Effects of pharmaceutical processing on pepsin activity during the formulation of solid dosage forms.

Science.gov (United States)

Kristó, Katalin; Pintye-Hódi, Klára

2013-02-01

The main aim of this study was to investigate the effects of pharmaceutical technological methods on pepsin activity during the formulation of solid dosage forms. The circumstances of direct compression and wet granulation were modeled. During direct compression, the heat and the compression force must be taken into consideration. The effects of these parameters were investigated in three materials (pure pepsin, and 1:1 (w/w) pepsin-tartaric acid and 1:1 (w/w) pepsin-citric acid powder mixtures). It was concluded that direct compression is appropriate for the formulation of solid dosage forms containing pepsin through application without acids or with acids at low compression force. The effects of wet granulation were investigated with a factorial design for the same three materials. The factors were time, temperature and moisture content. There was no significant effect of the factors when acids were not applied. Temperature was a significant factor when acids were applied. The negative effect was significantly higher for citric acid than for tartaric acid. It was found that wet granulation can be utilized for the processing of pepsin into solid dosage forms under well-controlled circumstances. The application of citric acid is not recommended during the formulation of solid dosage forms through wet granulation. A mathematically based optimization may be necessary for preformulation studies of the preparation of dosage forms containing sensitive enzymes.

Development of Direct Reversed-Phase High Performance liquid chromatographic method for quantitative determination of gabapentin in pharmaceutical dosage

International Nuclear Information System (INIS)

Hassan, W.; Zaman, B.; Rahman, S.; Rahman, A.U.; Ali, N.; Mohammadzai, I.U.

2012-01-01

The objective of the present work was to develop and validate a rapid analytical method for quantitative determination of Gabapentin in pharmaceutical dosage tablets and capsules. An accurate, simple, and sensitive reversed-phase high performance liquid chromatographic (HPLC) method, UV detection at 215 nm and flow rate at 1.0 ml/min has been developed. Isocratic elution was used instead of gradient elution to reduce the time and cost of serial analysis. The mobile phase was a mixture of water and methanol (HPLC grade). The retention time (Rt) of Gabapentin was 4.681 +- 0.013 minutes. Recovery, Precision, accuracy, and linearity were determined for the stated method. The calibration curve was linear and the correlation coefficient was 0.9996. There was no chromatographic interference from other excipients present in dosage form. The method was validated appropriately and successfully used for determination of Gabapentin in Pharmaceutical formulations. (author)

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)...

Advances in solid dosage form manufacturing technology.

Science.gov (United States)

Andrews, Gavin P

2007-12-15

Currently, the pharmaceutical and healthcare industries are moving through a period of unparalleled change. Major multinational pharmaceutical companies are restructuring, consolidating, merging and more importantly critically assessing their competitiveness to ensure constant growth in an ever-more demanding market where the cost of developing novel products is continuously increasing. The pharmaceutical manufacturing processes currently in existence for the production of solid oral dosage forms are associated with significant disadvantages and in many instances provide many processing problems. Therefore, it is well accepted that there is an increasing need for alternative processes to dramatically improve powder processing, and more importantly to ensure that acceptable, reproducible solid dosage forms can be manufactured. Consequently, pharmaceutical companies are beginning to invest in innovative processes capable of producing solid dosage forms that better meet the needs of the patient while providing efficient manufacturing operations. This article discusses two emerging solid dosage form manufacturing technologies, namely hot-melt extrusion and fluidized hot-melt granulation.

Continuous powder feeding for pharmaceutical solid dosage form manufacture: a short review.

Science.gov (United States)

Blackshields, Caroline A; Crean, Abina M

2018-07-01

There has been a noticeable shift from pharmaceutical batch processing towards a more continuous mode of manufacture for solid oral dosage forms. Continuous solid oral dose processes would not be possible in the absence of a highly accurate feeding system. The performance of feeders defines the content of formulations and is therefore a critical operation in continuous manufacturing of solid dosage forms. It was the purpose of this review to review the role of the initial powder feeding step in a continuous manufacturing process. Different feeding mechanisms are discussed with a particular emphasis on screw controlled loss in weight (LIW) feeding. The importance of understanding the physical properties of the raw materials and its impact on the feeding process is reviewed. Prior knowledge of materials provides an initial indication of how the powders will behave through processing and facilitates in the selection of the most suitable (i) feeder (capacity), (ii) feeding mechanism, and (iii) in the case of screw feeder - screw type. The studies identified in this review focus on the impact of material on powder feeding performance.

New Spectrophotometric and Conductometric Methods for Macrolide Antibiotics Determination in Pure and Pharmaceutical Dosage Forms Using Rose Bengal

Directory of Open Access Journals (Sweden)

Rania A. Sayed

2013-01-01

Full Text Available Two Simple, accurate, precise, and rapid spectrophotometric and conductometric methods were developed for the estimation of erythromycin thiocyanate (I, clarithromycin (II, and azithromycin dihydrate (III in both pure and pharmaceutical dosage forms. The spectrophotometric procedure depends on the reaction of rose bengal and copper with the cited drugs to form stable ternary complexes which are extractable with methylene chloride, and the absorbances were measured at 558, 557, and 560 nm for (I, (II, and (III, respectively. The conductometric method depends on the formation of an ion-pair complex between the studied drug and rose bengal. For the spectrophotometric method, Beer's law was obeyed. The correlation coefficient ( for the studied drugs was found to be 0.9999. The molar absorptivity (, Sandell’s sensitivity, limit of detection (LOD, and limit of quantification (LOQ were also calculated. The proposed methods were successfully applied for the determination of certain pharmaceutical dosage forms containing the studied drugs

Unveiling multiple solid-state transitions in pharmaceutical solid dosage forms using multi-series hyperspectral imaging and different curve resolution approaches

DEFF Research Database (Denmark)

Alexandrino, Guilherme L; Amigo Rubio, Jose Manuel; Khorasani, Milad Rouhi

2017-01-01

Solid-state transitions at the surface of pharmaceutical solid dosage forms (SDF) were monitored using multi-series hyperspectral imaging (HSI) along with Multivariate Curve Resolution – Alternating Least Squares (MCR-ALS) and Parallel Factor Analysis (PARAFAC and PARAFAC2). First, the solid-stat...

Development and Validation of a HPLC Method for the Determination of Lacidipine in Pure Form and in Pharmaceutical Dosage Form

International Nuclear Information System (INIS)

Vinodh, M.; Vinayak, M.; Rahul, K.; Pankaj, P.

2012-01-01

A simple and reliable high-performance liquid chromatography (HPLC) method was developed and validated for Lacidipine in pure form and pharmaceutical dosage form. The method was developed on X bridge C-18 column (150 mm x 4.6 mm, 5 μm) with a mobile phase gradient system of ammonium acetate and acetonitrile. The effluent was monitored by PDA detector at 240 nm. Calibration curve was linear over the concentration range of 50-250 μg/ml. For Intra-day and inter-day precision % RSD values were found to be 0.83 % and 0.41 % respectively. Recovery of Lacidipine was found to be in the range of 99.78-101.76 %. The limits of detection (LOD) and quantification (LOQ) were 1.0 and 7.3 μg/ml respectively. The developed RP-HPLC method was successfully applied for the quantitative determination of lacidipine in pharmaceutical dosage. (author)

Colorimetric determination of a paracetamole in raw material and in pharmaceutical dosage forms

International Nuclear Information System (INIS)

Usifoh, C.O; Adelusi, S.A.; Adebambo, R.F.

2002-01-01

A rapid, accurate and simple method is proposed for the determination of p-acetaminophen (paracetamole) in raw material, tablets and syrups. The method is based on measuring the intensity of the yellow color that developed when acute acetaminophen is allowed to react with p-dimethylaminobenzaldehyde in 2M HCl after heating. The color which absorbs in the visible region of gamma 450 nm is stable for several hours and the intensity is directly proportional to the concentration of the drug, that is, Beer lambert law is obeyed. The method can be used to analyse paracetamole in raw material and in pharmaceutical dosage forms. (author)

Simultaneous determination of linagliptin and metformin by reverse phase-high performance liquid chromatography method: An application in quantitative analysis of pharmaceutical dosage forms

Directory of Open Access Journals (Sweden)

Prathyusha Vemula

2015-01-01

Full Text Available To enhance patient compliance toward treatment in diseases like diabetes, usually a combination of drugs is prescribed. Therefore, an anti-diabetic fixed-dose combination of 2.5 mg of linagliptin 500 mg of metformin was taken for simultaneous estimation of both the drugs by reverse phase-high performance liquid chromatography (RP-HPLC method. The present study aimed to develop a simple and sensitive RP-HPLC method for the simultaneous determination of linagliptin and metformin in pharmaceutical dosage forms. The chromatographic separation was designed and evaluated by using linagliptin and metformin working standard and sample solutions in the linearity range. Chromatographic separation was performed on a C 18 column using a mobile phase of 70:30 (v/v mixture of methanol and 0.05 M potassium dihydrogen orthophosphate (pH adjusted to 4.6 with orthophosphoric acid delivered at a flow rate of 0.6 mL/min and UV detection at 267 nm. Linagliptin and metformin shown linearity in the range of 2-12 μg/mL and 400-2400 μg/mL respectively with correlation co-efficient of 0.9996 and 0.9989. The resultant findings analyzed for standard deviation (SD and relative standard deviation to validate the developed method. The retention time of linagliptin and metformin was found to be 6.3 and 4.6 min and separation was complete in <10 min. The method was validated for linearity, accuracy and precision were found to be acceptable over the linearity range of the linagliptin and metformin. The method was found suitable for the routine quantitative analysis of linagliptin and metformin in pharmaceutical dosage forms.

Prevalence and trends of cellulosics in pharmaceutical dosage forms.

Science.gov (United States)

Mastropietro, David J; Omidian, Hossein

2013-02-01

Many studies have shown that cellulose derivatives (cellulosics) can provide various benefits when used in virtually all types of dosage forms. Nevertheless, the popularity of their use in approved drug products is rather unknown. This research reports the current prevalence and trends of use for 15 common cellulosics in prescription drug products. The cellulosics were powdered and microcrystalline cellulose (MCC), ethyl cellulose, hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), hypromellose (HPMC), HPMC phthalate, HPMC acetate succinate, cellulose acetate (CA), CA phthalate, sodium (Na) and calcium (Ca) carboxymethylcellulose (CMC), croscarmellose sodium (XCMCNa), methyl cellulose, and low substituted HPC. The number of brand drug products utilizing each cellulosics was determined using the online drug index Rxlist. A total of 607 brand products were identified having one or more of the cellulosics as an active or inactive ingredient. An array of various dosage forms was identified and revealed HPMC and MCC to be the most utilized cellulosics in all products followed by XCMCNa and HPC. Many products contained two or more cellulosics in the formulation (42% containing two, 23% containing three, and 4% containing 4-5). The largest combination occurrence was HPMC with MCC. The use of certain cellulosics within different dosage form types was found to contain specific trends. All injectables utilized only CMCNa, and the same with all ophthalmic solutions utilizing HPMC, and otic suspensions utilizing HEC. Popularity and trends regarding cellulosics use may occur based on many factors including functionality, safety, availability, stability, and ease of manufacturing.

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.

Chemometric simultaneous determination of Sofosbuvir and Ledipasvir in pharmaceutical dosage form

Science.gov (United States)

Khalili, Mahsa; Sohrabi, Mahmoud Reza; Mirzabeygi, Vahid; Torabi Ziaratgahi, Nahid

2018-04-01

Partial least squares (PLS), different families of continuous wavelet transform (CWT), and first derivative spectrophotometry (DS) techniques were studied for quantification of Sofosbuvir (SFB) and Ledipasvir (LDV) simultaneously without separation step. The components were dissolved in Acetonitrile and the spectral behaviors were evaluated in the range of 200 to 400 nm. The ultraviolet (UV) absorbance of LDV exhibits no interferences between 300 and 400 nm and it was decided to predict the LDV amount through the classic spectrophotometry (CS) method in this spectral region as well. Data matrix of concentrations and calibrated models were developed, and then by applying a validation set the accuracy and precision of each model were studied. Actual concentrations versus predicted concentrations plotted and good correlation coefficients by each method resulted. Pharmaceutical dosage form was quantified by developed methods and the results were compared with the High Performance Liquid Chromatography (HPLC) reference method. Analysis Of Variance (ANOVA) in 95% confidence level showed no significant differences among methods.

Zein as a Pharmaceutical Excipient in Oral Solid Dosage Forms: State of the Art and Future Perspectives.

Science.gov (United States)

Berardi, Alberto; Bisharat, Lorina; AlKhatib, Hatim S; Cespi, Marco

2018-05-07

Zein is the main storage protein of corn and it has several industrial applications. Mainly in the last 10-15 years, zein has emerged as a potential pharmaceutical excipient with unique features. Zein is a natural, biocompatible and biodegradable material produced from renewable sources. It is insoluble, yet due to its amphiphilic nature, it has self-assembling properties, which have been exploited for the formation of micromicroparticle and nanoparticle and films. Moreover, zein can hydrate so it has been used in swellable matrices for controlled drug release. Other pharmaceutical applications of zein in oral drug delivery include its incorporation in solid dispersions of poorly soluble drugs and in colonic drug delivery systems. This review describes the features of zein significant for its use as a pharmaceutical excipient for oral drug delivery, and it summaries the literature relevant to macroscopic zein-based oral dosage forms, i.e. tablets, capsules, beads and powders. Particular attention is paid to the most novel formulations and applications of zein. Moreover, gaps of knowledge as well as possible venues for future investigations on zein are highlighted.

Simultaneous in vivo visualization and localization of solid oral dosage forms in the rat gastrointestinal tract by magnetic resonance imaging (MRI).

Science.gov (United States)

Christmann, V; Rosenberg, J; Seega, J; Lehr, C M

1997-08-01

Bioavailability of orally administered drugs is much influenced by the behavior, performance and fate of the dosage form within the gastrointestinal (GI) tract. Therefore, MRI in vivo methods that allow for the simultaneous visualization of solid oral dosage forms and anatomical structures of the GI tract have been investigated. Oral contrast agents containing Gd-DTPA were used to depict the lumen of the digestive organs. Solid oral dosage forms were visualized in a rat model by a 1H-MRI double contrast technique (magnetite-labelled microtablets) and a combination of 1H- and 19F-MRI (fluorine-labelled minicapsules). Simultaneous visualization of solid oral dosage forms and the GI environment in the rat was possible using MRI. Microtablets could reproducibly be monitored in the rat stomach and in the intestines using a 1H-MRI double contrast technique. Fluorine-labelled minicapsules were detectable in the rat stomach by a combination of 1H- and 19F-MRI in vivo. The in vivo 1H-MRI double contrast technique described allows solid oral dosage forms in the rat GI tract to be depicted. Solid dosage forms can easily be labelled by incorporating trace amounts of non-toxic iron oxide (magnetite) particles. 1H-MRI is a promising tool for observing such pharmaceutical dosage forms in humans. Combined 1H- and 19F-MRI offer a means of unambiguously localizing solid oral dosage forms in more distal parts of the GI tract. Studies correlating MRI examinations with drug plasma levels could provide valuable information for the development of pharmaceutical dosage forms.

Non-Conventional Applications of Computerized Tomography: Analysis of Solid Dosage Forms Produced by Pharmaceutical Industry

International Nuclear Information System (INIS)

Martins de Oliveira, Jose Jr.; Germano Martins, Antonio Cesar

2010-01-01

X-ray computed tomography (CT) refers to the cross-sectional imaging of an object measuring the transmitted radiation at different directions. In this work, we describe a non-conventional application of computerized tomography: visualization and improvements in the understanding of some internal structural features of solid dosage forms. A micro-CT X-ray scanner, with a minimum resolution of 30 μm was used to characterize some pharmaceutical tablets, granules, controlled-release osmotic tablet and liquid-filled soft-gelatin capsules. The analysis presented in this work are essentially qualitative, but quantitative parameters, such as porosity, density distribution, tablets dimensions, etc. could also be obtained using the related CT techniques.

Study of base influence on the active pharmaceutical ingredients releasing from combined ointments with antimycotic action

Directory of Open Access Journals (Sweden)

V. V. Luc

2018-03-01

characteristics of medicine and its efficacy. The aim of this work is biopharmaceutical validation of rational composition of semisolid dosage form for external use containing the combination of 2-mercaptobenzothiazole and chinosolum. Materials and methods. As a delivery vehicle for developing pharmacotherapeutical medicine the bases widely used in manufacturing of semisolid dosage forms, providing easy “wipe-off" effect after application, non-allergic and non-sensibilic after tracing, available for national producer and described in literature were studied. As the active pharmaceutical ingredients for antimycotic ointment 2-mercaptobenzothiazole and chinosolum in concentration 1% and 1% accordingly providing with suitable level of antifungal activity were used. Taking into account the advisability of high dispersion degree of medical substances in semisolid dosage forms for external use and physical-chemical properties of active pharmaceutical ingredients 2-mercaptobenzothiazole was added in all bases after preliminary dissolution in polyethylenoxyde 400 with heating and chinosolum was added after dissolution in prescribed or minimal amount of water. 2-mercaptobenzothiazole and chinosolum releasing from ointment compositions was studied with equilibrium dialysis method by Kruvchinsky at the temperature 32±0,5˚С through the semipermeable film “Kuprofan” in the Franz cell apparatus (producer PermeGear, Inc., USA. As a dialysis medium taking into account 2-mercaptobenzothiazole solubility we used solution containing methanol and water 1:1 and chinosolum releasing was carried out into water. Concentration of active pharmaceutical substances released from experimental ointments after 30 min was determined by spectrophotometric method. Results. The obtained results indicate significant advantage of the hydrophilic ointment bases, which provide an optimal level of release of 2-mercaptobenzothiazole and chinosolum from the experimental composite soft dosage forms for external

PAT: From Western solid dosage forms to Chinese materia medica preparations using NIR-CI.

Science.gov (United States)

Zhou, Luwei; Xu, Manfei; Wu, Zhisheng; Shi, Xinyuan; Qiao, Yanjiang

2016-01-01

Near-infrared chemical imaging (NIR-CI) is an emerging technology that combines traditional near-infrared spectroscopy with chemical imaging. Therefore, NIR-CI can extract spectral information from pharmaceutical products and simultaneously visualize the spatial distribution of chemical components. The rapid and non-destructive features of NIR-CI make it an attractive process analytical technology (PAT) for identifying and monitoring critical control parameters during the pharmaceutical manufacturing process. This review mainly focuses on the pharmaceutical applications of NIR-CI in each unit operation during the manufacturing processes, from the Western solid dosage forms to the Chinese materia medica preparations. Finally, future applications of chemical imaging in the pharmaceutical industry are discussed. Copyright © 2015 John Wiley & Sons, Ltd.

New Stability Indicating RP-HPLC Method for the Estimation of Cefpirome Sulphate in Bulk and Pharmaceutical Dosage Forms

OpenAIRE

Rao, Kareti Srinivasa; Kumar, Keshar Nargesh; Joydeep, Datta

2011-01-01

A simple stability indicating reversed-phase HPLC method was developed and subsequently validated for estimation of Cefpirome sulphate (CPS) present in pharmaceutical dosage forms. The proposed RP-HPLC method utilizes a LiChroCART-Lichrosphere100, C18 RP column (250 mm ? 4mm ? 5 ?m) in an isocratic separation mode with mobile phase consisting of methanol and water in the proportion of 50:50 % (v/v), at a flow rate 1ml/min, and the effluent was monitored at 270 nm. The retention time of CPS wa...

Microbiological assay for the determination of meropenem in pharmaceutical dosage form.

Science.gov (United States)

Mendez, Andreas S L; Weisheimer, Vanessa; Oppe, Tércio P; Steppe, Martin; Schapoval, Elfrides E S

2005-04-01

Meropenem is a highly active carbapenem antibiotic used in the treatment of a wide range of serious infections. The present work reports a microbiological assay, applying the cylinder-plate method, for the determination of meropenem in powder for injection. The validation method yielded good results and included linearity, precision, accuracy and specificity. The assay is based on the inhibitory effect of meropenem upon the strain of Micrococcus luteus ATCC 9341 used as the test microorganism. The results of assay were treated statistically by analysis of variance (ANOVA) and were found to be linear (r=0.9999) in the range of 1.5-6.0 microg ml(-1), precise (intra-assay: R.S.D.=0.29; inter-assay: R.S.D.=0.94) and accurate. A preliminary stability study of meropenem was performed to show that the microbiological assay is specific for the determination of meropenem in the presence of its degradation products. The degraded samples were also analysed by the HPLC method. The proposed method allows the quantitation of meropenem in pharmaceutical dosage form and can be used for the drug analysis in routine quality control.

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.

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.

Electrospun poly(ε-caprolactone) matrices containing silver sulfadiazine complexed with β-cyclodextrin as a new pharmaceutical dosage form to wound healing: preliminary physicochemical and biological evaluation.

Science.gov (United States)

Souza, Sarah Oliveira Lamas; Cotrim, Monique Alvarenga Pinto; Oréfice, Rodrigo Lambert; Carvalho, Suzana Gonçalves; Dutra, Jessyca Aparecida Paes; de Paula Careta, Francisco; Resende, Juliana Alves; Villanova, Janaina Cecília Oliveira

2018-05-10

Cooperation between researchers in the areas of medical, pharmaceutical and materials science has facilitated the development of pharmaceutical dosage forms that elicit therapeutic effects and protective action with a single product. In addition to optimizing pharmacologic action, such dosage forms provide greater patient comfort and increase success and treatment compliance. In the present work, we prepared semipermeable bioactive electrospun fibers for use as wound dressings containing silver sulfadiazine complexed with β-cyclodextrin in a poly(Ɛ-caprolactone) nanofiber matrix aiming to reduce the direct contact between silver and skin and to modulate the drug release. Wound dressings were prepared by electrospinning, and were subjected to ATR-FT-IR and TG/DTG assays to evaluate drug stability. The hydrophilicity of the fibrous nanostructure in water and PBS buffer was studied by goniometry. Electrospun fibers permeability and swelling capacity were assessed, and a dissolution test was performed. In vitro biological tests were realized to investigate the biological compatibility and antimicrobial activity. We obtained flexible matrices that were each approximately 1.0 g in weight. The electrospun fibers were shown to be semipermeable, with water vapor transmission and swelling indexes compatible with the proposed objective. The hydrophilicity was moderate. Matrices containing pure drug modulated drug release adequately during 24 h but presented a high hemolytic index. Complexation promoted a decrease in the hemolytic index and in the drug release but did not negatively impact antimicrobial activity. The drug was released predominantly by diffusion. These results indicate that electrospun PCL matrices containing β-cyclodextrin/silver sulfadiazine inclusion complexes are a promising pharmaceutical dosage form for wound healing.

Assessment of Human Pharmaceutical Products Registered in ...

African Journals Online (AJOL)

... in order to determine the most common routes of administration and type of dosage forms that are used. Registered pharmaceutical products were categorized by route of administration and then sub-categorized by the dosage form. Oral dosage forms were the most common accounting for 73% of all registered products.

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.

Spectrophotometric methods for the simultaneous estimation of ofloxacin and tinidazole in bulk and pharmaceutical dosage form

Directory of Open Access Journals (Sweden)

Kareti Srinivasa Rao

2011-01-01

Full Text Available Aim: This work deals with the simultaneous estimation of Ofloxacin (OFL and Tinidazole (TNZ in in bulk and pharmaceutical dosage form, without prior separation, by three different techniques (Simultaneous equation, Absorbance ratio method and First order derivative method. Materials and Methods: The present work was carried out on Shimadzu electron UV1800 double beam UV-Visible spectrophotometer. The absorption spectra of reference and test solutions were carried out in 1 cm matched quartz cell over the range of 200 - 400 nm. Standard gift sample of OFL and TNZ obtain from Torrent pharmaceuticals Ltd., Baddi, Himachal Pradesh. Combined OFL and TNZ tablets were purchased from local market. Methanol from Merck Ltd and distilled water are used as solvent. Results: The first method is the application of simultaneous equation. Where the linearity ranges for OFL and TNZ were 5-30 μg/ml and 10-50 μg/ml respectively. The second method is the determination of ratio of absorbance at 278nm, the maximum absorption of TNZ and isobestic wavelength 283 nm, the linearity ranges for OFL and TNZ were 5-30 μg/ml and 10-50μg/ml respectively. The third method is the first order derivative method, where the linearity ranges for OFL and TNZ were 5-30 μg/ml and 10-50 μg/ml respectively. The results of the analysis have been validated statistically and by recovery studies, where the percentage recovery was found to be 100.9±0.49 and 97.30±0.20 using the simultaneous equation method, 98±0.45 and 100.4±0.48 using the graphical absorbance ratio method and 99.10±0.40 and 84.70±0.70 using first derivative method, for OFL and TNZ respectively. Conclusions: The proposed procedures are rapid, simple, require no preliminary separation steps and can be used for routine analysis of both drugs in quality control laboratories.

Three-dimensional printing in pharmaceutics: promises and problems.

Science.gov (United States)

Yu, Deng Guang; Zhu, Li-Min; Branford-White, Christopher J; Yang, Xiang Liang

2008-09-01

Three-dimensional printing (3DP) is a rapid prototyping (RP) technology. Prototyping involves constructing specific layers that uses powder processing and liquid binding materials. Reports in the literature have highlighted the many advantages of the 3DP system over other processes in enhancing pharmaceutical applications, these include new methods in design, development, manufacture, and commercialization of various types of solid dosage forms. For example, 3DP technology is flexible in that it can be used in applications linked to linear drug delivery systems (DDS), colon-targeted DDS, oral fast disintegrating DDS, floating DDS, time controlled, and pulse release DDS as well as dosage form with multiphase release properties and implantable DDS. In addition 3DP can also provide solutions for resolving difficulties relating to the delivery of poorly water-soluble drugs, peptides and proteins, preparation of DDS for high toxic and potent drugs and controlled-release of multidrugs in a single dosage forms. Due to its flexible and highly reproducible manufacturing process, 3DP has some advantages over conventional compressing and other RP technologies in fabricating solid DDS. This enables 3DP to be further developed for use in pharmaceutics applications. However, there are some problems that limit the further applications of the system, such as the selections of suitable excipients and the pharmacotechnical properties of 3DP products. Further developments are therefore needed to overcome these issues where 3DP systems can be successfully combined with conventional pharmaceutics. Here we present an overview and the potential 3DP in the development of new drug delivery systems.

QR encoded smart oral dosage forms by inkjet printing.

Science.gov (United States)

Edinger, Magnus; Bar-Shalom, Daniel; Sandler, Niklas; Rantanen, Jukka; Genina, Natalja

2018-01-30

The use of inkjet printing (IJP) technology enables the flexible manufacturing of personalized medicine with the doses tailored for each patient. In this study we demonstrate, for the first time, the applicability of IJP in the production of edible dosage forms in the pattern of a quick response (QR) code. This printed pattern contains the drug itself and encoded information relevant to the patient and/or healthcare professionals. IJP of the active pharmaceutical ingredient (API)-containing ink in the pattern of QR code was performed onto a newly developed porous and flexible, but mechanically stable substrate with a good absorption capacity. The printing did not affect the mechanical properties of the substrate. The actual drug content of the printed dosage forms was in accordance with the encoded drug content. The QR encoded dosage forms had a good print definition without significant edge bleeding. They were readable by a smartphone even after storage in harsh conditions. This approach of efficient data incorporation and data storage combined with the use of smart devices can lead to safer and more patient-friendly drug products in the future. Copyright © 2017 Elsevier B.V. All rights reserved.

Potential of Hibiscus Sabdariffa and Jatropha Curcas as Natural Coagulants in the Treatment of Pharmaceutical Wastewater

Directory of Open Access Journals (Sweden)

Sibartie Sheena

2018-01-01

Full Text Available Pharmaceutical wastewater is one of the most difficult wastewater to treat due to the presence of pharmaceutical compounds resulting in high concentration of organic matter, high turbidity and Chemical Oxygen Demand (COD. Chemical-based coagulation is a common method used to treat wastewater. However, the issue that has been raised with the use of chemical coagulants is their presence in water after treatment that can cause risks to the human health such as Alzheimer and cancer. Natural coagulants can be used as a safe alternative to these chemicals instead. Therefore, the objective of this experiment was to study the effect of H. Sabdariffa and J. Curcas as natural coagulants, separately and as a combination, on the treatment of pharmaceutical wastewater. Jar test experiment were carried out where beakers of 0.5L wastewater were mixed with the coagulants. The pH of the wastewater was varied from 2 to 12 while the coagulant dosage was varied from 40 to 200 mg/L. It was found that H. Sabdariffa works best at pH 4 and at a coagulant dosage of 190 mg/L with a highest turbidity removal of 35.8% and a decrease of COD by 29%. J. Curcas was found to perform best at pH 3 and with a coagulant dosage of 200 mg/L with a highest turbidity removal of 51% and a decrease of COD by 32%. When J. Curcas and H. Sabdariffa were used in combination, the optimum composition was found to be 80% J. Curcas and 20% H. Sabdariffa by weight with a maximum turbidity removal of 46.8% and a decrease in COD by 46%. In comparison between the two natural coagulants, J. Curcas is found to be a better and more suited coagulative agent for the treatment of pharmaceutical wastewater. The same experiment was carried with alum at pH 6 and coagulant dosage of 750 mg/L and a turbidity removal of 48% and a decrease in COD by 38% were recorded. In comparison with alum, J. Curcas was a better coagulant in treating the pharmaceutical wastewater. This shows that natural coagulants can be

Pharmaceutical spray drying: solid-dose process technology platform for the 21st century.

Science.gov (United States)

Snyder, Herman E

2012-07-01

Requirement for precise control of solid-dosage particle properties created with a scalable process technology are continuing to expand in the pharmaceutical industry. Alternate methods of drug delivery, limited active drug substance solubility and the need to improve drug product stability under room-temperature conditions are some of the pharmaceutical applications that can benefit from spray-drying technology. Used widely for decades in other industries with production rates up to several tons per hour, pharmaceutical uses for spray drying are expanding beyond excipient production and solvent removal from crystalline material. Creation of active pharmaceutical-ingredient particles with combinations of unique target properties are now more common. This review of spray-drying technology fundamentals provides a brief perspective on the internal process 'mechanics', which combine with both the liquid and solid properties of a formulation to enable high-throughput, continuous manufacturing of precision powder properties.

Spectrophotometric Quantification of Vilazodone Hydrochloride in Pharmaceutical Dosage Form Using Quality by Design Approach

International Nuclear Information System (INIS)

Panda, S.S.; Kumar, B.V.V.R.K.; Beg, S.; Behera, S.

2015-01-01

The present work deals with development and validation of a novel, robust, precise and accurate spectrophotometric method, for the estimation of vilazodone hydrochloride in tablets using the principle of Quality by Design (QbD). A fractional factorial design (FFD) was employed for initial parameter screening. Further the screened parameters were subjected to central composite design (CCD) for evaluating method robustness and method optimization. Different statistical parameters were evaluated to decide appropriateness of experimental data. Vilazodone shows absorption maximum at 285 nm using methanol. Factor screening slit width and sampling interval were identified as critical method variables, which were further evaluated by a CCD. Good linearity was obtained for vilazodone in the range of 5-60 μg/ mL with R"2 > 0.999. The method was found to be accurate with good average % recovery (more than 100 %). Developed method was validated as per ICH guidelines. Based on QbD development of spectrophotometric method ensured that quality is built into the method. The method was robust and can be applied for determination of the vilazodone in pharmaceutical dosage form. (author)

Thermal Analysis by Structural Characterization as a Method for Assessing Heterogeneity in Complex Solid Pharmaceutical Dosage Forms.

Science.gov (United States)

Alhijjaj, Muqdad; Reading, Mike; Belton, Peter; Qi, Sheng

2015-11-03

Characterizing inter- and intrasample heterogeneity of solid and semisolid pharmaceutical products is important both for rational design of dosage forms and subsequent quality control during manufacture; however, most pharmaceutical products are multicomponent formulations that are challenging in this regard. Thermal analysis, in particular differential scanning calorimetry, is commonly used to obtain structural information, such as degree of crystallinity, or identify the presence of a particular polymorph, but the results are an average over the whole sample; it cannot directly provide information about the spatial distribution of phases. This study demonstrates the use of a new thermo-optical technique, thermal analysis by structural characterization (TASC), that can provide spatially resolved information on thermal transitions by applying a novel algorithm to images acquired by hot stage microscopy. We determined that TASC can be a low cost, relatively rapid method of characterizing heterogeneity and other aspects of structure. In the examples studied, it was found that high heating rates enabled screening times of 3-5 min per sample. In addition, this study demonstrated the higher sensitivity of TASC for detecting the metastable form of polyethylene glycol (PEG) compared to conventional differential scanning calorimetry (DSC). This preliminary work suggests that TASC will be a worthwhile additional tool for characterizing a broad range of materials.

Development and Validation of a UV Spectrophotometric and a RP-HPLC Methods for Moexipril Hydrochloride in Pure Form and Pharmaceutical Dosage Form

International Nuclear Information System (INIS)

Mastiholimath, V.S.; Gupte, P.P.; Mannur, V.S.

2012-01-01

A simple and reliable UV spectrophotometric and high-performance liquid chromatography (HPLC) methods were developed and validated for Moexipril hydrochloride in pure form and pharmaceutical dosage form. The RP-HPLC method was developed on agilant eclipse C 18 , (150 mm x 4.6 mm, 5 μm) with a mobile phase gradient system of 60 % (methanol:acetonitrile (70:30 % v/v)) : 40 % 20 mM ammonium acetate buffer pH 4.5 (v/v) and UV spectrophotometric method was developed in phosphate buffer pH 6.8. The effluent was monitored by SPD-M20A, prominence PDA detector at 210 nm. Calibration curve was linear over the concentration range of 10-35 μg/ml and 1-9 μg/ml for RP-HPLC and UV with a regression coefficient of 0.999. For RP-HPLC method Inter-day and intra-day precision % RSD values were found to be 1.00078 % and 1.49408 % respectively. For UV method 0.73386 % to 1.44111 % for inter day 0.453864 to 1.15542 intra-day precision. Recovery of Moexipril hydrochloride was found to be in the range of 99.8538 % to 101.5614 % and 100.5297586 % to 100.6431587 % for UV and RP-HPLC respectively. The limits of detection (LOD) and quantification (LOQ) for HPLC were 0.98969 and 2.99907 μg/ml, respectively. The developed RP-HPLC and UV spectrophotometric method was successfully applied for the quantitative determination of Moexipril hydrochloride in pharmaceutical dosage. (author)

Stability indicating RP-LC-PDA method for the quantitative analysis of saxagliptin in pharmaceutical dosage form

Directory of Open Access Journals (Sweden)

Laís Engroff Scheeren

2015-06-01

Full Text Available Saxagliptin is a potent and selective inhibitor of the enzyme dipeptidyl peptidase 4. It is effective in the treatment of type 2 diabetes mellitus because it stimulates the pancreas to produce insulin. In the present study, a liquid chromatography method was developed and validated to quantify the drug in tablets. This method was based on the isocratic elution of saxagliptin, using a mobile phase consisting of 0.1% phosphoric acid at pH 3.0 - methanol (70: 30, v/v at a flow rate of 1 mL.min-1 with UV detection at 225 nm. The chromatographic separation was achieved in 8 minutes on a Waters XBridge C18 column (250 mm x 4.6 mm, 5µm maintained at ambient temperature. The proposed method proved to be specific and robust for the quality control of saxagliptin in pharmaceutical dosage forms, showing good linearity in the range of 15.0 - 100.0 µg.mL-1 (r>0.999, precision (RSD

Cathodic adsorptive stripping voltammetric determination of Ribavirin in pharmaceutical dosage form, urine and serum

Directory of Open Access Journals (Sweden)

Ahmed A. Abdel Gaber

2017-05-01

Full Text Available A sensitive, simple and rapid square-wave adsorptive stripping voltammetric method was developed and validated for the determination of Ribavirin in pharmaceutical formulations. The proposed method was based on the electrochemical reduction of Ribavirin at a hanging mercury drop electrode in Britton Robinson buffer at pH 10. A well-defined peak was observed at 880 mV with 30 s of accumulation time and 50 mV of accumulation potential. Under these optimized conditions, the square-wave adsorptive stripping voltammetric peak current showed a linear correlation on drug concentration over the range of 1 × 10−10–2 × 10−7 mol L−1 with a correlation coefficient of 0.9995 for the proposed method. The detection and quantitation limits for this method were 2.02 × 10−10 and 6.80 × 10−10 mol L−1, respectively. The results obtained for intra-day and inter-day precision (as RSD % were between 0.447% and 1.024%. This method was applied successfully for the determination of Ribavirin in its pharmaceutical dosage forms with mean recoveries of 99.68 ± 0.13 with RSD % of 0.81% and 99.20 ± 0.24 with RSD % of 0.49% for two concentrations 5 × 10−9 and 5 × 10−8 mol L−1, respectively for 200 mg capsules. The results obtained from the developed square-wave adsorptive stripping voltammetric method were compared with those obtained by the analytical method reported in the literature.

A validated stability-indicating UPLC method for desloratadine and its impurities in pharmaceutical dosage forms.

Science.gov (United States)

Rao, Dantu Durga; Satyanarayana, N V; Malleswara Reddy, A; Sait, Shakil S; Chakole, Dinesh; Mukkanti, K

2010-02-05

A novel stability-indicating gradient reverse phase ultra-performance liquid chromatographic (RP-UPLC) method was developed for the determination of purity of desloratadine in presence of its impurities and forced degradation products. The method was developed using Waters Aquity BEH C18 column with mobile phase containing a gradient mixture of solvents A and B. The eluted compounds were monitored at 280nm. The run time was 8min within which desloratadine and its five impurities were well separated. Desloratadine was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal and photolytic degradation. Desloratadine was found to degrade significantly in oxidative and thermal stress conditions and stable in acid, base, hydrolytic and photolytic degradation conditions. The degradation products were well resolved from main peak and its impurities, thus proved the stability-indicating power of the method. The developed method was validated as per 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 desloratadine in pharmaceutical dosage forms.

Comprehensive review on additives of topical dosage forms for drug delivery.

Science.gov (United States)

Garg, Tarun; Rath, Goutam; Goyal, Amit K

2015-12-01

Skin is the largest organ of the human body and plays the most important role in protecting against pathogen and foreign matter. Three important modes such as topical, regional and transdermal are widely used for delivery of various dosage forms. Among these modes, the topical dosage forms are preferred because it provides local therapeutic activity when applied to the skin or mucous membranes. Additives or pharmaceutical excipients (non-drug component of dosage form) are used as inactive ingredients in dosage form or tools for structuring dosage forms. The main use of topical dosage form additives are controling the extent of absorption, maintaining the viscosity, improving the stability as well as organoleptic property and increasing the bulk of the formulation. The overall goal of this article is to provide the clinician with information related to the topical dosage form additives and their current major applications against various diseases.

Analytical Method Development and Validation of Solifenacin in Pharmaceutical Dosage Forms by RP-HPLC

OpenAIRE

Shaik, Rihana Parveen; Puttagunta, Srinivasa Babu; Kothapalli Bannoth, Chandrasekar; Challa, Bala Sekhara Reddy

2014-01-01

A new, accurate, precise, and robust HPLC method was developed and validated for the determination of solifenacin in tablet dosage form. The chromatographic separation was achieved on an Inertsil ODS 3V C18 (150 mm × 4.6 mm, 5 μm) stationary phase maintained at ambient temperature with a mobile phase combination of monobasic potassium phosphate (pH 3.5) containing 0.1% triethylamine and methanol (gradient mode) at a flow rate of 1.5 mL/min, and the detection was carried out by using UV detect...

[Pharmaceutical counseling of non-conventional dosage forms concerning the health-literacy and the patient adherence in public medication dispensing -Questionnaire surveys in Hungarian community pharmacies.

Science.gov (United States)

Somogyi, O; Zelko, R

Although the non-conventional dosage forms (e.g. modified release per oral systems or transdermal patches) have more significant advantages than other conventional dosage forms, the pa- tients have to apply them correctly in their home medicine using to reach the effective and safe therapy. A guideline of relevant application instructions contribute to development of an effective pharmaceutical counseling in community pharmacies. The counseling and advices can improve the patients' knowledge concerning application rules of different new dosage forms (health- literacy) with patient adherence. Finally it will result more effective and safer therapies. The aim of our Hungarian questionnaire surveys was to explore the patients' drug application habits or application errors and improve special verbal counseling of mentioned non-conventional dosage forms in community pharmacies. Understandable patient information leaflets were developed about application rules and besides the levels of patients' reading comprehension was evaluated in case of the leaflet of medicinal patches. The results show that a properly developed text is useful for the majority of patients but they need the verbal explanation as well, moreover there is a demand for the verbal counseling in community pharmacies. The most common application errors were explored and the most effective instructions or application rules were collected for the pharmacists and patients concerning the modified release tablets or capsules and transdermal patches.

Simultaneous Estimation of Ibuprofen and Phenylephrine Hydrochloride in Bulk and Combined Dosage Form by First Derivative UV Spectrophotometry Method

Directory of Open Access Journals (Sweden)

Mehul Patel

2013-01-01

Full Text Available A simple, precise, rapid, and economic method was developed for the simultaneous determination of Ibuprofen and Phenylephrine HCl in bulk and combined dosage form. This method involves first-order derivative spectroscopy using 248 nm and 237 nm as zero crossing points for Ibuprofen and Phenylephrine HCl, respectively. For spectrophotometric method 0.1 N NaOH was used as a solvent. The linearity was established over the concentration range of 12–72 μg/mL and 1.5–22 μg/mL for Ibuprofen and Phenylephrine HCl with correlation coefficient (r2 of 0.9972 and 0.9981, respectively. The mean % recoveries were found to be in the range of 98.88% and 98.54% for Ibuprofen and Phenylephrine HCl, respectively. Interday and intraday studies showed repeatability of the method. The method was found to be specific and robust. The method was successfully applied to pharmaceutical formulation, with no interference from excipients as indicated by the recovery study. Results of analysis were validated statistically and by recovery studies.

[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.

Validation of HPLC and UV spectrophotometric methods for the determination of meropenem in pharmaceutical dosage form.

Science.gov (United States)

Mendez, Andreas S L; Steppe, Martin; Schapoval, Elfrides E S

2003-12-04

A high-performance liquid chromatographic method and a UV spectrophotometric method for the quantitative determination of meropenem, a highly active carbapenem antibiotic, in powder for injection were developed in present work. The parameters linearity, precision, accuracy, specificity, robustness, limit of detection and limit of quantitation were studied according to International Conference on Harmonization guidelines. Chromatography was carried out by reversed-phase technique on an RP-18 column with a mobile phase composed of 30 mM monobasic phosphate buffer and acetonitrile (90:10; v/v), adjusted to pH 3.0 with orthophosphoric acid. The UV spectrophotometric method was performed at 298 nm. The samples were prepared in water and the stability of meropenem in aqueous solution at 4 and 25 degrees C was studied. The results were satisfactory with good stability after 24 h at 4 degrees C. Statistical analysis by Student's t-test showed no significant difference between the results obtained by the two methods. The proposed methods are highly sensitive, precise and accurate and can be used for the reliable quantitation of meropenem in pharmaceutical dosage form.

Materials for Pharmaceutical Dosage Forms: Molecular Pharmaceutics and Controlled Release Drug Delivery Aspects

Directory of Open Access Journals (Sweden)

Patrick P. DeLuca

2010-09-01

Full Text Available Controlled release delivery is available for many routes of administration and offers many advantages (as microparticles and nanoparticles over immediate release delivery. These advantages include reduced dosing frequency, better therapeutic control, fewer side effects, and, consequently, these dosage forms are well accepted by patients. Advances in polymer material science, particle engineering design, manufacture, and nanotechnology have led the way to the introduction of several marketed controlled release products and several more are in pre-clinical and clinical development.

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...

Artificial Neural Networks in Evaluation and Optimization of Modified Release Solid Dosage Forms

Directory of Open Access Journals (Sweden)

Zorica Djurić

2012-10-01

Full Text Available Implementation of the Quality by Design (QbD approach in pharmaceutical development has compelled researchers in the pharmaceutical industry to employ Design of Experiments (DoE as a statistical tool, in product development. Among all DoE techniques, response surface methodology (RSM is the one most frequently used. Progress of computer science has had an impact on pharmaceutical development as well. Simultaneous with the implementation of statistical methods, machine learning tools took an important place in drug formulation. Twenty years ago, the first papers describing application of artificial neural networks in optimization of modified release products appeared. Since then, a lot of work has been done towards implementation of new techniques, especially Artificial Neural Networks (ANN in modeling of production, drug release and drug stability of modified release solid dosage forms. The aim of this paper is to review artificial neural networks in evaluation and optimization of modified release solid dosage forms.

Pharmaceutical development of an intravenous dosage form of diacetylmorphine hydrochloride

NARCIS (Netherlands)

Klous, Marjolein G.; Nuijen, Bastiaan; van den Brink, Wim; van Ree, Jan M.; Beijnen, Jos H.

2004-01-01

A solid dosage form for multiple use was developed for parenteral administration of diacetylmorphine in a clinical trial on co-prescription of heroin to heroin addicts. A 300-mg/mL diacetylmorphine hydrochloride solution was lyophilised as 10-mL aliquots in 30-mL glass vials, to be reconstituted to

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.

Emergence of 3D Printed Dosage Forms: Opportunities and Challenges.

Science.gov (United States)

Alhnan, Mohamed A; Okwuosa, Tochukwu C; Sadia, Muzna; Wan, Ka-Wai; Ahmed, Waqar; Arafat, Basel

2016-08-01

The recent introduction of the first FDA approved 3D-printed drug has fuelled interest in 3D printing technology, which is set to revolutionize healthcare. Since its initial use, this rapid prototyping (RP) technology has evolved to such an extent that it is currently being used in a wide range of applications including in tissue engineering, dentistry, construction, automotive and aerospace. However, in the pharmaceutical industry this technology is still in its infancy and its potential yet to be fully explored. This paper presents various 3D printing technologies such as stereolithographic, powder based, selective laser sintering, fused deposition modelling and semi-solid extrusion 3D printing. It also provides a comprehensive review of previous attempts at using 3D printing technologies on the manufacturing dosage forms with a particular focus on oral tablets. Their advantages particularly with adaptability in the pharmaceutical field have been highlighted, which enables the preparation of dosage forms with complex designs and geometries, multiple actives and tailored release profiles. An insight into the technical challenges facing the different 3D printing technologies such as the formulation and processing parameters is provided. Light is also shed on the different regulatory challenges that need to be overcome for 3D printing to fulfil its real potential in the pharmaceutical industry.

Determination of Carvedilol Enantiomers in Pharmaceutical Dosages by SBSE-HPLC Based on Diastereomer Formation.

Science.gov (United States)

Taraji, Maryam; Talebpour, Zahra; Adib, Nuoshin; Karimi, Shima; Haghighi, Farideh; Aboul-Enein, Hassan Y

2015-09-01

A sensitive, selective and simple method for the simultaneous determination of carvedilol enantiomers in aqueous solution has been developed using stir bar sorptive extraction (SBSE) followed by high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. This method is based on the reaction of carvedilol enantiomers with (-)-menthyl chloroformate (MCF) after extraction by the SBSE method to produce diastereomeric derivatives. The separation was achieved by use of a C18 analytical column and the influence of mobile phase composition on the enantioseparation of carvedilol was studied. The applicability of two sorptive phases, poly(methyl methacrylate/ethyleneglycol dimethacrylate) (PA-EG) and polydimethylsiloxane, were tested for extraction of carvedilol enantiomers from aqueous samples. The obtained results showed excellent linear dynamic ranges and precisions for each of them. The least limit of detection for (S)- and (R)-carvedilol obtained 8 and 11 µg L(-1), respectively, using the PA-EG sorptive phase. Inter- and intra-mean recoveries were also satisfactory, ranging from 98 to 103%, with coefficient of variation in the range of 1-5% at three fortified levels using a PA-EG coated stir bar. The proposed SBSE (PA-EG)-MCF derivatization-HPLC-UV method was successfully applied to enantioselective analysis of carvedilol in water and pharmaceutical dosages, confirming the application of this method. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Miniaturized approach for excipient selection during the development of oral solid dosage form

DEFF Research Database (Denmark)

Raijada, Dharaben Kaushikkumar; Müllertz, Anette; Cornett, Claus

2014-01-01

The present study introduces a miniaturized high-throughput platform to understand the influence of excipients on the performance of oral solid dosage forms during early drug development. Wet massing of binary mixtures of the model drug (sodium naproxen) and representative excipients was followed...... for excipient selection and for early-stage performance testing of active pharmaceutical ingredient intended for oral solid dosage form. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:900-908, 2014....

New Stability Indicating RP-HPLC Method for the Estimation of Cefpirome Sulphate in Bulk and Pharmaceutical Dosage Forms.

Science.gov (United States)

Rao, Kareti Srinivasa; Kumar, Keshar Nargesh; Joydeep, Datta

2011-01-01

A simple stability indicating reversed-phase HPLC method was developed and subsequently validated for estimation of Cefpirome sulphate (CPS) present in pharmaceutical dosage forms. The proposed RP-HPLC method utilizes a LiChroCART-Lichrosphere100, C18 RP column (250 mm × 4mm × 5 μm) in an isocratic separation mode with mobile phase consisting of methanol and water in the proportion of 50:50 % (v/v), at a flow rate 1ml/min, and the effluent was monitored at 270 nm. The retention time of CPS was 2.733 min and its formulation was exposed to acidic, alkaline, photolytic, thermal and oxidative stress conditions, and the stressed samples were analyzed by the proposed method. The described method was linear over a range of 0.5-200μg/ml. The percentage recovery was 99.46. F-test and t-test at 95% confidence level were used to check the intermediate precision data obtained under different experimental setups; the calculated value was found to be less than the critical value.

Myrrh a traditional medicine or a multipurpose pharmaceutical excipient

Directory of Open Access Journals (Sweden)

Fatemeh Erfanfar

2015-12-01

Full Text Available A drug dosage form contains excipients as well as active pharmaceutical ingredients. Formerly, excipients were considered inert components that were used by a formulator to provide the suitable volume, weight and consistency of a dosage form. Today, however, excipients are expected to perform multifunctional roles such as enhancing physical, chemical and microbial stabilities of the dosage form, improving the color or odor of the formulation, and influencing the release and bioavailability of the active ingredient. Among various excipients, natural ones seem to be more beneficial to use, since they are economical, safe, biodegradable, and biocompatible. In this article, myrrh oleo-gum-resin is introduced as a potential natural multipurpose excipient that can perform many useful roles in pharmaceutical dosage forms. Scopus and Google scholar electronic databases were searched to find different properties of myrrh as an excipient. Moreover, ten famous traditional Iranian medicine books were studied to find semisolid formulations named Sabgh, which contained myrrh. One of these formulations was prepared, and its physical and microbiological stabilities were assessed. The role of myrrh as an excipient in this formulation is discussed here. Antibacterial and preservative effects shown in the formulation were related to the essential oil of myrrh. The gum portion was found to be a potential surfactant. In addition, myrrh is a natural muco-adhesive and film forming material. These properties were observed for myrrh in the Sabgh formulation in this study as well. So we can conclude that myrrh could be a potential multipurpose excipient in pharmaceutical industries, which needs further research.

Development and Validation of a Precise, Single HPLC Method for the Determination of Tolperisone Impurities in API and Pharmaceutical Dosage Forms.

Science.gov (United States)

Raju, Thummala Veera Raghava; Seshadri, Raja Kumar; Arutla, Srinivas; Mohan, Tharlapu Satya Sankarsana Jagan; Rao, Ivaturi Mrutyunjaya; Nittala, Someswara Rao

2013-01-01

A novel, sensitive, stability-indicating HPLC method has been developed for the quantitative estimation of Tolperisone-related impurities in both bulk drugs and pharmaceutical dosage forms. Effective chromatographic separation was achieved on a C18 stationary phase with a simple mobile phase combination delivered in a simple gradient programme, and quantitation was by ultraviolet detection at 254 nm. The mobile phase consisted of a buffer and acetonitrile delivered at a flow rate 1.0 ml/min. The buffer consisted of 0.01 M potassium dihydrogen phosphate with the pH adjusted to 8.0 by using diethylamine. In the developed HPLC method, the resolution between Tolperisone and its four potential impurities was found to be greater than 2.0. Regression analysis showed an R value (correlation coefficient) of greater than 0.999 for the Tolperisone impurities. This method was capable of detecting all four impurities of Tolperisone at a level of 0.19 μg/mL with respect to the test concentration of 1000 μg/mL for a 10 µl injection volume. The tablets were subjected to the stress conditions of hydrolysis, oxidation, photolysis, and thermal degradation. Considerable degradation was found to occur in base hydrolysis, water hydrolysis, and oxidation. The stress samples were assayed against a qualified reference standard and the mass balance was found to be close to 100%. The established method was validated and found to be linear, accurate, precise, specific, robust, and rugged.

