugs were obtained from a survey of 10 pharmaceutical firms. These data were used to estimate the average pre-tax cost of new drug and biologics development. The costs of compounds abandoned during testing were linked to the costs of compounds that obtained marketing approval. The estimated average out-of-pocket cost per approved new compound is $1395 million (2013 dollars). Capitalizing out-of-pocket costs to the point of marketing approval at a real discount rate of 10.5% yields a total pre-approval cost estimate of $2558 million (2013 dollars). When compared to the results of the previous study in this series, total capitalized costs were shown to have increased at an annual rate of 8.5% above general price inflation. Adding an estimate of post-approval R&D costs increases the cost estimate to $2870 million (2013 dollars). Copyright © 2016 Elsevier B.V. All rights reserved.

  5. The role of radiolabelled compounds in preclinical drug development

    International Nuclear Information System (INIS)

    Hawkins, D.R.

    1988-01-01

    The role of radiolabelled compounds in the development of new drugs is discussed, with particular reference to their use in toxicological, metabolic and pharmacokinetic studies for the pre-clinical safety evaluation of new drugs. (U.K.)

  6. Complementation of biotransformations with chemical C-H oxidation: copper-catalyzed oxidation of tertiary amines in complex pharmaceuticals.

    Science.gov (United States)

    Genovino, Julien; Lütz, Stephan; Sames, Dalibor; Touré, B Barry

    2013-08-21

    The isolation, quantitation, and characterization of drug metabolites in biological fluids remain challenging. Rapid access to oxidized drugs could facilitate metabolite identification and enable early pharmacology and toxicity studies. Herein, we compared biotransformations to classical and new chemical C-H oxidation methods using oxcarbazepine, naproxen, and an early compound hit (phthalazine 1). These studies illustrated the low preparative efficacy of biotransformations and the inability of chemical methods to oxidize complex pharmaceuticals. We also disclose an aerobic catalytic protocole (CuI/air) to oxidize tertiary amines and benzylic CH's in drugs. The reaction tolerates a broad range of functionalities and displays a high level of chemoselectivity, which is not generally explained by the strength of the C-H bonds but by the individual structural chemotype. This study represents a first step toward establishing a chemical toolkit (chemotransformations) that can selectively oxidize C-H bonds in complex pharmaceuticals and rapidly deliver drug metabolites.

  7. Analysis of pharmaceutical pellets: An approach using near-infrared chemical imaging

    International Nuclear Information System (INIS)

    Sabin, Guilherme P.; Breitkreitz, Marcia C.; Souza, Andre M. de; Fonseca, Patricia da; Calefe, Lupercio; Moffa, Mario; Poppi, Ronei J.

    2011-01-01

    Highlights: → Near-Infrared Chemical Imaging was used for pellets analysis. → Distribution of the components throughout the coatings layers and core of the pellets was estimated. → Classical Least Squares (CLS) was used for calculation of the concentration maps. - Abstract: Pharmaceutical pellets are spherical or nearly spherical multi-unit dosage forms designed to optimize pharmacokinetics and pharmacodynamics features of drug release. The distribution of the pharmaceutical ingredients in the layers and core is a very important parameter for appropriate drug release, especially for pellets manufactured by the process of layer gain. Physical aspects of the sample are normally evaluated by Scanning Electron Microscopy (SEM), but it is in many cases unsuitable to provide conclusive chemical information about the distribution of the pharmaceutical ingredients in both layers and core. On the other hand, methods based on spectroscopic imaging can be very promising for this purpose. In this work, a Near-Infrared Chemical Imaging (NIR-CI) method was developed and applied to the analysis of diclophenac sodium pellets. Since all the compounds present in the sample were known in advance, Classical Least Squares (CLS) was used for calculations. The results have shown that the method was capable of providing chemical information about the distribution of the active ingredient and excipients in the core and coating layers and therefore can be complementary to SEM for the pharmaceutical development of pellets.

  8. Analysis of pharmaceutical pellets: An approach using near-infrared chemical imaging

    Energy Technology Data Exchange (ETDEWEB)

    Sabin, Guilherme P.; Breitkreitz, Marcia C.; Souza, Andre M. de [Institute of Chemistry, University of Campinas, P.O. Box 6154, 13084-971 Campinas, SP (Brazil); Fonseca, Patricia da; Calefe, Lupercio; Moffa, Mario [Zelus Servicos para Industria Farmaceutica Ltda., Av. Professor Lineu Prestes n. 2242, Sao Paulo, SP (Brazil); Poppi, Ronei J., E-mail: ronei@iqm.unicamp.br [Institute of Chemistry, University of Campinas, P.O. Box 6154, 13084-971 Campinas, SP (Brazil)

    2011-11-07

    Highlights: {yields} Near-Infrared Chemical Imaging was used for pellets analysis. {yields} Distribution of the components throughout the coatings layers and core of the pellets was estimated. {yields} Classical Least Squares (CLS) was used for calculation of the concentration maps. - Abstract: Pharmaceutical pellets are spherical or nearly spherical multi-unit dosage forms designed to optimize pharmacokinetics and pharmacodynamics features of drug release. The distribution of the pharmaceutical ingredients in the layers and core is a very important parameter for appropriate drug release, especially for pellets manufactured by the process of layer gain. Physical aspects of the sample are normally evaluated by Scanning Electron Microscopy (SEM), but it is in many cases unsuitable to provide conclusive chemical information about the distribution of the pharmaceutical ingredients in both layers and core. On the other hand, methods based on spectroscopic imaging can be very promising for this purpose. In this work, a Near-Infrared Chemical Imaging (NIR-CI) method was developed and applied to the analysis of diclophenac sodium pellets. Since all the compounds present in the sample were known in advance, Classical Least Squares (CLS) was used for calculations. The results have shown that the method was capable of providing chemical information about the distribution of the active ingredient and excipients in the core and coating layers and therefore can be complementary to SEM for the pharmaceutical development of pellets.

  9. Institutional corruption of pharmaceuticals and the myth of safe and effective drugs.

    Science.gov (United States)

    Light, Donald W; Lexchin, Joel; Darrow, Jonathan J

    2013-01-01

    Over the past 35 years, patients have suffered from a largely hidden epidemic of side effects from drugs that usually have few offsetting benefits. The pharmaceutical industry has corrupted the practice of medicine through its influence over what drugs are developed, how they are tested, and how medical knowledge is created. Since 1906, heavy commercial influence has compromised congressional legislation to protect the public from unsafe drugs. The authorization of user fees in 1992 has turned drug companies into the FDA's prime clients, deepening the regulatory and cultural capture of the agency. Industry has demanded shorter average review times and, with less time to thoroughly review evidence, increased hospitalizations and deaths have resulted. Meeting the needs of the drug companies has taken priority over meeting the needs of patients. Unless this corruption of regulatory intent is reversed, the situation will continue to deteriorate. We offer practical suggestions including: separating the funding of clinical trials from their conduct, analysis, and publication; independent FDA leadership; full public funding for all FDA activities; measures to discourage R&D on drugs with few, if any, new clinical benefits; and the creation of a National Drug Safety Board. © 2013 American Society of Law, Medicine & Ethics, Inc.

  10. Advanced biological activated carbon filter for removing pharmaceutically active compounds from treated wastewater.

    Science.gov (United States)

    Sbardella, Luca; Comas, Joaquim; Fenu, Alessio; Rodriguez-Roda, Ignasi; Weemaes, Marjoleine

    2018-04-28

    Through their release of effluents, conventional wastewater treatment plants (WWTPs) represent a major pollution point sources for pharmaceutically active compounds (PhACs) in water bodies. The combination of a biological activated carbon (BAC) filter coupled with an ultrafiltration (UF) unit was evaluated as an advanced treatment for PhACs removal at pilot scale. The BAC-UF pilot plant was monitored for one year. The biological activity of the biofilm that developed on the granular activated carbon (GAC) particles and the contribution of this biofilm to the overall removal of PhACs were evaluated. Two different phases were observed during the long-term monitoring of PhACs removal. During the first 9200 bed volumes (BV; i.e., before GAC saturation), 89, 78, 83 and 79% of beta-blockers, psychiatric drugs, antibiotics and a mix of other therapeutic groups were removed, respectively. The second phase was characterized by deterioration of the overall performances during the period between 9200 and 13,800 BV. To quantify the respective contribution of adsorption and biodegradation, a lab-scale setup was operated for four months and highlighted the essential role played by GAC in biofiltration units. Physical adsorption was indeed the main removal mechanism. Nevertheless, a significant contribution due to biological activity was detected for some PhACs. The biofilm contributed to the removal of 22, 25, 30, 32 and 35% of ciprofloxacin, bezafibrate, ofloxacin, azithromycin and sulfamethoxazole, respectively. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  11. Cost-containment as part of pharmaceutical policy

    DEFF Research Database (Denmark)

    Almarsdóttir, Anna Birna; Traulsen, Janine Marie

    2005-01-01

    and profit controls; 2) reimbursement system charges; 3) other fiscal measures; 4) quality measures. Pharmaceuticals policy has suffered from the pervasive misunderstanding that drugs are like any other commodity; resulting in policy makers viewing pharmaceuticals expenditures without thinking about drugs...

  12. Biocatalytic Synthesis of Chiral Pharmaceutical Intermediates

    Directory of Open Access Journals (Sweden)

    Ramesh N. Patel

    2004-01-01

    Full Text Available The production of single enantiomers of drug intermediates has become increasingly important in the pharmaceutical industry. Chiral intermediates and fine chemicals are in high demand from both the pharmaceutical and agrochemical industries for the preparation of bulk drug substances and agricultural products. The enormous potential of microorganisms and enzymes for the transformation of synthetic chemicals with high chemo-, regio- and enantioselectivities has been demonstrated. In this article, biocatalytic processes are described for the synthesis of chiral pharmaceutical intermediates.

  13. Pharmaceutical cocrystals, salts and polymorphs: Advanced characterization techniques.

    Science.gov (United States)

    Pindelska, Edyta; Sokal, Agnieszka; Kolodziejski, Waclaw

    2017-08-01

    The main goal of a novel drug development is to obtain it with optimal physiochemical, pharmaceutical and biological properties. Pharmaceutical companies and scientists modify active pharmaceutical ingredients (APIs), which often are cocrystals, salts or carefully selected polymorphs, to improve the properties of a parent drug. To find the best form of a drug, various advanced characterization methods should be used. In this review, we have described such analytical methods, dedicated to solid drug forms. Thus, diffraction, spectroscopic, thermal and also pharmaceutical characterization methods are discussed. They all are necessary to study a solid API in its intrinsic complexity from bulk down to the molecular level, gain information on its structure, properties, purity and possible transformations, and make the characterization efficient, comprehensive and complete. Furthermore, these methods can be used to monitor and investigate physical processes, involved in the drug development, in situ and in real time. The main aim of this paper is to gather information on the current advancements in the analytical methods and highlight their pharmaceutical relevance. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. New Antimicrobial Approaches: Reuse of Old Drugs.

    Science.gov (United States)

    Savoia, Dianella

    2016-01-01

    The global situation of antibiotic resistance and the reduction of investments in antibiotics research by the pharmaceutical industry suggest the need for specific cost-effective approaches in order to identify drugs for the therapy of many microbial infections. Among the viable alternative anti-infective compounds, drug repurposing, i.e. to find new uses for previously approved medicines, revealed some encouraging in vitro and in vivo results. In this article the reader has a panoramic view of the updated references on the strategies encountered during the repositioning process. New findings are reported about the anti-microbial efficacy of antipsychotic, cardiovascular, anti-inflammatory and anti-neoplastic drugs. This approach may enhance the portfolio of pharmaceutical companies reducing the need for pharmacokinetic and toxicity studies; the development of new uses of old drugs for different infectious diseases, leading to better health for patients, also in poor, tropical countries, appears to be having better results.

  15. [New research on the significance of polymers in pharmaceutical formulations].

    Science.gov (United States)

    Amighi, K

    2001-01-01

    During these last few decades, a lot of work has been made in pharmaceutical area in order to control the drug delivery from various pharmaceutical dosage forms. The use of polymers in pharmaceutical technology have led to the development of the first drug delivery systems proposed in order to prolong or to delay the drug delivery, or to enhance drug release for drugs showing bioavailability shortcomings. The wide range of polymers available for pharmaceutical use, their low reactivity towards drugs and other formulation ingredients and their safe nature, have permitted a widespread use of polymers to improve manufacturing processes or for the formulation of pharmaceutical dosage forms for various administration routes. More over, the preparation of new polymeric materials by the synthesis of new polymers with unique properties or by the modification of available natural or synthetic polymers, offer to the formulator a wide range of applications in order to optimise the drug delivery for each specific case.

  16. Microstructure of Pharmaceutical Semicrystalline Dispersions: The Significance of Polymer Conformation.

    Science.gov (United States)

    Van Duong, Tu; Goderis, Bart; Van Humbeeck, Jan; Van den Mooter, Guy

    2018-02-05

    The microstructure of pharmaceutical semicrystalline solid dispersions has attracted extensive attention due to its complexity that might result in the diversity in physical stability, dissolution behavior, and pharmaceutical performance of the systems. Numerous factors have been reported that dictate the microstructure of semicrystalline dispersions. Nevertheless, the importance of the complicated conformation of the polymer has never been elucidated. In this study, we investigate the microstructure of dispersions of polyethylene glycol and active pharmaceutical ingredients by small-angle X-ray scattering and high performance differential scanning calorimetry. Polyethylene glycol with molecular weight of 2000 g/mol (PEG2000) and 6000 g/mol (PEG6000) exhibited remarkable discrepancy in the lamellar periodicity in dispersions with APIs which was attributed to the differences in their folding behavior. The long period of PEG2000 always decreased upon aging-induced exclusion of APIs from the interlamellar region of extended chain crystals whereas the periodicity of PEG6000 may decrease or increase during storage as a consequence of the competition between the drug segregation and the lamellar thickening from nonintegral-folded into integral-folded chain crystals. These processes were in turn significantly influenced by the crystallization tendency of the pharmaceutical compounds, drug-polymer interactions, as well as the dispersion composition and crystallization temperature. This study highlights the significance of the polymer conformation on the microstructure of semicrystalline systems that is critical for the preparation of solid dispersions with consistent and reproducible quality.

  17. Pharmaceutical policies for the Third World--whose responsibility?

    Science.gov (United States)

    1983-07-16

    Several developing countries, such as Bangladesh, Cuba, India, and Mozambique, are currently formulating national pharmaceutical policies to reduce expenditures on drugs while increasing their availability to those in greatest need. 5 components of such national policies have been identified: 1) elimination of ineffective and inappropriate preparations through concentrating on a selection such as the World Health Organization's 200 "basic and essential drugs", coupled with national drug pricing policies that discriminate between essential drugs and non-essential or luxury drugs; 2) public systems of drug distribution which would reduce costs to the consumer; 3) importation of the limited number of drugs distributed through the public system in bulk, which might reduce costs by 20-25%; 4) use of generic rather than brand name drugs; and 5) establishment of domestic pharmaceutical industries within developing countries to encourage research into drugs for local health problems, reduce use of foreign exchange to import drugs, and increase local self-reliance in dealing with disease. In November 1982, Health Action International, a coordinating body for more than 50 publish interest groups seeking to promote rational use of pharmaceuticals, presented a draft internationl code on pharmaceuticals to the UN Conference on Trade and Development. A voluntary code produced in 1981 by the International Federation of Pharmaceutical Manufacturers' Associations paid little attention to monitoring and enforcement. Little progress has been made, and the need for sensible policy making at the international and national levels has long been apparent.

  18. Funding pharmaceutical innovation through direct tax credits.

    Science.gov (United States)

    Lybecker, Kristina M; Freeman, Robert A

    2007-07-01

    Rising pharmaceutical prices, increasing demand for more effective innovative drugs and growing public outrage have heightened criticism of the pharmaceutical industry. The public debate has focused on drug prices and access. As a consequence, the patent system is being reexamined as an efficient mechanism for encouraging pharmaceutical innovation and drug development. We propose an alternative to the existing patent system, instead rewarding the innovating firm with direct tax credits in exchange for marginal cost pricing. This concept is based on the fundamental assumption that innovation that benefits society at large may be financed publicly. As an industry which produces a social good characterized by high fixed costs, high information and regulatory costs, and relatively low marginal costs of production, pharmaceuticals are well-suited to such a mechanism. Under this proposal, drug prices fall, consumer surplus increases, access is enhanced, and the incentives to innovate are preserved.

  19. Prioritizing veterinary pharmaceuticals for aquatic environment in Korea.

    Science.gov (United States)

    Kim, Younghee; Jung, Jinyong; Kim, Myunghyun; Park, Jeongim; Boxall, Alistair B A; Choi, Kyungho

    2008-09-01

    Pharmaceutical residues may have serious impacts on nontarget biological organisms in aquatic ecosystems, and have therefore precipitated numerous investigations worldwide. Many pharmaceutical compounds available on the market need to be prioritized based on their potential ecological and human health risks in order to develop sound management decisions. We prioritized veterinary pharmaceuticals in Korea by their usage, potential to enter the environment, and toxicological hazard. Twenty compounds were identified in the top priority class, most of which were antibiotics. Among these compounds, 8 were identified as deserving more immediate attention: amoxicillin, enramycin, fenbendazole, florfenicol, ivermectin, oxytetracycline, tylosin, and virginiamycin. A limitation of this study is that we initially screened veterinary pharmaceuticals by sales tonnage for veterinary use only. However, this is the first attempt to prioritize veterinary pharmaceuticals in Korea, and it provides important concepts for developing environmental risk management plans for such contaminants in aquatic systems. Copyright © 2008 Elsevier B.V. All rights reserved.

  20. 78 FR 72841 - List of Bulk Drug Substances That May Be Used in Pharmacy Compounding; Bulk Drug Substances That...

    Science.gov (United States)

    2013-12-04

    .... FDA-2013-N-1525] List of Bulk Drug Substances That May Be Used in Pharmacy Compounding; Bulk Drug... proposed rule to list bulk drug substances used in pharmacy compounding and preparing to develop a list of... Formulary monograph, if a monograph exists, and the United States Pharmacopoeia chapter on pharmacy...

  1. Systematic analysis of cell cycle effects of common drugs leads to the discovery of a suppressive interaction between gemfibrozil and fluoxetine.

    Science.gov (United States)

    Hoose, Scott A; Duran, Camille; Malik, Indranil; Eslamfam, Shabnam; Shasserre, Samantha C; Downing, S Sabina; Hoover, Evelyn M; Dowd, Katherine E; Smith, Roger; Polymenis, Michael

    2012-01-01

    Screening chemical libraries to identify compounds that affect overall cell proliferation is common. However, in most cases, it is not known whether the compounds tested alter the timing of particular cell cycle transitions. Here, we evaluated an FDA-approved drug library to identify pharmaceuticals that alter cell cycle progression in yeast, using DNA content measurements by flow cytometry. This approach revealed strong cell cycle effects of several commonly used pharmaceuticals. We show that the antilipemic gemfibrozil delays initiation of DNA replication, while cells treated with the antidepressant fluoxetine severely delay progression through mitosis. Based on their effects on cell cycle progression, we also examined cell proliferation in the presence of both compounds. We discovered a strong suppressive interaction between gemfibrozil and fluoxetine. Combinations of interest among diverse pharmaceuticals are difficult to identify, due to the daunting number of possible combinations that must be evaluated. The novel interaction between gemfibrozil and fluoxetine suggests that identifying and combining drugs that show cell cycle effects might streamline identification of drug combinations with a pronounced impact on cell proliferation.

  2. Systematic analysis of cell cycle effects of common drugs leads to the discovery of a suppressive interaction between gemfibrozil and fluoxetine.

    Directory of Open Access Journals (Sweden)

    Scott A Hoose

    Full Text Available Screening chemical libraries to identify compounds that affect overall cell proliferation is common. However, in most cases, it is not known whether the compounds tested alter the timing of particular cell cycle transitions. Here, we evaluated an FDA-approved drug library to identify pharmaceuticals that alter cell cycle progression in yeast, using DNA content measurements by flow cytometry. This approach revealed strong cell cycle effects of several commonly used pharmaceuticals. We show that the antilipemic gemfibrozil delays initiation of DNA replication, while cells treated with the antidepressant fluoxetine severely delay progression through mitosis. Based on their effects on cell cycle progression, we also examined cell proliferation in the presence of both compounds. We discovered a strong suppressive interaction between gemfibrozil and fluoxetine. Combinations of interest among diverse pharmaceuticals are difficult to identify, due to the daunting number of possible combinations that must be evaluated. The novel interaction between gemfibrozil and fluoxetine suggests that identifying and combining drugs that show cell cycle effects might streamline identification of drug combinations with a pronounced impact on cell proliferation.

  3. Supercritical fluid technology: concepts and pharmaceutical applications.

    Science.gov (United States)

    Deshpande, Praful Balavant; Kumar, G Aravind; Kumar, Averineni Ranjith; Shavi, Gopal Venkatesh; Karthik, Arumugam; Reddy, Meka Sreenivasa; Udupa, Nayanabhirama

    2011-01-01

    In light of environmental apprehension, supercritical fluid technology (SFT) exhibits excellent opportunities to accomplish key objectives in the drug delivery sector. Supercritical fluid extraction using carbon dioxide (CO(2)) has been recognized as a green technology. It is a clean and versatile solvent with gas-like diffusivity and liquid-like density in the supercritical phase, which has provided an excellent alternative to the use of chemical solvents. The present commentary provides an overview of different techniques using supercritical fluids and their future opportunity for the drug delivery industry. Some of the emerging applications of SFT in pharmaceuticals, such as particle design, drug solubilization, inclusion complex, polymer impregnation, polymorphism, drug extraction process, and analysis, are also covered in this review. The data collection methods are based on the recent literature related to drug delivery systems using SFT platforms. SFT has become a much more versatile and environmentally attractive technology that can handle a variety of complicated problems in pharmaceuticals. This cutting-edge technology is growing predominantly to surrogate conventional unit operations in relevance to the pharmaceutical production process. Supercritical fluid technology has recently drawn attention in the field of pharmaceuticals. It is a distinct conception that utilizes the solvent properties of supercritical fluids above their critical temperature and pressure, where they exhibit both liquid-like and gas-like properties, which can enable many pharmaceutical applications. For example, the liquid-like properties provide benefits in extraction processes of organic solvents or impurities, drug solubilization, and polymer plasticization, and the gas-like features facilitate mass transfer processes. It has become a much more versatile and environmentally attractive technology that can handle a variety of complicated problems in pharmaceuticals. This review is

  4. Analysis of the importance of drug packaging quality for end users and pharmaceutical industry as a part of the quality management system

    Directory of Open Access Journals (Sweden)

    Lončar Irma M.

    2013-01-01

    Full Text Available In this study, we collected and analyzed information on the importance of drug packaging quality to end users and pharmaceutical industry, as an indicator of the process of traceability and originality of drugs. Two surveys were conducted: one among the end users of drugs (252 patients and the other among professionals working in seven pharmaceutical companies in Serbia. For most end users (82.5% quality on the packaging of drugs was important, but only 41.8% of them thought that the appearance of the packaging could be an indicator of genuinity of drugs. The existence of the control marks (KM on drug packaging was not of great importance, since most of them (86.9% know, its function, but majority (60.2% would nevertheless decide to buy the drug without KM. Regarding the experts from the pharmaceutical industry, more then two-thirds of them (68.4% believed that the existence of KM did not contribute to efficient operations. Although a great number of pharmaceutical industry professionals (84.2% answered that the introduction of GS1 DataMatrix system would allow for complete traceability of the drug from the manufacturer to the end user, only 22.2% of them introduced this system to their products. This study also showed that domestic producers did not have a great interest for additional protection (special inks, holograms, special graphics, smart multicolor design, watermark, chemically labeled paper and cardboard etc.. on their products, given that only 15.8 % of them had some kind of additional protection against counterfeiting. Monitoring drug traceability from a manufacturer to end user is achieved by many complex activities regulated by law. A high percentage of responders said they were satisfied with the functionality of traceability systems used in their companies. As a way to increase the quality of drug packaging and business performance most responders saw in the continuous improvement of the system of traceability within the company

  5. Validation of an ultra-high-performance liquid chromatography-tandem mass spectrometry method to quantify illicit drug and pharmaceutical residues in wastewater using accuracy profile approach.

    Science.gov (United States)

    Hubert, Cécile; Roosen, Martin; Levi, Yves; Karolak, Sara

    2017-06-02

    The analysis of biomarkers in wastewater has become a common approach to assess community behavior. This method is an interesting way to estimate illicit drug consumption in a given population: by using a back calculation method, it is therefore possible to quantify the amount of a specific drug used in a community and to assess the consumption variation at different times and locations. Such a method needs reliable analytical data since the determination of a concentration in the ngL -1 range in a complex matrix is difficult and not easily reproducible. The best analytical method is liquid chromatography - mass spectrometry coupling after solid-phase extraction or on-line pre-concentration. Quality criteria are not specially defined for this kind of determination. In this context, it was decided to develop an UHPLC-MS/MS method to analyze 10 illicit drugs and pharmaceuticals in wastewater treatment plant influent or effluent using a pre-concentration on-line system. A validation process was then carried out using the accuracy profile concept as an innovative tool to estimate the probability of getting prospective results within specified acceptance limits. Influent and effluent samples were spiked with known amounts of the 10 compounds and analyzed three times a day for three days in order to estimate intra-day and inter-day variations. The matrix effect was estimated for each compound. The developed method can provide at least 80% of results within ±25% limits except for compounds that are degraded in influent. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Photostability and Photostabilization of Drugs and Drug Products

    Directory of Open Access Journals (Sweden)

    Iqbal Ahmad

    2016-01-01

    Full Text Available Photostability studies of drugs and drug products are an integral part of the product development process in the pharmaceutical industry. These studies are carried out to ensure quality, efficacy, and safety of the formulated products during manufacture, storage, and use. This review deals with the concept of photostability and related aspects and the literature available in the field. It highlights the role of the photochemistry in the photostability studies, describes the functional groups important for the photoreactivity of drugs, explains photophysical processes, and deals with the kinetics of photochemical reactions. The various modes of photodegradation of drugs with examples of selected compounds are presented. The biological consequences of the effect of light on the drug degradation are described. The photostability testing of drugs and drug products and the requirements under ICH guideline are discussed. Some information on the packaging requirements for the formulated products is provided. The various methods used for the photostabilization of solid and liquid dosage forms are also discussed.

  7. Accuracy of drug advertisements in medical journals under new law regulating the marketing of pharmaceutical products in Switzerland.

    Science.gov (United States)

    Santiago, Macarena Gonzalez; Bucher, Heiner C; Nordmann, Alain J

    2008-12-31

    New legal regulations for the marketing of pharmaceutical products were introduced in 2002 in Switzerland. We investigated whether claims in drug advertisements citing published scientific studies were justified by these studies after the introduction of these new regulations. In this cross-sectional study, two independent reviewers screened all issues of six major Swiss medical journals published in the year 2005 to identify all drug advertisements for analgesic, gastrointestinal and psychopharmacologic drugs and evaluated all drug advertisements referring to at least one publication. The pharmaceutical claim was rated as being supported, being based on a potentially biased study or not to be supported by the cited study according to pre-specified criteria. We also explored factors likely to be associated with supported advertisement claims. Of 2068 advertisements 577 (28%) promoted analgesic, psychopharmacologic or gastrointestinal drugs. Among them were 323 (56%) advertisements citing at least one reference. After excluding multiple publications of the same drug advertisement and advertisements with non-informative references, there remained 29 unique advertisements with at least one reference to a scientific study. These 29 advertisements contained 78 distinct pairs of claims of analgesic, gastrointestinal and psychopharmacologic drugs and referenced studies. Thirty-seven (47%) claims were supported, 16 (21%) claims were not supported by the corresponding reference, and 25 (32%) claims were based on potentially biased evidence, with no relevant differences between drug groups. Studies with conflict of interest and studies stating industry funding were more likely to support the corresponding claim (RR 1.52, 95% CI 1.07-2.17 and RR 1.50, 95% CI 0.98-2.28) than studies without identified conflict of interest and studies without information on type of funding. Following the introduction of new regulations for drug advertisement in Switzerland, 53% of all assessed

  8. Spectrophotometric determination of dopaminergic drugs used for Parkinson's disease, cabergoline and ropinirole, in pharmaceutical preparations.

    Science.gov (United States)

    Onal, Armağan; Cağlar, Sena

    2007-04-01

    Simple and reproducible spectrophotometric methods have been developed for determination of dopaminergic drugs used for Parkinson's disease, cabergoline (CAB) and ropinirole hydrochloride (ROP), in pharmaceutical preparations. The methods are based on the reactions between the studied drug substances and ion-pair agents [methyl orange (MO), bromocresol green (BCG) and bromophenol blue (BPB)] producing yellow colored ion-pair complexes in acidic buffers, after extracting in dichloromethane, which are spectrophotometrically determined at the appropriate wavelength of ion-pair complexes. Beer's law was obeyed within the concentration range from 1.0 to 35 microg ml(-1). The developed methods were applied successfully for the determination of these drugs in tablets.

  9. Introduction: Institutional corruption and the pharmaceutical policy.

    Science.gov (United States)

    Rodwin, Marc A

    2013-01-01

    Today, the goals of pharmaceutical policy and medical practice are often undermined due to institutional corruption - that is, widespread or systemic practices, usually legal, that undermine an institution's objectives or integrity. In this symposium, 16 articles investigate the corruption of pharmaceutical policy, each taking a different look at the sources of corruption, how it occurs, and what is corrupted. We will see that the pharmaceutical industry's own purposes are often undermined. Furthermore, pharmaceutical industry funding of election campaigns and lobbying skews the legislative process that sets pharmaceutical policy. Moreover, certain practices have corrupted medical research, the production of medical knowledge, the practice of medicine, drug safety, the Food and Drug Administration's oversight of the pharmaceutical market, and the trustworthiness of patient advocacy organizations. © 2013 American Society of Law, Medicine & Ethics, Inc.

  10. Diffuse Scattering as an Aid to the Understanding of Polymorphism in Pharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Welberry, T.R.; Chan, E.J.; Goossens, D.J.; Heerdegen, A.P. (ANU)

    2012-04-30

    Polymorphism occurs when the same molecular compound can crystallize in more than one distinct crystal structure. Its study is a field of great interest and activity. This is largely driven by its importance in the pharmaceutical industry, but polymorphism is also an issue in the pigments, dyes, and explosives industries. The polymorph formed by a compound generally exerts a strong influence on its solid-state properties. The polymorphic form of a drug molecule may affect the ease of manufacture and processing, shelf life, and most significantly the rate of uptake of the molecule by the human body. They can even vary in toxicity; one polymorph may be safe, while a second may be toxic. In this review of recently published work, we show how diffuse scattering experiments coupled with Monte Carlo (MC) computer modeling can aid in the understanding of polymorphism. Examples of the two common pharmaceuticals, benzocaine and aspirin, both of which are bimorphic, at ambient temperatures, are discussed.

  11. Optimization of the THP-1 activation assay to detect pharmaceuticals with potential to cause immune mediated drug reactions.

    Science.gov (United States)

    Corti, Daniele; Galbiati, Valentina; Gatti, Nicolò; Marinovich, Marina; Galli, Corrado L; Corsini, Emanuela

    2015-10-01

    Despite important impacts of systemic hypersensitivity induced by pharmaceuticals, for such endpoint no reliable preclinical approaches are available. We previously established an in vitro test to identify contact and respiratory allergens based on interleukin-8 (IL-8) production in THP-1 cells. Here, we challenged it for identification of pharmaceuticals associated with systemic hypersensitivity reactions, with the idea that drug sensitizers share common mechanisms of cell activation. Cells were exposed to drugs associated with systemic hypersensitivity reactions (streptozotocin, sulfamethoxazole, neomycin, probenecid, clonidine, procainamide, ofloxacin, methyl salicylate), while metformin was used as negative drug. Differently to chemicals, drugs tested were well tolerated, except clonidine and probenecid, with no signs of cytotoxicity up to 1-2mg/ml. THP-1 activation assay was adjusted, and conditions, that allow identification of all sensitizing drugs tested, were established. Next, using streptozotocin and selective inhibitors of PKC-β and p38 MAPK, two pathways involved in chemical allergen-induced cell activation, we tested the hypothesis that similar pathways were also involved in drug-induced IL-8 production and CD86 upregulation. Results indicated that drugs and chemical allergens share similar activation pathways. Finally, we made a structure-activity hypothesis related to hypersensitivity reactions, trying to individuate structural requisite that can be involved in immune mediated adverse reactions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Microbial Removal of the Pharmaceutical Compounds Ibuprofen and Diclofenac from Wastewater

    NARCIS (Netherlands)

    Langenhoff, A.A.M.; Inderfurth, N.S.; Veuskens, T.; Schraa, G.; Blokland, M.; Kujawa-Roeleveld, K.; Rijnaarts, H.H.M.

    2013-01-01

    Studies on the occurrence of pharmaceuticals show that the widely used pharmaceuticals ibuprofen and diclofenac are present in relevant concentrations in the environment. A pilot plant treating hospital wastewater with relevant concentrations of these pharmaceuticals was evaluated for its

  13. [HERA-QUEST: HTA evaluation of generic pharmaceutical products to improve quality, economic efficiency, patient safety and transparency in drug product changes in hospitals].

    Science.gov (United States)

    Gyalrong-Steur, Miriam; Kellermann, Anita; Bernard, Rudolf; Berndt, Georg; Bindemann, Meike; Nusser-Rothermundt, Elfriede; Amann, Steffen; Brakebusch, Myga; Brüggmann, Jörg; Tydecks, Eva; Müller, Markus; Dörje, Frank; Kochs, Eberhard; Riedel, Rainer

    2017-04-01

    In view of the rising cost pressure and an increasing number of drug shortages, switches between generic drug preparations have become a daily routine in hospitals. To ensure consistently high treatment quality and best possible patient safety, the equivalence of the new and the previous drug preparation must be ensured before any change in the purchase of pharmaceutical products takes place. So far, no easily usable, transparent and standardized instrument for this kind of comparison between generic drug products has been available. A group of pharmaceutical experts has developed the drug HTA (health technology assessment) model "HERA" (HTA Evaluation of geneRic phArmaceutical products) through a multi-step process. The instrument is designed to perform both a qualitative and economic comparison of equivalent drug preparations ("aut idem" substitution) before switching products. The economic evaluation does not only consider unit prices and consumption quantity, but also the processing costs associated with a product change process. The qualitative comparison is based on the evaluation of 34 quality criteria belonging to six evaluation fields (e.g., approval status, practical handling, packaging design). The objective evaluation of the quality criteria is complemented by an assessment of special features of the individual hospital for complex drug switches, including the feedback of the physicians utilizing the drug preparation. Thus potentially problematic switches of pharmaceutical products can be avoided at the best possible rate, contributing to the improvement of patient safety. The novel drug HTA model HERA is a tool used in clinical practice that can add to an increase in quality, therapeutic safety and transparency of drug use while simultaneously contributing to the economic optimization of drug procurement in hospitals. Combining these two is essential for hospitals facing the tension between rising cost pressure and at the same time increasing demands

  14. Simultaneous Determination of 25 Common Pharmaceuticals in Whole Blood Using Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry

    DEFF Research Database (Denmark)

    Nielsen, Marie Katrine Klose; Johansen, Sys Stybe

    2012-01-01

    An ultra-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the quantification of 25 common pharmaceuticals in whole blood. The selected pharmaceuticals represent the most frequently detected drugs in our forensic laboratory with basic properties....../kg depending on the analyte. A good linear behavior was achieved for all analytes in the range from LOQ to 1.0 or 2.0 mg/kg blood. The absolute recoveries were between 55-87% for all compounds except norfluoxetine (44%). The method showed acceptable precision and accuracy for almost all analytes. Only unstable...

  15. Novel inhibitors of HIV discovered among existing classes of pharmaceutical compounds indicated for unrelated clinical indications.

    Science.gov (United States)

    Kucherov, I I; Rytik, P G; Podol'skaya, I A; Mistryukova, L O; Korjev, M O

    2009-01-01

    In vitro screening of 307 drugs with various clinical indications (cardiotropic, neurotropic, antibacterial, etc.) has revealed 6 compounds which displayed remarkable antiretroviral activity. Three of these drugs had a tendency to have undesirable side effects and were thus excluded from further consideration. Remaining three, i.e., Xantinol Nicotinate, Tardiferon, and Trental may become valid candidates for inclusion into antiviral regimens such as HAART. In vitro tests have shown that xantinol and trental display synergistic effect with azidothymidine, inhibit the replication AZT-resistant strains of HIV, and have no competing undesirable activities. These compounds should be evaluated in safety studies to determine optimal doses for patients with HIV. If these studies confirm in vitro results these compounds may become valid candidates as safe and affordable means to be added into the arsenal of antiretroviral drugs.

  16. The Effectiveness of Pharmaceutical Marketing

    NARCIS (Netherlands)

    E.R. Kappe

    2011-01-01

    textabstractPharmaceutical marketing effectiveness comprises the measurement of marketing efforts of pharmaceutical firms towards doctors and patients. These firms spend billions of dollars yearly to promote their prescription drugs. This dissertation provides empirical analyses and methods to

  17. Pharmaceutical cocrystals: along the path to improved medicines.

    Science.gov (United States)

    Duggirala, Naga K; Perry, Miranda L; Almarsson, Örn; Zaworotko, Michael J

    2016-01-14

    Cocrystals, a long known but understudied class of crystalline solids, have attracted interest from crystal engineers and pharmaceutical scientists in the past decade and are now an integral part of the preformulation stage of drug development. This is largely because cocrystals that contain a drug molecule, pharmaceutical cocrystals, can modify physicochemical properties without the need for covalent modification of the drug molecule. This review presents a brief history of cocrystals before addressing recent advances in design, discovery and development of pharmaceutical cocrystals that have occurred since an earlier review published in 2004. We address four aspects of cocrystals: nomenclature; design using hydrogen-bonded supramolecular synthons; methods of discovery and synthesis; development of pharmaceutical cocrystals as drug products. Cocrystals can be classified into molecular cocrystals (MCCs) that contain only neutral components (coformers) and ionic cocrystals (ICCs), which are comprised of at least one ionic coformer that is a salt. That cocrystals, especially ICCs, offer much greater diversity in terms of composition and properties than single component crystal forms and are amenable to design makes them of continuing interest. Seven recent case studies that illustrate how pharmaceutical cocrystals can improve physicochemical properties and clinical performance of drug substances, including a recently approved drug product based upon an ICC, are presented.