The characteristics of novel dosage forms

Directory of Open Access Journals (Sweden)

Milić-Aškrabić Jela

2003-01-01

Full Text Available The objective of pharmaceutical-technological development is to find a procedure of transforming an active substance (a drug into a drug dosage form which is not only acceptable for application, but also enables the active substance to be released following administration, pursuant to therapy objectives. The aim is that the concentration of the active substance in the action location rapidly reaches a therapeutic level and maintains an approximately constant level in the course of a particular time, according to the established therapeutic goal. The primary objective is to present the active ingredient (drug in the form and concentration/quantity that enables the corresponding therapeutic response, i.e. to control the site and rate of medicinal substance release from the drug, as well as the rate at which it reaches the membranes and surfaces to which it is absorbed, while applying a common method of administration. The procedures used to achieve this goal are becoming highly complex and demanding and are aiming at sophisticated drug delivery systems and functional packaging material. Development from the existing drug molecule, through the conventional drug dosage form, to a new system of drug "delivery" (novel delivery system, can improve the drug (active substance characteristics significantly in view of compliance (acceptability by the patient, safety and efficiency. The paper presents an overview of the most important examples of pharmaceutical forms with controlled release and advanced drug "carriers".

Co-extrusion as a processing technique to manufacture a dual sustained release fixed-dose combination product.

Science.gov (United States)

Vynckier, An-Katrien; Voorspoels, Jody; Remon, Jean Paul; Vervaet, Chris

2016-05-01

This study aimed to design a fixed-dose combination dosage form which provides a sustained release profile for both the freely water-soluble metformin HCl and the poorly soluble gliclazide, two antidiabetic compounds used to treat diabetes mellitus. Hot-melt co-extrusion was used as an innovative manufacturing technique for a pharmaceutical fixed-dose combination product. In this way, a matrix formulation that sustained metformin release could be developed, despite the high drug load in the formulation and the freely soluble nature of the drug. It was clear that co-extrusion was perfectly suited to produce a fixed-dose combination product with adequate properties for each of the incorporated APIs. A coat layer, containing at least 30% CAPA(®) 6506 as a hydrophobic polymer, was necessary to adequately sustain the release of the highly dosed freely soluble drug from the 70% metformin HCl-loaded CAPA(®) 6506 core of the co-extrudate. To obtain a complete gliclazide release over 24-h solubilization in Kollidon(®) VA, added as a second polymer to the CAPA(®) 6506 in the coat, was needed. Both active pharmaceutical ingredients (APIs), which have different physicochemical characteristics, were formulated in a single dosage form, using co-extrusion. © 2016 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology.

A Validated Stability Indicating RP-HPLC Method for the Determination of Emtricitabine, Tenofovir Disoproxil Fumarate, Elvitegravir and Cobicistat in Pharmaceutical Dosage Form

Science.gov (United States)

Runja, Chinnalalaiah; Ravi Kumar, Pigili; Avanapu, Srinivasa Rao

2016-01-01

A new simple, rapid stability indicating assay method has been developed and validated for the determination of emtricitabine, tenofovir disoproxil fumarate, elvitegravir and cobicistat using reverse-phase high-performance liquid chromatography in their pharmaceutical dosage form. The chromatographic separation was performed on an ODS column (250 × 4.6 mm, 5 µm) using mobile phase A (potassium dihydrogen orthophosphate, pH adjusted to 2.5) and mobile phase B (acetonitrile) in the ratio of 55:45% v/v at a flow rate of 1 mL/min. The analytes were detected at 250 nm. The method was found to be linear in the concentration range of 2–12 µg/mL for EMT, 3–18 µg/mL for TNDF, 1.5–9 µg/mL for ELV and COB, with the coefficient value (R2) of >0.9990. The accuracy was measured via recovery studies and found to be acceptable, and the percentage recoveries were found in the range of 99.93–100.08 ± 0.5%. Forced degradation studies were also conducted, and the drugs were subjected to various stress conditions such as acid hydrolysis, base hydrolysis, oxidative, photolytic and thermal degradation. The proposed method was successfully validated and applied for the quantitative estimation of these drugs in both bulk and tablet dosage forms. PMID:26865655

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.

Rheology as a tool for evaluation of melt processability of innovative dosage forms

DEFF Research Database (Denmark)

Aho, Johanna Maaria; Boetker, Johan P; Baldursdottir, Stefania

2015-01-01

) printing, will have an increasingly important role when designing products for flexible dosing, since dosage forms based on compacting of a given powder mixture do not enable manufacturing of optimal pharmaceutical products for personalized treatments. The melt processability of polymers and API...

Combination of ozonation and photocatalysis for pharmaceutical wastewater treatment

Science.gov (United States)

Ratnawati, Enjarlis, Slamet

2017-11-01

The chemical oxygen demand (COD) and phenol removal from pharmaceutical wastewater were investigated using configuration of two circulation batch reactors in a series with ozonation and photocatalytic processes. The ozonation is conducted with O3/granulated activated carbon (O3/GAC), whereas photocatalysis with TiO2 that immobilized on pumice stone (PS-TiO2). The effect of circulation flow rate (10; 12; 15 L/min) and the amount PS-TiO2 (200 g, 250 g, 300 g) were examined. Wastewater of 20 L was circulated pass through the pipe that injected with O3 by the ozone generator, and subsequently flow through two GAC columns, and finally, go through photoreactor that contains photocatalyst PS-TiO2 which equipped with mercury lamp as a photon source. At a time interval, COD and phenol concentration were measured to assess the performance of the process. FESEM imaging confirmed that TiO2 was successfully impregnated on PS, as corroborated by EDX spectra. Meanwhile, degradation process indicated that the combined ozonation and photocatalytic processes (O3/GAC-TiO2) is more efficient compared to the ozonation and photocatalysis alone. For combination process with the circulation flow rate of 10 L/min and 300 g of PS-TiO2,the influent COD of around 1000 ppm are effectively degraded to a final effluent COD of 290 ppm (71% removal) and initial phenol concentration of 4.75 ppm down to 0 ppm for 4 h which this condition fulfill the discharge standards quality. Therefore, this portable prototype reactor is effective that can be used in the pharmaceutical wastewater treatment. For the future, this process condition will be developed for orientation on the industrial applications (portable equipment) since pharmaceutical industries produce wastewater relatively in the small amount.

Stability-Indicating Validated HPLC Method for Analysis of Berberine Hydrochloride and Trimethoprim in Pharmaceutical Dosage Form

Directory of Open Access Journals (Sweden)

Jing-Chun Wang

2013-01-01

Full Text Available A stability-indicating HPLC method was developed and validated for the determination of berberine hydrochloride and trimethoprim in pharmaceutical dosage form in the presence of degradation products. The proposed RP-HPLC method utilizes an Agilent TC-C18, 4.6 mm × 250 mm, 5 μm, column using a mobile phase consisting of acetonitrile-50 mM potassium dihydrogen phosphate (30 : 70, v/v, pH adjusted to 3 with orthophosphoric acid at a flow rate of 1.0 mL/min and UV detection at 271 nm. The linearity of berberine hydrochloride and trimethoprim was in the range of 2 to 60 μg/mL (r=0.9996 and 1 to 30 μg/mL (r=0.9995, respectively. Repeatability and intermediate precisions were also determined with percentage relative standard deviation (% RSD less than 2.0%. The limits of detection were found to be 9.8 ng/mL for berberine hydrochloride and 2.5 ng/mL for trimethoprim. The mean recoveries for berberine hydrochloride and trimethoprim were 99.8 and 98.8%, respectively. The stability of the two drugs was determined under different conditions and the proposed method has shown effective separation for their degradation products. And the proposed assays method can thus be considered stability-indicating.

Clarification of Pharmaceutical Wastewater with Moringa Oleifera: Optimization Through Response Surface Methodology

Directory of Open Access Journals (Sweden)

Iva Rustanti Eri

2018-05-01

Full Text Available Herbal pharmaceutical industrial wastewater contains a high amount of suspended solids and alkaline (pH > 8; therefore it requires approprite coagulant and flocculant compounds for its wastewater treatment. The most widely used flocculant is a synthetic that has certain problems such as non-biodegradability and releases of toxic residual monomers. The use of eco-friendly flocculants as alternative materials for conventional flocculant in water and wastewater treatments is increasing. Numerous factors influence the performance of coagulation-flocculation process, such as coagulant dosage, flocculant dosage, initial potential of hydrogen (pH and velocity gradient of coagulation-flocculation. The main aim of this research is to evaluate the capability and effectiveness of Moringa oleifera extract for removal of suspended solid in herbal pharmaceutical industry. A coagulation-flocculation test was done by performing jar test at various speeds, according to the variation of the conducted treatment research. In this study, response surface methodology (RSM approach was used to optimize the concentration of coagulant dosage, flocculant dosage and flocculation velocity gradient (G, and the results were measured as maximum percentage of suspended solid removal. The wastewater used in this research originally came from the inlet of herbal pharmaceutical industry wastewater treatment plant, which was collected over 3 days. The wastewater has a total suspended solids of more than 1250 mg/L, and was alkaline (pH 9-10. The moringa extract was made from the extraction of a fat free moringa powder with a salt solution in a certain ratio. The percentage removal of suspended solid was 93.42-99.54%. The final results of the analysis of response surface showed that the variables of flocculant dosage and the flocculation velocity gradient (G have a huge impact on the amount of suspended solid removal, compared with the coagulant dosage. The model generated from the

Evaluation of Pharmaceutical and Microbial Qualities of Some ...

African Journals Online (AJOL)

The tablet formulation (Product A) showed acceptable crushing strength and friability but failed the test for disintegration time. The angle of repose of the powder dosage ... Keywords: Herbal medicinal products, microbial quality, pharmaceutical quality. > Tropical Journal of ... Featuring journals from 32 Countries: Algeria (5) ...

Advances in combination therapy of lung cancer

DEFF Research Database (Denmark)

Wu, Lan; Leng, Donglei; Cun, Dongmei

2017-01-01

Lung cancer is a complex disease caused by a multitude of genetic and environmental factors. The progression of lung cancer involves dynamic changes in the genome and a complex network of interactions between cancer cells with multiple, distinct cell types that form tumors. Combination therapy......, including small molecule drugs and biopharmaceuticals, which make the optimization of dosing and administration schedule challenging. This article reviews the recent advances in the design and development of combinations of pharmaceuticals for the treatment of lung cancer. Focus is primarily on rationales...... for the selection of specific combination therapies for lung cancer treatment, and state of the art of delivery technologies and dosage regimens for the combinations, tested in preclinical and clinical trials....

The coefficient of rolling resistance (CoRR) of some pharmaceutical tablets.

Science.gov (United States)

Ketterhagen, William R; Bharadwaj, Rahul; Hancock, Bruno C

2010-06-15

Experiments have been conducted to measure the coefficient of rolling resistance (CoRR) of some pharmaceutical tablets and several common materials, such as glass beads and steel ball bearings. CoRR values are required as inputs for discrete element method (DEM) models which can be used to model particulate flows and solid dosage form manufacturing processes. Until now there have been no CoRR data reported for pharmaceutical materials, and thus these new data will help to facilitate more accurate modeling of pharmaceutical systems. Copyright 2010 Elsevier B.V. All rights reserved.

Validated RP-HPLC Method for the Assay of Etoricoxib (A Non-Steroidal Anti-Inflammatory Drug in Pharmaceutical Dosage Forms

Directory of Open Access Journals (Sweden)

Srinivasu Topalli

2012-01-01

Full Text Available A simple, accurate, sensitive and reproducible reverse phase high performance liquid chromatographic method has been developed for the quantitative determination of Etoricoxib in pharmaceutical dosage forms. The assay was performed on Hypersil ODS C-18 (250 x 4.6 mm., 5µm particle size column using acetonitrile and potassium dihydrogen phosphate buffer (pH 4.2 (46:54 % v/v as mobile phase with UV detection at 280 nm (flow rate 1.2 ml/min. Bromhexine was used as an internal standard. Quantization was achieved by measurement of the peak area ratio of the drug to the internal standard. The limit of detection (LOD and the limit of quantification (LOQ were 0.0704 µg ml-1 and 0.2134 µg ml-1 respectively. Each analysis required no longer than 10 minutes. The calibration curve was linear over the concentration range from 0.5-85.0 µg ml-1. The retention times of Etoricoxib and Bromhexine were found to be 3.083 and 7.631 minutes respectively. The proposed method was validated according to the ICH guidelines and can be used successfully to analyse marketed formulations.

Stability indicating RP-HPLC method development and validation for the simultaneous determination of aminexil and minoxidil in pharmaceutical dosage form.

Science.gov (United States)

Siddiraju, S; Sahithi, M

2015-03-01

The objective of the present work is to develop stability indicating high-performance liquid chromatographic method for the simultaneous determination of aminexil and minoxidil in pharmaceutical dosage form. The chromatographic separation was achieved with BDS Hypersil C18 column (250 mm×4.6 mm×5 μ) as stationary phase and phosphate buffer and acetonitrile (78:22) as mobile phase. The method was employed by using a flow rate of 1.1 mL/min kept at 30°C. The detection wavelength was kept at 238 nm by using photo-diode array detector. The retention times of the aminexil and minoxidil were found to be 2.3 min and 3.9 min, respectively. The method developed was validated in accordance with ICH guidelines with respect to the stability indicating capacity of the method including system suitability, accuracy, precision, linearity, range, limit of detection, limit of quantification and robustness. The linearity responses of aminexil and minoxidil were found to be in the concentration ranges of 18.75-112.5 μg/mL and 25-150 μg/mL, respectively. The LOD and LOQ values for aminexil were found to be 0.31 and 0.92 μg/mL and minoxidil were found to be 0.03 and 0.10 μg/mL respectively. The percentage recoveries for both the drugs were found in the range of 98-101%. This method is accurate, precise and sensitive; hence, it can be employed for routine quality control of aminexil and minoxidil in pharmaceutical industries and drug testing laboratories. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

A Study of Method Development, Validation, and Forced Degradation for Simultaneous Quantification of Paracetamol and Ibuprofen in Pharmaceutical Dosage Form by RP-HPLC Method

OpenAIRE

Jahan, Md. Sarowar; Islam, Md. Jahirul; Begum, Rehana; Kayesh, Ruhul; Rahman, Asma

2014-01-01

A rapid and stability-indicating reversed phase high-performance liquid chromatography (RP-HPLC) method was developed for simultaneous quantification of paracetamol and ibuprofen in their combined dosage form especially to get some more advantages over other methods already developed for this combination. The method was validated according to United States Pharmacopeia (USP) guideline with respect to accuracy, precision, specificity, linearity, solution stability, robustness, sensitivity, and...

Combined crystal structure prediction and high-pressure crystallization in rational pharmaceutical polymorph screening

DEFF Research Database (Denmark)

Neumann, M A; van de Streek, J; Fabbiani, F P A

2015-01-01

Organic molecules, such as pharmaceuticals, agro-chemicals and pigments, frequently form several crystal polymorphs with different physicochemical properties. Finding polymorphs has long been a purely experimental game of trial-and-error. Here we utilize in silico polymorph screening in combination...

Chemometrical aspects of quality in pharmaceutical technology : the application of robustness criteria and multi criteria decision making in optimization procedures for pharmaceutical formulations

NARCIS (Netherlands)

Boer, Jan Hendrik de

1992-01-01

In pharmaceutical technology one is often engaged with the design and analysis of formulations. A formulation of a solid dosage form is normally a mixture of components. This formulation usually consists of a number of components with fixed concentrations like the the medicinal substance(s) (drug),

Pharmaceutical Particle Engineering via Spray Drying

Science.gov (United States)

2007-01-01

This review covers recent developments in the area of particle engineering via spray drying. The last decade has seen a shift from empirical formulation efforts to an engineering approach based on a better understanding of particle formation in the spray drying process. Microparticles with nanoscale substructures can now be designed and their functionality has contributed significantly to stability and efficacy of the particulate dosage form. The review provides concepts and a theoretical framework for particle design calculations. It reviews experimental research into parameters that influence particle formation. A classification based on dimensionless numbers is presented that can be used to estimate how excipient properties in combination with process parameters influence the morphology of the engineered particles. A wide range of pharmaceutical application examples—low density particles, composite particles, microencapsulation, and glass stabilization—is discussed, with specific emphasis on the underlying particle formation mechanisms and design concepts. PMID:18040761

Validated sensitive spectrofluorimetric method for determination of antihistaminic drug azelastine HCl in pure form and in pharmaceutical dosage forms: application to stability study.

Science.gov (United States)

El-Masry, Amal A; Hammouda, Mohammed E A; El-Wasseef, Dalia R; El-Ashry, Saadia M

2017-03-01

A highly sensitive, simple and rapid spectrofluorimetric method was developed for the determination of azelastine HCl (AZL) in either its pure state or pharmaceutical dosage form. The proposed method was based on measuring the native fluorescence of the studied drug in 0.2 M H 2 SO 4 at λ em  = 364 nm after excitation at λ ex  = 275 nm. Different experimental parameters were studied and optimized carefully to obtain the highest fluorescence intensity. The proposed method showed a linear dependence of the fluorescence intensity on drug concentration over a concentration range of 10-250 ng/mL, with a limit of detection of 1.52 ng/mL and limit of quantitation of 4.61 ng/mL. Moreover, the method was successfully applied to pharmaceutical preparations, with percent recovery values (± SD) of 99.96 (± 0.4) and 100.1 (± 0.52) for nasal spray and eye drops, respectively. The results were in good agreement with those obtained by the comparison method, as revealed by Student's t-test and the variance ratio F-test. The method was extended to study the stability of AZL under stress conditions, where the drug was exposed to neutral, acidic, alkaline, oxidative and photolytic degradation according to International Conference on Harmonization (ICH) guidelines. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

A Validated RP-HPLC Method for the Determination of Atazanavir in Pharmaceutical Dosage Form

Directory of Open Access Journals (Sweden)

K. Srinivasu

2011-01-01

Full Text Available A validated RP HPLC method for the estimation of atazanavir in capsule dosage form on YMC ODS 150 × 4.6 mm, 5 μ column using mobile phase composition of ammonium dihydrogen phosphate buffer (pH 2.5 with acetonitrile (55:45 v/v. Flow rate was maintained at 1.5 mL/min with 288 nm UV detection. The retention time obtained for atazanavir was at 4.7 min. The detector response was linear in the concentration range of 30 - 600 μg/mL. This method has been validated and shown to be specific, sensitive, precise, linear, accurate, rugged, robust and fast. Hence, this method can be applied for routine quality control of atazanavir in capsule dosage forms as well as in bulk drug.

Synergistic Effect of Combining Plutella xylostella Granulovirus and Bacillus thuringiensis at Sublethal Dosages on Controlling of Diamondback Moth (Lepidoptera: Plutellidae).

Science.gov (United States)

Han, Guangjie; Li, Chuanming; Liu, Qin; Xu, Jian

2015-10-01

Plutella xylostella granulovirus (PxGV) and Bacillus thuringiensis (Bt) are both entomo-pathogens to the diamondback moth, Plutella xylostella (L.). The purpose of the present study was to measure the effect of the combination of PxGV and Bt at sublethal dosages on the development and mortality of diamondback moth in a laboratory setting. Bt and PxGV exhibited synergistic effect on diamondback moth larval mortality and effectively controlled diamondback moth populations with low dose combination treatment. The combination of three parts per million Bt and 1.3 × 10(3) occlusion bodies per milliliter of PxGV revealed a higher larval mortality compared with the treatment of Bt or PxGV alone. Combination of Bt and PxGV at sublethal concentrations also increased larval duration, reduced oviposition and decreased adult longevity remarkably, resulting in the lowest population trend index among the treatments. The results suggested that the combination of Bt and PxGV at sublethal dosages might provide a valuable way to improve the control efficacy of diamondback moth compared with treatment of Bt or PxGV alone. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Folic Acid.

Science.gov (United States)

Hofsäss, Martin A; Souza, Jacqueline de; Silva-Barcellos, Neila M; Bellavinha, Karime R; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D W; Parr, Alan; Langguth, Peter; Polli, James E; Shah, Vinod P; Tajiri, Tomokazu; Mehta, Mehul U; Dressman, Jennifer B

2017-12-01

This work presents a review of literature and experimental data relevant to the possibility of waiving pharmacokinetic bioequivalence studies in human volunteers for approval of immediate-release solid oral pharmaceutical forms containing folic acid as the single active pharmaceutical ingredient. For dosage forms containing 5 mg folic acid, the highest dose strength on the World Health Organization Essential Medicines List, the dose/solubility ratio calculated from solubility studies was higher than 250 mL, corresponding to a classification as "not highly soluble." Small, physiological doses of folic acid (≤320 μg) seem to be absorbed completely via active transport, but permeability data for higher doses of 1-5 mg are inconclusive. Following a conservative approach, folic acid is classified as a Biopharmaceutics Classification System class IV compound until more reliable data become available. Commensurate with its solubility characteristics, the results of dissolution studies indicated that none of the folic acid products evaluated showed rapid dissolution in media at pH 1.2 or 4.5. Therefore, according to the current criteria of the Biopharmaceutics Classification System, the biowaiver approval procedure cannot be recommended for immediate-release solid oral dosage forms containing folic acid. Copyright © 2017 American Pharmacists Association®. All rights reserved.

Accelerated in-vitro release testing methods for extended-release parenteral dosage forms.

Science.gov (United States)

Shen, Jie; Burgess, Diane J

2012-07-01

This review highlights current methods and strategies for accelerated in-vitro drug release testing of extended-release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in-situ depot-forming systems and implants. Extended-release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, 'real-time' in-vitro release tests for these dosage forms are often run over a long time period. Accelerated in-vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in-vitro release methods using United States Pharmacopeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended-release parenteral dosage forms, along with the accelerated in-vitro release testing methods currently employed are discussed. Accelerated in-vitro release testing methods with good discriminatory ability are critical for quality control of extended-release parenteral products. Methods that can be used in the development of in-vitro-in-vivo correlation (IVIVC) are desirable; however, for complex parenteral products this may not always be achievable. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

Material Considerations for Fused-Filament Fabrication of Solid Dosage Forms

Directory of Open Access Journals (Sweden)

Evert Fuenmayor

2018-04-01

Full Text Available Material choice is a fundamental consideration when it comes to designing a solid dosage form. The matrix material will ultimately determine the rate of drug release since the physical properties (solubility, viscosity, and more of the material control both fluid ingress and disintegration of the dosage form. The bulk properties (powder flow, concentration, and more of the material should also be considered since these properties will influence the ability of the material to be successfully manufactured. Furthermore, there is a limited number of approved materials for the production of solid dosage forms. The present study details the complications that can arise when adopting pharmaceutical grade polymers for fused-filament fabrication in the production of oral tablets. The paper also presents ways to overcome each issue. Fused-filament fabrication is a hot-melt extrusion-based 3D printing process. The paper describes the problems encountered in fused-filament fabrication with Kollidon® VA64, which is a material that has previously been utilized in direct compression and hot-melt extrusion processes. Formulation and melt-blending strategies were employed to increase the printability of the material. The paper defines for the first time the essential parameter profile required for successful 3D printing and lists several pre-screening tools that should be employed to guide future material formulation for the fused-filament fabrication of solid dosage forms.

Confused ionic liquid ions--a "liquification" and dosage strategy for pharmaceutically active salts.

Science.gov (United States)

Bica, Katharina; Rogers, Robin D

2010-02-28

We present a strategy to expand the liquid and compositional ranges of ionic liquids, specifically pharmaceutically active ionic liquids, by simple mixing with a solid acid or base to form oligomeric ions.

Development of a stability-indicating UPLC method for determining olanzapine and its associated degradation products present in active pharmaceutical ingredients and pharmaceutical dosage forms.

Science.gov (United States)

Krishnaiah, Ch; Vishnu Murthy, M; Kumar, Ramesh; Mukkanti, K

2011-03-25

A simple, sensitive and reproducible ultra performance liquid chromatography (UPLC) coupled with a photodiode array detector method was developed for the quantitative determination of olanzapine (OLN) in API and pharmaceutical dosage forms. The method is applicable to the quantification of related substances and assays of drug substances. Chromatographic separation was achieved on Acquity UPLC BEH 100-mm, 2.1-mm, and 1.7-μm C-18 columns, and the gradient eluted within a short runtime, i.e., within 10.0 min. The eluted compounds were monitored at 250 nm, the flow rate was 0.3 mL/min, and the column oven temperature was maintained at 27°C. The resolution of OLN and eight (potential, bi-products and degradation) impurities was greater than 2.0 for all pairs of components. The high correlation coefficient (r(2)>0.9991) values indicated clear correlations between the investigated compound concentrations and their peak areas within the test ranges. The repeatability and intermediate precision, expressed by the RSD, were less than 2.4%. The accuracy and validity of the method were further ascertained by performing recovery studies via a spike method. The accuracy of the method expressed as relative error was satisfactory. No interference was observed from concomitant substances normally added to the tablets. The drug was subjected to the International Conference on Harmonization (ICH)-prescribed hydrolytic, oxidative, photolytic and thermal stress conditions. The performance of the method was validated according to the present ICH guidelines for specificity, limit of detection, limit of quantification, linearity, accuracy, precision, ruggedness and robustness. Copyright © 2010 Elsevier B.V. All rights reserved.

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)

Validated UV-Spectrophotometric Methods for Determination of Gemifloxacin Mesylate in Pharmaceutical Tablet Dosage Forms

Directory of Open Access Journals (Sweden)

R. Rote Ambadas

2010-01-01

Full Text Available Two simple, economic and accurate UV spectrophotometric methods have been developed for determination of gemifloxacin mesylate in pharmaceutical tablet formulation. The first UV-spectrophotometric method depends upon the measurement of absorption at the wavelength 263.8 nm. In second area under curve method the wavelength range for detection was selected from 268.5-258.5 nm. Beer’s law was obeyed in the range of 2 to 12 μgmL-1 for both the methods. The proposed methods was validated statistically and applied successfully to determination of gemifloxacin mesylate in pharmaceutical formulation.

On the exfoliating polymeric cellular dosage forms for immediate drug release.

Science.gov (United States)

Blaesi, Aron H; Saka, Nannaji

2016-06-01

The most prevalent pharmaceutical dosage forms at present-the oral immediate-release tablets and capsules-are granular solids. Though effective in releasing drug rapidly, development and manufacture of such dosage forms are fraught with difficulties inherent to particulate processing. Predictable dosage form manufacture could be achieved by liquid-based processing, but cast solid dosage forms are not suitable for immediate drug release due to their resistance to fluid percolation. To overcome this limitation, we have recently introduced cellular dosage forms that can be readily prepared from polymeric melts. It has been shown that open-cell structures comprising polyethylene glycol 8000 (PEG 8k) excipient and a drug exfoliate upon immersion in a dissolution medium. The drug is then released rapidly due to the large specific surface area of the exfoliations. In this work, we vary the molecular weight of the PEG excipient and investigate its effect on the drug release kinetics of structures with predominantly open-cell topology. We demonstrate that the exfoliation rate decreases substantially if the excipient molecular weight is increased from 12 to 100kg/mol, which causes the drug dissolution time to increase by more than a factor of ten. A model is then developed to elucidate the exfoliation behavior of cellular structures. Diverse transport processes are considered: percolation due to capillarity, diffusion of dissolution medium through the cell walls, and viscous flow of the saturated excipient. It is found that the lower exfoliation rate and the longer dissolution time of the dosage forms with higher excipient molecular weight are primarily due to the greater viscosity of the cell walls after fluid penetration. Copyright © 2016 Elsevier B.V. All rights reserved.

Paper analytical devices for fast field screening of beta lactam antibiotics and antituberculosis pharmaceuticals.

Science.gov (United States)

Weaver, Abigail A; Reiser, Hannah; Barstis, Toni; Benvenuti, Michael; Ghosh, Debarati; Hunckler, Michael; Joy, Brittney; Koenig, Leah; Raddell, Kellie; Lieberman, Marya

2013-07-02

Reports of low-quality pharmaceuticals have been on the rise in the past decade, with the greatest prevalence of substandard medicines in developing countries, where lapses in manufacturing quality control or breaches in the supply chain allow substandard medicines to reach the marketplace. Here, we describe inexpensive test cards for fast field screening of pharmaceutical dosage forms containing beta lactam antibiotics or combinations of the four first-line antituberculosis (TB) drugs. The devices detect the active pharmaceutical ingredients (APIs) ampicillin, amoxicillin, rifampicin, isoniazid, ethambutol, and pyrazinamide and also screen for substitute pharmaceuticals, such as acetaminophen and chloroquine that may be found in counterfeit pharmaceuticals. The tests can detect binders and fillers such as chalk, talc, and starch not revealed by traditional chromatographic methods. These paper devices contain 12 lanes, separated by hydrophobic barriers, with different reagents deposited in the lanes. The user rubs some of the solid pharmaceutical across the lanes and dips the edge of the paper into water. As water climbs up the lanes by capillary action, it triggers a library of different chemical tests and a timer to indicate when the tests are completed. The reactions in each lane generate colors to form a "color bar code" which can be analyzed visually by comparison with standard outcomes. Although quantification of the APIs is poor compared with conventional analytical methods, the sensitivity and selectivity for the analytes is high enough to pick out suspicious formulations containing no API or a substitute API as well as formulations containing APIs that have been "cut" with inactive ingredients.

Biowaiver monograph for immediate-release solid oral dosage forms: bisoprolol fumarate.

Science.gov (United States)

Charoo, Naseem A; Shamsher, Areeg A A; Lian, Lai Y; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James; Shah, Vinod P; Dressman, Jennifer

2014-02-01

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate-release (IR) solid oral dosage forms containing bisoprolol as the sole active pharmaceutical ingredient (API) are reviewed. Bisoprolol is classified as a Class I API according to the current Biopharmaceutics Classification System (BCS). In addition to the BCS class, its therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions, and reported BE/bioavailability problems are taken into consideration. Qualitative compositions of IR tablet dosage forms of bisoprolol with a marketing authorization (MA) in ICH (International Conference on Harmonisation) countries are tabulated. It was inferred that these tablets had been demonstrated to be bioequivalent to the innovator product. No reports of failure to meet BE standards have been made in the open literature. On the basis of all these pieces of evidence, a biowaiver can currently be recommended for bisoprolol fumarate IR dosage forms if (1) the test product contains only excipients that are well known, and used in normal amounts, for example, those tabulated for products with MA in ICH countries and (2) both the test and comparator dosage form are very rapidly dissolving, or, rapidly dissolving with similarity of the dissolution profiles demonstrated at pH 1.2, 4.5, and 6.8. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Chemometrics-Assisted UV Spectrophotometric and RP-HPLC Methods for the Simultaneous Determination of Tolperisone Hydrochloride and Diclofenac Sodium in their Combined Pharmaceutical Formulation.

Science.gov (United States)

Gohel, Nikunj Rameshbhai; Patel, Bhavin Kiritbhai; Parmar, Vijaykumar Kunvarji

2013-01-01

Chemometrics-assisted UV spectrophotometric and RP-HPLC methods are presented for the simultaneous determination of tolperisone hydrochloride (TOL) and diclofenac sodium (DIC) from their combined pharmaceutical dosage form. Chemometric methods are based on principal component regression and partial least-square regression models. Two sets of standard mixtures, calibration sets, and validation sets were prepared. Both models were optimized to quantify each drug in the mixture using the information included in the UV absorption spectra of the appropriate solution in the range 241-290 nm with the intervals λ = 1 nm at 50 wavelengths. The optimized models were successfully applied to the simultaneous determination of these drugs in synthetic mixture and pharmaceutical formulation. In addition, an HPLC method was developed using a reversed-phase C18 column at ambient temperature with a mobile phase consisting of methanol:acetonitrile:water (60:30:10 v/v/v), pH-adjusted to 3.0, with UV detection at 275 nm. The methods were validated in terms of linearity, accuracy, precision, sensitivity, specificity, and robustness in the range of 3-30 μg/mL for TOL and 1-10 μg/mL for DIC. The robustness of the HPLC method was tested using an experimental design approach. The developed HPLC method, and the PCR and PLS models were used to determine the amount of TOL and DIC in tablets. The data obtained from the PCR and PLS models were not significantly different from those obtained from the HPLC method at 95% confidence limit.

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

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.

Determining S-1 dosage at hospitals prioritizing cancer chemotherapy

International Nuclear Information System (INIS)

Morimoto, Shigefumi; Kitada, Noriaki; Anami, Setsuko

2008-01-01

Although it is recommended that the standard S-1 dosage should be based on how large the body surface area is, an on-site setting of the appropriate dosage is often lower than the standard one, depending on the individual's condition and considering possible side effects and so, on. Here, we investigated usage conditions for S-1 as a part of field training for expert pharmacists at our hospital that performs total clinical treatments. Decreases in dosage per day for elderly patients were although the standard dosage is generally determined according to the amount of a patient's body surface. We conducted a retrospective survey with a total 90 patients by creating a tree-diagram to identify a reduction standard. It was found that the S-1 dosage was decreased when there were side effects, aggravation in performance status, decrease in kidney function, old age, combined injection chemotherapy, and a decrease in radiation therapy performance. The dosage decreases without such medical reasons were seen in only 4 of the 90 patients. At hospitals giving priority to chemotherapy, it became clear that appropriate treatment was promoted by decreasing. The individual target dosage on the basis of daily medical examination. (author)

Intelligent system for improving dosage control

Directory of Open Access Journals (Sweden)

Fabio Cosme Rodrigues dos Santos

2017-02-01

Full Text Available Coagulation is one of the most important processes in a drinking-water treatment plant, and it is applied to destabilize impurities in water for the subsequent flocculation stage. Several techniques are currently used in the water industry to determine the best dosage of the coagulant, such as the jar-test method, zeta potential measurements, artificial intelligence methods, comprising neural networks, fuzzy and expert systems, and the combination of the above-mentioned techniques to help operators and engineers in the water treatment process. Current paper presents an artificial neural network approach to evaluate optimum coagulant dosage for various scenarios in raw water quality, using parameters such as raw water color, raw water turbidity, clarified and filtered water turbidity and a calculated Dose Rate to provide the best performance in the filtration process. Another feature in current approach is the use of a backpropagation neural network method to estimate the best coagulant dosage simultaneously at two points of the water treatment plant. Simulation results were compared to the current dosage rate and showed that the proposed system may reduce costs of raw material in water treatment plant.

UPLC and LC-MS studies on degradation behavior of irinotecan hydrochloride and development of a validated stability-indicating ultra-performance liquid chromatographic method for determination of irinotecan hydrochloride and its impurities in pharmaceutical dosage forms.

Science.gov (United States)

Kumar, Navneet; Sangeetha, Dhanaraj; Reddy, Sunil P

2012-10-01

The objective of the current investigation was to study the degradation behavior of irinotecan hydrochloride under different International Conference on Harmonization (ICH) recommended stress conditions using ultra-performance liquid chromatography and liquid chromatography-mass spectrometry and to establish a validated stability-indicating reverse-phase ultra-performance liquid chromatographic method for the quantitative determination of irinotecan hydrochloride and its seven impurities and degradation products in pharmaceutical dosage forms. Irinotecan hydrochloride was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal and photolytic degradation. Irinotecan hydrochloride was found to degrade significantly in oxidative and base hydrolysis and photolytic degradation conditions. The degradation products were well resolved from the main peak and its impurities, thus proving the stability-indicating power of the method. Chromatographic separation was achieved on a Waters Acquity BEH C8 (100 × 2.1 mm) 1.7-µm column with a mobile phase containing a gradient mixture of solvent A (0.02M KH(2)PO(4) buffer, pH 3.4) and solvent B (a mixture of acetonitrile and methanol in the ratio of 62:38 v/v). The mobile phase was delivered at a flow rate of 0.3 mL/min with ultraviolet detection at 220 nm. The run time was 8 min, within which irinotecan and its seven impurities and degradation products were satisfactorily separated. The developed method was validated as per 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 irinotecan hydrochloride in pharmaceutical dosage forms.

Biowaiver monograph for immediate-release solid oral dosage forms: fluconazole.

Science.gov (United States)

Charoo, Naseem; Cristofoletti, Rodrigo; Graham, Alexandra; Lartey, Paul; Abrahamsson, Bertil; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James; Shah, Vinod P; Dressman, Jennifer

2014-12-01

Literature data pertaining to the decision to allow a waiver of in vivo bioequivalence (BE) testing requirements for the approval of immediate release (IR) solid oral dosage forms containing fluconazole as the only active pharmaceutical ingredient (API) are reviewed. The decision is based on solubility, dissolution, permeability, therapeutic index, pharmacokinetic parameters, pharmacodynamic properties, and other relevant data. BE/bioavailability (BA) problems and drug-excipients interaction data were also reviewed and taken into consideration. According to the biopharmaceutics classification system (BCS), fluconazole in polymorphic forms II and III is a BCS class I drug and has a wide therapeutic index. BE of test formulations from many different manufacturers containing different excipients confirmed that the risk of bioinequivalence because of formulation and manufacturing factors is low. It was inferred that risk can be further reduced if in vitro studies are performed according to biowaiver guidelines. Thus, it is concluded that a biowaiver can be recommended for fluconazole IR dosage forms if (a) fluconazole is present as polymorphic form II or III or any other form/mixture showing high solubility, (b) the selection of excipients be limited to those found in IR drug products approved in International Conference on Harmonisation (ICH) countries for the same dosage form and used in their usual amounts, and (c) both the test and comparator dosage form are very rapidly dissolving, or, rapidly dissolving throughout the shelf life with similar dissolution profiles at pH 1.2, 4.5, and 6.8. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

[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.

Laūq: A Sustained-Release Dosage Form for Respiratory Disorders in Traditional Persian Medicine.

Science.gov (United States)

Karegar-Borzi, Hossein; Salehi, Mehdi; Rahimi, Roja

2016-01-01

Laūq is a pharmaceutical dosage form that had been mainly used for the treatment of various respiratory disorders in traditional Persian medicine. It is important from 2 aspects: a dosage form with efficient and optimum delivery of drugs to the respiratory tract and biological effects of its ingredients. Natural medicine in laūq has been demonstrated to act in respiratory disorders by their antitussive, antiallergic, anti-inflammatory, antioxidant, spasmolytic, and antibacterial activities. Some of these natural remedies act by most of the mentioned mechanisms such as Cydonia oblonga, Glycyrrhiza glabra, Crocus sativus, Hyssopus officinalis, Foeniculum vulgare, and honey. However, the evidence is limited including Cassia fistula, Papaver somniferum, and Drimia maritima. According to positive pharmacokinetic and pharmacodynamic aspects of laūqs, they may be considered as efficient dosage forms for delivery of drugs to the respiratory tract. For better compatibility of patients, it could be substituted laūqs with newer drug delivery systems like lozenges. © The Author(s) 2015.

[Oral films as perspective dosage form].

Science.gov (United States)

Walicová, Veronika; Gajdziok, Jan

Oral films, namely buccal mucoadhesive films and orodispersible films represent innovative formulations for administration of a wide range of drugs. Oral films show many advantageous properties and are intended for systemic drug delivery or for local treatment of the oral mucosa. In both cases, the film represents a thin layer, which could be intended to adhere to the oral mucosa by means of mucoadhesion; or to rapid dissolution and subsequent swallowing without the need of liquid intake, in the case of orodispersible films. Main constitutive excipients are film-forming polymers, which must in the case of mucoadhesive forms remain on the mucosa within the required time interval. Oral films are currently available on the pharmaceutical market and could compete with conventional oral dosage forms in the future. oral cavity oral films buccal mucoadhesive films orodispersible films film-forming polymers.

[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.

Pharmaceutical quality by design: product and process development, understanding, and control.

Science.gov (United States)

Yu, Lawrence X

2008-04-01

The purpose of this paper is to discuss the pharmaceutical Quality by Design (QbD) and describe how it can be used to ensure pharmaceutical quality. The QbD was described and some of its elements identified. Process parameters and quality attributes were identified for each unit operation during manufacture of solid oral dosage forms. The use of QbD was contrasted with the evaluation of product quality by testing alone. The QbD is a systemic approach to pharmaceutical development. It means designing and developing formulations and manufacturing processes to ensure predefined product quality. Some of the QbD elements include: Defining target product quality profile; Designing product and manufacturing processes; Identifying critical quality attributes, process parameters, and sources of variability; Controlling manufacturing processes to produce consistent quality over time. Using QbD, pharmaceutical quality is assured by understanding and controlling formulation and manufacturing variables. Product testing confirms the product quality. Implementation of QbD will enable transformation of the chemistry, manufacturing, and controls (CMC) review of abbreviated new drug applications (ANDAs) into a science-based pharmaceutical quality assessment.

Investigating physical properties of solid dosage forms during pharmaceutical processing : Process analytical applications of vibrational spectroscopy

OpenAIRE

Römer, Meike

2008-01-01

In order to improve and continuously develop the quality of pharmaceutical products, the process analytical technology (PAT) framework has been adopted by the US Food and Drug Administration. One of the aims of PAT is to identify critical process parameters and their effect on the quality of the final product. Real time analysis of the process data enables better control of the processes to obtain a high quality product. The main purpose of this work was to monitor crucial pharmaceutical...

HPLC DETERMINATION OF FENBENDAZOLE AND IVERMECTIN SIMULTANEOUSLY IN BULK AND PHARMACEUTICAL DOSAGE FORMS

OpenAIRE

Battula Sreenivasa Rao, Mandapati Varaprasad Reddy*, Bhatraju Sreenivasa Rao

2017-01-01

In the present study, a simple, precise and accurate high performance liquid chromatography with photodiode array detector was developed for the simultaneous estimation of ivermectin & fenbendazole in bulk and tablet dosage forms. A Zorbax C8 column (250 cm × 4.6 mm × 5 μm) with mobile phase consisting of 0.1 M potassium dihydrogen orthophosphate and methanol (60:40 v/v) having pH 4.5 (adjusted with orthophosphoric acid) was used. The flow rate was 1.2 ml/min and the effluents were detected a...

Biowaiver monographs for immediate release solid oral dosage forms: efavirenz.

Science.gov (United States)

Cristofoletti, Rodrigo; Nair, Anita; Abrahamsson, Bertil; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James E; Shah, Vinod P; Dressman, Jennifer B

2013-02-01

Literature data pertaining to the decision to allow a waiver of in vivo bioequivalence testing for the approval of immediate-release (IR) solid oral dosage forms containing efavirenz as the only active pharmaceutical ingredient (API) are reviewed. Because of lack of conclusive data about efavirenz's permeability and its failure to comply with the "high solubility" criteria according to the Biopharmaceutics Classification System (BCS), the API can be classified as BCS Class II/IV. In line with the solubility characteristics, the innovator product does not meet the dissolution criteria for a "rapidly dissolving product." Furthermore, product variations containing commonly used excipients or in the manufacturing process have been reported to impact the rate and extent of efavirenz absorption. Despite its wide therapeutic index, subtherapeutic levels of efavirenz can lead to treatment failure and also facilitate the emergence of efavirenz-resistant mutants. For all these reasons, a biowaiver for IR solid oral dosage forms containing efavirenz as the sole API is not scientifically justified for reformulated or multisource drug products. Copyright © 2012 Wiley Periodicals, Inc.

A Localized Surface Plasmon Resonance Sensing Method for Simultaneous Determination of Atenolol and Amiloride in Pharmaceutical Dosage Forms and Urine Samples

Directory of Open Access Journals (Sweden)

Marwa R. El-Zahry

2018-01-01

Full Text Available This contribution describes a simple, fast, and sensitive application of localized surface plasmon resonance effect of silver nanoparticles for simultaneous determination of antihypertensive drugs’ mixture atenolol and amiloride in both pharmaceutical dosage forms and in biological samples (urine. Silver nanoparticles were prepared by chemical reduction of silver nitrate using hydroxylamine HCL in an alkaline medium. Application of silver-hydroxylamine nanoparticles (SH NPs provides many advantages including reproducibility, sensitivity, and cost effective way of analyte determination. Amiloride has four amino groups which act as attachment points on the surface of silver nanoparticles resulting in a synergistic effect on the absorption intensity of atenolol, leading to increase the sensitivity of the determination of both compounds. This method shows excellent advantages comparing with the previously reported methods, including accuracy, precision, and selectivity. The linear range of atenolol is 1 × 10−5–1 × 10−4 mol·L−1 and of amiloride is 1 × 10−6–1 × 10−5 mol·L−1. The limit of detection (LOD values of atenolol and amiloride are 0.89 × 10−5 and 0.42 × 10−6 mol·L−1, respectively.

Development of the fast, simple and fully validated high performance liquid chromatographic method with diode array detector for quantification of testosterone esters in an oil-based injectable dosage form.

Science.gov (United States)

Kozlik, Petr; Tircova, Barbora

2016-11-01

Counterfeit steroids are available on the black market, ultimately to consumers who believe they are buying a legitimate pharmaceutical item from the labeled company. In many cases, counterfeit steroids can contain lower doses or some products can be overdosed. This can unwittingly expose users to a significant health risks. The mixture of testosterone propionate, phenylpropionate, isocaproate and decanoate in an oil-based injectable dosage form belongs to the one of the most misused illicit drugs by a variety of athletes. This study developed a new, fast, simple and reliable HPLC method combined with a simple sample preparation step to determine testosterone propionate, phenylpropionate, isocaproate and decanoate in an oil-based injectable dosage form without the use of sophisticated and expensive instrumentation. The developed analytical procedure provides high throughput of samples where LC analysis takes only 6min and sample preparation of oil matrix in one step takes approximately 10min with precision ranging from 1.03 to 3.38% (RSD), and accuracy (relative error %) within ±2.01%. This method was found to be precise, linear, accurate, sensitive, selective and robust for routine application in screening of commercial pharmaceutical products based on content of mentioned testosterone esters in their oil-based injectable dosage form for counterfeit drugs. This method was successfully applied to the analysis of nine samples of commercial testosterone mixtures purchased from various sources and will be further used as an effective screening method for determination of previously mentioned testosterone esters in samples confiscated by Institute of Forensic Science (Slovakia) during the illegal trade. Copyright © 2016 Elsevier Inc. All rights reserved.

Multicomponent Pharmaceutical Cocrystals: A Novel Approach for Combination Therapy.

Science.gov (United States)

Fatima, Zeeshan; Srivastava, Dipti; Kaur, Chanchal Deep

2018-03-05

Cocrystallization is a technique for modifying the physicochemical and pharmacokinetic properties of an active pharmaceutical ingredient (API) embodying the concept of supramolecular synthon. Most of the examples cited in the literature are of cocrystals formed between an API and a coformer chosen from the generally recognized as safe (GRAS) substance list, however, few examples exist where a cocrystal consists of two or more APIs. These cocrystals are commonly known as multi API, multi drug or drug- drug cocrystals. The formation of such cocrystals is feasible by virtue of non covalent interactions between the APIs, which help them in retaining their biologic activity. In addition, drug- drug cocrystals also offer the potential solution to the limitations such as solubility, stability differences and chemical interaction between the APIs which is often faced during the traditional combination therapy. Cocrystallization of two or more APIs can be employed for delivery of combination drugs for the better and efficacious management of many complex disorders where existing monotherapies do not furnish the desired therapeutic effect. This review on the existing drug-drug cocrystals is to gain insight for better designing of multi API cocrystals with improved physicochemical and pharmacokinetic profile and its application in multiple target therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Stability of Pharmaceuticals in Space

Science.gov (United States)

Nguyen, Y-Uyen

2009-01-01

Stability testing is a tool used to access shelf life and effects of storage conditions for pharmaceutical formulations. Early research from the International Space Station (ISS) revealed that some medications may have degraded while in space. This potential loss of medication efficacy would be very dangerous to Crew health. The aim of this research project, Stability of Pharmacotherapeutic Compounds, is to study how the stability of pharmaceutical compounds is affected by environmental conditions in space. Four identical pharmaceutical payload kits containing medications in different dosage forms (liquid for injection, tablet, capsule, ointment and suppository) were transported to the ISS aboard a Space Shuttle. One of the four kits was stored on that Shuttle and the other three were stored on the ISS for return to Earth at various time intervals aboard a pre-designated Shuttle flight. The Pharmacotherapeutics laboratory used stability test as defined by the United States Pharmacopeia (USP), to access the degree of degradation to the Payload kit medications that may have occurred during space flight. Once these medications returned, the results of stability test performed on them were compared to those from the matching ground controls stored on Earth. Analyses of the results obtained from physical and chemical stability assessments on these payload medications will provide researchers additional tools to promote safe and efficacious medications for space exploration.

Combined aerobic and physicochemical treatment of pharmaceutical industry sludge

International Nuclear Information System (INIS)

Asia, Q.I.; Ademoroti, A.M.C.

2005-01-01

Composite samples of sludge obtained from a pharmaceutical factory were analysed for their pollution characteristics. The samples were then treated by integrated aerobic biological and physicochemical methods. The analysis revealed that the BOD and COD of the sludge liquor were high, as well as were the levels of solids concentration, nitrogen, phosphorus and bacterial count. These showed that sludge from this industry had a high pollution potential, and therefore needed treatment before disposal or reuse in other applications. Percentage solids reduction achieved were in the range of 26.1 to 29% of total soluble solids, 26.1 to 33% of suspended solids, and 43 to 52% of volatile solids, BOD and COD reductions were in the range of 96.1 to 98.2% and 96.8 to 98.4% respectively. Ammonia nitrogen reductions in this sludge were about 85.2 to 93.3%. Total nitrogen and phosphorus were also found to be appreciably reduced by the combined aerobic and physicochemical treatment methods. (author)

Simultaneous HPTLC Determination of Rabeprazole and Itopride Hydrochloride From Their Combined Dosage Form.

Science.gov (United States)

Suganthi, A; John, Sofiya; Ravi, T K

2008-01-01

A simple, precise, sensitive, rapid and reproducible HPTLC method for the simultaneous estimation of the rabeprazole and itopride hydrochloride in tablets was developed and validated. This method involves separation of the components by TLC on precoated silica gel G60F254 plate with solvent system of n-butanol, toluene and ammonia (8.5:0.5:1 v/v/v) and detection was carried out densitometrically using a UV detector at 288 nm in absorbance mode. This system was found to give compact spots for rabeprazole (Rf value of 0.23 0.02) and for itopride hydrochloride (Rf value of 0.75+/-0.02). Linearity was found to be in the range of 40-200 ng/spot and 300-1500 ng/spot for rabeprazole and itopride hydrochloride. The limit of detection and limit of quantification for rabeprazole were 10 and 20 ng/spot and for itopride hydrochloride were 50 and 100 ng/spot, respectively. The method was found to be beneficial for the routine analysis of combined dosage form.

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.

[Impact of pharmaceutical interventions on antibiotic therapy of urinary tract infections in rehabilitation center].

Science.gov (United States)

Rochefolle, A; Maison, O; Chazaud, C; Rioufol, C; Rode, G; Luaute, J; Jacquin-Courtois, S; Guinet-Lacoste, A; Carré, E

2017-06-01

The aim of this study was to assess the impact of medico-pharmaceutical partnership on the quality of antibiotic treatment in urinary tract infection (UTI) within rehabilitation center. All antibiotic prescriptions were validated by the pharmacist at the start of treatment and twice a week. All patients with symptomatic urinary tract infection between January 1, 2014 to December 31, 2015 were included in this study. Addition to awareness among specifiers to promoting the appropriate use of antibiotics, the pharmacist suggested pharmaceutical interventions (PI) in order to improve the quality of antibiotic treatments. At the same time, 3 quality indicators (QI) were followed: duration, dosage, antibiotic susceptibility. The compliance rates of this 3 QI allowed to assess the quality of the antibiotic treatment in urinary tract infection. The study population included 154 patients corresponding to 252 UTI. Sixty-eight PI were made by pharmacist about urinary tract infection treatment (overdosage or under-dosing, duration unknown, inadequate route of administration). These QI achieved 96.4% compliance with duration, 98.8% compliance with dosage and 99.2% with the antibiotic susceptibility. This study allowed showing the medico-pharmaceutical impact on the quality of antibiotic treatments in UTI. The awareness among specifiers with a daily validation of prescription by the pharmacist allowed to improve urinary tract infections care in rehabilitation center. 4. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The effect of dosages of microbial consortia formulation and synthetic fertilizer on the growth and yield of field-grown chili

Science.gov (United States)

Istifadah, N.; Sapta, D.; Krestini, H.; Natalie, B.; Suryatmana, P.; Nurbaity, A.; Hidersah, R.

2018-03-01

Chili (Capsicum annuum, L) is one of important horticultural crop in Indonesia. Formulation of microbial consortia containing Bacillus subtilis, Pseudomonas sp., Azotobacter chroococcum and Trichoderma harzianum has been developed. This study evaluated the effects of dosage of the microbial formulation combined with NPK fertilizer on growth and yield of chili plants in the field experiment. The experiment was arranged in completely randomized design of factorial, in which the first factor was dosage of formulation (0, 2.5, 5.0, 7.5, 10 g per plant) and the second factor was NPK fertilizer dosage (0, 25, 50 and 75% of the standard dosage). The treatments were replicated three times. For application, the formulation was mixed with chicken manure 1:10 (w/v). The results showed that application of microbial formulation solely improved the chili growth. There was interaction between dosages of the microbial formulation and NPK fertilizer in improving plant height, nitrogen availability and the chili yield, while there was no interaction between those dosages in improving the root length. Combination between microbial formulation at the dosage of 5.0-7.5 g per plant combined with NPK fertilizer with the dosage 50 or 75% of the standard dosage support relatively better growth and the chili yield.

Dry coating of solid dosage forms: an overview of processes and applications.

Science.gov (United States)

Foppoli, Anastasia Anna; Maroni, Alessandra; Cerea, Matteo; Zema, Lucia; Gazzaniga, Andrea

2017-12-01

Dry coating techniques enable manufacturing of coated solid dosage forms with no, or very limited, use of solvents. As a result, major drawbacks associated with both organic solvents and aqueous coating systems can be overcome, such as toxicological, environmental, and safety-related issues on the one hand as well as costly drying phases and impaired product stability on the other. The considerable advantages related to solventless coating has been prompting a strong research interest in this field of pharmaceutics. In the article, processes and applications relevant to techniques intended for dry coating are analyzed and reviewed. Based on the physical state of the coat-forming agents, liquid- and solid-based techniques are distinguished. The former include hot-melt coating and coating by photocuring, while the latter encompass press coating and powder coating. Moreover, solventless techniques, such as injection molding and three-dimensional printing by fused deposition modeling, which are not purposely conceived for coating, are also discussed in that they would open new perspectives in the manufacturing of coated-like dosage forms.

Application of different spectrophotometric methods for simultaneous determination of elbasvir and grazoprevir in pharmaceutical preparation

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Attia, Khalid A. M.; El-Abasawi, Nasr M.; El-Olemy, Ahmed; Abdelazim, Ahmed H.

2018-01-01

The first three UV spectrophotometric methods have been developed of simultaneous determination of two new FDA approved drugs namely; elbasvir and grazoprevir in their combined pharmaceutical dosage form. These methods include simultaneous equation, partial least squares with and without variable selection procedure (genetic algorithm). For simultaneous equation method, the absorbance values at 369 (λmax of elbasvir) and 253 nm (λmax of grazoprevir) have been selected for the formation of two simultaneous equations required for the mathematical processing and quantitative analysis of the studied drugs. Alternatively, the partial least squares with and without variable selection procedure (genetic algorithm) have been applied in the spectra analysis because the synchronous inclusion of many unreal wavelengths rather than by using a single or dual wavelength which greatly increases the precision and predictive ability of the methods. Successfully assay of the drugs in their pharmaceutical formulation has been done by the proposed methods. Statistically comparative analysis for the obtained results with the manufacturing methods has been performed. It is noteworthy to mention that there was no significant difference between the proposed methods and the manufacturing one with respect to the validation parameters.

Development of polymer film dosage forms of lidocaine for buccal administration: II. Comparison of preparation methods.

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Okamoto, Hirokazu; Nakamori, Takahiko; Arakawa, Yotaro; Iida, Kotaro; Danjo, Kazumi

2002-11-01

In previous studies, we prepared film dosage forms of lidocaine (LC) with hydroxypropylcellulose (HPC) as a film base using the solvent evaporation (SE) method. However, from the viewpoint of environmental issues, a reduction in organic solvent use in pharmaceutical and other industries is required. In this study, we prepared the LC films by direct compression of the physical mixture (DCPM method) and direct compression of the spray dried powder (DCSD method). Magnesium stearate, which was required as a lubricant for direct compression, showed no effect on the LC release rate. The LC release rate (%/h) was independent of the compression pressure, but a higher pressure was preferable to easily remove the film from the punches. An increase in the film weight decreased the LC release rate expressed in %/h, whereas no significant effect of film weight was observed on the LC release rate from unit surface area expressed in mg/h/cm(2). The LC release rate (%/h) was independent of the LC content, suggesting that the LC release rate (mg/h) can be quantitatively controlled by changing the LC content in the formulation. The LC release rate and penetration rate were affected by the preparation method; that is, DCPM method dosage form. Copyright 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:2424-2432, 2002

Preparation and characterization of solid oral dosage forms containing soy isoflavones

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Stela R. de Oliveira

2013-02-01

Full Text Available Soy isoflavones have been extensively used for menopausal symptoms and prevention of hormone-related cancer, osteoporosis and cardiovascular diseases. Commercially available forms of isoflavones include supplements, capsules and tablets. However, the non-standardization of soy isoflavones extracts and different dissolution profiles of these solid dosage forms highlight the need of additional studies on the development of well characterized pharmaceutical dosage forms of isoflavones. In this work, immediate release oral tablets of soy isoflavones were obtained and evaluated. Genistein and daidzein, were the main constituents of the dried soy extract. Preparation of the tables was accomplished in a rotary tableting machine following either a dry mixture for direct compression or wet granulation with different excipients. Powder, granules and tablets were evaluated for several parameters, including flow properties, Carr and Hausner indexes, hardness, friability, disintegration time and drug release profile. Also, a fast and validated HPLC analytical method for both genistein and daidzein was developed. Formulations containing sodium croscarmellose and sodium dodecyl sulfate resulted in better flowability as indicated by the flow rate and angle of repose, faster disintegration time and immediate release dissolution profile.

Development and Validation of a Rapid RP-HPLC Method for the Determination of Venlafaxine Hydrochloride in Pharmaceutical Dosage forms using Experimental Design

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Vanita Somasekhar

2009-01-01

Full Text Available The objective of the current study was to develop a simple, accurate, precise and rapid reversed-phase HPLC method and subsequent validation as per ICH guidelines for the determination of venlafaxine hydrochloride in pharmaceutical dosage forms. The proposed RP-HPLC method utilizes a 5 μm Varian® Microsorb-MV 100 C18 column (250 mmx4.6 mm at ambient temperature. A 23 factorial design consisting of 3 factors at 2 levels was set up to standardize the chromatographic conditions. A numerical optimization technique employing the desirability approach was used to locate the optimum chromatographic conditions. The optimum mobile phase consisted of acetonitrile, 0.04 M potassium dihydrogen phosphate buffer and methanol (45:25:30, v/v, with pH adjusted to 5.5 using 10% phosphoric acid solution. The mobile phase was delivered isocratically at a flow rate of 1 mL/min with UV detection at 224 nm. The calibration plots constructed using the optimized chromatographic conditions displayed good linear relationship in the concentration range of 1-50 μg/mL with r=0.9992. The method was validated for precision, accuracy, robustness and recovery. The minimum detectable and minimum quantifiable amounts were found to be 0.568 and 1.72 μg/mL, respectively and the method was found to be reproducible from the statistical data generated. Venlafaxine hydrochloride was eluted at 3.43 min

Development and validation of RP-HPLC method for determination of famotidine and its application in quality control of different pharmaceutical dosage forms

International Nuclear Information System (INIS)

Hassan, S.S.; Ayub, M.; Ishtiaq, S.; Ahmad; I; Khalid, N.

2013-01-01

A precise and fast novel high-performance liquid chromatography method was developed and validated for the quantitative determination of Famotidine (FMT) in commercially available pharmaceutical dosage forms. An Agilent 1200 Series High Performance Liquid Chromatography (HPLC) system having the column C 1 8 (5 micro m particle size, 150*4.6 mm) was used in this study and detection (diode array detector) was made at 280 nm. The mobile phase was acetonitrile, distilled water, triethylamine and phosphoric acid (49.9:49.9:0.1:0.1, v/v), isocratic elution under ambient temperature at flow rate of 1.5 mL min/sup -1/ with injection volume 5 micro L. In this method, the retention times for FMT pure, tablets and suspension were 0.787 min, 0.789 min and 0.839 minutes respectively. The new method was validated by different validation parameters. The procedure provided a linear response over the concentration range of 0.1-1.0 mg mL/sup -1/ (r/sup 2/ =0.998) and equation was y=3902.6+18.651. The mean % recovery for inter-day (96.56%) and intra-day (97.36%) assuring a good precision and accuracy was 96-98%. The method was found to be very rapid and the overall assay time was less than 2 minutes and the results obtained were accurate, precise and selective enough to allow the determination of FMT in the presence of certain excipients. (author)

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

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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

Evaluation of Extractables in Processed and Unprocessed Polymer Materials Used for Pharmaceutical Applications

OpenAIRE

Stults, Cheryl L. M.; Ansell, Jennifer M.; Shaw, Arthur J.; Nagao, Lee M.

2014-01-01

Polymeric materials are often used in pharmaceutical packaging, delivery systems, and manufacturing components. There is continued concern that chemical entities from polymeric components may leach into various dosage forms, particularly those that are comprised of liquids such as parenterals, injectables, ophthalmics, and inhalation products. In some cases, polymeric components are subjected to routine extractables testing as a control measure. To reduce the risk of discovering leachables du...

The effect of miscellaneous oral dosage forms on the environmental pollution of sulfonamides in pig holdings.

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Stahl, Jessica; Zessel, Katrin; Schulz, Jochen; Finke, Jan Henrik; Müller-Goymann, Christel Charlotte; Kietzmann, Manfred

2016-04-01

Due to antibiotic treatment of humans and animals, the prevalence of bacterial resistances increases worldwide. Especially in livestock farming, large quantities of faeces contaminated with antibiotics pose a risk of the carryover of the active ingredient to the environment. Accordingly, the aim of the present study was the evaluation of the benefit of different oral dosage forms (powder, pellets, granula) in pigs concerning the environmental pollution of sulfadiazine. Two subtherapeutic dosages were evaluated in powder mixtures to gain information about their potential to pollute the pig barn. Furthermore, a new group of pigs was kept in the stable after powder feeding of another pig group to determine the possible absorption of environmentally distributed antibiotics. Pigs were orally treated with three dosage forms. Simultaneously, sedimentation and airborne dust were collected and plasma and urine levels were determined. All formulations result in comparable plasma and urine levels, but massive differences in environmental pollution (powder > pellets, granula). Pigs housing in a contaminated barn exhibit traces of sulfadiazine in plasma and urine. Using pharmaceutical formulations like pellets or granula, the environmental pollution of sulfonamides can significantly be diminished due to massive dust reduction during feeding.

Maintenance of Clinical Expertise and Clinical Research by the Clinical Professors at Gifu Pharmaceutical University.

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Tachi, Tomoya; Noguchi, Yoshihiro; Teramachi, Hitomi

2017-01-01

The clinical professors at Gifu Pharmaceutical University (GPU) provide pharmaceutical services at GPU Pharmacy, Gifu University Hospital, and Gifu Municipal Hospital to keep their clinical skills up-to-date; they also perform clinical research in collaboration with many clinical institutes. The Laboratory of Clinical Pharmacy is part of the Department of Pharmacy Practice and Science, to which the clinical professors belong, and is composed of three clinical professors (a professor, an associate professor, and an assistant professor). The professor administers the GPU Pharmacy as its director, while the associate professor and assistant professor provide pharmaceutical services to patients at Gifu Municipal Hospital, and also provide practical training for students in the GPU Pharmacy. Collectively, they have performed research on such topics as medication education for students, clinical communication education, and analysis of clinical big data. They have also conducted research in collaboration with clinical institutes, hospitals, and pharmacies. Here, we introduce the collaborative research between the Laboratory of Clinical Pharmacy and Gifu Municipal Hospital. These studies include "Risk factors contributing to urinary protein expression resulting from bevacizumab combination chemotherapy", "Hyponatremia and hypokalemia as risk factors for falls", "Economic evaluation of adjustments of levofloxacin dosage by dispensing pharmacists for patients with renal dysfunction", and "Effect of patient education upon discharge for use of a medication notebook on purchasing over-the-counter drugs and health foods". In this symposium, we would like to demonstrate one model of the association and collaborative research between these clinical professors and clinical institutes.

Stability-Indicating RP-UPLC Method for the Simultaneous Determination of Potential Degradation and Process Impurities of Amlodipine Basylate and Benazepril HCl in Pharmaceutical Dosage Form

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Gajanan B. Kasawar

2014-10-01

Full Text Available A stability-indicating RP-UPLC method was developed for the quantification of related impurities of amlodipine basylate (AB and Benazepril hydrochloride (BH in solid pharmaceutical dosages form. The chromatographic separation employs a C18 column using a gradient elution, being solvent-A (1.36 g of potassium dihydrogen phosphate dissolved in one liter of water, adjusted to pH 3.0 with orthophosphoric acid and solvent-B (acetonitrile delivered at a flow rate of 0.3 mL min-1. The analytes were detected and quantified at 217 nm and 240 nm using photo diode-array detector. The method was validated demonstrating to be accurate and precise within the corresponding linear range of all components. The stability of the method was investigated under different stress conditions including hydrolytic, oxidative, exposed to photolytic, humidity and thermal as recommended by ICH guidelines. Relevant degradation was found under hydrolytic and oxidative conditions. Robustness against small modification in mobile phase pH, column oven temperature, flow rate and percentage of the mobile phase composition was ascertained. Lower limit of quantification and detection was also determined. The peak purity indices (purity angle < purity threshold obtained with the aid of PDA detector and satisfactory resolution between related impurities established the specificity of the determination.

Drop-on-Demand System for Manufacturing of Melt-based Solid Oral Dosage: Effect of Critical Process Parameters on Product Quality.

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Içten, Elçin; Giridhar, Arun; Nagy, Zoltan K; Reklaitis, Gintaras V

2016-04-01

The features of a drop-on-demand-based system developed for the manufacture of melt-based pharmaceuticals have been previously reported. In this paper, a supervisory control system, which is designed to ensure reproducible production of high quality of melt-based solid oral dosages, is presented. This control system enables the production of individual dosage forms with the desired critical quality attributes: amount of active ingredient and drug morphology by monitoring and controlling critical process parameters, such as drop size and product and process temperatures. The effects of these process parameters on the final product quality are investigated, and the properties of the produced dosage forms characterized using various techniques, such as Raman spectroscopy, optical microscopy, and dissolution testing. A crystallization temperature control strategy, including controlled temperature cycles, is presented to tailor the crystallization behavior of drug deposits and to achieve consistent drug morphology. This control strategy can be used to achieve the desired bioavailability of the drug by mitigating variations in the dissolution profiles. The supervisor control strategy enables the application of the drop-on-demand system to the production of individualized dosage required for personalized drug regimens.

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

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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.

Colorimetric microdetermination of captopril in pure form and in pharmaceutical formulations

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Shama, Sayed Ahmed; El-Sayed Amin, Alla; Omara, Hany

2006-11-01

A simple, rapid, accurate, precise and sensitive colorimetric method for the determination of captopril (CAP) in bulk sample and in dosage forms is described. The method is based on oxidation of the drug by potassium permanganate in acidic medium and determination of the unreacted oxidant by measuring the decrease in absorbance for five different dyes; methylene blue (MB); acid blue 74 (AB), acid red 73 (AR), amaranth dye (AM) and acid orange 7 (AO) at a suitable λmax (660, 610, 510, 520, and 485 nm), respectively. Regression analysis of Beer's plots showed good correlation in the concentration ranges (0.4 12.5, 0.3 10, 0.5 11, 0.4 8.3 and 0.5 9.3 μg ml-1), respectively. The apparent molar absorbtivity, Sandell sensitivity, detection and quantitation limits were calculated. For more accurate results, Ringbom optimum concentration ranges were 0.5 12, 0.5 9.6, 0.6 10.5, 0.5 8.0 and 0.7 9.0 μg ml-1, respectively. The validity of the proposed method was tested by analyzing in pure and dosage forms containing CAP whether alone or in combination with hydrochlorothiazide. Statistical analysis of the results reflects that the proposed procedures are precise, accurate and easily applicable for the determination of CAP in pure form and in pharmaceutical preparations. Also, the stability constant was determined and the free energy change was calculated potentiometrically.

Application of Ring Shear Testing to Optimize Pharmaceutical Formulation and Process Development of Solid Dosage Forms

DEFF Research Database (Denmark)

Søgaard, Søren Vinter; Pedersen, Troels; Allesø, Morten

This study investigates how shear and wall friction tests performed at small stresses can be applied to predict critical flow properties of powders, such as flow patterns and arching tendencies, in pharmaceutical manufacturing operations. The study showed that this approach is a promising method...

Oral Solid Dosage Form Disintegration Testing - The Forgotten Test.

Science.gov (United States)

Al-Gousous, Jozef; Langguth, Peter

2015-09-01

Since its inception in the 1930s, disintegration testing has become an important quality control (QC) test in pharmaceutical industry, and disintegration test procedures for various dosage forms have been described by the different pharmacopoeias, with harmonization among them still not quite complete. However, because of the fact that complete disintegration does not necessarily imply complete dissolution, much more research has been focused on dissolution rather than on disintegration testing. Nevertheless, owing to its simplicity, disintegration testing seems to be an attractive replacement to dissolution testing as recognized by the International Conference on Harmonization guidelines, in some cases. Therefore, with proper research being carried out to overcome the associated challenges, the full potential of disintegration testing could be tapped saving considerable efforts allocated to QC testing and quality assurance. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Investigation of the Sensitivity of Transmission Raman Spectroscopy for Polymorph Detection in Pharmaceutical Tablets.

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Feng, Hanzhou; Bondi, Robert W; Anderson, Carl A; Drennen, James K; Igne, Benoît

2017-08-01

Polymorph detection is critical for ensuring pharmaceutical product quality in drug substances exhibiting polymorphism. Conventional analytical techniques such as X-ray powder diffraction and solid-state nuclear magnetic resonance are utilized primarily for characterizing the presence and identity of specific polymorphs in a sample. These techniques have encountered challenges in analyzing the constitution of polymorphs in the presence of other components commonly found in pharmaceutical dosage forms. Laborious sample preparation procedures are usually required to achieve satisfactory data interpretability. There is a need for alternative techniques capable of probing pharmaceutical dosage forms rapidly and nondestructively, which is dictated by the practical requirements of applications such as quality monitoring on production lines or when quantifying product shelf lifetime. The sensitivity of transmission Raman spectroscopy for detecting polymorphs in final tablet cores was investigated in this work. Carbamazepine was chosen as a model drug, polymorph form III is the commercial form, whereas form I is an undesired polymorph that requires effective detection. The concentration of form I in a direct compression tablet formulation containing 20% w/w of carbamazepine, 74.00% w/w of fillers (mannitol and microcrystalline cellulose), and 6% w/w of croscarmellose sodium, silicon dioxide, and magnesium stearate was estimated using transmission Raman spectroscopy. Quantitative models were generated and optimized using multivariate regression and data preprocessing. Prediction uncertainty was estimated for each validation sample by accounting for all the main variables contributing to the prediction. Multivariate detection limits were calculated based on statistical hypothesis testing. The transmission Raman spectroscopic model had an absolute prediction error of 0.241% w/w for the independent validation set. The method detection limit was estimated at 1.31% w/w. The

Dosage and dose schedule screening of drug combinations in agent-based models reveals hidden synergies

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Lisa Corina Barros de Andrade e Sousa1

2016-01-01

Full Text Available The fungus Candida albicans is the most common causative agent of human fungal infections and better drugs or drug combination strategies are urgently needed. Here, we present an agent-based model of the interplay of C. albicans with the host immune system and with the microflora of the host. We took into account the morphological change of C. albicans from the yeast to hyphae form and its dynamics during infection. The model allowed us to follow the dynamics of fungal growth and morphology, of the immune cells and of microflora in different perturbing situations. We specifically focused on the consequences of microflora reduction following antibiotic treatment. Using the agent-based model, different drug types have been tested for their effectiveness, namely drugs that inhibit cell division and drugs that constrain the yeast-to-hyphae transition. Applied individually, the division drug turned out to successfully decrease hyphae while the transition drug leads to a burst in hyphae after the end of the treatment. To evaluate the effect of different drug combinations, doses, and schedules, we introduced a measure for the return to a healthy state, the infection score. Using this measure, we found that the addition of a transition drug to a division drug treatment can improve the treatment reliability while minimizing treatment duration and drug dosage. In this work we present a theoretical study. Although our model has not been calibrated to quantitative experimental data, the technique of computationally identifying synergistic treatment combinations in an agent based model exemplifies the importance of computational techniques in translational research.

ORGANIZATIONAL AND LEGAL STUDY OF THE CIRCULATION OF THE COMBINED MEDICINES CONTAINING DEXTROPROPOXYPHENE

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Shapovalov VV

2016-03-01

dekstropropoksyfen-containing medicines should be discharged on a single prescription form F-1. To streamline the rules trafficking controlled drugs, which include controlled narcotic, have restrictions on their circulation stages of prescribing and dispensing, which is associated with quantitative content of psychoactive substances. Thus, for controlled medicines containing in its composition dekstropropoksyfen amount set for delivery in one recipe is not more than 0.6 grams of narcotic drug (p. 1.22.2 Order. In order to control the traffic of controlled medicines containing in its composition dekstropropoksyfen, regardless of its quantity and dosage form, all dekstropropoksyfen-containing medicines be subject-quantifiable in health care institutions that adopted Annex 3 of this order. Conclusions. During the organizational and legal studies analyzed the current pharmaceutical legislation-governing circulation of combined dextropropoxyphene-containing medicines. The particularities of the prescription of dextropropoxyphene-containing medicines were shown. On the example of the medicine of "Spazmoleks" showed the change in the regulatory framework of the combined circulation of the medicines and changing availability dextropropoxyphene-containing medicines for forensic and pharmaceutical criteria of "control mode". During the organizational and legal research conducted a retrospective analysis of prescription turnover dextropropoxyphene-containing medicines. According to the analysis revealed that these drugs are sold from pharmacies and structural units by the prescription F-1. Furthermore, according to existing pharmaceutical legislation it is possible to write and dispense recipe of the F-1 in combined dextropropoxyphene medicaments in an amount of more than 0.6 g in the case when packing products contains not more than 50 tablets. It was fixed that today dextropropoxyphene-containing medicines are subject-quantifiable. In the format of organizational and legal studies analyzed

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

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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.

Dosage compensation and demasculinization of X chromosomes in Drosophila.

Science.gov (United States)

Bachtrog, Doris; Toda, Nicholas R T; Lockton, Steven

2010-08-24

The X chromosome of Drosophila shows a deficiency of genes with male-biased expression, whereas mammalian X chromosomes are enriched for spermatogenesis genes expressed premeiosis and multicopy testis genes. Meiotic X-inactivation and sexual antagonism can only partly account for these patterns. Here, we show that dosage compensation (DC) in Drosophila may contribute substantially to the depletion of male genes on the X. To equalize expression between X-linked and autosomal genes in the two sexes, male Drosophila hypertranscribe their single X, whereas female mammals silence one of their two X chromosomes. We combine fine-scale mapping data of dosage compensated regions with genome-wide expression profiles and show that most male-biased genes on the D. melanogaster X are located outside dosage compensated regions. Additionally, X-linked genes that have newly acquired male-biased expression in D. melanogaster are less likely to be dosage compensated, and parental X-linked genes that gave rise to an autosomal male-biased retrocopy are more likely located within compensated regions. This suggests that DC contributes to the observed demasculinization of X chromosomes in Drosophila, both by limiting the emergence of male-biased expression patterns of existing X genes, and by contributing to gene trafficking of male genes off the X. Copyright 2010 Elsevier Ltd. All rights reserved.

Porosity measurement of solid pharmaceutical dosage forms by gamma-ray transmission

International Nuclear Information System (INIS)

Martins de Oliveira, Jose; Andreo Filho, Newton; Vinicius Chaud, Marco; Angiolucci, Tatiana; Aranha, Norberto; Germano Martins, Antonio Cesar

2010-01-01

The aim of the present work is the determination of porosity in tablets by using the gamma-ray transmission technique. Tablet dissolution depends on some inherent characteristics of the manufacturing process, such as compression force, tablet volume, density and porosity, nature of excipients, preparation methods and its physical-chemical properties. Porosity is a measure of empty spaces in a material and can be determined by various techniques. In this paper, we propose the use of a gamma-ray transmission technique to obtain the porosity of experimental formulation of tablets. The results of porosity were compared with those obtained by using conventional methodology (density and mercury intrusion). The experimental setup for gamma-ray transmission consists of a gamma-ray source of 241 Am (photons of 59.6 keV and an activity of 3.7x10 9 Bq), an NaI(Tl) scintillation detector, collimators and a standard gamma-ray spectrometry electronics. Our results suggest that the gamma-ray transmission technique is a powerful tool for non-destructive porosity quantification of solid pharmaceutical forms and presents smaller errors than those obtained with conventional methodologies.

Overview of PAT process analysers applicable in monitoring of film coating unit operations for manufacturing of solid oral dosage forms.

Science.gov (United States)

Korasa, Klemen; Vrečer, Franc

2018-01-01

Over the last two decades, regulatory agencies have demanded better understanding of pharmaceutical products and processes by implementing new technological approaches, such as process analytical technology (PAT). Process analysers present a key PAT tool, which enables effective process monitoring, and thus improved process control of medicinal product manufacturing. Process analysers applicable in pharmaceutical coating unit operations are comprehensibly described in the present article. The review is focused on monitoring of solid oral dosage forms during film coating in two most commonly used coating systems, i.e. pan and fluid bed coaters. Brief theoretical background and critical overview of process analysers used for real-time or near real-time (in-, on-, at- line) monitoring of critical quality attributes of film coated dosage forms are presented. Besides well recognized spectroscopic methods (NIR and Raman spectroscopy), other techniques, which have made a significant breakthrough in recent years, are discussed (terahertz pulsed imaging (TPI), chord length distribution (CLD) analysis, and image analysis). Last part of the review is dedicated to novel techniques with high potential to become valuable PAT tools in the future (optical coherence tomography (OCT), acoustic emission (AE), microwave resonance (MR), and laser induced breakdown spectroscopy (LIBS)). Copyright © 2017 Elsevier B.V. All rights reserved.

Analysis of pharmaceutical market of nootropic drugs in Ukraine

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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 %

Development and Statistical Validation of Spectrophotometric Methods for the Estimation of Nabumetone in Tablet Dosage Form

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A. R. Rote

2010-01-01

Full Text Available Three new simple, economic spectrophotometric methods were developed and validated for the estimation of nabumetone in bulk and tablet dosage form. First method includes determination of nabumetone at absorption maxima 330 nm, second method applied was area under curve for analysis of nabumetone in the wavelength range of 326-334 nm and third method was First order derivative spectra with scaling factor 4. Beer law obeyed in the concentration range of 10-30 μg/mL for all three methods. The correlation coefficients were found to be 0.9997, 0.9998 and 0.9998 by absorption maxima, area under curve and first order derivative spectra. Results of analysis were validated statistically and by performing recovery studies. The mean percent recoveries were found satisfactory for all three methods. The developed methods were also compared statistically using one way ANOVA. The proposed methods have been successfully applied for the estimation of nabumetone in bulk and pharmaceutical tablet dosage form.

Use of in-line near-infrared spectroscopy in combination with chemometrics for improved understanding of pharmaceutical processes

DEFF Research Database (Denmark)

Rantanen, Jukka; Wikström, Håkan; Turner, Rebecca

2005-01-01

was extracted. Principal component loadings were fully interpreted to validate the conclusions drawn from scores and predictions. Thus NIR spectroscopy could be used to determine the end points of the three subphases of high shear wet granulation and, as such, provide a fast in-line quality control tool....... solid dosage form. In this study, the use of in-line near-infrared (NIR) spectroscopy as a process analytical tool for high shear granulation was investigated. In combination with principal component-based methods, process analysis of three separate phases of high shear wet granulation (mixing, spraying...

Rheology in Pharmaceutical Sciences

DEFF Research Database (Denmark)

Aho, Johanna; Hvidt, Søren; Baldursdottir, Stefania

2016-01-01

Rheology is the science of flow and deformation of matter. Particularly gels and non-Newtonian fluids, which exhibit complex flow behavior, are frequently encountered in pharmaceutical engineering and manufacturing, or when dealing with various in vivo fluids. Therefore understanding rheology......, together with the common measurement techniques and their practical applications. Examples of the use of rheological techniques in the pharmaceutical field, as well as other closely related fields such as food and polymer science, are also given....... is important, and the ability to use rheological characterization tools is of great importance for any pharmaceutical scientist involved in the field. Flow can be generated by shear or extensional deformations, or a combination of both. This chapter introduces the basics of both shear and extensional rheology...

Development of an HPLC-UV Method for the Analysis of Drugs Used for Combined Hypertension Therapy in Pharmaceutical Preparations and Human Plasma

Directory of Open Access Journals (Sweden)

Serife Evrim Kepekci Tekkeli

2013-01-01

Full Text Available A simple, rapid, and selective HPLC-UV method was developed for the determination of antihypertensive drug substances: amlodipine besilat (AML, olmesartan medoxomil (OLM, valsartan (VAL, and hydrochlorothiazide (HCT in pharmaceuticals and plasma. These substances are mostly used as combinations. The combinations are found in various forms, especially in current pharmaceuticals as threesome components: OLM, AML, and HCT (combination I and AML, VAL, and HCT (combination II. The separation was achieved by using an RP-CN column, and acetonitrile-methanol-10 mmol orthophosphoric acid pH 2.5 (7 : 13 : 80, v/v/v was used as a mobile phase; the detector wavelength was set at 235 nm. The linear ranges were found as 0.1–18.5 μg/mL, 0.4–25.6 μg/mL, 0.3–15.5 μg/mL, and 0.3–22 μg/mL for AML, OLM, VAL, and HCT, respectively. In order to check the selectivity of the method for pharmaceutical preparations, forced degradation studies were carried out. According to the validation studies, the developed method was found to be reproducible and accurate as shown by RSD ≤6.1%, 5.7%, 6.9%, and 4.6% and relative mean error (RME ≤10.6%, 5.8%, 6.5%, and 6.8% for AML, OLM, VAL, and HCT, respectively. Consequently, the method was applied to the analysis of tablets and plasma of the patients using drugs including those substances.

Cost containment through pharmaceutical procurement: a Caribbean case study.

Science.gov (United States)

Huff-Rousselle, M; Burnett, F

1996-01-01

This article discusses the potential for health sector cost containment in developing countries through improved pharmaceutical procurement. By describing the specific example of the Eastern Caribbean Drug Service (ECDS), which provides a pooled procurement service to nine ministries of health in the small island nations of the Caribbean, it examines the elements of the procurement operation that allowed ECDS to reduce unit costs for pharmaceuticals by over 50 per cent during its first procurement cycle. The analysis of ECDS considers: (1) political will, institutional alliances, and the creation of a public sector monopsony; (2) pooling demand; (3) restricted international tendering and the pharmaceutical industry; (4) estimating demand and supplier guarantees; (5) reducing variety and increasing volume through standardizing pack sizes, dosage forms and strengths; (6) generic bidding and therapeutic alternative bidding; (7) mode of transport from foreign suppliers; (8) financing mechanisms, including choice of currency, foreign exchange, and terms of payment; (9) market conditions and crafting and enforcing supplier contracts; and, (10) the adjudication process, including consideration of suppliers' past performance, precision requirements in the manufacturing process, number of products awarded to suppliers, and issues of judgment. The authors consider the relevance of this agency's experience to other developing countries by providing a blueprint that can be adopted or modified to suit other situations.

General Requirements to the Preparation of Tinctures, Decoctions. Dosage of Phytopreparations

Directory of Open Access Journals (Sweden)

I.B. Yershovа

2016-09-01

Full Text Available The article describes the advantages and disadvantages of using herbal medicine, general information for the collection of medicinal plants. According to the World Health Organization, the classification of herbal medicine is an integral part of traditional medicine. It refers to the variety of metabolic therapy. This treatment meets the requirements of pathogenetic therapy. Currently, more than 30 % of medicines on the pharmaceutical market have herbal origin. According to the World Health Organization, about 80 % of the world population use mainly traditional medicines of natural origin within the framework of primary health care system. Analysis of publications on phytotherapy revealed insufficient coverage of contraindications and side effects of certain plants. This was the basis for opening in our magazine this column, and we wanted to start with what would be the advantages and disadvantages of phytotherapy. Benefits of herbal medi­cine: biological proximity of the active substances of plants and active substances of the body, harmony therapy for the human body, the prolonged effect of herbal medicines after the completion of therapy, the opportunity to prepare a wide variety of different dosage forms, for both indoor and outdoor use, compatibility with many synthetic pharmaceuticals drugs, comprehensive multilateral action of plants, no side effects, simplicity and ease of preparation of herbal remedies at home, the availability for the majority of patients due to the low cost of the medicines. Limitations of herbal medicine: the complexity of the standardization of the treatment effect of herbal drugs, the complexity of establishing a dose, selectivity of diseases, in which typical herbal remedies are prescribed, the risk of poisoning, particularly in self-collection of medicinal plants. The article also provides methods for the preparation of various forms of herbal remedies, dosage for adults and children. With all the advantages of

Determination of dasatinib in the tablet dosage form by ultra high performance liquid chromatography, capillary zone electrophoresis, and sequential injection analysis.

Science.gov (United States)

Gonzalez, Aroa Garcia; Taraba, Lukáš; Hraníček, Jakub; Kozlík, Petr; Coufal, Pavel

2017-01-01

Dasatinib is a novel oral prescription drug proposed for treating adult patients with chronic myeloid leukemia. Three analytical methods, namely ultra high performance liquid chromatography, capillary zone electrophoresis, and sequential injection analysis, were developed, validated, and compared for determination of the drug in the tablet dosage form. The total analysis time of optimized ultra high performance liquid chromatography and capillary zone electrophoresis methods was 2.0 and 2.2 min, respectively. Direct ultraviolet detection with detection wavelength of 322 nm was employed in both cases. The optimized sequential injection analysis method was based on spectrophotometric detection of dasatinib after a simple colorimetric reaction with folin ciocalteau reagent forming a blue-colored complex with an absorbance maximum at 745 nm. The total analysis time was 2.5 min. The ultra high performance liquid chromatography method provided the lowest detection and quantitation limits and the most precise and accurate results. All three newly developed methods were demonstrated to be specific, linear, sensitive, precise, and accurate, providing results satisfactorily meeting the requirements of the pharmaceutical industry, and can be employed for the routine determination of the active pharmaceutical ingredient in the tablet dosage form. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Challenges and opportunities of using liquid chromatography and mass spectrometry methods to develop complex vaccine antigens as pharmaceutical dosage forms.

Science.gov (United States)

Hickey, John M; Sahni, Neha; Toth, Ronald T; Kumru, Ozan S; Joshi, Sangeeta B; Middaugh, C Russell; Volkin, David B

2016-10-01

Liquid chromatographic methods, combined with mass spectrometry, offer exciting and important opportunities to better characterize complex vaccine antigens including recombinant proteins, virus-like particles, inactivated viruses, polysaccharides, and protein-polysaccharide conjugates. The current abilities and limitations of these physicochemical methods to complement traditional in vitro and in vivo vaccine potency assays are explored in this review through the use of illustrative case studies. Various applications of these state-of-the art techniques are illustrated that include the analysis of influenza vaccines (inactivated whole virus and recombinant hemagglutinin), virus-like particle vaccines (human papillomavirus and hepatitis B), and polysaccharide linked to protein carrier vaccines (pneumococcal). Examples of utilizing these analytical methods to characterize vaccine antigens in the presence of adjuvants, which are often included to boost immune responses as part of the final vaccine dosage form, are also presented. Some of the challenges of using chromatographic and LC-MS as physicochemical assays to routinely test complex vaccine antigens are also discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

A progressive review of Sandhana kalpana (Biomedical fermentation): An advanced innovative dosage form of Ayurveda

Science.gov (United States)

Chaudhary, Anand; Singh, Neetu; Dalvi, Madhuri; Wele, Asmita

2011-01-01

Sandhana kalpana (biomedical fermented formulations) are one of the best dosage forms of Ayurveda in practice since thousands of years. In order to prepare these medicaments, certain sets of conditions are prearranged, which lead to fermentation. Thus, products bequeath with self-generated ethyl alcohol, which potentiate these preparations (Asava–Arishta), pharmaceutically and therapeutically. Commonly, medicinal and commercial components of these formulations are prompting many researchers to contribute in manufacturing, quality control, safety, and efficacy of these formulations. To cope up with this, literature related to Asava–Arishta has been surveyed from the Vedic period to recent publications of Government of India, ie, Ayurvedic Formulary of India, and presented briefly here. In this review paper, we have discussed pioneering facts such as nature and amount of carbohydrate, type of containers, optimum temperature, variety and relevance of initiator of fermentation, manufacturing, regulatory rules, and business aspects of Asava-Arishta. After going through this basic information, any academician or researcher may show a way to further strengthen this dosage form. PMID:22529661

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.

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.

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.

Smart manipulation of ratio spectra for resolving a pharmaceutical mixture of Methocarbamol and Paracetamol

Science.gov (United States)

Essam, Hebatallah M.; Abd-El Rahman, Mohamed K.

2015-04-01

Two smart, specific, accurate and precise spectrophotometric methods manipulating ratio spectra are developed for simultaneous determination of Methocarbamol (METH) and Paracetamol (PAR) in their combined pharmaceutical formulation without preliminary separation. Method A, is an extended ratio subtraction one (EXRSM) coupled with ratio subtraction method (RSM), which depends on subtraction of the plateau values from the ratio spectrum. Method B is a ratio difference spectrophotometric one (RDM) which measures the difference in amplitudes of ratio spectra between 278 and 286 nm for METH and 247 and 260 nm for PAR. The calibration curves are linear over the concentration range of 10-100 μg mL-1 and 2-20 μg mL-1 for METH and PAR, respectively. The specificity of the developed methods was investigated by analyzing different laboratory prepared mixtures of the two drugs. Both methods were applied successfully for the determination of the selected drugs in their combined dosage form. Furthermore, validation was performed according to ICH guidelines; accuracy, precision and repeatability are found to be within the acceptable limits. Statistical studies showed that both methods can be competitively applied in quality control laboratories.

Hediste diversicolor as bioindicator of pharmaceutical pollution: Results from single and combined exposure to carbamazepine and caffeine.

Science.gov (United States)

Pires, Adília; Almeida, Ângela; Calisto, Vânia; Schneider, Rudolf J; Esteves, Valdemar I; Wrona, Frederick J; Soares, Amadeu M V M; Figueira, Etelvina; Freitas, Rosa

2016-10-01

Several environmental stressors have been identified as key and/or emerging drivers of habitat change that could significantly influence marine near-shore ecosystems. These include increasing discharges of pharmaceutical contaminants into the aquatic coastal systems. Pharmaceutical drugs are often detected in aquatic environments but still information on their toxicity impacts on inhabiting species is scarce, especially when acting in combination. Furthermore, almost no information is available on the impacts of pharmaceuticals in polychaetes, often the most abundant taxon in benthic communities and commonly used as indicator species of environmental conditions. Therefore, the present study aimed to evaluate the biochemical alterations induced in the polychaete Hediste diversicolor, from a low contaminated area at the Ria de Aveiro lagoon (Portugal), by the antiepileptic drug carbamazepine (0.0 - control, 0.3, 3.0, 6.0 and 9.0μg/L) and the stimulant caffeine (0.0 - control, 0.5, 3.0, and 18.0μg/L), acting alone and in combination (0.3 CBZ+0.5 CAF and 6.0 CBZ+3.0 CAF). Glutathione S-transferases (GSTs), superoxide dismutase (SOD) and catalase (CAT) activities was determined in Hediste diversicolor from each condition. Lipid peroxidation (LPO), glutathione reduced and oxidized (GSH and GSSG), glycogen and electron transport system (ETS) were also measured. The results obtained clearly revealed that both drugs induced oxidative stress in H. diversicolor, shown by the increase on LPO levels and decrease on total glutathione and GSH/GSSG ratio with the increase of exposure concentrations. Furthermore, the present findings demonstrated that polychaetes biotransformation capacity as well as antioxidant defense mechanisms were not sufficiently efficient to fight against the excess of reactive oxygen species (ROS) leading to LPO when organisms were exposed to both drugs. Our results also demonstrated that polychaetes tended to decrease the activity of ETS when exposed to

Risk identification for quality on stage of pharmaceutical development of combined eye drops for glaucoma treatment

Directory of Open Access Journals (Sweden)

Олександр Миколайович Якубчук

2015-12-01

Full Text Available Aim: To identify the possible risks associated with critical quality attribute of combined eye drops for the treatment of glaucoma using of common risk evaluation methodologies for plannig a drug quality on the stage of pharmaceutical development. Methods: The paper used method of causal analysis. The maximal number of factors has been define to identify potential factors that provide most significant impact on the drug quality and Ishikawa diagram - graphical representation of causes and effects has been built.Results: Analysis allowed to organize the possible factors affecting the drug quality in the generalized categories: quality control methods, medicines and excipients, primary packaging, proper manufacturing conditions and the stage of the process. The most important factors that are carriers of the risk factors and may lead to negative effects have been identified for the generalized categories.Conclusions: Determined at the stage of pharmaceutical development potential critical quality attribute of AFI, excipients and primary packaging, critical parameters of the process, provide a better understanding, reduction and adoption of risk in subsequent stages of the life cycle of the drug

Polymer adhesion predictions for oral dosage forms to enhance drug administration safety. Part 3: Review of in vitro and in vivo methods used to predict esophageal adhesion and transit time.

Science.gov (United States)

Drumond, Nélio; Stegemann, Sven

2018-05-01

The oral cavity is frequently used to administer pharmaceutical drug products. This route of administration is seen as the most accessible for the majority of patients and supports an independent therapy management. For current oral dosage forms under development, the prediction of their unintended mucoadhesive properties and esophageal transit profiles would contribute for future administration safety, as concerns regarding unintended adhesion of solid oral dosage forms (SODF) during oro-esophageal transit still remain. Different in vitro methods that access mucoadhesion of polymers and pharmaceutical preparations have been proposed over the years. The same methods might be used to test non-adhesive systems and contribute for developing safe-to-swallow technologies. Previous works have already investigated the suitability of non-animal derived in vitro methods to assess such properties. The aim of this work was to review the in vitro methodology available in the scientific literature that used animal esophageal tissue to evaluate mucoadhesion and esophageal transit of pharmaceutical preparations. Furthermore, in vivo methodology is also discussed. Since none of the in vitro methods developed are able to mimic the complex swallowing process and oro-esophageal transit, in vivo studies in humans remain as the gold standard. Copyright © 2018 Elsevier B.V. All rights reserved.

Social aspects in additive manufacturing of pharmaceutical products.

Science.gov (United States)

Lind, Johanna; Kälvemark Sporrong, Sofia; Kaae, Susanne; Rantanen, Jukka; Genina, Natalja

2017-08-01

Additive manufacturing (AM) techniques, such as drug printing, represent a new engineering approach that can implement the concept of personalized medicine via on-demand manufacturing of dosage forms with individually adjusted doses. Implementation of AM principles, such as pharmacoprinting, will challenge the entire drug distribution chain and affect the society at different levels. Areas covered: This work summarizes the concept of personalized medicine and gives an overview of possibilities for monitoring patients' health. The most recent activities in the field of printing technologies for fabrication of dosage forms and 'polypills' with flexible doses and tailored release profiles are reviewed. Different scenarios for the drug distribution chain with the required adjustments in drug logistics, quality systems and environmental safety are discussed, as well as whether AM will be used for production of on-demand medicine. The impact of such changes in the distribution chain on regulation, healthcare professionals and patients are highlighted. Expert opinion: Drug manufacturing by traditional methods is well-established, but it lacks the possibility for on-demand personalized drug production. With the recent approval of the first printed medicine, society should be prepared for the changes that will follow the introduction of printed pharmaceuticals.

Boxing and mixed martial arts: preliminary traumatic neuromechanical injury risk analyses from laboratory impact dosage data.

Science.gov (United States)

Bartsch, Adam J; Benzel, Edward C; Miele, Vincent J; Morr, Douglas R; Prakash, Vikas

2012-05-01

In spite of ample literature pointing to rotational and combined impact dosage being key contributors to head and neck injury, boxing and mixed martial arts (MMA) padding is still designed to primarily reduce cranium linear acceleration. The objects of this study were to quantify preliminary linear and rotational head impact dosage for selected boxing and MMA padding in response to hook punches; compute theoretical skull, brain, and neck injury risk metrics; and statistically compare the protective effect of various glove and head padding conditions. An instrumented Hybrid III 50th percentile anthropomorphic test device (ATD) was struck in 54 pendulum impacts replicating hook punches at low (27-29 J) and high (54-58 J) energy. Five padding combinations were examined: unpadded (control), MMA glove-unpadded head, boxing glove-unpadded head, unpadded pendulum-boxing headgear, and boxing glove-boxing headgear. A total of 17 injury risk parameters were measured or calculated. All padding conditions reduced linear impact dosage. Other parameters significantly decreased, significantly increased, or were unaffected depending on padding condition. Of real-world conditions (MMA glove-bare head, boxing glove-bare head, and boxing glove-headgear), the boxing glove-headgear condition showed the most meaningful reduction in most of the parameters. In equivalent impacts, the MMA glove-bare head condition induced higher rotational dosage than the boxing glove-bare head condition. Finite element analysis indicated a risk of brain strain injury in spite of significant reduction of linear impact dosage. In the replicated hook punch impacts, all padding conditions reduced linear but not rotational impact dosage. Head and neck dosage theoretically accumulates fastest in MMA and boxing bouts without use of protective headgear. The boxing glove-headgear condition provided the best overall reduction in impact dosage. More work is needed to develop improved protective padding to minimize

The combination of sugammadex and neostigmine can reduce the dosage of sugammadex during recovery from the moderate neuromuscular blockade.

Science.gov (United States)

Cheong, Soon Ho; Ki, Seunghee; Lee, Jiyong; Lee, Jeong Han; Kim, Myoung-Hun; Hur, Dongki; Cho, Kwangrae; Lim, Se Hun; Lee, Kun Moo; Kim, Young-Jae; Lee, Wonjin

2015-12-01

Sugammadex is a novel neuromuscular reversal agent, but its associated hypersensitivity reaction and high cost have been obstacles to its widespread use. In the interest of reducing the necessary dosage of sugammadex, the reversal time of the combined use of sugammadex and neostigmine from moderate neuromuscular blockade were investigated. The patients enrolled ranged in age from 18 to 65 years old with American Society of Anesthesiologists class 1 or 2. The subjects were randomly assigned into one of the four groups (Group S2, S1, SN, and N; n = 30 per group). The reversal agents of each groups were as follows: S2 - sugammadex 2 mg/kg, S1 - sugammadex 1 mg/kg, SN - sugammadex 1 mg/kg + neostigmine 50 µg/kg + glycopyrrolate 10 µg/kg, N - neostigmine 50 µg/kg + glycopyrrolate 10 µg/kg. The time to recovery of the train-of-four (TOF) ratio was checked in each group. The time to 90% recovery of TOF ratio was 182.6 ± 88.9, 371.1 ± 210.4, 204.3 ± 103.2, 953.2 ± 379.7 sec in group S2, S1, SN and N, respectively. Group SN showed a significantly shorter recovery time than did group S1 and N (P sugammadex and neostigmine may be helpful to decrease the recovery time and can also reduce the required dosage of sugammadex. However, the increased incidence of systemic muscarinic side effects must be considered.

Packaging and labeling of pharmaceutical products obtained from the internet.

Science.gov (United States)

Veronin, Michael

2011-02-15

For patients, the prescription container label may be the only source of instructions on how to take their medicines. In the United States, the legal requirements for a prescription label are set by federal law and state statutes. The container should be comparable to that which manufacturers use to package drug products and should preserve a product's identity, strength, quality, and purity and prevent contamination. Safety features such as a child-resistant closure should be provided. Pharmaceutical products purchased from international online pharmacies are not approved by the Food and Drug Administration (FDA) and may not meet US guidelines for labeling and packaging. The study objective was to determine whether commonly purchased pharmaceutical products obtained from international online pharmacies are comparable to products dispensed in the United States with regard to labeling and packaging. During March 2006 through January 2007, 41 pharmaceutical oral dosage form samples were obtained from international Internet pharmacy websites for evaluation: 18 generic simvastatin samples, 18 generic amlodipine samples, and 5 generic sildenafil samples. Contents for each package were observed and recorded and comparison of the prescription labeling and packaging of these products was made with prescription labeling and packaging requirements in the United States. Of the 41 drug products obtained from online pharmacies from 12 different countries, only 1 product (from Canada) would meet both labeling and packaging guidelines for products dispensed in the United States. Of those not meeting the requirements, 7 were dispensed in paper envelopes with label affixed that was either handwritten or typed and contained missing information such as name and address of dispenser, name of prescriber, name of patient, and directions for use. Another 3 products did not have a label affixed to the drug product, but information was printed on a paper document enclosed in the shipping

Combining cationic and anionic mixed-mode sorbents in a single cartridge to extract basic and acidic pharmaceuticals simultaneously from environmental waters.

Science.gov (United States)

Salas, Daniela; Borrull, Francesc; Fontanals, Núria; Marcé, Rosa Maria

2018-01-01

The aim of the present study is to broaden the applications of mixed-mode ion-exchange solid-phase extraction sorbents to extract both basic and acidic compounds simultaneously by combining the sorbents in a single cartridge and developing a simplified extraction procedure. Four different cartridges containing negative and positive charges in the same configuration were evaluated and compared to extract a group of basic, neutral, and acidic pharmaceuticals selected as model compounds. After a thorough optimization of the extraction conditions, the four different cartridges showed to be capable of retaining basic and acidic pharmaceuticals simultaneously through ionic interactions, allowing the introduction of a washing step with 15 mL methanol to eliminate interferences retained by hydrophobic interactions. Using the best combined cartridge, a method was developed, validated, and further applied to environmental waters to demonstrate that the method is promising for the extraction of basic and acidic compounds from very complex samples.

New spectrofluorimetric method for the determination of nizatidine in bulk form and in pharmaceutical preparations

Science.gov (United States)

Karasakal, Ayça; Ulu, Sevgi Tatar

2013-08-01

A simple, accurate and highly sensitive spectrofluorimetric method has been developed for determination of nizatidine in pure form and in pharmaceutical dosage forms. The method is based on the reaction between nizatidine and 1-dimethylaminonaphthalene-5-sulphonyl chloride in carbonate buffer, pH 10.5, to yield a highly fluorescent derivative peaking at 513 nm after excitation at 367 nm. Various factors affecting the fluorescence intensity of nizatidin-dansyl derivative were studied and conditions were optimized. The method was validated as per ICH guidelines. The fluorescence concentration plot was rectilinear over the range of 25-300 ng/mL. Limit of detection and limit of quantification were calculated as 11.71 and 35.73 ng/mL, respectively. The proposed method was successfully applied to pharmaceutical preparations.