  18. Pharmaceutical expenditure on drugs for rare diseases in Canada: a historical (2007-13) and prospective (2014-18) MIDAS sales data analysis.

    Science.gov (United States)

    Divino, Victoria; DeKoven, Mitch; Kleinrock, Michael; Wade, Rolin L; Kim, Tony; Kaura, Satyin

    2016-05-21

    Health Canada has defined rare diseases as life-threatening, seriously debilitating, or serious chronic conditions affecting a very small number of patients (~1 in 2,000 persons). An estimated 9 % of Canadians suffer from a rare disease. Drugs treating rare diseases (DRDs) are also known as orphan drugs. While Canada is currently developing an orphan drug framework, in the United States (US), the Orphan Drug Act (ODA) of 1983 established incentives for the development of orphan drugs. This study measured total annual expenditure of orphan drugs in Canada (2007-13) and estimated future (2014-18) orphan drug expenditure. Orphan drugs approved by the US Food and Drug Administration (FDA) in the US were used as a proxy for the orphan drug landscape in Canada. Branded, orphan drugs approved by the FDA between 1983 through 2013 were identified (N = 356 unique products). Only US orphan drugs with the same orphan indication(s) approved in Canada were included in the analysis. Adjustment via an indication factoring was applied to products with both orphan and non-orphan indications using available data sources to isolate orphan-indication sales. The IMS Health MIDAS database of audited biopharmaceutical sales was utilized to measure total orphan drug expenditure, calculated annually from 2007-2013 and evaluated as a proportion of total annual pharmaceutical drug expenditure (adjusted to 2014 CAD). Between 2007 and 2013, expenditure was measured for a final N = 147 orphan drugs. Orphan drug expenditure totaled $610.2 million (M) in 2007 and $1,100.0 M in 2013, representing 3.3- 5.6 % of total Canadian pharmaceutical drug expenditure in 2007-2013, respectively. Future trend analysis suggests orphan drug expenditure will remain under 6 % of total expenditure in 2014-18. While the number of available orphan drugs and associated expenditure increased over time, access remains an issue, and from the perspectives of society and equity, overall spending on orphan drugs

  19. Five un-easy pieces of pharmaceutical policy reform.

    Science.gov (United States)

    Rodwin, Marc A

    2013-01-01

    Improper dependencies slant policy over a drug's life span, biasing the development of new drugs, the testing and marketing approval for new drugs, and the monitoring of patient safety after drugs are marketed. This article examines five ways in which the public improperly depends on pharmaceutical firms that compromise the integrity of pharmaceutical policy. Today the public relies on pharmaceutical firms: (1) to set priorities on drug research and development; (2) to conduct clinical trials to test whether drugs are safe and effective; (3) to decide what clinical trial data to disclose to the public; (4) to monitor post marketing drug safety; (5) to supply product information to physicians and to finance continuing medical education and other professional activities. The article suggests options to overcome each of these dependencies. © 2013 American Society of Law, Medicine & Ethics, Inc.

  20. The pharmaceutics used in medicine, using fields and discarding of wastes

    International Nuclear Information System (INIS)

    Oezyurt, M.

    2009-01-01

    Radioisotopes are being used in medicine, industry, environmental pollution, agriculture, hydrology etc. The medical diagnosis by radiation is the main source of synthetic radiation exposure source of public. Radioisotopes are used in different topics both for diagnosis and therapy. Naturally as a result of the usage of these radioactive elements, radioactive wastes are formed and discarding rules of these wastes must be applied very carefully. Solid or liquid all the radioactive medical wastes are subject to utmost care of disposing process under control of the health physics authorities. Pharmaceutics used in humans are consumed at high amounts in the world. Pharmaceutical compounds discharged into surface waters threaten the water life and reenter the water cycle. At a thesis work, it was showed that the medical drugs were absorbed by the active sludge in specific ratios. Therefore, the waters and treated sludges discharged from wastewater treatment plants must never be used for agricultural purposes without the necessary analysis. The receptor media where wastewaters are discharged , also at the places where advanced treatment technologies are not used, presence of medical drug residues cause potential risk for the livings and human health. At this work, the characteristics of radio pharmaceutics, the using places and also discarding ways are told.

  1. Comparison of pharmaceutical, illicit drug, alcohol, nicotine and caffeine levels in wastewater with sale, seizure and consumption data for 8 European cities.

    Science.gov (United States)

    Baz-Lomba, Jose Antonio; Salvatore, Stefania; Gracia-Lor, Emma; Bade, Richard; Castiglioni, Sara; Castrignanò, Erika; Causanilles, Ana; Hernandez, Felix; Kasprzyk-Hordern, Barbara; Kinyua, Juliet; McCall, Ann-Kathrin; van Nuijs, Alexander; Ort, Christoph; Plósz, Benedek G; Ramin, Pedram; Reid, Malcolm; Rousis, Nikolaos I; Ryu, Yeonsuk; de Voogt, Pim; Bramness, Jorgen; Thomas, Kevin

    2016-10-01

    Monitoring the scale of pharmaceuticals, illicit and licit drugs consumption is important to assess the needs of law enforcement and public health, and provides more information about the different trends within different countries. Community drug use patterns are usually described by national surveys, sales and seizure data. Wastewater-based epidemiology (WBE) has been shown to be a reliable approach complementing such surveys. This study aims to compare and correlate the consumption estimates of pharmaceuticals, illicit drugs, alcohol, nicotine and caffeine from wastewater analysis and other sources of information. Wastewater samples were collected in 2015 from 8 different European cities over a one week period, representing a population of approximately 5 million people. Published pharmaceutical sale, illicit drug seizure and alcohol, tobacco and caffeine use data were used for the comparison. High agreement was found between wastewater and other data sources for pharmaceuticals and cocaine, whereas amphetamines, alcohol and caffeine showed a moderate correlation. methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) and nicotine did not correlate with other sources of data. Most of the poor correlations were explained as part of the uncertainties related with the use estimates and were improved with other complementary sources of data. This work confirms the promising future of WBE as a complementary approach to obtain a more accurate picture of substance use situation within different communities. Our findings suggest further improvements to reduce the uncertainties associated with both sources of information in order to make the data more comparable.

  2. Drug nanocrystals for the formulation of poorly soluble drugs and its application as a potential drug delivery system

    International Nuclear Information System (INIS)

    Gao Lei; Zhang Dianrui; Chen Minghui

    2008-01-01

    Formulation of poorly soluble drugs is a general intractable problem in pharmaceutical field, especially those compounds poorly soluble in both aqueous and organic media. It is difficult to resolve this problem using conventional formulation approaches, so many drugs are abandoned early in discovery. Nanocrystals, a new carrier-free colloidal drug delivery system with a particle size ranging from 100 to 1000 nm, is thought as a viable drug delivery strategy to develop the poorly soluble drugs, because of their simplicity in preparation and general applicability. In this article, the product techniques of the nanocrystals were reviewed and compared, the special features of drug nanocrystals were discussed. The researches on the application of the drug nanocrystals to various administration routes were described in detail. In addition, as introduced later, the nanocrystals could be easily scaled up, which was the prerequisite to the development of a delivery system as a market product

  3. Pharmaceutical production of nano particles using supercritical or dense gas technology

    International Nuclear Information System (INIS)

    Regtop, H.

    2002-01-01

    Full text: The primary aim of our proposed research is to develop pharmaceutical formulations with enhanced pharmacokinetics and increased bioavailability. The particular drug delivery systems of interest are, oral, aerosols, injectable and topical with well-recognised and distinct problems of bioavailability. More than 40% of all drugs in the USP or BP are insoluble or have some problem with solubility. It is estimated in 2000, the total combined sales of drugs that are insoluble or poorly soluble was US$37 billion. Precise and predictable drug delivery is made more possible by producing uniform micron size particles or powders, which can improve the efficiency and effectiveness of therapeutical formulations. Hence the purpose of micronisation is to increase bioavailability and also to allow other modes of administration, eg insulin is a protein, which is an injectable for the treatment of diabetes, but recently particles of 1-4 microns of insulin are in phase 3 clinical trials to deliver the drug to diabetics as an inhalant. In addition aerosolised drugs such as mucolytics, antibiotics, antiinflammatory drugs and hormones have recently been trailed. Finely powdered pharmaceuticals are however difficult to process by current techniques. In spray drying the operating temperatures are often too high for heat sensitive drugs. Thermal degradation of compounds can also be experienced in milling due to high rates of shear and requires high energy inputs and do not produce particles within a narrow range distribution. A relatively new technique which has been used and developed by Eiffel Technologies to produce uniform micron and sub micron size particles is a dense gas process in which the gas is used as an antisolvent to precipitate compounds from solution. Pharmaceutical processing with dense gas is relatively new and is an efficient process for producing high purity micronised particles with defined morphological structures and with a narrow size distribution rate

  4. The impact of assay technology as applied to safety assessment in reducing compound attrition in drug discovery.

    Science.gov (United States)

    Thomas, Craig E; Will, Yvonne

    2012-02-01

    Attrition in the drug industry due to safety findings remains high and requires a shift in the current safety testing paradigm. Many companies are now positioning safety assessment at each stage of the drug development process, including discovery, where an early perspective on potential safety issues is sought, often at chemical scaffold level, using a variety of emerging technologies. Given the lengthy development time frames of drugs in the pharmaceutical industry, the authors believe that the impact of new technologies on attrition is best measured as a function of the quality and timeliness of candidate compounds entering development. The authors provide an overview of in silico and in vitro models, as well as more complex approaches such as 'omics,' and where they are best positioned within the drug discovery process. It is important to take away that not all technologies should be applied to all projects. Technologies vary widely in their validation state, throughput and cost. A thoughtful combination of validated and emerging technologies is crucial in identifying the most promising candidates to move to proof-of-concept testing in humans. In spite of the challenges inherent in applying new technologies to drug discovery, the successes and recognition that we cannot continue to rely on safety assessment practices used for decades have led to rather dramatic strategy shifts and fostered partnerships across government agencies and industry. We are optimistic that these efforts will ultimately benefit patients by delivering effective and safe medications in a timely fashion.

  5. Pharmaceutical compounds in Merrimack River water used for public supply, Lowell, Massachusetts, 2008-09

    Science.gov (United States)

    Massey, Andrew J.; Waldron, Marcus C.

    2011-01-01

    This report presents results of a study conducted by the U.S. Geological Survey (USGS), in cooperation with the Massachusetts Department of Environmental Protection, to determine the occurrence of 14 commonly used human-health pharmaceutical compounds and fecal-indicator bacteria in Merrimack River water used as a drinking-water source by 135,000 residents in eastern Massachusetts. The study was designed to complement the USGS National Water-Quality Assessment Program's Source Water-Quality Assessment, which identifies patterns of occurrence of 280 primarily unregulated organic wastewater contaminants in source water used by community water systems and determines whether these patterns also occur in treated drinking water prior to distribution. The study involved periodic collection and analysis of raw Merrimack River water and treated drinking water over the course of 1 year. Water samples were collected periodically without regard to flow regime or antecedent weather conditions at the Lowell Regional Water Utility's Merrimack River intake upstream from Lowell, Mass. The same parcel of water was then sampled as finished water following treatment. Despite the presence of many potential sources of contamination in the drinking-water source area, only 2 of the 14 pharmaceutical analytes were detected at reportable concentrations in the source-water samples, and these occurred in only one set of periodic samples. Acetaminophen, a nonprescription analgesic, and caffeine were detected in the September source-water samples at concentrations of 0.084 and 0.068 micrograms per liter, respectively. Three other compounds-carbamazepine, an antiepileptic; cotinine, a metabolite of nicotine; and diphenhydramine, a nonprescription antihistamine-were detected in source-water samples, but at concentrations too low to be reliably quantified. None of the 14 pharmaceuticals was found in the finished water at a reportable concentration, defined as two times the long-term detection

  6. Bismuth absorption from sup 205 Bi-labelled pharmaceutical bismuth compounds used in the treatment of peptic ulcer disease

    Energy Technology Data Exchange (ETDEWEB)

    Dresow, B.; Fischer, R.; Gabbe, E.E.; Wendel, J.; Heinrich, H.C. (Eppendorf University Hospital, Hamburg (Germany))

    1992-04-01

    The absorption of bismuth from five {sup 205}Bi-labelled pharmaceutically used bismuth compounds was studied in man. From single oral doses of all compounds under investigation only <0.1% bismuth was absorbed and excreted with the urine. A significantly higher absorption was observed from the colloidal bismuth subcitrate and the basic bismuth gallate than from the basic bismuth salicylate, nitrate and aluminate. No retention of bismuth in the whole body was found from the single dose experiment. The biologic fast-term half-lives of absorbed bismuth were calculated to be 0.12 and 1.5 days. 14 refs., 2 figs., 1 tab.

  7. Raw material variability of an active pharmaceutical ingredient and its relevance for processability in secondary continuous pharmaceutical manufacturing.

    Science.gov (United States)

    Stauffer, F; Vanhoorne, V; Pilcer, G; Chavez, P-F; Rome, S; Schubert, M A; Aerts, L; De Beer, T

    2018-06-01

    Active Pharmaceutical Ingredients (API) raw material variability is not always thoroughly considered during pharmaceutical process development, mainly due to low quantities of drug substance available. However, synthesis, crystallization routes and production sites evolve during product development and product life cycle leading to changes in physical material attributes which can potentially affect their processability. Recent literature highlights the need for a global approach to understand the link between material synthesis, material variability, process and product quality. The study described in this article aims at explaining the raw material variability of an API using extensive material characterization on a restricted number of representative batches using multivariate data analysis. It is part of a larger investigation trying to link the API drug substance manufacturing process, the resulting physical API raw material attributes and the drug product continuous manufacturing process. Eight API batches produced using different synthetic routes, crystallization, drying, delumping processes and processing equipment were characterized, extensively. Seventeen properties from seven characterization techniques were retained for further analysis using Principal Component Analysis (PCA). Three principal components (PCs) were sufficient to explain 92.9% of the API raw material variability. The first PC was related to crystal length, agglomerate size and fraction, flowability and electrostatic charging. The second PC was driven by the span of the particle size distribution and the agglomerates strength. The third PC was related to surface energy. Additionally, the PCA allowed to summarize the API batch-to-batch variability in only three PCs which can be used in future drug product development studies to quantitatively evaluate the impact of the API raw material variability upon the drug product process. The approach described in this article could be applied to any

  8. Pharmacogenetics in diverse ethnic populations--implications for drug discovery and development.

    Science.gov (United States)

    McCarthy, Linda C; Davies, Kirstie J; Campbell, David A

    2002-07-01

    It is widely acknowledged that the vast quantities of data now publicly available as a result of the human genome initiative have the potential to revolutionize the pharmaceutical industry. More tangibly to the drug development business, the dawn of the pharmacogenetics era has the potential to impact not only the discovery of new medicines but also the safety and efficacy of pharmaceutical agents. Coincident with these scientific advances is the emergence of new markets for pharmaceutical agents. Japan, which represents the world's second biggest market, is a good example. With the ICH E5 agreement in 1998 and a rapid change in the drug registration process in Japan, there are increasing opportunities to improve access to more medicines in all parts of the world. However, it is increasingly clear that significant genetic variation still exists between populations, with a host of data on interethnic variation in drug metabolizing enzyme and drug transporter activity. Evidence suggesting that this genetic variation may play an important role in defining some of the interethnic variation in drug response to currently marketed compounds is reviewed here, and future possibilities of using such information to better streamline the drug development process are discussed.

  9. Genotoxic and immunotoxic potential effects of selected psychotropic drugs and antibiotics on blue mussel (Mytilus edulis) hemocytes

    International Nuclear Information System (INIS)

    Lacaze, Emilie; Pédelucq, Julie; Fortier, Marlène; Brousseau, Pauline; Auffret, Michel; Budzinski, Hélène; Fournier, Michel

    2015-01-01

    The potential toxicity of pharmaceuticals towards aquatic invertebrates is still poorly understood and sometimes controversial. This study aims to document the in vitro genotoxicity and immunotoxicity of psychotropic drugs and antibiotics on Mytilus edulis. Mussel hemocytes were exposed to fluoxetine, paroxetine, venlafaxine, carbamazepine, sulfamethoxazole, trimethoprim and erythromycin, at concentrations ranging from μg/L to mg/L. Paroxetine at 1.5 μg/L led to DNA damage while the same concentration of venlafaxine caused immunomodulation. Fluoxetine exposure resulted in genotoxicity, immunotoxicity and cytotoxicity. In the case of antibiotics, trimethoprim was genotoxic at 200 μg/L and immunotoxic at 20 mg/L whereas erythromycin elicited same detrimental effects at higher concentrations. DNA metabolism seems to be a highly sensitive target for psychotropic drugs and antibiotics. Furthermore, these compounds affect the immune system of bivalves, with varying intensity. This attests the relevance of these endpoints to assess the toxic mode of action of pharmaceuticals in the aquatic environment. - Highlights: • Psychotropic drugs and antibiotics affect the immune system of Mytilus edulis. • Genotoxic and immunotoxic endpoints were relevant to assess pharmaceuticals toxicity. • DNA metabolism is a highly sensitive target for pharmaceuticals. • Fluoxetine and paroxetine were the most toxic compounds on mussel hemocytes. - Psychotropic drugs and antibiotics have the potential to cause immune toxicity and genotoxicity on Mytilus edulis hemocytes

  10. A strategy to find novel candidate anti-Alzheimer's disease drugs by constructing interaction networks between drug targets and natural compounds in medical plants.

    Science.gov (United States)

    Chen, Bi-Wen; Li, Wen-Xing; Wang, Guang-Hui; Li, Gong-Hua; Liu, Jia-Qian; Zheng, Jun-Juan; Wang, Qian; Li, Hui-Juan; Dai, Shao-Xing; Huang, Jing-Fei

    2018-01-01

    Alzheimer' disease (AD) is an ultimately fatal degenerative brain disorder that has an increasingly large burden on health and social care systems. There are only five drugs for AD on the market, and no new effective medicines have been discovered for many years. Chinese medicinal plants have been used to treat diseases for thousands of years, and screening herbal remedies is a way to develop new drugs. We used molecular docking to screen 30,438 compounds from Traditional Chinese Medicine (TCM) against a comprehensive list of AD target proteins. TCM compounds in the top 0.5% of binding affinity scores for each target protein were selected as our research objects. Structural similarities between existing drugs from DrugBank database and selected TCM compounds as well as the druggability of our candidate compounds were studied. Finally, we searched the CNKI database to obtain studies on anti-AD Chinese plants from 2007 to 2017, and only clinical studies were included. A total of 1,476 compounds (top 0.5%) were selected as drug candidates. Most of these compounds are abundantly found in plants used for treating AD in China, especially the plants from two genera Panax and Morus. We classified the compounds by single target and multiple targets and analyzed the interactions between target proteins and compounds. Analysis of structural similarity revealed that 17 candidate anti-AD compounds were structurally identical to 14 existing approved drugs. Most of them have been reported to have a positive effect in AD. After filtering for compound druggability, we identified 11 anti-AD compounds with favorable properties, seven of which are found in anti-AD Chinese plants. Of 11 anti-AD compounds, four compounds 5,862, 5,863, 5,868, 5,869 have anti-inflammatory activity. The compound 28,814 mainly has immunoregulatory activity. The other six compounds have not yet been reported for any biology activity at present. Natural compounds from TCM provide a broad prospect for the

  11. Recent advances in medicinal chemistry and pharmaceutical technology--strategies for drug delivery to the brain.

    Science.gov (United States)

    Denora, Nunzio; Trapani, Adriana; Laquintana, Valentino; Lopedota, Angela; Trapani, Giuseppe

    2009-01-01

    This paper provides a mini-review of some recent approaches for the treatment of brain pathologies examining both medicinal chemistry and pharmaceutical technology contributions. Medicinal chemistry-based strategies are essentially aimed at the chemical modification of low molecular weight drugs in order to increase their lipophilicity or the design of appropriate prodrugs, although this review will focus primarily on the use of prodrugs and not analog development. Recently, interest has been focused on the design and evaluation of prodrugs that are capable of exploiting one or more of the various endogenous transport systems at the level of the blood brain barrier (BBB). The technological strategies are essentially non-invasive methods of drug delivery to malignancies of the central nervous system (CNS) and are based on the use of nanosystems (colloidal carriers) such as liposomes, polymeric nanoparticles, solid lipid nanoparticles, polymeric micelles and dendrimers. The biodistribution of these nanocarriers can be manipulated by modifying their surface physico-chemical properties or by coating them with surfactants and polyethylene-glycols (PEGs). Liposomes, surfactant coated polymeric nanoparticles, and solid lipid nanoparticles are promising systems for delivery of drugs to tumors of the CNS. This mini-review discusses issues concerning the scope and limitations of both the medicinal chemistry and technological approaches. Based on the current findings, it can be concluded that crossing of the BBB and drug delivery to CNS is extremely complex and requires a multidisciplinary approach such as a close collaboration and common efforts among researchers of several scientific areas, particularly medicinal chemists, biologists and pharmaceutical technologists.

  12. Stability-indicating UPLC method for determination of Valsartan and their degradation products in active pharmaceutical ingredient and pharmaceutical dosage forms.

    Science.gov (United States)

    Krishnaiah, Ch; Reddy, A Raghupathi; Kumar, Ramesh; Mukkanti, K

    2010-11-02

    A simple, precise, accurate stability-indicating gradient reverse phase ultra-performance liquid chromatographic (RP-UPLC) method was developed for the quantitative determination of purity of Valsartan drug substance and drug products in bulk samples and pharmaceutical dosage forms in the presence of its impurities and degradation products. The method was developed using Waters Aquity BEH C18 (100 mm x 2.1 mm, 1.7 microm) column with mobile phase containing a gradient mixture of solvents A and B. The eluted compounds were monitored at 225 nm, the run time was within 9.5 min, which Valsartan and its seven impurities were well separated. Valsartan was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal and photolytic degradation. Valsartan was found to degrade significantly in acid and oxidative stress conditions and stable in base, hydrolytic and photolytic degradation conditions. The degradation products were well resolved from main peak and its impurities, proving the stability-indicating power of the method. The developed method was validated as per international conference on harmonization (ICH) guidelines with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision and robustness. This method was also suitable for the assay determination of Valsartan in pharmaceutical dosage forms.

  13. Electrochemical biosensors in pharmaceutical analysis

    OpenAIRE

    Gil, Eric de Souza; Melo, Giselle Rodrigues de

    2010-01-01

    Given the increasing demand for practical and low-cost analytical techniques, biosensors have attracted attention for use in the quality analysis of drugs, medicines, and other analytes of interest in the pharmaceutical area. Biosensors allow quantification not only of the active component in pharmaceutical formulations, but also the analysis of degradation products and metabolites in biological fluids. Thus, this article presents a brief review of biosensor use in pharmaceutical analysis, fo...

  14. [Written pharmaceutical advertising--still unreliable?].

    Science.gov (United States)

    Gladsø, Kristin Haugen; Garberg, Hedda Rosland; Spigset, Olav; Slørdal, Lars

    2014-09-02

    Marketing by the pharmaceutical industry affects doctors' prescribing habits. All pharmaceutical advertising received by nine doctors in two GP offices over a period of three months was collected. The advertising material was sorted by compound. For each compound, the advert with the highest number of references was selected. The cited references were obtained, and the claims in the adverts were assessed in terms of their consistency with the source data based on the provisions in the Norwegian regulations on pharmaceuticals. The references were also assessed with regard to the incidence of conflicts of interest among authors. The doctors received a total of 270 shipments of advertising for 46 different compounds. Altogether 95% of the 173 references cited in the 46 selected adverts could be obtained. The adverts contained a total of 156 claims. Of these, 56% were assessed as correct when compared to the source data and as having clinical relevance. Altogether 75% of the journal articles reported relevant conflicts of interest for the authors. About half the claims in the adverts were found to be correct and clinically relevant. These results concur with those from a methodologically identical study based on advertising material collected in 2004. The cited literature was of varying quality and often funded by the pharmaceutical companies. The findings indicate that the target group should be sceptical of this type of marketing.

  15. Emerging trends in the stabilization of amorphous drugs.

    Science.gov (United States)

    Laitinen, Riikka; Löbmann, Korbinian; Strachan, Clare J; Grohganz, Holger; Rades, Thomas

    2013-08-30

    The number of active pharmaceutical substances having high therapeutic potential but low water solubility is constantly increasing, making it difficult to formulate these compounds as oral dosage forms. The solubility and dissolution rate, and thus potentially the bioavailability, of these poorly water-soluble drugs can be increased by the formation of stabilized amorphous forms. Currently, formulation as solid polymer dispersions is the preferred method to enhance drug dissolution and to stabilize the amorphous form of a drug. The purpose of this review is to highlight emerging alternative methods to amorphous polymer dispersions for stabilizing the amorphous form of drugs. First, an overview of the properties and stabilization mechanisms of amorphous forms is provided. Subsequently, formulation approaches such as the preparation of co-amorphous small-molecule mixtures and the use of mesoporous silicon and silica-based carriers are presented as potential means to increase the stability of amorphous pharmaceuticals. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Pharmaceutical advertising in emergency departments.

    Science.gov (United States)

    Marco, Catherine A

    2004-04-01

    Promotion of prescription drugs represents a growing source of pharmaceutical marketing expenditures. This study was undertaken to identify the frequency of items containing pharmaceutical advertising in clinical emergency departments (EDs). In this observational study, emergency physician on-site investigators quantified a variety of items containing pharmaceutical advertising present at specified representative times and days, in clinical EDs. Measurements were obtained by 65 on-site investigators, representing 22 states. Most EDs in this study were community EDs (87% community and 14% university or university affiliate), and most were in urban settings (50% urban, 38% suburban, and 13% rural). Investigators measured 42 items per ED (mean = 42; median = 31; interquartile range of 14-55) containing pharmaceutical advertising in the clinical area. The most commonly observed items included pens (mean 15 per ED; median 10), product brochures (mean 5; median 3), stethoscope labels (mean 4; median 2), drug samples (mean 3; median 0), books (mean 3.4), mugs (mean 2.4), and published literature (mean 3.1). EDs with a policy restricting pharmaceutical representatives in the ED had significantly fewer items containing pharmaceutical advertising (median 7.5; 95% CI = 0 to 27) than EDs without such a policy (median 35; 95% CI = 27 to 47, p = 0.005, nonparametric Wilcoxon two-sample test). There were no differences in quantities of pharmaceutical advertising for EDs in community compared with university settings (p = 0.5), rural compared with urban settings (p = 0.3), or annual ED volumes (p = 0.9). Numerous items containing pharmaceutical advertising are frequently observed in EDs. Policies restricting pharmaceutical representatives in the ED are associated with reduced pharmaceutical advertising.

  17. Pharmaceutical characterization of novel tenofovir liposomal formulations for enhanced oral drug delivery: in vitro pharmaceutics and Caco-2 permeability investigations

    Directory of Open Access Journals (Sweden)

    Spinks CB

    2017-02-01

    Full Text Available Crystal B Spinks,1 Ahmed S Zidan,2,3 Mansoor A Khan,4 Muhammad J Habib,1 Patrick J Faustino2 1Department of Pharmaceutical Sciences, School of Pharmacy, Howard University, Washington, DC, 2Division of Product Quality Research, Office of Pharmaceutical Quality, Food and Drug Administration, Silver Spring, MD, USA; 3Faculty of Pharmacy, Zagazig University, Zagazig, Egypt; 4Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, College Station, TX, USA Abstract: Tenofovir, currently marketed as the prodrug tenofovir disoproxil fumarate, is used clinically to treat patients with HIV/AIDS. The oral bioavailability of tenofovir is relatively low, limiting its clinical effectiveness. Encapsulation of tenofovir within modified long-circulating liposomes would deliver this hydrophilic anti-HIV drug to the reticuloendothelial system for better therapeutic efficacy. The objectives of the current study were to prepare and pharmaceutically characterize model liposomal tenofovir formulations in an attempt to improve their bioavailability. The entrapment process was performed using film hydration method, and the formulations were characterized in terms of encapsulation efficiency and Caco-2 permeability. An efficient reverse-phase high-performance liquid chromatography method was developed and validated for tenofovir quantitation in both in vitro liposomal formulations and Caco-2 permeability samples. Separation was achieved isocratically on a Waters Symmetry C8 column using 10 mM Na2PO4/acetonitrile pH 7.4 (95:5 v/v. The flow rate was 1 mL/min with a 12 min elution time. Injection volume was 10 µL with ultraviolet detection at 270 nm. The method was validated according to United States Pharmacopeial Convention category I requirements. The obtained result showed that tenofovir encapsulation within the prepared liposomes was dependent on the employed amount of the positive charge-imparting agent. The obtained results indicated that

  18. Case histories in pharmaceutical risk management.

    Science.gov (United States)

    McCormick, Cynthia G; Henningfield, Jack E; Haddox, J David; Varughese, Sajan; Lindholm, Anders; Rosen, Susan; Wissel, Janne; Waxman, Deborah; Carter, Lawrence P; Seeger, Vickie; Johnson, Rolley E

    2009-12-01

    The development and implementation of programs in the U.S. to minimize risks and assess unintended consequences of new medications has been increasingly required by the Food and Drug Administration (FDA) since the mid 1990s. This paper provides four case histories of risk management and post-marketing surveillance programs utilized recently to address problems associated with possible abuse, dependence and diversion. The pharmaceutical sponsors of each of these drugs were invited to present their programs and followed a similar template for their summaries that are included in this article. The drugs and presenting companies were OxyContin, an analgesic marketed by Purdue Pharma L.P., Daytrana and Vyvanse, ADHD medications marketed by Shire Pharmaceuticals, Xyrem for narcolepsy marketed by Jazz Pharmaceuticals, and Subutex and Suboxone for opioid dependence marketed by Reckitt Benckiser Pharmaceuticals Inc. These case histories and subsequent discussions provide invaluable real-world examples and illustrate both the promise of risk management programs in providing a path to market and/or for keeping on the market drugs with serious potential risks. They also illustrate the limitations of such programs in actually controlling unintended consequences, as well as the challenge of finding the right balance of reducing risks without posing undue barriers to patient access. These experiences are highly relevant as the FDA increasingly requires pharmaceutical sponsors to develop and implement the more formalized and enforceable versions of the risk management term Risk Evaluation and Mitigation Strategies (REMS).

  19. Comparison of pharmaceutical, illicit drug, alcohol, nicotine and caffeine levels in wastewater with sale, seizure and consumption data for 8 European cities

    Directory of Open Access Journals (Sweden)

    Jose Antonio Baz-Lomba

    2016-10-01

    Full Text Available Abstract Background Monitoring the scale of pharmaceuticals, illicit and licit drugs consumption is important to assess the needs of law enforcement and public health, and provides more information about the different trends within different countries. Community drug use patterns are usually described by national surveys, sales and seizure data. Wastewater-based epidemiology (WBE has been shown to be a reliable approach complementing such surveys. Method This study aims to compare and correlate the consumption estimates of pharmaceuticals, illicit drugs, alcohol, nicotine and caffeine from wastewater analysis and other sources of information. Wastewater samples were collected in 2015 from 8 different European cities over a one week period, representing a population of approximately 5 million people. Published pharmaceutical sale, illicit drug seizure and alcohol, tobacco and caffeine use data were used for the comparison. Results High agreement was found between wastewater and other data sources for pharmaceuticals and cocaine, whereas amphetamines, alcohol and caffeine showed a moderate correlation. methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA and nicotine did not correlate with other sources of data. Most of the poor correlations were explained as part of the uncertainties related with the use estimates and were improved with other complementary sources of data. Conclusions This work confirms the promising future of WBE as a complementary approach to obtain a more accurate picture of substance use situation within different communities. Our findings suggest further improvements to reduce the uncertainties associated with both sources of information in order to make the data more comparable.

  20. Physicians' decision process for drug prescription and the impact of pharmaceutical marketing mix instruments.

    Science.gov (United States)

    Campo, Katia; De Staebel, Odette; Gijsbrechts, Els; van Waterschoot, Walter

    2005-01-01

    This paper provides an in-depth, qualitative analysis of the physicians' decision process for drug prescription. Drugs in the considered therapeutic classes are mainly prescribed by specialists, treating patients with obligatory medical insurance, for a prolonged period of time. The research approach is specifically designed to capture the full complexity and sensitive nature of the physician's choice behavior, which appears to be more hybrid and less rational in nature than is often assumed in quantitative, model-based analyses of prescription behavior. Several interesting findings emerge from the analysis: (i) non-compensatory decision rules seem to dominate the decision process, (ii) consideration sets are typically small and change-resistant, (iii) drug cost is not a major issue for most physicians, (iv) detailing remains one of the most powerful pharmaceutical marketing instruments and is highly appreciated as a valuable and quick source of information, and (v) certain types of non-medical marketing incentives (such as free conference participation) may in some situations also influence drug choices.

  1. A Simple Model of Pharmaceutical Price Dynamics

    OpenAIRE

    Bhattacharya, Jayanta; Vogt, William B

    2003-01-01

    Branded pharmaceutical firms use price and promotional strategy to manage public knowledge about their drugs. We propose a dynamic theory of pharmaceutical pricing and conduct an exploratory empirical analysis inspired by the theory. Our theory predicts a pattern of increasing prices and decreasing promotional activities over a drug's life cycle. Prices are kept low and advertising levels high early in the life cycle in order to build public knowledge about the drug. As knowledge grows, price...

  2. Pharmaceutical cocrystals: an overview.

    Science.gov (United States)

    Qiao, Ning; Li, Mingzhong; Schlindwein, Walkiria; Malek, Nazneen; Davies, Angela; Trappitt, Gary

    2011-10-31

    Pharmaceutical cocrystals are emerging as a new class of solid drugs with improved physicochemical properties, which has attracted increased interests from both industrial and academic researchers. In this paper a brief and systematic overview of pharmaceutical cocrystals is provided, with particular focus on cocrystal design strategies, formation methods, physicochemical property studies, characterisation techniques, and recent theoretical developments in cocrystal screening and mechanisms of cocrystal formations. Examples of pharmaceutical cocrystals are also summarised in this paper. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Occurrence of pharmaceutically active and non-steroidal estrogenic compounds in three different wastewater recycling schemes in Australia

    OpenAIRE

    Al-Rifai, J.; Gabelish, C. L.; Schaefer, Andrea

    2007-01-01

    The discovery that natural and synthetic chemicals, in the form of excreted hormones and pharmaceuticals, as well as a vast array of compounds with domestic and industrial applications, can enter the environment via wastewater treatment plants and cause a wide variety of environmental and health problems even at very low concentrations, suggests the need for improvement of water recycling. Three Australian wastewater recycling schemes, two of which employ reverse osmosis (RO) technology, ...

  4. Review on potential phytocompounds in drug development for Parkinson disease: A pharmacoinformatic approach

    Directory of Open Access Journals (Sweden)

    S. Vijayakumar

    Full Text Available Parkinson's disease (PD is caused by human physiological function and is ranked as the second most common neurodegenerative disorder. One of the prominent therapies currently available for PD is the use of dopamine agonists which mimic the natural action of dopamine in the brain and stimulate dopamine receptors directly. Currently, available pharmaceutical drugs provide only temporary relief of the disease. Phytocompounds have been identified as promising target of research in the quest for new pharmaceutical compounds as they can produce secondary metabolites with novel chemical structure. In this review the drug development of Parkinson disease has been analyzed using computational tools. Keywords: Parkinson disease, Phytocompounds, Computational methods, Drug development and design

  5. Study of pharmaceuticals in surface and wastewater from Cuernavaca, Morelos, Mexico: Occurrence and environmental risk assessment.