Tailoring controlled-release oral dosage forms by combining inkjet and flexographic printing techniques

DEFF Research Database (Denmark)

Genina, Natalja; Fors, Daniela; Vakili, Hossein

2012-01-01

substrates: A (uncoated woodfree paper), B (triple-coated inkjet paper) and C (double-coated sheet fed offset paper) were used as porous model carriers for drug delivery. Active pharmaceutical ingredient (API) containing solutions were printed onto 1 cm × 1 cm substrate areas using an inkjet printer...

Development and application of spectrophotometric method for the determination of cefaclor in pharmaceutical formulations

Directory of Open Access Journals (Sweden)

Asad Raza

2009-01-01

Full Text Available A simple, fast and sensitive spectrophotometric method for the determination of cefaclor in pharmaceutical raw and dosage forms based on reaction with ninhydrin is developed, optimized and validated. The purple color (Ruhemenn's purple that resulted from the reaction was stabilized and measured at 560 nm. Beer's law is obeyed in the concentration range of 4-80 µg mL-1 with molar absorptivity of 1.42 × 10(5 L mole-1 cm-1. All variables including the reagent concentration, heating time, reaction temperature, color stability period, and cefaclor/ninhydrin ratio were studied in order to optimize the reaction conditions. No interference was observed from common pharmaceutical adjuvant. The developed method is easy to use, accurate and highly cost-effective for routine studies relative to HPLC and other techniques.

Artificial neural network combined with principal component analysis for resolution of complex pharmaceutical formulations.

Science.gov (United States)

Ioele, Giuseppina; De Luca, Michele; Dinç, Erdal; Oliverio, Filomena; Ragno, Gaetano

2011-01-01

A chemometric approach based on the combined use of the principal component analysis (PCA) and artificial neural network (ANN) was developed for the multicomponent determination of caffeine (CAF), mepyramine (MEP), phenylpropanolamine (PPA) and pheniramine (PNA) in their pharmaceutical preparations without any chemical separation. The predictive ability of the ANN method was compared with the classical linear regression method Partial Least Squares 2 (PLS2). The UV spectral data between 220 and 300 nm of a training set of sixteen quaternary mixtures were processed by PCA to reduce the dimensions of input data and eliminate the noise coming from instrumentation. Several spectral ranges and different numbers of principal components (PCs) were tested to find the PCA-ANN and PLS2 models reaching the best determination results. A two layer ANN, using the first four PCs, was used with log-sigmoid transfer function in first hidden layer and linear transfer function in output layer. Standard error of prediction (SEP) was adopted to assess the predictive accuracy of the models when subjected to external validation. PCA-ANN showed better prediction ability in the determination of PPA and PNA in synthetic samples with added excipients and pharmaceutical formulations. Since both components are characterized by low absorptivity, the better performance of PCA-ANN was ascribed to the ability in considering all non-linear information from noise or interfering excipients.

Development and Validation of a Stability-Indicating RP-HPLC ...

African Journals Online (AJOL)

Development and Validation of a Stability-Indicating RP-HPLC Method for ... of Paracetamol, Tramadol HCl and Domperidone in a Combined Dosage Form. ... testing, as well as for quality control of the combined drugs in pharmaceutical ...

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.

In vitro dissolution of generic immediate-release solid oral dosage forms containing BCS class I drugs: comparative assessment of metronidazole, zidovudine, and amoxicillin versus relevant comparator pharmaceutical products in South Africa and India.

Science.gov (United States)

Reddy, Nallagundla H S; Patnala, Srinivas; Löbenberg, Raimar; Kanfer, Isadore

2014-10-01

Biowaivers are recommended for immediate-release solid oral dosage forms using dissolution testing as a surrogate for in vivo bioequivalence studies. Several guidance are currently available (the World Health Organization (WHO), the US FDA, and the EMEA) where the conditions are described. In this study, definitions, criteria, and methodologies according to the WHO have been applied. The dissolution performances of immediate-release metronidazole, zidovudine, and amoxicillin products purchased in South African and Indian markets were compared to the relevant comparator pharmaceutical product (CPP)/reference product. The dissolution performances were studied using US Pharmacopeia (USP) apparatus 2 (paddle) set at 75 rpm in each of three dissolution media (pH1.2, 4.5, and 6.8). Concentrations of metronidazole, zidovudine, and amoxicillin in each dissolution media were determined by HPLC. Of the 11 metronidazole products tested, only 8 could be considered as very rapidly dissolving products as defined by the WHO, whereas 2 of those products could be considered as rapidly dissolving products but did not comply with the f 2 acceptance criteria in pH 6.8. All 11 zidovudine products were very rapidly dissolving, whereas in the case of the 14 amoxicillin products tested, none of those products met any of the WHO criteria. This study indicates that not all generic products containing the same biopharmaceutics classification system (BCS) I drug and in similar strength and dosage form are necessarily in vitro equivalent. Hence, there is a need for ongoing market surveillance to determine whether marketed generic products containing BCS I drugs meet the release requirements to confirm their in vitro bioequivalence to the respective reference product.

Simultaneous Estimation and Validation of Atorvastatin Calcium and Aspirin in Combined Capsule Dosage Form by RP HPLC Method

Directory of Open Access Journals (Sweden)

B. V. Suma

2012-01-01

Full Text Available A new simple, specific, precise and accurate revere phase liquid chromatography method has been developed for estimation of atorvastatin calcium (AST and ASPIRIN (ASP simultaneously in a combined capsule dosage forms. The chromatographic separation was achieved on a 5 – micron C 18 column (250x 4.6mm using a mobile phase consisting of a mixture of Acetonitrile: Ammonium Acetate buffer 0.02M (68:32 pH 4.5. The flow rate was maintained at 0.8 ml/min. The detection of the constituents was done using UV detector at 245 nm for AST and ASP. The retention time of AST and ASP were found be 4.5915 ± 0.0031 min and 3.282 ±0.0024 min respectively. The developed method was validated for accuracy, linearity, precision, limit of detection (LOD and limit of quantification (LOQ and robustness as per the ICH guidelines.

Adaptation of pharmaceutical excipients to FDM 3D printing for the fabrication of patient-tailored immediate release tablets.

Science.gov (United States)

Sadia, Muzna; Sośnicka, Agata; Arafat, Basel; Isreb, Abdullah; Ahmed, Waqar; Kelarakis, Antonios; Alhnan, Mohamed A

2016-11-20

This work aims to employ fused deposition modelling 3D printing to fabricate immediate release pharmaceutical tablets with several model drugs. It investigates the addition of non-melting filler to methacrylic matrix to facilitate FDM 3D printing and explore the impact of (i) the nature of filler, (ii) compatibility with the gears of the 3D printer and iii) polymer: filler ratio on the 3D printing process. Amongst the investigated fillers in this work, directly compressible lactose, spray-dried lactose and microcrystalline cellulose showed a level of degradation at 135°C whilst talc and TCP allowed consistent flow of the filament and a successful 3D printing of the tablet. A specially developed universal filament based on pharmaceutically approved methacrylic polymer (Eudragit EPO) and thermally stable filler, TCP (tribasic calcium phosphate) was optimised. Four model drugs with different physicochemical properties were included into ready-to-use mechanically stable tablets with immediate release properties. Following the two thermal processes (hot melt extrusion (HME) and fused deposition modelling (FDM) 3D printing), drug contents were 94.22%, 88.53%, 96.51% and 93.04% for 5-ASA, captopril, theophylline and prednisolone respectively. XRPD indicated that a fraction of 5-ASA, theophylline and prednisolone remained crystalline whilst captopril was in amorphous form. By combining the advantages of thermally stable pharmaceutically approved polymers and fillers, this unique approach provides a low cost production method for on demand manufacturing of individualised dosage forms. Copyright © 2016 Elsevier B.V. All rights reserved.

Pharmaceutical wastewater treatment: a physicochemical study

International Nuclear Information System (INIS)

Saleem, M.

2007-01-01

A physicochemical study for the treatment of pharmaceutical wastewater was performed. Objective of the laboratory investigation was to study the removal of color, Total Dissolved Solids (TDS), Biochemical Oxygen Demand (BOD), Chemical Oxygen Demand (COD), turbidity and phenol and bring them up to the allowable limits for reuse purposes. Efficiency of coagulation, flocculation, sedimentation, sand filtration followed by activated carbon adsorption was determined. It was found that tested coagulants (alum, ferric chloride, and ferrous sulphate) are not much effective and required high dosage for the removal; of TSS, BOD, COD and turbidity. Alum was found to be more effective among tested coagulants and reduce TSS, BOD, COD and turbidity 79.6%, 34.8, 48.6% and 69.2% respectively. Sand filtration further reduced the studied parameters 97.7%, 95.7%, 93.9% and 76.9% respectively. As the concentration of phenol in the studied pharmaceutical wastewater was 100 mg/l, granular activated carbon was used to remove phenol up to the allowable limit for reuse purpose. Activated carbon adsorption further reduces phenol, TDS, TSS, BOD, and COD up to 99.9%, 99.1%, 21.4%, 81.3% and 71.1% respectively. High removal of color observed after activated carbon adsorption. It was concluded that the suggested treatment scheme is suitable to bring the effluent quality up to the water quality standards. (author)

COMBINATION OF A MINIMAL DOSAGE OF DEPOT MEDROXY PROGESTERONE ACETATE AND JAVANESSE LONG PEPPER EXTRACT ON THE BODY WEIGHT, HEMATOLOGY, AND BLOOD BIOCHEMISTRY OF MALE RATS AS A SAFETY CONTRACEPTION MODEL

Directory of Open Access Journals (Sweden)

Nukman Moeloek

2011-11-01

Full Text Available The development of male hormonal contraception is based on the decrease in the sperm concentration and it does notaffect libido and sexual potency. The combination of depot medroxy progesterone acetate (DMPA + extract ofJavanese long pepper (JLP with dosages of 0.94 mg and 1.88 mg decreases the concentration of spermatozoa.However, it remains unknown whether the combination influences body weight, hematology, and blood biochemistry.Therefore, it is necessary to investigate the effect of DMPA + JLP extracts on the body weight, hematology, and bloodbiochemistry of male rats (Rattus norvegicus L. strains of Sprague-Dawley. The research uses a completelyrandomized design (CRD; one group control and two treatment groups. In the first group, the castration rats were givenoral administration extracts of JLP (CJ with doses of 0, 0.94, 1.88, 2.82, and 3.76 mg. In the second group, the ratswere injected with 1.25 mg DMPA and given an oral administration extract of JLP. Injection was given in week-0 and12. Administration was conducted every day from week 7-18. Analysis of the normality and homogeneity of data isdone before the test ANOVA. Data that is abnormal and not homogeneous are tested with non-parametric statisticalKruskal-Wallis. This study shows that the combination of minimal doses of DMPA and administration various doses ofextracts of JLP does not affect body weight and hematology (erythrocyte, hemoglobin, hematocrite, and the bloodbiochemistry of rats, such as the values of SGPT, SGOT, HDL, and triglycerides (p < 0.05, but rather the totalcholesterol and LDL (p < 0.05. Furthermore, it is concluded that the combination of the minimal dosage of DMPA andweaned various dosages of JLP extracts affect the total value and LDL cholesterol but do not influence body weight,nor hematology and blood biochemistry. Such combination can be drawn on for a male contraceptive model that is safeby taking into account the value of the total cholesterol and LDL

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

quality evaluation of paracetamol in the bulk, dosage forms

African Journals Online (AJOL)

Prince Acheampong

assay of paracetamol-codeine combination drug as well as estimation of the amount of ... post-market is very essential in the policy and technical guidelines of drug regulatory authorities such as the Food and Drugs Board. ... Pharmaceutical industries may also have simple analytical procedures for both in-process and.

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

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

Advances in simultaneous DSC-FTIR microspectroscopy for rapid solid-state chemical stability studies: some dipeptide drugs as examples.

Science.gov (United States)

Lin, Shan-Yang; Wang, Shun-Li

2012-04-01

The solid-state chemistry of drugs has seen growing importance in the pharmaceutical industry for the development of useful API (active pharmaceutical ingredients) of drugs and stable dosage forms. The stability of drugs in various solid dosage forms is an important issue because solid dosage forms are the most common pharmaceutical formulation in clinical use. In solid-state stability studies of drugs, an ideal accelerated method must not only be selected by different complicated methods, but must also detect the formation of degraded product. In this review article, an analytical technique combining differential scanning calorimetry and Fourier-transform infrared (DSC-FTIR) microspectroscopy simulates the accelerated stability test, and simultaneously detects the decomposed products in real time. The pharmaceutical dipeptides aspartame hemihydrate, lisinopril dihydrate, and enalapril maleate either with or without Eudragit E were used as testing examples. This one-step simultaneous DSC-FTIR technique for real-time detection of diketopiperazine (DKP) directly evidenced the dehydration process and DKP formation as an impurity common in pharmaceutical dipeptides. DKP formation in various dipeptides determined by different analytical methods had been collected and compiled. Although many analytical methods have been applied, the combined DSC-FTIR technique is an easy and fast analytical method which not only can simulate the accelerated drug stability testing but also at the same time enable to explore phase transformation as well as degradation due to thermal-related reactions. This technique offers quick and proper interpretations. Copyright © 2012 Elsevier B.V. All rights reserved.

Gene dosage compensation calibrates four regulatory RNAs to control Vibrio cholerae quorum sensing

DEFF Research Database (Denmark)

Svenningsen, Sine L; Tu, Kimberly C; Bassler, Bonnie L

2009-01-01

the quorum regulatory RNAs 1-4 (Qrr1-4). The four Qrr sRNAs are functionally redundant. That is, expression of any one of them is sufficient for wild-type quorum-sensing behaviour. Here, we show that the combined action of two feedback loops, one involving the sRNA-activator LuxO and one involving the sRNA......Quorum sensing is a mechanism of cell-to-cell communication that allows bacteria to coordinately regulate gene expression in response to changes in cell-population density. At the core of the Vibrio cholerae quorum-sensing signal transduction pathway reside four homologous small RNAs (sRNAs), named......-target HapR, promotes gene dosage compensation between the four qrr genes. Gene dosage compensation adjusts the total Qrr1-4 sRNA pool and provides the molecular mechanism underlying sRNA redundancy. The dosage compensation mechanism is exquisitely sensitive to small perturbations in Qrr levels. Precisely...

Pharmaceutical services and health promotion: how far have we gone and how are we faring? Scientific output in pharmaceutical studies

Directory of Open Access Journals (Sweden)

Carina Akemi Nakamura

2014-12-01

Full Text Available The objective of this study was to investigate the scientific output on health promotion within the pharmaceutical field and its relation with the development of pharmaceutical services within health systems. A comprehensive review of published scientific articles from the Medline and Lilacs databases was carried out. The review comprised articles published until December 2011, and used combinations of the terms 'health promotion' or 'health education' and 'pharmacy', 'pharmacist' or 'pharmaceutical'. The articles were selected according to inclusion and exclusion criteria. A total of 170 full texts and 87 indexed abstracts were analyzed, evidencing that most described actions of health promotion in community pharmacies and other services. Following the Ottawa Charter, most of the studies dealt with new guidance of the service and the supply of pharmaceutical information and services. It was concluded that there is a lack of theoretical background on health promotion in the pharmaceutical field to sustain the professional education and practice required by the health system and the population.

PHARMACEUTICAL AEROSOLS FOR THE TREATMENT AND PREVENTION OF TUBERCULOSIS

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Shumaila N Muhammad Hanif

2012-09-01

Full Text Available Historically, pharmaceutical aerosols have been employed for the treatment of obstructive airway diseases, such as asthma and chronic obstructive pulmonary disease, but in the past decades their use has been expanded to treat lung infections associated with cystic fibrosis and other respiratory diseases. Tuberculosis (TB is acquired after inhalation of aerosol droplets containing the bacilli from the cough of infected individuals. Even though TB affects other organs, the lungs are the primary site of infection, which makes the pulmonary route an ideal alternative route to administer vaccines or drug treatments. Optimization of formulations and delivery systems for anti-TB vaccines and drugs, as well as the proper selection of the animal model to evaluate those is of paramount importance if novel vaccines or drug treatments are to be successful. Pharmaceutical aerosols for patient use are generated from metered dose inhalers, nebulizers and dry powder inhalers. In addition to the advantages of providing more efficient delivery of the drug, low cost and portability, pharmaceutical dry powder aerosols are more stable than inhalable liquid dosage forms and do not require refrigeration. Methods to manufacture dry powders in respirable sizes include micronization, spray drying and other proprietary technologies. Inhalable dry powders are characterized in terms of their drug content, particle size and dispersibility to ensure deposition in the appropriate lung region and effective aerosolization from the device. These methods will be illustrated as they were applied for the manufacture and characterization of powders containing anti-tubercular agents and vaccines for pulmonary administration. The influence of formulation, selection of animal model, method of aerosol generation and administration on the efficacy demonstrated in a given study will be illustrated by the evaluation of pharmaceutical aerosols of anti-TB drugs and vaccines in guinea pigs by

Validated HPTLC methods for determination of some selected antihypertensive mixtures in their combined dosage forms

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Rasha A. Shaalan

2014-12-01

Full Text Available Simple and selective HPTLC methods were developed for the simultaneous determination of the antihypertensive drugs; carvedilol and hydrochlorothiazide in their binary mixture (Mixture I and amlodipine besylate, valsartan, and hydrochlorothiazide in their combined ternary formulation (Mixture II. Effective chromatographic separation was achieved on Fluka TLC plates 20 × 20 cm aluminum cards, 0.2 mm thickness through linear ascending development. For Mixture I, the mobile phase composed of chloroform–methanol in the ratio 8:2 v/v. Detection was performed at 254 nm for both carvedilol and hydrochlorothiazide. For Mixture II, the mobile phase was chloroform–methanol–ammonia in the volume ratio 8:2:0.1. Detection was performed at 254 nm for valsartan and hydrochlorothiazide, and at 365 nm for amlodipine. Quantification was based on spectrodensitometric analysis. Analytical performance of the proposed HPTLC procedures was statistically validated with respect to linearity, ranges, precision, accuracy, specificity, robustness, detection and quantification limits. The linearity ranges were 0.05–1.0 and 0.1–2.0 μg/spot for carvedilol and hydrochlorothiazide, respectively in Mixture I, 0.1–2.0, 0.1–2.0 and 0.2–4.0 μg/spot for amlodipine, hydrochlorothiazide and valsartan, respectively in Mixture II, with correlation coefficients >0.9992. The validated HPTLC methods were applied to the analysis of the cited antihypertensive drugs in their combined pharmaceutical tablets. The proposed methods confirmed peak identity and purity.

Identification and analcime quantification; Identification et dosage de l'analcime

Energy Technology Data Exchange (ETDEWEB)

Chantret, F; Guillemaut, A; Pouget, R

1962-07-01

The authors are comparing thermal analysis and X-ray diffraction methods for the estimation of analcime in rocks. From application to the analcimolithes of Agades - Republic of Niger - it appears that X-ray diffractometry is better convenient, both for identification and estimation; nevertheless, thermal analysis combined with chemical analysis allows to detect variations in the composition of analcime inside a given series. [French] Les auteurs comparent les techniques d'analyse thermique et de diffraction X pour le dosage de l'analcime dans les roches. L'application aux analcimolites d'Agades - Republique du Niger - montre que la diffractometrie X est mieux adaptee a la fois dans l'identification et le dosage; neanmoins, l'analyse thermique, associee a l'analyse chimique, permet de suivre les fluctuations de composition de l'analcime a l'interieur d'une serie determinee. (auteurs)

Combined sub-threshold dosages of phenobarbital and low-frequency stimulation effectively reduce seizures in amygdala-kindled rats.

Science.gov (United States)

Asgari, Azam; Semnanian, Saeed; Atapour, Nafiseh; Shojaei, Amir; Moradi, Homeira; Mirnajafi-Zadeh, Javad

2014-08-01

Low-frequency stimulation (LFS) is a potential therapy utilized in patients who do not achieve satisfactory control of seizures with pharmacological treatments. Here, we investigated the interaction between anticonvulsant effects of LFS and phenobarbital (a commonly used medicine) on amygdala-kindled seizures in rats. Animals were kindled by electrical stimulation of basolateral amygdala in a rapid manner (12 stimulations/day). Fully kindled animals randomly received one of the three treatment choices: phenobarbital (1, 2, 3, 4 and 8 mg/kg; i.p.; 30 min before kindling stimulation), LFS (one or 4 packages contained 100 or 200 monophasic square wave pulses, 0.1-ms pulse duration at 1 Hz, immediately before kindling stimulation) or a combination of both (phenobarbital at 3 mg/kg and LFS). Phenobarbital alone at the doses of 1, 2 and 3 mg/kg had no significant effect on the main seizure parameters. LFS application always produced anticonvulsant effects unless applied with the pattern of one package of 100 pulses, which is considered as non-effective. All the seizure parameters were significantly reduced when phenobarbital (3 mg/kg) was administered prior to the application of the non-effective pattern of LFS. Phenobarbital (3 mg/kg) also increased the anticonvulsant actions of the effective LFS pattern. Our results provide an evidence of a positive cumulative anticonvulsant effect of LFS and phenobarbital, suggesting a potential combination therapy at sub-threshold dosages of phenobarbital and LFS to achieve a satisfactory clinical effect.

Quantifying Pharmaceutical Film Coating with Optical Coherence Tomography and Terahertz Pulsed Imaging: An Evaluation

Science.gov (United States)

Lin, Hungyen; Dong, Yue; Shen, Yaochun; Zeitler, J Axel

2015-01-01

Spectral domain optical coherence tomography (OCT) has recently attracted a lot of interest in the pharmaceutical industry as a fast and non-destructive modality for quantification of thin film coatings that cannot easily be resolved with other techniques. Because of the relative infancy of this technique, much of the research to date has focused on developing the in-line measurement technique for assessing film coating thickness. To better assess OCT for pharmaceutical coating quantification, this paper evaluates tablets with a range of film coating thickness measured using OCT and terahertz pulsed imaging (TPI) in an off-line setting. In order to facilitate automated coating quantification for film coating thickness in the range of 30–200 μm, an algorithm that uses wavelet denoising and a tailored peak finding method is proposed to analyse each of the acquired A-scan. Results obtained from running the algorithm reveal an increasing disparity between the TPI and OCT measured intra-tablet variability when film coating thickness exceeds 100 μm. The finding further confirms that OCT is a suitable modality for characterising pharmaceutical dosage forms with thin film coatings, whereas TPI is well suited for thick coatings. © 2015 The Authors. Journal of Pharmaceutical Sciences published by Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3377–3385, 2015 PMID:26284354

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.

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.

Uncertainty of quantitative microbiological methods of pharmaceutical analysis.

Science.gov (United States)

Gunar, O V; Sakhno, N G

2015-12-30

The total uncertainty of quantitative microbiological methods, used in pharmaceutical analysis, consists of several components. The analysis of the most important sources of the quantitative microbiological methods variability demonstrated no effect of culture media and plate-count techniques in the estimation of microbial count while the highly significant effect of other factors (type of microorganism, pharmaceutical product and individual reading and interpreting errors) was established. The most appropriate method of statistical analysis of such data was ANOVA which enabled not only the effect of individual factors to be estimated but also their interactions. Considering all the elements of uncertainty and combining them mathematically the combined relative uncertainty of the test results was estimated both for method of quantitative examination of non-sterile pharmaceuticals and microbial count technique without any product. These data did not exceed 35%, appropriated for a traditional plate count methods. Copyright © 2015 Elsevier B.V. All rights reserved.

Stability Indicating LC-Method for Estimation of Paracetamol and Lornoxicam in Combined Dosage Form

OpenAIRE

Shah, Dimal A.; Patel, Neel J.; Baldania, Sunil L.; Chhalotiya, Usman K.; Bhatt, Kashyap K.

2011-01-01

A simple, specific and stability indicating reversed phase high performance liquid chromatographic method was developed for the simultaneous determination of paracetamol and lornoxicam in tablet dosage form. A Brownlee C-18, 5 μm column having 250×4.6 mm i.d. in isocratic mode, with mobile phase containing 0.05 M potassium dihydrogen phosphate:methanol (40:60, v/v) was used. The flow rate was 1.0 ml/min and effluents were monitored at 266 nm. The retention times of paracetamol and lornoxicam ...

A novel accelerated oxidative stability screening method for pharmaceutical solids.

Science.gov (United States)

Zhu, Donghua Alan; Zhang, Geoff G Z; George, Karen L S T; Zhou, Deliang

2011-08-01

Despite the fact that oxidation is the second most frequent degradation pathway for pharmaceuticals, means of evaluating the oxidative stability of pharmaceutical solids, especially effective stress testing, are still lacking. This paper describes a novel experimental method for peroxide-mediated oxidative stress testing on pharmaceutical solids. The method utilizes urea-hydrogen peroxide, a molecular complex that undergoes solid-state decomposition and releases hydrogen peroxide vapor at elevated temperatures (e.g., 30°C), as a source of peroxide. The experimental setting for this method is simple, convenient, and can be operated routinely in most laboratories. The fundamental parameter of the system, that is, hydrogen peroxide vapor pressure, was determined using a modified spectrophotometric method. The feasibility and utility of the proposed method in solid form selection have been demonstrated using various solid forms of ephedrine. No degradation was detected for ephedrine hydrochloride after exposure to the hydrogen peroxide vapor for 2 weeks, whereas both anhydrate and hemihydrate free base forms degraded rapidly under the test conditions. In addition, both the anhydrate and the hemihydrate free base degraded faster when exposed to hydrogen peroxide vapor at 30°C under dry condition than at 30°C/75% relative humidity (RH). A new degradation product was also observed under the drier condition. The proposed method provides more relevant screening conditions for solid dosage forms, and is useful in selecting optimal solid form(s), determining potential degradation products, and formulation screening during development. Copyright © 2011 Wiley-Liss, Inc.

High performance liquid chromatography for simultaneous determination of xipamide, triamterene and hydrochlorothiazide in bulk drug samples and dosage forms.

Science.gov (United States)

Abd El-Hay, Soad S; Hashem, Hisham; Gouda, Ayman A

2016-03-01

A novel, simple and robust high-performance liquid chromatography (HPLC) method was developed and validated for simultaneous determination of xipamide (XIP), triamterene (TRI) and hydrochlorothiazide (HCT) in their bulk powders and dosage forms. Chromatographic separation was carried out in less than two minutes. The separation was performed on a RP C-18 stationary phase with an isocratic elution system consisting of 0.03 mol L(-1) orthophosphoric acid (pH 2.3) and acetonitrile (ACN) as the mobile phase in the ratio of 50:50, at 2.0 mL min(-1) flow rate at room temperature. Detection was performed at 220 nm. Validation was performed concerning system suitability, limits of detection and quantitation, accuracy, precision, linearity and robustness. Calibration curves were rectilinear over the range of 0.195-100 μg mL(-1) for all the drugs studied. Recovery values were 99.9, 99.6 and 99.0 % for XIP, TRI and HCT, respectively. The method was applied to simultaneous determination of the studied analytes in their pharmaceutical dosage forms.

Attitude and perception of patients and health care practitioners toward oral sustained release dosage forms in Palestine.

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Zaid, Abdel Naser

2010-10-01

To evaluate the knowledge of health professionals in Palestine regarding the advantages of sustained release dosage forms (SRDFs) over conventional therapy. Data were gathered from a questionnaire that was handed out to community pharmacists, physicians and patients. Pharmaceutical industry decision makers were enrolled in this study. Data were analyzed using the SPSS. Pharmacists (92.9%) and 89.2% of physicians thought that SRDFs improve patient compliance. 81.5% of pharmacists and 77% of physicians were in agreement regarding the capacity of SRDFs to maintain therapeutic activity during night. In this study, 81.5% of pharmacists and 81% of physicians believed that SRDFs provide further advantage with psychiatric patients who forget to take their medications. Pharmacists (63.1%) and only 63.5% of physicians believed that SRDFs yield a time saving for nurses who use SRDFs in hospital. Only 45.3% of physicians and 43.4% of pharmacists thought that SRDFs result in cost saving due to better disease management. Pharmacists (95.2%) and 95.9% of physicians agreed that SRDFs could be the right choice for faith patient's who must take their medication during the month of Ramadan. Pharmacists (66.7%) and 50.7% of physicians recognize that SRDFs may be unsafe if they are improperly formulated. Bad swallowing was also recognized as inconveniences of SRDFs by 67.9% of pharmacists and 57.3% of physicians. Given the above advantages, 75% of patients showed economical problems regarding the cost of the single course therapy of SRDFs and 100% of interviewed patients were enthusiastic about the advantage of SRDFs during Ramadan. The advantages of SRDFs are not completely understood by Palestinian health professionals. Pharmaceutical industries should pay more attention to the development and advertising of SRDFs due to the valuable advantages of these dosage forms.

3D printing of high drug loaded dosage forms using thermoplastic polyurethanes.

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Verstraete, G; Samaro, A; Grymonpré, W; Vanhoorne, V; Van Snick, B; Boone, M N; Hellemans, T; Van Hoorebeke, L; Remon, J P; Vervaet, C

2018-01-30

It was the aim of this study to develop high drug loaded (>30%, w/w), thermoplastic polyurethane (TPU)-based dosage forms via fused deposition modelling (FDM). Model drugs with different particle size and aqueous solubility were pre-processed in combination with diverse TPU grades via hot melt extrusion (HME) into filaments with a diameter of 1.75 ± 0.05 mm. Subsequently, TPU-based filaments which featured acceptable quality attributes (i.e. consistent filament diameter, smooth surface morphology and good mechanical properties) were printed into tablets. The sustained release potential of the 3D printed dosage forms was tested in vitro. Moreover, the impact of printing parameters on the in vitro drug release was investigated. TPU-based filaments could be loaded with 60% (w/w) fine drug powder without observing severe shark skinning or inconsistent filament diameter. During 3D printing experiments, HME filaments based on hard TPU grades were successfully converted into personalized dosage forms containing a high concentration of crystalline drug (up to 60%, w/w). In vitro release kinetics were mainly affected by the matrix composition and tablet infill degree. Therefore, this study clearly demonstrated that TPU-based FDM feedstock material offers a lot of formulation freedom for the development of personalized dosage forms. Copyright © 2017 Elsevier B.V. All rights reserved.

76 FR 3488 - Implantation or Injectable Dosage Form New Animal Drugs; Oxytetracycline and Flunixin

Science.gov (United States)

2011-01-20

.... FDA-2010-N-0002] Implantation or Injectable Dosage Form New Animal Drugs; Oxytetracycline and Flunixin... combination drug injectable solution containing oxytetracycline and flunixin meglumine in cattle. [[Page 3489... veterinary prescription use of HEXASOL (oxytetracycline and flunixin meglumine) Injection for the treatment...

A possible application of magnetic resonance imaging for pharmaceutical research.

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Kowalczuk, Joanna; Tritt-Goc, Jadwiga

2011-03-18

Magnetic resonance imaging (MRI) is a non-destructive and non-invasive method, the experiment can be conducted in situ and allows the studying of the sample and the different processes in vitro or in vivo. 1D, 2D or 3D imaging can be undertaken. MRI is nowadays most widely used in medicine as a clinical diagnostic tool, but has still seen limited application in the food and pharmaceutical sciences. The different imaging pulse sequences of MRI allow to image the processes that take place in a wide scale range from ms (dissolution of compact tablets) to hours (hydration of drug delivery systems) for mobile as well as for rigid spins, usually protons. The paper gives examples of MRI application of in vitro imaging of pharmaceutical dosage based on hydroxypropyl methylcellulose which have focused on water-penetration, diffusion, polymer swelling, and drug release, characterized with respect to other physical parameters such as pH and the molecular weight of polymer. Tetracycline hydrochloride was used as a model drug. NMR imaging of density distributions and fast kinetics of the dissolution behavior of compact tablets is presented for paracetamol tablets. Copyright © 2010 Elsevier B.V. All rights reserved.

A model of the prescription-pharmaceutical sales process

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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.

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...

Endotoxin dosage in sepsis

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Vincenzo Rondinelli

2012-03-01

Full Text Available Introduction. Endotoxin, a component of the cell wall of Gram-negative bacteria is a major contributor to the pathogenesis of septic shock and multiple organ failure (MOF. Its entry into the bloodstream stimulates monocytes/macrophages which once activated produce and release cytokines, nitric oxide and other mediators that induce systemic inflammation, endothelial damage, organ dysfunction, hypotension (shock and MOF.The aim of this study is to evaluate the usefulness of a quantitative test for the dosage of endotoxin to determine the risk of severe Gram-negative sepsis. Materials and methods. In the period January 2009 - June 2011 we performed 897 tests for 765 patients, mostly coming from the emergency room and intensive care, of which 328 (43% women (mean age 53 and 437 (57% male (mean age 49. Fifty-nine patients, no statistically significant difference in sex, were monitored by an average of two determinations of EA.All patients had procalcitonin values significantly altered.The kit used was EAA (Endotoxin Activity Assay Estor Company, Milan, which has three ranges of endotoxin activity (EA: low risk of sepsis if <0.40 units, medium if between 0.40 and 0.59; high if 0.60. Results. 78 out of 765 patients (10% had a low risk, 447 (58% a medium risk and 240 (32% a high risk.The dosage of EA, combined with that of procalcitonin, has allowed a more targeted antibiotic therapy. Six patients in serious clinical conditions were treated by direct hemoperfusion with Toraymyxin, a device comprising a housing containing a fiber polypropylene and polystyrene with surface-bound polymyxin B, an antibiotic that removes bacterial endotoxins from the blood. Conclusions.The test is useful in risk stratification as well as Gram negative sepsis, to set and monitor targeted therapies, also based on the neutralization of endotoxin.

Simultaneous Estimation of Gemcitabine Hydrochloride and Capecitabine Hydrochloride in Combined Tablet Dosage Form by RP-HPLC Method

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V. Rajesh

2011-01-01

Full Text Available A new reverse phase high performance liquid chromatography (RP-HPLC method has been developed for the simultaneous estimation of gemcitabine hydrochloride and capecitabine hydrochloride in combined tablet dosage form. An inertsil ODS-3 C-18 column having dimensions of 250×4.6 mm and particle size of 5 µm, with mobile phase containing a mixture of acetonitrile : water : triethyelamine in the ratio of (70 : 28 : 2v/v was used. The pH of mobile phase was adjusted to 4.0 with ortho-phosphoric acid. The flow rate was 1 mL/min and the column effluents were monitored at 260 nm. The retention time for gemcitabine hydrochloride and capecitabine hydrochloride was found to be 2.76 and 2.3 min respectively. The proposed method was validated in terms of linearity, accuracy, precision, limit of detection, limit of quantitation and robustness. The method was found to be linear in the range of 10-50 µg/mL and 4-24 µg/mL for gemcitabine hydrochloride and capecitabine hydrochloride, with regression coefficient r = 0.999 and r = 0.999, respectively.

[Pharmaceutical care of patients with rheumatoid and psoriatic arthritis receiving etanercept].

Science.gov (United States)

Romero Crespo, I; Antón Torres, R; Borrás Blasco, J; Navarro Ruiz, A

2005-01-01

To evaluate a pharmaceutical care protocol for patients with rheumatoid arthritis (RA) or psoriatic arthritis who begin treatment with etanercept with the objective of identifying potential medication-related problems and implementing therapeutic measures to improve the way this drug is used. An observational, prospective, 3-month study of patients with RA receiving etanercept therapy from March to December 2003 was conducted and a pharmaceutical care protocol was set up. During the first visit, a pharmacotherapeutic record was initiated for each patient, including socio-demographic data, personal history, diagnosis, DMARDs (disease-modifying anti-rheumatic drugs) previously received, and concomitant therapies for other underlying conditions. Patients were briefed on dosage, administration route, and potential adverse events both orally and in writing. Correct drug administration and preservation were verified during the second visit, where potential adverse effects were identified, treatment adherence was confirmed, and, if needed, potential drug interactions with other ongoing medications were disclosed. During the third visit, adherence was assessed, adverse events were recorded, and patients evaluated their response to treatment. Fifty patients were included, 40 with a diagnosis of rheumatoid arthritis (80%) and 10 diagnosed with psoriatic arthritis (20%). In all, 72% had received previous treatment with methotrexate (MTX), 40% with leflunomide, 20% with infliximab, 56% with corticoids, 2% with analgesics, 56% with NSAIDs, and 30% with other DMARDs. No significant drug interactions were found. Regarding adherence to treatment, 7.7% of patients skipped one or more doses, with travelling being the most common reason. Adverse events reported included: injection site reaction (27%), headache (7.7%) and nausea (7.7%). At 3 months after treatment onset, a reduction of MTX doses was seen in 18% of patients, of leflunomide dosage in 8%, of corticoids in 18%, of

Spectrophotometric method for simultaneous estimation of atazanavir sulfate and ritonavir in tablet dosage form

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Disha A Patel

2015-01-01

Full Text Available Background: Ritonavir (RTV and atazanavir sulfate (ATV are protease inhibitor and RTV mostly used as a booster for increasing the bioavailability of other protease inhibitors like ATV. Aims: Quality assessment of the new dosage form of RTV and ATV i.e., tablets is very essential and hence this work deals with to develop sensitive, simple and precise method for simultaneous estimation of ATV and RTV in tablet dosage form by absorbance correction method. Materials and Methods: The present work was carried out on Shimadzu Ultraviolate(UV-1700 double beam spectrophotometer with 1 cm path length supported by S Shimadzu, model-1700(Japan, UV-Probe software, version 2.31 was used for spectral measurements with 10 mm matched quartz cells. Standard ATV and RTV were supplied by Cipla Pharmaceutical Ltd. Methanol was purchased from Finar Chemicals Pvt. Ltd. Results and Conclusion: The λmax or the absorption maxima for ATV and RTV were found to be 279 and 240 nm, respectively in methanol as solvent. The drugs follow Beer-Lambert′s law in the concentration range 30-90 and 10-30 μg/mL for ATV and RTV, respectively. The percentage recovery was found to be 100-100.33% and 100-101.5% for ATV and RTV, respectively. The method was validated for different parameters as per the International Conference for Harmonization Guidelines.

Recent trends and future of pharmaceutical packaging technology

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Nityanand Zadbuke

2013-01-01

Full Text Available The pharmaceutical packaging market is constantly advancing and has experienced annual growth of at least five percent per annum in the past few years. The market is now reckoned to be worth over $20 billion a year. As with most other packaged goods, pharmaceuticals need reliable and speedy packaging solutions that deliver a combination of product protection, quality, tamper evidence, patient comfort and security needs. Constant innovations in the pharmaceuticals themselves such as, blow fill seal (BFS vials, anti-counterfeit measures, plasma impulse chemical vapor deposition (PICVD coating technology, snap off ampoules, unit dose vials, two-in-one prefilled vial design, prefilled syringes and child-resistant packs have a direct impact on the packaging. The review details several of the recent pharmaceutical packaging trends that are impacting packaging industry, and offers some predictions for the future.

Recent trends and future of pharmaceutical packaging technology.

Science.gov (United States)

Zadbuke, Nityanand; Shahi, Sadhana; Gulecha, Bhushan; Padalkar, Abhay; Thube, Mahesh

2013-04-01

The pharmaceutical packaging market is constantly advancing and has experienced annual growth of at least five percent per annum in the past few years. The market is now reckoned to be worth over $20 billion a year. As with most other packaged goods, pharmaceuticals need reliable and speedy packaging solutions that deliver a combination of product protection, quality, tamper evidence, patient comfort and security needs. Constant innovations in the pharmaceuticals themselves such as, blow fill seal (BFS) vials, anti-counterfeit measures, plasma impulse chemical vapor deposition (PICVD) coating technology, snap off ampoules, unit dose vials, two-in-one prefilled vial design, prefilled syringes and child-resistant packs have a direct impact on the packaging. The review details several of the recent pharmaceutical packaging trends that are impacting packaging industry, and offers some predictions for the future.

Recent trends and future of pharmaceutical packaging technology

Science.gov (United States)

Zadbuke, Nityanand; Shahi, Sadhana; Gulecha, Bhushan; Padalkar, Abhay; Thube, Mahesh

2013-01-01

The pharmaceutical packaging market is constantly advancing and has experienced annual growth of at least five percent per annum in the past few years. The market is now reckoned to be worth over $20 billion a year. As with most other packaged goods, pharmaceuticals need reliable and speedy packaging solutions that deliver a combination of product protection, quality, tamper evidence, patient comfort and security needs. Constant innovations in the pharmaceuticals themselves such as, blow fill seal (BFS) vials, anti-counterfeit measures, plasma impulse chemical vapor deposition (PICVD) coating technology, snap off ampoules, unit dose vials, two-in-one prefilled vial design, prefilled syringes and child-resistant packs have a direct impact on the packaging. The review details several of the recent pharmaceutical packaging trends that are impacting packaging industry, and offers some predictions for the future. PMID:23833515

At-line determination of pharmaceuticals small molecule's blending end point using chemometric modeling combined with Fourier transform near infrared spectroscopy

Science.gov (United States)

Tewari, Jagdish; Strong, Richard; Boulas, Pierre

2017-02-01

This article summarizes the development and validation of a Fourier transform near infrared spectroscopy (FT-NIR) method for the rapid at-line prediction of active pharmaceutical ingredient (API) in a powder blend to optimize small molecule formulations. The method was used to determine the blend uniformity end-point for a pharmaceutical solid dosage formulation containing a range of API concentrations. A set of calibration spectra from samples with concentrations ranging from 1% to 15% of API (w/w) were collected at-line from 4000 to 12,500 cm- 1. The ability of the FT-NIR method to predict API concentration in the blend samples was validated against a reference high performance liquid chromatography (HPLC) method. The prediction efficiency of four different types of multivariate data modeling methods such as partial least-squares 1 (PLS1), partial least-squares 2 (PLS2), principal component regression (PCR) and artificial neural network (ANN), were compared using relevant multivariate figures of merit. The prediction ability of the regression models were cross validated against results generated with the reference HPLC method. PLS1 and ANN showed excellent and superior prediction abilities when compared to PLS2 and PCR. Based upon these results and because of its decreased complexity compared to ANN, PLS1 was selected as the best chemometric method to predict blend uniformity at-line. The FT-NIR measurement and the associated chemometric analysis were implemented in the production environment for rapid at-line determination of the end-point of the small molecule blending operation. FIGURE 1: Correlation coefficient vs Rank plot FIGURE 2: FT-NIR spectra of different steps of Blend and final blend FIGURE 3: Predictions ability of PCR FIGURE 4: Blend uniformity predication ability of PLS2 FIGURE 5: Prediction efficiency of blend uniformity using ANN FIGURE 6: Comparison of prediction efficiency of chemometric models TABLE 1: Order of Addition for Blending Steps

Estimating post-marketing exposure to pharmaceutical products using ex-factory distribution data.

Science.gov (United States)

Telfair, Tamara; Mohan, Aparna K; Shahani, Shalini; Klincewicz, Stephen; Atsma, Willem Jan; Thomas, Adrian; Fife, Daniel

2006-10-01

The pharmaceutical industry has an obligation to identify adverse reactions to drug products during all phases of drug development, including the post-marketing period. Estimates of population exposure to pharmaceutical products are important to the post-marketing surveillance of drugs, and provide a context for assessing the various risks and benefits, including drug safety, associated with drug treatment. This paper describes a systematic approach to estimating post-marketing drug exposure using ex-factory shipment data to estimate the quantity of medication available, and dosage information (stratified by indication or other factors as appropriate) to convert the quantity of medication to person time of exposure. Unlike the non-standardized methods often used to estimate exposure, this approach provides estimates whose calculations are explicit, documented, and consistent across products and over time. The methods can readily be carried out by an individual or small group specializing in this function, and lend themselves to automation. The present estimation approach is practical and relatively uncomplicated to implement. We believe it is a useful innovation. Copyright 2006 John Wiley & Sons, Ltd.

Antioxidant activity evaluation of new dosage forms as vehicles for dehydrated vegetables.

Science.gov (United States)

Romero-de Soto, María Dolores; García-Salas, Patricia; Fernández-Arroyo, Salvador; Segura-Carretero, Antonio; Fernández-Campos, Francisco; Clares-Naveros, Beatriz

2013-06-01

A dehydrated vegetables mixture loaded in four pharmaceutical dosage forms as powder, effervescent granulate, sugar granulate and gumdrops were investigated for their antioxidant capacity using 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) radical scavenging capacity assay, oxygen radical absorbance capacity assay and ferric reducing antioxidant potential assay. Total phenolic content of dehydrated vegetables powder mixture was also measured by the Folin-Ciocalteu method, so as to evaluate its contribution to their total antioxidant function. The effect of different temperatures on stability of these systems after 90 days storage was also evaluated. These formulations presented strong antioxidant properties and high phenolic content (279 mg gallic acid equivalent/g of sample) and thus could be potential rich sources of natural antioxidants. Antioxidant properties differed significantly among selected formulations (p forms are new and innovative approach for vegetable intakes in population with special requirements providing an improvement in the administration of vegetables and fruits.

Combinatorial nanodiamond in pharmaceutical and biomedical applications.

Science.gov (United States)

Lim, Dae Gon; Prim, Racelly Ena; Kim, Ki Hyun; Kang, Eunah; Park, Kinam; Jeong, Seong Hoon

2016-11-30

One of the newly emerging carbon materials, nanodiamond (ND), has been exploited for use in traditional electric materials and this has extended into biomedical and pharmaceutical applications. Recently, NDs have attained significant interests as a multifunctional and combinational drug delivery system. ND studies have provided insights into granting new potentials with their wide ranging surface chemistry, complex formation with biopolymers, and combination with biomolecules. The studies that have proved ND inertness, biocompatibility, and low toxicity have made NDs much more feasible for use in real in vivo applications. This review gives an understanding of NDs in biomedical engineering and pharmaceuticals, focusing on the classified introduction of ND/drug complexes. In addition, the diverse potential applications that can be obtained with chemical modification are presented. Copyright © 2016 Elsevier B.V. All rights reserved.

Low starting dosage of infliximab with possible escalating dosage in psoriatic arthritis gives the same treatment results as standard dosage of adalimumab or etanercept: results from the nationwide Icelandic ICEBIO registry

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Gudbjornsson B

2018-05-01

Full Text Available Bjorn Gudbjornsson,1,2 Arni Jon Geirsson,3,4 Niels Steen Krogh5 1Centre for Rheumatology Research, University Hospital, Reykjavik, Iceland; 2Faculty of Medicine, University of Iceland, Reykjavik, Iceland; 3Department of Rheumatology, University Hospital, Reykjavik, Iceland; 4Laeknasetrid - Medical Clinic, University of Iceland, Reykjavik, Iceland; 5Zitelab Aps, Copenhagen, Denmark Objective: To explore differences in response to a low dosage regimen of infliximab with an escalating dosage in comparison to a standard dosage of etanercept and adalimumab in patients with psoriatic arthritis (PsA. Methods: Biologically naïve PsA patients who were beginning anti-TNF-α therapy were selected from the ICEBIO registry. Demographics and clinical differences were compared in four treatment groups: infliximab <4 mg/kg; infliximab >4 mg/kg; etanercept or adalimumab at baseline and on follow-up (6 and 12 months, last visit. The Kruskal–Wallis rank sum test was used for comparison of the groups and the Wilcoxon test to compare the two infliximab dosage regimens. Results: One hundred and eighty-five patients (61% female were identified; 84 patients received infliximab, 66 etanercept, and 35 adalimumab. A total of 19% of the patients treated with infliximab escalated their dosage ≥4 mg/kg. No significant differences were observed at baseline in respect to visual analog scale (VAS pain, VAS fatigue, Health Assessment Questionnaire, C-reactive protein (CRP, numbers of swollen or tender joints, or Disease Activity Score (DAS 28-CRP values. A similar treatment response was observed in all four treatment groups on follow-up. Conclusion: In respect to treatment effects, a low dosage of infliximab with possible escalating dosage is acceptable for the majority of PsA patients who are in need of biological treatment. Keywords: psoriatic arthritis, outcome, biological treatment, routine care, clinical nationwide registry

Effect of occasional epoetin use in combination with a stable darbepoetin dosage on anemia management in hemodialysis patients

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Shimamatsu K

2014-12-01

.05. Conclusion: The occasional use of EPO in combination with a stable DA dosage may be useful for Hb control within a narrow range of the target level. Keywords: combination therapy, erythropoiesis-stimulating agents, hemoglobin cycling, hemoglobin SD

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

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V. L. Shevina

2014-12-01

was to identify the value of drugs. In the market of Ukraine manufacturers mainly offer the medicines of natural origin, which is 66.66%. For further study of this segment, the products were subject to analysis regarding their pharmaceutical form. The studies have revealed that in the pharmaceutical market of Ukraine the drugs are presented in the following pharmaceutical forms: tablets - 32%, capsules - 11 %, syrups - 16 %, drops - 17 %, gel, powders, granules and teas - 6 % of each. Thus, the most common dosage form is tablets. It is worth mentioning that to date, in the pharmaceutical market of Ukraine the main portfolio of the medicinal products in tablets is compiled by the medicinal products of foreign origin. The share of registered medicinal products in tablets manufactured by Ukrainian manufacturers versus imported medicines is 33.33 % to 66.66 %. However, only one domestic manufacturer present in the market produces the tablets of plant crude: knotweed extract powder, St. John's wort extract powder, horsetail extract dry, avisan. Conclusions The study of the market of medicinal products used for treatment of urolithiasis approved in Ukraine has been performed. It has been established that the pharmaceutical market of Ukraine presents 21 trade names of drugs used to treat urolithiasis. Preparations are analyzed depending on the origin and content of active components, presentation, type of dosage form. Based on the marketing analysis, it has been established that regardless of the general quantity of medicines of plant origin, in the study group the share of herbal medicines in tablets is insignificant (1 manufacturer. The feasibility of study regarding the development of products of plant origin in tablets for treatment of urolithiasis has been confirmed.

Novel microwell-based spectrophotometric assay for determination of atorvastatin calcium in its pharmaceutical formulations

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Abdel-Rahman Hamdy M

2011-10-01

Full Text Available Abstract The formation of a colored charge-transfer (CT complex between atorvastatin calcium (ATR-Ca as a n-electron donor and 2, 3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ as a π-electron acceptor was investigated, for the first time. The spectral characteristics of the CT complex have been described, and the reaction mechanism has been proved by computational molecular modeling. The reaction was employed in the development of a novel microwell-based spectrophotometric assay for determination of ATR-Ca in its pharmaceutical formulations. The proposed assay was carried out in 96-microwell plates. The absorbance of the colored-CT complex was measured at 460 nm by microwell-plate absorbance reader. The optimum conditions of the reaction and the analytical procedures of the assay were established. Under the optimum conditions, linear relationship with good correlation coefficient (0.9995 was found between the absorbance and the concentration of ATR-Ca in the range of 10-150 μg/well. The limits of detection and quantitation were 5.3 and 15.8 μg/well, respectively. No interference was observed from the additives that are present in the pharmaceutical formulation or from the drugs that are co-formulated with ATR-Ca in its combined formulations. The assay was successfully applied to the analysis of ATR-Ca in its pharmaceutical dosage forms with good accuracy and precision. The assay described herein has great practical value in the routine analysis of ATR-Ca in quality control laboratories, as it has high throughput property, consumes minimum volume of organic solvent thus it offers the reduction in the exposures of the analysts to the toxic effects of organic solvents, and reduction in the analysis cost by 50-fold. Although the proposed assay was validated for ATR-Ca, however, the same methodology could be used for any electron-donating analyte for which a CT reaction can be performed.

The Pharmaceutical Industry Beamline of Pharmaceutical Consortium for Protein Structure Analysis

International Nuclear Information System (INIS)

Nishijima, Kazumi; Katsuya, Yoshio

2002-01-01

The Pharmaceutical Industry Beamline was constructed by the Pharmaceutical Consortium for Protein Structure Analysis which was established in April 2001. The consortium is composed of 22 pharmaceutical companies affiliating with the Japan Pharmaceutical Manufacturers Association. The beamline is the first exclusive on that is owned by pharmaceutical enterprises at SPring-8. The specification and equipments of the Pharmaceutical Industry Beamline is almost same as that of RIKEN Structural Genomics Beamline I and II. (author)

The use of net analyte signal (NAS) in near infrared spectroscopy pharmaceutical applications: interpretability and figures of merit.