    Science.gov (United States)

    Rivera-Jaimes, José Abraham; Postigo, Cristina; Melgoza-Alemán, Rosa María; Aceña, Jaume; Barceló, Damia; López de Alda, Miren

    2018-02-01

    The present work describes the first known study to date on the occurrence of pharmaceuticals in surface water and wastewater of Cuernavaca, the capital of the state of Morelos (México). Selected pharmaceuticals (a total of 35) were extracted from the collected water samples with a generic solid phase extraction (SPE) protocol and determined in the sample extracts by means of high-performance liquid chromatography coupled to electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS). A screening level risk assessment combining the measured environmental concentrations (MECs) with dose-response data based on predicted no-effect concentrations (PNECs) was also applied to estimate Hazard Quotients (HQs) for the pharmaceuticals detected in the investigated area. A total of twelve pharmaceuticals were found in the water samples analyzed, with detection frequencies above 78% and in most cases of 100%. Overall, the most abundant pharmaceuticals in surface water were the analgesic and anti-inflammatory drugs naproxen (732-4880ng/L), acetaminophen (354-4460ng/L), and diclofenac (258-1398ng/L), and the lipid regulator bezafibrate (286-2100ng/L). On the contrary, other compounds like the β-blocker atenolol and the psychiatric drug carbamazepine were found at only a few ng or tens of ng per liter in the Apatlaco River. Despite the fact that some of the most abundant compounds showed good removal (>97%) during wastewater treatment, concentrations downstream the WWTP were only slightly lower than upstream. This indicates the existence of additional inputs of untreated wastewater into the river. Based on the obtained HQ-values, the concentrations of ibuprofen, sulfamethoxazole, diclofenac and naproxen present in the river could pose a high toxicity risk for the aquatic ecosystem. These findings highlight these pharmaceuticals as relevant organic contaminants in the area of study and the need to further monitor them in order to adopt appropriate measures to safeguard the

  6. Pharmaceutical counseling: Between evidence-based medicine and profits.

    Science.gov (United States)

    Egorova, S N; Akhmetova, T

    2015-01-01

    The number of pharmacies, which produce drug formulations locally, has recently considerably reduced in Russia. Pharmacies mainly operate as retailers of industrially manufactured drugs.Pharmaceutical consultation of customers at pharmacies aimed at responsible self-medication is the most popular and accessible feature of pharmaceutical care. In Russia there is a significant list of medicines approved for sale in pharmacies on a non-prescription basis that is specified in the product label. In this regard, the role of pharmacists in public health in Russia increases. Pharmacist, working directly with population, is an important figure for the rational use of medicines. This type of work requires high level of professional training and appropriate ethics. To explore the current status of pharmaceutical counseling in Russia. Situation analysis, surveys of pharmacists. Our experience in the system of postgraduate professional education, the results of the survey of pharmacists, and the long-term dialogue with pharmacists allowed us to identify several unresolved issues in the work of a pharmacist selling non-prescription drugs.Lack of differentiation in the functions of a pharmacist with a higher education and pharmaceutical technologist: In production/industrial pharmacy technicians are engaged in manufacturing of pharmaceutical formulations. However, due to the loss of production functions technologists had to move away from production laboratories of apothecaries to the sales area. Currently, the apothecary's assignment to receive prescriptions and dispense medications can be fulfilled by either a pharmacist or a pharmaceutical technician. It significantly discerns the pharmacy from the medical organization with clearly delineated functions of doctors and nurses. Russian regulations should consider the level of education required for high-quality pharmaceutical counseling.Contradiction between the pharmacist's special functions and trade procedure with the lack of

  7. A Very Simple and Sensitive Spectrofluorimetric Method Based on the Oxidation with Cerium (IV for the Determination of Four Different Drugs in Their Pharmaceutical Formulations

    Directory of Open Access Journals (Sweden)

    Ahad Bavili-Tabrizi, Farshad Bahrami, Hossein Badrouj

    2017-03-01

    Full Text Available Background: Methyldopa is a catecholamine widely used as an antihypertensive agent. Pioglitazone is an oral anti-hyperglycemic agent. It is used for the treatment of diabetes mellitus type 2. A survey of the literature reveals that only one spectrofluorimetric method has been reported for the determination of pioglitazone in pharmaceutical preparations. Atenolol and metoprolol are prescription drugs of the β-blocker class with hypotensive action to treat angina, MI, alcohol syndrome, hypertension, and arrhythmias. A survey of the literature reveals that several spectrofluorimetric methods have been reported for the determination of atenolol and metoprolol in pharmaceutical preparations. In continuing of our studies on the developing of simple and fast spectrofluorimetric methods for determination of drugs and active ingredients, in this work we have developed a spectrofluorimetric method based on the oxidation with cerium (IV for the determination of studied drugs in their pharmaceutical formulations. Methods: A simple, rapid and sensitive spectrofluorimetric method was developed for the determination of studied drugs in pharmaceutical formulations. Proposed method is based on the oxidation of these drugs with Ce (IV to produce Ce (III, and its fluorescence was monitored at 356 ± 3 nm after excitation at 254 ± 3 nm. Results: The variables affecting oxidation of each drug were studied and optimized. Under the experimental conditions used, the calibration graphs were linear over the range of 25-450, 50-550, 15-800 and 15-800 ng/mL in the case of atenolol, metoprolol, pioglitazone and methyldopa, respectively. The limit of detection was found to be 8.27, 16.5, 1.52 and 5.08 ng/mL in the case of atenolol, metoprolol, pioglitazone and methyldopa, respectively. Intra- and inter-day assay precisions, expressed as the relative standard deviation (RSD, were lower than 3% in all cases. Conclusion: The proposed method was applied to the determination of

  8. Pharmaceutical companies vs. the State: who is responsible for post-trial provision of drugs in Brazil?

    Science.gov (United States)

    Wang, Daniel Wei L; Ferraz, Octavio Luiz Motta

    2012-01-01

    This paper discusses the post-trial access to drugs for patients who participated in clinical trials in Brazil. The ethical guidance for clinical trials in Brazil is arguably one of the clearest in the world in attributing to research sponsors the responsibility for providing post-trial drugs to patients who participated in their experiments. The Federal Constitution recognizes health as a fundamental right to be fulfilled by the State. Based on the Brazilian constitution and on the National Health Council resolutions, courts have been accepting patients' claims and ordering the State and the pharmaceutical companies to provide these patients with the tested treatment in the quantity and duration they need it. This generous interpretation of the duties of the pharmaceutical companies and the State makes the Brazilian model for post-trial access unique when compared to the experience of other countries and thus should be followed with attention by future research in order to assess its consequences for patients, research sponsors, and the public health system. © 2012 American Society of Law, Medicine & Ethics, Inc.

  9. Effect of long-term physical aging on the kinetic parameters in a common pharmaceutical drug: Flutab

    International Nuclear Information System (INIS)

    Abu-Sehly, A.A.; Elabbar, A.A.

    2011-01-01

    Differential scanning calorimetry (DSC) measurements were performed to investigate the effects of long-term physical aging on kinetic parameters of the pharmaceutical drug (Flutab). Kinetics parameters such as activation energy (E) and fragility parameter (m) of the glass transition for aged and rejuvenated glasses were determined using different kinetic models. Evidence of variation of E with temperature is presented. It is shown in this work that natural storage of the drug introduced significant physical aging as indicated by changes in the glass transition temperature, activation energy and fragility parameter.

  10. Identifying problematic drugs based on the characteristics of their targets.

    Science.gov (United States)

    Lopes, Tiago J S; Shoemaker, Jason E; Matsuoka, Yukiko; Kawaoka, Yoshihiro; Kitano, Hiroaki

    2015-01-01

    Identifying promising compounds during the early stages of drug development is a major challenge for both academia and the pharmaceutical industry. The difficulties are even more pronounced when we consider multi-target pharmacology, where the compounds often target more than one protein, or multiple compounds are used together. Here, we address this problem by using machine learning and network analysis to process sequence and interaction data from human proteins to identify promising compounds. We used this strategy to identify properties that make certain proteins more likely to cause harmful effects when targeted; such proteins usually have domains commonly found throughout the human proteome. Additionally, since currently marketed drugs hit multiple targets simultaneously, we combined the information from individual proteins to devise a score that quantifies the likelihood of a compound being harmful to humans. This approach enabled us to distinguish between approved and problematic drugs with an accuracy of 60-70%. Moreover, our approach can be applied as soon as candidate drugs are available, as demonstrated with predictions for more than 5000 experimental drugs. These resources are available at http://sourceforge.net/projects/psin/.

  11. Identifying problematic drugs based on the characteristics of their targets

    Directory of Open Access Journals (Sweden)

    Tiago Jose eDa Silva Lopes

    2015-09-01

    Full Text Available Identifying promising compounds during the early stages of drug development is a major challenge for both academia and the pharmaceutical industry. The difficulties are even more pronounced when we consider multi-target pharmacology, where the compounds often target more than one protein, or multiple compounds are used together. Here, we address this problem by using machine learning and network analysis to process sequence and interaction data from human proteins to identify promising compounds. We used this strategy to identify properties that make certain proteins more likely to cause harmful effects when targeted; such proteins usually have domains commonly found throughout the human proteome. Additionally, since currently marketed drugs hit multiple targets simultaneously, we combined the information from individual proteins to devise a score that quantifies the likelihood of a compound being harmful to humans. This approach enabled us to distinguish between approved and problematic drugs with an accuracy of 60%¬–70%. Moreover, our approach can be applied as soon as candidate drugs are available, as demonstrated with predictions for more than 5000 experimental drugs. These resources are available at http://sourceforge.net/projects/psin/.

  12. Interpretation of animal data in the calculation of doses from new radiolabelled compounds

    International Nuclear Information System (INIS)

    Ellender, M.; Naylor, G.P.L.

    1992-01-01

    The Radionuclide Biokinetics Group of the Biomedical Effects Department at NRPB provides a dose calculation service for pharmaceutical companies and associated laboratories which plan to administer radiolabelled drugs to human volunteers as part of their research and development programmes for new compounds. Animal data provided by these companies are used to estimate the likely doses to humans from administration of the compound. The dose estimate then accompanies the pharmaceutical company's application for approval from the UK Administration of Radioactive Substances Advisory Committee (ARSAC). The method of calculation, the interpretation of the animal data and the range of results obtained are discussed. In addition, the effect of the use of the new ICRP tissue weighting factors in the calculations is considered. (Author)

  13. Applying Quality by Design Concepts to Pharmacy Compounding.

    Science.gov (United States)

    Timko, Robert J

    2015-01-01

    Compounding of medications is an important part of the practice of the pharmacy profession. Because compounded medications do not have U.S. Food and Drug Administration approval, a pharmacist has the responsibility to ensure that compounded medications are of suitable quality, safety, and efficacy. The Federal Government and numerous states have updated their laws and regulations regarding pharmacy compounding as a result of recent quality issues. Compounding pharmacists are expected to follow good preparation prodecures in their compounding practices in much the same way pharmaceutical manufacturers are required to follow Current Good Manufacturing Procedures as detailed in the United States Code of Federal Regulations. Application of Quality by Design concepts to the preparation process for a compounded medication can help in understanding the potential pitfalls and the means to mitigate their impact. The goal is to build quality into the compounding process to ensure that the resultant compounded prescription meets the human or animal patients' requirements.

  14. Nano spray drying for encapsulation of pharmaceuticals.

    Science.gov (United States)

    Arpagaus, Cordin; Collenberg, Andreas; Rütti, David; Assadpour, Elham; Jafari, Seid Mahdi

    2018-05-17

    Many pharmaceuticals such as pills, capsules, or tablets are prepared in a dried and powdered form. In this field, spray drying plays a critical role to convert liquid pharmaceutical formulations into powders. In addition, in many cases it is necessary to encapsulate bioactive drugs into wall materials to protect them against harsh process and environmental conditions, as well as to deliver the drug to the right place and at the correct time within the body. Thus, spray drying is a common process used for encapsulation of pharmaceuticals. In view of the rapid progress of nanoencapsulation techniques in pharmaceutics, nano spray drying is used to improve drug formulation and delivery. The nano spray dryer developed in the recent years provides ultrafine powders at nanoscale and high product yields. In this paper, after explaining the concept of nano spray drying and understanding the key elements of the equipment, the influence of the process parameters on the final powders properties, like particle size, morphology, encapsulation efficiency, drug loading and release, will be discussed. Then, numerous application examples are reviewed for nano spray drying and encapsulation of various drugs in the early stages of product development along with a brief overview of the obtained results and characterization techniques. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Occurrence of pharmaceutical contaminants and screening of treatment alternatives for southeastern Louisiana.

    Science.gov (United States)

    Boyd, G R; Grimm, D A

    2001-12-01

    Recent studies conducted in Germany, Switzerland, Denmark, Brazil, Canada, the United States, and elsewhere indicate that low-level concentrations of pharmaceuticals and personal-care products (PPCPs) and their metabolites may be widespread contaminants in our aquatic environment. The persistence of pharmaceutical contaminants has been attributed to (1) human consumption of drugs and subsequent discharges from sewage treatment plants, and (2) veterinary use of drugs and nonpoint discharges from agricultural runoff. Contamination of water resources by these compounds, particularly endocrine disrupting chemicals (EDCs), is emerging as an international environmental concern. The long-term effects of continuous, low-level exposure to PPCPs is not well understood. Preliminary data for raw water samples collected from the Mississippi River and Lake Pontchartrain, Louisiana, are summarized. Three PPCP compounds (clofibric acid, naproxen, and estrone) were analyzed using solid-phase extraction, derivatization, and GC/MS. Batch experiments also were conducted to determine equilibrium capacity of activated carbon for clofibric acid. Preliminary results indicate the occurrence of the selected PPCP contaminants in raw water samples at or near method-detection limits. For batch equilibrium experiments, preliminary results indicate that activated carbon potentially can be used to remove clofibric acid from water. More research is needed to develop rapid and reliable methods for PPCP analysis and to determine the effectiveness of treatment processes for removal of PPCP contaminants in water.

  16. Inkjet Printing of Drug-Loaded Mesoporous Silica Nanoparticles—A Platform for Drug Development

    Directory of Open Access Journals (Sweden)

    Henrika Wickström

    2017-11-01

    Full Text Available Mesoporous silica nanoparticles (MSNs have shown great potential in improving drug delivery of poorly water soluble (BCS class II, IV and poorly permeable (BCS class III, IV drugs, as well as facilitating successful delivery of unstable compounds. The nanoparticle technology would allow improved treatment by reducing adverse reactions of currently approved drugs and possibly reintroducing previously discarded compounds from the drug development pipeline. This study aims to highlight important aspects in mesoporous silica nanoparticle (MSN ink formulation development for digital inkjet printing technology and to advice on choosing a method (2D/3D for nanoparticle print deposit characterization. The results show that both unfunctionalized and polyethyeleneimine (PEI surface functionalized MSNs, as well as drug-free and drug-loaded MSN–PEI suspensions, can be successfully inkjet-printed. Furthermore, the model BCS class IV drug remained incorporated in the MSNs and the suspension remained physically stable during the processing time and steps. This proof-of-concept study suggests that inkjet printing technology would be a flexible deposition method of pharmaceutical MSN suspensions to generate patterns according to predefined designs. The concept could be utilized as a versatile drug screening platform in the future due to the possibility of accurately depositing controlled volumes of MSN suspensions on various materials.

  17. Inkjet Printing of Drug-Loaded Mesoporous Silica Nanoparticles-A Platform for Drug Development.

    Science.gov (United States)

    Wickström, Henrika; Hilgert, Ellen; Nyman, Johan O; Desai, Diti; Şen Karaman, Didem; de Beer, Thomas; Sandler, Niklas; Rosenholm, Jessica M

    2017-11-21

    Mesoporous silica nanoparticles (MSNs) have shown great potential in improving drug delivery of poorly water soluble (BCS class II, IV) and poorly permeable (BCS class III, IV) drugs, as well as facilitating successful delivery of unstable compounds. The nanoparticle technology would allow improved treatment by reducing adverse reactions of currently approved drugs and possibly reintroducing previously discarded compounds from the drug development pipeline. This study aims to highlight important aspects in mesoporous silica nanoparticle (MSN) ink formulation development for digital inkjet printing technology and to advice on choosing a method (2D/3D) for nanoparticle print deposit characterization. The results show that both unfunctionalized and polyethyeleneimine (PEI) surface functionalized MSNs, as well as drug-free and drug-loaded MSN-PEI suspensions, can be successfully inkjet-printed. Furthermore, the model BCS class IV drug remained incorporated in the MSNs and the suspension remained physically stable during the processing time and steps. This proof-of-concept study suggests that inkjet printing technology would be a flexible deposition method of pharmaceutical MSN suspensions to generate patterns according to predefined designs. The concept could be utilized as a versatile drug screening platform in the future due to the possibility of accurately depositing controlled volumes of MSN suspensions on various materials.

  18. Alginate: Current Use and Future Perspectives in Pharmaceutical and Biomedical Applications

    Directory of Open Access Journals (Sweden)

    Marta Szekalska

    2016-01-01

    Full Text Available Over the last decades, alginates, natural multifunctional polymers, have increasingly drawn attention as attractive compounds in the biomedical and pharmaceutical fields due to their unique physicochemical properties and versatile biological activities. The focus of the paper is to describe biological and pharmacological activity of alginates and to discuss the present use and future possibilities of alginates as a tool in drug formulation. The recent technological advancements with using alginates, issues related to alginates suitability as matrix for three-dimensional tissue cultures, adjuvants of antibiotics, and antiviral agents in cell transplantation in diabetes or neurodegenerative diseases treatment, and an update on the antimicrobial and antiviral therapy of the alginate based drugs are also highlighted.

  19. Testing antidepressant compounds in a neuropsychological model of drug action

    NARCIS (Netherlands)

    Cerit, Hilal

    2015-01-01

    Although much research effort has been put into the development of new antidepressant drugs, the process of developing a drug often fails at the stage of large randomized controlled trials (RCTs) in which an initially promising compound appears to lack efficacy after all. Several experimental

  20. Emerging technologies and challenges for better and safer drugs.

    Science.gov (United States)

    Theodosiou, Maria; Amir-Aslani, Arsia; Mégarbane, Bruno

    2014-04-01

    Regardless of stringent safety regulations and increased compound selectivity by pharmaceutical companies, prediction of toxicity in humans is still far from perfect and adverse drug reactions are still detected after drug marketing. High costs of failures due to toxicity has led pharmaceutical companies to search for screening methods that would allow detection of toxicity issues at an early stage and improve their preclinical and clinical toxicology. Thanks to the last decade's biotechnology revolution, new technologies like toxicogenomics have demonstrated the capacity to improve toxicity assessment. However, our understanding of toxicological mechanisms is still incomplete and a wide range of approaches must be used to gain insight into toxicity issues. Consequently, an array of in silico, in vitro and in vivo methods is utilized to predict toxicity and its causative mechanisms, improving drug development processes and minimizing costs of failure.

  1. Drug Repurposing Screening Identifies Novel Compounds That Effectively Inhibit Toxoplasma gondii Growth

    Science.gov (United States)

    Dittmar, Ashley J.; Drozda, Allison A.

    2016-01-01

    ABSTRACT The urgent need to develop new antimicrobial therapies has spawned the development of repurposing screens in which well-studied drugs and other types of compounds are tested for potential off-label uses. As a proof-of-principle screen to identify compounds effective against Toxoplasma gondii, we screened a collection of 1,120 compounds for the ability to significantly reduce Toxoplasma replication. A total of 94 compounds blocked parasite replication with 50% inhibitory concentrations of parasite invasion and replication but did so independently of inhibition of dopamine or other neurotransmitter receptor signaling. Tamoxifen, which is an established inhibitor of the estrogen receptor, also reduced parasite invasion and replication. Even though Toxoplasma can activate the estrogen receptor, tamoxifen inhibits parasite growth independently of this transcription factor. Tamoxifen is also a potent inducer of autophagy, and we find that the drug stimulates recruitment of the autophagy marker light chain 3-green fluorescent protein onto the membrane of the vacuolar compartment in which the parasite resides and replicates. In contrast to other antiparasitic drugs, including pimozide, tamoxifen treatment of infected cells leads to a time-dependent elimination of intracellular parasites. Taken together, these data suggest that tamoxifen restricts Toxoplasma growth by inducing xenophagy or autophagic destruction of this obligate intracellular parasite. IMPORTANCE There is an urgent need to develop new therapies to treat microbial infections, and the repurposing of well-characterized compounds is emerging as one approach to achieving this goal. Using the protozoan parasite Toxoplasma gondii, we screened a library of 1,120 compounds and identified several compounds with significant antiparasitic activities. Among these were pimozide and tamoxifen, which are well-characterized drugs prescribed to treat patients with psychiatric disorders and breast cancer

  2. Simultaneous screening and quantification of 52 common pharmaceuticals and drugs of abuse in hair using UPLC-TOF-MS

    DEFF Research Database (Denmark)

    Nielsen, Marie Katrine Klose; Johansen, Sys Stybe; Dalsgaard, Petur Weihe

    2010-01-01

    An UPLC-TOF-MS method for simultaneous screening and quantification of 52 drugs in hair was developed and validated. The selected drugs represent the most common classes of pharmaceuticals and drugs of abuse such as amphetamines, analgesics, antidepressants, antipsychotics, benzodiazepines, cocaine.......05 ng/mg for 87% of the analytes. A good linear behaviour was achieved for most of the analytes in the range from LOQ to 10 or 25 ng/mg except for the amphetamines. The method showed an acceptable precision and trueness, since the obtained CV and BIAS values were...

  3. Parallel Imports, Drag Price Control and Pharmaceutical Innovation

    OpenAIRE

    Ken Tabata; Testuya Shinkai; Satoru Tanaka; Makoto Okamura

    2005-01-01

    This paper examines how parallel importation influences pharmaceutical innovation and the welfare of the economy, when crossnational drug price differentials occur not only because of demand elasticity based factors, but also governmental drug price control based factors. By explicitly considering the governmental drug price control baaed factors, this paper shows that parallel importation may enhance pharmaceutical innovation, when the bargaining power of a foreign government is strong and t...

  4. Polymers in life sciences: Pharmaceutical and biomedical applications

    Science.gov (United States)

    Barba, Anna Angela; Dalmoro, Annalisa; d'Amore, Matteo; Lamberti, Gaetano; Cascone, Sara; Titomanlio, Giuseppe

    2015-12-01

    This paper deals with the work done by prof. Titomanlio and his group in the fields of pharmaceutical and biomedical applications of polymers. In particular, the main topics covered are: i) controlled drug release from pharmaceuticals based on hydrogel for oral delivery of drugs; ii) production and characterization of micro and nanoparticles based on stimuli-responsive polymers; iii) use of polymers for coronary stent gel-paving; iv) design and realization of novel methods (in-vitro and in-silico) to test polymer-based pharmaceuticals.

  5. Compound immobilization and drug-affinity chromatography.

    Science.gov (United States)

    Rix, Uwe; Gridling, Manuela; Superti-Furga, Giulio

    2012-01-01

    Bioactive small molecules act through modulating a yet unpredictable number of targets. It is therefore of critical importance to define the cellular target proteins of a compound as an entry point to understanding its mechanism of action. Often, this can be achieved in a direct fashion by chemical proteomics. As with any affinity chromatography, immobilization of the bait to a solid support is one of the earliest and most crucial steps in the process. Interfering with structural features that are important for identification of a target protein will be detrimental to binding affinity. Also, many molecules are sensitive to heat or to certain chemicals, such as acid or base, and might be destroyed during the process of immobilization, which therefore needs to be not only efficient, but also mild. The subsequent affinity chromatography step needs to preserve molecular and conformational integrity of both bait compound and proteins in order to result in the desired specific enrichment while ensuring a high level of compatibility with downstream analysis by mass spectrometry. Thus, the right choice of detergent, buffer, and protease inhibitors is also essential. This chapter describes a widely applicable procedure for the immobilization of small molecule drugs and for drug-affinity chromatography with subsequent protein identification by mass spectrometry.

  6. [Bioequivalence studies of pharmaceutical preparations].

    Science.gov (United States)

    Vetchý, D; Frýbortová, K; Rabisková, M; Danecková, H

    2007-01-01

    Bioequivalence studies are very important for the development of a pharmaceutical preparation in the pharmaceutical industry. Their rationale is the monitoring of pharmacokinetic and pharmacodynamic parameters after the administration of tested drugs. The target of such study is to evaluate the therapeutic compatibility of tested drugs (pharmaceutical equivalents or pharmaceutical alternatives). The importance of bioequivalence studies is increasing also due to the large growth of the production and consumption of generic products. Generic products represent approximately 50 % of the whole consumption in many European countries and USA. The search output of bioequivalence study is together with the pharmaceutical quality data of medical product one of the main part of the registration file submitted to a national regulatory authorities. The registration of generic products does not demand complicated and expensive clinical study contrary to original product. The comparison of the original and the generic product via bioequivalence study is suggested as sufficient. The aim of this article is to provide to a medical public a summary about the types of bioequivalence studies, their range, rules of their practise and let them gain their own attitude to this question.

  7. Real-time potentiometric sensor; an innovative tool for monitoring hydrolysis of chemo/bio-degradable drugs in pharmaceutical sciences.

    Science.gov (United States)

    Ma'mun, Ahmed; Abd El-Rahman, Mohamed K; Abd El-Kawy, Mohamed

    2018-05-30

    In recent years, the whole field of ion-selective electrodes(ISEs) in pharmaceutical sciences has expanded far beyond its original roots. The diverse range of opportunities offered by ISEs was broadly used in a number of pharmaceutical applications, with topics presented ranging from bioanalysis of drugs and metabolites, to protein binding studies, green analytical chemistry, impurity profiling, and drug dissolution in biorelevant media. Inspired from these advances and with the aim of extending the functional capabilities of ISEs, the primary focus of the present paper is the utilization of ISE as a tool in personalized medicine. Given the opportunity to explore biological events in real-time (such as drug metabolism) could be central to personalized medicine. (ATR) is a chemo-degradable and bio-degradable pharmaceutically active drug. Laudanosine (LDS) is the major degradation product and metabolite of ATR and is potentially toxic and reported to possess epileptogenic activity which increases the risk of convulsive effects. In this work, ATR have been subjected to both chemical and biological hydrolysis, and the course of the reactions is monitored by means of a ISE. In this study, we have designed an efficient real-time tracking strategy which substantially resolve the challenges of the ATR chemical and biological degradation kinetics. By utilizing a potentiometric sensor, tracking of ATR chemical and biological degradation kinetics can be performed in a very short time with excellent accuracy. The LOD was calculated to be 0.23 μmol L -1 , the potential drift was investigated over a period of 60 min and the value was 0.25 mV h -1 . Real serum samples for measurement the rate of in vitro metabolism of ATR was performed. Furthermore, a full description of the fabricated screen-printed sensor was presented. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Rapid screening of pharmaceutical drugs using thermal desorption – SALDI mass spectrometry

    International Nuclear Information System (INIS)

    Grechnikov, A A; Kubasov, A E; Borodkov, A S; Georgieva, V B; Nikiforov, S M; Simanovsky, Ya O; Alimpiev, S S

    2012-01-01

    A novel approach to the rapid screening of pharmaceutical drugs by surface assisted laser desorption-ionization (SALDI) mass spectrometry with the rotating ball interface coupled with temperature programmed thermal desorption has been developed. Analytes were thermally desorbed and deposited onto the surface of amorphous silicon substrate attached to the rotating ball. The ball was rotated and the deposited analytes were analyzed using SALDI. The effectiveness of coupling SALDI mass spectrometry with thermal desorption was evaluated by the direct and rapid analysis of tablets containing lidocaine, diphenhydramine and propranolol without any sample pretreatment. The overall duration of the screening procedure was 30÷40 sec. Real urine samples were studied for drug analysis. It is shown that with simple preparation steps, urine samples can be quantitatively analyzed using the proposed technique with the detection limits in the range of 0.2÷0.5 ng/ml.

  9. [E-commerce of pharmaceuticals].

    Science.gov (United States)

    Shani, Segev

    2003-05-01

    The emergence of the Internet as a new communications and information technology caused major social and cultural changes. The dramatic increase in accessibility and availability of information empowered the consumer by closing the information gap between the consumer and different suppliers. The objective of this article is to review many new internet-supported applications related to the pharmaceutical market. E-commerce is divided into two major components: Business to Consumer (B to C), and Business to Business (B to B). The main applications in B to C are dissemination of medical and drug information, and the sale of drugs through the Internet. Medical information on the Internet is vast and very helpful for patients, however, its reliability is not guaranteed. Online pharmacies increase the accessibility and availability of drugs. Nevertheless, several obstacles such as security of the data provided (both financial and clinical) prevent the widespread use of online pharmacies. Another risk is the health authorities' inability to regulate Internet sites effectively. Therefore, unregulated sale of prescription drugs, fake or substandard, often occurs on the Internet. B to B relates to physicians, clinics, hospitals, HMO's and pharmaceutical companies. There is a vast number of applications ranging from clinical research, marketing and sales promotion, to drug distribution and logistics. In conclusion, the Internet is dynamic and has contributed to the development of numerous new applications in the field of pharmaceuticals. Regulatory authorities should be active in developing new policies that will deal with those new Internet-based applications.

  10. Occurrence and removal of pharmaceutically active compounds in sewage treatment plants with different technologies

    Science.gov (United States)

    Ying, Guang-Guo; Kookana, Rai S.; Kolpin, Dana W.

    2009-01-01

    Occurrence of eight selected pharmaceutically active compounds (PhACs; caffeine, carbamazepine, triclosan, gemfibrozil, diclofenac, ibuprofen, ketoprofen and naproxen) were investigated in effluents from fifteen sewage treatment plants (STPs) across South Australia. In addition, a detailed investigation into the removal of these compounds was also carried out in four STPs with different technologies (Plant A: conventional activated sludge; plant B: two oxidation ditches; plant C: three bioreactors; and plant D: ten lagoons in series). The concentrations of these compounds in the effluents from the fifteen STPs showed substantial variations among the STPs, with their median concentrations ranging from 26 ng/L for caffeine to 710 ng/L for carbamazepine. Risk assessment based on the "worst case scenario" of the monitoring data from the present study suggested potential toxic risks to aquatic organisms posed by carbamazepine, triclosan and diclofenac associated with such effluent discharge. With the exception of carbamazepine and gemfibrozil, significant concentration decreases between influent and effluent were observed in the four STPs studied in more detail. Biodegradation was found to be the main mechanism for removing concentrations from the liquid waste stream for the PhACs within the four STPs, while adsorption onto sludge appeared to be a minor process for all target PhACs except for triclosan. Some compounds (e.g. gemfibrozil) exhibited variable removal efficiencies within the four STPs. Plant D (10 lagoons in series) was least efficient in the removal of the target PhACs; significant biodegradation of these compounds only occurred from the sixth or seventh lagoon.

  11. Pharmaceuticals and Their Impact on the Environment

    Directory of Open Access Journals (Sweden)

    Tomić, S

    2010-07-01

    Full Text Available Pharmaceuticals are a class of emerging environmental contaminants that are extensively and increasingly being used in human and veterinary medicine and are released continuously into the environment. A variety of pharmaceuticals have been detected in many environmental samples worldwide. The establishment of chemical analysis methods able to determine more polar compounds allow the determination and identification of trace quantities of drugs and their metabolites. Most regulatory agencies require that environmental risk assessment is performed as an integral part of their approval procedures for the marketing for medicinal products. Marketing approval for medicinal products in the European Union is regulated by the Directive 2001/83/EC. Based on the Directive, the European Medicines Agency (EMA has published guidelines describing the procedure for the environmental risk assessment for medicinal products marketed in the EU. The requirements for the Environmental risk assessment (ERA in Croatia are regulated by the Medicinal Products Act (Official Gazette No. 71/07 and the Ordinance on the Procedure and Method for Granting Marketing Authorisations for Medicinal Products (Official Gazette No. 113/08.

  12. Supramolecular Pharmaceutical Sciences: A Novel Concept Combining Pharmaceutical Sciences and Supramolecular Chemistry with a Focus on Cyclodextrin-Based Supermolecules.

    Science.gov (United States)

    Higashi, Taishi; Iohara, Daisuke; Motoyama, Keiichi; Arima, Hidetoshi

    2018-01-01

    Supramolecular chemistry is an extremely useful and important domain for understanding pharmaceutical sciences because various physiological reactions and drug activities are based on supramolecular chemistry. However, it is not a major domain in the pharmaceutical field. In this review, we propose a new concept in pharmaceutical sciences termed "supramolecular pharmaceutical sciences," which combines pharmaceutical sciences and supramolecular chemistry. This concept could be useful for developing new ideas, methods, hypotheses, strategies, materials, and mechanisms in pharmaceutical sciences. Herein, we focus on cyclodextrin (CyD)-based supermolecules, because CyDs have been used not only as pharmaceutical excipients or active pharmaceutical ingredients but also as components of supermolecules.

  13. Pharmaceutical R&D performance by firm size: approval success rates and economic returns.

    Science.gov (United States)

    DiMasi, Joseph A

    2014-01-01

    The R&D productivity of pharmaceutical firms has become an increasingly significant concern of industry, regulators, and policymakers. To address an important aspect of R&D performance, public and private data sources were used to estimate clinical phase transition and clinical approval probabilities for the pipelines of the 50 largest pharmaceutical firms (by sales) by 3 firms size groups (top 10 firms, top 11-20 firms, and top 21-50 firms). For self-originated compounds, the clinical approval success rates were 14.3%, 16.4%, and 18.4% for top 10 firms, top 11-20 firms, and top 21-50 firms, respectively. The results showing higher success rates for smaller firms were largely driven by outcomes for the small-molecule drugs. Adjustments for the relatively small differences in therapeutic class distributions across the firm size groups showed that the success rate for small-molecule self-originated drugs was 6% below average for top 10 firms and 17% above average for top 21-50 firms. Although success rates for small firms were higher, this advantage was offset to some degree by lower returns on approved drugs, suggesting different strategic objectives with regard to risk and reward by firm size.

  14. Impact of sludge stabilization processes and sludge origin (urban or hospital) on the mobility of pharmaceutical compounds following sludge landspreading in laboratory soil-column experiments.

    Science.gov (United States)

    Lachassagne, Delphine; Soubrand, Marilyne; Casellas, Magali; Gonzalez-Ospina, Adriana; Dagot, Christophe

    2015-11-01

    This study aimed to determine the effect of sludge stabilization treatments (liming and anaerobic digestion) on the mobility of different pharmaceutical compounds in soil amended by landspreading of treated sludge from different sources (urban and hospital). The sorption and desorption potential of the following pharmaceutical compounds: carbamazepine (CBZ), ciprofloxacin (CIP), sulfamethoxazole (SMX), salicylic acid (SAL), ibuprofen (IBU), paracetamol (PAR), diclofenac (DIC), ketoprofen (KTP), econazole (ECZ), atenolol (ATN), and their solid-liquid distribution during sludge treatment (from thickening to stabilization) were investigated in the course of batch testing. The different sludge samples were then landspread at laboratory scale and leached with an artificial rain simulating 1 year of precipitation adapted to the surface area of the soil column used. The quality of the resulting leachate was investigated. Results showed that ibuprofen had the highest desorption potential for limed and digested urban and hospital sludge. Ibuprofen, salicylic acid, diclofenac, and paracetamol were the only compounds found in amended soil leachates. Moreover, the leaching potential of these compounds and therefore the risk of groundwater contamination depend mainly on the origin of the sludge because ibuprofen and diclofenac were present in the leachates of soils amended with urban sludge, whereas paracetamol and salicylic acid were found only in the leachates of soils amended with hospital sludge. Although carbamazepine, ciprofloxacin, sulfamethoxazole, ketoprofen, econazole, and atenolol were detected in some sludge, they were not present in any leachate. This reflects either an accumulation and/or (bio)degradation of these compounds (CBZ, CIP, SMX, KTP, ECZ, and ATN ), thus resulting in very low mobility in soil. Ecotoxicological risk assessment, evaluated by calculating the risk quotients for each studied pharmaceutical compound, revealed no high risk due to the

  15. The role of cocrystals in pharmaceutical science.

    Science.gov (United States)

    Shan, Ning; Zaworotko, Michael J

    2008-05-01

    Pharmaceutical cocrystals, a subset of a long known but little-studied class of compounds, represent an emerging class of crystal forms in the context of pharmaceutical science. They are attractive to pharmaceutical scientists because they can significantly diversify the number of crystal forms that exist for a particular active pharmaceutical ingredient (API), and they can lead to improvements in physical properties of clinical relevance. In this article we address pharmaceutical cocrystals from the perspective of design (crystal engineering) and present a series of case studies that demonstrate how they can enhance the solubility, bioavailability, and/or stability of API crystal forms.

  16. Establishment of cocrystal cocktail grinding method for rational screening of pharmaceutical cocrystals.

    Science.gov (United States)

    Yamamoto, Katsuhiko; Tsutsumi, Shunichirou; Ikeda, Yukihiro

    2012-11-01

    Cocrystals (CCs) used in the pharmaceutical industry are defined as complex crystals formed by reaction between an API and a cocrystal former (CCF); unlike salts, CCs do not show proton transfer. Recently, pharmaceutical CCs have been used to improve the drug-likeness of APIs, such as solubility and stability. Grinding is more effective for CC synthesis than crystallization from solution because in the former case, the API can predominantly interact with the CCF without being affected by solvents. However, this method is tedious because the API is ground with only one CCF at a time. We developed a cocktail cocrystal grinding (CCG) method, in which a mixture of CCFs having the same functional group was used. No false negatives/positives were observed in CCG when carbamazepine was used as the model compound. This method could be used to obtain CCs of piroxicam and spironolactone. False negatives were observed for only one compound from among three model compounds, indicating that CCG facilitates efficient CC detection and that it has higher throughput than does the conventional method. Further, CCG is fast and suitable for rational CC screening, and it helps identify the partial structure of CCFs that forms synthons with an API. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Characterization of soluble microbial products (SMPs) in a membrane bioreactor (MBR) treating synthetic wastewater containing pharmaceutical compounds.

    Science.gov (United States)

    Zhang, Dongqing; Trzcinski, Antoine Prandota; Kunacheva, Chinagarn; Stuckey, David C; Liu, Yu; Tan, Soon Keat; Ng, Wun Jern

    2016-10-01

    This study investigated the behaviour and characteristics of soluble microbial products (SMP) in two anoxic-aerobic membrane bioreactors (MBRs): MBRcontrol and MBRpharma, for treating municipal wastewater. Both protein and polysaccharides measured exhibited higher concentrations in the MBRpharma than the MBRcontrol. Molecular weight (MW) distribution analysis revealed that the presence of pharmaceuticals enhanced the accumulation of SMPs with macro- (13,091 kDa and 1587 kDa) and intermediate-MW (189 kDa) compounds in the anoxic MBRpharma, while a substantial decrease was observed in both MBR effluents. Excitation emission matrix (EEM) fluorescence contours indicated that the exposure to pharmaceuticals seemed to stimulate the production of aromatic proteins containing tyrosine (10.1-32.6%) and tryptophan (14.7-43.1%), compared to MBRcontrol (9.9-29.1% for tyrosine; 11.8-42.5% for tryptophan). Gas chromatography-mass spectrometry (GC-MS) analysis revealed aromatics, long-chain alkanes and esters were the predominant SMPs in the MBRs. More peaks were present in the aerobic MBRpharma (196) than anoxic MBRpharma (133). The SMPs identified exhibited both biodegradability and recalcitrance in the MBR treatment processes. Only 8 compounds in the MBRpharma were the same as in the MBRcontrol. Alkanes were the most dominant SMPs (51%) in the MBRcontrol, while aromatics were dominant (40%) in the MBRpharma. A significant decrease in aromatics (from 16 to 7) in the MBRpharma permeate was observed, compared to the aerobic MBRpharma. Approximately 21% of compounds in the aerobic MBRcontrol were rejected by membrane filtration, while this increased to 28% in the MBRpharma. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Membrane Bioprocesses for Pharmaceutical Micropollutant Removal from Waters

    Directory of Open Access Journals (Sweden)

    Matthias de Cazes

    2014-10-01

    Full Text Available The purpose of this review work is to give an overview of the research reported on bioprocesses for the treatment of domestic or industrial wastewaters (WW containing pharmaceuticals. Conventional WW treatment technologies are not efficient enough to completely remove all pharmaceuticals from water. Indeed, these compounds are becoming an actual public health problem, because they are more and more present in underground and even in potable waters. Different types of bioprocesses are described in this work: from classical activated sludge systems, which allow the depletion of pharmaceuticals by bio-degradation and adsorption, to enzymatic reactions, which are more focused on the treatment of WW containing a relatively high content of pharmaceuticals and less organic carbon pollution than classical WW. Different aspects concerning the advantages of membrane bioreactors for pharmaceuticals removal are discussed, as well as the more recent studies on enzymatic membrane reactors to the depletion of these recalcitrant compounds.

  19. Green Pharmaceutical Analysis of Drugs Coformulated with Highly Different Concentrations Using Spiking and Manipulation of Their Ratio Spectra.

    Science.gov (United States)

    Ayoub, Bassam M

    2017-07-01

    Introducing green analysis to pharmaceutical products is considered a significant approach to preserving the environment. This method can be an environmentally friendly alternative to the existing methods, accompanied by a validated automated procedure for the analysis of a drug with the lowest possible number of samples. Different simple spectrophotometric methods were developed for the simultaneous determination of empagliflozin (EG) and metformin (MT) by manipulating their ratio spectra in their application on a recently approved pharmaceutical combination, Synjardy tablets. A spiking technique was used to increase the concentration of EG in samples prepared from the tablets to allow for the simultaneous determination of EG with MT without prior separation. Validation parameters according to International Conference on Harmonization guidelines were acceptable over a concentration range of 2-12 μg/mL for both drugs using derivative ratio and ratio subtraction coupled with extended ratio subtraction. The optimized methods were compared using one-way analysis of variance and proved to be suitable as ecofriendly approaches for industrial QC laboratories.

  20. Novel methodology for pharmaceutical expenditure forecast

    OpenAIRE

    Vataire, Anne-Lise; Cetinsoy, Laurent; Aball?a, Samuel; R?muzat, C?cile; Urbinati, Duccio; Kornfeld, ?sa; Mzoughi, Olfa; Toumi, Mondher

    2014-01-01

    Background and objective: The value appreciation of new drugs across countries today features a disruption that is making the historical data that are used for forecasting pharmaceutical expenditure poorly reliable. Forecasting methods rarely addressed uncertainty. The objective of this project was to propose a methodology to perform pharmaceutical expenditure forecasting that integrates expected policy changes and uncertainty (developed for the European Commission as the ‘EU Pharmaceutical e...

  1. Can biochemistry drive drug discovery beyond simple potency measurements?

    Science.gov (United States)

    Chène, Patrick

    2012-04-01

    Among the fields of expertise required to develop drugs successfully, biochemistry holds a key position in drug discovery at the interface between chemistry, structural biology and cell biology. However, taking the example of protein kinases, it appears that biochemical assays are mostly used in the pharmaceutical industry to measure compound potency and/or selectivity. This limited use of biochemistry is surprising, given that detailed biochemical analyses are commonly used in academia to unravel molecular recognition processes. In this article, I show that biochemistry can provide invaluable information on the dynamics and energetics of compound-target interactions that cannot be obtained on the basis of potency measurements and structural data. Therefore, an extensive use of biochemistry in drug discovery could facilitate the identification and/or development of new drugs. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Diagnostic and therapeutic radio pharmaceutical capsules

    International Nuclear Information System (INIS)

    Haney, T.A.; Wedeking, P.W.; Morcos, N.A.

    1981-01-01

    An improved pharmaceutical radioactive capsule consisting of a non-toxic, water soluble material adapted to being ingested and rapidly disintegrating on contact with fluids of the gastro-intestinal tract is described. Each capsule is provided with filler material supporting a pharmaceutically useful radioactive compound absorbable from the gastro-intestinal tract. The capsule is preferably of gelatin, methyl cellulose or polyvinyl alcohol and the filler is a polyethylene glycol. The radioactive compound may be iodine e.g. sodium radioiodide I-131 or 123. The capsule may also contain a reducing agent e.g. sodium thiosulphate, sulphite, or bisulphite. (author)

  3. Effects of effluent organic matter characteristics on the removal of bulk organic matter and selected pharmaceutically active compounds during managed aquifer recharge: Column study

    KAUST Repository

    Maeng, Sungkyu; Sharma, Saroj K.; Abel, Chol D T; Magic-Knezev, Aleksandra; Song, Kyungguen; Amy, Gary L.

    2012-01-01

    Soil column experiments were conducted to investigate the effects of effluent organic matter (EfOM) characteristics on the removal of bulk organic matter (OM) and pharmaceutically active compounds (PhACs) during managed aquifer recharge (MAR

  4. Drug repurposing for aging research using model organisms.

    Science.gov (United States)

    Ziehm, Matthias; Kaur, Satwant; Ivanov, Dobril K; Ballester, Pedro J; Marcus, David; Partridge, Linda; Thornton, Janet M

    2017-10-01

    Many increasingly prevalent diseases share a common risk factor: age. However, little is known about pharmaceutical interventions against aging, despite many genes and pathways shown to be important in the aging process and numerous studies demonstrating that genetic interventions can lead to a healthier aging phenotype. An important challenge is to assess the potential to repurpose existing drugs for initial testing on model organisms, where such experiments are possible. To this end, we present a new approach to rank drug-like compounds with known mammalian targets according to their likelihood to modulate aging in the invertebrates Caenorhabditis elegans and Drosophila. Our approach combines information on genetic effects on aging, orthology relationships and sequence conservation, 3D protein structures, drug binding and bioavailability. Overall, we rank 743 different drug-like compounds for their likelihood to modulate aging. We provide various lines of evidence for the successful enrichment of our ranking for compounds modulating aging, despite sparse public data suitable for validation. The top ranked compounds are thus prime candidates for in vivo testing of their effects on lifespan in C. elegans or Drosophila. As such, these compounds are promising as research tools and ultimately a step towards identifying drugs for a healthier human aging. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  5. Optimization of the pharmaceutical care system for diabetes patients using modern pharmaceutical informatics methodology

    Directory of Open Access Journals (Sweden)

    Андрій Ігорович Бойко

    2016-04-01

    Full Text Available Aim. Implementation of pharmaceutical informatics methods in the system of pharmaceutical care for diabetes patients in Ukraine.Methods. System method was used for the analysis of status and reforming the pharmaceutical care for patients with diabetes; program-oriented management at informatization project realization; pharmaceutical informatics in the creation of computer pharmaceutical knowledge bases; methods of data synthesis and summarizing.Results. System analysis of the basic directions of reforming the pharmaceutical care for patients with diabetes in Ukraine was carried out. Ways of it’s of optimization were processed: establishment of specialized pharmacies with implementation of modern information technologies and special postgraduate education for pharmacists. Structure and information providing of computer knowledge base “Pharmaceutical care for patients with diabetes” was substantiated.Conclusion. Based on the regional project “Informatization of prescription antidiabetic drugs circulation in Ukraine” realization, the necessity of establishment of specialized pharmacies providing pharmaceutical care for patients with diabetes was substantiated. Ways for optimization of postgraduate education for pharmacists of the specialized pharmacies by implementation of special thematic improvement cycles were proceed. Computer knowledge base as an effective tool for optimization of pharmaceutical care for patients with diabetes was realized

  6. Microbiological assay for the analysis of certain macrolides in pharmaceutical dosage forms.

    Science.gov (United States)

    Mahmoudi, A; Fourar, R E-A; Boukhechem, M S; Zarkout, S

    2015-08-01

    Clarithromycin (CLA) and roxithromycin (ROX) are macrolide antibiotics with an expanded spectrum of activity that are commercially available as tablets. A microbiological assay, applying the cylinder-plate method and using a strain of Micrococcus luteus ATCC 9341 as test organism, has been used and validated for the quantification of two macrolide drugs; CLA and ROX in pure and pharmaceutical formulations. The validation of the proposed method was carried out for linearity, precision, accuracy and specificity. The linear dynamic ranges were from 0.1 to 0.5μg/mL for both compounds. Logarithmic calibration curve was obtained for each macrolide (r>0.989) with statistically equal slopes varying from 3.275 to 4.038, and a percentage relative standard deviation in the range of 0.24-0.92%. Moreover, the method was applied successfully for the assay of the studied drugs in pharmaceutical tablet dosage forms. Recovery from standard addition experiments in commercial products was 94.71-96.91% regarding clarithromycin and 93.94-98.12% regarding roxithromycin, with a precision (%RSD) 1.32-2.11%. Accordingly, this microbiological assay can be used for routine quality control analysis of titled drugs in tablet formulations. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Electrochemical Analysis of Antichemotherapeutic Drug Zanosar in Pharmaceutical and Biological Samples by Differential Pulse Polarography

    OpenAIRE

    Reddy, Chennupalle Nageswara; ReddyPrasad, Puthalapattu; Sreedhar, NeelamYughandhar

    2013-01-01

    The electrochemical reduction of zanosar was investigated systematically by direct current polarography, cyclic voltammetry, and differential pulse polarography (DPP). A simple DPP technique was proposed for the direct quantitative determination of anticancer drug zanosar in pharmaceutical formulation and spiked human urine samples for the first time. The reduction potential was −0.28 V versus Ag/AgCl with a hanging mercury drop electrode in Britton-Robinson buffer as supporting electrolyte. ...

  8. Drug discovery for schistosomiasis: hit and lead compounds identified in a library of known drugs by medium-throughput phenotypic screening.

    Directory of Open Access Journals (Sweden)

    Maha-Hamadien Abdulla

    2009-07-01

    Full Text Available Praziquantel (PZQ is the only widely available drug to treat schistosomiasis. Given the potential for drug resistance, it is prudent to search for novel therapeutics. Identification of anti-schistosomal chemicals has traditionally relied on phenotypic (whole organism screening with adult worms in vitro and/or animal models of disease-tools that limit automation and throughput with modern microtiter plate-formatted compound libraries.A partially automated, three-component phenotypic screen workflow is presented that utilizes at its apex the schistosomular stage of the parasite adapted to a 96-well plate format with a throughput of 640 compounds per month. Hits that arise are subsequently screened in vitro against adult parasites and finally for efficacy in a murine model of disease. Two GO/NO GO criteria filters in the workflow prioritize hit compounds for tests in the animal disease model in accordance with a target drug profile that demands short-course oral therapy. The screen workflow was inaugurated with 2,160 chemically diverse natural and synthetic compounds, of which 821 are drugs already approved for human use. This affords a unique starting point to 'reposition' (re-profile drugs as anti-schistosomals with potential savings in development timelines and costs.Multiple and dynamic phenotypes could be categorized for schistosomula and adults in vitro, and a diverse set of 'hit' drugs and chemistries were identified, including anti-schistosomals, anthelmintics, antibiotics, and neuromodulators. Of those hits prioritized for tests in the animal disease model, a number of leads were identified, one of which compares reasonably well with PZQ in significantly decreasing worm and egg burdens, and disease-associated pathology. Data arising from the three components of the screen are posted online as a community resource.To accelerate the identification of novel anti-schistosomals, we have developed a partially automated screen workflow that

  9. Pharmaceutical Cocrystals: Regulatory and Strategic Aspects, Design and Development

    OpenAIRE

    Gadade, Dipak Dilip; Pekamwar, Sanjay Sudhakar

    2016-01-01

    Cocrystal is a concept of the supramolecular chemistry which is gaining the extensive interest of researchers from pharmaceutical and chemical sciences and of drug regulatory agencies. The prominent reason of which is its ability to modify physicochemical properties of active pharmaceutical ingredients. During the development of the pharmaceutical product, formulators have to optimize the physicochemical properties of active pharmaceutical ingredients. Pharmaceutical cocrystals can be employe...

  10. Occurrence, distribution and partitioning of nonionic surfactants and pharmaceuticals in the urbanized Long Island Sound Estuary (NY)

    International Nuclear Information System (INIS)

    Lara-Martín, Pablo A.; González-Mazo, Eduardo; Petrovic, Mira; Barceló, Damià; Brownawell, Bruce J.

    2014-01-01

    Highlights: • Surfactant levels were one order of magnitude higher than those for pharmaceuticals. • Concentrations of analytes in seawater were influenced by tides and sampling depth. • Surfactants were found in all suspended solids samples at more than 1 μg g −1 . • Presence of pharmaceuticals in sewage impacted surface sediments was minimal. • Among all analytes, polyethylene glycols show highest concentrations in sediments. - Abstract: This work deals with the environmental distribution of nonionic surfactants (nonylphenol and alcohol ethoxylates), their metabolites (NP, nonylphenol; NPEC, nonylphenol ethoxycarboxylates; and PEG, polyethylene glycols) and a selection of 64 pharmaceuticals in the Long Island Sound (LIS) Estuary which receives important sewage discharges from New York City (NYC). Most target compounds were efficiently removed (>95%) in one wastewater treatment plant monitored, with the exception of NPEC and some specific drugs (e.g., hydrochlorothiazide). Concentrations of surfactants (1.4–4.5 μg L −1 ) and pharmaceuticals (0.1–0.3 μg L −1 ) in seawater were influenced by tides and sampling depth, consistent with salinity differences. Surfactants levels in suspended solids samples were higher than 1 μg g −1 , whereas only most hydrophobic or positively charged pharmaceuticals could be found (e.g., tamoxifen, clarithromycin). Maximum levels of target compounds in LIS sediments (PEG at highest concentrations, 2.8 μg g −1 ) were measured nearest NYC, sharply decreasing with distance from major sewage inputs

  11. Heterocyclic Anticancer Compounds: Recent Advances and the Paradigm Shift towards the Use of Nanomedicine's Tool Box.

    Science.gov (United States)

    Martins, Pedro; Jesus, João; Santos, Sofia; Raposo, Luis R; Roma-Rodrigues, Catarina; Baptista, Pedro Viana; Fernandes, Alexandra R

    2015-09-16

    The majority of heterocycle compounds and typically common heterocycle fragments present in most pharmaceuticals currently marketed, alongside with their intrinsic versatility and unique physicochemical properties, have poised them as true cornerstones of medicinal chemistry. Apart from the already marketed drugs, there are many other being investigated for their promising activity against several malignancies. In particular, anticancer research has been capitalizing on the intrinsic versatility and dynamic core scaffold of these compounds. Nevertheless, as for any other promising anticancer drugs, heterocyclic compounds do not come without shortcomings. In this review, we provide for a concise overview of heterocyclic active compounds and families and their main applications in medicine. We shall focus on those suitable for cancer therapy while simultaneously addressing main biochemical modes of action, biological targets, structure-activity relationships as well as intrinsic limitation issues in the use of these compounds. Finally, considering the advent of nanotechnology for effective selective targeting of drugs, we shall discuss fundamental aspects and considerations on nanovectorization of such compounds that may improve pharmacokinetic/pharmacodynamic properties of heterocycles.

  12. Formation, Physicochemical Characterization, and Thermodynamic Stability of the Amorphous State of Drugs and Excipients.

    Science.gov (United States)

    Martino, Piera Di; Magnoni, Federico; Peregrina, Dolores Vargas; Gigliobianco, Maria Rosa; Censi, Roberta; Malaj, Ledjan

    2016-01-01

    Drugs and excipients used for pharmaceutical applications generally exist in the solid (crystalline or amorphous) state, more rarely as liquid materials. In some cases, according to the physicochemical nature of the molecule, or as a consequence of specific technological processes, a compound may exist exclusively in the amorphous state. In other cases, as a consequence of specific treatments (freezing and spray drying, melting and co-melting, grinding and compression), the crystalline form may convert into a completely or partially amorphous form. An amorphous material shows physical and thermodynamic properties different from the corresponding crystalline form, with profound repercussions on its technological performance and biopharmaceutical properties. Several physicochemical techniques such as X-ray powder diffraction, thermal methods of analysis, spectroscopic techniques, gravimetric techniques, and inverse gas chromatography can be applied to characterize the amorphous form of a compound (drug or excipient), and to evaluate its thermodynamic stability. This review offers a survey of the technologies used to convert a crystalline solid into an amorphous form, and describes the most important techniques for characterizing the amorphous state of compounds of pharmaceutical interest.

  13. Non-medical use of prescription drugs among illicit drug users: A case study on an online drug forum.

    Science.gov (United States)

    Rönkä, Sanna; Katainen, Anu

    2017-01-01

    The non-medical use of prescription drugs is a growing phenomenon associated with increasing health-related harms. However, little is known about the drivers of this process among illicit drug users. Our aim is to show how the qualities of pharmaceutical drugs, pharmaceutical related knowledge, online communities sharing this knowledge and medical professionals mediate and transform the consumption behaviour related to pharmaceutical drugs. The data consist of discussion threads from an online drug use forum. Using actor network theory (ANT), we analysed translations that mediate the online user community's relationship with pharmaceutical drugs. Differences in experienced drug effects are explained both as a process of 'learning' and as differences in brain chemistry at the receptor level. Both science- and experience-based information are shared on best practices to optimise use, avoid adverse health effects and maximise the experience of intoxication. The expanded context of doctors' practices places stress on the medical framework for drug use. Our analysis shows how the non-medical use of psychoactive pharmaceuticals relates to joint, medicalised ideas of bodies as sites of medical experimentation, as well as to the collective process of constructing 'pharmaceutical competences' in user networks. Understandings of intoxication have increasingly been permeated with the pharmacological and scientific logic of knowledge. The forum works as a platform for harm reduction inspired exchange of knowledge. However, the user community's knowledge sharing practices can generate a shared perception of a sufficient or even superior drug use experience and knowledge. This may lead to overdoses and other risky behaviour, and thereby contribute to increased harms related to non-medical use of prescription drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Ecotoxicological assessment of the pharmaceutical compound Triclosan to freshwater invertebrates with emphasis to spiked sediment tests

    International Nuclear Information System (INIS)

    Pusceddu, Fabio Hermes

    2009-01-01

    The increasing of Pharmaceutical and Personal Care Products (PPCPs) occurrence in the aquatic environment cause adverse effects on the human health and aquatic communities. The environmental risk of the PPCPs associated with the possibility of synergic effects between PCPPs and the increase of the use of synthetic organic compounds, unchained a great concern on the toxic potential to biota aquatic. Triclosan (5-chloro-2-(2,4-dichlorophenoxy)-phenol) is a pharmaceutical compound widely used due your antibacterial mechanism effect, found in at least 932 products such as shampoos, toilet soaps, deodorants, lotions, toothpaste, detergents, socks and underwear, among others. Currently, studies about the Triclosan toxicity in the water and, mainly in the sediment, are poorly. We have the knowledge that the photodegradation of this product results into dichlorodibenzo-p-dioxin, and now it has great discussion on environmental agencies, like EPA, about the release or restriction of this product. The aim of this work is to assess the effects of Triclosan on mortality of insect larvae Chironomus xanthus and mortality and reproduction inhibition of microcrustacea Ceriodaphnia dubia exposed to Triclosan spiked sediments based on standard methods EPA and OECD. The EC50;96H obtained on acute toxicity tests with C. xanthus was 45,26 mg.Kg -1 . The chronic toxicity tests with C. dubia using spiked sediments were performed following the procedure in Burton and MacPherson (1995). A no-observed-effect concentrations and lowest-observed-effect concentration were 5,78 e 6,94 mg.Kg -1 , respectively. (author)

  15. Small-molecule compounds exhibiting target-mediated drug disposition - A case example of ABT-384.

    Science.gov (United States)

    An, Guohua; Liu, Wei; Dutta, Sandeep

    2015-10-01

    Nonlinearities are frequently encountered in pharmacokinetics, and they can occur when 1 or more processes of absorption, distribution, metabolism, and excretion are saturable. One special source of nonlinearity that has been noticed recently is the saturable binding of the drug to a high-affinity-low-capacity target, a phenomenon known as target-mediated drug disposition (TMDD). Although TMDD can occur in both small-molecule compounds and large-molecule compounds, the latter has received much more attention because of its high prevalence. With the development of more potent small-molecule drugs acting on highly specific targets and the availability of increasingly sensitive analytical techniques, small-molecule compounds exhibiting TMDD have been increasingly reported in the past several years. ABT-384 is a small-molecule drug candidate that exhibited significant nonlinear pharmacokinetics, potentially imparted by TMDD, in a first-in-human clinical trial conducted in healthy volunteers. Compared with published small-molecule compounds exhibiting TMDD, ABT-384 pharmacokinetic characteristics are more consistent with TMDD. To expand current knowledge of TMDD of small-molecule compounds and increase awareness of this interesting and clinically important phenomenon, in this review the general features of small-molecule compounds exhibiting TMDD are highlighted, with ABT-384 provided as an example. © 2015, The American College of Clinical Pharmacology.

  16. Drug Policy in Cyprus

    Directory of Open Access Journals (Sweden)

    George Charalambous

    2012-01-01

    Full Text Available Background: The provision of pharmaceutical drugs is of enormous significance in our lives. Notable progress made inthe domain of Public Health, combined with a general increase in the standard of living, has had a direct impact on thediscovery of new drugs and cures and has shifted pharmaceutical policies further in line with the current needs of boththe country’s health system and, its population.Aim: This research aims to both shed light on and analyse the current state of pharmaceutical policy in Cyprus, as well asto try to seek out its weaknesses, making suggestions, where possible, as to how to keep these to the minimum.Results, and Conclusions: The lack of both high level research and major industrial facilities relating to the discovery ofnew pharmaceutical drugs in Cyprus, has hindered the effectiveness of pharmaceutical policy in general domains such ascontrol over the circulation and production of pharmaceutical products in the country, their pricing and distribution andthe monitoring of our drug supplies. The lack of transparency in a number of pharmaceutical procedures, and ofinformation on drugs does not enhance the industry’s reliability, but rather exacerbates an underlying feeling of insecurityrelating to it among the population.

  17. Pharmaceutical crystallography: is there a devil in the details?

    DEFF Research Database (Denmark)

    Bond, A. D.

    2012-01-01

    Modern instruments for small-molecule crystallography continue to become more sophisticated and more automated. This technical progress provides a basis for frontier research in chemical and pharmaceutical crystallography, but it also encourages analytical crystallographers to become more...... are presented for pharmaceutical compounds, and the potential importance of the "details" in pharmaceutical crystallography is discussed....

  18. Determination of pharmaceutical and illicit drugs in oral fluid by ultra-high performance liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Di Corcia, D; Lisi, S; Pirro, V; Gerace, E; Salomone, A; Vincenti, M

    2013-05-15

    A simple and extremely fast procedure for the quantitative determination in oral fluid samples of 44 substances, including the most common drugs of abuse and several pharmaceutical drugs, was developed and fully validated. Preliminary sample treatment was limited to protein precipitation. The resulting acetonitrile solution was directly injected into an ultra-high performance liquid chromatograph (UHPLC) equipped with a C18 column (100mm×2.1mm, 1.7μm). The mobile phase eluted with linear gradient (water/formic acid 5mM: acetonitrile/formic acid 5mM; v:v) from 98:2 to 0:100 in 5.0min, followed by isocratic elution at 100% B for 1.0min. The flow rate was 0.6mL/min and the total run time was 9.0min including re-equilibration at the initial conditions. The analytes were revealed by a triple quadrupole mass spectrometer operating in the selected reaction monitoring mode. The method proved to be simple, accurate, rapid and highly sensitive, allowing the simultaneous detection of all compounds. The ease of sample treatment, together with the wide range of detectable substances, all with remarkable analytical sensitivity, make this procedure ideal for the screening of large populations in several forensic and clinical contexts, whenever oral fluid sampling has to be preferred to blood sampling, as for example in short retrospective investigations. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Unlock your Compound Management

    OpenAIRE

    Steffen Eller

    2016-01-01

    Pharmaceutical industry faces the increased demand for innovative medicines against various diseases. In this regard, the compound library in pharmaceutical industry is the most valuable asset. However, the compound distribution from the library into the screening plates is often still done manually and binds highly qualified resources to very time-consuming, tedious and error-prone tasks. To overcome these challenges, Chemspeed launched the first automated true one-to-one gravimetric "pi...

  20. Computational Fragment-Based Drug Design: Current Trends, Strategies, and Applications.

    Science.gov (United States)

    Bian, Yuemin; Xie, Xiang-Qun Sean

    2018-04-09

    Fragment-based drug design (FBDD) has become an effective methodology for drug development for decades. Successful applications of this strategy brought both opportunities and challenges to the field of Pharmaceutical Science. Recent progress in the computational fragment-based drug design provide an additional approach for future research in a time- and labor-efficient manner. Combining multiple in silico methodologies, computational FBDD possesses flexibilities on fragment library selection, protein model generation, and fragments/compounds docking mode prediction. These characteristics provide computational FBDD superiority in designing novel and potential compounds for a certain target. The purpose of this review is to discuss the latest advances, ranging from commonly used strategies to novel concepts and technologies in computational fragment-based drug design. Particularly, in this review, specifications and advantages are compared between experimental and computational FBDD, and additionally, limitations and future prospective are discussed and emphasized.

  1. Raman spectroscopy in pharmaceutical product design

    DEFF Research Database (Denmark)

    Paudel, Amrit; Raijada, Dhara; Rantanen, Jukka

    2015-01-01

    Almost 100 years after the discovery of the Raman scattering phenomenon, related analytical techniques have emerged as important tools in biomedical sciences. Raman spectroscopy and microscopy are frontier, non-invasive analytical techniques amenable for diverse biomedical areas, ranging from...... molecular-based drug discovery, design of innovative drug delivery systems and quality control of finished products. This review presents concise accounts of various conventional and emerging Raman instrumentations including associated hyphenated tools of pharmaceutical interest. Moreover, relevant...... application cases of Raman spectroscopy in early and late phase pharmaceutical development, process analysis and micro-structural analysis of drug delivery systems are introduced. Finally, potential areas of future advancement and application of Raman spectroscopic techniques are discussed....

  2. Quantization of buspirone hydrochloride in pure and pharmaceutical formulation by spectrophotometric method

    International Nuclear Information System (INIS)

    Kazi, A.A.; Mumtaz, A.; Sabri, M.U.

    2008-01-01

    A simple and sensitive method is described for the determination of bus pirone hydrochloride in bulk drug and in formulations employing spectrophotometric technique. The method is based on the interaction orbuspirone hydrochloride with ammonium molybdate in acidic media and the absorbance is measured at 700 nm. Beer's Law is obeyed in the range of 5 macro g to 350 micro g/ml and RSD is 0.96% for buspirone hydrochloride. Analytical data for the determination of pure compound is presented along with the application of the proposed method for the analysis of pharmaceutical formulation. (author)

  3. Navigating the human metabolome for biomarker identification and design of pharmaceutical molecules

    DEFF Research Database (Denmark)

    Kouskoumvekaki, Irene; Panagiotou, Gianni

    2010-01-01

    medical practice, as well as drug discovery. In this paper, we present the most up-to-date metabolite and metabolic pathway resources, and we summarize the statistical, and machine-learning tools used for the analysis of data from clinical metabolomics. Through specific applications on cancer, diabetes...... Metabolome Database (HMDB) and the Chinese Natural Product Database (CNPD), we demonstrate the close relatedness of the two data sets of compounds, and we further illustrate how structural similarity with human metabolites could assist in the design of novel pharmaceuticals and the elucidation...

  4. 42 CFR 416.48 - Condition for coverage-Pharmaceutical services.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Condition for coverage-Pharmaceutical services. 416... Coverage § 416.48 Condition for coverage—Pharmaceutical services. The ASC must provide drugs and... direction of an individual designated responsible for pharmaceutical services. (a) Standard: Administration...

  5. Electrochemical Analysis of Antichemotherapeutic Drug Zanosar in Pharmaceutical and Biological Samples by Differential Pulse Polarography

    Directory of Open Access Journals (Sweden)

    Chennupalle Nageswara Reddy

    2013-01-01

    Full Text Available The electrochemical reduction of zanosar was investigated systematically by direct current polarography, cyclic voltammetry, and differential pulse polarography (DPP. A simple DPP technique was proposed for the direct quantitative determination of anticancer drug zanosar in pharmaceutical formulation and spiked human urine samples for the first time. The reduction potential was −0.28 V versus Ag/AgCl with a hanging mercury drop electrode in Britton-Robinson buffer as supporting electrolyte. The dependence of the intensities of currents and potentials on pH, concentration, scan rate, deposition time, and nature of the supporting electrolyte was investigated. The calibration curve was found to be linear with the following equation: y=0.4041x+0.012, with a correlation coefficient of 0.992 (R2 over a concentration range from 1.0×10-7 M to 1.0×10-3 M. In the present investigation, the achieved limit of detection (LOD and limit of quantization (LQD were 7.42×10-8 M and 2.47×10-8 M; respectively. Excipients did not interfere with the determination of zanosar in pharmaceutical formulation and spiked urine samples. Precision and accuracy of the developed method were checked by recovery studies in pharmaceutical formulation and spiked human urine samples.

  6. Electrochemical analysis of antichemotherapeutic drug zanosar in pharmaceutical and biological samples by differential pulse polarography.

    Science.gov (United States)

    Reddy, Chennupalle Nageswara; Reddyprasad, Puthalapattu; Sreedhar, Neelamyughandhar

    2013-01-01

    The electrochemical reduction of zanosar was investigated systematically by direct current polarography, cyclic voltammetry, and differential pulse polarography (DPP). A simple DPP technique was proposed for the direct quantitative determination of anticancer drug zanosar in pharmaceutical formulation and spiked human urine samples for the first time. The reduction potential was -0.28 V versus Ag/AgCl with a hanging mercury drop electrode in Britton-Robinson buffer as supporting electrolyte. The dependence of the intensities of currents and potentials on pH, concentration, scan rate, deposition time, and nature of the supporting electrolyte was investigated. The calibration curve was found to be linear with the following equation: y = 0.4041x + 0.012, with a correlation coefficient of 0.992 (R (2)) over a concentration range from 1.0 × 10(-7) M to 1.0 × 10(-3) M. In the present investigation, the achieved limit of detection (LOD) and limit of quantization (LQD) were 7.42 × 10(-8) M and 2.47 × 10(-8) M; respectively. Excipients did not interfere with the determination of zanosar in pharmaceutical formulation and spiked urine samples. Precision and accuracy of the developed method were checked by recovery studies in pharmaceutical formulation and spiked human urine samples.

  7. Reaction between drug substances and pharmaceutical excipients

    DEFF Research Database (Denmark)

    Larsen, Jesper; Cornett, Claus; Jaroszewski, Jerzy Witold

    2009-01-01

    The reactivity of citric acid towards drug substances in the solid state was examined using the beta-blocker carvedilol as a model compound. The reaction mixtures were analysed by LC-MS, the reaction products were isolated by preparative HPLC, and the structures were elucidated by microprobe NMR...... spectroscopy. Heating a mixture of solid carvedilol and solid citric acid monohydrate for 96h at 50 degrees C resulted in the formation of about 3% of a symmetrical ester as well as of a number of other reaction products in smaller amounts. Formation of the symmetrical ester was also observed at room...... temperature. At 70 degrees C, the amounts of three isomeric esters formed reached 6-8%. The minor reaction products were citric acid amides, O-acetylcarvedilol, and esters of itaconic acid....

  8. Drug Pollution from Manufacturing and Antimicrobial Resistance: How Does the European Union Manage the Potential Environmental and Health Risks of Importing Pharmaceutical Active Ingredients From Third Countries?

    DEFF Research Database (Denmark)

    le Gal, Elodie Jeanine Odette

    pollution and anti-micro-bacterial resistance within their own borders by buying and importing drugs manufactured in third countries, such as India and China. With a focus on drug pollution from manufacturing, the goal of this paper is to explore the European drug import safety regime. It intends to better...... and environmental failures. Over the past three decades, the scientific literature has been increasingly reporting case studies on environmental pollution from drug manufacturing, human excretions and improper disposal of unused or expired drug residues in different parts of the world. Active ingredients, which...... are responsible for the biological activity of drugs, have been identified as the main vector of pharmaceutical pollution. Associated with the environmental risk of pharmaceutical pollution in soils and waterways is the predicted risk of antimicrobial resistance (AMR) expected to increase and to dramatically...

  9. Heterocyclic Anticancer Compounds: Recent Advances and the Paradigm Shift towards the Use of Nanomedicine’s Tool Box

    Directory of Open Access Journals (Sweden)

    Pedro Martins

    2015-09-01

    Full Text Available The majority of heterocycle compounds and typically common heterocycle fragments present in most pharmaceuticals currently marketed, alongside with their intrinsic versatility and unique physicochemical properties, have poised them as true cornerstones of medicinal chemistry. Apart from the already marketed drugs, there are many other being investigated for their promising activity against several malignancies. In particular, anticancer research has been capitalizing on the intrinsic versatility and dynamic core scaffold of these compounds. Nevertheless, as for any other promising anticancer drugs, heterocyclic compounds do not come without shortcomings. In this review, we provide for a concise overview of heterocyclic active compounds and families and their main applications in medicine. We shall focus on those suitable for cancer therapy while simultaneously addressing main biochemical modes of action, biological targets, structure-activity relationships as well as intrinsic limitation issues in the use of these compounds. Finally, considering the advent of nanotechnology for effective selective targeting of drugs, we shall discuss fundamental aspects and considerations on nanovectorization of such compounds that may improve pharmacokinetic/pharmacodynamic properties of heterocycles.

  10. Private versus social incentives for pharmaceutical innovation.

    Science.gov (United States)

    González, Paula; Macho-Stadler, Inés; Pérez-Castrillo, David

    2016-12-01

    We provide a theoretical framework to contribute to the current debate regarding the tendency of pharmaceutical companies to direct their R&D toward marketing products that are "follow-on" drugs of already existing drugs, rather than toward the development of breakthrough drugs. We construct a model with a population of patients who can be treated with drugs that are horizontally and vertically differentiated. In addition to a pioneering drug, a new drug can be marketed as the result of an innovative process. We analyze physician prescription choices and the optimal pricing decision of an innovative firm. We also characterize the incentives of the innovative firm to conduct R&D activities, disentangling the quest for breakthrough drugs from the firm effort to develop follow-on drugs. Our results offer theoretical support for the conventional wisdom that pharmaceutical firms devote too many resources to conducting R&D activities that lead to incremental innovations. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Anaerobic stabilization and conversion of transformed intermediates of antibiotic pharmaceutical effluent in a fluidized bed reactor.

    Science.gov (United States)

    Tamijevendane, S; Saravanane, R; Rajesh, R; Sivacoumar, R

    2011-07-01

    The formulation and implementation of regulatory standards for the ultimate disposal and reuse of transformed products of antibiotic drugs and solvents have been a pending issue in the waste management of pharmaceutical industries especially in the developing countries like India. A case study has been identified and the current issues in one of the major pharmaceutical industry (manufacturing cephalosporin drugs) located in Chennai, India, has been discussed for the possible implementation of anaerobically transformed intermediates of antibiotic pharmaceutical waste sludge. The objective of the study was to determine the effect of bioaugmentation on the convertibility of anaerobically transformed intermediates of antibiotic pharmaceutical waste sludge into residuals and biocompost. Cephalosporin is a common name refers to cephradine (C16H19N3O4S) and cephalexin (C16H17N3O4S.H2O). Based on the critical examination of results, the industry is looking for the alternatives of either direct disposal of 7-amino-3-deacetoxycephalosporanic acid (7-ADCA) and phenyl acetic acid or for further degradation and disposal, which will essentially require additional cost and maintenance. The present regulatory standard implemented in India does not envisage such disposal alternatives and hence this would invite suggestions and recommendations of the expertise for the possible implementation on the pending issue in the antibiotic based pharmaceutical industries. The presence of cephalosporin increases total strength (Chemical Oxygen Demand) of the effluent and indirectly increases the cost of the treatment. Hence the biotransformation of cephalosporin either alone or in combination with other energetic compounds, offers the potential for an economical and environment friendly disposal alternative for the anaerobically transformed intermediates of antibiotic pharmaceutical waste sludge.