Science.gov (United States)

Sarraguça, Mafalda Cruz; Lopes, João Almeida

2009-05-29

Near infrared spectroscopy (NIRS) has been extensively used as an analytical method for quality control of solid dosage forms for the pharmaceutical industry. Pharmaceutical formulations can be extremely complex, containing typically one or more active product ingredients (API) and various excipients, yielding very complex near infrared (NIR) spectra. The NIR spectra interpretability can be improved using the concept of net analyte signal (NAS). NAS is defined as the part of the spectrum unique to the analyte of interest. The objective of this work was to compare two different methods to estimate the API's NAS vector of different pharmaceutical formulations. The main difference between the methods is the knowledge of API free formulations NIR spectra. The comparison between the two methods was assessed in a qualitative and quantitative way. Results showed that both methods produced good results in terms of the similarity between the NAS vector and the pure API spectrum, as well as in the ability to predict the API concentration of unknown samples. Moreover, figures of merit such as sensitivity, selectivity, and limit of detection were estimated in a straightforward manner.

Chronic exposure to low doses of pharmaceuticals disturbs the hepatic expression of circadian genes in lean and obese mice

Energy Technology Data Exchange (ETDEWEB)

Anthérieu, Sébastien; Le Guillou, Dounia; Coulouarn, Cédric; Begriche, Karima [INSERM, U991, Université de Rennes 1, 35000 Rennes (France); Trak-Smayra, Viviane [Pathology Department, Saint-Joseph University, Beirut (Lebanon); Martinais, Sophie [INSERM, U991, Université de Rennes 1, 35000 Rennes (France); Porceddu, Mathieu [Mitologics SAS, Hôpital Robert Debré, 48 Boulevard Sérurier, 75019 Paris (France); Robin, Marie-Anne [INSERM, U991, Université de Rennes 1, 35000 Rennes (France); Fromenty, Bernard, E-mail: bernard.fromenty@inserm.fr [INSERM, U991, Université de Rennes 1, 35000 Rennes (France)

2014-04-01

Drinking water can be contaminated with pharmaceuticals. However, it is uncertain whether this contamination can be harmful for the liver, especially during obesity. Hence, the goal of our study was to determine whether chronic exposure to low doses of pharmaceuticals could have deleterious effects on livers of lean and obese mice. To this end, lean and ob/ob male mice were treated for 4 months with a mixture of 11 drugs provided in drinking water at concentrations ranging from 10 to 10{sup 6} ng/l. At the end of the treatment, some liver and plasma abnormalities were observed in ob/ob mice treated with the cocktail containing 10{sup 6} ng/l of each drug. For this dosage, a gene expression analysis by microarray showed altered expression of circadian genes (e.g. Bmal1, Dbp, Cry1) in lean and obese mice. RT-qPCR analyses carried out in all groups of animals confirmed that expression of 8 different circadian genes was modified in a dose-dependent manner. For some genes, a significant modification was observed for dosages as low as 10{sup 2}–10{sup 3} ng/l. Drug mixture and obesity presented an additive effect on circadian gene expression. These data were validated in an independent study performed in female mice. Thus, our study showed that chronic exposure to trace pharmaceuticals disturbed hepatic expression of circadian genes, particularly in obese mice. Because some of the 11 drugs can be found in drinking water at such concentrations (e.g. acetaminophen, carbamazepine, ibuprofen) our data could be relevant in environmental toxicology, especially for obese individuals exposed to these contaminants. - Highlights: • The contamination of drinking water with drugs may have harmful effects on health. • Some drugs can be more hepatotoxic in the context of obesity and fatty liver. • Effects of chronic exposure of trace drugs were studied in lean and obese mouse liver. Drugs and obesity present additive effects on circadian gene expression and toxicity. • Trace

Spectrophotometric and Spectrofluorimetric Studies on Azilsartan Medoxomil and Chlorthalidone to be Utilized in Their Determination in Pharmaceuticals

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Walid M. Ebeid

2014-01-01

Full Text Available The recently approved angiotensin II receptor blocker, azilsartan medoxomil (AZL, was determined spectrophotometrically and spectrofluorimetrically in its combination with chlorthalidone (CLT in their combined dosage form. The UV-spectrophotometric technique depends on simultaneous measurement of the first derivative spectra for AZL and CLT at 286 and 257 nm, respectively, in methanol. The spectrofluorimetric technique depends on measurement of the fourth derivative of the synchronous spectra intensities of AZL in presence of CLT at 298 nm in methanol. The effects of different solvents on spectrophotometric and spectrofluorimetric responses were studied. For, the spectrofluorimetric study, the effect of pH and micelle-assisted fluorescence enhancement were also studied. Linearity, accuracy, and precision were found to be satisfactory over the concentration ranges of 8-50 μg mL −1 and 2-20 μg mL −1 for AZL and CLT, respectively, in the spectrophotometric method as well as 0.01-0.08 μg mL −1 for AZL in the spectrofluorimetric method. The methods were successfully applied for the determination of the studied drugs in their co-formulated tablets. The developed methods are inexpensive and simple for the quality control and routine analysis of the cited drugs in bulk and in pharmaceuticals.

Correlated changes of serum sFas/sFasL and TRAb concentrations in patients with Graves' disease after treatment with lesser dosage of 131i combined with traditional Chinese medicine

International Nuclear Information System (INIS)

Zhang Jinshan; Deng Yongmei; Li Min; Huang Guimin; Feng Chonglian

2005-01-01

Objective: To investigate the rule of changes of serum sFas/sFasL and TRAb concentrations in patients with Graves' disease after treatment with lesser dosage of 131 I combined with traditional chinese medicine. Methods: Thirty-one patients with Graves' disease were treated with a lesser dosage (85.1-207.2 MBq, mean--about 2/3 of conventional dose) of 131 I combined with traditional chinese medicine. Serum sFas, sFasL (with ELISA), TRAb (with RRA) and other thyroid-related hormones (TT 3 , TT 4 , FT 3 , FT 4 , TSH, TGA, TMA with RIA) concentrations were determined before and after the treatment. Seventeen controls participated in this experiment. Results: 1) Serum sFas contents in the patients before treatment (179.8 ± 64.2 pg/ml) were significantly higher than those in patients clinically cured (104.2 ± 23.5 pg/ml) and controls (110.6 ± 18.1 pg/ml) (both P 131 I and traditional chinese medicine was satisfactory. The treatment was immediately effective in 100% of the patients (31/31) with a permanent cure rate of 74.2% (23/31) (one dose only) and late hypothyroidism rate of 9.7% (3/31). Conclusion: Reversal of the dominant expression of sFas after the combined treatment indirectly showed the role of apoptosis in the cure of Graves' disease. TRAb was a practical laboratory diagnostic criterion for Graves' disease. (authors)

Evaluation of students' knowledge about paediatric dosage calculations.

Science.gov (United States)

Özyazıcıoğlu, Nurcan; Aydın, Ayla İrem; Sürenler, Semra; Çinar, Hava Gökdere; Yılmaz, Dilek; Arkan, Burcu; Tunç, Gülseren Çıtak

2018-01-01

Medication errors are common and may jeopardize the patient safety. As paediatric dosages are calculated based on the child's age and weight, risk of error in dosage calculations is increasing. In paediatric patients, overdose drug prescribed regardless of the child's weight, age and clinical picture may lead to excessive toxicity and mortalities while low doses may delay the treatment. This study was carried out to evaluate the knowledge of nursing students about paediatric dosage calculations. This research, which is of retrospective type, covers a population consisting of all the 3rd grade students at the bachelor's degree in May, 2015 (148 students). Drug dose calculation questions in exam papers including 3 open ended questions on dosage calculation problems, addressing 5 variables were distributed to the students and their responses were evaluated by the researchers. In the evaluation of the data, figures and percentage distribution were calculated and Spearman correlation analysis was applied. Exam question on the dosage calculation based on child's age, which is the most common method in paediatrics, and which ensures right dosages and drug dilution was answered correctly by 87.1% of the students while 9.5% answered it wrong and 3.4% left it blank. 69.6% of the students was successful in finding the safe dose range, and 79.1% in finding the right ratio/proportion. 65.5% of the answers with regard to Ml/dzy calculation were correct. Moreover, student's four operation skills were assessed and 68.2% of the students were determined to have found the correct answer. When the relation among the questions on medication was examined, a significant relation (correlation) was determined between them. It is seen that in dosage calculations, the students failed mostly in calculating ml/dzy (decimal). This result means that as dosage calculations are based on decimal values, calculations may be ten times erroneous when the decimal point is placed wrongly. Moreover, it

Safety and regulatory review of dyes commonly used as excipients in pharmaceutical and nutraceutical applications.

Science.gov (United States)

Pérez-Ibarbia, Leire; Majdanski, Tobias; Schubert, Stephanie; Windhab, Norbert; Schubert, Ulrich S

2016-10-10

Color selection is one of the key elements of building a strong brand development and product identity in the pharmaceutical industry, besides to prevent counterfeiting. Moreover, colored pharmaceutical dosage forms may increase patient compliance and therapy enhancement. Although most synthetic dyes are classified as safe, their regulations are stricter than other classes of excipients. Safety concerns have increased during the last years but the efforts to change to natural dyes seem to be not promising. Their instability problems and the development of "non-toxic" dyes is still a challenge. This review focuses specifically on the issues related to dye selection and summarizes the current regulatory status. A deep awareness of toxicological data based on the public domain, making sure the compliance of standards for regulation and safety for successful product development is provided. In addition, synthetic strategies are provided to covalently bind dyes on polymers to possibly overcome toxicity issues. Copyright © 2016 Elsevier B.V. All rights reserved.

Dosage sensitivity shapes the evolution of copy-number varied regions.

Directory of Open Access Journals (Sweden)

Benjamin Schuster-Böckler

2010-03-01

Full Text Available Dosage sensitivity is an important evolutionary force which impacts on gene dispensability and duplicability. The newly available data on human copy-number variation (CNV allow an analysis of the most recent and ongoing evolution. Provided that heterozygous gene deletions and duplications actually change gene dosage, we expect to observe negative selection against CNVs encompassing dosage sensitive genes. In this study, we make use of several sources of population genetic data to identify selection on structural variations of dosage sensitive genes. We show that CNVs can directly affect expression levels of contained genes. We find that genes encoding members of protein complexes exhibit limited expression variation and overlap significantly with a manually derived set of dosage sensitive genes. We show that complexes and other dosage sensitive genes are underrepresented in CNV regions, with a particular bias against frequent variations and duplications. These results suggest that dosage sensitivity is a significant force of negative selection on regions of copy-number variation.

Fast-Scan DSC and its role in pharmaceutical physical form characterisation and selection.

Science.gov (United States)

Ford, James L; Mann, Timothy E

2012-04-01

Conventional rate Differential Scanning Calorimetry (DSC) has been used for many years as a tool in the analysis of pharmaceutical materials. In recent years an extension of the technique to include fast heating and cooling rates has become more prevalent. Broadly termed Fast-Scan DSC, this review examines the current applications of this technique to the characterisation and selection of pharmaceutical materials. Its increasing use encompasses the characterisation of amorphousness in crystalline materials, the characterisation of polymorphs and polymorphic transitions, the solubility of drugs in polymers, and characterisation of dosage forms. Notwithstanding the advantages of analytical speed in analytical turnover, the review emphasises the advantages of Fast-Scan DSC in its sensitivity which allows the separation of overlapping thermal events, the reduction it provides in degradation during the scanning process and its role in determining solubility in waxy and polymeric based systems. A comparison of the uses of Fast-Scan DSC to modulated DSC techniques and localised thermal analysis is also given. © 2011 Elsevier B.V. All rights reserved.

Designing concept maps for a precise and objective description of pharmaceutical innovations

Directory of Open Access Journals (Sweden)

Iordatii Maia

2013-01-01

Full Text Available Abstract Background When a new drug is launched onto the market, information about the new manufactured product is contained in its monograph and evaluation report published by national drug agencies. Health professionals need to be able to determine rapidly and easily whether the new manufactured product is potentially useful for their practice. There is therefore a need to identify the best way to group together and visualize the main items of information describing the nature and potential impact of the new drug. The objective of this study was to identify these items of information and to bring them together in a model that could serve as the standard for presenting the main features of new manufactured product. Methods We developed a preliminary conceptual model of pharmaceutical innovations, based on the knowledge of the authors. We then refined this model, using a random sample of 40 new manufactured drugs recently approved by the national drug regulatory authorities in France and covering a broad spectrum of innovations and therapeutic areas. Finally, we used another sample of 20 new manufactured drugs to determine whether the model was sufficiently comprehensive. Results The results of our modeling led to three sub models described as conceptual maps representingi the medical context for use of the new drug (indications, type of effect, therapeutical arsenal for the same indications, ii the nature of the novelty of the new drug (new molecule, new mechanism of action, new combination, new dosage, etc., and iii the impact of the drug in terms of efficacy, safety and ease of use, compared with other drugs with the same indications. Conclusions Our model can help to standardize information about new drugs released onto the market. It is potentially useful to the pharmaceutical industry, medical journals, editors of drug databases and medical software, and national or international drug regulation agencies, as a means of describing the main

Development and validation of a simple spectrophotometric method for the determination of methyldopa in both bulk and marketed dosage formulations

Directory of Open Access Journals (Sweden)

Paulo Roberto da Silva Ribeiro

2014-09-01

Full Text Available A simple, precise, sensitive, rapid, specific and economical spectrophotometric method was developed to determine methyldopa (MTD content in bulk and pharmaceutical dosage formulations. The proposed method was based on the formation of a colored product from the nitrosation reaction of MTD with sodium nitrite in an acid medium. The resultant nitroso derivative species reacts further with sodium hydroxide and is converted it into a more stable compound. This yellow nitrosation product exhibited an absorption maximum at 430 nm. Beer's Law was obeyed in a concentration range of 6.37 to 82.81 μg mL-1 MTD with an excellent coefficient of determination (R2 = 0.9998. No interference was observed from common excipients in formulations. The results showed the method to be simple, accurate and readily applied for the determination of MTD in pure form and in pharmaceutical preparations. The analytical results obtained for these products using the proposed method are in agreement with those of the Brazilian Pharmacopoeia procedure at a 95% confidence level.

Microbial quality of some herbal solid dosage forms

African Journals Online (AJOL)

STORAGESEVER

2010-03-15

Mar 15, 2010 ... Key words: Microbial quality, herbal, contamination, solid dosage form ... The type of dosage form, packaging, manufacturing and expiration dates of subject solid herbal .... According to WHO report (2002), Salmonella food.

Parental genome dosage imbalance deregulates imprinting in Arabidopsis.

Directory of Open Access Journals (Sweden)

Pauline E Jullien

2010-03-01

Full Text Available In mammals and in plants, parental genome dosage imbalance deregulates embryo growth and might be involved in reproductive isolation between emerging new species. Increased dosage of maternal genomes represses growth while an increased dosage of paternal genomes has the opposite effect. These observations led to the discovery of imprinted genes, which are expressed by a single parental allele. It was further proposed in the frame of the parental conflict theory that parental genome imbalances are directly mirrored by antagonistic regulations of imprinted genes encoding maternal growth inhibitors and paternal growth enhancers. However these hypotheses were never tested directly. Here, we investigated the effect of parental genome imbalance on the expression of Arabidopsis imprinted genes FERTILIZATION INDEPENDENT SEED2 (FIS2 and FLOWERING WAGENINGEN (FWA controlled by DNA methylation, and MEDEA (MEA and PHERES1 (PHE1 controlled by histone methylation. Genome dosage imbalance deregulated the expression of FIS2 and PHE1 in an antagonistic manner. In addition increased dosage of inactive alleles caused a loss of imprinting of FIS2 and MEA. Although FIS2 controls histone methylation, which represses MEA and PHE1 expression, the changes of PHE1 and MEA expression could not be fully accounted for by the corresponding fluctuations of FIS2 expression. Our results show that parental genome dosage imbalance deregulates imprinting using mechanisms, which are independent from known regulators of imprinting. The complexity of the network of regulations between expressed and silenced alleles of imprinted genes activated in response to parental dosage imbalance does not support simple models derived from the parental conflict hypothesis.

Fixed-Dose Combination Drug Approvals, Patents and Market Exclusivities Compared to Single Active Ingredient Pharmaceuticals.

Science.gov (United States)

Hao, Jing; Rodriguez-Monguio, Rosa; Seoane-Vazquez, Enrique

2015-01-01

Fixed-dose combinations (FDC) contain two or more active ingredients. The effective patent and exclusivity life of FDC compared to single active ingredient has not been assessed. Trends in FDA approved FDC in the period 1980-2012 and time lag between approval of FDC and single active ingredients in the combination were assessed, and the effective patent and exclusivity life of FDC was compared with their single active ingredients. New molecular entities (NMEs), new therapeutic biologics license applications (BLAs) and FDC data were collected from the FDA Orange Book and Drugs@FDA. Analysis included FDC containing one or more NMEs or BLAs at first FDA approval (NMEs-FDC) and only already marketed drugs (Non-NMEs-FDC). Descriptive, Kruskal-Wallis and Wilcoxon Rank Sum analyses were performed. During the study period, the FDA approved 28 NMEs-FDC (3.5% of NMEs) and 117 non-NMEs-FDC. FDC approvals increased from 12 in the 1980s to 59 in the 2000s. Non-NMEs-FDC entered the market at a median of 5.43 years (interquartile range 1.74, 10.31) after first FDA approval of single active ingredients in the combination. The Non-NMEs-FDC entered the market at a median of 2.33 years (-7.55, 2.39) before approval of generic single active ingredient. Non-NME-FDC added a median of 9.70 (2.75, 16.24) years to the patent and exclusivity life of the single active ingredients in the combination. FDC approvals significantly increased over the last twenty years. Pharmaceutical companies market FDC drugs shortly before the generic versions of the single ingredients enter the market extending the patent and exclusivity life of drugs included in the combination.

Fixed-Dose Combination Drug Approvals, Patents and Market Exclusivities Compared to Single Active Ingredient Pharmaceuticals.

Directory of Open Access Journals (Sweden)

Jing Hao

Full Text Available Fixed-dose combinations (FDC contain two or more active ingredients. The effective patent and exclusivity life of FDC compared to single active ingredient has not been assessed.Trends in FDA approved FDC in the period 1980-2012 and time lag between approval of FDC and single active ingredients in the combination were assessed, and the effective patent and exclusivity life of FDC was compared with their single active ingredients.New molecular entities (NMEs, new therapeutic biologics license applications (BLAs and FDC data were collected from the FDA Orange Book and Drugs@FDA. Analysis included FDC containing one or more NMEs or BLAs at first FDA approval (NMEs-FDC and only already marketed drugs (Non-NMEs-FDC. Descriptive, Kruskal-Wallis and Wilcoxon Rank Sum analyses were performed.During the study period, the FDA approved 28 NMEs-FDC (3.5% of NMEs and 117 non-NMEs-FDC. FDC approvals increased from 12 in the 1980s to 59 in the 2000s. Non-NMEs-FDC entered the market at a median of 5.43 years (interquartile range 1.74, 10.31 after first FDA approval of single active ingredients in the combination. The Non-NMEs-FDC entered the market at a median of 2.33 years (-7.55, 2.39 before approval of generic single active ingredient. Non-NME-FDC added a median of 9.70 (2.75, 16.24 years to the patent and exclusivity life of the single active ingredients in the combination.FDC approvals significantly increased over the last twenty years. Pharmaceutical companies market FDC drugs shortly before the generic versions of the single ingredients enter the market extending the patent and exclusivity life of drugs included in the combination.

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

Authentication of gold nanoparticle encoded pharmaceutical tablets using polarimetric signatures.

Science.gov (United States)

Carnicer, Artur; Arteaga, Oriol; Suñé-Negre, Josep M; Javidi, Bahram

2016-10-01

The counterfeiting of pharmaceutical products represents concerns for both industry and the safety of the general public. Falsification produces losses to companies and poses health risks for patients. In order to detect fake pharmaceutical tablets, we propose producing film-coated tablets with gold nanoparticle encoding. These coated tablets contain unique polarimetric signatures. We present experiments to show that ellipsometric optical techniques, in combination with machine learning algorithms, can be used to distinguish genuine and fake samples. To the best of our knowledge, this is the first report using gold nanoparticles encoded with optical polarimetric classifiers to prevent the counterfeiting of pharmaceutical products.

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

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

The distribution dynamics and desorption behaviour of mobile pharmaceuticals and caffeine to combined sewer sediments.

Science.gov (United States)

Hajj-Mohamad, M; Darwano, H; Duy, S Vo; Sauvé, S; Prévost, M; Arp, H P H; Dorner, S

2017-01-01

Pharmaceuticals are discharged to the environment from wastewater resource recovery facilities, sewer overflows, and illicit sewer connections. To understand the fate of pharmaceuticals, there is a need to better understand their sorption dynamics to suspended sediments (SS) and settled sediments (StS) in sewer systems. In this study, such sorption dynamics to both SS and StS were assessed using a batch equilibrium method under both static and dynamic conditions. Experiments were performed with natively occurring and artificially modified concentrations of sewer pharmaceuticals (acetaminophen, theophylline, carbamazepine, and a metabolite of carbamazepine) and caffeine. Differences in apparent distribution coefficients, K d,app , between SS and StS were related to differences in their organic carbon (OC) content, and the practice of artificially modifying the concentration. K d,app values of modified contaminant concentrations and high OC sediments were substantially higher. Pseudo-second order desorption rates for these mobile compounds were also quantified. Successive flushing events to simulate the addition of stormwater to sewer networks revealed that aqueous concentrations would not necessarily decrease, because the added water will rapidly return to equilibrium concentrations with the sediments. Sorption and desorption kinetics must be considered in addition to dilution, to avoid underestimating the influence of dilution on concentrations of pharmaceuticals discharged to the environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Expansion of GA Dinucleotide Repeats Increases the Density of CLAMP Binding Sites on the X-Chromosome to Promote Drosophila Dosage Compensation.

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Guray Kuzu

2016-07-01

Full Text Available Dosage compensation is an essential process that equalizes transcript levels of X-linked genes between sexes by forming a domain of coordinated gene expression. Throughout the evolution of Diptera, many different X-chromosomes acquired the ability to be dosage compensated. Once each newly evolved X-chromosome is targeted for dosage compensation in XY males, its active genes are upregulated two-fold to equalize gene expression with XX females. In Drosophila melanogaster, the CLAMP zinc finger protein links the dosage compensation complex to the X-chromosome. However, the mechanism for X-chromosome identification has remained unknown. Here, we combine biochemical, genomic and evolutionary approaches to reveal that expansion of GA-dinucleotide repeats likely accumulated on the X-chromosome over evolutionary time to increase the density of CLAMP binding sites, thereby driving the evolution of dosage compensation. Overall, we present new insight into how subtle changes in genomic architecture, such as expansions of a simple sequence repeat, promote the evolution of coordinated gene expression.

21 CFR 520.905 - Fenbendazole oral dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Fenbendazole oral dosage forms. 520.905 Section 520.905 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Fenbendazole oral dosage forms. ...

Buccal Dosage Forms: General Considerations for Pediatric Patients.

Science.gov (United States)

Montero-Padilla, Soledad; Velaga, Sitaram; Morales, Javier O

2017-02-01

The development of an appropriate dosage form for pediatric patients needs to take into account several aspects, since adult drug biodistribution differs from that of pediatrics. In recent years, buccal administration has become an attractive route, having different dosage forms under development including tablets, lozenges, films, and solutions among others. Furthermore, the buccal epithelium can allow quick access to systemic circulation, which could be used for a rapid onset of action. For pediatric patients, dosage forms to be placed in the oral cavity have higher requirements for palatability to increase acceptance and therapy compliance. Therefore, an understanding of the excipients required and their functions and properties needs to be particularly addressed. This review is focused on the differences and requirements relevant to buccal administration for pediatric patients (compared to adults) and how novel dosage forms can be less invasive and more acceptable alternatives.

Decomposition of persistent pharmaceuticals in wastewater by ionizing radiation

International Nuclear Information System (INIS)

Kimura, Atsushi; Osawa, Misako; Taguchi, Mitsumasa

2012-01-01

Pharmaceuticals in wastewater were treated by the combined method of activated sludge and ionizing radiation in laboratory scale. Oseltamivir, aspirin, and ibuprofen at 5 μmol dm −3 in wastewater were decomposed by the activated sludge at reaction time for 4 h. Carbamazepine, ketoprofen, mefenamic acid, clofibric acid, and diclofenac were not biodegraded completely, but were eliminated by γ-ray irradiation at 2 kGy. The rate constants of the reactions of these pharmaceuticals with hydroxyl radicals were estimated by the competition reaction method to be 4.0–10×10 9 mol −1 dm 3 s −1 . Decompositions of the pharmaceuticals in wastewater by ionizing radiation were simulated by use of the rate constants and the amount of total organic carbon as parameters. Simulation curves of concentrations of these pharmaceuticals as a function of dose described the experimental data, and the required dose for the elimination of them in wastewater by ionizing radiation can be estimated by this simulation. - Highlights: ► We treat pharmaceuticals in wastewater by activated sludge and ionizing radiation. ► Activated sludge decreases the amounts of total organic carbons in wastewater. ► Pharmaceuticals were decomposed by γ-ray irradiation at 2 kGy. ► We construct simulation for treatment of pharmaceuticals by ionizing radiation.

On the role of API in determining porosity, pore structure and bulk modulus of the skeletal material in pharmaceutical tablets formed with MCC as sole excipient.

Science.gov (United States)

Ridgway, Cathy; Bawuah, Prince; Markl, Daniel; Zeitler, J Axel; Ketolainen, Jarkko; Peiponen, Kai-Erik; Gane, Patrick

2017-06-30

The physical properties and mechanical integrity of pharmaceutical tablets are of major importance when loading with active pharmaceutical ingredient(s) (API) in order to ensure ease of processing, control of dosage and stability during transportation and handling prior to patient consumption. The interaction between API and excipient, acting as functional extender and binder, however, is little understood in this context. The API indomethacin is combined in this study with microcrystalline cellulose (MCC) at increasing loading levels. Tablets from the defined API/MCC ratios are made under conditions of controlled porosity and tablet thickness, resulting from different compression conditions, and thus compaction levels. Mercury intrusion porosimetry is used to establish the accessible pore volume, pore size distribution and, adopting the observed region of elastic intrusion-extrusion at high pressure, an elastic bulk modulus of the skeletal material is recorded. Porosity values are compared to previously published values derived from terahertz (THz) refractive index data obtained from exactly the same tablet sample sets. It is shown that the elastic bulk modulus is dependent on API wt% loading under constant tablet preparation conditions delivering equal dimensions and porosity. The findings are considered of novel value in respect to establishing consistency of tablet production and optimisation of physical properties. Copyright © 2017 Elsevier B.V. All rights reserved.

Intercavitary implants dosage calculation

International Nuclear Information System (INIS)

Rehder, B.P.

The use of spacial geometry peculiar to each treatment for the attainment of intercavitary and intersticial implants dosage calculation is presented. The study is made in patients with intercavitary implants by applying a modified Manchester technique [pt

21 CFR 522.1660 - Oxytetracycline injectable dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline injectable dosage forms. 522.1660 Section 522.1660 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... § 522.1660 Oxytetracycline injectable dosage forms. ...

Radiation dosage

Energy Technology Data Exchange (ETDEWEB)

Finston, Roland [Health Physics, Stanford University, Stanford, CA (United States)

1986-07-01

Radiation dosage at Bikini Atoll is the result of current soil contamination, a relic of the nuclear weapons testing program of some 30 years ago. The principal contaminants today and some of their physical properties are listed: cesium-137, strontium-90, plutonium -239, 240 and americium-241. Cobalt-60 contributes less than 1 to the dose and is not considered significant. A resident of the atoll would accumulate radiation dose (rem) in two ways -- by exposure to radiation emanating from the ground and vegetation, and by exposure to radiation released in the spontaneous decay of radionuclides that have entered his body during the ingestion of locally grown foods. The latter process would account for some 90% of the dose; cesium-137 would be responsible for 0 90% of it. Since BARC's method of estimating dosage differs in some respects from that employed by the Lawrence Livermore National Laboratory (LLNL), (Ref.1, LLNL 1982) we are presenting our method in detail. The differences have two sources. First, the numbers used by BARC for the daily ingestion of radionuclides via the diet are higher than LLNL's. Second, BARC's calculation of dose from radionuclide intake utilizes the ICRP system. The net result is that BARC doses are consistently higher than LLNL doses, and in this respect are more conservative.

Radiation dosage

International Nuclear Information System (INIS)

Finston, Roland

1986-01-01

Radiation dosage at Bikini Atoll is the result of current soil contamination, a relic of the nuclear weapons testing program of some 30 years ago. The principal contaminants today and some of their physical properties are listed: cesium-137, strontium-90, plutonium -239, 240 and americium-241. Cobalt-60 contributes less than 1 to the dose and is not considered significant. A resident of the atoll would accumulate radiation dose (rem) in two ways -- by exposure to radiation emanating from the ground and vegetation, and by exposure to radiation released in the spontaneous decay of radionuclides that have entered his body during the ingestion of locally grown foods. The latter process would account for some 90% of the dose; cesium-137 would be responsible for 0 90% of it. Since BARC's method of estimating dosage differs in some respects from that employed by the Lawrence Livermore National Laboratory (LLNL), (Ref.1, LLNL 1982) we are presenting our method in detail. The differences have two sources. First, the numbers used by BARC for the daily ingestion of radionuclides via the diet are higher than LLNL's. Second, BARC's calculation of dose from radionuclide intake utilizes the ICRP system. The net result is that BARC doses are consistently higher than LLNL doses, and in this respect are more conservative

Radiation dosage of various CT-methods in lung diagnostics

International Nuclear Information System (INIS)

Heinz-Peer, G.; Weninger, F.; Nowotny, R.; Herold, C.J.

1996-01-01

Introduction of the computed tomography index CTDI and the multiple scan average dose (MSAD) has led to standardization of the dose description in CT examinations. Despite the use of these dose parameters, many different dosages are reported in the literature for different CT methods. In addition, there is still a wide range of radiation dosimetry results reported for conventional CT, helical CT, and HRCT used in chest examinations. The variations in dosage are mainly due to difference in factors affecting the dose, i.e. beam geometry, beam quality, scanner geometry ('generation'), and operating parameters. In addition, CT dosimetry instrumentation and methodology make a contribution to dosages. Recent studies calculating differences in factors affecting dosage and CT dosimetry and using similar operating parameters, show similar results in CT dosimetry for conventional and helical CT. On the other hand, dosages for HRCT were greatly reduced. This was mainly caused by narrow beam collimation and increasing section spacing. (orig.) [de

Understanding the glass-forming ability of active pharmaceutical ingredients for designing supersaturating dosage forms.

Science.gov (United States)

Kawakami, Kohsaku; Usui, Toshinori; Hattori, Mitsunari

2012-09-01

Amorphous solid dispersions have great potential for enhancing oral absorption of poorly soluble drugs. Crystallization behavior during storage and after exposure to aqueous media must be examined in detail for designing stable and effective amorphous formulations, and it is significantly affected by the intrinsic properties of an amorphous drug. Many attempts have been made to correlate various thermodynamic parameters of pharmaceutical glasses with their crystallization behavior; however, variations in model drugs that could be used for such investigation has been limited because the amorphous characteristics of drugs possessing a high crystallization tendency are difficult to evaluate. In this study, high-speed differential scanning calorimetry, which could inhibit their crystallization using high cooling rates up to 2000°C/s, was employed for assessing such drugs. The thermodynamic parameters of the glasses, including glass transition temperature (T(g)) and fragility, were obtained to show that their crystallization tendency cannot be explained simply by the parameters, although there have been general thought that fragility may be correlated with crystallization tendency. Also investigated was correlation between the thermodynamic parameters and crystallization tendency upon contact with water, which influences in vivo efficacy of amorphous formulations. T(g) was correlated well with the crystallization tendency upon contact with water. Copyright © 2012 Wiley Periodicals, Inc.

Hydraulic Modular Dosaging Systems for Machine Drives

Directory of Open Access Journals (Sweden)

A. J. Kotlobai

2005-01-01

Full Text Available The justified principle of making modular dosaging systems for positive-displacement multimotor hydraulic drives used in running gear and technological equipment of mobile construction, road and agricultural machines makes it possible to synchronize motion of running parts. The examples of the realization of modular dosaging systems and an algorithm of their operation are given in the paper.

[Benefits and usability of a pharmaceutical record in medical practice. A survey of hospital doctors and pharmacists (MATRIX study)].

Science.gov (United States)

Schuers, M; Timsit, M; Gillibert, A; Fred, A; Griffon, N; Bénichou, J; Darmoni, S J; Staccini, P

2016-09-01

To evaluate the impact of the pharmaceutical patient record use in emergency, geriatric and anaesthesia and intensive care departments, an experimentation was launched in 2013 in 55 hospitals. The purpose of the study was to assess the opinions of physicians and pharmacists about the benefits and usability of the patient pharmaceutical record. An e-mailed self-administered questionnaire was sent to all the pharmacists, anaesthesiologists, geriatricians and emergency physicians of the 55 hospitals involved in the patient pharmaceutical record experimentation. The questionnaire assessed the usability of the patient pharmaceutical record using the "System Usability Scale", as well as its use, its benefits and limitations perceived in clinical practice, and overall user satisfaction. Questionnaires were collected from November 2014 to January 2015. Ninety-six questionnaires were collected, from 47 hospitals, representing 86% of the hospitals involved in the experimentation. The patient pharmaceutical record was effectively operational in 36 hospitals. Data from 73 questionnaires filled by physicians and pharmacists with potential experience with the patient pharmaceutical record were used for evaluation. Forty-two respondents were pharmacists (57%) and 31 were physicians (43%), including 13 geriatricians, 11 emergency physicians and 7 anaesthesiologists. Patient pharmaceutical record overall usability score was 62.5 out of 100. It did not vary with the profession or seniority of the respondent. It was positively correlated with the frequency of use. More than half of respondents reported that they never or uncommonly used the patient pharmaceutical record. The length of access to data period was considered as insufficient. Main obstacles to more utilization of the patient pharmaceutical record were the lack of information about the dosage of dispensed drugs, the low number of patients in possession of their health card and the low number of patients with an activated

Decomposition of persistent pharmaceuticals in wastewater by ionizing radiation

Science.gov (United States)

Kimura, Atsushi; Osawa, Misako; Taguchi, Mitsumasa

2012-09-01

Pharmaceuticals in wastewater were treated by the combined method of activated sludge and ionizing radiation in laboratory scale. Oseltamivir, aspirin, and ibuprofen at 5 μmol dm-3 in wastewater were decomposed by the activated sludge at reaction time for 4 h. Carbamazepine, ketoprofen, mefenamic acid, clofibric acid, and diclofenac were not biodegraded completely, but were eliminated by γ-ray irradiation at 2 kGy. The rate constants of the reactions of these pharmaceuticals with hydroxyl radicals were estimated by the competition reaction method to be 4.0-10×109 mol-1 dm3 s-1. Decompositions of the pharmaceuticals in wastewater by ionizing radiation were simulated by use of the rate constants and the amount of total organic carbon as parameters. Simulation curves of concentrations of these pharmaceuticals as a function of dose described the experimental data, and the required dose for the elimination of them in wastewater by ionizing radiation can be estimated by this simulation.

Incomplete sex chromosome dosage compensation in the Indian meal moth, Plodia interpunctella, based on de novo transcriptome assembly.

Science.gov (United States)

Harrison, Peter W; Mank, Judith E; Wedell, Nina

2012-01-01

Males and females experience differences in gene dose for loci in the nonrecombining region of heteromorphic sex chromosomes. If not compensated, this leads to expression imbalances, with the homogametic sex on average exhibiting greater expression due to the doubled gene dose. Many organisms with heteromorphic sex chromosomes display global dosage compensation mechanisms, which equalize gene expression levels between the sexes. However, birds and Schistosoma have been previously shown to lack chromosome-wide dosage compensation mechanisms, and the status in other female heterogametic taxa including Lepidoptera remains unresolved. To further our understanding of dosage compensation in female heterogametic taxa and to resolve its status in the lepidopterans, we assessed the Indian meal moth, Plodia interpunctella. As P. interpunctella lacks a complete reference genome, we conducted de novo transcriptome assembly combined with orthologous genomic location prediction from the related silkworm genome, Bombyx mori, to compare Z-linked and autosomal gene expression levels for each sex. We demonstrate that P. interpunctella lacks complete Z chromosome dosage compensation, female Z-linked genes having just over half the expression level of males and autosomal genes. This finding suggests that the Lepidoptera and possibly all female heterogametic taxa lack global dosage compensation, although more species will need to be sampled to confirm this assertion.

One- and two-stage Arrhenius models for pharmaceutical shelf life prediction.

Science.gov (United States)

Fan, Zhewen; Zhang, Lanju

2015-01-01

One of the most challenging aspects of the pharmaceutical development is the demonstration and estimation of chemical stability. It is imperative that pharmaceutical products be stable for two or more years. Long-term stability studies are required to support such shelf life claim at registration. However, during drug development to facilitate formulation and dosage form selection, an accelerated stability study with stressed storage condition is preferred to quickly obtain a good prediction of shelf life under ambient storage conditions. Such a prediction typically uses Arrhenius equation that describes relationship between degradation rate and temperature (and humidity). Existing methods usually rely on the assumption of normality of the errors. In addition, shelf life projection is usually based on confidence band of a regression line. However, the coverage probability of a method is often overlooked or under-reported. In this paper, we introduce two nonparametric bootstrap procedures for shelf life estimation based on accelerated stability testing, and compare them with a one-stage nonlinear Arrhenius prediction model. Our simulation results demonstrate that one-stage nonlinear Arrhenius method has significant lower coverage than nominal levels. Our bootstrap method gave better coverage and led to a shelf life prediction closer to that based on long-term stability data.

Enhanced Quality Control in Pharmaceutical Applications by Combining Raman Spectroscopy and Machine Learning Techniques

Science.gov (United States)

Martinez, J. C.; Guzmán-Sepúlveda, J. R.; Bolañoz Evia, G. R.; Córdova, T.; Guzmán-Cabrera, R.

2018-06-01

In this work, we applied machine learning techniques to Raman spectra for the characterization and classification of manufactured pharmaceutical products. Our measurements were taken with commercial equipment, for accurate assessment of variations with respect to one calibrated control sample. Unlike the typical use of Raman spectroscopy in pharmaceutical applications, in our approach the principal components of the Raman spectrum are used concurrently as attributes in machine learning algorithms. This permits an efficient comparison and classification of the spectra measured from the samples under study. This also allows for accurate quality control as all relevant spectral components are considered simultaneously. We demonstrate our approach with respect to the specific case of acetaminophen, which is one of the most widely used analgesics in the market. In the experiments, commercial samples from thirteen different laboratories were analyzed and compared against a control sample. The raw data were analyzed based on an arithmetic difference between the nominal active substance and the measured values in each commercial sample. The principal component analysis was applied to the data for quantitative verification (i.e., without considering the actual concentration of the active substance) of the difference in the calibrated sample. Our results show that by following this approach adulterations in pharmaceutical compositions can be clearly identified and accurately quantified.

Micellar HPLC and derivative spectrophotometric methods for the simultaneous determination of fluconazole and tinidazole in pharmaceuticals and biological fluids.

Science.gov (United States)

Belal, F; Sharaf El-Din, M K; Eid, M I; El-Gamal, R M

2014-04-01

Micellar high-performance liquid chromatography (HPLC) and first-derivative ultraviolet spectrophotometry were used to simultaneously determine fluconazole (FLZ) and tinidazole (TNZ) in combined pharmaceutical dosage forms. The derivative procedure is based on the linear relationship between the drug concentration and the first derivative amplitudes at 220 and 288 nm for FLZ and TNZ, respectively. The calibration graphs were linear in the range of 1.5-9.0 µg/mL for FLZ and 10.0-60.0 µg/mL for TNZ. Furthermore, an HPLC procedure with ultraviolet detection at 210 nm was developed. For the HPLC procedure, good chromatographic separation was achieved using an ODS C18 column (250 × 4.6 mm i.d.). The mobile phase containing 0.15M sodium dodecyl sulphate, 0.3% triethylamine and 12% n-propanol in 0.02M orthophosphoric acid at pH 5.5 was pumped at a flow rate of 1 mL/min. Indapamide was used as an internal standard. The method showed good linearity over the concentration ranges of 1.5-30.0 and 10.0-200.0 µg/mL, with limits of detection of 0.36 and 2.70 µg/mL and limits of quantification of 1.1 and 8.2 µg/mL for FLZ and TNZ, respectively. The suggested methods were successfully applied for the simultaneous analysis of the drugs in their laboratory prepared mixture, co-formulated tablet and single dosage forms. Moreover the second method was also extended to the determination of the drugs in biological fluids.

Indirect potentiometric titration of ascorbic acid in pharmaceutical preparations using copper based mercury film electrode.

Science.gov (United States)

Abdul Kamal Nazer, Meeran Mohideen; Hameed, Abdul Rahman Shahul; Riyazuddin, Patel

2004-01-01

A simple and rapid potentiometric method for the estimation of ascorbic acid in pharmaceutical dosage forms has been developed. The method is based on treating ascorbic acid with iodine and titration of the iodide produced equivalent to ascorbic acid with silver nitrate using Copper Based Mercury Film Electrode (CBMFE) as an indicator electrode. Interference study was carried to check possible interference of usual excipients and other vitamins. The precision and accuracy of the method was assessed by the application of lack-of-fit test and other statistical methods. The results of the proposed method and British Pharmacopoeia method were compared using F and t-statistical tests of significance.

21 CFR 526.1696 - Penicillin intramammary dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin intramammary dosage forms. 526.1696 Section 526.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS INTRAMAMMARY DOSAGE FORMS § 526.1696 Penicillin...

Taking the lead from our colleagues in medical education: the use of images of the in-vivo setting in teaching concepts of pharmaceutical science.

Science.gov (United States)

Curley, Louise E; Kennedy, Julia; Hinton, Jordan; Mirjalili, Ali; Svirskis, Darren

2017-01-01

Despite pharmaceutical sciences being a core component of pharmacy curricula, few published studies have focussed on innovative methodologies to teach the content. This commentary identifies imaging techniques which can visualise oral dosage forms in-vivo and observe formulation disintegration in order to achieve a better understanding of in-vivo performance. Images formed through these techniques can provide students with a deeper appreciation of the fate of oral formulations in the body compared to standard disintegration and dissolution testing, which is conducted in-vitro. Such images which represent the in-vivo setting can be used in teaching to give context to both theory and experimental work, thereby increasing student understanding and enabling teaching of pharmaceutical sciences supporting students to correlate in-vitro and in-vivo processes.

High-throughput prediction of tablet weight and trimethoprim content of compound sulfamethoxazole tablets for controlling the uniformity of dosage units by NIR.

Science.gov (United States)

Dong, Yanhong; Li, Juan; Zhong, Xiaoxiao; Cao, Liya; Luo, Yang; Fan, Qi

2016-04-15

This paper establishes a novel method to simultaneously predict the tablet weight (TW) and trimethoprim (TMP) content of compound sulfamethoxazole tablets (SMZCO) by near infrared (NIR) spectroscopy with partial least squares (PLS) regression for controlling the uniformity of dosage units (UODU). The NIR spectra for 257 samples were measured using the optimized parameter values and pretreated using the optimized chemometric techniques. After the outliers were ignored, two PLS models for predicting TW and TMP content were respectively established by using the selected spectral sub-ranges and the reference values. The TW model reaches the correlation coefficient of calibration (R(c)) 0.9543 and the TMP content model has the R(c) 0.9205. The experimental results indicate that this strategy expands the NIR application in controlling UODU, especially in the high-throughput and rapid analysis of TWs and contents of the compound pharmaceutical tablets, and may be an important complement to the common NIR on-line analytical method for pharmaceutical tablets. Copyright © 2016 Elsevier B.V. All rights reserved.

GENE-dosage effects on fitness in recent adaptive duplications: ace-1 in the mosquito Culex pipiens.

Science.gov (United States)

Labbé, Pierrick; Milesi, Pascal; Yébakima, André; Pasteur, Nicole; Weill, Mylène; Lenormand, Thomas

2014-07-01

Gene duplications have long been advocated to contribute to the evolution of new functions. The role of selection in their early spread is more controversial. Unless duplications are favored for a direct benefit of increased expression, they are likely detrimental. In this article, we investigated the case of duplications favored because they combine already functionally divergent alleles. Their gene-dosage/fitness relations are poorly known because selection may operate on both overall expression and duplicates relative dosage. Using the well-documented case of Culex pipiens resistance to insecticides, we compared strains with various ace-1 allele combinations, including two duplicated alleles carrying both susceptible and resistant copies. The overall protein activity was nearly additive, but, surprisingly, fitness correlated better with the relative proportion of susceptible and resistant copies rather than any absolute measure of activity. Gene dosage is thus crucial, duplications stabilizing a "heterozygote" phenotype. It corroborates the view that these were favored because they fix a permanent heterosis, thereby solving the irreducible trade-off between resistance and synaptic transmission. Moreover, we showed that the contrasted successes of the two duplicated alleles in natural populations depend on genetic changes unrelated to ace-1, confirming the probable implication of recessive sublethal mutations linked to structural rearrangements in some duplications. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Effects of soil properties on the uptake of pharmaceuticals into earthworms

International Nuclear Information System (INIS)

Carter, Laura J.; Ryan, Jim J.; Boxall, Alistair B.A.

2016-01-01

Pharmaceuticals can enter the soil environment when animal slurries and sewage sludge are applied to land as a fertiliser or during irrigation with contaminated water. These pharmaceuticals may then be taken up by soil organisms possibly resulting in toxic effects and/or exposure of organisms higher up the food chain. This study investigated the influence of soil properties on the uptake and depuration of pharmaceuticals (carbamazepine, diclofenac, fluoxetine and orlistat) in the earthworm Eisenia fetida. The uptake and accumulation of pharmaceuticals into E. fetida changed depending on soil type. Orlistat exhibited the highest pore water based bioconcentration factors (BCFs) and displayed the largest differences between soil types with BCFs ranging between 30.5 and 115.9. For carbamazepine, diclofenac and fluoxetine BCFs ranged between 1.1 and 1.6, 7.0 and 69.6 and 14.1 and 20.4 respectively. Additional analysis demonstrated that in certain treatments the presence of these chemicals in the soil matrices changed the soil pH over time, with a statistically significant pH difference to control samples. The internal pH of E. fetida also changed as a result of incubation in pharmaceutically spiked soil, in comparison to the control earthworms. These results demonstrate that a combination of soil properties and pharmaceutical physico-chemical properties are important in terms of predicting pharmaceutical uptake in terrestrial systems and that pharmaceuticals can modify soil and internal earthworm chemistry which may hold wider implications for risk assessment. - Highlights: • Uptake of pharmaceuticals into earthworms is influenced by soil parameters. • Presence of pharmaceuticals in the terrestrial environment influences soil pH. • Uptake of pharmaceuticals by earthworms changes internal earthworm pH. - The uptake of pharmaceuticals into soil invertebrates is dependent on the complex interplay between pharmaceutical physico-chemical properties and soil

Purifying Selection Maintains Dosage-Sensitive Genes during Degeneration of the Threespine Stickleback Y Chromosome

Science.gov (United States)

White, Michael A.; Kitano, Jun; Peichel, Catherine L.

2015-01-01

Sex chromosomes are subject to unique evolutionary forces that cause suppression of recombination, leading to sequence degeneration and the formation of heteromorphic chromosome pairs (i.e., XY or ZW). Although progress has been made in characterizing the outcomes of these evolutionary processes on vertebrate sex chromosomes, it is still unclear how recombination suppression and sequence divergence typically occur and how gene dosage imbalances are resolved in the heterogametic sex. The threespine stickleback fish (Gasterosteus aculeatus) is a powerful model system to explore vertebrate sex chromosome evolution, as it possesses an XY sex chromosome pair at relatively early stages of differentiation. Using a combination of whole-genome and transcriptome sequencing, we characterized sequence evolution and gene expression across the sex chromosomes. We uncovered two distinct evolutionary strata that correspond with known structural rearrangements on the Y chromosome. In the oldest stratum, only a handful of genes remain, and these genes are under strong purifying selection. By comparing sex-linked gene expression with expression of autosomal orthologs in an outgroup, we show that dosage compensation has not evolved in threespine sticklebacks through upregulation of the X chromosome in males. Instead, in the oldest stratum, the genes that still possess a Y chromosome allele are enriched for genes predicted to be dosage sensitive in mammals and yeast. Our results suggest that dosage imbalances may have been avoided at haploinsufficient genes by retaining function of the Y chromosome allele through strong purifying selection. PMID:25818858

Development and Validation of a Stability-Indicating RP-HPLC Method for Rapid Determination of Doxycycline in Pharmaceutical Bulk and Dosage Forms

OpenAIRE

Shabnam Pourmoslemi, Soroush Mirfakhraee, Saeid Yaripour, Ali Mohammadi

2016-01-01

Background: A rapid stability-indicating RP-HPLC method for analysis of doxycycline in the presence of its degradation products was developed and validated. Methods: Forced degradation studies were carried out on bulk samples and capsule dosage forms of doxycycline using acid, base, H2O2, heat, and UV light as described by ICH for stress conditions to demonstrate the stability-indicating power of the method. Separations were performed on a Perfectsil® Target ODS column (3-5µm, 125 mm×4 mm), u...

Development and Validation of UV Spectrophotometric Method For Determination of Bisoprolol Fumarate in Bulk and Pharmaceutical Dosage Forms

Directory of Open Access Journals (Sweden)

Shahinaz Mohammed

2017-10-01

Full Text Available In this study a simple, accurate and precise UV- spectrophotometric method was developed for the estimation of bisoprolol fumarate (BF in bulk and tablet dosage form. The method was based on measurement of absorbance of BF aqueous solution at 225 nm. Validation was conducted in accordance to ICH guidelines. The calibration curve was linear in the concentration range 5.0-30.0 µg/mL with correlation coefficient not less than 0.996. The limit of detection and limit of quantification were 0.22 μg/ml and 0.66 μg/ml, respectively. Intraday and intermediate precision of the developed method were reflected by the low RSD% values (1.19 and 0.854, respectively. The recovery percentage was 100.6 ± 0.6%, n=3. The proposed method was applied for the assay of BF in three different brands.

Biowaiver monograph for immediate-release solid oral dosage forms: acetylsalicylic acid.

Science.gov (United States)

Dressman, Jennifer B; Nair, Anita; Abrahamsson, Bertil; Barends, Dirk M; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James E; Shah, Vinod P; Zimmer, Markus

2012-08-01

A biowaiver monograph for acetylsalicylic acid (ASA) is presented. Literature and experimental data indicate that ASA is a highly soluble and highly permeable drug, leading to assignment of this active pharmaceutical ingredient (API) to Class I of the Biopharmaceutics Classification System (BCS). Limited bioequivalence (BE) studies reported in the literature indicate that products that have been tested are bioequivalent. Most of the excipients used in products with a marketing authorization in Europe are not considered to have an impact on gastrointestinal motility or permeability. Furthermore, ASA has a wide therapeutic index. Thus, the risks to the patient that might occur if a nonbioequivalent product were to be incorrectly deemed bioequivalent according to the biowaiver procedure appear to be minimal. As a result, the BCS-based biowaiver procedure can be recommended for approval of new formulations of solid oral dosage forms containing ASA as the only API, including both multisource and reformulated products, under the following conditions: (1) excipients are chosen from those used in ASA products already registered in International Conference on Harmonization and associated countries and (2) the dissolution profiles of the test and the comparator products comply with the BE guidance. Copyright © 2012 Wiley Periodicals, Inc.

21 CFR 520.1696 - Penicillin oral dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin oral dosage forms. 520.1696 Section 520.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1696 Penicillin oral...

21 CFR 520.45 - Albendazole oral dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Albendazole oral dosage forms. 520.45 Section 520.45 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.45 Albendazole oral...