  12. Recent trends in the impurity profile of pharmaceuticals

    Directory of Open Access Journals (Sweden)

    Kavita Pilaniya

    2010-01-01

    Full Text Available Various regulatory authorities such as the International Conference on Harmonization (ICH, the United States Food and Drug administration (FDA, and the Canadian Drug and Health Agency (CDHA are emphasizing on the purity requirements and the identification of impurities in Active Pharmaceutical Ingredients (APIs. The various sources of impurity in pharmaceutical products are - reagents, heavy metals, ligands, catalysts, other materials like filter aids, charcoal, and the like, degraded end products obtained during \\ after manufacturing of bulk drugs from hydrolysis, photolytic cleavage, oxidative degradation, decarboxylation, enantiomeric impurity, and so on. The different pharmacopoeias such as the British Pharmacopoeia, United State Pharmacopoeia, and Indian Pharmacopoeia are slowly incorporating limits to allowable levels of impurities present in APIs or formulations. Various methods are used to isolate and characterize impurities in pharmaceuticals, such as, capillary electrophoresis, electron paramagnetic resonance, gas-liquid chromatography, gravimetric analysis, high performance liquid chromatography, solid-phase extraction methods, liquid-liquid extraction method, Ultraviolet Spectrometry, infrared spectroscopy, supercritical fluid extraction column chromatography, mass spectrometry, Nuclear magnetic resonance (NMR spectroscopy, and RAMAN spectroscopy. Among all hyphenated techniques, the most exploited techniques for impurity profiling of drugs are Liquid Chromatography (LC-Mass Spectroscopy (MS, LC-NMR, LC-NMR-MS, GC-MS, and LC-MS. This reveals the need and scope of impurity profiling of drugs in pharmaceutical research.

  13. Drugs in Your Drinking Water: Removing Pharmaceutical Pollution

    Science.gov (United States)

    Richardson, K.

    2017-12-01

    Pharmaceuticals, mostly estrogen-based hormones and antibiotics, are increasingly polluting waterways and contaminating municipal drinking water sources. A 2008 study funded by the American Water Works Association Research Foundation and the WateReuse Foundation tested 19 drinking water treatment plants across the United States. The study found pharmaceuticals and metabolites at all of the locations tested. These plants provide drinking water for over 28 million Americans - yet only five states test for pharmaceuticals. A 2007 US Government Accountability Office study of male smallmouth bass showed ovarian tissue in their gonads and concluded the combination of EDCs (Endocrine Disrupting Chemicals) likely caused the feminization of the male fish. The purpose of this project is to determine whether bivalves can effectively remove pharmaceuticals as well as other CECs (Contaminants of Emerging Concern).Pharmaceuticals, specifically ibuprofen, were found to be resistant to chemical and mechanical filtration methods, such as coffee grounds and activated carbon, so biological filtration methods are used. Three types of common mollusks (Sphaeriidae `fingernail clams', freshwater mussels, scallops) will be used to assess the potential for biological remediation of the chemical pollutants. Fifteen specimens of each species will be used - a total of 45 individuals. Each group of five will be introduced to either an NSAID (ibuprofen), oil (vegetable) or hormone (estrogen, pending approval). This creates an array of 3 species and 3 contaminants, for a 3x3 grid of nine sample groups. Water is contaminated with pollutant levels similar to EPA measurements. The concentration will be measured before and after the introduction of the specimens using a UV spectrophotometer, at regular time intervals. As mollusks are capable of filtering up to two liters of water a day, the 37.8 liter tanks are filtered at a rate of 10 liters a day. A successful trial of bivalves reducing and

  14. "1H NMR-based metabolomics reveals sub-lethal toxicity of a mixture of diabetic and lipid-regulating pharmaceuticals on amphibian larvae

    International Nuclear Information System (INIS)

    Melvin, Steven D.; Habener, Leesa J.; Leusch, Frederic D.L.; Carroll, Anthony R.

    2017-01-01

    Highlights: • Pharmaceutical pollutants are a concern for eliciting adverse effects in wildlife. • Diabetes and lipid regulating drugs are widely used and poorly removed from sewage. • We explored the toxicity of a mixture of metformin, atorvastatin and bezafibrate on tadpoles. • Exposure caused increased growth and development but no effects on lipids or cholesterol. • "1H NMR-based metabolomics reveal increased lactic acid and BCAAs in exposed animals. - Abstract: Pharmaceuticals are widely used for the treatment of various physical and psychological ailments. Due to incomplete removal during sewage treatment many pharmaceuticals are frequently detected in aquatic waterways at trace concentrations. The diversity of pharmaceutical contaminants and potential for complex mixtures to occur makes it very difficult to predict the toxicity of these compounds on wildlife, and robust methods are therefore needed to explore sub-lethal effects. Metabolic syndrome is one of the most widespread health concerns currently facing the human population, and various drugs, including anti-diabetic medications and lipid- and cholesterol-lowering fibrates and statins, are widely prescribed as treatment. In this study, we exposed striped marsh frog (Limnodynastes peronii) tadpoles to a mixture of the drugs metformin, atorvastatin and bezafibrate at 0.5, 5, 50 and 500 μg/L to explore possible effects on growth and development, energy reserves (triglycerides and cholesterol), and profiles of small polar metabolites extracted from hepatic tissues. It was hypothesised that exposure would result in a general reduction in energy reserves, and that this would subsequently correspond with reduced growth and development. Responses differed from expected outcomes based on the known mechanisms of these compounds in humans, with no changes to hepatic triglycerides or cholesterol and a general increase in mass and condition with increasing exposure concentration. Deviation from the

  15. Unwarranted claims of drug efficacy in pharmaceutical sales visits: are drugs approved on the basis of surrogate outcomes promoted appropriately?

    Science.gov (United States)

    Habibi, Roojin; Lexchin, Joel; Mintzes, Barbara; Holbrook, Anne

    2017-11-01

    This study compares physicians' recall of the claims of benefits on cardiovascular disease and diabetes made by pharmaceutical sales representatives for drugs approved on the basis of a surrogate outcome, i.e., an off-label claim, compared with those approved on the basis of a serious morbidity or mortality (clinical) outcome. Physicians in primary care practices in Montreal, Vancouver, Sacramento and Toulouse, who saw sales representatives as part of their usual practice and served a non-referral population, were contacted in blocks of 25 from a randomized list of all physicians practising in the relevant metropolitan area. We compared how frequently physicians reported that sales reps made claims of serious morbidity or mortality (clinically meaningful) benefits for drugs approved on the basis of surrogate outcomes vs. drugs approved on the basis of clinical outcomes. There were 448 promotions for 58 unique brand name cardiovascular and diabetes drugs. Claims of clinically meaningful benefit were reported in 156 (45%) of the 347 promotions for surrogate outcome drugs, constituting unwarranted efficacy claims, i.e., off-label promotion. Claims of clinical benefit were reported in 72 of the 101 promotions (71%) for drugs approved on the basis of clinical outcomes, adjusted OR = 0.3 (95% CI 0.2, 0.6), P sales visit promotions for drugs approved only on the basis of surrogate outcomes extended beyond the regulator-approved efficacy information for the product in almost half of promotions. Unapproved claims of drug efficacy constitute a form of off-label promotion and merit greater attention from regulators. © 2017 The British Pharmacological Society.

  16. Drug-disease modeling in the pharmaceutical industry - where mechanistic systems pharmacology and statistical pharmacometrics meet.

    Science.gov (United States)

    Helmlinger, Gabriel; Al-Huniti, Nidal; Aksenov, Sergey; Peskov, Kirill; Hallow, Karen M; Chu, Lulu; Boulton, David; Eriksson, Ulf; Hamrén, Bengt; Lambert, Craig; Masson, Eric; Tomkinson, Helen; Stanski, Donald

    2017-11-15

    Modeling & simulation (M&S) methodologies are established quantitative tools, which have proven to be useful in supporting the research, development (R&D), regulatory approval, and marketing of novel therapeutics. Applications of M&S help design efficient studies and interpret their results in context of all available data and knowledge to enable effective decision-making during the R&D process. In this mini-review, we focus on two sets of modeling approaches: population-based models, which are well-established within the pharmaceutical industry today, and fall under the discipline of clinical pharmacometrics (PMX); and systems dynamics models, which encompass a range of models of (patho-)physiology amenable to pharmacological intervention, of signaling pathways in biology, and of substance distribution in the body (today known as physiologically-based pharmacokinetic models) - which today may be collectively referred to as quantitative systems pharmacology models (QSP). We next describe the convergence - or rather selected integration - of PMX and QSP approaches into 'middle-out' drug-disease models, which retain selected mechanistic aspects, while remaining parsimonious, fit-for-purpose, and able to address variability and the testing of covariates. We further propose development opportunities for drug-disease systems models, to increase their utility and applicability throughout the preclinical and clinical spectrum of pharmaceutical R&D. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. The behaviour of pharmaceuticals in anaerobic digester sludge

    OpenAIRE

    Campbell, Alison

    2013-01-01

    Pharmaceuticals are biologically active compounds that may be consumed in hundreds of tonnes per year, and which are excreted into municipal sewerage systems. Many pharmaceuticals persist during sewage treatment, and significant environmental risk has been linked to incomplete removal of pharmaceuticals. Evaluation of this risk is important and should be as representative as possible, taking into consideration all significant exposure routes and removal processes. Sludge treatment processes a...

  18. Analysis of solid-state transformations of pharmaceutical compounds using vibrational spectroscopy

    DEFF Research Database (Denmark)

    Heinz, Andrea; Strachan, Clare J; Gordon, Keith C

    2009-01-01

    OBJECTIVES: Solid-state transformations may occur during any stage of pharmaceutical processing and upon storage of a solid dosage form. Early detection and quantification of these transformations during the manufacture of solid dosage forms is important since the physical form of an active...... pharmaceutical ingredient can significantly influence its processing behaviour, including powder flow and compressibility, and biopharmaceutical properties such as solubility, dissolution rate and bioavailability. KEY FINDINGS: Vibrational spectroscopic techniques such as infrared, near-infrared, Raman and, most...... multivariate approaches where even overlapping spectral bands can be analysed. SUMMARY: This review discusses the applications of different vibrational spectroscopic techniques to detect and monitor solid-state transformations possible for crystalline polymorphs, hydrates and amorphous forms of pharmaceutical...

  19. Analytic Methods Used in Quality Control in a Compounding Pharmacy.

    Science.gov (United States)

    Allen, Loyd V

    2017-01-01

    Analytical testing will no doubt become a more important part of pharmaceutical compounding as the public and regulatory agencies demand increasing documentation of the quality of compounded preparations. Compounding pharmacists must decide what types of testing and what amount of testing to include in their quality-control programs, and whether testing should be done in-house or outsourced. Like pharmaceutical compounding, analytical testing should be performed only by those who are appropriately trained and qualified. This article discusses the analytical methods that are used in quality control in a compounding pharmacy. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

  20. Design of Continuous Crystallizers for Production of Active Pharmaceutical Ingredients

    DEFF Research Database (Denmark)

    Capellades Mendez, Gerard; Christensen, Troels V.

    The production of Active Pharmaceutical Ingredients (APIs) is conducted primarily in batch processes. This manufacturing approach is reinforced by a patent-driven business model and the need to minimize the process development times for newly patented drugs. However, the regulatory and business...... environments are now changing. The increasing costs of drug development, combined with the strict regulations and the competition from generic manufacturers, have pushed pharmaceutical companies to seek cheaper and more sustainable production methods. Transition from batch to Continuous Pharmaceutical...

  1. [AIDS and social justice: pharmaceutical industry and economics].

    Science.gov (United States)

    López Guzmán, José

    2008-01-01

    This article takes a broad look at the complicated framework of relationships between the third world and pharmaceutical companies. In the first part of the work reference is made to the poverty of these countries, their lack of education in terms of health, the scarcity of basic hygiene, and their greatly limited access to medicines, especially those for treating AIDS. The article then proceeds to the issue of the pharmaceutical companies' degree of responsibility for the reduced availability of medicines in certain areas of the world. One of the factors that most limits access to medicines is their price, and many sectors of society propose taking action on the patents of drugs (rescinding or limiting them) in order to lower their price. However, the problem of patent exemption is more complicated than it seems at first glance, and comes with its own risks. If, for lack of funds or the uncertainty concerning a return on the capital invested, pharmaceutical companies discontinue research and development of new drugs, AIDS therapy would worsen. It is imperative and urgent to develop new drugs against the AIDS because of its resistance to the drugs currently available. The article concludes with the pharmaceutical industry's effort to look for possible forms of collaboration with developing countries.

  2. Adsorption of Selected Pharmaceutical Compounds onto Activated Carbon in Dilute Aqueous Solutions Exemplified by Acetaminophen, Diclofenac, and Sulfamethoxazole

    Science.gov (United States)

    Chang, E.-E.; Wan, Jan-Chi; Liang, Chung-Huei; Dai, Yung-Dun; Chiang, Pen-Chi

    2015-01-01

    The adsorption of three pharmaceuticals, namely, acetaminophen, diclofenac, and sulfamethoxazole onto granular activated carbon (GAC), was investigated. To study competitive adsorption, both dynamic and steady-state adsorption experiments were conducted by careful selection of pharmaceuticals with various affinities and molecular size. The effective diffusion coefficient of the adsorbate was increased with decease in particle size of GAC. The adsorption affinity represented as Langmuir was consistent with the ranking of the octanol-water partition coefficient, K ow. The adsorption behavior in binary or tertiary systems could be described by competition adsorption. In the binary system adsorption replacement occurred, under which the adsorbate with the smaller K ow was replaced by the one with larger K ow. Results also indicated that portion of the micropores could be occupied only by the small target compound, but not the larger adsorbates. In multiple-component systems the competition adsorption might significantly be affected by the macropores and less by the meso- or micropores. PMID:26078989

  3. Influence of dietary iodine on drug-induced hypothyrodism in the rat.

    Science.gov (United States)

    Beyssen, M L; Lagorce, J F; Cledat, D; Buxeraud, J

    1999-06-01

    Several compounds of pharmaceutical importance from a variety of chemical families, for example chlorpromazine and clomipramine, have been found to form charge-transfer complexes with iodine. We have investigated the influence of dietary iodine on thyroid-gland dysfunction induced by clomipramine, chlorpromazine or 2-thiazoline-2-thiol. We suggest that iodine is partly diverted from its metabolic pathway by complexation with drugs, and so the urinary concentration of iodide is increased. Both chlorpromazine and clomipramine, at doses which do not inhibit thyroperoxidase, enhanced urinary iodine excretion when dietary iodine was restricted (3.944+/-0.96 microg/day for chlorpromazine-tested rats, 3.43+/-1.33 microg/day for clomipramine-tested rats, compared with 2.34+/-0.11 microg/day in control rats). Concurrently, these pharmaceutical compounds increased the level of free thyroid-stimulating hormone (TSH) in comparison with controls and induced histological modifications in, and enlargement of, the thyroid gland. We have demonstrated that drug-induced loss of iodine in the urine was associated with antithyroid action when iodine intake was limited.

  4. Applications of Polymers as Pharmaceutical Excipients in Solid Oral Dosage Forms.

    Science.gov (United States)

    Debotton, Nir; Dahan, Arik

    2017-01-01

    Over the last few decades, polymers have been extensively used as pharmaceutical excipients in drug delivery systems. Pharmaceutical polymers evolved from being simply used as gelatin shells comprising capsule to offering great formulation advantages including enabling controlled/slow release and specific targeting of drugs to the site(s) of action (the "magic bullets" concept), hence hold a significant clinical promise. Oral administration of solid dosage forms (e.g., tablets and capsules) is the most common and convenient route of drug administration. When formulating challenging molecules into solid oral dosage forms, polymeric pharmaceutical excipients permit masking undesired physicochemical properties of drugs and consequently, altering their pharmacokinetic profiles to improve the therapeutic effect. As a result, the number of synthetic and natural polymers available commercially as pharmaceutical excipients has increased dramatically, offering potential solutions to various difficulties. For instance, the different polymers may allow increased solubility, swellability, viscosity, biodegradability, advanced coatings, pH dependency, mucodhesion, and inhibition of crystallization. The aim of this article is to provide a wide angle prospect of the different uses of pharmaceutical polymers in solid oral dosage forms. The various types of polymeric excipients are presented, and their distinctive role in oral drug delivery is emphasized. The comprehensive know-how provided in this article may allow scientists to use these polymeric excipients rationally, to fully exploit their different features and potential influence on drug delivery, with the overall aim of making better drug products. © 2016 Wiley Periodicals, Inc.

  5. Adsorption of selected pharmaceuticals and an endocrine disrupting compound by granular activated carbon. 2. Model prediction

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Z.; Peldszus, S.; Huck, P.M. [University of Waterloo, Waterloo, ON (Canada). NSERC Chair in Water Treatment

    2009-03-01

    The adsorption of two representative pharmaceutically active compounds (PhACs) naproxen and carbamazepine and one endocrine disrupting compound (EDC) nonylphenol was studied in pilot-scale granular activated carbon (GAC) adsorbers using post-sedimentation (PS) water from a full-scale drinking water treatment plant. The GAC adsorbents were coal-based Calgon Filtrasorb 400 and coconut shell-based PICA CTIF TE. Acidic naproxen broke through fastest while nonylphenol was removed best, which was consistent with the degree to which fouling affected compound removals. Model predictions and experimental data were generally in good agreement for all three compounds, which demonstrated the effectiveness and robustness of the pore and surface diffusion model (PSDM) used in combination with the time-variable parameter approach for predicting removals at environmentally relevant concentrations (i.e., ng/L range). Sensitivity analyses suggested that accurate determination of film diffusion coefficients was critical for predicting breakthrough for naproxen and carbamazepine, in particular when high removals are targeted. Model simulations demonstrated that GAC carbon usage rates (CURs) for naproxen were substantially influenced by the empty bed contact time (EBCT) at the investigated conditions. Model-based comparisons between GAC CURs and minimum CURs for powdered activated carbon (PAC) applications suggested that PAC would be most appropriate for achieving 90% removal of naproxen, whereas GAC would be more suitable for nonylphenol. 25 refs., 4 figs., 1 tab.

  6. Journal of Pharmaceutical and Allied Sciences

    African Journals Online (AJOL)

    The Journal of Pharmaceutical and Allied Sciences (JOPHAS) publishes original scientific and technical research works carried out on drugs and drug-related products, within and outside Nigeria in the fields of pharmacy, microbiology, biochemistry, biotechnology, pharmacology, medical sciences and veterinary medicine.

  7. Network on veterinary medicines initiated by the European Federation For Pharmaceutical Sciences.

    Science.gov (United States)

    Mochel, J P; Tyden, E; Hellmann, K; Vendrig, J C; Şenel, S; Dencker, L; Cristina, R T; Linden, H; Schmerold, I

    2018-06-01

    The European Federation for Pharmaceutical Sciences (EUFEPS) was founded 25 years ago by more than 20 national pharmaceutical societies and faculty members. As a pan-European organization, it brings together pharmaceutical societies as well as academic, industrial and regulatory scientists engaged in drug research and development, drug regulation and education of professionals working in these fields. EUFEPS represents pharmaceutical sciences in Europe and is recognized as such by both the European Commission and the European Medicines Agency. EUFEPS cooperates with the European Federation of Pharmaceutical Industries and other European organizations and maintains global connections with agencies such as the US Food and Drug Administration and the American Association of Pharmaceutical Scientists. EUFEPS has established specified networks forming the basis of its activities. The creation of a Network on Veterinary Medicines is prompted by the manifold problems resulting from the use of veterinary drugs and its inherent interconnections with human medicine, environmental and public health. A long-term goal of this initiative was to expand the spectrum of available therapeutics for use in animals, including the development of innovative delivery systems. © 2017 John Wiley & Sons Ltd.

  8. "The same thing in a different box": similarity and difference in pharmaceutical sex hormone consumption and marketing.

    Science.gov (United States)

    Sanabria, Emilia

    2014-12-01

    The contraceptive pill has given way to a multitude of products, kinds of packaging, and modes of administration. This article draws on work on the pharmaceutical copy, extending the analysis to differentiating between forms of administration for contraceptive medicines as well as between brand-name drugs, generics, and similares, as they are known in Brazil. It explores how Brazilian prescribers and users-within the divergent structural constraints afforded by private and public health-apprehend and negotiate distinctions between the drugs available to them. This ethnographic account of hormone use reveals new fault lines through which the pharmakon exerts its influence. The attention that industry places on pharmacodynamics as it produces new products from similar compounds suggests that pharmaceutical effects are at once symbolic and real. The article concludes with a reflection on the future of the generic form in a field increasingly crowded by branded copies. © 2014 by the American Anthropological Association.

  9. Pharmaceutically active compounds and endocrine disrupting chemicals in water, sediments and mollusks in mangrove ecosystems from Singapore.

    Science.gov (United States)

    Bayen, Stéphane; Estrada, Elvagris Segovia; Juhel, Guillaume; Kit, Lee Wei; Kelly, Barry C

    2016-08-30

    This study investigated the occurrence of bisphenol A (BPA), atrazine and selected pharmaceutically active compounds (PhACs) in mangrove habitats in Singapore in 2012-2013, using multiple tools (sediment sampling, POCIS and filter feeder molluscs). Using POCIS, the same suite of contaminants (atrazine, BPA and eleven PhACs) was detected in mangrove waters in 28-days deployments in both 2012 and 2013. POCIS concentrations ranged from pg/L to μg/L. Caffeine, BPA, carbamazepine, E1, triclosan, sulfamerazine, sulfamethazine, and lincomycin were also detected in mangrove sediments from the low pg/g dw (e.g. carbamazepine) to ng/g dw (e.g. BPA). The detection of caffeine, carbamazepine, BPA, sulfamethoxazole or lincomycin in bivalve tissues also showed that these chemicals are bioavailable in the mangrove habitat. Since there are some indications that some pharmaceutically active substances may be biologically active in the low ppb range in marine species, further assessment should be completed based on ecotoxicological data specific to mangrove species. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Analysis of Trace Pharmaceuticals and Related Compounds in Municipal Wastewaters by Preconcentration, Chromatography, Derivatization, and Separation Methods

    Directory of Open Access Journals (Sweden)

    Petra Camilla Lindholm

    2014-05-01

    Full Text Available A significant portion of pharmaceuticals and other organic chemicals consumed by people and animals are released into municipal wastewater treatment plants. Most of them are degraded during the wastewater treatment processes, but some of them degrade only partially and may be widely transported and dispersed into the aquatic environment. This is why efficient and fast analytical methods are needed for detection of organic compounds in wastewaters at trace levels. Because wastewaters often consist of complex matrices and high-molecular mass materials, e.g., lignocellulosic biomass, which may bring challenges to the sample preparation procedures, efficient pre-concentration methods such as solid phase extraction (SPE solid phase microextraction (SPME, or single drop microextraction (SDME are needed. The most common analysis methods are gas chromatography (GC and liquid chromatography (LC coupled with tandem mass spectrometry (MS/MS. The aim of this review is to give an overview of chromatographic and spectroscopic methods when characterizing low- and medium-molecular weight organic pollutants, mainly focusing on pharmaceuticals, biocides, and personal care products in environmental matrices.

  11. The impacts of pharmaceutical drugs under ocean acidification: New data on single and combined long-term effects of carbamazepine on Scrobicularia plana.

    Science.gov (United States)

    Freitas, Rosa; Almeida, Ângela; Calisto, Vânia; Velez, Cátia; Moreira, Anthony; Schneider, Rudolf J; Esteves, Valdemar I; Wrona, Frederick J; Figueira, Etelvina; Soares, Amadeu M V M

    2016-01-15

    Ocean acidification and increasing discharges of pharmaceutical contaminants into aquatic systems are among key and/or emerging drivers of environmental change affecting marine ecosystems. A growing body of evidence demonstrates that ocean acidification can have direct and indirect impacts on marine organisms although combined effects with other stressors, namely with pharmaceuticals, have received very little attention to date. The present study aimed to evaluate the impacts of the pharmaceutical drug Carbamazepine and pH 7.1, acting alone and in combination, on the clam Scrobicularia plana. For this, a long-term exposure (28 days)was conducted and a set of oxidative stress markers was investigated. The results obtained showed that S. plana was able to develop mechanisms to prevent oxidative damage when under low pH for a long period, presenting higher survival when exposed to this stressor compared to CBZ or the combination of CBZ with pH 7.1. Furthermore, the toxicity of CBZ on S. plana was synergistically increased under ocean acidification conditions (CBZ + pH 7.1): specimens survival was reduced and oxidative stress was enhanced when compared to single exposures. These findings add to the growing body of evidence that ocean acidification will act to increase the toxicity of CBZ to marine organisms,which has clear implications for coastal benthic ecosystems suffering chronic pollution from pharmaceutical drugs.

  12. {sup 1}H NMR-based metabolomics reveals sub-lethal toxicity of a mixture of diabetic and lipid-regulating pharmaceuticals on amphibian larvae

    Energy Technology Data Exchange (ETDEWEB)

    Melvin, Steven D., E-mail: s.melvin@griffith.edu.au [Australian Rivers Institute, Griffith University, Southport, QLD 4222 (Australia); Habener, Leesa J. [Griffith School of Environment, Griffith University, Southport, QLD 4222 (Australia); Leusch, Frederic D.L. [Australian Rivers Institute, Griffith University, Southport, QLD 4222 (Australia); Griffith School of Environment, Griffith University, Southport, QLD 4222 (Australia); Carroll, Anthony R. [Griffith School of Environment, Griffith University, Southport, QLD 4222 (Australia)

    2017-03-15

    Highlights: • Pharmaceutical pollutants are a concern for eliciting adverse effects in wildlife. • Diabetes and lipid regulating drugs are widely used and poorly removed from sewage. • We explored the toxicity of a mixture of metformin, atorvastatin and bezafibrate on tadpoles. • Exposure caused increased growth and development but no effects on lipids or cholesterol. • {sup 1}H NMR-based metabolomics reveal increased lactic acid and BCAAs in exposed animals. - Abstract: Pharmaceuticals are widely used for the treatment of various physical and psychological ailments. Due to incomplete removal during sewage treatment many pharmaceuticals are frequently detected in aquatic waterways at trace concentrations. The diversity of pharmaceutical contaminants and potential for complex mixtures to occur makes it very difficult to predict the toxicity of these compounds on wildlife, and robust methods are therefore needed to explore sub-lethal effects. Metabolic syndrome is one of the most widespread health concerns currently facing the human population, and various drugs, including anti-diabetic medications and lipid- and cholesterol-lowering fibrates and statins, are widely prescribed as treatment. In this study, we exposed striped marsh frog (Limnodynastes peronii) tadpoles to a mixture of the drugs metformin, atorvastatin and bezafibrate at 0.5, 5, 50 and 500 μg/L to explore possible effects on growth and development, energy reserves (triglycerides and cholesterol), and profiles of small polar metabolites extracted from hepatic tissues. It was hypothesised that exposure would result in a general reduction in energy reserves, and that this would subsequently correspond with reduced growth and development. Responses differed from expected outcomes based on the known mechanisms of these compounds in humans, with no changes to hepatic triglycerides or cholesterol and a general increase in mass and condition with increasing exposure concentration. Deviation from the

  13. Early repositioning through compound set enrichment analysis: a knowledge-recycling strategy.

    Science.gov (United States)

    Temesi, Gergely; Bolgár, Bence; Arany, Adám; Szalai, Csaba; Antal, Péter; Mátyus, Péter

    2014-04-01

    Despite famous serendipitous drug repositioning success stories, systematic projects have not yet delivered the expected results. However, repositioning technologies are gaining ground in different phases of routine drug development, together with new adaptive strategies. We demonstrate the power of the compound information pool, the ever-growing heterogeneous information repertoire of approved drugs and candidates as an invaluable catalyzer in this transition. Systematic, computational utilization of this information pool for candidates in early phases is an open research problem; we propose a novel application of the enrichment analysis statistical framework for fusion of this information pool, specifically for the prediction of indications. Pharmaceutical consequences are formulated for a systematic and continuous knowledge recycling strategy, utilizing this information pool throughout the drug-discovery pipeline.

  14. Application of ion chromatography in pharmaceutical and drug analysis.

    Science.gov (United States)

    Jenke, Dennis

    2011-08-01

    Ion chromatography (IC) has developed and matured into an important analytical methodology in a number of diverse applications and industries, including pharmaceuticals. This manuscript provides a review of IC applications for the determinations of active and inactive ingredients, excipients, degradation products, and impurities relevant to pharmaceutical analyses and thus serves as a resource for investigators looking for insights into the use of the IC methodology in this field of application.

  15. Safe handling of cytotoxic compounds in a biopharmaceutical environment.

    Science.gov (United States)

    Hensgen, Miriam I; Stump, Bernhard

    2013-01-01

    Handling cytotoxic drugs such as antibody-drug conjugates (ADCs) in a biopharmaceutical environment represents a challenge based on the potency of the compounds. These derivatives are dangerous to humans if they accidentally get in contact with the skin, are inhaled, or are ingested, either as pure compounds in their solid state or as a solution dissolved in a co-solvent. Any contamination of people involved in the manufacturing process has to be avoided. On the other hand, biopharmaceuticals need to be protected simultaneously against any contamination from the manufacturing personnel. Therefore, a tailor-made work environment is mandatory in order to manufacture ADCs. This asks for appropriate technical equipment to keep potential hazardous substances contained. In addition, clearly defined working procedures based on risk assessments as well as proper training for all personnel involved in the manufacturing process are needed to safely handle these highly potent pharmaceuticals.

  16. Bacteriological quality of some pharmaceutical products marketed ...

    African Journals Online (AJOL)

    Bacteriological quality of some pharmaceutical products purchased from open markets, buses and drug stores in Uyo metropolis was studied in order to determine the level of contamination of the drugs. The drug samples examined were Tetracycline capsules, Paracetamol tablets, Ampicillin capsules, Chloroquine tablets, ...

  17. Does Increased Spending on Pharmaceutical Marketing Inhibit Pioneering Innovation?

    Science.gov (United States)

    Arnold, Denis G; Troyer, Jennifer L

    2016-04-01

    The pharmaceutical industry has been criticized for developing and aggressively marketing drugs that do not provide significant health benefits relative to existing drugs but retain the benefits of patent protection. Critics argue that drug marketing increases health care expenditures and provides a disincentive for pioneering drug innovation. However, evidence that marketing expenditures have any relationship to new drug approvals has been anecdotal. We hypothesized that, at publicly traded pharmaceutical firms, increased marketing expenditures will result in a reduced volume of pioneering new drugs in comparison to less innovative new drugs. We also hypothesized that additional research and development spending will result in an increased volume of pioneering new drugs in comparison to less innovative drugs. Results confirm our hypotheses. Specific policy recommendations for altering firms' incentives for the development of pioneering drugs are provided. Copyright © 2016 by Duke University Press.

  18. [Do pharmaceutical waste and drug residue pose a risk to public health?].

    Science.gov (United States)

    Haguenoer, Jean-Marie

    2010-01-01

    Recently, awareness has developed of the environmental consequences of drug waste and disposal. These residues are identified as coming from either diffuse sources, the most significant of which is via the discharge of these residues in urine and feces, and thus the sewage system and water contains these drug remnants and their metabolites, or from point sources, sometimes with very high levels of concentration in waste from chemical and pharmaceutical industries, health care settings, but also from intensive livestock farming and aquaculture. Depending on their physical chemistry properties, these substances are more or less naturally biodegradable and easily treated in sewage purification plants. The effectiveness of these treatment processes is highly random and unpredictable, but is overall around 60%, nevertheless with variations of 2-99% according to the molecules. The silt from these treatment plants, sometimes very rich in lipophilic substances is on occasion reused for agricultural application as fertilizer, paving the way for a possible contamination of crops. Furthermore, the use of veterinary drugs in animals can lead to soil contamination either directly or through manure and slurry. The contamination can equally reach and affect surface water, groundwater and sometimes the water intended for human consumption. The National academy of Pharmacy has established some general recommendations on the proper use of drugs, environmental monitoring and surveillance, risk assessment for humans and the environment, prevention and the need for prevention. Several categories of drugs are more worrying: cancer treatments, antibiotics as well as transfers of anti-bio-resistance, and hormonal derivatives which has been previously demonstrated to contribute, along with other molecules, to detrimental effects on endocrines.

  19. Open Innovation Drug Discovery (OIDD): a potential path to novel therapeutic chemical space.

    Science.gov (United States)

    Alvim-Gaston, Maria; Grese, Timothy; Mahoui, Abdelaziz; Palkowitz, Alan D; Pineiro-Nunez, Marta; Watson, Ian

    2014-01-01

    The continued development of computational and synthetic methods has enabled the enumeration or preparation of a nearly endless universe of chemical structures. Nevertheless, the ability of this chemical universe to deliver small molecules that can both modulate biological targets and have drug-like physicochemical properties continues to be a topic of interest to the pharmaceutical industry and academic researchers alike. The chemical space described by public, commercial, in-house and virtual compound collections has been interrogated by multiple approaches including biochemical, cellular and virtual screening, diversity analysis, and in-silico profiling. However, current drugs and known chemical probes derived from these efforts are contained within a remarkably small volume of the predicted chemical space. Access to more diverse classes of chemical scaffolds that maintain the properties relevant for drug discovery is certainly needed to meet the increasing demands for pharmaceutical innovation. The Lilly Open Innovation Drug Discovery platform (OIDD) was designed to tackle barriers to innovation through the identification of novel molecules active in relevant disease biology models. In this article we will discuss several computational approaches towards describing novel, biologically active, drug-like chemical space and illustrate how the OIDD program may facilitate access to previously untapped molecules that may aid in the search for innovative pharmaceuticals.

  20. A model of the prescription-pharmaceutical sales process

    Directory of Open Access Journals (Sweden)

    Michael Stros

    2018-06-01

    Full Text Available The purpose of this paper is to determine the factors in marketing most relevant to achieving pharmaceutical sales success and their interrelations, as well as providing a prescription-pharmaceuticals sales process model. This will enable scholars to obtain a better understanding of the marketing process for prescription pharmaceuticals, as well as enabling marketers to apply more efficient marketing approaches. The study uses a unique data set, combining primary data and secondary data from the Swiss prescription-pharmaceuticals market. The data is analysed using a multiple-regression based model. A multi-level data structure is found, suggesting that factors concerning the specific brand and also the pharmaceutical substance itself are relevant to sales success. It is revealed that the factors most relevant to sales success are: order of market entry, perceived product-quality, average price, and marketing expenditures, leading to practical recommendations for scholars and marketing professionals. The study focuses only on the Swiss prescription-pharmaceuticals market, investigating five medical drug classes. The assumption is made that these results can be generalised to similar markets and drug classes. The study develops a conceptual prescription-pharmaceuticals sales-process model; offers practical guidelines and a good basis for further scholarly research are provided; and identifies several research gaps by giving proposals for future research.

  1. BIOTECHNOLOGY, NANOTECHNOLOGY, AND PHARMACOGENOMICS AND PHARMACEUTICAL COMPOUNDING, PART 2.

    Science.gov (United States)

    Allen, Loyd V

    2015-01-01

    This article, which represents part 2 of a two part article, completes the discussion on the rapidly changing world of pharmaceuticals as biotechnology continues to grow and nanotechnology appears on the horizon.

  2. 'Linkage' pharmaceutical evergreening in Canada and Australia

    Science.gov (United States)

    Faunce, Thomas A; Lexchin, Joel

    2007-01-01

    'Evergreening' is not a formal concept of patent law. It is best understood as a social idea used to refer to the myriad ways in which pharmaceutical patent owners utilise the law and related regulatory processes to extend their high rent-earning intellectual monopoly privileges, particularly over highly profitable (either in total sales volume or price per unit) 'blockbuster' drugs. Thus, while the courts are an instrument frequently used by pharmaceutical brand name manufacturers to prolong their patent royalties, 'evergreening' is rarely mentioned explicitly by judges in patent protection cases. The term usually refers to threats made to competitors about a brand-name manufacturer's tactical use of pharmaceutical patents (including over uses, delivery systems and even packaging), not to extension of any particular patent over an active product ingredient. This article focuses in particular on the 'evergreening' potential of so-called 'linkage' provisions, imposed on the regulatory (safety, quality and efficacy) approval systems for generic pharmaceuticals of Canada and Australia, by specific articles in trade agreements with the US. These 'linkage' provisions have also recently appeared in the Korea-US Free Trade Agreement (KORUSFTA). They require such drug regulators to facilitate notification of, or even prevent, any potential patent infringement by a generic pharmaceutical manufacturer. This article explores the regulatory lessons to be learnt from Canada's and Australia's shared experience in terms of minimizing potential adverse impacts of such 'linkage evergreening' provisions on drug costs and thereby potentially on citizen's access to affordable, essential medicines. PMID:17543113

  3. Heterogeneous photo-Fenton treatment for the reduction of pharmaceutical contamination in Madrid rivers and ecotoxicological evaluation by a miniaturized fern spores bioassay.

    Science.gov (United States)

    Rodríguez-Gil, José L; Catalá, Myriam; Alonso, Silvia González; Maroto, Raúl Romo; Valcárcel, Yolanda; Segura, Yolanda; Molina, Raúl; Melero, Juan A; Martínez, Fernando

    2010-06-01

    Fifty-six pharmaceuticals of various chemical groups, such as anti-inflammatory, antibacterial and cardiovascular drugs, were detected in four selected river waters receiving sewage effluents in the Community of Madrid (Spain). A promising approach for the degradation of those residues is the application of a photo-Fenton treatment. Several new bioassays using fern spores were employed for the evaluation of acute and chronic toxicity based on mitochondrial activity, DNA and chlorophyll quantifications of as-received river water and photo-Fenton-treated samples. photo-Fenton treatment provided a high degree of total organic carbon mineralization with up to 70% reduction for river water samples. In addition, the elimination of most of the studied pharmaceutical compounds was confirmed. A few compounds, however (salicylic acid, ofloxacin, caffeine, cotinine and nicotine), seemed more resistant, with after-treatment concentrations between 4 and 44ngL(-1). Nicotine showed the most refractory behaviour with concentrations ranging from 29 to 224ngL(-1) for treated samples. Photo-Fenton treatment yielded a significant decrease in acute and chronic toxicity, even though some residual toxicity remained after treatment. This fact seemed to be related to the presence of toxicants in the water matrix, probably of inorganic nature, rather than the toxic effect of the studied pharmaceutical compounds, as revealed by the effective removal of these compounds and high TOC mineralization of photo-Fenton treatments.