Development and Validation of a Stability-Indicating RP-HPLC Method for Rapid Determination of Doxycycline in Pharmaceutical Bulk and Dosage Forms

Directory of Open Access Journals (Sweden)

Shabnam Pourmoslemi, Soroush Mirfakhraee, Saeid Yaripour, Ali Mohammadi

2016-06-01

Full Text Available Background: A rapid stability-indicating RP-HPLC method for analysis of doxycycline in the presence of its degradation products was developed and validated. Methods: Forced degradation studies were carried out on bulk samples and capsule dosage forms of doxycycline using acid, base, H2O2, heat, and UV light as described by ICH for stress conditions to demonstrate the stability-indicating power of the method. Separations were performed on a Perfectsil® Target ODS column (3-5µm, 125 mm×4 mm, using a mobile phase consisting of methanol-50 mM ammonium acetate buffer (containing 0.1% v/v trifluoroacetic acid and 0.1% v/v triethylamine, pH 2.5 (50:50 v/v at room temperature. The flow rate was 0.8 mL/min. Results: The method linearity was investigated in the range of 25–500 µg/mL (r > 0.9999. The LOD and LOQ were 5 and 25 µg/mL, respectively. The method selectivity was evaluated by peak purity test using a diode array detector. There was no interference among detection of doxycycline and its stressed degradation products. Total peak purity numbers were in the range of 0.94-0.99, indicating the homogeneity of DOX peaks. Conclusion: These data show the stability-indicating nature of the method for quality control of doxycycline in bulk samples and capsule dosage forms.

Utility of Hantzsch reaction for development of highly sensitive spectrofluorimetric method for determination of alfuzosin and terazosin in bulk, dosage forms and human plasma.

Science.gov (United States)

Hammad, Mohamed A; Omar, Mahmoud A; Salman, Baher I

2017-09-01

A highly sensitive, cheap, simple and accurate spectrofluorimetric method has been developed and validated for the determination of alfuzosin hydrochloride and terazosin hydrochloride in their pharmaceutical dosage forms and in human plasma. The developed method is based on the reaction of the primary amine moiety in the studied drugs with acetylacetone and formaldehyde according to the Hantzsch reaction, producing yellow fluorescent products that can be measured spectrofluorimetrically at 480 nm after excitation at 415 nm. Different experimental parameters affecting the development and stability of the reaction products were carefully studied and optimized. The fluorescence-concentration plots of alfuzosin and terazosin were rectilinear over a concentration range of 70-900 ng ml -1 , with quantitation limits 27.1 and 32.2 ng ml -1 for alfuzosin and terazosin, respectively. The proposed method was validated according to ICH guidelines and successfully applied to the analysis of the investigated drugs in dosage forms, content uniformity test and spiked human plasma with high accuracy. Copyright © 2017 John Wiley & Sons, Ltd.

Pharmaceutical optimization of lipid-based dosage forms for the improvement of taste-masking, chemical stability and solubilizing capacity of phenobarbital.

Science.gov (United States)

Monteagudo, Ezequiel; Langenheim, Mariana; Salerno, Claudia; Buontempo, Fabián; Bregni, Carlos; Carlucci, Adriana

2014-06-01

Microemulsions (MEs) and self-emulsifying drug delivery systems (SEEDS) containing phenobarbital (Phe) were developed to improve its chemical stability, solubilizing capacity and taste-masking in oral liquid dosage forms. Cremophor® RH40 and Labrasol® were used as surfactants for the screening of ME regions, Capmul® MCM L, Captex® 355, Imwitor® 408, Myglyol® 840 and Isopropyl myristate were the oil phases assayed; Transcutol® P, Polyethylene-glycol 400, glycerol, Propylene-glycol and ethanol the cosurfactants. Phe stability assay was carried out (20:4:20:56% and 20:4:35:41% (w/w); surfactant:oily phase:cosurfactant:water) for both surfactants; only one containing ethanol showed significant dismissing in its drug content. Solubility capacity for these selected formulations were also evaluated, an amount between 17 and 58 mg/mL of Phe could be loaded. At last, an optimized ME formulation with Cremophor® RH40 20%, Capmul® MCM L 4%, PEG 400 35% and sucralose 2% (w/w) was chosen in order to optimize taste-masking using an electronic tongue. Strawberry along with banana and tutti-frutti flavors plus mint flavor proved to be the best ones. Labrasol-based pre-concentrates were tested for (micro)emulsifying properties; all of them resulted to behave as SEDDS. In summary, a rationale experimental design conducted to an optimized ME for Phe oral pediatric administration which was able to load 5-fold times the currently used dose (4 mg/mL), with no sign of physical or chemical instability and with improved taste; SEDDS for capsule filling were also obtained. The biopharmaceutical advantages described for these dosage forms encourage furthering in vivo evaluation.

Combined electrocoagulation and TiO2 photoassisted treatment applied to wastewater effluents from pharmaceutical and cosmetic industries

International Nuclear Information System (INIS)

Boroski, Marcela; Rodrigues, Angela Claudia; Garcia, Juliana Carla; Sampaio, Luiz Carlos; Nozaki, Jorge; Hioka, Noboru

2009-01-01

The treated wastewater consists of refractory materials and high organic content of hydrolyzed peptone residues from pharmaceutical factory. The combination of electrocoagulation (EC) followed by heterogeneous photocatalysis (TiO 2 ) conditions was maximized. The EC: iron cathode/anode (12.50 cm x 2.50 cm x 0.10 cm), current density 763 A m -2 , 90 min and initial pH 6.0. As EC consequence, the majority of the dissolved organic and suspended material was removed (about 91% and 86% of the turbidity and chemical oxygen demand (COD), respectively). After EC, refractory residues still remained in the effluent. The subsequent photocatalysis: UV/TiO 2 /H 2 O 2 (mercury lamps), pH 3.0, 4 h irradiation, 0.25 g L -1 TiO 2 and 10 mmol L -1 H 2 O 2 shows high levels of inorganic and organic compounds eliminations. The obtained COD values: 1753 mg L -1 for the sample from the factory, 160 mg L -1 after EC and 50 mg L -1 after EC/photocatalyzed effluents pointed out that the combined treatment stresses this water purification

Predicting AEA dosage by Foam Index and adsorption on Fly Ash

OpenAIRE

Jacobsen, Stefan; Ollendorff, Margrethe; Geiker, Mette Rica; Tunstall, Lori; Scherer, George W.

2012-01-01

Abstract: The unpredictable air entrainment in fly ash concrete caused by carbon in fly ash was studied by measuring adsorption of Air Entraining Agents (AEA) on the fly ash and by Foam Index (FI) testing. The FI test measures the mass ratio of AEA/binder required to obtain stable foam when shaking a mixture of water, binder powder and AEA, while increasing AEA-dosage stepwise. A review of concrete air entrainment and new studies combining adsorption (TGA, NMR) of AEA on fly ash with various ...

Determination of Tannin and Saponin Dosage for Defaunation Improvement Feed Fermentability

OpenAIRE

Wahyuni, I.M. D; Muktiani, A; Christianto, M

2014-01-01

The research was conducted to evaluate the effect of addition of tannin, saponin or combination of tannin and saponin to the concentrate of the ration on the microbial population and fermentability of feed in vitro and to assess the best dosage of uses. The research was arranged according to completely randomized design with four treatments and 3 replications. The treatments were ration without tannin and saponin (T0), ration with 1.2% saponin (T1), ration with 0.5% tannin and 0.9% saponin (T...

Extraction and characterization of artocarpus integer gum as pharmaceutical excipient.

Science.gov (United States)

Farooq, Uzma; Malviya, Rishabha; Sharma, Pramod Kumar

2014-01-01

Natural polymers are widely used as excipients in pharmaceutical formulations. They are easily available, cheap and less toxic as compared to synthetic polymers. This study involves the extraction and characterization of kathal (Artocarpus integer) gum as a pharmaceutical excipient. Water was used as a solvent for extraction of the natural polymer. Yield was calculated with an aim to evaluate the efficacy of the process. The product was screened for the presence of Micrometric properties, and swelling index, flow behavior, surface tension, and viscosity of natural polymers were calculated. Using a water based extraction method, the yield of gum was found to be 2.85%. Various parameters such as flow behavior, organoleptic properties, surface tension, viscosity, loss on drying, ash value and swelling index together with microscopic studies of particles were done to characterize the extracted gum. The result showed that extracted kathal gum exhibited excellent flow properties. The gum was investigated for purity by carrying out chemical tests for different phytochemical constituents and only carbohydrates were found to be present. It had a good swelling index (13 ± 1). The pH and surface tension of the 1% gum solution were found to be 6 ± 0.5 and 0.0627 J/m2, respectively. The ash values such as total ash, acid insoluble ash, and water soluble ash were found to be 18.9%, 0.67% and 4% respectively. Loss on drying was 6.61%. The extracted gum was soluble in warm water and insoluble in organic solvents. The scanning electron micrograph (SEM) revealed rough and irregular particles of the isolated polymer. The results of the evaluated properties showed that kathal-derived gum has acceptable pH and organoleptic properties and can be used as a pharmaceutical excipient to formulate solid oral dosage forms.

beta. -Amyloid gene dosage in Alzheimer's disease

Energy Technology Data Exchange (ETDEWEB)

Murdoch, G H; Manuelidis, L; Kim, J H; Manuelidis, E E

1988-01-11

The 4-5 kd amyloid ..beta..-peptide is a major constituent of the characteristic amyloid plaque of Alzheimer's disease. It has been reported that some cases of sporatic Alzheimer's disease are associated with at least a partial duplication of chromosome 21 containing the gene corresponding to the 695 residue precursor of this peptide. To contribute to an understanding of the frequency to such a duplication event in the overall Alzheimer's population, the authors have determined the gene dosage of the ..beta..-amyloid gene in this collection of cases. All cases had a clinical diagnosis of Alzheimer's confirmed neuropathologically. Each Alzheimer's case had an apparent normal diploid ..beta..-amyloid gene dosage, while control Down's cases had the expected triploid dosage. Thus partial duplication of chromosome 21 may be a rare finding in Alzheimer's disease. Similar conclusions were just reported in several studies of the Harvard Alzheimer collection.

21 CFR 524.1662 - Oxytetracycline hydrochloride ophthalmic and topical dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride ophthalmic and topical dosage forms. 524.1662 Section 524.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... DOSAGE FORM NEW ANIMAL DRUGS § 524.1662 Oxytetracycline hydrochloride ophthalmic and topical dosage forms. ...

Using design science research to develop online enhanced pharmaceutical care services.

Science.gov (United States)

Lapão, Luís Velez; Gregório, João; Mello, Diogo; Cavaco, Afonso; Mira Da Silva, Miguel; Lovis, Christian

2014-01-01

The ePharmaCare project aims at assessing the potential of eHealth services for the provision of pharmaceutical services interacting actively with patients. The results presented here focus on the first three steps of Design Science Research Methodology. A mixed methods approach was used with an online survey to collect data on use of information technologies in community pharmacy, followed by an exploratory observational time and business processes study, which use the shadowing method to identify and assess the opportunity to lunch online services. Combining this with the Service Experiment Blueprint and the Dáder method an enhanced pharmaceutical service was designed. Next, an artifact is developed and a prototype is implemented to demonstrate the value of online pharmaceutical services' delivery. This new service could represent a new perspective for pharmaceutical services integration within the health system.

Performance Evaluation of Ozonation Combined with Persulfate Application for Removal of Furfural from Aqueous Solutions

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Alireza Rahmani

2017-03-01

Full Text Available Background: Furfural is an organic compound which derived from a variety industrial, including petrochemicals, pulping, pharmaceutical, food. Also is a main agent in many industries and aromatic organic compounds entrance in the environment. There are several methods of treating including physical, chemical, biological and physicochemical for remove this matter. Among advanced oxidation methods can be combined ozonation process with persulfate catalytic are noted. The purpose of this study was to evaluate the efficiency of ozonation process with the use of persulfate in removal furfural from aqueous solution. Materials and Methods: In this study, the efficiency of the process with a concentration furfural 5 to 30 mg/L, concentration persulfate 4 to 15 mM, pH = 3-11 and reaction time of 35 minutes in the semi-continuous reactor with a capacity of one liter was obtained. Results: The results of this study have been shown in  conditions of operation optimal , pH =,3 persulfate dosage 12 mM, ozone dosage of 1 g/min and the initial concentration of furfural  5 mg/L, this process is capable  remove of %93/34 percent Furfural and %70 of the initial COD. Conclusion: The results of this study showed that the ozone/persulfate process can be a suitable process for the removal of organic aromatic compounds including pollutants of interest.

Unlicensed pharmaceutical preparations for clinical patient care: Ensuring safety.

Science.gov (United States)

de Wilde, Sofieke; de Jong, Maria G H; Le Brun, Paul P H; Guchelaar, Henk-Jan; Schimmel, Kirsten J M

2018-01-01

Most medicinal products dispensed to patients have marketing authorization (MA) to ensure high quality of the product, safety, and efficacy. However, in daily practice, to treat patients adequately, there is a medical need for drugs that do not hold MA. To meet this medical need, medicinal products are used in clinical care without MA (unlicensed), such as products prepared by (local) pharmacies: the pharmaceutical preparations. Three types of pharmaceutical preparations are distinguished: (i) reconstitution in excess of summary of product characteristics; (ii) adaptation of a licensed medicinal product (outside its official labeling); (iii) medicinal products from an active pharmaceutical ingredient. Although unlicensed, patients may expect the same quality for these unlicensed pharmaceutical preparations as for the licensed medicinal products. To assure this quality, a proper risk-benefit assessment and proper documentation in (centralized) patient registries and linking to a national pharmacovigilance database should be in place. Based on a risk assessment matrix, requirements for quality assurance can be determined, which has impact on the level of documentation of a pharmaceutical preparation. In this paper, the approach for good documentation including quality assurance and benefit-risk assessment will be discussed and possibilities for patient registries are described to make these crucial preparations available for regular patient care. KEY POINTS Ensuring pharmaceutical quality and performing a proper benefit-risk assessment will guarantee safe use of pharmaceutical preparations. Good documentation of (ultra-)orphan treatments can be collected in centralized patient registries and should be combined with existing information in (inter)national databases and self-reflection of patients. Linking patient registries to a centralized database for adverse drug events is highly recommended as it increases safety control of the (ultra) orphan pharmaceutical

Elimination of pharmaceutical residues in biologically pre-treated hospital wastewater using advanced UV irradiation technology: A comparative assessment

Energy Technology Data Exchange (ETDEWEB)

Koehler, C., E-mail: christian.koehler@tudor.lu [Public Research Centre Henri Tudor/Resource Centre for Environmental Technologies, 66 rue de Luxembourg, BP 144, L-4002 Esch-sur-Alzette (Luxembourg); Venditti, S.; Igos, E.; Klepiszewski, K.; Benetto, E.; Cornelissen, A. [Public Research Centre Henri Tudor/Resource Centre for Environmental Technologies, 66 rue de Luxembourg, BP 144, L-4002 Esch-sur-Alzette (Luxembourg)

2012-11-15

UV irradiation technology as a membrane bioreactor (MBR) post-treatment was investigated and assessed. Both UV low pressure (LP) and medium pressure (MP) lamps were examined. The technology was installed in a pilot plant treating hospital wastewater to provide the study with adequate field data. The effect of the UV irradiation was enhanced with varying dosages of H{sub 2}O{sub 2} to establish an advanced oxidation process (AOP). The efficiency of the pharmaceutical removal process was assessed by examining 14 micropollutants (antibiotics, analgesics, anticonvulsants, beta-blockers, cytostatics and X-ray contrast media) which are typically released by hospitals and detected with liquid chromatography coupled tandem mass spectrometry (LC-MS/MS). While the MBR treatment generally showed only a low degradation capacity for persistent pharmaceuticals, much better degradation was obtained by applying UV irradiation and H{sub 2}O{sub 2} as AOP. The 'conventional' cost-benefit analysis of the different technology options taking into account both electrical energy consumption and pharmaceutical removal efficiency, revealed clearly better performance of low pressure UV lamps as AOP. However, a holistic comparison between the different scenarios was carried out by evaluating their environmental impacts using the life cycle assessment (LCA) methodology. Decisive advantages were highlighted to include this approach in the decision making process.

Elimination of pharmaceutical residues in biologically pre-treated hospital wastewater using advanced UV irradiation technology: A comparative assessment

International Nuclear Information System (INIS)

Köhler, C.; Venditti, S.; Igos, E.; Klepiszewski, K.; Benetto, E.; Cornelissen, A.

2012-01-01

UV irradiation technology as a membrane bioreactor (MBR) post-treatment was investigated and assessed. Both UV low pressure (LP) and medium pressure (MP) lamps were examined. The technology was installed in a pilot plant treating hospital wastewater to provide the study with adequate field data. The effect of the UV irradiation was enhanced with varying dosages of H 2 O 2 to establish an advanced oxidation process (AOP). The efficiency of the pharmaceutical removal process was assessed by examining 14 micropollutants (antibiotics, analgesics, anticonvulsants, beta-blockers, cytostatics and X-ray contrast media) which are typically released by hospitals and detected with liquid chromatography coupled tandem mass spectrometry (LC–MS/MS). While the MBR treatment generally showed only a low degradation capacity for persistent pharmaceuticals, much better degradation was obtained by applying UV irradiation and H 2 O 2 as AOP. The “conventional” cost-benefit analysis of the different technology options taking into account both electrical energy consumption and pharmaceutical removal efficiency, revealed clearly better performance of low pressure UV lamps as AOP. However, a holistic comparison between the different scenarios was carried out by evaluating their environmental impacts using the life cycle assessment (LCA) methodology. Decisive advantages were highlighted to include this approach in the decision making process.

21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ketamine hydrochloride injectable dosage forms. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms. ...

Transport and deposition of cohesive pharmaceutical powders in human airway

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Wang Yuan

2017-01-01

Full Text Available Pharmaceutical powders used in inhalation therapy are in the size range of 1-5 microns and are usually cohesive. Understanding the cohesive behaviour of pharmaceutical powders during their transportation in human airway is significant in optimising aerosol drug delivery and targeting. In this study, the transport and deposition of cohesive pharmaceutical powders in a human airway model is simulated by a well-established numerical model which combines computational fluid dynamics (CFD and discrete element method (DEM. The van der Waals force, as the dominant cohesive force, is simulated and its influence on particle transport and deposition behaviour is discussed. It is observed that even for dilute particle flow, the local particle concentration in the oral to trachea region can be high and particle aggregation happens due to the van der Waals force of attraction. It is concluded that the deposition mechanism for cohesive pharmaceutical powders, on one hand, is dominated by particle inertial impaction, as proven by previous studies; on the other hand, is significantly affected by particle aggregation induced by van der Waals force. To maximum respiratory drug delivery efficiency, efforts should be made to avoid pharmaceutical powder aggregation in human oral-to-trachea airway.

Transport and deposition of cohesive pharmaceutical powders in human airway

Science.gov (United States)

Wang, Yuan; Chu, Kaiwei; Yu, Aibing

2017-06-01

Pharmaceutical powders used in inhalation therapy are in the size range of 1-5 microns and are usually cohesive. Understanding the cohesive behaviour of pharmaceutical powders during their transportation in human airway is significant in optimising aerosol drug delivery and targeting. In this study, the transport and deposition of cohesive pharmaceutical powders in a human airway model is simulated by a well-established numerical model which combines computational fluid dynamics (CFD) and discrete element method (DEM). The van der Waals force, as the dominant cohesive force, is simulated and its influence on particle transport and deposition behaviour is discussed. It is observed that even for dilute particle flow, the local particle concentration in the oral to trachea region can be high and particle aggregation happens due to the van der Waals force of attraction. It is concluded that the deposition mechanism for cohesive pharmaceutical powders, on one hand, is dominated by particle inertial impaction, as proven by previous studies; on the other hand, is significantly affected by particle aggregation induced by van der Waals force. To maximum respiratory drug delivery efficiency, efforts should be made to avoid pharmaceutical powder aggregation in human oral-to-trachea airway.

Investigation of contrast agent dosage for perfusion-weighted MRI

International Nuclear Information System (INIS)

Erb, G.; Benner, T.; Heiland, S.; Reith, W.; Sartor, K.; Forsting, M.

1997-01-01

Purpose: In this study we investigated, whether increasing the dosage of a paramagnetic contrast agent results in a stronger signal decrease in T 2 *-weighted perfusion sequences and therefore more meaningful parameter maps. Material and methods: In a prospective study bolus injection of gadolinium-DTPA was performed at dosages of 0.1, 0.2, and 0.3 mmol/kg body weight (BW) in 10 patients each. Before, during and after bolus injection 40 T 2 *-weighted images of a reference brain slice were acquired within 65.6 seconds on a 1.0 T clinical scanner and perfusion parameters were calculated. Results: Due to the limited signal decrease during bolus passage and the resulting low signal-difference-to-noise ratio (ΔS/N) no reliable differentiation of gray and white matter was possible at a contrast agent dosage of 0.1 mmol/kg BW. Only at higher dosages, both, signal decrease and ΔS/N were strong enough to allow differentiation of gray and white matter and to yield reliable parameter maps. Conclusion: For meaningful MR perfusion imaging at 1.0 T and with the given sequence a contrast agent dosage of at least 0.2 mmol/kg BW is necessary, if a 0.5-molar contrast agent is used. (orig.) [de

Separation and determination of impurities in paracetamol, codeine and pitophenone in the presence of fenpiverinium in combined suppository dosage form.

Science.gov (United States)

Vojta, Jiří; Hanzlík, Pavel; Jedlička, Aleš; Coufal, Pavel

2015-01-01

A new HPLC method for separation and determination of impurities in paracetamol, codeine phosphate hemihydrate and pitophenone hydrochloride in the presence of fenpiverinium bromide in combined suppository dosage form was developed and validated. The separation of paracetamol and its impurities 4-aminophenol, 4-nitrophenol, 4-chloracetanilid; codeine and its impurities methylcodeine, morphine, codeine dimer and 10-hydroxycodeine; pitophenone and its impurities 2-[4-[2-(1-piperidinyl)ethoxy]benzoyl] benzoic acid, 2-[4-[2-(1-piperidinyl)ethoxy]benzoyl]benzoic acid 2-(1-piperidinyl)-ethyl ester, methyl ester of 2-(4-hydroxybenzoyl) benzoic acid and fenpiverinium was achieved by using ion-pair reversed phase liquid chromatography with UV detection. Validation parameters such as the precision, accuracy, linearity, limit of detection (LOD), limit of quantification (LOQ) and robustness were verified for all the mentioned impurities of codeine phosphate hemihydrate and 4-aminophenol and 2-[4-[2-(1-piperidinyl)ethoxy]benzoyl] benzoic acid as the main degradation products of paracetamol and pitophenone hydrochloride, respectively. The described method was found to be useful for analysis of the stability samples and therefore suitable for routine purity testing of the drug product. Copyright © 2014 Elsevier B.V. All rights reserved.

Does brand differentiate pharmaceuticals?

Science.gov (United States)

Bednarik, Josef

2005-12-01

Role of marketing in pharmaceutical industry is increasing and inspiration by successful brands known from consumer goods market influenced pharmaceutical companies enough to switch their attention to branding initiatives. Still there is little evidence that pharmaceutical brands represent anything more than product only. This study aims to explore the area of branding in pharmaceutical industry. Central hypothesis of the research has been that brand and its emotional content differentiate pharmaceuticals as well as rational data derived from clinical studies. It has been tested by extensive review of available literature as well as by primary research focused on drivers of physicians' attitudes towards products and their influence on prescribing behavior. The research has been conducted in the sample of psychiatrists in the Czech Republic. No evidence about pharmaceutical brand exceeding value of product has been found in reviewed literature. Nevertheless, the primary research conducted in the sample of Czech psychiatrists indicates that emotional brand in pharmaceutical industry exists and enables author to draw a model of Customer/product life cycle that describes likely impact of functional, emotional and self-expressive benefits throughout pharmaceutical product's market presence. Pharmaceutical brand is likely to develop differently than the same of consumer goods products--it seems to be built predominantly on long-term positive experience. Marketing role in this process should lie in finding relevant product position and building brand identity compliant with real product capabilities.

Pharmaceutical manufacturing facility discharges can substantially increase the pharmaceutical load to U.S. wastewaters

Science.gov (United States)

Scott, Tia-Marie; Phillips, Patrick J.; Kolpin, Dana W.; Colella, Kaitlyn M.; Furlong, Edward T.; Foreman, William T.; Gray, James L.

2018-01-01

Discharges from pharmaceutical manufacturing facilities (PMFs) previously have been identified as important sources of pharmaceuticals to the environment. Yet few studies are available to establish the influence of PMFs on the pharmaceutical source contribution to wastewater treatment plants (WWTPs) and waterways at the national scale. Consequently, a national network of 13 WWTPs receiving PMF discharges, six WWTPs with no PMF input, and one WWTP that transitioned through a PMF closure were selected from across the United States to assess the influence of PMF inputs on pharmaceutical loading to WWTPs. Effluent samples were analyzed for 120 pharmaceuticals and pharmaceutical degradates. Of these, 33 pharmaceuticals had concentrations substantially higher in PMF-influenced effluent (maximum 555,000 ng/L) compared to effluent from control sites (maximum 175 ng/L). Concentrations in WWTP receiving PMF input are variable, as discharges from PMFs are episodic, indicating that production activities can vary substantially over relatively short (several months) periods and have the potential to rapidly transition to other pharmaceutical products. Results show that PMFs are an important, national-scale source of pharmaceuticals to the environment.

Rapid and Simultaneous Determination of Acetylsalicylic Acid, Paracetamol, and Their Degradation and Toxic Impurity Products by HPLC in Pharmaceutical Dosage Forms

OpenAIRE

AKAY, Cemal

2008-01-01

Aims: Determinations of drug impurity and drug degradation products are very important from both pharmacological and toxicological perspectives. Establishment of monitoring methods for impurities and degradation products during pharmaceutical development is necessary because of their potential toxicity. The aim of this study was to develop a rapid and simultaneous determination method for paracetamol and acetylsalicylic acid (ACA) and their degradation and toxic impurity products by high perf...

Decomposition of persistent pharmaceuticals in wastewater by ionizing radiation

International Nuclear Information System (INIS)

Kimura, A.; Taguchi, M.; Osawa, M.

2011-01-01

Complete text of publication follows. The environmental movement and risk evaluation of some pharmaceuticals are studied recently, and the concentrations of the pharmaceuticals in the water environment increased gradually because of population growth and the diversification of advanced medical worldwide. Some anti-inflammatory medications, anticonvulsant drugs, antiviral drugs, antilipemic agents and so on were detected at the downstream of water treatment plant, and could not be decomposed by the activated sludge system completely. However, it is difficult to manage the environment risk of the pharmaceuticals having great benefits for human life. The development of new treatment method is required to minimized their risk. The purpose of this work is to treat the pharmaceuticals in combination of the activated sludge and the ionizing radiation. Oseltamivir, aspirin and ibuprofen at 5 μmol dm -3 in wastewater were decomposed by activated sludge at reaction time for 4 h. Carbamazepine, ketoprofen, mefenamic acid, clofibric acid, and diclofenac were not biodegraded completely, but eliminated by γ-ray irradiation at 2 kGy. The rate constants of the reactions of these pharmaceuticals with hydroxyl radicals produced by water radiolysis were estimated by the competition reaction method to be 3.4 - 10 x 10 9 mol -1 dm 3 s -1 . Decompositions of the pharmaceuticals in wastewater by ionizing radiation were simulated using parameters of the obtained rate constants and the amount of total organic carbon. Simulation curves of concentrations of these pharmaceuticals as function of dose were responsible for the experimental data, and the required dose for the elimination of them in wastewater by ionizing radiation can be estimated by this simulation.

[Pharmaceutical logistic in turnover of pharmaceutical products of Azerbaijan].

Science.gov (United States)

Dzhalilova, K I

2009-11-01

Development of pharmaceutical logistic system model promotes optimal strategy for pharmaceutical functioning. The goal of such systems is organization of pharmaceutical product's turnover in required quantity and assortment, at preset time and place, at a highest possible degree of consumption readiness with minimal expenses and qualitative service. Organization of the optimal turnover chain in the region is offered to start from approximate classification of medicaments by logistic characteristics. Supplier selection was performed by evaluation of timeliness of delivery, quality of delivered products (according to the minimum acceptable level of quality) and time-keeping of time spending for orders delivery.

Effectiveness of different benfotiamine dosage regimens in the treatment of painful diabetic neuropathy.

Science.gov (United States)

Winkler, G; Pál, B; Nagybéganyi, E; Ory, I; Porochnavec, M; Kempler, P

1999-03-01

The therapeutic effectiveness of a benfotiamine (CAS 22457-89-2)-vitamin B combination (Milgamma-N), administered in high (4 x 2 capsules/day, = 320 mg benfotiamine/day) and medium doses (3 x 1 capsules/day), was compared to a monotherapy with benfotiamine (Benfogamma) (3 x 1 tablets/day, = 150 mg benfotiamine/day) in diabetic patients suffering from painful peripheral diabetic neuropathy (DNP). In a 6-week open clinical trial, 36 patients (aged 40 to 70 yrs) having acceptable metabolic control (HbA1c benfotiamine (p benfotiamine is most effective in large doses, although even in smaller daily dosages, either in combination or in monotherapy, it is effective.

Stability-indicating liquid chromatographic method for quantification of new anti-epileptic drug lacosamide in bulk and pharmaceutical formulation

Directory of Open Access Journals (Sweden)

Chhalotiya Usmangani K.

2012-01-01

Full Text Available An isocratic stability indicating reversed-phase liquid chromatographic determination was developed for the quantitative determination of lacosamide in the pharmaceutical dosage form. A Hypersil C-18, 4.5μm column with mobile phase containing acetonitrile-water (20:80, v/v was used. The flow rate was 1.0 mL min-1 and effluents were monitored at 258 nm. The retention time of lacosamide was 8.9 min. The method was found to be linear in the concentration range of 5-100 μg/ml and the recovery was found to be in the range of 99.15 - 100.09 %. The limit of detection and limit of quantification were found to be 2 μg/ml and 5 μg/ml, respectively. Lacosamide stock solutions were subjected to acid and alkali hydrolysis, chemical oxidation and dry heat degradation. The drug was found to be stable to the dry heat and acidic condition attempted. The proposed method was validated and successfully applied to the estimation of lacosamide in tablet dosage forms.

Optimization of the pharmaceutical care system for diabetes patients using modern pharmaceutical informatics methodology

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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

Determination of glibenclamide, metformin hydrochloride and rosiglitazone maleate by reversed phase liquid chromatographic technique in tablet dosage form

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Havele Shweta S.

2014-01-01

Full Text Available A simple, precise and accurate high performance liquid chromatography (HPLC method was developed for the simultaneous estimation of metformin hydrochloride, rosiglitazone maleate, glibenclamide present in multicomponent dosage forms. Chromatography was performed on a 25 cm × 4.6 mm i.d., 5-μm particle, C18 column with 78:22 (v/v methanol: 20 mM potassium dihydrogen phosphate buffer as mobile phase at a flow rate of 1.0 ml/min and UV detection at 238 nm for metformin hydrochloride, rosiglitazone maleate, and glibenclamide. The total elution time was shorter than 9 min. This method was found to be precise and reproducible. This proposed method was successfully applied for the analysis of metformin hydrochloride, rosiglitazone maleate, glibenclamide as a bulk drug and in pharmaceutical formulation without any interference from the excipients.

Browse Title Index - African Journals Online

African Journals Online (AJOL)

Items 501 - 550 of 1932 ... Vol 10, No 1 (2011), Colorimetric Determination of Cefadroxil and Ceftriazone in Pharmaceutical Dosage Forms, Abstract PDF. CA Kumar, BM Gurupadayya, SN Sloka, RS Chandan, JC Thejaswini. Vol 14, No 6 (2015), Combined Effect of Vorinostat and Grape Seed Proanthocyanidins on Modulation ...

Dosage of boron traces in graphite, uranium and beryllium oxide; Dosage de traces de bore dans le graphite, l'uranium et l'oxyde de beryllium

Energy Technology Data Exchange (ETDEWEB)

Coursier, J [Ecole Nationale Superieure de Physique et Chimie Industrielles, 75 - Paris (France); Hure, J; Platzer, R [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1955-07-01

The problem of the dosage of the boron in the materials serving to the construction of nuclear reactors arises of the following way: to determine to about 0,1 ppm close to the quantities of boron of the order of tenth ppm. We have chosen the colorimetric analysis with curcumin as method of dosage. To reach the indicated contents, it is necessary to do a previous separation of the boron and the materials of basis, either by extraction of tetraphenylarsonium fluoborate in the case of the boron dosage in uranium and the beryllium oxide, either by the use of a cations exchanger resin of in the case of graphite. (M.B.) [French] Le probleme du dosage du bore dans les materiaux servant a la construction de reacteurs nucleaires se pose de la facon suivante: determiner a environ 0,1 ppm pres des quantites de bore de l'ordre de quelques dixiemes de ppm. Nous avons choisit la colorimetrie a la curcumine comme methode de dosage. Pour atteindre les teneurs indiquees, il est necessaire d'effectuer une separation prealable du bore et des materiaux de base, soit par extraction du fluoborate de tetraphenylarsonium dans le cas du dosage de bore dans l'uranium et l'oxyde de beryllium, soit par l'utilisation d'une resine echangeuse de cations dans le cas du graphite. (M.B.)

Dosage compensation of serine-4 transfer RNA in Drosophila melanogaster

International Nuclear Information System (INIS)

Birchler, J.A.; Owenby, R.K.; Jacobson, K.B.

1982-01-01

A dosage series of the X chromosome site for serine-4 transfer RNA consisting of one of three copies in females and one to two in males was constructed to test whether transfer RNA expression is governed by dosage compensation. A dosage effect on the level of the serine-4 isoacceptor was observed in both females and males when the structural locus was varied. However, in males, each dose had a relatively greater expression so the normal one dose was slightly greater than the total female value and the duplicated male had the highest relative expression of all the types examined. Serine-4 levels in males and females from an isogenic Oregon-R stock were similar. Thus the transfer RNA levels conform to the expectations of dosage compensation

THz spectroscopy: An emerging technology for pharmaceutical development and pharmaceutical Process Analytical Technology (PAT) applications

Science.gov (United States)

Wu, Huiquan; Khan, Mansoor

2012-08-01

As an emerging technology, THz spectroscopy has gained increasing attention in the pharmaceutical area during the last decade. This attention is due to the fact that (1) it provides a promising alternative approach for in-depth understanding of both intermolecular interaction among pharmaceutical molecules and pharmaceutical product quality attributes; (2) it provides a promising alternative approach for enhanced process understanding of certain pharmaceutical manufacturing processes; and (3) the FDA pharmaceutical quality initiatives, most noticeably, the Process Analytical Technology (PAT) initiative. In this work, the current status and progress made so far on using THz spectroscopy for pharmaceutical development and pharmaceutical PAT applications are reviewed. In the spirit of demonstrating the utility of first principles modeling approach for addressing model validation challenge and reducing unnecessary model validation "burden" for facilitating THz pharmaceutical PAT applications, two scientific case studies based on published THz spectroscopy measurement results are created and discussed. Furthermore, other technical challenges and opportunities associated with adapting THz spectroscopy as a pharmaceutical PAT tool are highlighted.

The Dosage Form of Aragh in Treatment, from the Iranian Traditional Medicine Perspective.

Science.gov (United States)

Adl, Mehdi; Emtiazi, Majid

2016-05-01

The Iranian traditional medicine is one of the branches of complementary medicine and it is based on using the dosage forms of plants. One of the most common forms of pharmaceutical plants is Aragh. Due to ease-of-use, distillate is a more acceptable form among the public. In this article, it is attempted to study the usage forms and effects of Aragh according to the valid traditional medicine resources. This article is a review of Iranian traditional medicine textbooks such as Makhzan-ul-dawiah, Gharabadin Kabir, Cannon of Medicine, and other recent texts on medical plants. According to the traditional medicine, the process of getting Aragh is a kind of distillation, which is performed by using Ghar and Alembic (the equipment that are used in distillation). Distillation is the process of extracting and refining the fluid of a plant. Aragh of the plants is much more effective on the body than the plant itself. Traditional medicine regards Aragh as a new kind of drug (medicine) that is rarely mentioned in older texts (except for golab). However, the modern medicine regards it as a dosage form of essence, which is dissolved in water. The more the essence, the better the distillate gets. According to the traditional medicine sources, since the time of Hakim Aghil Khorasani, Aragh was used more and more every day. About 100 kinds of Araghs are mentioned in ancient texts, which are extracted from simple plants. Considering the distillation process and the way it performs, and by knowing that Aragh is a plant's softest and the most influential entity, it seems that it has a huge effect on Arvah and Ghova, the main parts like heart and brain and nervous parts.

Comparative pathophysiology, toxicology, and human cancer risk assessment of pharmaceutical-induced hibernoma

International Nuclear Information System (INIS)

Radi, Zaher; Bartholomew, Phillip; Elwell, Michael; Vogel, W. Mark

2013-01-01

In humans, hibernoma is a very rare, benign neoplasm of brown adipose tissue (BAT) that typically occurs at subcutaneous locations and is successfully treated by surgical excision. No single cause has been accepted to explain these very rare human tumors. In contrast, spontaneous hibernoma in rats is rare, often malignant, usually occurs in the thoracic or abdominal cavity, and metastases are common. In recent years, there has been an increased incidence of spontaneous hibernomas in rat carcinogenicity studies, but overall the occurrence remains relatively low and highly variable across studies. There have only been four reported examples of pharmaceutical-induced hibernoma in rat carcinogenicity studies. These include phentolamine, an alpha-adrenergic antagonist; varenicline, a nicotine partial agonist; tofacitinib, a Janus kinase (JAK) inhibitor; and hydromorphone, an opiod analgesic. Potential non-genotoxic mechanisms that may contribute to the pathogenesis of BAT activation/proliferation and/or subsequent hibernoma development in rats include: (1) physiological stimuli, (2) sympathetic stimulation, (3) peroxisome proliferator-activated receptor (PPAR) agonism, and/or (4) interference or inhibition of JAK/Signal Transducer and Activator of Transcription (JAK/STAT) signaling. The evaluation of an apparent increase of hibernoma in rats from 2-year carcinogenicity studies of novel pharmaceutical therapeutics and its relevance to human safety risk assessment is complex. One should consider: the genotoxicity of the test article, dose/exposure and safety margins, and pathophysiologic and morphologic differences and similarities of hibernoma between rats and humans. Hibernomas observed to date in carcinogenicity studies of pharmaceutical agents do not appear to be relevant for human risk at therapeutic dosages. - Highlights: • Highly variable incidence of spontaneous hibernoma in carcinogenicity studies • Recent increase in the spontaneous incidence of hibernomas

Comparative pathophysiology, toxicology, and human cancer risk assessment of pharmaceutical-induced hibernoma

Energy Technology Data Exchange (ETDEWEB)

Radi, Zaher, E-mail: zaher.radi@pfizer.com [Pfizer Worldwide Research and Development, Drug Safety R and D, 1 Burtt Rd., Andover, MA 01810 (United States); Bartholomew, Phillip, E-mail: phillip.m.bartholomew@pfizer.com [Pfizer Worldwide Research and Development, Drug Safety R and D, Eastern Point Road, Groton, CT 06340 (United States); Elwell, Michael, E-mail: michael.elwell@covance.com [Covance Laboratories, Chantilly, VA 20151 (United States); Vogel, W. Mark, E-mail: w.mark.vogel@pfizer.com [Pfizer Worldwide Research and Development, Drug Safety R and D, 1 Burtt Rd., Andover, MA 01810 (United States)

2013-12-15

In humans, hibernoma is a very rare, benign neoplasm of brown adipose tissue (BAT) that typically occurs at subcutaneous locations and is successfully treated by surgical excision. No single cause has been accepted to explain these very rare human tumors. In contrast, spontaneous hibernoma in rats is rare, often malignant, usually occurs in the thoracic or abdominal cavity, and metastases are common. In recent years, there has been an increased incidence of spontaneous hibernomas in rat carcinogenicity studies, but overall the occurrence remains relatively low and highly variable across studies. There have only been four reported examples of pharmaceutical-induced hibernoma in rat carcinogenicity studies. These include phentolamine, an alpha-adrenergic antagonist; varenicline, a nicotine partial agonist; tofacitinib, a Janus kinase (JAK) inhibitor; and hydromorphone, an opiod analgesic. Potential non-genotoxic mechanisms that may contribute to the pathogenesis of BAT activation/proliferation and/or subsequent hibernoma development in rats include: (1) physiological stimuli, (2) sympathetic stimulation, (3) peroxisome proliferator-activated receptor (PPAR) agonism, and/or (4) interference or inhibition of JAK/Signal Transducer and Activator of Transcription (JAK/STAT) signaling. The evaluation of an apparent increase of hibernoma in rats from 2-year carcinogenicity studies of novel pharmaceutical therapeutics and its relevance to human safety risk assessment is complex. One should consider: the genotoxicity of the test article, dose/exposure and safety margins, and pathophysiologic and morphologic differences and similarities of hibernoma between rats and humans. Hibernomas observed to date in carcinogenicity studies of pharmaceutical agents do not appear to be relevant for human risk at therapeutic dosages. - Highlights: • Highly variable incidence of spontaneous hibernoma in carcinogenicity studies • Recent increase in the spontaneous incidence of hibernomas

Development and Validation of Spectrophotometric Methods for Simultaneous Estimation of Valsartan and Hydrochlorothiazide in Tablet Dosage Form

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Monika L. Jadhav

2014-01-01

Full Text Available Two UV-spectrophotometric methods have been developed and validated for simultaneous estimation of valsartan and hydrochlorothiazide in a tablet dosage form. The first method employed solving of simultaneous equations based on the measurement of absorbance at two wavelengths, 249.4 nm and 272.6 nm, λmax for valsartan and hydrochlorothiazide, respectively. The second method was absorbance ratio method, which involves formation of Q-absorbance equation at 258.4 nm (isoabsorptive point and also at 272.6 nm (λmax of hydrochlorothiazide. The methods were found to be linear between the range of 5–30 µg/mL for valsartan and 4–24 μg/mL for hydrochlorothiazide using 0.1 N NaOH as solvent. The mean percentage recovery was found to be 100.20% and 100.19% for the simultaneous equation method and 98.56% and 97.96% for the absorbance ratio method, for valsartan and hydrochlorothiazide, respectively, at three different levels of standard additions. The precision (intraday, interday of methods was found within limits (RSD<2%. It could be concluded from the results obtained in the present investigation that the two methods for simultaneous estimation of valsartan and hydrochlorothiazide in tablet dosage form are simple, rapid, accurate, precise and economical and can be used, successfully, in the quality control of pharmaceutical formulations and other routine laboratory analysis.

A Study of Method Development, Validation, and Forced Degradation for Simultaneous Quantification of Paracetamol and Ibuprofen in Pharmaceutical Dosage Form by RP-HPLC Method

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Md. Sarowar Jahan

2014-01-01

Full Text Available A rapid and stability-indicating reversed phase high-performance liquid chromatography (RP-HPLC method was developed for simultaneous quantification of paracetamol and ibuprofen in their combined dosage form especially to get some more advantages over other methods already developed for this combination. The method was validated according to United States Pharmacopeia (USP guideline with respect to accuracy, precision, specificity, linearity, solution stability, robustness, sensitivity, and system suitability. Forced degradation study was validated according to International Conference on Harmonisation (ICH. For this, an isocratic condition of mobile phase comprising phosphate buffer (pH 6.8 and acetonitrile in a ratio of 65:35, v/v at a flow rate of 0.7 mL/minute over RP C18 (octadecylsilane (ODS, 150 × 4.6 mm, 5 μm, Phenomenex Inc. column at ambient temperature was maintained. The method showed excellent linear response with correlation coefficient ( R 2 values of 0.999 and 1.0 for paracetamol and ibuprofen respectively, which were within the limit of correlation coefficient ( R 2 > 0.995. The percent recoveries for two drugs were found within the acceptance limit of (97.0-103.0%. Intra-and inter-day precision studies of the new method were less than the maximum allowable limit percentage of relative standard deviation (%RSD ≤ 2.0. Forced degradation of the drug product was carried out as per the ICH guidelines with a view to establishing the stability-indicating property of this method and providing useful information about the degradation pathways, degradation products, and how the quality of a drug substance and drug product changes with time under the influence of various stressing conditions. The degradation of ibuprofen was within the limit (5-20%, according to the guideline of ICH, while paracetamol showed <20% degradation in oxidation and basic condition.

A Study of Method Development, Validation, and Forced Degradation for Simultaneous Quantification of Paracetamol and Ibuprofen in Pharmaceutical Dosage Form by RP-HPLC Method.

Science.gov (United States)

Jahan, Md Sarowar; Islam, Md Jahirul; Begum, Rehana; Kayesh, Ruhul; Rahman, Asma

2014-01-01

A rapid and stability-indicating reversed phase high-performance liquid chromatography (RP-HPLC) method was developed for simultaneous quantification of paracetamol and ibuprofen in their combined dosage form especially to get some more advantages over other methods already developed for this combination. The method was validated according to United States Pharmacopeia (USP) guideline with respect to accuracy, precision, specificity, linearity, solution stability, robustness, sensitivity, and system suitability. Forced degradation study was validated according to International Conference on Harmonisation (ICH). For this, an isocratic condition of mobile phase comprising phosphate buffer (pH 6.8) and acetonitrile in a ratio of 65:35, v/v at a flow rate of 0.7 mL/minute over RP C18 (octadecylsilane (ODS), 150 × 4.6 mm, 5 μm, Phenomenex Inc.) column at ambient temperature was maintained. The method showed excellent linear response with correlation coefficient (R (2)) values of 0.999 and 1.0 for paracetamol and ibuprofen respectively, which were within the limit of correlation coefficient (R (2) > 0.995). The percent recoveries for two drugs were found within the acceptance limit of (97.0-103.0%). Intra-and inter-day precision studies of the new method were less than the maximum allowable limit percentage of relative standard deviation (%RSD) ≤ 2.0. Forced degradation of the drug product was carried out as per the ICH guidelines with a view to establishing the stability-indicating property of this method and providing useful information about the degradation pathways, degradation products, and how the quality of a drug substance and drug product changes with time under the influence of various stressing conditions. The degradation of ibuprofen was within the limit (5-20%, according to the guideline of ICH), while paracetamol showed degradation in oxidation and basic condition.

Evaluating the effect of a proposed logistics fee cap on pharmaceuticals in South Africa--a pre and post analysis.

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Bangalee, Varsha; Suleman, Fatima

2015-11-26

South Africa has proposed the implementation of a maximum logistics fee paid by pharmaceutical manufacturers to wholesalers and distributors. However very little knowledge exists of the effects, unintended or otherwise, of the implementation of these proposed regulations, which are required to guide further policy development and implementation. The objectives of this study was to therefore evaluate the effects of the proposed logistics fee cap on different pharmaceuticals and different dosage forms, as well as to observe the logistics fee contribution to the Single Exit Price. Private sector medicine prices were sourced from the South African Medicine Price Registry as at 20 December 2013. For each medicine the maximum logistics fee was calculated based on the 2012 proposed government guidelines. The logistics fee as a percentage of the final Single Exit Price was calculated, as part of the analysis of results. Out of the 47 medicines in the overall sample from the current study, only 16 medicines showed a decrease in the Single Exit Price with the application of the maximum logistics fee cap. This study reveals the need for greater transparency of the mark ups along the distribution chain as well as further research with regards to the costing of logistics fees of similar pharmaceuticals.

Combined electrocoagulation and TiO{sub 2} photoassisted treatment applied to wastewater effluents from pharmaceutical and cosmetic industries

Energy Technology Data Exchange (ETDEWEB)

Boroski, Marcela; Rodrigues, Angela Claudia; Garcia, Juliana Carla; Sampaio, Luiz Carlos; Nozaki, Jorge [Departamento de Quimica, Universidade Estadual de Maringa, Avenida Colombo 5790, Maringa-PR 87020-900 (Brazil); Hioka, Noboru [Departamento de Quimica, Universidade Estadual de Maringa, Avenida Colombo 5790, Maringa-PR 87020-900 (Brazil)], E-mail: nhioka2@yahoo.com.br

2009-02-15

The treated wastewater consists of refractory materials and high organic content of hydrolyzed peptone residues from pharmaceutical factory. The combination of electrocoagulation (EC) followed by heterogeneous photocatalysis (TiO{sub 2}) conditions was maximized. The EC: iron cathode/anode (12.50 cm x 2.50 cm x 0.10 cm), current density 763 A m{sup -2}, 90 min and initial pH 6.0. As EC consequence, the majority of the dissolved organic and suspended material was removed (about 91% and 86% of the turbidity and chemical oxygen demand (COD), respectively). After EC, refractory residues still remained in the effluent. The subsequent photocatalysis: UV/TiO{sub 2}/H{sub 2}O{sub 2} (mercury lamps), pH 3.0, 4 h irradiation, 0.25 g L{sup -1} TiO{sub 2} and 10 mmol L{sup -1} H{sub 2}O{sub 2} shows high levels of inorganic and organic compounds eliminations. The obtained COD values: 1753 mg L{sup -1} for the sample from the factory, 160 mg L{sup -1} after EC and 50 mg L{sup -1} after EC/photocatalyzed effluents pointed out that the combined treatment stresses this water purification.

'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.

Combined Effects of Egg Age and Gamma Radiation Dosage on egg hatch of Scolytus Amygdali/guer

International Nuclear Information System (INIS)

Tadros, A.W.; Abdallah, F.F.; Abdelsalam, K.A.; Hashem, A.G.

1992-01-01

Eggs of Scolytus Amygdali were irradiated with 5 to 300 gray of gamma radiation at a dose rate of 7.87 rad/second. One-to five-day-old eggs were used. Results showed that one-and-tow-day-old eggs were the most sensitive as 100% mortality were obtained at 40 and 50 gray, respectively. Three-day-old-eggs required 100 gray to prevent hatch ability; while 300 gray were needed to prevent the 4-and 5-day-old eggs from hatching. There was 7.2-fold increase in resistance as eggs matured from 1 to 5 days measured by dosages required to produce LD 50. 2 fig

THE DETERMINATION OF BUPROPION HYDROCHLORIDE IN PHARMACEUTICAL DOSAGE FORMS BY ORIGINAL UV- AND SECOND DERIVATIVE UV SPECTROPHOTOMETRY, POTENTIOMETRIC AND CONDUCTOMETRIC METHODS

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Duygu YENİCELİ

2010-08-01

Full Text Available Spectrophotometric, potentiometric and conductometric methods are developed for the determination of bupropion hydrochloride (BLIP in pharmaceutical tablets. For the first method, original UV-spectrophotometry, 252 nm was determined as the optimum wavelength and used for the determinations. For the other method, second derivative UV spectrophotometry, the absorbances were measured at 217.4 and 221.8 nm and the distance between these extremum values was determined according to peak to peak method. Two spectrophotometric methods were validated over the concentration range of 5.72 - 20.03 ug/mL. The limit of detection and limit of quantitation values of original UV-spectrophotometry were 0.75 ug/mL and 2.28 jug/mL. Also, these parameters were determined as 0.23 ug/mL and 0.68 ug/mL respectively, for the second derivative UV spectrophotometry. Developed methods were fully validated and the applicability of the methods for the determination of BUP in pharmaceuticals were demonstrated. Also, simple potentiometric and conductometric methods were developed and the applicability of these methods were demonstrated. The results of four analytical methods were compared with ANOVA test and no significant difference was found statistically. As a result, the developed methods could be proposed to the rutin content analysis to be simple, cheap, accurate, and precise

Assessing the environmental hazard of individual and combined pharmaceuticals: acute and chronic toxicity of fluoxetine and propranolol in the crustacean Daphnia magna.

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Varano, Valentina; Fabbri, Elena; Pasteris, Andrea

2017-08-01

Pharmaceuticals are widespread emerging contaminants and, like all pollutants, are present in combination with others in the ecosystems. The aim of the present work was to evaluate the toxic response of the crustacean Daphnia magna exposed to individual and combined pharmaceuticals. Fluoxetine, a selective serotonin re-uptake inhibitor widely prescribed as antidepressant, and propranolol, a non-selective β-adrenergic receptor-blocking agent used to treat hypertension, were tested. Several experimental trials of an acute immobilization test and a chronic reproduction test were performed. Single chemicals were first tested separately. Toxicity of binary mixtures was then assessed using a fixed ratio experimental design. Five concentrations and 5 percentages of each substance in the mixture (0, 25, 50, 75, and 100%) were tested. The MIXTOX model was applied to analyze the experimental results. This tool is a stepwise statistical procedure that evaluates if and how observed data deviate from a reference model, either concentration addition (CA) or independent action (IA), and provides significance testing for synergism, antagonism, or more complex interactions. Acute EC50 values ranged from 6.4 to 7.8 mg/L for propranolol and from 6.4 to 9.1 mg/L for fluoxetine. Chronic EC50 values ranged from 0.59 to 1.00 mg/L for propranolol and from 0.23 to 0.24 mg/L for fluoxetine. Results showed a significant antagonism between chemicals in both the acute and the chronic mixture tests when CA was adopted as the reference model, while absence of interactive effects when IA was used.