  4. Aspects of research and development contract terms in the bio/pharmaceutical sector.

    Science.gov (United States)

    Banerjee, Tannista

    2012-01-01

    The cost of new drug development is increasing every year. Pharmaceutical companies use R&D joint ventures, mergers, and outsource different stages of pharmaceutical R&D activities for a faster and cost minimizing method of innovation. Pharmaceutical companies outsource R&D activities to independent small biotech or pharmaceutical companies that specialize in different stages of pharmaceutical R&D. This chapter examines the determinants of the payment structure of research contracts between large bio/pharmaceutical companies and specialized research firms. Determinants of R&D contracts are analyzed using detailed R&D contract data between bio/pharmaceutical companies and independent research firms for 10 years. A multinomial logit model is used in order to understand the determinants of three different types of contracts; royalty contracts, fixed payment contracts, and the mixed contracts. Under uncertainty, the likelihood of a royalty contract rises for the early stages of the research and with the patent stock of the research firm. It is more likely to observe both royalty and fixed payment if the pharmaceutical client has past contracts with the same research firm. The results also suggest that if Food and Drug Administration (FDA) is more stringent in any disease area in reviewing the new drug application, then the likelihood of signing pure royalty contract decreases. Understanding the nature of R&D contracts and the effects of FDA's behavior on the pharmaceutical R&D contract is important because these contracts not only affect the cost of new drug invention but also the quality and the rate of invention. VALUE: Results are useful for both the pharmaceutical companies and the economic/business researchers.

  5. Nanoprecipitation process: From encapsulation to drug delivery.

    Science.gov (United States)

    Martínez Rivas, Claudia Janeth; Tarhini, Mohamad; Badri, Waisudin; Miladi, Karim; Greige-Gerges, Hélène; Nazari, Qand Agha; Galindo Rodríguez, Sergio Arturo; Román, Rocío Álvarez; Fessi, Hatem; Elaissari, Abdelhamid

    2017-10-30

    Drugs encapsulation is a suitable strategy in order to cope with the limitations of conventional dosage forms such as unsuitable bioavailability, stability, taste, and odor. Nanoprecipitation technique has been used in the pharmaceutical and agricultural research as clean alternative for other drug carrier formulations. This technique is based on precipitation mechanism. Polymer precipitation occurs after the addition of a non-solvent to a polymer solution in four steps mechanism: supersaturation, nucleation, growth by condensation, and growth by coagulation that leads to the formation of polymer nanoparticles or aggregates. The scale-up of laboratory-based nanoprecipitation method shows a good reproducibility. In addition, flash nanoprecipitation is a good strategy for industrial scale production of nanoparticles. Nanoprecipitation is usually used for encapsulation of hydrophobic or hydrophilic compounds. Nanoprecipitation was also shown to be a good alternative for the encapsulation of natural compounds. As a whole, process and formulation related parameters in nanoprecipitation technique have critical effect on nanoparticles characteristics. Biodegradable or non-biodegradable polymers have been used for the preparation of nanoparticles intended to in vivo studies. Literature studies have demonstrated the biodistribution of the active loaded nanoparticles in different organs after administration via various routes. In general, in vitro drug release from nanoparticles prepared by nanoprecipitation includes two phases: a first phase of "burst release" which is followed by a second phase of prolonged release. Moreover, many encapsulated active molecules have been commercialized in the pharmaceutical market. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Drugs for Neglected Diseases initiative model of drug development for neglected diseases: current status and future challenges.

    Science.gov (United States)

    Ioset, Jean-Robert; Chang, Shing

    2011-09-01

    The Drugs for Neglected Diseases initiative (DNDi) is a patients' needs-driven organization committed to the development of new treatments for neglected diseases. Created in 2003, DNDi has delivered four improved treatments for malaria, sleeping sickness and visceral leishmaniasis. A main DNDi challenge is to build a solid R&D portfolio for neglected diseases and to deliver preclinical candidates in a timely manner using an original model based on partnership. To address this challenge DNDi has remodeled its discovery activities from a project-based academic-bound network to a fully integrated process-oriented platform in close collaboration with pharmaceutical companies. This discovery platform relies on dedicated screening capacity and lead-optimization consortia supported by a pragmatic, structured and pharmaceutical-focused compound sourcing strategy.

  7. Improved removal of estrogenic and pharmaceutical compounds in sewage effluent by full scale granular activated carbon: impact on receiving river water.

    Science.gov (United States)

    Grover, D P; Zhou, J L; Frickers, P E; Readman, J W

    2011-01-30

    Sewage effluents are widely recognised as the main source of emerging contaminants, such as endocrine disrupting chemicals (EDCs) and pharmaceuticals in surface waters. A full-scale granular activated carbon (GAC) plant has been installed as an advanced technology for the removal of these contaminants, in a major sewage treatment works (STW) in South-West England as part of the UK National Demonstration Programme for EDCs. This study presented for the first time, an assessment of the impact of a recently commissioned, post-tertiary GAC plant in the removal of emerging contaminants in a working STW. Through regular sampling followed by solid-phase extraction and analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS), a significant reduction in the concentrations of steroidal estrogens was observed (>43-64%). In addition, significant reductions were observed for many of the pharmaceutical compounds such as mebeverine (84-99%), although the reduction was less dramatic for some of the more widely used pharmaceuticals analysed, including carbamazepine and propranolol (17-23%). Copyright © 2010 Elsevier B.V. All rights reserved.

  8. Paving roads for new drugs in oncology.

    Science.gov (United States)

    Zaenker, Kurt S; Entschladen, Frank

    2009-06-01

    Low productivity and the escalating costs of drug development have been well documented over the past years. A fraction of new pre-clinical compounds successfully pass experimental test batteries, and less than 10% of these compounds that enter clinical trials ultimately make it to the market. These challenges in the "critical path" of drug development will be discussed for drugs in the field of oncology, regarding the i) the impact of FDA and EMEA guidelines, and ii) microdosing studies/phase 0 trials before a drug enters phase I to III, to inform drug development, compressing drug development timelines and decision-making for continuation into clinical trials. Moreover, this review should embark on i) how to find new key molecules involved in life-and-death decision of a cell, how ii) old drugs will have a revival for new indications, because of novel information for their mode of action, and iii) how the revolutionary advances - high-throughput technologies, gene therapy and the deciphering of the human genome - do have their potential to develop personalized therapy. Therapy has progressed from an age of administering herbal remedies and organ extracts to an era of meticulously planned drug discovery, when pharmaceutical industry was born in a Western understanding. The relevant patents are discussed.

  9. The occurrence and distribution of pharmaceutical compounds in the effluents of a major sewage treatment plant in Northern Taiwan and the receiving coastal waters

    International Nuclear Information System (INIS)

    Fang, Tien-Hsi; Nan, Fan-Hua; Chin, Tzong-Shean; Feng, Hui-Min

    2012-01-01

    The pharmaceutical residues in waste water from the largest sewage treatment plant (STP) in Northern Taiwan and in seawater around the effluent discharged area were determined. An environmental risk assessment for the marine environment was conducted based on the environment risk quotient (ERQ). The concentrations of the analyzed compounds in STP influent and effluent were generally higher than those found in coastal seawater. Relatively higher values were found at the estuarine mouth and the discharged area, suggesting that the STP effluent is a point source. The removal efficiency and half life of the analyzed compounds were 6.3–46.8% and 3–18 days, respectively. The ERQ value theoretical calculation was generally greater than 1. However, when the measured concentrations replaced the predicated concentrations, the ERQ values were considerably lower than 1. Therefore, our results call for a re-evaluation of the risks posed by pharmaceuticals to coastal marine ecosystems in Northern Taiwan.

  10. PRINTING TECHNIQUES: RECENT DEVELOPMENTS IN PHARMACEUTICAL TECHNOLOGY.

    Science.gov (United States)

    Jamroz, Witold; Kurek, Mateusz; Lyszczarz, Ewelina; Brniak, Witold; Jachowicz, Renata

    2017-05-01

    In the last few years there has been a huge progress in a development of printing techniques and their application in pharmaceutical sciences and particularly in the pharmaceutical technology. The variety of printing methods makes it necessary to systemize them, explain the principles of operation, and specify the possibilities of their use in pharmaceutical technology. This paper aims to review the printing techniques used in a drug development process. The growing interest in 2D and 3D printing methods results in continuously increasing number of scientific papers. Introduction of the first printed drug Spritam@ to the market seems to be a milestone of the 3D printing development. Thus, a particular aim of this review is to show the latest achievements of the researchers in the field of the printing medicines.

  11. Refining stability and dissolution rate of amorphous drug formulations

    DEFF Research Database (Denmark)

    Grohganz, Holger; Priemel, Petra A; Löbmann, Korbinian

    2014-01-01

    Introduction: Poor aqueous solubility of active pharmaceutical ingredients (APIs) is one of the main challenges in the development of new small molecular drugs. Additionally, the proportion of poorly soluble drugs among new chemical entities is increasing. The transfer of a crystalline drug to its...... and on the interaction of APIs with small molecular compounds rather than polymers. Finally, in situ formation of an amorphous form might be an option to avoid storage problems altogether. Expert opinion: The diversity of poorly soluble APIs formulated in an amorphous drug delivery system will require different...... approaches for their stabilisation. Thus, increased focus on emerging techniques can be expected and a rational approach to decide the correct formulation is needed....

  12. HOW ADVERSE DRUG-REACTIONS CAN PLAY A ROLE IN INNOVATIVE DRUG RESEARCH - SIMILARITIES IN ADVERSE DRUG REACTION PROFILES OF CAPTOPRIL AND PENICILLAMINE

    NARCIS (Netherlands)

    RIKKEN, F; VOS, R

    1995-01-01

    We describe how adverse drug reactions (ADRs) can play an important role in pharmaceutical research and drug development. Not only do ADRs represent the risks and drawbacks associated with drugs but they can also be related to other knowledge available in pharmaceutical and medical research. We

  13. Application of a simple column-switching ion chromatography technique for removal of matrix interferences and sensitive fluorescence determination of acidic compounds (pharmaceutical drugs) in complex samples.

    Science.gov (United States)

    Muhammad, Nadeem; Subhani, Qamar; Wang, Fenglian; Guo, Dandan; Zhao, Qiming; Wu, Shuchao; Zhu, Yan

    2017-09-15

    This work illustrates the introduction of a simple, rugged and flexible column-switching ion chromatography (IC) technique for an automated on-line QuEChERS extracted samples extracts washing followed by sensitive fluorescence (FLD) determination of five acidic pharmaceutical drugs namely; clofibric acid (CLO), ibuprofen (IBU), aspirin (ASP), naproxen (NAP) and flurobrofen (FLU) in three complex samples (spinach, apple and hospital sewage sludge). An old anion exchange column IonPac ® AS11-HC was utilized as a pre-treatment column for on-line washing of inorganic and organic interferences followed by isocratic separation of five acidic drugs with another anion exchange IonPac ® AS12A analytical column by exploiting the column-switching technique. This novel method exhibited good linearity with correlation coefficients (r 2 ) for all drugs were in the range 0.976-0.996. The limit of detection and quantification of all five acidic drugs were in the range 0.024μg/kg to 8.70μg/kg and 0.082μg/kg to 0.029mg/kg, respectively, and better recoveries in the range 81.17-112.5% with percentage relative standard deviations (RSDs) less than 17.8% were obtained. This on-line sample pre-treatment method showed minimum matrix effect in the range of 0.87-1.25 except for aspirin. This simple rugged and flexible column-switching system required only 28min for maximum elimination of matrices and interferences in three complex samples extracts, isocratic separation of five acidic drugs and for the continuous regeneration of pre-treatment column prior to every subsequent analysis. Finally, this simple automated IC system was appeared so rugged and flexible, which can eliminate and wash out most of interference, impurities and matrices in complex samples, simply by adjusting the NaOH and acetonitrile concentration in washing mobile phase with maximum recoveries of acidic analytes of interest. Copyright © 2017. Published by Elsevier B.V.

  14. EU pharmaceutical expenditure forecast.

    Science.gov (United States)

    Urbinati, Duccio; Rémuzat, Cécile; Kornfeld, Åsa; Vataire, Anne-Lise; Cetinsoy, Laurent; Aballéa, Samuel; Mzoughi, Olfa; Toumi, Mondher

    2014-01-01

    With constant incentives for healthcare payers to contain their pharmaceutical budgets, forecasting has become critically important. Some countries have, for instance, developed pharmaceutical horizon scanning units. The objective of this project was to build a model to assess the net effect of the entrance of new patented medicinal products versus medicinal products going off-patent, with a defined forecast horizon, on selected European Union (EU) Member States' pharmaceutical budgets. This model took into account population ageing, as well as current and future country-specific pricing, reimbursement, and market access policies (the project was performed for the European Commission; see http://ec.europa.eu/health/healthcare/key_documents/index_en.htm). In order to have a representative heterogeneity of EU Member States, the following countries were selected for the analysis: France, Germany, Greece, Hungary, Poland, Portugal, and the United Kingdom. A forecasting period of 5 years (2012-2016) was chosen to assess the net pharmaceutical budget impact. A model for generics and biosimilars was developed for each country. The model estimated a separate and combined effect of the direct and indirect impacts of the patent cliff. A second model, estimating the sales development and the risk of development failure, was developed for new drugs. New drugs were reviewed individually to assess their clinical potential and translate it into commercial potential. The forecast was carried out according to three perspectives (healthcare public payer, society, and manufacturer), and several types of distribution chains (retail, hospital, and combined retail and hospital). Probabilistic and deterministic sensitivity analyses were carried out. According to the model, all countries experienced drug budget reductions except Poland (+€41 million). Savings were expected to be the highest in the United Kingdom (-€9,367 million), France (-€5,589 million), and, far behind them

  15. Novel methodology for pharmaceutical expenditure forecast.

    Science.gov (United States)

    Vataire, Anne-Lise; Cetinsoy, Laurent; Aballéa, Samuel; Rémuzat, Cécile; Urbinati, Duccio; Kornfeld, Åsa; Mzoughi, Olfa; Toumi, Mondher

    2014-01-01

    The value appreciation of new drugs across countries today features a disruption that is making the historical data that are used for forecasting pharmaceutical expenditure poorly reliable. Forecasting methods rarely addressed uncertainty. The objective of this project was to propose a methodology to perform pharmaceutical expenditure forecasting that integrates expected policy changes and uncertainty (developed for the European Commission as the 'EU Pharmaceutical expenditure forecast'; see http://ec.europa.eu/health/healthcare/key_documents/index_en.htm). 1) Identification of all pharmaceuticals going off-patent and new branded medicinal products over a 5-year forecasting period in seven European Union (EU) Member States. 2) Development of a model to estimate direct and indirect impacts (based on health policies and clinical experts) on savings of generics and biosimilars. Inputs were originator sales value, patent expiry date, time to launch after marketing authorization, price discount, penetration rate, time to peak sales, and impact on brand price. 3) Development of a model for new drugs, which estimated sales progression in a competitive environment. Clinical expected benefits as well as commercial potential were assessed for each product by clinical experts. Inputs were development phase, marketing authorization dates, orphan condition, market size, and competitors. 4) Separate analysis of the budget impact of products going off-patent and new drugs according to several perspectives, distribution chains, and outcomes. 5) Addressing uncertainty surrounding estimations via deterministic and probabilistic sensitivity analysis. This methodology has proven to be effective by 1) identifying the main parameters impacting the variations in pharmaceutical expenditure forecasting across countries: generics discounts and penetration, brand price after patent loss, reimbursement rate, the penetration of biosimilars and discount price, distribution chains, and the time

  16. Biomembrane models and drug-biomembrane interaction studies: Involvement in drug design and development

    Directory of Open Access Journals (Sweden)

    R Pignatello

    2011-01-01

    Full Text Available Contact with many different biological membranes goes along the destiny of a drug after its systemic administration. From the circulating macrophage cells to the vessel endothelium, to more complex absorption barriers, the interaction of a biomolecule with these membranes largely affects its rate and time of biodistribution in the body and at the target sites. Therefore, investigating the phenomena occurring on the cell membranes, as well as their different interaction with drugs in the physiological or pathological conditions, is important to exploit the molecular basis of many diseases and to identify new potential therapeutic strategies. Of course, the complexity of the structure and functions of biological and cell membranes, has pushed researchers toward the proposition and validation of simpler two- and three-dimensional membrane models, whose utility and drawbacks will be discussed. This review also describes the analytical methods used to look at the interactions among bioactive compounds with biological membrane models, with a particular accent on the calorimetric techniques. These studies can be considered as a powerful tool for medicinal chemistry and pharmaceutical technology, in the steps of designing new drugs and optimizing the activity and safety profile of compounds already used in the therapy.

  17. Fruit Pod Extracts as a Source of Nutraceuticals and Pharmaceuticals

    Directory of Open Access Journals (Sweden)

    Azrina Azlan

    2012-10-01

    Full Text Available Fruit pods contain various beneficial compounds that have biological activities and can be used as a source of pharmaceutical and nutraceutical products. Although pods or pericarps are usually discarded when consuming the edible parts of fruits, they contain some compounds that exhibit biological activities after extraction. Most fruit pods included in this review contain polyphenolic components that can promote antioxidant effects on human health. Additionally, anti-inflammatory, antibacterial, antifungal and chemopreventive effects are associated with these fruit pod extracts. Besides polyphenolics, other compounds such as xanthones, carotenoids and saponins also exhibit health effects and can be potential sources of nutraceutical and pharmaceutical components. In this review, information on fruit pods or pericarp of Garcinia mangostana, Ceratonia siliqua, Moringa oleifera, Acacia nilotica, Sapindus rarak and Prosopis cineraria is presented and discussed with regard to their biological activity of the major compounds existing in them. The fruit pods of other ethno- botanical plants have also been reviewed. It can be concluded that although fruit pods are considered as being of no practical use and are often being thrown away, they nevertheless contain compounds that might be useful sources of nutraceutical and other pharmaceutical components.

  18. Anaerobic manganese- or iron-mediated pharmaceutical degradation in water

    NARCIS (Netherlands)

    Liu, Wenbo

    2018-01-01

    Pharmaceutical compounds, originating mainly from industrial production and public consumption, are detected at extremely low levels (ng·L-1 –µg·L-1) in groundwater, surface water, and wastewater. So far, the adverse effects of pharmaceuticals and their intermediates have been widely reported,

  19. Capacity to deliver pharmaceutical care by community pharmacies ...

    African Journals Online (AJOL)

    Pharmacy practice has transcended from largely a dispensary practice to pharmaceutical care practice. The capacity of community pharmacies to deliver pharmaceutical care was studied using pretested self survey methods. Ninety five percent (95%) of the respondents always educated customers on drug related needs, ...

  20. Health risks of counterfeit pharmaceuticals.

    Science.gov (United States)

    ten Ham, Martijn

    2003-01-01

    Pharmaceutical products are not exempt from the practice of counterfeiting. In recent years, many reports have become available demonstrating the presence of fake medicines on the market. Several studies have demonstrated that they are quite often of bad quality. It is estimated that 5% of all world trade in branded goods is counterfeit, leading to huge financial losses for the pharmaceutical industry. But much more important, from a public health point of view, is that history has shown that such products may lead to a great health risk. The essence of counterfeit products and the reason they are so dangerous is the complete absence of quality control, since they are often indistinguishable from the genuine product. The existence of counterfeit drugs has long been ignored both by the pharmaceutical industry and by drug regulatory authorities. At present initiatives are being taken, nationally and internationally, to curb counterfeiting. It is now realised that a strong regulatory agency is essential, but the initiatives can only be successful if all parties concerned actively co-operate.

  1. The argument for pharmaceutical policy.

    Science.gov (United States)

    Traulsen, Janine Morgall; Almarsdóttir, Anna Birna

    2005-02-01

    Pharmaceutical policy is a global concern. It has become a hot political topic in most countries--developed as well as developing--and can be found on the agenda of international organizations such as WHO, OECD, EU, WTO and even the World Bank. Pharmaceutical policy affects everyone in the world of pharmacy and it is therefore imperative that it be understood, discussed and debated within the pharmacy profession and included in the curriculum of schools of pharmacy. This, the first article in a series, argues for the importance of the academic discipline of pharmaceutical policy analysis and the involvement of pharmacists in this endeavour. The aim of the authors is to stimulate an informed and critical appreciation of this field. The authors begin with an introduction to the field of pharmaceutical policy, introducing several important concepts and current trends including: medicines regulation; how pharmaceutical policy is made; pharmaceutical policy as a dynamic process; and the new public health as a global issue. The article ends with a short description of the remaining five articles in the series which will deal with important aspects of pharmaceutical policy. The topics include: economic pressures on health care systems; drug utilization from the clinical viewpoint (rational use of medicines); the impact of pharmaceutical policy on patients and the patient impact on pharmaceutical policy; the professional perspective; and finally the last article which deals with studying and evaluating pharmaceutical policy.

  2. [Research and development on efficacy of Chinese herbal compound].

    Science.gov (United States)

    Liu, Jian-Xun; Ren, Jian-Xun; Lin, Cheng-Ren

    2016-03-01

    The efficacy not only is summarized by clinical effect of Chinese herbal compound on theory of traditional Chinese medicine, but also is manifested to clinical effect by interaction of many intricate chemical substances. The efficacy of Chinese herbal compound is current research focus in field of traditional Chinese medicine. By currently knowing in different aspects which included the progression in efficacy of Chinese herbal compound, symptomatic efficacy of Chinese herbal compound, the relationship between the efficacy and pharmacologic effect of Chinese herbal compound, the efficacy related pharmacodynamic substance and the evaluation of efficacy, it had been summarized mainly problems and methods in research and development process of the efficacy of Chinese herbal compound in this paper. Paper also elucidated problems that need to pay attention in research of efficacy in order to provide references for clinical and experimental studies of efficacy in Chinese herbal compound, boost research and development level of new traditional Chinese drug and facilitate modernization of traditional Chinese medicines. Copyright© by the Chinese Pharmaceutical Association.

  3. Photoreactivity of biologically active compounds. VIII. Photosensitized polymerization of lens proteins by antimalarial drugs in vitro.

    Science.gov (United States)

    Kristensen, S; Wang, R H; Tønnesen, H H; Dillon, J; Roberts, J E

    1995-02-01

    The drugs commonly used in the treatment of malaria are photochemically unstable. Several of these compounds cause dermal and ocular toxic reactions that may be light induced. The in vitro photopolymerization of calf lens proteins in the presence of antimalarial drugs was studied as part of a screening of the photochemical properties and phototoxic capabilities of these compounds. The pseudo-first-order rate constant for the reaction was calculated, and related to the amount of light absorbed by the compounds in order to determine the relative photosensitizing effect of each drug. The reaction mechanisms were evaluated by adding a variety of quenchers to the reaction medium during irradiation. Based on the results obtained in this study and previous knowledge about the pharmacokinetic behavior of these compounds, several of the drugs investigated have to be considered as potential photosensitizers in the human lens, the retina and the skin.

  4. Artifacts Generated During Azoalkane Peroxy Radical Oxidative Stress Testing of Pharmaceuticals Containing Primary and Secondary Amines.

    Science.gov (United States)

    Nefliu, Marcela; Zelesky, Todd; Jansen, Patrick; Sluggett, Gregory W; Foti, Christopher; Baertschi, Steven W; Harmon, Paul A

    2015-12-01

    We report artifactual degradation of pharmaceutical compounds containing primary and secondary amines during peroxy radical-mediated oxidative stress carried out using azoalkane initiators. Two degradation products were detected when model drug compounds dissolved in methanol/water were heated to 40°C with radical initiators such as 2,2'-azobis(2-methylpropionitrile) (AIBN). The primary artifact was identified as an α-aminonitrile generated from the reaction of the amine group of the model drug with formaldehyde and hydrogen cyanide, generated as byproducts of the stress reaction. A minor artifact was generated from the reaction between the amine group and isocyanic acid, also a byproduct of the stress reaction. We report the effects of pH, initiator/drug molar ratio, and type of azoalkane initiator on the formation of these artifacts. Mass spectrometry and nuclear magnetic resonance were used for structure elucidation, whereas mechanistic studies, including stable isotope labeling experiments, cyanide analysis, and experiments exploring the effects of butylated hydroxyanisole addition, were employed to support the degradation pathways. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  5. International price comparisons for pharmaceuticals. Measurement and policy issues.

    Science.gov (United States)

    Danzon, P M; Kim, J D

    1998-01-01

    Cross-national price comparisons for pharmaceuticals are commonly used for two purposes. Comparisons based on a sample of products are used to draw conclusions about differences in average price levels. Cross-national comparisons applied to individual products are also used by governments to set domestic prices. This paper examines the major methodological issues raised by international price comparisons, focusing on measurement of differences in average price levels and the validity of policy conclusions drawn from such price comparison studies. It argues that valid measures of average price levels can only be obtained from comparisons based on a comprehensive or representative sample of products, appropriately weighted, following standard index number methods. Comparisons of individual product prices should take into account the manufacturer's entire product portfolio over time rather than focus narrowly on a single product at a point in time. Because of the great variation across countries in both the range of drug compounds available and the dosage forms, strengths and pack sizes for each compound, obtaining a broadly comprehensive or representative sample is problematical. If products are required to match on all dimensions, including molecule, manufacturer, strength and pack, as is common in most international price comparisons, then only a very small and unrepresentative sample of the drugs available in each country can be included in the analysis. A trade-off between the desire to compare only identical products and the need to compare a truly representative sample of a country's pharmaceutical market is therefore necessary. A valid comparison of average drug prices should include generics and over-the-counter products that are good substitutes for branded prescription drugs, with all forms, strengths and packs. To achieve this broad representation, however, the requirements of same manufacturer, same brand, dosage form, strength and pack size must be

  6. Development of immunotoxicity testing strategies for immunomodulatory drugs.

    Science.gov (United States)

    Kawabata, Thomas T; Evans, Ellen W

    2012-01-01

    The ICH S8 immunotoxicity testing guideline for human pharmaceuticals was published in 2006 and was intended to provide guidance for assessing the immunotoxicity potential of low-molecular-weight drugs that are not intended to alter the immune system. For drugs intended to modulate the immune system, immunotoxicity testing strategies are generally developed on a case-by-case approach since the targets, intended patient population, and mechanisms of action of the test compound will determine the type of testing needed. Some of the general principles of ICH S8, however, may be applied to immunotoxicity testing strategies for immunomodulatory drugs. A weight-of-evidence approach using factors discussed in ICH S8 in concert with an assessment of the potential value of additional immunotoxicity testing should be considered. For most situations, immunotoxicity studies with immunomodulatory compounds evaluate off-target effects on the immune system and exaggerated pharmacology. The potential use of data from these studies and considerations such as translatability to humans are discussed.

  7. Chiral chromatography and its application to the pharmaceutical ...

    African Journals Online (AJOL)

    Chiral chromatographic enantioseparation has been in practice by researchers. There has been a considerable interest in the synthesis and separation of enantiomers of organic compounds especially because of their importance in the biochemical and pharmaceutical industries. Often, these compounds are purified rather ...

  8. Discovery and development of new antibacterial drugs: learning from experience?

    Science.gov (United States)

    Jackson, Nicole; Czaplewski, Lloyd; Piddock, Laura J V

    2018-06-01

    Antibiotic (antibacterial) resistance is a serious global problem and the need for new treatments is urgent. The current antibiotic discovery model is not delivering new agents at a rate that is sufficient to combat present levels of antibiotic resistance. This has led to fears of the arrival of a 'post-antibiotic era'. Scientific difficulties, an unfavourable regulatory climate, multiple company mergers and the low financial returns associated with antibiotic drug development have led to the withdrawal of many pharmaceutical companies from the field. The regulatory climate has now begun to improve, but major scientific hurdles still impede the discovery and development of novel antibacterial agents. To facilitate discovery activities there must be increased understanding of the scientific problems experienced by pharmaceutical companies. This must be coupled with addressing the current antibiotic resistance crisis so that compounds and ultimately drugs are delivered to treat the most urgent clinical challenges. By understanding the causes of the failures and successes of the pharmaceutical industry's research history, duplication of discovery programmes will be reduced, increasing the productivity of the antibiotic drug discovery pipeline by academia and small companies. The most important scientific issues to address are getting molecules into the Gram-negative bacterial cell and avoiding their efflux. Hence screening programmes should focus their efforts on whole bacterial cells rather than cell-free systems. Despite falling out of favour with pharmaceutical companies, natural product research still holds promise for providing new molecules as a basis for discovery.

  9. Regulation and competition in the Taiwanese pharmaceutical market under national health insurance.

    Science.gov (United States)

    Liu, Ya-Ming; Yang, Yea-Huei Kao; Hsieh, Chee-Ruey

    2012-05-01

    This article investigates the determinants of the prices of pharmaceuticals and their impact on the demand for prescription drugs in the context of Taiwan's pharmaceutical market where medical providers earn profit directly from prescribing and dispensing drugs. Based on product-level data, we find evidence that the profit-seeking behavior of the medical providers in the prescription drug market transfers the force of competition from the unregulated wholesale market to the regulated retail market and hence market competition still plays an important role in the determination of the regulated price. We also find that the profit-seeking behavior plays a similar role to advertising in that it increases the brand loyalty and hence lowers price elasticity. An important implication of our study is that the institutional features in the pharmaceutical market matter in shaping the nature of pharmaceutical competition and the responsiveness of pharmaceutical consumption with respect to changes in price. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Exploiting pluripotent stem cell technology for drug discovery, screening, safety, and toxicology assessments.

    Science.gov (United States)

    McGivern, Jered V; Ebert, Allison D

    2014-04-01

    In order for the pharmaceutical industry to maintain a constant flow of novel drugs and therapeutics into the clinic, compounds must be thoroughly validated for safety and efficacy in multiple biological and biochemical systems. Pluripotent stem cells, because of their ability to develop into any cell type in the body and recapitulate human disease, may be an important cellular system to add to the drug development repertoire. This review will discuss some of the benefits of using pluripotent stem cells for drug discovery and safety studies as well as some of the recent applications of stem cells in drug screening studies. We will also address some of the hurdles that need to be overcome in order to make stem cell-based approaches an efficient and effective tool in the quest to produce clinically successful drug compounds. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Illicit drugs and pharmaceuticals in the environment--forensic applications of environmental data. Part 1: Estimation of the usage of drugs in local communities.

    Science.gov (United States)

    Kasprzyk-Hordern, Barbara; Dinsdale, Richard M; Guwy, Alan J

    2009-06-01

    Pharmaceuticals and recently also illicit drugs have been recognised as emerging environmental contaminants due to their potential environmental impact: frequent occurrence, persistence and risk to aquatic life and humans. This manuscript is part one of the two-part study aiming to provide a better understanding and application of environmental data not only for environmental aims but also to meet forensic objectives. An attempt to use wastewater data is made in order to verify patterns of the usage of drugs (in particular illicit) in local communities. The average usage of cocaine in South Wales was estimated at 0.9 g day(-1) 1000 people(-1), which equals 1 tonne of this drug used or disposed of to sewage annually in Wales. The calculated usage of amphetamine denoted 2.5 g day(-1) 1000 people(-1) and is suspected to be an overestimate. Because no analysis of enantiomers of amphetamine was undertaken, no distinction between amphetamine's legal and illicit usage could be made.

  12. Orphan drugs: trends and issues in drug development.

    Science.gov (United States)

    Rana, Proteesh; Chawla, Shalini

    2018-04-12

    Research in rare diseases has contributed substantially toward the current understanding in the pathophysiology of the common diseases. However, medical needs of patients with rare diseases have always been neglected by the society and pharmaceutical industries based on their small numbers and unprofitability. The Orphan Drug Act (1983) was the first serious attempt to address the unmet medical needs for patients with rare diseases and to provide impetus for the pharmaceutical industry to promote orphan drug development. The process of drug development for rare diseases is no different from common diseases but involves significant cost and infrastructure. Further, certain aspect of drug research may not be feasible for the rare diseases. The drug-approving authority must exercise their scientific judgment and ensure due flexibility while evaluating data at various stages of orphan drug development. The emergence of patent cliff combined with the government incentives led the pharmaceutical industry to realize the good commercial prospects in developing an orphan drug despite the small market size. Indeed, many drugs that were given orphan designation ended up being blockbusters. The orphan drug market is projected to reach $178 billion by 2020, and the prospects of research and development in rare diseases appears to be quite promising and rewarding.

  13. Public awareness of Pharmaceutical care availability in community ...

    African Journals Online (AJOL)

    Furthermore, the awareness of availability of pharmaceutical care services in community pharmacies was 3% while 75% of the respondents believed a community pharmacy was just a place drugs can be obtained. As the profession and pharmacists endeavour to improve knowledge and skill to deliver pharmaceutical care ...

  14. Pharmaceutical and pharmacological approaches for bioavailability

    Indian Academy of Sciences (India)

    Much research has been done to determine drug–drug and herb–drug interactions for improving the bioavailability of etoposide. The present article gives insight on pharmaceutical and pharmacological attempts made from time to time to overcome the erratic inter- and intra-patient variability for improving the bioavailability ...

  15. Nanomedicine Drug Delivery across Mucous Membranes

    Science.gov (United States)

    Lancina, Michael George, III

    Control over the distribution of therapeutic compounds is a complex and somewhat overlooked field of pharmaceutical research. When swallowing a pill or receiving an injection, it is commonly assumed that drug will spread throughout the body in a more or less uniform concentration and find its way to wherever it is needed. In truth, drug biodistribuition is highly non-uniform and dependent on a large number of factors. The development of advanced drug delivery systems to control biodistribution can produce significant advances in clinical treatments without the need to discover new therapeutic compounds. This work focuses on a number of nanostructured materials designed to improve drug delivery by direct and efficient transfer of drugs across one of the body's external mucous membranes. Chapter 1 outlines the central concept that unites these studies: nanomaterials and cationic particles can be used to delivery therapeutic compounds across mucous membranes. Special attention is given to dendritic nanoparticles. In chapter 2, uses for dendrimers in ocular drug delivery are presented. The studies are divided into two main groups: topical and injectable formulations. Chapter 3 does not involve dendrimers but instead another cationic particle used in transmembrane drug delivery, chitosan. Next, a dendrimer based nanofiber mat was used to deliver anti-glaucoma drugs in chapter 4. A three week in vivo efficacy trial showed dendrimer nanofiber mats outperformed traditional eye drops in terms of intra-ocular pressure decrease in a normotensive rat model. Finally, we have developed a new dendrimer based anti-glaucoma drug in chapter 5. Collectively, these studies demonstrate some of the potential applications for nanotechnology to improve transmembrane drug delivery. These particles and fibers are able to readily adhere and penetrate across epithelial cell lays. Utilizing these materials to improve drug absorption through these portals has the potential to improve the

  16. Basics of Sterile Compounding: Ophthalmic Preparations, Part 1: Ophthalmic Solutions.

    Science.gov (United States)

    Allen, Loyd V

    2016-01-01

    Ophthalmic preparations are used to treat allergies, bacterial and viral infections, glaucoma, and numerous other eye conditions. When the eye's natural defensive mechanisms are compromised or overcome, an ophthalmic preparation, in a solution, suspension, or ointment form, may be indicated, with solutions being the most common form used to deliver a drug to the eye. This article provides a general discussion on ophthalmic preparations and specifically discusses the preparation of solutions. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

  17. Characterizing Active Pharmaceutical Ingredient Binding to Human Serum Albumin by Spin-Labeling and EPR Spectroscopy.

    Science.gov (United States)

    Hauenschild, Till; Reichenwallner, Jörg; Enkelmann, Volker; Hinderberger, Dariush

    2016-08-26

    Drug binding to human serum albumin (HSA) has been characterized by a spin-labeling and continuous-wave (CW) EPR spectroscopic approach. Specifically, the contribution of functional groups (FGs) in a compound on its albumin-binding capabilities is quantitatively described. Molecules from different drug classes are labeled with EPR-active nitroxide radicals (spin-labeled pharmaceuticals (SLPs)) and in a screening approach CW-EPR spectroscopy is used to investigate HSA binding under physiological conditions and at varying ratios of SLP to protein. Spectral simulations of the CW-EPR spectra allow extraction of association constants (KA ) and the maximum number (n) of binding sites per protein. By comparison of data from 23 SLPs, the mechanisms of drug-protein association and the impact of chemical modifications at individual positions on drug uptake can be rationalized. Furthermore, new drug modifications with predictable protein binding tendency may be envisaged. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Transdermal Drug Delivery: Innovative Pharmaceutical Developments Based on Disruption of the Barrier Properties of the Stratum Corneum

    Directory of Open Access Journals (Sweden)

    Ahlam Zaid Alkilani

    2015-10-01

    Full Text Available The skin offers an accessible and convenient site for the administration of medications. To this end, the field of transdermal drug delivery, aimed at developing safe and efficacious means of delivering medications across the skin, has in the past and continues to garner much time and investment with the continuous advancement of new and innovative approaches. This review details the progress and current status of the transdermal drug delivery field and describes numerous pharmaceutical developments which have been employed to overcome limitations associated with skin delivery systems. Advantages and disadvantages of the various approaches are detailed, commercially marketed products are highlighted and particular attention is paid to the emerging field of microneedle technologies.

  19. Transdermal Drug Delivery: Innovative Pharmaceutical Developments Based on Disruption of the Barrier Properties of the stratum corneum

    Science.gov (United States)

    Zaid Alkilani, Ahlam; McCrudden, Maelíosa T.C.; Donnelly, Ryan F.