Hot-melt extruded filaments based on pharmaceutical grade polymers for 3D printing by fused deposition modeling.

Science.gov (United States)

Melocchi, Alice; Parietti, Federico; Maroni, Alessandra; Foppoli, Anastasia; Gazzaniga, Andrea; Zema, Lucia

2016-07-25

Fused deposition modeling (FDM) is a 3D printing technique based on the deposition of successive layers of thermoplastic materials following their softening/melting. Such a technique holds huge potential for the manufacturing of pharmaceutical products and is currently under extensive investigation. Challenges in this field are mainly related to the paucity of adequate filaments composed of pharmaceutical grade materials, which are needed for feeding the FDM equipment. Accordingly, a number of polymers of common use in pharmaceutical formulation were evaluated as starting materials for fabrication via hot melt extrusion of filaments suitable for FDM processes. By using a twin-screw extruder, filaments based on insoluble (ethylcellulose, Eudragit(®) RL), promptly soluble (polyethylene oxide, Kollicoat(®) IR), enteric soluble (Eudragit(®) L, hydroxypropyl methylcellulose acetate succinate) and swellable/erodible (hydrophilic cellulose derivatives, polyvinyl alcohol, Soluplus(®)) polymers were successfully produced, and the possibility of employing them for printing 600μm thick disks was demonstrated. The behavior of disks as barriers when in contact with aqueous fluids was shown consistent with the functional application of the relevant polymeric components. The produced filaments were thus considered potentially suitable for printing capsules and coating layers for immediate or modified release, and, when loaded with active ingredients, any type of dosage forms. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of 18F-FDG dosage alternation on final PET image

International Nuclear Information System (INIS)

Yin Dayi; Yao Shulin; Chen Yingmao; Shao Mingzhe; Tian Jiahe

2002-01-01

Objective: To assess PET reconstructed image effected by different 18 F-FDG dosages with quantitative and qualitative analysis. Methods: To perform PET phantom acquisition by routine clinical parameters after filled with different doses of 18 F-FDG solution. An identical slice was extracted from reconstructed image for doing following analysis: the hot area standard uptake value (SUV), the ratio of hot area to cold area, the standard deviation on background area, the ratio of true coincidence to random. Results: 296 MBq: The image uniformity was terribly worse, T/R=0.83, other indexes were irregular. 148 MBq: The image presentation looked like the image without attenuation correction, T/R=1.64, other indexes were moderate. 74, 37 and 18.5 MBq: The images were with excellent uniformity, resolution and contrast, the background noise was suitable, all of the quantitative indexes were good. 9.25 and 4.625 MBq: The uniformity and resolution was degraded terribly because of the higher noise and lower information. Conclusion: Combining above results with other considerations, such as radiation exposure, information amount and acquisition time, the authors think the optimal dosage should be 4.625-11.1 MBq/kg

Evolution of vertebrate sex chromosomes and dosage compensation.

Science.gov (United States)

Graves, Jennifer A Marshall

2016-01-01

Differentiated sex chromosomes in mammals and other vertebrates evolved independently but in strikingly similar ways. Vertebrates with differentiated sex chromosomes share the problems of the unequal expression of the genes borne on sex chromosomes, both between the sexes and with respect to autosomes. Dosage compensation of genes on sex chromosomes is surprisingly variable - and can even be absent - in different vertebrate groups. Systems that compensate for different gene dosages include a wide range of global, regional and gene-by-gene processes that differ in their extent and their molecular mechanisms. However, many elements of these control systems are similar across distant phylogenetic divisions and show parallels to other gene silencing systems. These dosage systems cannot be identical by descent but were probably constructed from elements of ancient silencing mechanisms that are ubiquitous among vertebrates and shared throughout eukaryotes.

Evaluation of P-Listed Pharmaceutical Residues in Empty Pharmaceutical Containers

Science.gov (United States)

Under the Resource Conservation and Recovery Act (RCRA), some pharmaceuticals are considered acute hazardous wastes because their sole active pharmaceutical ingredients are P-listed commercial chemical products (40 CFR 261.33). Hospitals and other healthcare facilities have stru...

Semi-solid dosage form of clonazepam for rapid oral mucosal absorption.

Science.gov (United States)

Sakata, Osamu; Machida, Yoshiharu; Onishi, Hiraku

2011-07-01

In order to obtain an alternative to the intravenous (i.v.) dosage form of clonazepam (CZ), an oral droplet formulation of CZ was developed previously; however, the droplet was physically unstable. Therefore, in the present study, it was attempted to develop an easily-handled dosage form, which was more physically stable and allowed rapid drug absorption from oral mucosa. A semi-solid dosage form, composed of polyethylene glycol 1500 (PEG), CZ, and oleic acid (OA) at 37/1/2 (w/w) and named PEG/CZ/OA, and a semi-solid dosage form containing PEG and CZ at 39/1 (w/w), called PEG/CZ, were prepared. Their physical stability in air at room temperature and oral mucosal absorption in rats were investigated. The semi-solid dosage forms were much more stable physically than the droplet, that is, no recrystallization of CZ was observed for at least 8 days. The effective concentration for humans and rats (20 ng/mL or more) was achieved within 30 min after buccal administration for both PEG/CZ/OA and PEG/CZ. The plasma concentration increased gradually and less varied at each time point for PEG/CZ/OA. PEG/CZ/OA was found to show more rapid and higher absorption of CZ in buccal administration than in sublingual administration. Buccal administration with the semi-solid dosage PEG/CZ with or without OA was suggested to be a possibly useful novel dosage form as an alternative to i.v. injection.

Evaluation of insecticides in different dosages to control cicadas in parica plantations

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Odineila Martins Monteiro

2014-07-01

Full Text Available This study aimed to determine the more efficient and economically viable dosage of chemical insecticide to control Quesada gigas (Hemiptera: Cicadidae nymphs in parica plantations. Three dosages of three products (carbofuran, imidacloprid and thiamethoxam were tested based on the maximum recommended dosage for the control of cicadas in coffee plants and applied in total area. The dosage of one kilogram of a commercial product based in thiamethoxam per hectare was more efficient economically and environmentally to control nymphs of Q. gigas in parica plantations.

Russian Pharmaceutical Companies Export Potential in Emerging Regional Clusters

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Elena Vladimirovna Sapir

2016-12-01

Full Text Available This article analyzes a diverse range of the enterprise’s export potential growth factors in emerging pharmaceutical clusters of Central European Russia. Classification and comparative analysis were used to identify export potential attributes (production, finance, labor and marketing, which have allowed to reveal the strong connection of cluster and regional factor groups with the results of export performance. The purpose of the study is to provide exports-seeking pharmaceutical companies with a set of tools to enhance their export potential. The hypothesis that the cumulative impact of the specified attributes leads to the strengthening of pharmaceutical cluster export potential and promotes an effective integration of the region in the world economic space, is developed and tested. The methodology combines the geo-economy-based theory with the theory of clusters competitive advantages. The impacts of export potential growth factors are estimated by using an econometric model based on math statistics. Thus, five Russian regional pharmaceutical clusters (Belgorod, Kaluga, Moscow, Oryol, Yaroslavl are shown. Findings identify an objective causal link between enterprise export potential growth and competitiveness factors of cluster origin (network business chains, production functions interconnectedness and flexibility, production localization. An action plan for the purpose of the maximum use of competitive advantages of the cluster organization for export activities of the entities of the pharmaceutical industry is developed. Conclusions and recommendations of the study are intended to enterprises in pharmaceutical industry and regions’ public authorities, implementing cluster development strategies. It is thus essential to improve marketing and organizational innovations, reduction of commercial expenses under the cluster environment, development of drugs production and delivery chains from R&D to end-users in order to enjoy greater

21 CFR 522.1696 - Penicillin G procaine implantation and injectable dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin G procaine implantation and injectable dosage forms. 522.1696 Section 522.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... DOSAGE FORM NEW ANIMAL DRUGS § 522.1696 Penicillin G procaine implantation and injectable dosage forms. ...

Comparative study between univariate spectrophotometry and multivariate calibration as analytical tools for quantitation of Benazepril alone and in combination with Amlodipine.

Science.gov (United States)

Farouk, M; Elaziz, Omar Abd; Tawakkol, Shereen M; Hemdan, A; Shehata, Mostafa A

2014-04-05

Four simple, accurate, reproducible, and selective methods have been developed and subsequently validated for the determination of Benazepril (BENZ) alone and in combination with Amlodipine (AML) in pharmaceutical dosage form. The first method is pH induced difference spectrophotometry, where BENZ can be measured in presence of AML as it showed maximum absorption at 237nm and 241nm in 0.1N HCl and 0.1N NaOH, respectively, while AML has no wavelength shift in both solvents. The second method is the new Extended Ratio Subtraction Method (EXRSM) coupled to Ratio Subtraction Method (RSM) for determination of both drugs in commercial dosage form. The third and fourth methods are multivariate calibration which include Principal Component Regression (PCR) and Partial Least Squares (PLSs). A detailed validation of the methods was performed following the ICH guidelines and the standard curves were found to be linear in the range of 2-30μg/mL for BENZ in difference and extended ratio subtraction spectrophotometric method, and 5-30 for AML in EXRSM method, with well accepted mean correlation coefficient for each analyte. The intra-day and inter-day precision and accuracy results were well within the acceptable limits. Copyright © 2013 Elsevier B.V. All rights reserved.

21 CFR 330.3 - Imprinting of solid oral dosage form drug products.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Imprinting of solid oral dosage form drug products... AS SAFE AND EFFECTIVE AND NOT MISBRANDED General Provisions § 330.3 Imprinting of solid oral dosage form drug products. A requirement to imprint an identification code on solid oral dosage form drug...

Optimal dosage and duration of pivmecillinam treatment for uncomplicated lower urinary tract infections: a systematic review and meta-analysis

Directory of Open Access Journals (Sweden)

Mariona Pinart

2017-05-01

Conclusions: There is insufficient evidence to support the use of an optimal combination of dosage, frequency, and duration of PIV therapy for the treatment of uncomplicated lower UTI. Evidence is limited due to the high risk of bias, poor reporting, and heterogeneous study data.

Automatic identification and normalization of dosage forms in drug monographs

Science.gov (United States)

2012-01-01

Background Each day, millions of health consumers seek drug-related information on the Web. Despite some efforts in linking related resources, drug information is largely scattered in a wide variety of websites of different quality and credibility. Methods As a step toward providing users with integrated access to multiple trustworthy drug resources, we aim to develop a method capable of identifying drug's dosage form information in addition to drug name recognition. We developed rules and patterns for identifying dosage forms from different sections of full-text drug monographs, and subsequently normalized them to standardized RxNorm dosage forms. Results Our method represents a significant improvement compared with a baseline lookup approach, achieving overall macro-averaged Precision of 80%, Recall of 98%, and F-Measure of 85%. Conclusions We successfully developed an automatic approach for drug dosage form identification, which is critical for building links between different drug-related resources. PMID:22336431

Evaluation of the effect of torsemide on warfarin dosage requirements.

Science.gov (United States)

Lai, Sophia; Momper, Jeremiah D; Yam, Felix K

2017-08-01

Background According to drug interaction databases, torsemide may potentiate the effects of warfarin. Evidence for this drug-drug interaction, however, is conflicting and the clinical significance is unknown. Objective The aim of this study is to evaluate the impact of torsemide initiation on warfarin dosage requirements. Setting This study was conducted at the Veterans Affairs Healthcare System in San Diego, California. Method A retrospective cohort study was conducted using Veterans Affairs data from patients who were converted from bumetanide to torsemide between March 2014 and July 2014. Patients were also prescribed and taking warfarin during the observation period. Warfarin dosage requirements were evaluated to determine if any changes occurred within the first 3 months of starting torsemide. Main outcome measure The primary outcome was the average weekly warfarin dose before and after torsemide initiation. Results Eighteen patients met study inclusion criteria. The weekly warfarin dose before and after initiation of torsemide was not significantly different (34 ± 15 and 34 ± 13 mg, p > 0.05). Of those eighteen patients, only two experienced elevations in INR that required a decrease in warfarin dosage after torsemide initiation. Between those two patients, dosage reductions ranged from 5.3 to 18%. Conclusion These results indicated that most patients did not require any warfarin dosage adjustments after torsemide was initiated. The potential for interaction, however, still exists. While empiric warfarin dosage adjustments are not recommended when initiating torsemide, increased monitoring is warranted to minimize the risk of adverse effects.

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.

Elimination of pharmaceutical residues in biologically pre-treated hospital wastewater using advanced UV irradiation technology: a comparative assessment.

Science.gov (United States)

Köhler, C; Venditti, S; Igos, E; Klepiszewski, K; Benetto, E; Cornelissen, A

2012-11-15

UV irradiation technology as a membrane bioreactor (MBR) post-treatment was investigated and assessed. Both UV low pressure (LP) and medium pressure (MP) lamps were examined. The technology was installed in a pilot plant treating hospital wastewater to provide the study with adequate field data. The effect of the UV irradiation was enhanced with varying dosages of H2O2 to establish an advanced oxidation process (AOP). The efficiency of the pharmaceutical removal process was assessed by examining 14 micropollutants (antibiotics, analgesics, anticonvulsants, beta-blockers, cytostatics and X-ray contrast media) which are typically released by hospitals and detected with liquid chromatography coupled tandem mass spectrometry (LC-MS/MS). While the MBR treatment generally showed only a low degradation capacity for persistent pharmaceuticals, much better degradation was obtained by applying UV irradiation and H2O2 as AOP. The "conventional" cost-benefit analysis of the different technology options taking into account both electrical energy consumption and pharmaceutical removal efficiency, revealed clearly better performance of low pressure UV lamps as AOP. However, a holistic comparison between the different scenarios was carried out by evaluating their environmental impacts using the life cycle assessment (LCA) methodology. Decisive advantages were highlighted to include this approach in the decision making process. Copyright © 2012 Elsevier B.V. All rights reserved.

76 FR 72391 - Privacy Act of 1974; System of Records

Science.gov (United States)

2011-11-23

...; military hospitalization and medical treatment, immunization, and pharmaceutical dosage records; home and... individuals. To detect fraud, waste and abuse pursuant to the authority contained in the Inspector General Act..., immunization, and pharmaceutical dosage records; home and work addresses; and identities of individuals...

[Application of FT-IR pattern recognition method for the quality control of pharmaceutical ingredients].

Science.gov (United States)

Horgos, József; Kóger, Péter; Zelkó, Romána

2009-01-01

Nowadays infrared spectroscopy and chemometrics have proven their effectiveness for both qualitative and quantitative analyses in different fields like agriculture, food, chemical and oil industry. Furier Transformation Infrared Spectroscopy (FT-IR) combined with Attenuated Total Reflectance (ATR) plate is a fast identification instrument. It is suitable for analysis of solid and liquid phase, too. Associated with chemometrics, it would be a powerful tool for the pharmaceutical wholesalers to detect the insufficient quality of pharmaceutical ingredients. In the present study beside the review of the infra red technology, pharmaceutical ingredients were examined with the help of our spectra library.

Solution Coating of Pharmaceutical Nanothin Films and Multilayer Nanocomposites with Controlled Morphology and Polymorphism.

Science.gov (United States)

Horstman, Elizabeth M; Kafle, Prapti; Zhang, Fengjiao; Zhang, Yifu; Kenis, Paul J A; Diao, Ying

2018-03-28

Nanosizing is rapidly emerging as an alternative approach to enhance solubility and thus the bioavailability of poorly aqueous soluble active pharmaceutical ingredients (APIs). Although numerous techniques have been developed to perform nanosizing of API crystals, precise control and modulation of their size in an energy and material efficient manner remains challenging. In this study, we present meniscus-guided solution coating as a new technique to produce pharmaceutical thin films of nanoscale thickness with controlled morphology. We demonstrate control of aspirin film thickness over more than 2 orders of magnitude, from 30 nm to 1.5 μm. By varying simple process parameters such as the coating speed and the solution concentration, the aspirin film morphology can also be modulated by accessing different coating regimes, namely the evaporation regime and the Landau-Levich regime. Using ellipticine-a poorly water-soluble anticancer drug-as another model compound, we discovered a new polymorph kinetically trapped during solution coating. Furthermore, the polymorphic outcome can be controlled by varying coating conditions. We further performed layer-by-layer coating of multilayer nanocomposites, with alternating thin films of ellipticine and a biocompatible polymer, which demonstrate the potential of additive manufacturing of multidrug-personalized dosage forms using this approach.

Development and Validation of Spectrophotometric Methods for the Determination of Rasagiline in Pharmaceutical Preparations

Directory of Open Access Journals (Sweden)

Serife Evrim Kepekci Tekkeli

2013-01-01

Full Text Available This study presents three simple, rapid, and accurate spectrophotometric methods for the determination of Rasagiline (RSG in pharmaceutical preparations. The determination procedures depend on the reaction of RSG with chloranilic acid for method A, tetrachloro-1,4-benzoquinone for method B, and 7,7,8,8-tetracyanoquinodimethane for method C. The colored products were quantitated spectrophotometrically at 524, 535, and 843 nm for methods A, B, and C, respectively. Different variables affecting the reaction were optimized. Linearity ranges of the methods with good correlation coefficients (0.9988–0.9996 were observed as 25–300 µg mL−1, 25–350 µg mL−1, and 50–500 µg mL−1 for methods A, B, and C, respectively. The formation of products takes place through different mechanisms. The sites of interaction were confirmed by elemental analysis using IR and 1H-NMR spectroscopy. The validation of the methods was carried out in terms of specificity, linearity, accuracy, precision, robustness, limit of detection, and limit of quantitation. No interference was observed from concomitants usually present in dosage forms. The methods were applied successfully to the determination of RSG in pharmaceutical preparations.

Application of DBNPA dosage for biofouling control in spiral wound membrane systems

KAUST Repository

Siddiqui, Amber

2017-05-30

Biocides may be used to control biofouling in spiral-wound reverse osmosis (RO) and nanofiltration (NF) systems. The objective of this study was to investigate the effect of biocide 2,2-dibromo-3-ni-trilopropionamide (DBNPA) dosage on biofouling control. Preventive biofouling control was studied applying a continuous dosage of substrate (0.5 mg/L) and DBNPA (1 mg/L). Curative biofouling control was studied on pre-grown biofilms, once again applying a continuous dosage of substrate (0.5 mg acetate C/L) and DBNPA (1 and 20 mg/L). Biofouling studies were performed in membrane fouling simulators (MFSs) supplied with biodegradable substrate and DBNPA. The pressure drop was monitored in time and at the end of the study, the accumulated biomass in MFS was quantified by adenosine triphosphate (ATP) and total organic carbon (TOC) analysis. Continuous dosage of DBNPA (1 mg/L) prevented pressure drop increase and biofilm accumulation in the MFSs during a run time of 7 d, showing that biofouling can be managed by preventive DBNPA dosage. For biofouled systems, continuous dosage of DBNPA (1 and 20 mg/L) inactivated the accumulated biomass but did not restore the original pressure drop and did not remove the accumulated inactive cells and extracellular polymeric substances (EPS), indicating DBNPA dosage is not suitable for curative biofouling control.

Quality of 'Climax' blueberries after low dosage electron beam irradiation

International Nuclear Information System (INIS)

Miller, W.R.; McDonald, R.E.; McCollum, T.G.; Smittle, B.J.

1994-01-01

Fruit of 'Climax' rabbiteye blueberries (Vaccinium ashei Reade) were irradiated by a linear accelerator at 0, 0.25, 0.5, 0.75, 1.0, and 1.25 kGy and evaluated for various quality attributes after storage for 1, 3, 7, or 14 days at 1C plus 2 days at 15C, respectively. Weight loss increased during storage and averaged 4.2% after the final inspection and was not affected by irradiation dosage. About 5% of total berries were decayed after 14 days at 1C, about 6% after the final inspection at 15C, but decay was not affected by the level of irradiation. Electrolyte leakage, skin color, total soluble solids, acidity, and pH were also not affected by irradiation dosage. There was a significant decline in berry firmness, flavor, and texture as dosage increased. Berries treated at 1.0 kGy or above were softer and had lower flavor and texture preference scores than berries treated at lower dosages or nontreated berries

Transforming lipid-based oral drug delivery systems into solid dosage forms: an overview of solid carriers, physicochemical properties, and biopharmaceutical performance.

Science.gov (United States)

Tan, Angel; Rao, Shasha; Prestidge, Clive A

2013-12-01

The diversity of lipid excipients available commercially has enabled versatile formulation design of lipid-based drug delivery systems for enhancing the oral absorption of poorly water-soluble drugs, such as emulsions, microemulsions, micelles, liposomes, niosomes and various self-emulsifying systems. The transformation of liquid lipid-based systems into solid dosage forms has been investigated for several decades, and has recently become a core subject of pharmaceutical research as solidification is regarded as viable means for stabilising lipid colloidal systems while eliminating stringent processing requirements associated with liquid systems. This review describes the types of pharmaceutical grade excipients (silica nanoparticle/microparticle, polysaccharide, polymer and protein-based materials) used as solid carriers and the current state of knowledge on the liquid-to-solid conversion approaches. Details are primarily focused on the solid-state physicochemical properties and redispersion capacity of various dry lipid-based formulations, and how these relate to the in vitro drug release and solubilisation, lipid carrier digestion and cell permeation performances. Numerous in vivo proof-of-concept studies are presented to highlight the viability of these dry lipid-based formulations. This review is significant in directing future research work in fostering translation of dry lipid-based formulations into clinical applications.

Main Strategies of Plant Expression System Glycoengineering for Producing Humanized Recombinant Pharmaceutical Proteins.

Science.gov (United States)

Rozov, S M; Permyakova, N V; Deineko, E V

2018-03-01

Most the pharmaceutical proteins are derived not from their natural sources, rather their recombinant analogs are synthesized in various expression systems. Plant expression systems, unlike mammalian cell cultures, combine simplicity and low cost of procaryotic systems and the ability for posttranslational modifications inherent in eucaryotes. More than 50% of all human proteins and more than 40% of the currently used pharmaceutical proteins are glycosylated, that is, they are glycoproteins, and their biological activity, pharmacodynamics, and immunogenicity depend on the correct glycosylation pattern. This review examines in detail the similarities and differences between N- and O-glycosylation in plant and mammalian cells, as well as the effect of plant glycans on the activity, pharmacokinetics, immunity, and intensity of biosynthesis of pharmaceutical proteins. The main current strategies of glycoengineering of plant expression systems aimed at obtaining fully humanized proteins for pharmaceutical application are summarized.

Spatial patterns of pharmaceuticals and wastewater tracers in the Hudson River Estuary.

Science.gov (United States)

Cantwell, Mark G; Katz, David R; Sullivan, Julia C; Shapley, Daniel; Lipscomb, John; Epstein, Jennifer; Juhl, Andrew R; Knudson, Carol; O'Mullan, Gregory D

2018-06-15

The widespread use of pharmaceuticals by human populations results in their sustained discharge to surface waters via wastewater treatment plants (WWTPs). In this study, 16 highly prescribed pharmaceuticals were quantified along a 250 km transect of the Hudson River Estuary and New York Harbor to describe their sources and spatial patterns. Sampling was conducted over two dry weather periods in May and July 2016, at 72 sites which included mid-channel and nearshore sites, as well as locations influenced by tributaries and WWTP outfalls. The detection frequency of the study pharmaceuticals was almost identical between the May and July sampling periods at 55% and 52%, respectively. Six pharmaceuticals were measurable at 92% or more of the sites during both sampling periods, illustrating their ubiquitous presence throughout the study area. Individual pharmaceutical concentrations were highly variable spatially, ranging from non-detect to 3810 ng/L during the study. Major factors controlling concentrations were proximity and magnitude of WWTP discharges, inputs from tributaries and tidal mixing. Two compounds, sucralose and caffeine, were evaluated as tracers to identify wastewater sources and assess pharmaceutical behavior. Sucralose was useful in identifying wastewater inputs to the river and concentrations showed excellent correlations with numerous pharmaceuticals in the study. Caffeine-sucralose ratios showed potential in identifying discharges of untreated wastewater occurring during a combined sewage overflow event. Many of the study pharmaceuticals were present throughout the Hudson River Estuary as a consequence of sustained wastewater discharge. Whereas some concentrations were above published effects levels, a more complete risk assessment is needed to understand the potential for ecological impacts due to pharmaceuticals in the Hudson River Estuary. Published by Elsevier Ltd.

PHARMACEUTICAL QUALITY OF GENERIC ATORVASTATIN PRODUCTS COMPARED WITH THE INNOVATOR PRODUCT: A NEED FOR REVISING PRICING POLICY IN PALESTINE.

Science.gov (United States)

Shawahna, Ramzi; Hroub, Abdel Kareem; Abed, Eliama; Jibali, Sondos; Al-Saghir, Ruba; Zaid, Abdel Naser

2016-01-01

Atorvastatin reduces morbidity and mortality due to cardiovascular events. This study was conducted to assess the prices and pharmaceutical quality of innovator atorvastatin 20 mg with its locally available generics in Palestine and to assess the suitability of their interchangeability. The prices of innovator and generic atorvastatin 20 mg were determined and compared. Innovator atorvastatin and four generic products were tested for their pharmaceutical quality. Tablets were tested for their drug contents, weight uniformity, hardness, disintegration and dissolution. Three out of four generics were less expensive than the innovator. Pharmaceutical quality assessments were satisfactory and within limits for all atorvastatin tested products. The average weight ranged from 206.6 ± 8.40 to 330 ± 3.92 mg and the %RSDs were within the permitted limits as per USP. Tablet hardness ranged from 102 ± 1.41 to 197.4 ± 6.88 kg and drug contents ranged from 92.2% to 105.3%. All products disintegrated within permitted time limits and showed very rapid dissolution. Products released more than 85% of their drug contents in less than 15 min. Our results showed that all tested innovator and generic atorvastatin products were of good pharmaceutical quality. Despite the lack of in vivo evaluation, our results indicate that these products are equivalent in vitro. Considering the in vitro release characteristics, these products might be used interchangeably. However, regulatory authorities permit the use of in vitro data in establishing similarity between immediate release oral dosage forms containing biopharmaceutical classification system class I and III drugs only.

Foreign matter identification from solid dosage forms

DEFF Research Database (Denmark)

Pekka Pajander, Jari; Haugshøj, Kenneth Brian; Bjørneboe, Kathrine

2013-01-01

Despite the increased request for robust quality systems, the end product may contain unidentified defects or discoloured regions. The foreign matter has to be monitored, identified and its source defined in order to prevent further contamination. However, the identification task can be complicated......, since the origin and nature of foreign matter are various. The aim of this study is to provide an efficient foreign matter identification procedure for various substances possibly originating from pharmaceutical manufacturing environment. The surface or cross-section of the uncoated and coated tablets...... was analysed by utilization of different analytical techniques, such as light microscopy (LM), scanning electron microscopy in combination with energy dispersive X-ray microanalysis (SEM/EDX), Fourier transform infrared spectroscopy (FT-IR) and time-of-flight secondary ion mass spectrometry (To...

[Logistics in the pharmaceutical service].

Science.gov (United States)

Stanko, P; Fulmeková, M

2005-11-01

The conception of the field of pharmaceutical service defines pharmaceutical service as the basic part of pharmacy, the principal task of which is to provide pharmaceutical care as an inseparable part of providing health care. It represents a set of professional activities of the pharmacist oriented to securing human and veterinary pharmaceutical products and health care products and to optimising effective, safe and quality pharmacotherapy. Technically, pharmaceutical service is an applied discipline, as it makes use of knowledge gained in other pharmaceutical, medical, psychological, social, and economic sciences. Because of its interdisciplinary character it is necessary to extend the theory of pharmaceutical service in such a way so that it may reflect all aspects of its sphere of activity. One of the possibilities is to define the pharmacy premises as an independent functional unit which operates on the basis of valid legal standards in such a way that on the one hand it secures the provision of health (pharmaceutical) care, and on the other hand it maintains its cost-effectiveness. To keep the quality of care of the patient and the economic aspect in balance, it is necessary to define the term pharmaceutical logistics also under the conditions of Slovak (Czech) pharmacy as early satisfaction of the requirements of the patient (client) in the pharmacy premises, which means that the appropriate pharmaceutical product or health care product and the appropriate information must be at the right time in the required amount and required quality in the right place.

Studies of beneficial interactions between active medicaments and excipients in pharmaceutical formulations.

Science.gov (United States)

Kalinkova, G N

1999-09-30

A review of "up to date" research findings leading to new concepts of the pharmaceutical formulations and their interactions has been presented. The rational approaches to the excipients choice as well as to their interactions with medicaments have been shown as a basis for modern modelling of pharmaceutical formulations. The importance of complexation, hydrogen bonding, ion-dipole, dipole-dipole and van der Waals attractions as the tools which can modify the physicochemical, pharmacological or pharmacokinetical behaviour of the medicaments has been emphasised. In vivo studies (carried out in healthy human subjects-volunteers, in beagle dogs, in rats etc.) and in vitro studies (on excised human skin, hairless mouse skin etc.) as well as studies of chemical stability and bioavailability serve also as a proof of these interactions. Therefore, excipients are important components of pharmaceutical formulations and they can take an active part in the improvement of the characteristics of formulations (but they may also reduce the effectiveness of some preparations). In this context, the so called active and inactive ingredients in pharmaceutical formulations are inexact, old and "out-of date". Their further use is only conventional. In conclusion, among the various modern techniques applied the combination of infrared spectroscopy and X-ray diffraction has been estimated as the most successful in proving the interactions between drugs and excipients. Finally, pharmaceutical formulations and their interactions have constituted a diverse and rapidly expanding field of Pharmacy (Pharmaceutical Technology, Pharmaceutical Industry and Pharmaceutical Sciences) which covers a wide range of numerical topics within an unified framework.

Pharmaceutical 3D printing: Design and qualification of a single step print and fill capsule.

Science.gov (United States)

Smith, Derrick M; Kapoor, Yash; Klinzing, Gerard R; Procopio, Adam T

2018-06-10

Fused deposition modeling (FDM) 3D printing (3DP) has a potential to change how we envision manufacturing in the pharmaceutical industry. A more common utilization for FDM 3DP is to build upon existing hot melt extrusion (HME) technology where the drug is dispersed in the polymer matrix. However, reliable manufacturing of drug-containing filaments remains a challenge along with the limitation of active ingredients which can sustain the processing risks involved in the HME process. To circumvent this obstacle, a single step FDM 3DP process was developed to manufacture thin-walled drug-free capsules which can be filled with dry or liquid drug product formulations. Drug release from these systems is governed by the combined dissolution of the FDM capsule 'shell' and the dosage form encapsulated in these shells. To prepare the shells, the 3D printer files (extension '.gcode') were modified by creating discrete zones, so-called 'zoning process', with individual print parameters. Capsules printed without the zoning process resulted in macroscopic print defects and holes. X-ray computed tomography, finite element analysis and mechanical testing were used to guide the zoning process and printing parameters in order to manufacture consistent and robust capsule shell geometries. Additionally, dose consistencies of drug containing liquid formulations were investigated in this work. Copyright © 2018 Elsevier B.V. All rights reserved.

Recent applications of Chemical Imaging to pharmaceutical process monitoring and quality control.

Science.gov (United States)

Gowen, A A; O'Donnell, C P; Cullen, P J; Bell, S E J

2008-05-01

Chemical Imaging (CI) is an emerging platform technology that integrates conventional imaging and spectroscopy to attain both spatial and spectral information from an object. Vibrational spectroscopic methods, such as Near Infrared (NIR) and Raman spectroscopy, combined with imaging are particularly useful for analysis of biological/pharmaceutical forms. The rapid, non-destructive and non-invasive features of CI mark its potential suitability as a process analytical tool for the pharmaceutical industry, for both process monitoring and quality control in the many stages of drug production. This paper provides an overview of CI principles, instrumentation and analysis. Recent applications of Raman and NIR-CI to pharmaceutical quality and process control are presented; challenges facing CI implementation and likely future developments in the technology are also discussed.

Pharmaceutical health care and Inuit language communications in Nunavut, Canada.

Science.gov (United States)

Romain, Sandra J

2013-01-01

Pharmaceutical communication is an essential component of pharmaceutical health care, optimally ensuring patients understand the proper administration and side effects of their medications. Communication can often be complicated by language and culture, but with pharmaceuticals, misunderstandings can prove particularly harmful. In Nunavut, to ensure the preservation and revitalization of Inuit languages, the Inuit Language Protection Act and Official Languages Act were passed requiring that all public and private sector essential services offer verbal and written communication in Inuit languages (Inuktitut and Inuinnaqtun) by 2012. While the legislation mandates compliance, policy implementation for pharmaceutical services is problematic. Not a single pharmacist in Nunavut is fluent in either of the Inuit languages. Pharmacists have indicated challenges in formally translating written documentation into Inuit languages based on concerns for patient safety. These challenges of negotiating the joint requirements of language legislation and patient safety have resulted in pharmacies using verbal on-site translation as a tenuous solution regardless of its many limitations. The complex issues of pharmaceutical health care and communication among the Inuit of Nunavut are best examined through multimethod research to encompass a wide range of perspectives. This methodology combines the richness of ethnographic data, the targeted depth of interviews with key informants and the breadth of cross-Canada policy and financial analyses. The analysis of this information would provide valuable insights into the current relationships between health care providers, pharmacists and Inuit patients and suggest future directions for policy that will improve the efficacy of pharmaceuticals and health care spending for the Inuit in Canada.

Pharmaceutical health care and Inuit language communications in Nunavut, Canada

Directory of Open Access Journals (Sweden)

Sandra J. Romain

2013-08-01

Full Text Available Background. Pharmaceutical communication is an essential component of pharmaceutical health care, optimally ensuring patients understand the proper administration and side effects of their medications. Communication can often be complicated by language and culture, but with pharmaceuticals, misunderstandings can prove particularly harmful. In Nunavut, to ensure the preservation and revitalization of Inuit languages, the Inuit Language Protection Act and Official Languages Act were passed requiring that all public and private sector essential services offer verbal and written communication in Inuit languages (Inuktitut and Inuinnaqtun by 2012. Methods. While the legislation mandates compliance, policy implementation for pharmaceutical services is problematic. Not a single pharmacist in Nunavut is fluent in either of the Inuit languages. Pharmacists have indicated challenges in formally translating written documentation into Inuit languages based on concerns for patient safety. These challenges of negotiating the joint requirements of language legislation and patient safety have resulted in pharmacies using verbal on-site translation as a tenuous solution regardless of its many limitations. Results. The complex issues of pharmaceutical health care and communication among the Inuit of Nunavut are best examined through multimethod research to encompass a wide range of perspectives. This methodology combines the richness of ethnographic data, the targeted depth of interviews with key informants and the breadth of cross-Canada policy and financial analyses. Conclusions. The analysis of this information would provide valuable insights into the current relationships between health care providers, pharmacists and Inuit patients and suggest future directions for policy that will improve the efficacy of pharmaceuticals and health care spending for the Inuit in Canada.

Understanding Pharmaceutical Sustainable Supply chains - A Case Study Application

Directory of Open Access Journals (Sweden)

Ana Margarida Santos Bravo

2013-06-01

Full Text Available A major paradigmchange is occurring in the pharmaceutical industry and an increase of returnsand recalls has been seen; although this industry in known for the continuoussearch for quality and regulatory compliance.Hence, in this paperwe combine the findings of previous literature reviews conducted by theauthors. Essentially, explore the links between pharmaceutical drugs quality,reverse logistics, and sustainability. A case study on a global corporationmanufacturing in the area of generic drug products has been selected andcorrelations are done with regards to returns and recalls from hospitalpharmacies, in particular. With this approach it is expected to link bothparties in the application of a quality by design risk management approach aswell as reduce variability and risk of noncompliance.

Pharmaceutical powder compaction technology

National Research Council Canada - National Science Library

Çelik, Metin

2011-01-01

"Revised to reflect modern pharmaceutical compacting techniques, this Second Edition guides pharmaceutical engineers, formulation scientists, and product development and quality assurance personnel...

Cancer therapy leading to state of cancer metabolism depression for efficient operation of small dosage cytotoxic drugs

Directory of Open Access Journals (Sweden)

Ponizovskiy MR

2015-04-01

Full Text Available “Prolonged medical starvation” as the method of cancer therapy was borrowed from folk healers Omelchenko A and Breuss R. Author was convinced in efficiency of this method of cancer treatment via examination of cured patients and on own experience. The mechanism of this method of cancer therapy operates via Warburg effect targeting that promotes efficient cancer treatment with small cytotoxic drugs. Just it was described the mechanism of Warburg effect as well as mechanism transmutation of mitochondrial function in cancer metabolism which are exhibited in connection with operation of described method cancer therapy. There were described the biochemical and biophysical mechanisms of formations resistance to some cytotoxic drugs and recurrence cancer disease after disease remission which occur sometimes as result of treatment with great dosage of cytotoxic drugs. Also it was described the benefits of use the method “Prolonged medical starvation” with decreased dosage of cytotoxic drugs for cancer treatment. The significance of this work that it was substantiated the mechanism operation of combination “Prolonged medical starvation” with small dosages cytotoxic drugs of cancer treatment, which mechanism leads to prevention recurrence cancer disease and resistance to anticancer drugs in comparison with intensive anticancer chemotherapy with great dosages of cytotoxic drugs in cancer therapy. Also the offered concepts of cancer therapy mechanism gave possibility to explain mechanisms of some results of experiments eliminating the doubts of the authors these experiments.

Preparation and evaluation of doxycycline hydrochloride and bromhexine hydrochloride dosage forms for pigeons / Marga le Roux

OpenAIRE

Le Roux, Marga

2004-01-01

Objective: To prepare and evaluate three different dosage forms, containing doxycycline hydrochloride (HCI) and bromhexine hydrochloride (HCI) respectively and in combination, for the treatment of respiratory diseases in pigeons. Background: Birds have held a place in man's affection since the ancient Egyptians and Romans kept birds. Europeans have successfully bred birds, especially smaller birds and pigeons, for centuries. Only in recent years, however, have science and me...

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.

Upgrade of deep bed filtration with activated carbon dosage for compact micropollutant removal from wastewater in technical scale.

Science.gov (United States)

Löwenberg, Jonas; Zenker, Armin; Krahnstöver, Thérèse; Boehler, Marc; Baggenstos, Martin; Koch, Gerhard; Wintgens, Thomas

2016-05-01

The removal of micropollutants from drinking and wastewater by powdered activated carbon (PAC) adsorption has received considerable attention in research over the past decade with various separation options having been investigated. With Switzerland as the first country in the world having adopted a new legislation, which forces about 100 wastewater treatment plants to be upgraded for the removal of organic micropollutants from municipal wastewater, the topic has reached practical relevance. In this study, the process combination of powdered activated carbon (PAC) adsorption and deep bed filtration (DBF) for advanced municipal wastewater treatment was investigated over an extended period exceeding one year of operation in technical scale. The study aimed to determine optimum process conditions to achieve sufficient micropollutant removal in agreement with the new Swiss Water Ordinance under most economic process design. It was shown that the addition of PAC and Fe(3+) as combined coagulation and flocculation agent improved effluent water quality with respect to dissolved organic pollutants as well as total suspended solids (TSS), turbidity and PO4-P concentration in comparison to a DBF operated without the addition of PAC and Fe(3+). Sufficient micropollutant (MP) removal of around 80% was achieved at PAC dosages of 10 mg/L revealing that PAC retained in the filter bed maintained considerable adsorption capacity. In the investigated process combination the contact reactor serves for adsorption as well as for flocculation and allowed for small hydraulic retention times of minimum 10 min while maintaining sufficient MP removal. The flocculation of two different PAC types was shown to be fully concluded after 10-15 min, which determined the flocculation reactor size while both PAC types proved suitable for the application in combination with DBF and showed no significant differences in MP removal. Finally, the capping of PAC dosage during rain water periods, which

Incremental impact of body mass status with modifiable unhealthy lifestyle behaviors on pharmaceutical expenditure.

Science.gov (United States)

Kim, Tae Hyun; Lee, Eui-Kyung; Han, Euna

Overweight/obesity is a growing health risk in Korea. The impact of overweight/obesity on pharmaceutical expenditure can be larger if individuals have multiple risk factors and multiple comorbidities. The current study estimated the combined effects of overweight/obesity and other unhealthy behaviors on pharmaceutical expenditure. An instrumental variable quantile regression model was estimated using Korea Health Panel Study data. The current study extracted data from 3 waves (2009, 2010, and 2011). The final sample included 7148 person-year observations for adults aged 20 years or older. Overweight/obese individuals had higher pharmaceutical expenditure than their non-obese counterparts only at the upper quantiles of the conditional distribution of pharmaceutical expenditure (by 119% at the 90th quantile and 115% at the 95th). The current study found a stronger association at the upper quantiles among men (152%, 144%, and 150% at the 75th, 90th, and 95th quantiles, respectively) than among women (152%, 150%, and 148% at the 75th, 90th, and 95th quantiles, respectively). The association at the upper quantiles was stronger when combined with moderate to heavy drinking and no regular physical check-up, particularly among males. The current study confirms that the association of overweight/obesity with modifiable unhealthy behaviors on pharmaceutical expenditure is larger than with overweight/obesity alone. Assessing the effect of overweight/obesity with lifestyle risk factors can help target groups for public health intervention programs. Copyright © 2015 Elsevier Inc. All rights reserved.

Pharmaceutical removal during managed aquifer recharge with pretreatment by advanced oxidation

KAUST Repository

Lekkerkerker-Teunissen, Karin

2012-10-01

Organic micropollutants (OMPs) are detected in sources for drinking water and treatment possibilities are investigated. Innovative removal technologies are available such as membrane filtration and advanced oxidation, but also biological treatment should be considered. By combining an advanced oxidation process with managed aquifer recharge (MAR), two complementary processes are expected to provide a hybrid system for OMP removal, according to the multiple barrier approach. Laboratory scale batch reactor experiments were conducted to investigate the removal of dissolved organic carbon (DOC) and 14 different pharmaceutically active compounds (PhACs) from MAR influent water and water subjected to oxidation, under different process conditions. A DOC removal of 10% was found in water under oxic (aerobic) conditions for batch reactor experiments, a similar value for DOC removal was observed in the field. Batch reactor experiments for the removal of PhACs showed that the removal of pharmaceuticals ranged from negligible to more than 90%. Under oxic conditions, seven out of 14 pharmaceuticals were removed over 90% and 12 out of 14 pharmaceuticals were removed at more than 50% during 30 days of experiments. Under anoxic conditions, four out of 14 pharmaceuticals were removed over 90% and eight out of 14 pharmaceuticals were removed at more than 50% over 30 days\\' experiments. Carbamazepine and phenazone were persistent both under oxic and anoxic conditions. The PhACs removal efficiency with oxidized water was, for most compounds, comparable to the removal with MAR influent water. Copyright © IWA Publishing 2012.

Pharmaceutical removal during managed aquifer recharge with pretreatment by advanced oxidation

KAUST Repository

Lekkerkerker-Teunissen, Karin; Chekol, E. T.; Maeng, Sungkyu; Ghebremichael, Kebreab A.; Houtman, Corine J.; Verliefde, Arne R. D.; Verberk, J. Q J C; Amy, Gary L.; Van Dijk, Johannis C.

2012-01-01

Organic micropollutants (OMPs) are detected in sources for drinking water and treatment possibilities are investigated. Innovative removal technologies are available such as membrane filtration and advanced oxidation, but also biological treatment should be considered. By combining an advanced oxidation process with managed aquifer recharge (MAR), two complementary processes are expected to provide a hybrid system for OMP removal, according to the multiple barrier approach. Laboratory scale batch reactor experiments were conducted to investigate the removal of dissolved organic carbon (DOC) and 14 different pharmaceutically active compounds (PhACs) from MAR influent water and water subjected to oxidation, under different process conditions. A DOC removal of 10% was found in water under oxic (aerobic) conditions for batch reactor experiments, a similar value for DOC removal was observed in the field. Batch reactor experiments for the removal of PhACs showed that the removal of pharmaceuticals ranged from negligible to more than 90%. Under oxic conditions, seven out of 14 pharmaceuticals were removed over 90% and 12 out of 14 pharmaceuticals were removed at more than 50% during 30 days of experiments. Under anoxic conditions, four out of 14 pharmaceuticals were removed over 90% and eight out of 14 pharmaceuticals were removed at more than 50% over 30 days' experiments. Carbamazepine and phenazone were persistent both under oxic and anoxic conditions. The PhACs removal efficiency with oxidized water was, for most compounds, comparable to the removal with MAR influent water. Copyright © IWA Publishing 2012.

Tropical Journal of Pharmaceutical Research

African Journals Online (AJOL)

Journal Homepage Image. We seek to encourage pharmaceutical and allied research of tropical and international relevance and to foster multidisciplinary research and collaboration among scientists, the pharmaceutical industry and the healthcare professionals. We publish articles in pharmaceutical sciences and related ...

The Korean Pharmaceutical Industry and the Expansion of the General Pharmaceuticals Market in the 1950-1960s

Directory of Open Access Journals (Sweden)

Kyu-Hwan SIHN

2015-12-01

Full Text Available After the Liberation, the Korean economy was dependent on relief supplies and aid after the ruin of the colonial regime and war. The pharmaceutical business also searched for their share in the delivery of military supplies and the distribution of relief supplies. The supply-side pharmaceutical policy made the pharmaceutical market a wholesale business. The gravity of the situation led to an increased importation of medical supplies, and wholesalers took the lead in establishing the distribution structure, whereas consumers and pharmaceutical business were relatively intimidated. The aid provided by the International Cooperation Administration (ICA marked a turning point in the Korean pharmaceutical industry after the middle of the 1950s. ICA supplied raw materials and equipment funds, while the pharmaceutical business imported advanced technology and capital. The government invited the local production of medical substances, whereas pharmaceutical businesses replaced imported medical substances with locally produced antibiotics. After the 1960s, the production of antibiotics reached saturation. Pharmaceutical businesses needed new markets to break through the stalemate, so they turned their attention to vitamins and health tonics as general pharmaceuticals, as these were suitable for mass production and mass consumption. The modernized patent medicine market after the Opening of Korea was transformed into the contemporized general pharmaceuticals market equipped with the up-to-date facilities and technology in 1960s. Pharmaceutical businesses had to advertise these new products extensively and reform the distribution structure to achieve high profits. With the introduction of TV broadcasting, these businesses invested in TV advertising and generated sizable sales figures. They also established retail pharmacy and chain stores to reform the distribution structure. The end result was a dramatic expansion of the general pharmaceuticals market. The

[The Korean Pharmaceutical Industry and the Expansion of the General Pharmaceuticals Market in the 1950-1960s].

Science.gov (United States)

Sihn, Kyu-Hwan

2015-12-01

After the Liberation, the Korean economy was dependent on relief supplies and aid after the ruin of the colonial regime and war. The pharmaceutical business also searched for their share in the delivery of military supplies and the distribution of relief supplies. The supply-side pharmaceutical policy made the pharmaceutical market a wholesale business. The gravity of the situation led to an increased importation of medical supplies, and wholesalers took the lead in establishing the distribution structure, whereas consumers and pharmaceutical business were relatively intimidated. The aid provided by the International Cooperation Administration (ICA) marked a turning point in the Korean pharmaceutical industry after the middle of the 1950s. ICA supplied raw materials and equipment funds, while the pharmaceutical business imported advanced technology and capital. The government invited the local production of medical substances, whereas pharmaceutical businesses replaced imported medical substances with locally produced antibiotics. After the 1960s, the production of antibiotics reached saturation. Pharmaceutical businesses needed new markets to break through the stalemate, so they turned their attention to vitamins and health tonics as general pharmaceuticals, as these were suitable for mass production and mass consumption. The modernized patent medicine market after the Opening of Korea was transformed into the contemporized general pharmaceuticals market equipped with the up-to-date facilities and technology in 1960s. Pharmaceutical businesses had to advertise these new products extensively and reform the distribution structure to achieve high profits. With the introduction of TV broadcasting, these businesses invested in TV advertising and generated sizable sales figures. They also established retail pharmacy and chain stores to reform the distribution structure. The end result was a dramatic expansion of the general pharmaceuticals market. The market for

The shaping and functional consequences of the dosage effect landscape in multiple myeloma.

Science.gov (United States)

Samur, Mehmet K; Shah, Parantu K; Wang, Xujun; Minvielle, Stéphane; Magrangeas, Florence; Avet-Loiseau, Hervé; Munshi, Nikhil C; Li, Cheng

2013-10-02

Multiple myeloma (MM) is a malignant proliferation of plasma B cells. Based on recurrent aneuploidy such as copy number alterations (CNAs), myeloma is divided into two subtypes with different CNA patterns and patient survival outcomes. How aneuploidy events arise, and whether they contribute to cancer cell evolution are actively studied. The large amount of transcriptomic changes resultant of CNAs (dosage effect) pose big challenges for identifying functional consequences of CNAs in myeloma in terms of specific driver genes and pathways. In this study, we hypothesize that gene-wise dosage effect varies as a result from complex regulatory networks that translate the impact of CNAs to gene expression, and studying this variation can provide insights into functional effects of CNAs. We propose gene-wise dosage effect score and genome-wide karyotype plot as tools to measure and visualize concordant copy number and expression changes across cancer samples. We find that dosage effect in myeloma is widespread yet variable, and it is correlated with gene expression level and CNA frequencies in different chromosomes. Our analysis suggests that despite the enrichment of differentially expressed genes between hyperdiploid MM and non-hyperdiploid MM in the trisomy chromosomes, the chromosomal proportion of dosage sensitive genes is higher in the non-trisomy chromosomes. Dosage-sensitive genes are enriched by genes with protein translation and localization functions, and dosage resistant genes are enriched by apoptosis genes. These results point to future studies on differential dosage sensitivity and resistance of pro- and anti-proliferation pathways and their variation across patients as therapeutic targets and prognosis markers. Our findings support the hypothesis that recurrent CNAs in myeloma are selected by their functional consequences. The novel dosage effect score defined in this work will facilitate integration of copy number and expression data for identifying driver

Pharmaceutical Formulation Facilities as Sources of Opioids and Other Pharmaceuticals to Wastewater Treatment Plant Effluents

Science.gov (United States)

2010-01-01

Facilities involved in the manufacture of pharmaceutical products are an under-investigated source of pharmaceuticals to the environment. Between 2004 and 2009, 35 to 38 effluent samples were collected from each of three wastewater treatment plants (WWTPs) in New York and analyzed for seven pharmaceuticals including opioids and muscle relaxants. Two WWTPs (NY2 and NY3) receive substantial flows (>20% of plant flow) from pharmaceutical formulation facilities (PFF) and one (NY1) receives no PFF flow. Samples of effluents from 23 WWTPs across the United States were analyzed once for these pharmaceuticals as part of a national survey. Maximum pharmaceutical effluent concentrations for the national survey and NY1 effluent samples were generally effluent had median concentrations ranging from 3.4 to >400 μg/L. Maximum concentrations of oxycodone (1700 μg/L) and metaxalone (3800 μg/L) in samples from NY3 effluent exceeded 1000 μg/L. Three pharmaceuticals (butalbital, carisoprodol, and oxycodone) in samples of NY2 effluent had median concentrations ranging from 2 to 11 μg/L. These findings suggest that current manufacturing practices at these PFFs can result in pharmaceuticals concentrations from 10 to 1000 times higher than those typically found in WWTP effluents. PMID:20521847

Doubled dosage of sofosbuviris expected for inhibiting Zika virus infection

Institute of Scientific and Technical Information of China (English)

Somsri Wiwanitkit; Viroj Wiwanitkit

2017-01-01

Sofosbuvir is a new antiviral drug that has been recommended for management of hepatitis C virus (HCV) for a few years. New researches support that sofosbuvir might be useful for the management of Zika virus infection. Based on the pharmacological activity, inhibiting the HCV RNA-dependent RNA polymerase (RdRp or NS5 protein), sofosbuvir is proposed for its effectiveness against Zika virus infection. Here, the authors used a mathematical modelling theoretical approach to predict the expected dosage of sofosbuvir for inhibiting Zika virus infection. Based on the modeling study, if sofosbuvir is assigned for management of Zika virus infection, doubled dosage of the present dosage for hepatitis C management is recommended.