    2015-01-01

    The skin offers an accessible and convenient site for the administration of medications. To this end, the field of transdermal drug delivery, aimed at developing safe and efficacious means of delivering medications across the skin, has in the past and continues to garner much time and investment with the continuous advancement of new and innovative approaches. This review details the progress and current status of the transdermal drug delivery field and describes numerous pharmaceutical developments which have been employed to overcome limitations associated with skin delivery systems. Advantages and disadvantages of the various approaches are detailed, commercially marketed products are highlighted and particular attention is paid to the emerging field of microneedle technologies. PMID:26506371

  20. Postgraduate Courses in Pharmaceutical Medicine in Italy

    Directory of Open Access Journals (Sweden)

    Domenico Criscuolo

    2017-06-01

    Full Text Available Italy has a significant tradition of excellence in the area of clinical trials (CTRs: important achievements in the clinical development of rifampicin and adriamycin, the two most famous drugs discovered in the research laboratories of two Italian pharmaceutical companies, paved the way to the establishment of a culture of clinical development, mainly in the areas of antimicrobials and oncology. Despite the fact that now the Italian market of pharmaceuticals is largely dominated by multinational companies with headquarters outside Italy, the contribution of Italian studies to the clinical development of new drugs is still significant. Indeed, it largely exceeds the percentage of Italian inhabitants versus the ones living in the remaining EU countries, as Italy has about 12% of EU population, but has a 17% share of the EU CTRs. Education in Pharmaceutical Medicine is now a must for all professionals interested to work either in pharma companies or in contract research organizations: several Italian universities are offering high quality courses, and in the last 10 years, more than 1,200 professionals received a postgraduate education in pharmaceutical medicine. This result places Italy on top of countries concerned about the professional education of people involved in drug development and will represent an asset for a larger involvement of Italian clinical sites in the global process of clinical research.

  1. Effects of Repeated Intraperitoneal Injection of Pharmaceutical-grade and Nonpharmaceutical-grade Corn Oil in Female C57BL/6J Mice.

    Science.gov (United States)

    Hubbard, Jennifer S; Chen, Patty H; Boyd, Kelli L

    2017-11-01

    Due to potential adverse effects on animal wellbeing, the use of nonpharmaceutical-grade substances in animal research must be scientifically justified in cases where a pharmaceutical-grade version of the substance exists. This requirement applies to all substances, including vehicles used to solubilize experimental drugs. To date, no studies have evaluated the direct effect of the pharmaceutical classification of a compound on animal wellbeing. In this study, we evaluated intraperitoneal administration of pharmaceutical-grade corn oil, nonpharmaceutical-grade corn oil, and saline in female C57BL/6J mice. Compounds were administered every 48 h for a total of 4 injections. Mice were evaluated clinically by using body weight, body condition score, visual assessment score, CBC, and serum chemistries. Animals were euthanized at 24 h and 14 d after the final injection. Inflammation of the peritoneal wall and mesenteric fat was assessed microscopically by using a semiquantitative scoring system. Saline-dosed groups had lower pathology scores at both time points. At day 21, pharmaceutical-grade corn oil had a significantly higher pathology score compared with nonpharmaceutical-grade corn oil. No other significant differences between the corn oil groups were observed. The use of nonpharmaceutical grade corn oil did not result in adverse clinical consequences and is presumed safe to use for intraperitoneal injection in mice. Differences in inflammation between the 2 groups suggest that the use of either pharmaceutical-grade or nonpharmaceutical-grade corn oil should be consistent within a study.

  2. Adsorption of selected endocrine disrupting compounds and pharmaceuticals on activated biochars

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Chanil [Department of Civil and Environmental Engineering, University of South Carolina, Columbia, SC 29208 (United States); Park, Junyeong [Department of Forest Biomaterials, North Carolina State University, Raleigh, NC 27695 (United States); Lim, Kwang Hun [Department of Chemistry, East Carolina University, Greenville, NC 27858 (United States); Park, Sunkyu [Department of Forest Biomaterials, North Carolina State University, Raleigh, NC 27695 (United States); Heo, Jiyong [Department of Civil and Environmental Engineering, Korea Army Academy at Young-Cheon, PO Box 135-1, Changhari, Gogyeongmeon, Young-cheon 770-849, Gyeongbuk (Korea, Republic of); Her, Namguk [Department of Chemistry and Environmental Sciences, Korea Army Academy at Young-Cheon, PO Box 135-1, Changhari, Gogyeongmeon, Young-cheon 770-849, Gyeongbuk (Korea, Republic of); Oh, Jeill; Yun, Soyoung [Department of Civil and Environmental Engineering, Chung-Ang University, Dongjak-Ku, Seoul 156-756 (Korea, Republic of); Yoon, Yeomin, E-mail: yoony@cec.sc.edu [Department of Civil and Environmental Engineering, University of South Carolina, Columbia, SC 29208 (United States)

    2013-12-15

    Highlights: • Biochars were prepared at different gas environments. • The competitive adsorption among EDCs/PhACs were investigated. • Aromaticity of adsorbent plays a significant role for EDCs/PhACs adsorption. -- Abstract: Chemically activated biochar produced under oxygenated (O-biochar) and oxygen-free (N-biochar) conditions were characterized and the adsorption of endocrine disrupting compounds (EDCs): bisphenol A (BPA), atrazine (ATR), 17 α-ethinylestradiol (EE2), and pharmaceutical active compounds (PhACs); sulfamethoxazole (SMX), carbamazepine (CBM), diclofenac (DCF), ibuprofen (IBP) on both biochars and commercialized powdered activated carbon (PAC) were investigated. Characteristic analysis of adsorbents by solid-state nuclear magnetic resonance (NMR) was conducted to determine better understanding about the EDCs/PhACs adsorption. N-biochar consisted of higher polarity moieties with more alkyl (0–45 ppm), methoxyl (45–63 ppm), O-alkyl (63–108 ppm), and carboxyl carbon (165–187 ppm) content than other adsorbents, while aromaticity of O-biochar was higher than that of N-biochar. O-biochar was composed mostly of aromatic moieties, with low H/C and O/C ratios compared to the highly polarized N-biochar that contained diverse polar functional groups. The higher surface area and pore volume of N-biochar resulted in higher adsorption capacity toward EDCs/PhACs along with atomic-level molecular structural property than O-biochar and PAC. N-biochar had a highest adsorption capacity of all chemicals, suggesting that N-biochar derived from loblolly pine chip is a promising sorbent for agricultural and environmental applications. The adsorption of pH-sensitive dissociable SMX, DCF, IBP, and BPA varied and the order of adsorption capacity was correlated with the hydrophobicity (K{sub ow}) of adsorbates throughout the all adsorbents, whereas adsorption of non-ionizable CBM, ATR, and EE2 in varied pH allowed adsorbents to interact with hydrophobic property

  3. Adsorption of selected endocrine disrupting compounds and pharmaceuticals on activated biochars

    International Nuclear Information System (INIS)

    Jung, Chanil; Park, Junyeong; Lim, Kwang Hun; Park, Sunkyu; Heo, Jiyong; Her, Namguk; Oh, Jeill; Yun, Soyoung; Yoon, Yeomin

    2013-01-01

    Highlights: • Biochars were prepared at different gas environments. • The competitive adsorption among EDCs/PhACs were investigated. • Aromaticity of adsorbent plays a significant role for EDCs/PhACs adsorption. -- Abstract: Chemically activated biochar produced under oxygenated (O-biochar) and oxygen-free (N-biochar) conditions were characterized and the adsorption of endocrine disrupting compounds (EDCs): bisphenol A (BPA), atrazine (ATR), 17 α-ethinylestradiol (EE2), and pharmaceutical active compounds (PhACs); sulfamethoxazole (SMX), carbamazepine (CBM), diclofenac (DCF), ibuprofen (IBP) on both biochars and commercialized powdered activated carbon (PAC) were investigated. Characteristic analysis of adsorbents by solid-state nuclear magnetic resonance (NMR) was conducted to determine better understanding about the EDCs/PhACs adsorption. N-biochar consisted of higher polarity moieties with more alkyl (0–45 ppm), methoxyl (45–63 ppm), O-alkyl (63–108 ppm), and carboxyl carbon (165–187 ppm) content than other adsorbents, while aromaticity of O-biochar was higher than that of N-biochar. O-biochar was composed mostly of aromatic moieties, with low H/C and O/C ratios compared to the highly polarized N-biochar that contained diverse polar functional groups. The higher surface area and pore volume of N-biochar resulted in higher adsorption capacity toward EDCs/PhACs along with atomic-level molecular structural property than O-biochar and PAC. N-biochar had a highest adsorption capacity of all chemicals, suggesting that N-biochar derived from loblolly pine chip is a promising sorbent for agricultural and environmental applications. The adsorption of pH-sensitive dissociable SMX, DCF, IBP, and BPA varied and the order of adsorption capacity was correlated with the hydrophobicity (K ow ) of adsorbates throughout the all adsorbents, whereas adsorption of non-ionizable CBM, ATR, and EE2 in varied pH allowed adsorbents to interact with hydrophobic property of

  4. Pharmaceutical technology management--profitable business avenue.

    Science.gov (United States)

    Puthli, Shivanand P

    2010-01-01

    Growing research expenditure, regulatory framework and generic erosion have forced pharmaceutical companies globally to resort to pharmaceutical technology management (PTM). Indeed, the pharmaceutical industry has witnessed the impact of innovative drug delivery and device technologies and their influence on business. PTM has given a new business insight with greater profits and enhancement of product franchise. Promising breakthrough technologies have not been able to reach a commercial platform largely owing to lack of capital at the preliminary stages of the product development program. Intellectual property plays a considerable role in protecting innovative technologies. Joint ventures and strategic alliances also become important for commercializing a new technology. The synergy of PTM with options of in-licensing is expected to infuse newer opportunities to the pharmaceutical business.

  5. Occurrence of human pharmaceuticals in water resources of the United States: A review

    Science.gov (United States)

    Focazio, M.J.; Kolpin, D.W.; Furlong, E.T.

    2004-01-01

    The widespread environmental presence of some pharmaceuticals and other organic wastewater compounds has been documented globally (e.g. Buser et al. 1998; Ternes 1998; Stumpf et al.1999; Heberer et al. 2001; Kümmerer 2001; Ternes et al. 2001; Scheytt et al. 2001; Golet et al. 2002; Kolpin et al. 2002; Boyd et al. 2003; Metcalf et al. 2003). Recently, there have been several literature reviews and summary studies of the occurrence, fate, transport, and treatment of targeted human pharmaceuticals in wastewater effluent and associated environmental waters across the globe (e.g. Daughton and Ternes 1999; Sedlak et al. 2000; Suter and Giger 2000; Daughton and Jones-Lepp 2001; Jones et al. 2001; Heberer 2002; and Drewes et al. 2002). The occurrence of pharmaceutical compounds in water resources is explained by their ubiquitous use, excretion of large percentages of the mass consumed, and incomplete removal during wastewater treatment (Stumpf et al.1999). The recent increase in detection of trace concentrations (typically less than a part per billion) of pharmaceuticals in water resources across the globe reflects improvements in laboratory analytical methods (Sedlak et al. 2000) and the associated increases in field surveys. The detection of pharmaceutical compounds in large rivers in Europe and in the North Sea (Buser et al. 1998; Ternes 1998; Stumpf et al. 1999) highlighted the fact that highly soluble, trace organic compounds, such as pharmaceuticals, may escape removal in wastewater treatment, and the mixing and concentration of wastewaters through conventional wastewater treatment processes could provide a means of delivering these chemicals to environmental waters in a manner that would contaminate water resources on a large scale at trace levels (Richardson and Bowron 1985). In the United States, some of the first detections of a limited number of pharmaceutically active compounds or their transformation products were found in waters associated with landfill

  6. Lipophilicity screening of novel drug-like compounds and comparison to clog P.

    Science.gov (United States)

    Lu, Dujuan; Chambers, Peter; Wipf, Peter; Xie, Xiang-Qun; Englert, Danielle; Weber, Stephen

    2012-10-05

    We determined the distribution coefficients of solutes between a polymer film phase (polyvinyl chloride (PVC) with 67% (w/w) dioctyl sebacate (DOS)) and an aqueous phase in a 96-well format. The parallel measurement approach is efficient and uses very little material. Polymer-water distribution coefficients (D(pw)) at different pH values yield the pKa and polymer-water partition coefficient values (P(pw)) of the solutes. log P(pw) of a prominent drug-like compound, 2H-1,2,6-thiadiazine, 3-methyl-5-phenyl-,1,1-dioxide, is in good agreement with clog P, while the pK(a) value is substantially different from calculated values. This method has been also successfully applied to a library of novel drug-like compounds. log D(pw) values (at pH 4.0, 7.0, 10.0) of 24 novel drug-like compounds have been determined with good reproducibility with the 96-well plate approach. Differences between experimental values and a variety of available calculated values are significant. This emphasizes the need for laboratory separations-based measurements of log D. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Capture compound mass spectrometry sheds light on the molecular mechanisms of liver toxicity of two Parkinson drugs.

    Science.gov (United States)

    Fischer, Jenny J; Michaelis, Simon; Schrey, Anna K; Graebner, Olivia Graebner nee; Glinski, Mirko; Dreger, Mathias; Kroll, Friedrich; Koester, Hubert

    2010-01-01

    Capture compound mass spectrometry (CCMS) is a novel technology that helps understand the molecular mechanism of the mode of action of small molecules. The Capture Compounds are trifunctional probes: A selectivity function (the drug) interacts with the proteins in a biological sample, a reactivity function (phenylazide) irreversibly forms a covalent bond, and a sorting function (biotin) allows the captured protein(s) to be isolated for mass spectrometric analysis. Tolcapone and entacapone are potent inhibitors of catechol-O-methyltransferase (COMT) for the treatment of Parkinson's disease. We aimed to understand the molecular basis of the difference of both drugs with respect to side effects. Using Capture Compounds with these drugs as selectivity functions, we were able to unambiguously and reproducibly isolate and identify their known target COMT. Tolcapone Capture Compounds captured five times more proteins than entacapone Capture Compounds. Moreover, tolcapone Capture Compounds isolated mitochondrial and peroxisomal proteins. The major tolcapone-protein interactions occurred with components of the respiratory chain and of the fatty acid beta-oxidation. Previously reported symptoms in tolcapone-treated rats suggested that tolcapone might act as decoupling reagent of the respiratory chain (Haasio et al., 2002b). Our results demonstrate that CCMS is an effective tool for the identification of a drug's potential off targets. It fills a gap in currently used in vitro screens for drug profiling that do not contain all the toxicologically relevant proteins. Thereby, CCMS has the potential to fill a technological need in drug safety assessment and helps reengineer or to reject drugs at an early preclinical stage.

  8. Occurrence of Chiral Bioactive Compounds in the Aquatic Environment: A Review

    Directory of Open Access Journals (Sweden)

    Cláudia Ribeiro

    2017-10-01

    Full Text Available In recent decades, the presence of micropollutants in the environment has been extensively studied due to their high frequency of occurrence, persistence and possible adverse effects to exposed organisms. Concerning chiral micropollutants in the environment, enantiomers are frequently ignored and enantiomeric composition often neglected. However, enantioselective toxicity is well recognized, highlighting the need to include enantioselectivity in environmental risk assessment. Additionally, the information about enantiomeric fraction (EF is crucial since it gives insights about: (i environmental fate (i.e., occurrence, distribution, removal processes and (biodegradation; (ii illicit discharges; (iii consumption pattern (e.g., illicit drugs, pharmaceuticals used as recreational drugs, illicit use of pesticides; and (iv enantioselective toxicological effects. Thus, the purpose of this paper is to provide a comprehensive review about the enantioselective occurrence of chiral bioactive compounds in aquatic environmental matrices. These include pharmaceuticals, illicit drugs, pesticides, polychlorinated biphenyls (PCBs and polycyclic musks (PCMs. Most frequently analytical methods used for separation of enantiomers were liquid chromatography and gas chromatography methodologies using both indirect (enantiomerically pure derivatizing reagents and direct methods (chiral stationary phases. The occurrence of these chiral micropollutants in the environment is reviewed and future challenges are outlined.

  9. Modulation of steroidogenic gene expression and hormone production of H295R cells by pharmaceuticals and other environmentally active compounds

    International Nuclear Information System (INIS)

    Gracia, Tannia; Hilscherova, Klara; Jones, Paul D.; Newsted, John L.; Higley, Eric B.; Zhang, Xiaowei; Hecker, Markus; Murphy, Margaret B.; Yu, Richard M.K.; Lam, Paul K.S.; Wu, Rudolf S.S.; Giesy, John P.

    2007-01-01

    The H295R cell bioassay was used to evaluate the potential endocrine disrupting effects of 18 of the most commonly used pharmaceuticals in the United States. Exposures for 48 h with single pharmaceuticals and binary mixtures were conducted; the expression of five steroidogenic genes, 3βHSD2, CYP11β1, CYP11β2, CYP17 and CYP19, was quantified by Q-RT-PCR. Production of the steroid hormones estradiol (E2), testosterone (T) and progesterone (P) was also evaluated. Antibiotics were shown to modulate gene expression and hormone production. Amoxicillin up-regulated the expression of CYP11β2 and CYP19 by more than 2-fold and induced estradiol production up to almost 3-fold. Erythromycin significantly increased CYP11β2 expression and the production of P and E2 by 3.5- and 2.4-fold, respectively, while production of T was significantly decreased. The β-blocker salbutamol caused the greatest induction of CYP17, more than 13-fold, and significantly decreased E2 production. The binary mixture of cyproterone and salbutamol significantly down-regulated expression of CYP19, while a mixture of ethynylestradiol and trenbolone, increased E2 production 3.7-fold. Estradiol production was significantly affected by changes in concentrations of trenbolone, cyproterone, and ethynylestradiol. Exposures with individual pharmaceuticals showed the possible secondary effects that drugs may exert on steroid production. Results from binary mixture exposures suggested the possible type of interactions that may occur between drugs and the joint effects product of such interactions. Dose-response results indicated that although two chemicals may share a common mechanism of action the concentration effects observed may be significantly different

  10. Pharmaceutical pollution of aquatic environment: an emerging and enormous challenge

    Directory of Open Access Journals (Sweden)

    Rzymski Piotr

    2017-06-01

    Full Text Available The global use of pharmaceuticals is on the systematic rise and leads to contamination of surface waters with xenobiotic compounds with a wide range of bioactivity. Waters that receive urban and medical effluents are particularly threatened. The presence of pharmaceuticals in these ecosystems can lead to unpredictable ecological impacts and responses, and may also have an impact on human health. At the same time the identification and quantification of these chemicals, to a large extent remains a subject to scientific investigation than part of a thorough monitoring programme. Their biological effects on aquatic organisms are mainly recognized experimentally and often using concentrations far exceeding environmentally relevant levels. This review paper defines the main sources of pharmaceuticals in the aquatic environment, discusses the fate of these compounds and summarizes the current state-of-the-art of pharmaceutical monitoring in Polish surface waters.

  11. Tropical Journal of Pharmaceutical Research

    African Journals Online (AJOL)

    We seek to encourage pharmaceutical and allied research of tropical and ... and related disciplines (including biotechnology, cell and molecular biology, drug ... with ibrutinib reduces proliferation, migration and invasion of lung cancer cells ...

  12. Head shop compound abuse amongst attendees of the Drug Treatment Centre Board.

    LENUS (Irish Health Repository)

    McNamara, S

    2010-05-01

    The use of "Head Shop" compounds has received much media attention lately. There is very little research in the current literature with regard to the extent of the usage of these substances amongst the drug using population in Ireland. We conducted a study to examine the extent of the usage of Mephedrone, Methylone and BZP amongst attendees of Methadone maintenance programs at the DTCB. Two hundred and nine samples in total were tested. The results showed significant usage of these compounds amongst this cohort of drug users, with 29 (13.9%) of samples tested being positive for Mephedrone, 7 (3.3%) positive for Methylone and 1 (0.5%) positive for BZP.

  13. Toxicity of anthelmintic drugs (fenbendazole and flubendazole) to aquatic organisms.

    Science.gov (United States)

    Wagil, Marta; Białk-Bielińska, Anna; Puckowski, Alan; Wychodnik, Katarzyna; Maszkowska, Joanna; Mulkiewicz, Ewa; Kumirska, Jolanta; Stepnowski, Piotr; Stolte, Stefan

    2015-02-01

    Flubendazole (FLU) and fenbendazole (FEN) belong to benzimidazoles-pharmaceuticals widely used in veterinary and human medicine for the treatment of intestinal parasites as well as for the treatment of systemic worm infections. In recent years, usage of these drugs increased, which resulted in a larger contamination of the environment and possible negative effects on biota. Hence, in our research, we investigated an aquatic ecotoxicity of these pharmaceuticals towards: marine bacteria (Vibrio fischeri), green algae (Scenedesmus vacuolatus), duckweed (Lemna minor) and crustacean (Daphnia magna). Ecotoxicity tests were combined with chemical analysis in order to investigate the actual exposure concentration of the compounds used in the experiment as well as to stability and adsorption studies. As a result, study evaluating sensitivity of different aquatic organisms to these compounds and new ecotoxicological data is presented. The strongest negative impact of FLU and FEN was observed to D. magna.

  14. Pharmaceutical biotechnology: drug discovery and clinical applications

    National Research Council Canada - National Science Library

    Kayser, Oliver; Müller, Rainer H

    2004-01-01

    .... The biopharmaceutical industry has changed dramatically since the first recombinant ® protein (Humulin ) was approved for marketing in 1982. The range of resources required for the pharmaceutical industry has expanded from its traditional fields. Advances in the field of recombinant genetics allows scientists to routinely clone genes and create ge...

  15. The Forty-Sixth Euro Congress on Drug Synthesis and Analysis: Snapshot †

    Directory of Open Access Journals (Sweden)

    Pavel Mucaji

    2017-10-01

    Full Text Available The 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017 was arranged within the celebration of the 65th Anniversary of the Faculty of Pharmacy at Comenius University in Bratislava, Slovakia from 5–8 September 2017 to get together specialists in medicinal chemistry, organic synthesis, pharmaceutical analysis, screening of bioactive compounds, pharmacology and drug formulations; promote the exchange of scientific results, methods and ideas; and encourage cooperation between researchers from all over the world. The topic of the conference, “Drug Synthesis and Analysis,” meant that the symposium welcomed all pharmacists and/or researchers (chemists, analysts, biologists and students interested in scientific work dealing with investigations of biologically active compounds as potential drugs. The authors of this manuscript were plenary speakers and other participants of the symposium and members of their research teams. The following summary highlights the major points/topics of the meeting.

  16. Application of surface-enhanced Raman spectroscopy (SERS) for cleaning verification in pharmaceutical manufacture.

    Science.gov (United States)

    Corrigan, Damion K; Cauchi, Michael; Piletsky, Sergey; Mccrossen, Sean

    2009-01-01

    Cleaning verification is the process by which pharmaceutical manufacturing equipment is determined as sufficiently clean to allow manufacture to continue. Surface-enhanced Raman spectroscopy (SERS) is a very sensitive spectroscopic technique capable of detection at levels appropriate for cleaning verification. In this paper, commercially available Klarite SERS substrates were employed in order to obtain the necessary enhancement of signal for the identification of chemical species at concentrations of 1 to 10 ng/cm2, which are relevant to cleaning verification. The SERS approach was combined with principal component analysis in the identification of drug compounds recovered from a contaminated steel surface.

  17. Automated evaluation of pharmaceutically active ionic liquids’ (eco)toxicity through the inhibition of human carboxylesterase and Vibrio fischeri

    International Nuclear Information System (INIS)

    Costa, Susana P.F.; Justina, Vanessa D.; Bica, Katharina; Vasiloiu, Maria; Pinto, Paula C.A.G.; Saraiva, M. Lúcia M.F.S.

    2014-01-01

    Highlights: • IL-APIs toxicity on humans and aquatic environment was evaluated by inhibition assays. • The inhibition assays were implemented through automated screening bioassays. • Automation of bioassays enabled a rigorous control of the reaction conditions. • EC 50 obtained provide vital information on IL-APIs safety and potential use as drugs. -- Abstract: The toxicity of 16 pharmaceutical active ionic liquids (IL-APIs) was evaluated by automated approaches based on sequential injection analysis (SIA). The implemented bioassays were centered on the inhibition of human carboxylesterase 2 and Vibrio fischeri, in the presence of the tested compounds. The inhibitory effects were quantified by calculating the inhibitor concentration required to cause 50% of inhibition (EC 50 ). The EC 50 values demonstrated that the cetylpyridinium group was one of the most toxic cations and that the imidazolium group was the less toxic. The obtained results provide important information about the safety of the studied IL-APIs and their possible use as pharmaceutical drugs. The developed automated SIA methodologies are robust screening bioassays, and can be used as a generic tools to identify the (eco)toxicity of the structural elements of ILs, contributing to a sustainable development of drugs

  18. Pharmaceutical costs of assisted reproduction in Spain.

    Science.gov (United States)

    Lorente, Maria-Reyes; Hernández, Juana; Antoñanzas, Fernando

    2013-11-01

    Assisted reproduction is one of the health services currently being considered for possible limitation or exclusion from the public health services portfolio in Spain. One of the main reasons claimed for this is the impact on the budget for pharmaceutical expenditure. The objective of this study was to assess the significance of the pharmaceutical costs of assisted reproduction in Spain. This study focused on medical practice in Spain, and is based on the opinions of experts in assisted reproduction and the results provided by professional societies' publications. The reference year is 2012 and the setting was secondary care. We have included all existing pharmaceutical modalities for assisted reproduction, as well as the most common drug for each modality. We have considered the pharmaceutical cost per cycle for artificial insemination, in vitro fertilisation with or without intracytoplasmic sperm injection (IVF_ICSI), and cryotransfer and donated fresh oocytes reception. In Spain, artificial insemination has a pharmaceutical cost per cycle of between €69.36 and €873.79. This amounts to an average cycle cost of €364.87 for partner's sperm and €327.10 for donor sperm. The pharmaceutical cost of IVF_ICSI ranges between €278.16 and €1,902.66, giving an average cost per cycle of €1,139.65. In the case of cryotransfer and donated fresh oocytes reception, the pharmaceutical cost per cycle is between €22.61 and €58.73, yielding an average cost of €40.67. The budgetary impact of pharmaceutical expenditure for assisted reproduction in Spain for the year 2012 was estimated at €98.7 million. In Spain, the total pharmaceutical cost of assisted reproduction is substantial. According to our results, we can say that about 29% of the total pharmaceutical expenditure for assisted reproduction techniques is funded by the National Health System and the rest represents 2.4% of the total annual out-of-pocket family expenditure on drugs.

  19. Screening of pharmaceuticals and illicit drugs in wastewater and surface waters of Spain and Italy by high resolution mass spectrometry using UHPLC-QTOF MS and LC-LTQ-Orbitrap MS.

    Science.gov (United States)

    Bade, Richard; Rousis, Nikolaos I; Bijlsma, Lubertus; Gracia-Lor, Emma; Castiglioni, Sara; Sancho, Juan V; Hernandez, Felix

    2015-12-01

    The existence of pharmaceuticals and illicit drugs (PIDs) in environmental waters has led many analytical chemists to develop screening methods for monitoring purposes. Water samples can contain a huge number of possible contaminants, commonly at low concentrations, which makes their detection and identification problematic. Liquid chromatography coupled with high resolution mass spectrometry (LC-HRMS) has proven itself effective in the screening of environmental contaminants. The present work investigates the use of the most popular HRMS instruments, quadrupole time-of-flight and linear trap quadrupole-Orbitrap, from two different laboratories. A suspect screening for PIDs was carried out on wastewater (influent and effluent) and surface water samples from Castellón, Eastern Spain, and Cremona, Northern Italy, incorporating a database of 107 PIDs (including 220 fragment ions). A comparison between the findings of both instruments and of the samples was made which highlights the advantages and drawbacks of the strategies applied in each case. In total, 28 compounds were detected and/or identified by either/both instruments with irbesartan, valsartan, benzoylecgonine and caffeine being the most commonly found compounds across all samples.

  20. Complex compounds of terbium(III) with some nonsteroidal anti-inflammatory drugs and their analytical applications

    International Nuclear Information System (INIS)

    Teslyuk, O.I.; Egorova, A.V.; Yagodkin, B.N.; Bel'tyukova, S.V.

    2007-01-01

    Luminescence properties of the complexes of terbium(III) with nonsteroidal anti-inflammatory drugs (ibuprofen and orthofen) were studied. It was demonstrated that in the presence of organic bases (2,2'-dipyridyl and 1,10-phenanthroline) mixed-ligand complexes are formed and the luminescence intensity of terbium(III) increases by a factor of up to 250. The optimum complexation conditions were determined. It was proposed to use these complexes as analytical forms for the luminescence determination of nonsteroidal anti-inflammatory drugs (ibuprofen and orthofen) in pharmaceutical dosage forms. The detection limits are 2 and 0.05 μg/ml, respectively [ru

  1. Pharmaceuticals as emerging contaminants and their removal from water. A review.

    Science.gov (United States)

    Rivera-Utrilla, José; Sánchez-Polo, Manuel; Ferro-García, María Ángeles; Prados-Joya, Gonzalo; Ocampo-Pérez, Raúl

    2013-10-01

    The main objective of this study was to conduct an exhaustive review of the literature on the presence of pharmaceutical-derived compounds in water and on their removal. The most representative pharmaceutical families found in water were described and related water pollution issues were analyzed. The performances of different water treatment systems in the removal of pharmaceuticals were also summarized. The water treatment technologies were those based on conventional systems (chlorine, chlorine dioxide, wastewater treatment plants), adsorption/bioadsorption on activated carbon (from lotus stalks, olive-waste cake, coal, wood, plastic waste, cork powder waste, peach stones, coconut shell, rice husk), and advanced oxidation processes by means of ozonation (O₃, O₃/H₂O₂, O₃/activated carbon, O₃/biological treatment), photooxidation (UV, UV/H₂O₂, UV/K₂S₂O₈, UV/TiO₂, UV/H₂O₂/TiO₂, UV/TiO₂/activated carbon, photo-Fenton), radiolysis (e-Beam, ⁶⁰Co, ¹³⁷Cs. Additives used: H₂O₂, SO₃²⁻, HCO₃⁻, CH₃₋OH, CO₃²⁻, or NO₃⁻), and electrochemical processes (Electrooxidation without and with active chlorine generation). The effect of these treatments on pharmaceutical compounds and the advantages and disadvantages of different methodologies used were described. The most important parameters of the above water treatment systems (experimental conditions, removal yield, pharmaceutical compound mineralization, TOC removal, toxicity evolution) were indicated. The key publications on pharmaceutical removal from water were summarized. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Recent advances of capillary electrophoresis in pharmaceutical analysis.

    Science.gov (United States)

    Suntornsuk, Leena

    2010-09-01

    This review covers recent advances of capillary electrophoresis (CE) in pharmaceutical analysis. The principle, instrumentation, and conventional modes of CE are briefly discussed. Advances in the different CE techniques (non-aqueous CE, microemulsion electrokinetic chromatography, capillary isotachophoresis, capillary electrochromatography, and immunoaffinity CE), detection techniques (mass spectrometry, light-emitting diode, fluorescence, chemiluminescence, and contactless conductivity), on-line sample pretreatment (flow injection) and chiral separation are described. Applications of CE to assay of active pharmaceutical ingredients (APIs), drug impurity testing, chiral drug separation, and determination of APIs in biological fluids published from 2008 to 2009 are tabulated.

  3. Concentrations of selected pharmaceuticals and antibiotics in south-central Pennsylvania waters, March through September 2006

    Science.gov (United States)

    Loper, Connie A.; Crawford, J. Kent; Otto, Kim L.; Manning, Rhonda L.; Meyer, Michael T.; Furlong, Edward T.

    2007-01-01

    This report presents environmental and quality-control data from analyses of 15 pharmaceutical and 31 antibiotic compounds in water samples from streams and wells in south-central Pennsylvania. The analyses are part of a study by the U.S. Geological Survey (USGS) in cooperation with the Pennsylvania Department of Environmental Protection (PADEP) to define concentrations of selected emerging contaminants in streams and well water in Pennsylvania. Sampling was conducted at 11 stream sites and at 6 wells in 9 counties of south-central Pennsylvania. Five of the streams received municipal wastewater and 6 of the streams received runoff from agricultural areas dominated by animal-feeding operations. For all 11 streams, samples were collected at locations upstream and downstream of the municipal effluents or animal-feeding operations. All six wells were in agricultural settings. A total of 120 environmental samples and 21 quality-control samples were analyzed for the study. Samples were collected at each site in March/April, May, July, and September 2006 to obtain information on changes in concentration that could be related to seasonal use of compounds.For streams, 13 pharmaceuticals and 11 antibiotics were detected at least 1 time. Detections included analytical results that were estimated or above the minimum reporting limits. Seventy-eight percent of all detections were analyzed in samples collected downstream from municipal-wastewater effluents. For streams receiving wastewater effluents, the pharmaceuticals caffeine and para-xanthine (a degradation product of caffeine) had the greatest concentrations, 4.75 μg/L (micrograms per liter) and 0.853 μg/L, respectively. Other pharmaceuticals and their respective maximum concentrations were carbamazepine (0.516 μg/L) and ibuprofen (0.277 μg/L). For streams receiving wastewater effluents, the antibiotic azithromycin had the greatest concentration (1.65 μg/L), followed by sulfamethoxazole (1.34 μg/L), ofloxacin (0.329

  4. Transformation of saturated nitrogen-containing heterocyclic compounds by microorganisms.

    Science.gov (United States)

    Parshikov, Igor A; Silva, Eliane O; Furtado, Niege A J C

    2014-02-01

    The saturated nitrogen-containing heterocyclic compounds include many drugs and compounds that may be used as synthons for the synthesis of other pharmacologically active substances. The need for new derivatives of saturated nitrogen-containing heterocycles for organic synthesis, biotechnology and the pharmaceutical industry, including optically active derivatives, has increased interest in microbial synthesis. This review provides an overview of microbial technologies that can be valuable to produce new derivatives of saturated nitrogen-containing heterocycles, including hydroxylated derivatives. The chemo-, regio- and enantioselectivity of microbial processes can be indispensable for the synthesis of new compounds. Microbial processes carried out with fungi, including Beauveria bassiana, Cunninghamella verticillata, Penicillium simplicissimum, Aspergillus niger and Saccharomyces cerevisiae, and bacteria, including Pseudomonas sp., Sphingomonas sp. and Rhodococcus erythropolis, biotransform many substrates efficiently. Among the biological activities of saturated nitrogen-containing heterocyclic compounds are antimicrobial, antitumor, antihypertensive and anti-HIV activities; some derivatives are effective for the treatment and prevention of malaria and trypanosomiasis, and others are potent glycosidase inhibitors.

  5. NPACT: Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database.

    Science.gov (United States)

    Mangal, Manu; Sagar, Parul; Singh, Harinder; Raghava, Gajendra P S; Agarwal, Subhash M

    2013-01-01

    Plant-derived molecules have been highly valued by biomedical researchers and pharmaceutical companies for developing drugs, as they are thought to be optimized during evolution. Therefore, we have collected and compiled a central resource Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database (NPACT, http://crdd.osdd.net/raghava/npact/) that gathers the information related to experimentally validated plant-derived natural compounds exhibiting anti-cancerous activity (in vitro and in vivo), to complement the other databases. It currently contains 1574 compound entries, and each record provides information on their structure, manually curated published data on in vitro and in vivo experiments along with reference for users referral, inhibitory values (IC(50)/ED(50)/EC(50)/GI(50)), properties (physical, elemental and topological), cancer types, cell lines, protein targets, commercial suppliers and drug likeness of compounds. NPACT can easily be browsed or queried using various options, and an online similarity tool has also been made available. Further, to facilitate retrieval of existing data, each record is hyperlinked to similar databases like SuperNatural, Herbal Ingredients' Targets, Comparative Toxicogenomics Database, PubChem and NCI-60 GI(50) data.

  6. NPACT: Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database

    Science.gov (United States)

    Mangal, Manu; Sagar, Parul; Singh, Harinder; Raghava, Gajendra P. S.; Agarwal, Subhash M.

    2013-01-01

    Plant-derived molecules have been highly valued by biomedical researchers and pharmaceutical companies for developing drugs, as they are thought to be optimized during evolution. Therefore, we have collected and compiled a central resource Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database (NPACT, http://crdd.osdd.net/raghava/npact/) that gathers the information related to experimentally validated plant-derived natural compounds exhibiting anti-cancerous activity (in vitro and in vivo), to complement the other databases. It currently contains 1574 compound entries, and each record provides information on their structure, manually curated published data on in vitro and in vivo experiments along with reference for users referral, inhibitory values (IC50/ED50/EC50/GI50), properties (physical, elemental and topological), cancer types, cell lines, protein targets, commercial suppliers and drug likeness of compounds. NPACT can easily be browsed or queried using various options, and an online similarity tool has also been made available. Further, to facilitate retrieval of existing data, each record is hyperlinked to similar databases like SuperNatural, Herbal Ingredients’ Targets, Comparative Toxicogenomics Database, PubChem and NCI-60 GI50 data. PMID:23203877

  7. Individual and mixture effects of selected pharmaceuticals on larval development of the estuarine shrimp Palaemon longirostris.

    Science.gov (United States)

    González-Ortegón, Enrique; Blasco, Julian; Nieto, Elena; Hampel, Miriam; Le Vay, Lewis; Giménez, Luis

    2016-01-01

    Few ecotoxicological studies incorporate within the experimental design environmental variability and mixture effects when assessing the impact of pollutants on organisms. We have studied the combined effects of selected pharmaceutical compounds and environmental variability in terms of salinity and temperature on survival, development and body mass of larvae of the estuarine shrimp Palaemon longirostris. Drug residues found in coastal waters occur as mixture, and the evaluation of combined effects of simultaneously occurring compounds is indispensable for their environmental risk assessment. All larval stages of P. longirostris were exposed to the nonsteroidal anti-inflammatory drug (NSAID) diclofenac sodium (DS: 40 and 750 μg L(-1)), the lipid regulator clofibric acid (CA: 17 and 361 μg L(-1)) and the fungicide clotrimazole (CLZ: 0.14 and 4 μg L(-1)). We observed no effect on larval survival of P. longirostris with the tested pharmaceuticals. However, and in contrast to previous studies on larvae of the related marine species Palaemon serratus, CA affected development through an increase in intermoult duration and reduced growth without affecting larval body mass. These developmental effects in P. longirostris larvae were similar to those observed in the mixture of DS and CA confirming the toxic effects of CA. In the case of CLZ, its effects were similar to those observed previously in P. serratus: high doses affected development altering intermoult duration, tended to reduce the number of larval instars and decreased significantly the growth rate. This study suggests that an inter-specific life histories approach should be taken into account to assess the effect of emergent compounds in coastal waters. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Pharmaceutical salts and cocrystals involving amino acids: a brief structural overview of the state-of-art.

    Science.gov (United States)

    Tilborg, Anaëlle; Norberg, Bernadette; Wouters, Johan

    2014-03-03

    Salification of new drug substances in order to improve physico-chemical or solid-state properties (e.g. dissolution rate or solubility, appropriate workup process, storage for further industrial and marketing development) is a well-accepted procedure. Amino acids, like aspartic acid, lysine or arginine take a great part in this process and are implicated in several different formulations of therapeutic agent families, including antibiotics (amoxicillin from beta lactam class or cephalexin from cephalosporin class), NSAIDs (ketoprofen, ibuprofen and naproxen from profen family, acetylsalicylic acid) or antiarrhythmic agents (e.g. ajmaline). Even if more than a half of known pharmaceutical molecules possess a salifiable moiety, what can be done for new potential drug entity that cannot be improved by transformation into a salt? In this context, after a brief review of pharmaceutical salts on the market and the implication of amino acids in these formulations, we focus on the advantage of using amino acids even when the target compound is not salifiable by exploiting their zwitterionic potentialities for cocrystal edification. We summarize here a series of new examples coming from literature to support the advantages of broadening the application of amino acids in formulation for new drug substances improvement research for non-salifiable molecules. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  9. Toxic Compounds Analysis With High Performance Liquid Chromatography Detected By Electro Chemical Detector (Ecd)

    OpenAIRE

    Hideharu Shintaniq

    2014-01-01

    The principal area of application of high performance liquid chromatography-electrochemical detector (HPLC-ECD) has been in the analysis of naturally-occurring analytes, such as catecholamines, and pharmaceuticals in biological samples, HPLC-ECD has also applied to the analysis of pesticides and other analytes of interest to the toxicologist. In this paper, toxic area is described. In these, ammatoxins, aromatic amine, nitro-compounds, algal toxins, fungal toxins, pesticides, veterinary drug ...

  10. Pharmaceutical policies: effects of financial incentives for prescribers.

    Science.gov (United States)

    Rashidian, Arash; Omidvari, Amir-Houshang; Vali, Yasaman; Sturm, Heidrun; Oxman, Andrew D

    2015-08-04

    The proportion of total healthcare expenditures spent on drugs has continued to grow in countries of all income categories. Policy-makers are under pressure to control pharmaceutical expenditures without adversely affecting quality of care. Financial incentives seeking to influence prescribers' behaviour include budgetary arrangements at primary care and hospital settings (pharmaceutical budget caps or targets), financial rewards for target behaviours or outcomes (pay for performance interventions) and reduced benefit margin for prescribers based on medicine sales and prescriptions (pharmaceutical reimbursement rate reduction policies). This is the first update of the original version of this review. To determine the effects of pharmaceutical policies using financial incentives to influence prescribers' practices on drug use, healthcare utilisation, health outcomes and costs (expenditures). We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (searched 29/01/2015); MEDLINE, Ovid SP (searched 29/01/2015); EMBASE, Ovid SP (searched 29/01/2015); International Network for Rational Use of Drugs (INRUD) Bibliography (searched 29/01/2015); National Health Service (NHS) Economic Evaluation Database (searched 29/01/2015); EconLit - ProQuest (searched 02/02/2015); and Science Citation Index and Social Sciences Citation Index, Institute for Scientific Information (ISI) Web of Knowledge (citation search for included studies searched 10/02/2015). We screened the reference lists of relevant reports and contacted study authors and organisations to identify additional studies. We included policies that intend to affect prescribing by means of financial incentives for prescribers. Included in this category are pharmaceutical budget caps or targets, pay for performance and drug reimbursement rate reductions and other financial policies, if they were specifically targeted at prescribing or drug utilisation. Policies in this review were defined as laws, rules

  11. Pharmaceutical removal in tropical subsurface flow constructed wetlands at varying hydraulic loading rates.

    Science.gov (United States)

    Zhang, Dong Qing; Gersberg, Richard M; Hua, Tao; Zhu, Junfei; Tuan, Nguyen Anh; Tan, Soon Keat

    2012-04-01

    Determining the fate of emerging organic contaminants in an aquatic ecosystem is important for developing constructed wetlands (CWs) treatment technology. Experiments were carried out in subsurface flow CWs in Singapore to evaluate the fate and transport of eight pharmaceutical compounds. The CW system included three parallel horizontal subsurface flow CWs and three parallel unplanted beds fed continuously with synthetic wastewater at different hydraulic retention times (HRTs). The findings of the tests at 2-6 d HRTs showed that the pharmaceuticals could be categorized as (i) efficiently removed compounds with removal higher than 85% (ketoprofen and salicylic acid); (ii) moderately removed compounds with removal efficiencies between 50% and 85% (naproxen, ibuprofen and caffeine); and (iii) poorly removed compounds with efficiency rate lower than 50% (carbamazepine, diclofenac, and clofibric acid). Except for carbamazepine and salicylic acid, removal efficiencies of the selected pharmaceuticals showed significant (pcaffeine, ketoprofen and clofibric acid were found to follow first order decay kinetics with decay constants higher in the planted beds than the unplanted beds. Correlations between pharmaceutical removal efficiencies and log K(ow) were not significant (p>0.05), implying that their removal is not well related to the compound's hydrophobicity. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Fate and distribution of pharmaceuticals in wastewater and sewage sludge of the conventional activated sludge (CAS) and advanced membrane bioreactor (MBR) treatment.

    Science.gov (United States)

    Radjenović, Jelena; Petrović, Mira; Barceló, Damià

    2009-02-01

    In this paper we report on the performances of full-scale conventional activated sludge (CAS) treatment and two pilot-scale membrane bioreactors (MBRs) in eliminating various pharmaceutically active compounds (PhACs) belonging to different therapeutic groups and with diverse physico-chemical properties. Both aqueous and solid phases were analysed for the presence of 31 pharmaceuticals included in the analytical method. The most ubiquitous contaminants in the sewage water were analgesics and anti-inflammatory drugs ibuprofen (14.6-31.3 microg/L) and acetaminophen (7.1-11.4 microg/L), antibiotic ofloxacin (0.89-31.7 microg/L), lipid regulators gemfibrozil (2.0-5.9 microg/L) and bezafibrate (1.9-29.8 microg/L), beta-blocker atenolol (0.84-2.8 microg/L), hypoglycaemic agent glibenclamide (0.12-15.9 microg/L) and a diuretic hydrochlorothiazide (2.3-4.8 microg/L). Also, several pharmaceuticals such as ibuprofen, ketoprofen, diclofenac, ofloxacin and azithromycin were detected in sewage sludge at concentrations up to 741.1, 336.3, 380.7, 454.7 and 299.6 ng/g dry weight. Two pilot-scale MBRs exhibited enhanced elimination of several pharmaceutical residues poorly removed by the CAS treatment (e.g., mefenamic acid, indomethacin, diclofenac, propyphenazone, pravastatin, gemfibrozil), whereas in some cases more stable operation of one of the MBR reactors at prolonged SRT proved to be detrimental for the elimination of some compounds (e.g., beta-blockers, ranitidine, famotidine, erythromycin). Moreover, the anti-epileptic drug carbamazepine and diuretic hydrochlorothiazide by-passed all three treatments investigated. Furthermore, sorption to sewage sludge in the MBRs as well as in the entire treatment line of a full-scale WWTP is discussed for the encountered analytes. Among the pharmaceuticals encountered in sewage sludge, sorption to sludge could be a relevant removal pathway only for several compounds (i.e., mefenamic acid, propranolol, and loratidine). Especially in the

  13. Tidal impact on the dynamic behavior of dissolved pharmaceuticals in the Yangtze Estuary, China.

    Science.gov (United States)

    Zhao, Heng; Zhou, Jun Liang; Zhang, Jing

    2015-12-01

    The dynamic behavior of 24 dissolved pharmaceuticals over tidal cycles in the Yangtze Estuary, China was studied to assess the tidal impact on the fate of pharmaceutical residues. The results show that most pharmaceuticals were frequently detected with concentrations from below detection to 27.2 ng/L, with sulfamethoxazole, sulfamethazine, erythromycin, thiamphenicol and florfenicol dominating. During tidal cycles, pharmaceutical concentrations decreased during tidal rise, then increasing during tidal receding for all locations, except at site S2 which showed an opposite trend due to unique water movement there. It was observed that most compounds showed a non-conservative behavior, while diazepam and sulfamethoxazole displayed a conservative behavior. The pharmaceutical concentrations were found to increase with dissolved organic carbon (DOC) concentration, suggesting DOC as a carrier of pharmaceuticals. In addition, many compounds showed a significant negative relationship with suspended particulate matter (SPM) concentration, indicating SPM-water interactions as a control of pharmaceutical behavior in estuarine environment. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Electromembrane extraction for pharmaceutical and biomedical analysis

    DEFF Research Database (Denmark)

    Huang, Chuixiu; Seip, Knut Fredrik; Gjelstad, Astrid

    2015-01-01

    . The present paper discusses recent development of EME. The paper focuses on the principles of EME, and discusses how to optimize operational parameters. In addition, pharmaceutical and biomedical applications of EME are reviewed, with emphasis on basic drugs, acidic drugs, amino acids, and peptides. Finally...

  15. The occurrence of pharmaceuticals, personal care products, endocrine disruptors and illicit drugs in surface water in South Wales, UK.

    Science.gov (United States)

    Kasprzyk-Hordern, Barbara; Dinsdale, Richard M; Guwy, Alan J

    2008-07-01

    The presence and fate of 56 pharmaceuticals, personal care products, endocrine disruptors and illicit drugs (PPCPs) were investigated in the South Wales region of the UK. Two contrasting rivers: River Taff and River Ely were chosen for this investigation and were monitored for a period of 10 months. The impact of the factors affecting the levels of concentration of PPCPs and illicit drugs in surface water such as surrounding area, proximity to wastewater effluent and weather conditions, mainly rainfall was also investigated. Most PPCPs were frequently found in river water at concentrations reaching single microgL(-1) and their levels depended mainly on the extent of water dilution resulting from rainfall. Discharge of treated wastewater effluent into the river course was found to be the main cause of water contamination with PPCPs. The most frequently detected PPCPs represent the group of pharmaceuticals dispensed at the highest levels in the Welsh community. These were antibacterial drugs (trimethoprim, erythromycin-H(2)O and amoxicillin), anti-inflammatories/analgesics (paracetamol, tramadol, codeine, naproxen, ibuprofen and diclofenac) and antiepileptic drugs (carbamazepine and gabapentin). Only four PPCPs out of 56 (simvastatin, pravastatin, digoxin and digoxigenin) were not quantified over the course of the study. Several PPCPs were found to be both ubiquitous and persistent in the aqueous environment (e.g. erythromycin-H(2)O, codeine, carbamazepine, gabapentin and valsartan). The calculated average daily loads of PPCPs indicated that in total almost 6 kg of studied PPCPs are discharged daily into the studied rivers. The illicit drugs studied were found in rivers at low levels of ng L(-1). Average daily loads of amphetamine, cocaine and its main metabolite benzoylecgonine were as follows: 8, 1.2 and 39 gday(-1), respectively. Their frequent occurrence in surface water is primarily associated with their high illegal usage and is strongly associated with the

  16. Emerging contaminants in Belgian marine waters: single toxicant and mixture risks of pharmaceuticals.

    Science.gov (United States)

    Claessens, Michiel; Vanhaecke, Lynn; Wille, Klaas; Janssen, Colin R

    2013-06-15

    Knowledge on the effects of pharmaceuticals on aquatic marine ecosystems is limited. The aim of this study was therefore to establish the effect thresholds of pharmaceutical compounds occurring in the Belgian marine environment for the marine diatom Phaeodactylum tricornutum, and subsequently perform an environmental risk assessment for these substances. Additionally, a screening-level risk assessment was performed for the pharmaceutical mixtures. No immediate risk for acute toxic effects of these compounds on P. tricornutum were apparent at the concentrations observed in the Belgian marine environment. In two Belgian coastal harbours however, a potential chronic risk was observed for the β-blocker propranolol. No additional risks arising from the exposure to mixtures of pharmaceuticals present in the sampling area could be detected. However, as risk characterization ratios for mixtures of up to 0.5 were observed, mixture effects could emerge should more compounds be taken into account. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Downstream Processability of Crystal Habit-Modified Active Pharmaceutical Ingredient

    DEFF Research Database (Denmark)

    Pudasaini, Nawin; Upadhyay, Pratik Pankaj; Parker, Christian Richard

    2017-01-01

    Efficient downstream processing of active pharmaceutical ingredients (APIs) can depend strongly on their particulate properties, such as size and shape distributions. Especially in drug products with high API content, needle-like crystal habit of an API may show compromised flowability and tablet......Efficient downstream processing of active pharmaceutical ingredients (APIs) can depend strongly on their particulate properties, such as size and shape distributions. Especially in drug products with high API content, needle-like crystal habit of an API may show compromised flowability...

  18. Impact of pharmaceutical care on adherence, hospitalisations and mortality in elderly patients

    DEFF Research Database (Denmark)

    Olesen, Charlotte; Harbig, Philipp; Buus, Kirsten Marie

    2014-01-01

    = 315) was designed. It involved patients aged 65+ years living in Aarhus, Denmark who used five drugs or more without assistance. Pharmacists visited the pharmaceuticalcare patients at home, once only, and followed them during the subsequent year with three telephone calls. Non-adherence was measured......, hospitalisation and mortality. Results The final analyses included 517 patients (median age 74 years; females 52 %). Dropouts were more frequent for the pharmaceutical-care group than for controls. Pharmacists encountered drug-related problems amongst 72 % of pharmaceutical-care patients. Pharmaceutical...

  19. Materials science tetrahedron--a useful tool for pharmaceutical research and development.

    Science.gov (United States)

    Sun, Changquan Calvin

    2009-05-01

    The concept of materials science tetrahedron (MST) concisely depicts the inter-dependent relationship among the structure, properties, performance, and processing of a drug. Similar to its role in traditional materials science, MST encompasses the development in the emerging field of pharmaceutical materials science and forms a scientific foundation to the design and development of new drug products. Examples are given to demonstrate the applicability of MST to both pharmaceutical research and product development. It is proposed that a systematic implementation of MST can expedite the transformation of pharmaceutical product development from an art to a science. By following the principle of MST, integration of research among different laboratories can be attained. The pharmaceutical science community as a whole can conduct more efficient, collaborative, and coherent research.

  20. 78 FR 19017 - Manufacturer of Controlled Substances; Notice of Application; Johnson Matthey Pharmaceutical...

    Science.gov (United States)

    2013-03-28

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances; Notice of Application; Johnson Matthey Pharmaceutical Materials, Inc. Pursuant to Sec. 1301.33(a), Title... Matthey Pharmaceutical Materials, Inc., Pharmaceutical Service, 25 Patton Road, Devens, Massachusetts...

  1. Tamoxifen from Failed Contraceptive Pill to Best-Selling Breast Cancer Medicine: A Case-Study in Pharmaceutical Innovation

    Directory of Open Access Journals (Sweden)

    Viviane M. Quirke

    2017-09-01

    Full Text Available Today, tamoxifen is one of the world's best-selling hormonal breast cancer drugs. However, it was not always so. Compound ICI 46,474 (as it was first known was synthesized in 1962 within a project to develop a contraceptive pill in the pharmaceutical laboratories of ICI (now part of AstraZeneca. Although designed to act as an anti-estrogen, the compound stimulated, rather than suppressed ovulation in women. This, and the fact that it could not be patented in the USA, its largest potential market, meant that ICI nearly stopped the project. It was saved partly because the team's leader, Arthur Walpole, threatened to resign, and pressed on with another project: to develop tamoxifen as a treatment for breast cancer. Even then, its market appeared small, because at first it was mainly used as a palliative treatment for advanced breast cancer. An important turning point in tamoxifen's journey from orphan drug to best-selling medicine occurred in the 1980s, when clinical trials showed that it was also useful as an adjuvant to surgery and chemotherapy in the early stages of the disease. Later, trials demonstrated that it could prevent its occurrence or re-occurrence in women at high risk of breast cancer. Thus, it became the first preventive for any cancer, helping to establish the broader principles of chemoprevention, and extending the market for tamoxifen and similar drugs further still. Using tamoxifen as a case study, this paper discusses the limits of the rational approach to drug design, the role of human actors, and the series of feedback loops between bench and bedside that underpins pharmaceutical innovation. The paper also highlights the complex evaluation and management of risk that are involved in all therapies, but more especially perhaps in life-threatening and emotion-laden diseases like cancer.

  2. Competitive pricing within pharmaceutical classes: evidence on "follow-on" drugs in Germany 1993-2008.

    Science.gov (United States)

    Mueller, Michael T; Frenzel, Alexander

    2015-01-01

    Competition from "follow-on" drugs has been a highly controversial issue. Manufacturers launching new molecules in existing drug classes have often been criticized for inflating health systems' expenses, but it has been argued that such drugs increase therapeutic options. Economic theory suggests that follow-on drugs induce price competition. We contribute to this discussion by addressing the topic of pricing at market entry and price development in the German market. We measure determinants of price strategies of follow-on drugs using regression analyses, considering all new molecules launched in the German market from 1993 to 2008. Prices of products are standardized on defined daily dosages controlling for sales volumes based on data from the IMS Health DPM database and for the therapeutic quality of a new product using ratings by Fricke/Klaus as a proxy for innovation. We identify prices correlating with therapeutic value at market entry. While the first two molecules engage in quality competition, price discounts below the market price can be observed from the third entrant on. Price discounts are even more distinct in development races with several drugs entering the market within 2 years and in classes with a low degree of therapeutic differentiation. Prices remain relatively constant over time. This study contributes to assessments of competition in pharmaceutical markets focusing on price strategies of new market entrants. After an initial phase of market building, further follow-on products induce price competition. Largely unchanged prices after 4 years may be interpreted as quality competition and can be attributed to prices in Germany being anchor points for international price referencing.

  3. Private versus social incentives for pharmaceutical innovation

    OpenAIRE

    González, Paula

    2016-01-01

    We provide a theoretical framework to contribute to the current debate regarding the tendency of pharmaceutical companies to direct their R&D toward marketing products that are follow-on drugs of already existing drugs, rather than toward the development of breakthrough drugs. We construct a model with a population of patients who can be treated with drugs that are horizontally and vertically differentiated. In addition to a pioneering drug, a new drug can be marketed as the result of an inno...

  4. Private versus Social Incentives for Pharmaceutical Innovation

    OpenAIRE

    González, Paula; Macho-Stadler, Ines; Pérez-Castrillo, David

    2015-01-01

    We provide a theoretical framework to contribute to the current debate regarding the tendency of pharmaceutical companies to direct their R&D toward marketing products that are “follow-on” drugs of already existing drugs, rather than toward the development of breakthrough drugs. We construct a model with a population of patients who can be treated with drugs that are horizontally and vertically differentiated. In addition to a pioneering drug, a new drug can be marketed as the result of an in...

  5. Natural Compounds from Mexican Medicinal Plants as Potential Drug Leads for Anti-Tuberculosis Drugs

    Directory of Open Access Journals (Sweden)

    ROCIO GÓMEZ-CANSINO

    Full Text Available ABSTRACT In Mexican Traditional Medicine 187 plant species are used in the treatment of respiratory conditions that may be associated with tuberculosis. In this contribution, we review the ethnobotany, chemistry and pharmacology of 63 species whose extracts have been assayed for antimycobacterial activity in vitro. Among these, the most potent is Aristolochia brevipes (MIC= 12.5 µg/mL, followed by Aristolochia taliscana, Citrus sinensis, Chrysactinia mexicana, Persea americana, and Olea europaea (MIC 95%, 50 µg/mL include: Amphipterygium adstringens, Larrea divaricata, and Phoradendron robinsoni. Several active compounds have been identified, the most potent are: Licarin A (isolated from A. taliscana, and 9-amino-9-methoxy-3,4-dihydro-2H-benzo[h]-chromen-2-one (transformation product of 9-methoxytariacuripyrone isolated from Aristolochia brevipes, both with MIC= 3.125 µg/mL, that is 8-fold less potent than the reference drug Rifampicin (MIC= 0.5 µg/mL. Any of the compounds or extracts here reviewed has been studied in clinical trials or with animal models; however, these should be accomplished since several are active against strains resistant to common drugs.

  6. Radiation sterilization of pharmaceuticals and biomedical products

    International Nuclear Information System (INIS)

    Blackburn, R.; Iddon, B.; Moore, J.S.; Phillips, G.O.; Power, D.M.; Woodward, T.W.

    1975-01-01

    Sterilization of pharmaceuticals by radiation is accompanied by chemical degradation which must be eliminated or minimised if the method is to be successfully applied. In order to devise ways in which the pharmaceutical can be protected it is necessary to know the yield and nature of the decomposition products, the mechanisms by which degradation occurs, and the rate constants for the reactions involved. We have obtained such data for a variety of pharmaceutical compounds, viz. vitamin B12, benzyl penicillin, sulphonamides, indoles, heparin, alginates and phenylmercurics, both in the solid state and in aqueous solution. The scope and limitations of radiation sterilization are discussed in the light of these results. (author)

  7. Stability-Indicating HPLC Assay for Determination of Idebenone in Pharmaceutical Forms

    Directory of Open Access Journals (Sweden)

    Sonoube Kombath

    2015-01-01

    Full Text Available A stability-indicating method was validated for the determination in pharmaceutical forms of idebenone a coenzyme Q10-like compound. The assay was achieved by liquid chromatography analysis using a reversed-phase C18 column and a detector set at 480 nm. The optimized mobile phase consisted of isocratic flow rate at 1.0 mL/min for 3 min with methanol. The linearity of the assay was demonstrated in the range of 3.0 to 8.0 mg/mL with a correlation coefficient r2>0.998. The limits of detection and quantification were 0.03 and 0.05 mg/mL, respectively. The intraday and interday precisions were less than 1.0%. Accuracy of the method ranged from 98.6 to 101.5% with RSD < 0.6%. Specificity of the assay showed no interference from tablets components and breakdown products formed by alkaline, acidic, oxidative, sunlight, and high temperature conditions. This method allows accurate and reliable determination of idebenone for drug stability assay in pharmaceutical studies.

  8. A Review for the Analysis of Antidepressant, Antiepileptic and Quinolone Type Drugs in Pharmaceuticals and Environmental Samples.

    Science.gov (United States)

    Rani, Susheela; Malik, Ashok Kumar; Kaur, Ramandeep; Kaur, Ripneel

    2016-09-02

    The analysis of drugs in various biological fluids is an important criterion for the determination of the physiological performance of a drug. After sampling of the biological fluid, the next step in the analytical process is sample preparation. Sample preparation is essential for isolation of desired components from complex biological matrices and greatly influences their reliable and accurate determination. The complexity of biological fluids adds to the challenge of direct determination of the drug by chromatographic analysis, therefore demanding a sample preparation step that is often time consuming, tedious and frequently overlooked. However, direct online injection methods offer the advantage of reducing sample preparation steps and enabling effective pre-concentration and clean-up of biological fluids. These procedures can be automated and therefore reduce the requirements for handling potentially infectious biomaterial, improve reproducibility, and minimize sample manipulations and potential contamination. This review is focused on the discovery and development of high-performance liquid chromatography (HPLC) and gas chromatography (GC) with different detectors. The drugs covered in this review are antiepileptics, antidepressant (AD), and quinolones. The application of these methods for determination of these drugs in biological, environmental and pharmaceutical samples has also been discussed.

  9. Pharmaceutical virtue.

    Science.gov (United States)

    Martin, Emily

    2006-06-01

    In the early history of psychopharmacology, the prospect of developing technologically sophisticated drugs to alleviate human ills was surrounded with a fervor that could be described as religious. This paper explores the subsequent history of the development of psychopharmacological agents, focusing on the ambivalent position of both the industry and its employees. Based on interviews with retired pharmaceutical employees who were active in the industry in the 1950s and 1960s when the major breakthroughs were made in the development of MAOIs and SSRIs, the paper explores the initial development of educational materials for use in sales campaigns. In addition, based on interviews with current employees in pharmaceutical sales and marketing, the paper describes the complex perspective of contemporary pharmaceutical employees who must live surrounded by the growing public vilification of the industry as rapacious and profit hungry and yet find ways to make their jobs meaningful and dignified. The paper will contribute to the understudied problem of how individuals function in positions that require them to be part of processes that on one description constitute a social evil, but on another, constitute a social good.

  10. Application of Emerging Pharmaceutical Technologies for Therapeutic Challenges of Space Exploration Missions

    Science.gov (United States)

    Putcha, Lakshmi

    2011-01-01

    An important requirement of therapeutics for extended duration exploration missions beyond low Earth orbit will be the development of pharmaceutical technologies suitable for sustained and preventive health care in remote and adverse environmental conditions. Availability of sustained, stable and targeted delivery pharmaceuticals for preventive health of major organ systems including gastrointestinal, hepato-renal, musculo-skeletal and immune function are essential to offset adverse effects of space environment beyond low Earth orbit. Specifically, medical needs may include multi-drug combinations for hormone replacement, radiation protection, immune enhancement and organ function restoration. Additionally, extended stability of pharmaceuticals dispensed in space must be also considered in future drug development. Emerging technologies that can deliver stable and multi-therapy pharmaceutical preparations and delivery systems include nanotechnology based drug delivery platforms, targeted-delivery systems in non-oral and non-parenteral formulation matrices. Synthetic nanomaterials designed with molecular precision offer defined structures, electronics, and chemistries to be efficient drug carriers with clear advantages over conventional materials of drug delivery matricies. Nano-carrier materials like the bottle brush polymers may be suitable for systemic delivery of drug cocktails while Superparamagnetic Iron Oxide Nanoparticles or (SPIONS) have great potential to serve as carriers for targeted drug delivery to a specific site. These and other emerging concepts of drug delivery and extended shelf-life technologies will be reviewed in light of their application to address health-care challenges of exploration missions. Innovations in alternate treatments for sustained immune enhancement and infection control will be also discussed.

  11. Technology-dependent children and the demand for pharmaceutical care.

    Science.gov (United States)

    Okido, Aline Cristiane Cavicchioli; Cunha, Suelen Teles da; Neves, Eliane Tatsch; Dupas, Giselle; Lima, Regina Aparecida Garcia de

    2016-01-01

    to understand the experience of mothers of technology-dependent children as regards pharmaceutical care. this was a qualitative, descriptive-exploratory study developed based on open interviews using a structured characterization tool, and applied during home visits to 12 mothers caring for technology-dependent children. The data was submitted to inductive content analysis. this study is split into two themes: (i) maternal overload during pharmaceutical care, demonstrating the need to administer drugs continuously and the repercussions of this exhaustive care on the caregivers; (ii) the ease or difficulty of access to the medicines required, showing informal strategies and support networks. pharmaceutical care is a daily challenge expressed in maternal overload and difficulty accessing the drugs, made worse by failures in the care network and coordinated care.

  12. Proposed changes to the reimbursement of pharmaceuticals and medical devices in Poland and their impact on market access and the pharmaceutical industry

    Science.gov (United States)

    Badora, Karolina; Caban, Aleksandra; Rémuzat, Cécile; Dussart, Claude; Toumi, Mondher

    2017-01-01

    ABSTRACT In Poland, two proposed amendments to the reimbursement act are currently in preparation; these are likely to substantially change the pricing and reimbursement landscape for both drugs and medical devices. Proposed changes include: alignment of medical device reimbursement with that of pharmaceuticals; relaxing the strict reimbursement criteria for ultra-orphan drugs; establishment of an additional funding category for vaccines; introduction of compassionate use, and a simplified reimbursement pathway for well-established off-label indications; appreciation of manufacturers’ innovation and research and development efforts by creating a dedicated innovation budget; introduction of a mechanism preventing excessive parallel import; prolonged duration of reimbursement decisions and reimbursement lists; and increased flexibility in defining drug programmes. Both amendments are still at a draft stage and many aspects of the new regulations remain unclear. Nonetheless, the overall direction of some of the changes is already evident and warrants discussion due to their high expected impact on pharmaceutical and device manufacturers. Here we evaluate the main changes proposed to the reimbursement of drugs, vaccines, and medical devices, and examine the impact they are likely to have on market access and pharmaceutical industry in Poland. PMID:29081924

  13. Scientific misconduct, the pharmaceutical industry, and the tragedy of institutions.

    Science.gov (United States)

    Cohen-Kohler, Jillian Clare; Esmail, Laura C

    2007-09-01

    This paper examines how current legislative and regulatory models do not adequately govern the pharmaceutical industry towards ethical scientific conduct. In the context of a highly profit-driven industry, governments need to ensure ethical and legal standards are not only in place for companies but that they are enforceable. We demonstrate with examples from both industrialized and developing countries how without sufficient controls, there is a risk that corporate behaviour will transgress ethical boundaries. We submit that there is a critical need for urgent drug regulatory reform. There must be robust regulatory structures in place which enforce corporate governance mechanisms to ensure that pharmaceutical companies maintain ethical standards in drug research and development and the marketing of pharmaceuticals. What is also needed is for the pharmaceutical industry to adopt authentic "corporate social responsibility" policies as current policies and practices are insufficient.

  14. Pharmaceutical product development: A quality by design approach

    Science.gov (United States)

    Pramod, Kannissery; Tahir, M. Abu; Charoo, Naseem A.; Ansari, Shahid H.; Ali, Javed

    2016-01-01

    The application of quality by design (QbD) in pharmaceutical product development is now a thrust area for the regulatory authorities and the pharmaceutical industry. International Conference on Harmonization and United States Food and Drug Administration (USFDA) emphasized the principles and applications of QbD in pharmaceutical development in their guidance for the industry. QbD attributes are addressed in question-based review, developed by USFDA for chemistry, manufacturing, and controls section of abbreviated new drug applications. QbD principles, when implemented, lead to a successful product development, subsequent prompt regulatory approval, reduce exhaustive validation burden, and significantly reduce post-approval changes. The key elements of QbD viz., target product quality profile, critical quality attributes, risk assessments, design space, control strategy, product lifecycle management, and continual improvement are discussed to understand the performance of dosage forms within design space. Design of experiments, risk assessment tools, and process analytical technology are also discussed for their role in QbD. This review underlines the importance of QbD in inculcating science-based approach in pharmaceutical product development. PMID:27606256

  15. Pharmaceutical product development: A quality by design approach.

    Science.gov (United States)

    Pramod, Kannissery; Tahir, M Abu; Charoo, Naseem A; Ansari, Shahid H; Ali, Javed

    2016-01-01

    The application of quality by design (QbD) in pharmaceutical product development is now a thrust area for the regulatory authorities and the pharmaceutical industry. International Conference on Harmonization and United States Food and Drug Administration (USFDA) emphasized the principles and applications of QbD in pharmaceutical development in their guidance for the industry. QbD attributes are addressed in question-based review, developed by USFDA for chemistry, manufacturing, and controls section of abbreviated new drug applications. QbD principles, when implemented, lead to a successful product development, subsequent prompt regulatory approval, reduce exhaustive validation burden, and significantly reduce post-approval changes. The key elements of QbD viz., target product quality profile, critical quality attributes, risk assessments, design space, control strategy, product lifecycle management, and continual improvement are discussed to understand the performance of dosage forms within design space. Design of experiments, risk assessment tools, and process analytical technology are also discussed for their role in QbD. This review underlines the importance of QbD in inculcating science-based approach in pharmaceutical product development.

  16. Pharmaceutically active secondary metabolites of marine actinobacteria.

    Science.gov (United States)

    Manivasagan, Panchanathan; Venkatesan, Jayachandran; Sivakumar, Kannan; Kim, Se-Kwon

    2014-04-01

    Marine actinobacteria are one of the most efficient groups of secondary metabolite producers and are very important from an industrial point of view. Many representatives of the order Actinomycetales are prolific producers of thousands of biologically active secondary metabolites. Actinobacteria from terrestrial sources have been studied and screened since the 1950s, for many important antibiotics, anticancer, antitumor and immunosuppressive agents. However, frequent rediscovery of the same compounds from the terrestrial actinobacteria has made them less attractive for screening programs in the recent years. At the same time, actinobacteria isolated from the marine environment have currently received considerable attention due to the structural diversity and unique biological activities of their secondary metabolites. They are efficient producers of new secondary metabolites that show a range of biological activities including antibacterial, antifungal, anticancer, antitumor, cytotoxic, cytostatic, anti-inflammatory, anti-parasitic, anti-malaria, antiviral, antioxidant, anti-angiogenesis, etc. In this review, an evaluation is made on the current status of research on marine actinobacteria yielding pharmaceutically active secondary metabolites. Bioactive compounds from marine actinobacteria possess distinct chemical structures that may form the basis for synthesis of new drugs that could be used to combat resistant pathogens. With the increasing advancement in science and technology, there would be a greater demand for new bioactive compounds synthesized by actinobacteria from various marine sources in future. Copyright © 2013 Elsevier GmbH. All rights reserved.

  17. 77 FR 60124 - Draft Guidance for Industry on Initial Completeness Assessments for Type II Active Pharmaceutical...

    Science.gov (United States)

    2012-10-02

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-1010] Draft Guidance for Industry on Initial Completeness Assessments for Type II Active Pharmaceutical... certain drug master files, namely, Type II active pharmaceutical ingredient (API) drug master files (DMFs...

  18. Stability-Indicating RP-HPLC Method for Determination of Guanfacine Hydrochloride in Bulk Drugs and in Pharmaceutical Dosage Form

    Directory of Open Access Journals (Sweden)

    Vinod K. Ahirrao

    2011-04-01

    Full Text Available A novel stability-indicating RP-HPLC method was developed and validated for quantitative determination of guanfacine hydrochloride in bulk drug and in pharmaceutical dosage form. An isocratic, reversed phase HPLC method was developed to separate the drug from the degradation products, using Apollo, C18 (250mm x 4.6mm, 5µm column with mobile phase of 50mM Ammonium acetate (volatile buffer and acetonitrile (65:35, v/v. UV detection has been done at wavelength 220 nm. The guanfacine hydrochloride was subjected to the stress conditions of hydrolysis (acid, base, oxidation, photolysis and thermal degradation. The stressed samples were analyzed by the proposed method. The analyte peak shape was excellent. The described method shows excellent linearity over a range of 30 – 450 µg/mL. The correlation coefficient for guanfacine hydrochloride was 0.999. The limit of detection for Guanfacine hydrochloride is 0.011 µg/mL and the limit of quantification is 0.038 µg/mL respectively.Degradation was observed for guanfacine hydrochloride in base, thermal and in 30% H2O2 conditions. The drug was found to be stable in the other stress conditions attempted. The degradation products were well resolved from main peak. The percentage recovery of guanfacine hydrochloride was ranged from (99.2% to 100.5% in pharmaceutical dosage form. The developed method was validated with respect to the linearity, accuracy (recovery, precision, specificity and robustness. The forced degradation studies prove the stability indicating power of the method.

  19. Pharmaceutical Applications of Polymeric Nano materials

    International Nuclear Information System (INIS)

    Wu, L.; Sun, L.

    2011-01-01

    With significant attention focused on nano science and nano technology in recent years, nano materials have been used in a wide variety of applications such as automotive, environmental, energy, catalysis, biomedical, drug delivery, and polymeric industries. Among those fields, the application of nano materials with pharmaceutical science is an emerging and rapidly growing field and has drawn increasing attention recently. Research and development in this field is mainly focused on several aspects such as the discoveries of novel functional nano materials, exploration on nanoparticles with controlled and targeted drug delivery characteristics, and investigation of bio functionalized and diagnostic nano materials. In this special issue, we have invited a few papers related to recent advances in pharmaceutical application of polymeric nano materials

  20. Pharmaceutical industry marketing: understanding its impact on women's health.

    Science.gov (United States)

    Sufrin, Carolyn B; Ross, Joseph S

    2008-09-01

    The delivery of modern health care entails significant involvement from the pharmaceutical industry, including developing and manufacturing drugs. However, the industry also has tremendous influence on the practice of medicine through its considerable marketing efforts, both to patients through direct to consumer advertising, and to physicians through detailing, providing samples, continuing medical education, and other efforts. This article will review the role that pharmaceutical marketing plays in health care, and the substantial evidence surrounding its influence on patient and physician behaviors, with additional discussion of the medical device industry, all with particular attention to women's health. Understanding the effects of pharmaceutical marketing on women's health, through discussion of relevant examples-including oral contraceptive pills, drugs for premenstrual dysphoric disorder, Pap smear cytology techniques, and neonatal herpes prophylaxis-will help ensure that women receive unbiased, evidenced-based care. We will conclude with a discussion of guidelines that have been proposed by professional organizations, policy makers, and universities, to assist physicians in managing exposure to pharmaceutical marketing.