Dosage of boron traces in graphite, uranium and beryllium oxide

International Nuclear Information System (INIS)

Coursier, J.; Hure, J.; Platzer, R.

1955-01-01

The problem of the dosage of the boron in the materials serving to the construction of nuclear reactors arises of the following way: to determine to about 0,1 ppm close to the quantities of boron of the order of tenth ppm. We have chosen the colorimetric analysis with curcumin as method of dosage. To reach the indicated contents, it is necessary to do a previous separation of the boron and the materials of basis, either by extraction of tetraphenylarsonium fluoborate in the case of the boron dosage in uranium and the beryllium oxide, either by the use of a cations exchanger resin of in the case of graphite. (M.B.) [fr

Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Amoxicillin Trihydrate.

Science.gov (United States)

Thambavita, Dhanusha; Galappatthy, Priyadarshani; Mannapperuma, Uthpali; Jayakody, Lal; Cristofoletti, Rodrigo; Abrahamsson, Bertil; Groot, Dirk W; Langguth, Peter; Mehta, Mehul; Parr, Alan; Polli, James E; Shah, Vinod P; Dressman, Jennifer

2017-10-01

Literature and experimental data relevant to waiver of in vivo bioequivalence (BE) testing for the approval of immediate-release solid oral dosage forms containing amoxicillin trihydrate are reviewed. Solubility and permeability characteristics according to the Biopharmaceutics Classification System (BCS), therapeutic uses, therapeutic index, excipient interactions, as well as dissolution and BE and bioavailability studies were taken into consideration. Solubility and permeability studies indicate that amoxicillin doses up to 875 mg belong to BCS class I, whereas 1000 mg belongs to BCS class II and doses of more than 1000 mg belong to BCS class IV. Considering all aspects, the biowaiver procedure can be recommended for solid oral products of amoxicillin trihydrate immediate-release preparations containing amoxicillin as the single active pharmaceutical ingredient at dose strengths of 875 mg or less, provided (a) only the excipients listed in this monograph are used, and only in their usual amounts, (b) the biowaiver study is performed according to the World Health Organization-, U.S. Food and Drug Administration-, or European Medicines Agency-recommended method using the innovator as the comparator, and (c) results comply with criteria for "very rapidly dissolving" or "similarly rapidly dissolving." Products containing other excipients and those containing more than 875 mg amoxicillin per unit should be subjected to an in vivo BE study. Copyright © 2017 American Pharmacists Association®. All rights reserved.

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

TaS2 nanosheet-based room-temperature dosage meter for nitric oxide

Directory of Open Access Journals (Sweden)

Qiyuan He

2014-09-01

Full Text Available A miniature dosage meter for toxic gas is developed based on TaS2 nanosheets, which is capable of indicating the toxic dosage of trace level NO at room temperature. The TaS2 film-based chemiresistor shows an irreversible current response against the exposure of NO. The unique non-recovery characteristic makes the TaS2 film-based device an ideal indicator of total dosage of chronicle exposure.

A brief history of dosage compensation

Indian Academy of Sciences (India)

depression of X-linked gene activity in the female, as well as by hyperexpression of the ... to the Harvey lecture, Muller had presented important ideas relative to dosage ... at Columbia. I do recall a talk by the popular physical anthro- pologist ...

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.

Nasal Drug Delivery in Traditional Persian Medicine

Science.gov (United States)

Zarshenas, Mohammad Mehdi; Zargaran, Arman; Müller, Johannes; Mohagheghzadeh, Abdolali

2013-01-01

Background Over one hundred different pharmaceutical dosage forms have been recorded in literatures of Traditional Persian Medicine among which nasal forms are considerable. Objectives This study designed to derive the most often applied nasal dosage forms together with those brief clinical administrations. Materials and Methods In the current study remaining pharmaceutical manuscripts of Persia during 9th to 18th century AD have been studied and different dosage forms related to nasal application of herbal medicines and their therapeutic effects were derived. Results By searching through pharmaceutical manuscripts of medieval Persia, different nasal dosage forms involving eleven types related to three main groups are found. These types could be derived from powder, solution or liquid and gaseous forms. Gaseous form were classified into fumigation (Bakhoor), vapor bath (Enkebab), inhalation (Lakhlakheh), aroma agents (Ghalieh) and olfaction or smell (Shomoom). Nasal solutions were as drops (Ghatoor), nasal snuffing drops (Saoot) and liquid snuff formulations (Noshoogh). Powders were as nasal insufflation or snorting agents (Nofookh) and errhine or sternutator medicine (Otoos). Nasal forms were not applied only for local purposes. Rather systemic disorders and specially CNS complications were said to be a target for these dosage forms. Discussion While this novel type of drug delivery is known as a suitable substitute for oral and parenteral administration, it was well accepted and extensively mentioned in Persian medical and pharmaceutical manuscripts and other traditional systems of medicine as well. Accordingly, medieval pharmaceutical standpoints on nasal dosage forms could still be an interesting subject of study. Therefore, the current work can briefly show the pharmaceutical knowledge on nasal formulations in medieval Persia and clarify a part of history of traditional Persian pharmacy. PMID:24624204

Pavor nocturnus: a complication of single daily tricyclic or neuroleptic dosage.

Science.gov (United States)

Flemenbaum, A

1976-05-01

The author tested the hypothesis that a single bedtime dosage schedule of tricyclic or neuroleptic medication produces increased frequency of night terrors by administering a questionnaire to 30 medical patients who were not receiving such medications and 100 psychiatric patients on either multiple- or single-dosage schedules. Psychiatric patients on multiple-dosage schedules reported no more frightening dreams than the medical patients, whereas almost three-fourths of those receiving single bedtime doses had frightening dreams, a significant difference from the medical sample. This preliminary report is presented to call attention to the possible undesirable effects of a single dose schedule.

Spectrofluorimetric protocol for antidepressant drugs in dosage forms and human plasma through derivatization with dansyl chloride

Directory of Open Access Journals (Sweden)

Mahmoud A. Omar

2017-05-01

Full Text Available A reliable, sensitive and selective spectrofluorimetric method has been developed for the determination of certain antidepressant drugs namely sertraline hydrochloride, fluoxetine hydrochloride, paroxetine hydrochloride, amineptine hydrochloride and bupropion hydrochloride in pure forms, pharmaceutical formulation and human plasma. The method is based on the reaction of investigated drugs with 5-(dimethylamino naphthalene-1-sulfonyl chloride (dansyl chloride in the presence of 0.5 M sodium carbonate to yield highly fluorescent derivatives, measured at 450 nm (excitation at 347 nm. The different experimental parameters affecting the development and stability of the reaction products were carefully studied and optimized. The calibration plots were constructed over the range of 0.02–0.14 μg mL−1. The proposed method was successfully applied for analysis of cited drugs in dosage forms. The high sensitivity of the proposed method allows the determination of investigated drugs in spiked and real human plasma. Statistical comparisons of the results with the reference methods show an excellent agreement and indicate no significant difference in accuracy and precision.

Simultaneous removal and evaluation of organic substrates and NH3-N by a novel combined process in treating chemical synthesis-based pharmaceutical wastewater

International Nuclear Information System (INIS)

Chen, Zhaobo; Wang, Hongcheng; Ren, Nanqi; Cui, Minhua; Nie, Shukai; Hu, Dongxue

2011-01-01

Highlights: ► We research a novel combined process to treat chemical synthesis-based pharmaceutical wastewater. ► The mechanism of amoxicillin verifies that the biodegradation, adsorption, hydrolysis and unknown mechanism were able to remove amoxicillin from wastewater. ► In this study demonstrates that biodegradation is the major factor for removal mechanism at work for amoxicillin. ► Mathematical statistic methods were employed to evaluate the performance of the WWTP. - Abstract: A full-scale novel combined anaerobic/micro-aerobic and two-stage aerobic biological process is used for the treatment of an actual chemical synthesis-based pharmaceutical wastewater containing amoxicillin. The anaerobic system is an up-flow anaerobic sludge blanket (UASB), the micro-aerobic system is a novel micro-aerobic hydrolysis acidification reactor (NHAR) and the two-stage aerobic process comprised cyclic activated sludge system (CASS) and biological contact oxidation tank (BCOT). The influent wastewater was high in COD, NH 3 -N varying daily 4016–13,093 mg-COD L −1 and 156.4–650.2 mg-NH 3 -N L −1 , amoxicillin varying weekly between 69.1 and 105.4 mg-amoxicillin L −1 , respectively; Almost all the COD, NH 3 -N, amoxicillin were removed by the biological combined system, with removal percentages 97%, 93.4% and 97.2%, respectively, leaving around 104 mg-COD L −1 , 9.4 mg-NH 3 -N L −1 and 2.6 ± 0.8 mg-amoxicillin L −1 in the final clarifier effluent. The performance evaluation of the wastewater treatment plant (WWTP) by mathematical statistic methods shown that at most of time effluent can meet the higher treatment discharge standard. In addition, the fate of amoxicillin in the full-scale WWTP and the amoxicillin removal rate of each different removal routes in UASB, NHAR, CASS, BCOT and final clarifier processes are investigated in this paper. The results show that biodegradation, adsorption and hydrolysis are the major mechanisms for amoxicillin removal.

The pharmaceutical death-ride of dihydroartemisinin.

Science.gov (United States)

Jansen, Frans Herwig

2010-07-22

In the 2010 second edition of WHO's guidelines for the treatment of malaria, the relatively new fixed dose combination dihydroartemisinin-piperaquine is included as one of the recommended artemisinin combination therapies. However, experimental testing demonstrates that, due to its intrinsic chemical instability, dihydroartemisinin is not suitable to be used in pharmaceutical formulations. In addition, data show that the currently available dihydroartemisinin preparations fail to meet the internationally accepted stability requirements. At a time when many efforts aim to ban counterfeit and substandard drugs from the malaria market, the obvious question rises how WHO and public-private partnerships, such as Medicine for Malaria venture (MMV), can support the production and marketing of anti-malarial drugs that do not even meet the International Pharmacopoeia requirements?

The pharmaceutical death-ride of dihydroartemisinin

Directory of Open Access Journals (Sweden)

Jansen Frans

2010-07-01

Full Text Available Abstract In the 2010 second edition of WHO's guidelines for the treatment of malaria, the relatively new fixed dose combination dihydroartemisinin-piperaquine is included as one of the recommended artemisinin combination therapies. However, experimental testing demonstrates that, due to its intrinsic chemical instability, dihydroartemisinin is not suitable to be used in pharmaceutical formulations. In addition, data show that the currently available dihydroartemisinin preparations fail to meet the internationally accepted stability requirements. At a time when many efforts aim to ban counterfeit and substandard drugs from the malaria market, the obvious question rises how WHO and public-private partnerships, such as Medicine for Malaria venture (MMV, can support the production and marketing of anti-malarial drugs that do not even meet the International Pharmacopoeia requirements?

21 CFR 522.1662 - Oxytetracycline hydrochloride implantation or injectable dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride implantation or injectable dosage forms. 522.1662 Section 522.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1662 Oxytetracycline hydrochloride implantation or injectable...

Sonochemical degradation of the pharmaceutical fluoxetine: Effect of parameters, organic and inorganic additives and combination with a biological system

Energy Technology Data Exchange (ETDEWEB)

Serna-Galvis, Efraím A.; Silva-Agredo, Javier [Grupo de Investigación en Remediación Ambiental y Biocatálisis, Instituto de Química, Facultad de Ciencias Exactas y Naturales, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín (Colombia); Giraldo-Aguirre, Ana L. [Grupo de Diseño y Formulación de Medicamentos, Cosméticos y Afines (DYFOMECO), Facultad de Química Farmacéutica, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín (Colombia); Torres-Palma, Ricardo A., E-mail: ricardo.torres@udea.edu.co [Grupo de Investigación en Remediación Ambiental y Biocatálisis, Instituto de Química, Facultad de Ciencias Exactas y Naturales, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín (Colombia)

2015-08-15

Fluoxetine (FLX), one of the most widely used antidepressants in the world, is an emergent pollutant found in natural waters that causes disrupting effects on the endocrine systems of some aquatic species. This work explores the total elimination of FLX by sonochemical treatment coupled to a biological system. The biological process acting alone was shown to be unable to remove the pollutant, even under favourable conditions of pH and temperature. However, sonochemical treatment (600 kHz) was shown to be able to remove the pharmaceutical. Several parameters were evaluated for the ultrasound application: the applied power (20–60 W), dissolved gas (air, Ar and He), pH (3–11) and initial concentration of fluoxetine (2.9–162.0 μmol L{sup −1}). Additionally, the presence of organic (1-hexanol and 2-propanol) and inorganic (Fe{sup 2+}) compounds in the water matrix and the degradation of FLX in a natural mineral water were evaluated. The sonochemical treatment readily eliminates FLX following a kinetic Langmuir. After 360 min of ultrasonic irradiation, 15% mineralization was achieved. Analysis of the biodegradability provided evidence that the sonochemical process transforms the pollutant into biodegradable substances, which can then be mineralized in a subsequent biological treatment. - Highlights: • The pharmaceutical fluoxetine was effectively eliminated upon ultrasonic action. • Ultrasonic power, dissolved gas, pH and concentration of fluoxetine were evaluated. • Fe{sup 2+}, sodium nitrate or nitric acid had a positive effect on the FLX degradation. • More hydrophobic or volatile compounds than fluoxetine diminished the efficiency. • A sonochemical-biological combined process led to the total mineralization of FLX.

Sonochemical degradation of the pharmaceutical fluoxetine: Effect of parameters, organic and inorganic additives and combination with a biological system

International Nuclear Information System (INIS)

Serna-Galvis, Efraím A.; Silva-Agredo, Javier; Giraldo-Aguirre, Ana L.; Torres-Palma, Ricardo A.

2015-01-01

Fluoxetine (FLX), one of the most widely used antidepressants in the world, is an emergent pollutant found in natural waters that causes disrupting effects on the endocrine systems of some aquatic species. This work explores the total elimination of FLX by sonochemical treatment coupled to a biological system. The biological process acting alone was shown to be unable to remove the pollutant, even under favourable conditions of pH and temperature. However, sonochemical treatment (600 kHz) was shown to be able to remove the pharmaceutical. Several parameters were evaluated for the ultrasound application: the applied power (20–60 W), dissolved gas (air, Ar and He), pH (3–11) and initial concentration of fluoxetine (2.9–162.0 μmol L −1 ). Additionally, the presence of organic (1-hexanol and 2-propanol) and inorganic (Fe 2+ ) compounds in the water matrix and the degradation of FLX in a natural mineral water were evaluated. The sonochemical treatment readily eliminates FLX following a kinetic Langmuir. After 360 min of ultrasonic irradiation, 15% mineralization was achieved. Analysis of the biodegradability provided evidence that the sonochemical process transforms the pollutant into biodegradable substances, which can then be mineralized in a subsequent biological treatment. - Highlights: • The pharmaceutical fluoxetine was effectively eliminated upon ultrasonic action. • Ultrasonic power, dissolved gas, pH and concentration of fluoxetine were evaluated. • Fe 2+ , sodium nitrate or nitric acid had a positive effect on the FLX degradation. • More hydrophobic or volatile compounds than fluoxetine diminished the efficiency. • A sonochemical-biological combined process led to the total mineralization of FLX

[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.

A Comparison Study of the Removal of Selected Pharmaceuticals in Waters by Chemical Oxidation Treatments

OpenAIRE

F. Javier Benitez; Juan Luis Acero; Francisco J. Real; Gloria Roldan; Francisco Casas

2011-01-01

The degradation of selected pharmaceuticals in some water matrices was studied by using several chemical treatments. The pharmaceuticals selected were the beta-blocker metoprolol, the nonsteroidal anti-inflammatory naproxen, the antibiotic amoxicillin, and the analgesic phenacetin; and their degradations were conducted by using UV radiation alone, ozone, Fenton-s reagent, Fenton-like system, photo-Fenton system, and combinations of UV radiation and ozone with H2O2, TiO2, ...

Sensing of chlorpheniramine in pharmaceutical applications by sequential injector coupled with potentiometer

Directory of Open Access Journals (Sweden)

Tawfik A. Saleh

2011-11-01

Full Text Available This paper reports on development of a system consisting of a portable sequential injector coupled with potentiometric unit for sensing of chlorpheniramine (CPA, based on the reaction of CPA with potassium permanganate in acidic media. Various experimental conditions affecting the potential intensity were studied and incorporated into the procedure. Under the optimum conditions, linear relationship between the CPA concentration and peak area was obtained for the concentration range of 0.1–50 ppm. The method reflects good recovery with relative standard deviation (RSD<3%. The detection limit was 0.05 ppm. The developed method was successfully applied for determination of CPA in pure form and in pharmaceutical dosage forms. The results, obtained using the method, are in accord with the results of the British pharmacopoeia method. In addition to its accuracy and precision, the method has the advantages of being simple, inexpensive and rapid. Keywords: Sensing, Flow injection, Chlorpheniramine, Potentiometry

Effect of alkaline addition on anaerobic sludge digestion with combined pretreatment of alkaline and high pressure homogenization.

Science.gov (United States)

Fang, Wei; Zhang, Panyue; Zhang, Guangming; Jin, Shuguang; Li, Dongyi; Zhang, Meixia; Xu, Xiangzhe

2014-09-01

To improve anaerobic digestion efficiency, combination pretreatment of alkaline and high pressure homogenization was applied to pretreat sewage sludge. Effect of alkaline dosage on anaerobic sludge digestion was investigated in detail. SCOD of sludge supernatant significantly increased with the alkaline dosage increase after the combined pretreatment because of sludge disintegration. Organics were significantly degraded after the anaerobic digestion, and the maximal SCOD, TCOD and VS removal was 73.5%, 61.3% and 43.5%, respectively. Cumulative biogas production, methane content in biogas and biogas production rate obviously increased with the alkaline dosage increase. Considering both the biogas production and alkaline dosage, the optimal alkaline dosage was selected as 0.04 mol/L. Relationships between biogas production and sludge disintegration showed that the accumulative biogas was mainly enhanced by the sludge disintegration. The methane yield linearly increased with the DDCOD increase as Methane yield (ml/gVS)=4.66 DDCOD-9.69. Copyright © 2014 Elsevier Ltd. All rights reserved.

Comparative pharmacokinetic study of dosage forms with morpholinium 2-[5-(pyridin-4-yl-1,2,4-triazol-3-ylthio] acetate

Directory of Open Access Journals (Sweden)

I. V. Bushueva

2014-12-01

Full Text Available Using mathematical models of income distribution and excretion of drugs greatly enhances the interpretation of the results of biopharmaceutical research. Pharmacokinetic modeling makes it possible to quantify the biological assessment of pharmaceutical factors, opens the possibility of a science-based regulation of the kinetics of substances introduced through targeted changesof pharmaceutical factors. Results of the study of kinetic models are used to solve some practical problems associated with pharmacological and clinical trials of medicines. Morpholinium 2-[5-(pyridin-4-yl-1,2,4-triazol-3-ylthio] acetate is new organic compound from the 1,2,4-triazole group obtained at the Department of Inorganic Chemistry, Zaporozhye State Medical University. The substance has antioxidant and anti-ischemic action, low toxicity. Aim of this work is to study the kinetics of absorption of morpholinium 2-[5-(pyridin-4-yl-1,2,4-triazol-3-ylthio] acetate developed formulations. MATERIALS AND METHODS Pharmacokinetic studies of oral and rectal dosage forms of morpholinium 2-[5-(pyridin-4-yl-1,2,4-triazol-3-ylthio] acetate was performed on Chinchilla rabbits weighing an average of 2.5 kg, divided into three groups. The third group for comparison was administered a 1% injectable solution of morpholinium 2-[5-(pyridin-4-yl-1,2,4-triazol-3-ylthio] acetate intravenously. Substance dose was 0.1 g and 0.5 g per kg of animal body weight, which were administered once. Sampling from the auricular vein of the rabbits was performed at 5, 10, 15, 30, 45, 60, 75, 90, 120, 150 and 180 minutes after oral administration and rectal dosage forms of morpholinium 2-[5-(pyridin-4-yl-1,2,4-triazol-3-ylthio] acetate and after 3, 5, 10, 15, 20, 30, 40, 50 and 60 minutes after intravenous injection. Morpholinium 2-[5-(pyridin-4-yl-1,2,4-triazol-3-ylthio] acetate concentration in serum was adjusted spectrophotometrically. Results.Morpholinium 2-[5-(pyridin-4-yl-1,2,4-triazol-3-ylthio

Evaluation of Combined Peracetic acid and UV treatment for ...

Science.gov (United States)

The current study evaluates the effectiveness of the combined application of Peracetic acid and ultraviolet radiation as alternative disinfectant agents to the traditional chlorination of wastewater effluents. Various pathogens (E. coli, enterococci and fecal coliforms) were evaluated in the study. Four experiments were conducted using low to high PAA levels and UV dosages. E. coli and enterococci were resistant to low to moderate PAA dosage (0.5- 1 mg/L). These microbes can be removed effectively at high PAA dosage (2.5 mg/L) with 30 min contact time. Fecal coliforms were completely inactivated even at a low PAA dose of 0.7 mg/L. E. coli was more susceptible to UV disinfection than enterococci at low UV dosages. Enterococci required at least 40 mJ/cm2 for 2.5 log inactivation. In combined PAA + UV treatment, low UV intensities between 7 – 40 mJ/cm2 showed poor disinfection performance at a low PAA concentration of 1.5 mg/L. High UV intensities of 120 and 60 mJ/cm2 inactivated all the pathogens to below detection levels even at low to moderate PAA (0.7 mg/L and 1 mg/L) pretreatment concentration. Combined PAA + UV treatment at 1 mg/L (for 15 and 30 min contact time) + 120 and 60 mJ/cm2 did not show any regrowth of microbes, whereas PAA only disinfection with 15 min contact time showed regrowth of enterococci and fecal coliforms. UV only disinfection showed E. coli regrowth. • This pilot scale study was designed for providing necessary parameter optimization

Validated spectrophotometric methods for simultaneous determination of troxerutin and carbazochrome in dosage form

Science.gov (United States)

Khattab, Fatma I.; Ramadan, Nesrin K.; Hegazy, Maha A.; Al-Ghobashy, Medhat A.; Ghoniem, Nermine S.

2015-03-01

Four simple, accurate, sensitive and precise spectrophotometric methods were developed and validated for simultaneous determination of Troxerutin (TXN) and Carbazochrome (CZM) in their bulk powders, laboratory prepared mixtures and pharmaceutical dosage forms. Method A is first derivative spectrophotometry (D1) where TXN and CZM were determined at 294 and 483.5 nm, respectively. Method B is first derivative of ratio spectra (DD1) where the peak amplitude at 248 for TXN and 439 nm for CZM were used for their determination. Method C is ratio subtraction (RS); in which TXN was determined at its λmax (352 nm) in the presence of CZM which was determined by D1 at 483.5 nm. While, method D is mean centering of the ratio spectra (MCR) in which the mean centered values at 300 nm and 340.0 nm were used for the two drugs in a respective order. The two compounds were simultaneously determined in the concentration ranges of 5.00-50.00 μg mL-1 and 0.5-10.0 μg mL-1 for TXN and CZM, respectively. The methods were validated according to the ICH guidelines and the results were statistically compared to the manufacturer's method.

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.

Experimental study of tensile strength of pharmaceutical tablets: effect of the diluent nature and compression pressure

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Juban Audrey

2017-01-01

Full Text Available In the pharmaceutical field, tablets are the most common dosage form for oral administration in the world. Among different manufacturing processes, direct compression is widely used because of its economics interest and it is a process which avoids the steps of wet granulation and drying processes. Tablets are composed of at least two ingredients: an active pharmaceutical ingredient (API which is mixed with a diluent. The nature of the powders and the processing conditions are crucial for the properties of the blend and, consequently, strongly influence the mechanical characteristics of tablets. Moreover, tablets have to present a suitable mechanical strength to avoid crumbling or breaking when handling, while ensuring an appropriate disintegration after administration. Accordingly, this mechanical property is an essential parameter to consider. Experimental results showed that proportion of the diluent, fragmentary (DCPA or plastic (MCC, had a large influence on the tensile strength evolution with API content as well as the compression load applied during tableting process. From these results a model was developed in order to predict the tensile strength of binary tablets by knowing the compression pressure. The validity of this model was demonstrated for the two studied systems and a comparison was made with two existing models.

Experimental study of tensile strength of pharmaceutical tablets: effect of the diluent nature and compression pressure

Science.gov (United States)

Juban, Audrey; Briançon, Stéphanie; Puel, François; Hoc, Thierry; Nouguier-Lehon, Cécile

2017-06-01

In the pharmaceutical field, tablets are the most common dosage form for oral administration in the world. Among different manufacturing processes, direct compression is widely used because of its economics interest and it is a process which avoids the steps of wet granulation and drying processes. Tablets are composed of at least two ingredients: an active pharmaceutical ingredient (API) which is mixed with a diluent. The nature of the powders and the processing conditions are crucial for the properties of the blend and, consequently, strongly influence the mechanical characteristics of tablets. Moreover, tablets have to present a suitable mechanical strength to avoid crumbling or breaking when handling, while ensuring an appropriate disintegration after administration. Accordingly, this mechanical property is an essential parameter to consider. Experimental results showed that proportion of the diluent, fragmentary (DCPA) or plastic (MCC), had a large influence on the tensile strength evolution with API content as well as the compression load applied during tableting process. From these results a model was developed in order to predict the tensile strength of binary tablets by knowing the compression pressure. The validity of this model was demonstrated for the two studied systems and a comparison was made with two existing models.

Removal of Pharmaceuticals from Wastewater by Intermittent Electrocoagulation

Directory of Open Access Journals (Sweden)

Benny Marie B. Ensano

2017-01-01

Full Text Available The continuous release of emerging contaminants (ECs in the aquatic environment, as a result of the inadequate removal by conventional treatment methods, has prompted research to explore viable solutions to this rising global problem. One promising alternative is the use of electrochemical processes since they represent a simple and highly efficient technology with less footprint. In this paper, the feasibility of treating ECs (i.e., pharmaceuticals using an intermittent electrocoagulation process, a known electrochemical technology, has been investigated. Diclofenac (DCF, carbamazepine (CBZ and amoxicillin (AMX were chosen as being representative of highly consumed drugs that are frequently detected in our water resources and were added in synthetic municipal wastewater. The removal efficiencies of both individual and combined pharmaceuticals were determined under different experimental conditions: hydraulic retention time (HRT (6, 19 and 38 h, initial concentration (0.01, 4 and 10 mg/L and intermittent application (5 min ON/20 min OFF of current density (0.5, 1.15 and 1.8 mA/cm2. Results have shown that these parameters have significant effects on pharmaceutical degradation. Maximum removals (DCF = 90%, CBZ = 70% and AMX = 77% were obtained at a current density of 0.5 mA/cm2, an initial concentration of 10 mg/L and HRT of 38 h.

A 1:1 pharmaceutical cocrystal of myricetin in combination with uncommon piracetam conformer: X-ray single crystal analysis and mechanochemical synthesis

Science.gov (United States)

Sowa, Michał; Ślepokura, Katarzyna; Matczak-Jon, Ewa

2014-01-01

Combination of two Active Pharmaceutical Ingredients, myricetin and piracetam, yields a 1:1 cocrystal characterized by X-ray single-crystal and powder diffraction, Raman spectroscopy, 1H NMR, thermal analysis (DSC and TG-DTA) methods. Constituents of the cocrystalline phase were also investigated in terms of Hirshfeld surfaces. Compounds in their neutral forms cocrystallize in the Pna21 space group of orthorhombic system. Notably, piracetam adopts an uncommon conformation, not encountered in its cocrystals previously described. In the crystal lattice, a three-dimensional hydrogen-bonded network is observed, including formation of a 2D molecular scaffolding motif. A scale-up procedure is readily available with use of solvent-drop grinding method, in which application of a variety of common solvents leads to formation of the cocrystal, as confirmed by XRPD and Raman spectroscopy.

In-line and Real-time Monitoring of Resonant Acoustic Mixing by Near-infrared Spectroscopy Combined with Chemometric Technology for Process Analytical Technology Applications in Pharmaceutical Powder Blending Systems.

Science.gov (United States)

Tanaka, Ryoma; Takahashi, Naoyuki; Nakamura, Yasuaki; Hattori, Yusuke; Ashizawa, Kazuhide; Otsuka, Makoto

2017-01-01

Resonant acoustic ® mixing (RAM) technology is a system that performs high-speed mixing by vibration through the control of acceleration and frequency. In recent years, real-time process monitoring and prediction has become of increasing interest, and process analytical technology (PAT) systems will be increasingly introduced into actual manufacturing processes. This study examined the application of PAT with the combination of RAM, near-infrared spectroscopy, and chemometric technology as a set of PAT tools for introduction into actual pharmaceutical powder blending processes. Content uniformity was based on a robust partial least squares regression (PLSR) model constructed to manage the RAM configuration parameters and the changing concentration of the components. As a result, real-time monitoring may be possible and could be successfully demonstrated for in-line real-time prediction of active pharmaceutical ingredients and other additives using chemometric technology. This system is expected to be applicable to the RAM method for the risk management of quality.

Short-time, high-dosage penicillin infusion therapy of syphilis

DEFF Research Database (Denmark)

Lomholt, Hans; Poulsen, Asmus; Brandrup, Flemming

2003-01-01

The optimal dosage and duration of penicillin treatment for the various stages of syphilis are not known. We present data on 20 patients with syphilis (primary, secondary or latent) treated with high-dose, short-time penicillin infusion therapy. Patients were given 10 MIU of penicillin G intraven......The optimal dosage and duration of penicillin treatment for the various stages of syphilis are not known. We present data on 20 patients with syphilis (primary, secondary or latent) treated with high-dose, short-time penicillin infusion therapy. Patients were given 10 MIU of penicillin G...

Principles of Micellar Electrokinetic Capillary Chromatography Applied in Pharmaceutical Analysis

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Árpád Gyéresi

2013-02-01

Full Text Available Since its introduction capillary electrophoresis has shown great potential in areas where electrophoretic techniques have rarely been used before, including here the analysis of pharmaceutical substances. The large majority of pharmaceutical substances are neutral from electrophoretic point of view, consequently separations by the classic capillary zone electrophoresis; where separation is based on the differences between the own electrophoretic mobilities of the analytes; are hard to achieve. Micellar electrokinetic capillary chromatography, a hybrid method that combines chromatographic and electrophoretic separation principles, extends the applicability of capillary electrophoretic methods to neutral analytes. In micellar electrokinetic capillary chromatography, surfactants are added to the buffer solution in concentration above their critical micellar concentrations, consequently micelles are formed; micelles that undergo electrophoretic migration like any other charged particle. The separation is based on the differential partitioning of an analyte between the two-phase system: the mobile aqueous phase and micellar pseudostationary phase. The present paper aims to summarize the basic aspects regarding separation principles and practical applications of micellar electrokinetic capillary chromatography, with particular attention to those relevant in pharmaceutical analysis.

Disintegration rate and properties of active pharmaceutical ingredient particles as determined from the dissolution time profile of a pharmaceutical formulation: an inverse problem.

Science.gov (United States)

Horkovics-Kovats, Stefan

2014-02-01

Dissolution profile of a finished dosage form (FDF) contains hidden information regarding the disintegration of the form and the particle properties of the active pharmaceutical ingredient. Here, an extraction of this information from the dissolution profile without limitation to sink conditions is provided. In the article, mathematical relationships between the continuously measured dissolution profile of an FDF containing uniform or heterogeneous particles and its disintegration rate are developed. Further, the determinability of the disintegration kinetics and particle properties released from an FDF using the derived recurrent procedure was analyzed. On the basis of the theoretical data sets, it was demonstrated that the introduced analysis of dissolution profiles correctly identifies the disintegration rate of FDF containing multiple particle types. Furthermore, for known disintegration rates, the intrinsic lifetime of particles (time needed for total particle dissolution in infinite volume) released from the FDF and their relative amount can be determined. The extractable information from FDF dissolution time profiles can be utilized in designing of the formulation process, resulting in improved understanding of FDF properties, contributing thus to the implementation of quality by design in the FDF development. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Simultaneous removal and evaluation of organic substrates and NH{sub 3}-N by a novel combined process in treating chemical synthesis-based pharmaceutical wastewater

Energy Technology Data Exchange (ETDEWEB)

Chen, Zhaobo [School of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin 150001 (China); State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150090 (China); Wang, Hongcheng [School of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin 150001 (China); Ren, Nanqi, E-mail: rnq@hit.edu.cn [State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150090 (China); Cui, Minhua; Nie, Shukai; Hu, Dongxue [School of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin 150001 (China)

2011-12-15

Highlights: Black-Right-Pointing-Pointer We research a novel combined process to treat chemical synthesis-based pharmaceutical wastewater. Black-Right-Pointing-Pointer The mechanism of amoxicillin verifies that the biodegradation, adsorption, hydrolysis and unknown mechanism were able to remove amoxicillin from wastewater. Black-Right-Pointing-Pointer In this study demonstrates that biodegradation is the major factor for removal mechanism at work for amoxicillin. Black-Right-Pointing-Pointer Mathematical statistic methods were employed to evaluate the performance of the WWTP. - Abstract: A full-scale novel combined anaerobic/micro-aerobic and two-stage aerobic biological process is used for the treatment of an actual chemical synthesis-based pharmaceutical wastewater containing amoxicillin. The anaerobic system is an up-flow anaerobic sludge blanket (UASB), the micro-aerobic system is a novel micro-aerobic hydrolysis acidification reactor (NHAR) and the two-stage aerobic process comprised cyclic activated sludge system (CASS) and biological contact oxidation tank (BCOT). The influent wastewater was high in COD, NH{sub 3}-N varying daily 4016-13,093 mg-COD L{sup -1} and 156.4-650.2 mg-NH{sub 3}-N L{sup -1}, amoxicillin varying weekly between 69.1 and 105.4 mg-amoxicillin L{sup -1}, respectively; Almost all the COD, NH{sub 3}-N, amoxicillin were removed by the biological combined system, with removal percentages 97%, 93.4% and 97.2%, respectively, leaving around 104 mg-COD L{sup -1}, 9.4 mg-NH{sub 3}-N L{sup -1} and 2.6 {+-} 0.8 mg-amoxicillin L{sup -1} in the final clarifier effluent. The performance evaluation of the wastewater treatment plant (WWTP) by mathematical statistic methods shown that at most of time effluent can meet the higher treatment discharge standard. In addition, the fate of amoxicillin in the full-scale WWTP and the amoxicillin removal rate of each different removal routes in UASB, NHAR, CASS, BCOT and final clarifier processes are investigated

Genetic basis for dosage sensitivity in Arabidopsis thaliana.

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Isabelle M Henry

2007-04-01

Full Text Available Aneuploidy, the relative excess or deficiency of specific chromosome types, results in gene dosage imbalance. Plants can produce viable and fertile aneuploid individuals, while most animal aneuploids are inviable or developmentally abnormal. The swarms of aneuploid progeny produced by Arabidopsis triploids constitute an excellent model to investigate the mechanisms governing dosage sensitivity and aneuploid syndromes. Indeed, genotype alters the frequency of aneuploid types within these swarms. Recombinant inbred lines that were derived from a triploid hybrid segregated into diploid and tetraploid individuals. In these recombinant inbred lines, a single locus, which we call SENSITIVE TO DOSAGE IMBALANCE (SDI, exhibited segregation distortion in the tetraploid subpopulation only. Recent progress in quantitative genotyping now allows molecular karyotyping and genetic analysis of aneuploid populations. In this study, we investigated the causes of the ploidy-specific distortion at SDI. Allele frequency was distorted in the aneuploid swarms produced by the triploid hybrid. We developed a simple quantitative measure for aneuploidy lethality and using this measure demonstrated that distortion was greatest in the aneuploids facing the strongest viability selection. When triploids were crossed to euploids, the progeny, which lack severe aneuploids, exhibited no distortion at SDI. Genetic characterization of SDI in the aneuploid swarm identified a mechanism governing aneuploid survival, perhaps by buffering the effects of dosage imbalance. As such, SDI could increase the likelihood of retaining genomic rearrangements such as segmental duplications. Additionally, in species where triploids are fertile, aneuploid survival would facilitate gene flow between diploid and tetraploid populations via a triploid bridge and prevent polyploid speciation. Our results demonstrate that positional cloning of loci affecting traits in populations containing ploidy and

The role of entrepreneurial activities in academic pharmaceutical science research.

Science.gov (United States)

Stinchcomb, Audra L

2010-06-01

Academic pharmaceutical science research is expanding further and further from the University setting to encompass the for-profit private company setting. This parallels the National Institutes of Health momentum to include multiple funding opportunities for University and private company collaboration. It has been recognized that the nonprofit and for-profit combination research model can accelerate the commercialization of pharmaceutical products, and therefore more efficiently improve human health. Entrepreneurial activities require unique considerations in the University environment, but can be modeled after the commercialization expansion of the academic healthcare enterprise. Challenges and barriers exist to starting a company as an entrepreneurial faculty member, but the rewards to one's personal and professional lives are incomparable. (c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association

Administered activity of Tc-99m MDP for bone scintigraphy, standard or individual dosage?

International Nuclear Information System (INIS)

Vestergren, E.; Gretarsdottir, J.; Jacobsson, L.

2002-01-01

Background and Aim: Adult patients are generally, irrespective of size, given the same amount of activity for a certain type of nuclear medicine examination, a standard dosage. Identical image quality is essential when comparing different patient studies. The aim of this study is to evaluate different dosage methods for Tc-99m-MDP bone scintigraphy and to investigate whether individual dosage will decrease the variations in image quality between different patients. Material and Methods: 100 consecutive adult patients (aged between 40 and 89 years) undergoing whole body bone scintigraphy were studied. Eight patients were excluded from the study because of abnormal high uptake in the areas of interest. The patient weight and height were registered. The activity in the syringes was measured before and after the injection of about 600 MBq Tc-99m MDP. Scanning was performed, with a dual head gamma camera (Maxxus or Millennium VG, General Electric) equipped with a high-resolution collimator, at approximately 4 hours (mean 3.8 h) post-injection. Regions of interest (ROI) were drawn over the lumbar spine (posterior view), the right femur (anterior view) and also soft tissue background regions for each area. The total counts, maximum counts/pixel and number of pixels in the ROIs were registered. The maximum number of counts/pixel (background-subtracted), SPINEmax and FEMURmax were chosen as the image quality parameters. For each patient, SPINEmax and FEMURmax where recalculated to the number that would have been obtained with standard dosage (exactly 600 MBq), and dosage proportional to body weight, body surface area and body height. All values were corrected to a scanning time 3.8 h after injection. Results: Both with a standard activity dosage and a dosage proportional to body height, SPINEmax decreases with increasing body weight. Dosage proportional to body weight gives increasing values of SPINEmax with increasing body weight. Dosage proportional to body surface area

In vitro and in vivo evaluation of combined calcitriol and cisplatin in dogs with spontaneously occurring tumors

Science.gov (United States)

Rassnick, Kenneth M.; Muindi, Josephia R.; Johnson, Candace S.; Balkman, Cheryl E.; Ramnath, Nithya; Yu, Wei-Dong; Engler, Kristie L.; Page, Rodney L.; Trump, Donald L.

2009-01-01

Purpose Calcitriol potentiates cisplatin-mediated activity in a variety of tumor models. We examine here, the effect of calcitriol and cisplatin pre-clinically and clinically in canine spontaneous tumors through in vitro studies on tumor cells and through a phase I study of calcitriol and cisplatin to identify the maximum-tolerated dosage (MTD) of this combination in dogs with cancer and to characterize the pharmacokinetic disposition of calcitriol in dogs. Methods Canine tumor cells were investigated for calcitriol/cisplatin interactions on proliferation using an MTT assay in a median-dose effect analysis; data were used to derive a combination index (CI). Cisplatin was given at a fixed dosage of 60 mg/m2. Calcitriol was given i.v. and the dosage was escalated in cohorts of three dogs until the MTD was defined. Serum calcitriol concentrations were quantified by radioimmunoassay. Results In vitro, CIs1.5 μg/kg achieved Cmax ≥ 9.8 ng/mL and dosages >1.0 μg/kg achieved AUC ≥ 45 h ng/mL. Conclusions Calcitriol and cisplatin have synergistic antiproliferative effects on multiple canine tumor cells and high-dosages of i.v. calcitriol in combination with cisplatin can be safely administered to dogs. Cmax and AUC at the MTD 3.75 μg/kg calcitriol exceed concentrations associated with antitumor activity in a murine model, indicating this combination might have significant clinical utility in dogs. PMID:18246349

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...

A fast ultra high pressure liquid chromatographic method for qualification and quantification of pharmaceutical combination preparations containing paracetamol, acetyl salicylic acid and/or antihistaminics.

Science.gov (United States)

Deconinck, E; Sacré, P Y; Baudewyns, S; Courselle, P; De Beer, J

2011-09-10

A fully validated UHPLC method for the identification and quantification of pharmaceutical preparations, containing paracetamol and/or acetyl salicylic acid, combined with anti-histaminics (phenylephrine, pheniramine maleate, diphenhydramine, promethazine) and/or other additives as quinine sulphate, caffeine or codeine phosphate, was developed. The proposed method uses a Waters Acquity BEH C18 column (2 mm × 100 mm, 1.7 μm) with a gradient using an ammonium acetate buffer pH 4.0 as aqueous phase and methanol as organic modifier. The obtained method was fully validated based on its measurement uncertainty (accuracy profile) and robustness tests. Calibration lines for all components were linear within the studied ranges. The relative bias and the relative standard deviations for all components were respectively smaller than 1.5% and 2%, the β-expectation tolerance limits did not exceed the acceptance limits of 10% and the relative expanded uncertainties were smaller than 5% for all of the considered components. A UHPLC method was obtained for the identification and quantification of these kind of pharmaceutical preparations, which will significantly reduce analysis times and workload for the laboratories charged with the quality control of these preparations. Copyright © 2011 Elsevier B.V. All rights reserved.

Dependence of surface smoothing, sputtering and etching phenomena on cluster ion dosage

CERN Document Server

Song, J H; Choi, W K

2002-01-01

The dependence of surface smoothing and sputtering phenomena of Si (1 0 0) solid surfaces irradiated by CO sub 2 cluster ions on cluster-ion dosage was investigated using an atomic force microscope. The flux and total ion dosage of impinging cluster ions at the acceleration voltage of 50 kV were fixed at 10 sup 9 ions/cm sup 2 s and were scanned from 5x10 sup 1 sup 0 to 5x10 sup 1 sup 3 ions/cm sup 2 , respectively. The density of hillocks induced by cluster ion impact was gradually increased with the dosage up to 5x10 sup 1 sup 1 ions/cm sup 2 , which caused that the irradiated surface became rough from 0.4 to 1.24 nm in root-mean-square roughness (sigma sub r sub m sub s). At the boundary of the ion dosage of 10 sup 1 sup 2 ions/cm sup 2 , the density of the induced hillocks was decreased and sigma sub r sub m sub s was about 1.21 nm, not being deteriorated further. At the dosage of 5x10 sup 1 sup 3 ions/cm sup 2 , the induced hillocks completely disappeared and the surface became very flat as much as sigma...

Cyclodextrin based nanosponges for pharmaceutical use: a review.

Science.gov (United States)

Tejashri, Gursalkar; Amrita, Bajaj; Darshana, Jain

2013-09-01

Nanosponges are a novel class of hyper-crosslinked polymer based colloidal structures consisting of solid nanoparticles with colloidal sizes and nanosized cavities. These nano-sized colloidal carriers have been recently developed and proposed for drug delivery, since their use can solubilize poorly water-soluble drugs and provide prolonged release as well as improve a drug's bioavailability by modifying the pharmacokinetic parameters of actives. Development of nanosponges as drug delivery systems, with special reference to cyclodextrin based nanosponges, is presented in this article. In the current review, attempts have been made to illustrate the features of cyclodextrin based nanosponges and their applications in pharmaceutical formulations. Special emphasis has been placed on discussing the methods of preparation, characterization techniques and applications of these novel drug delivery carriers for therapeutic purposes. Nanosponges can be referred to as solid porous particles having a capacity to load drugs and other actives into their nanocavity; they can be formulated as oral, parenteral, topical or inhalation dosage forms. Nanosponges offer high drug loading compared to other nanocarriers and are thus suitable for solving issues related to stability, solubility and delayed release of actives. Controlled release of the loaded actives and solubility enhancement of poorly water-soluble drugs are major advantages of nanosponge drug delivery systems.

Derivative spectrophotometric method for simultaneous determination of zofenopril and fluvastatin in mixtures and pharmaceutical dosage forms.

Science.gov (United States)

Stolarczyk, Mariusz; Maślanka, Anna; Apola, Anna; Rybak, Wojciech; Krzek, Jan

2015-09-05

Fast, accurate and precise method for the determination of zofenopril and fluvastatin was developed using spectrophotometry of the first (D1), second (D2), and third (D3) order derivatives in two-component mixtures and in pharmaceutical preparations. It was shown, that the developed method allows for the determination of the tested components in a direct manner, despite the apparent interference of the absorption spectra in the UV range. For quantitative determinations, "zero-crossing" method was chosen, appropriate wavelengths for zofenopril were: D1 λ=270.85 nm, D2 λ=286.38 nm, D3 λ=253.90 nm. Fluvastatin was determined at wavelengths: D1 λ=339.03 nm, D2 λ=252.57 nm, D3 λ=258.50 nm, respectively. The method was characterized by high sensitivity and accuracy, for zofenopril LOD was in the range of 0.19-0.87 μg mL(-1), for fluvastatin 0.51-1.18 μg mL(-1), depending on the class of derivative, and for zofenopril and fluvastatin LOQ was 0.57-2.64 μg mL(-1) and 1.56-3.57 μg mL(-1), respectively. The recovery of individual components was within the range of 100±5%. For zofenopril, the linearity range was estimated between 7.65 μg mL(-1) and 22.94 μg mL(-1), and for fluvastatin between 5.60 μg mL(-1) and 28.00 μg mL(-1). Copyright © 2015 Elsevier B.V. All rights reserved.

A step toward development of printable dosage forms for poorly soluble drugs

DEFF Research Database (Denmark)

Raijada, Dharaben Kaushikkumar; Genina, Natalja; Fors, Daniela

2013-01-01

The purpose of this study was to formulate printable dosage forms for a poorly soluble drug (piroxicam; PRX) and to gain understanding of critical parameters to be considered during development of such dosage forms. Liquid formulations of PRX were printed on edible paper using piezoelectric inkjet...

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

Maths anxiety and medication dosage calculation errors: A scoping review.

Science.gov (United States)

Williams, Brett; Davis, Samantha

2016-09-01

A student's accuracy on drug calculation tests may be influenced by maths anxiety, which can impede one's ability to understand and complete mathematic problems. It is important for healthcare students to overcome this barrier when calculating drug dosages in order to avoid administering the incorrect dose to a patient when in the clinical setting. The aim of this study was to examine the effects of maths anxiety on healthcare students' ability to accurately calculate drug dosages by performing a scoping review of the existing literature. This review utilised a six-stage methodology using the following databases; CINAHL, Embase, Medline, Scopus, PsycINFO, Google Scholar, Trip database (http://www.tripdatabase.com/) and Grey Literature report (http://www.greylit.org/). After an initial title/abstract review of relevant papers, and then full text review of the remaining papers, six articles were selected for inclusion in this study. Of the six articles included, there were three experimental studies, two quantitative studies and one mixed method study. All studies addressed nursing students and the presence of maths anxiety. No relevant studies from other disciplines were identified in the existing literature. Three studies took place in the U.S, the remainder in Canada, Australia and United Kingdom. Upon analysis of these studies, four factors including maths anxiety were identified as having an influence on a student's drug dosage calculation abilities. Ultimately, the results from this review suggest more research is required in nursing and other relevant healthcare disciplines regarding the effects of maths anxiety on drug dosage calculations. This additional knowledge will be important to further inform development of strategies to decrease the potentially serious effects of errors in drug dosage calculation to patient safety. Copyright © 2016 Elsevier Ltd. All rights reserved.

APPROACHES TO IMPLEMENTATION OF AN INTEGRATED MANAGEMENT SYSTEM IN THE PHARMACEUTICAL INDUSTRY. GALENICAL PHARMACEUTICAL PRODUCTION

Directory of Open Access Journals (Sweden)

Ershova Elena Vladimirovna

2015-10-01

Full Text Available This article reviews the issues associated with development of an integrated quality management system and its implementation into a galenical pharmaceutical company. Recently, the Russian pharmaceutical industry has been developing extensively: pharmaceutical clusters are being formed, new and innovative technologies are being developed. For the enterprises producing galenical pharmaceutical products, which feature low prices and a high level of competition, development and implementation of management systems is a way to prove their competitiveness. The purpose of this article is to review the architecture and the key elements of integrated management systems for pharmaceutical enterprises, develop an integrated management system in terms of the upcoming revision of ISO 9001:2015, as well as to describe the benefits of implementation of such systems. The presented approach is the result of an educational project implemented within the framework of the MBA programme in "Master of Business Administration (MBA" in the Federal State Budgetary Educational Institution of Continuing Professional Education Pastukhov State Academy of Industrial Management.

Pharmaceuticals labelled with stable isotopes

International Nuclear Information System (INIS)

Krumbiegel, P.

1986-11-01

The relatively new field of pharmaceuticals labelled with stable isotopes is reviewed. Scientific, juridical, and ethical questions are discussed concerning the application of these pharmaceuticals in human medicine. 13 C, 15 N, and 2 H are the stable isotopes mainly utilized in metabolic function tests. Methodical contributions are given to the application of 2 H, 13 C, and 15 N pharmaceuticals showing new aspects and different states of development in the field under discussion. (author)

Microwave enhanced Fenton-like process for the treatment of high concentration pharmaceutical wastewater

International Nuclear Information System (INIS)

Yang Yu; Wang Peng; Shi Shujie; Liu Yuan

2009-01-01

This paper explored a novel process for wastewater treatment, i.e. microwave enhanced Fenton-like process. This novel process was introduced to treat high concentration pharmaceutical wastewater with initial COD loading of 49,912.5 mg L -1 . Operating parameters were investigated and the optimal condition included as follows: microwave power was 300 W, radiation time was 6 min, initial pH was 4.42, H 2 O 2 dosage was 1300 mg L -1 and Fe 2 (SO 4 ) 3 dosage was 4900 mg L -1 , respectively. Within the present experimental condition used, the COD removal and UV 254 removal reached to 57.53% and 55.06%, respectively, and BOD 5 /COD was enhanced from 0.165 to 0.470. The variation of molecular weight distribution indicated that both macromolecular substances and micromolecular substances were eliminated quite well. The structure of flocs revealed that one ferric hydrated ion seemed to connect with another ferric hydrated ion and/or organic compound molecule to form large-scale particles by means of van der waals force and/or hydrogen bond. Subsequently, these particles aggregated to form flocs and settled down. Comparing with traditional Fenton-like reaction and conventional heating assisted Fenton-like reaction, microwave enhanced Fenton-like process displayed superior treatment efficiency. Microwave was in favor of improving the degradation efficiency, the settling quality of sludge, as well as reducing the yield of sludge and enhancing the biodegradability of effluent. Microwave enhanced Fenton-like process is believed to be a promising treatment technology for high concentration and biorefractory wastewater.

Effect of Injection Minimal Dosages of Depot Medroxyprogesterone acetate (DMPA to Body Weight and Blood Chemistry Male Rat Strain Sprague-Dawley

Directory of Open Access Journals (Sweden)

Nukman Moeloek

2009-11-01

Full Text Available Many family planning program focus more on men. Until now, vasectomy has been the commonly used method for male contraception. However, this method creates inconvenience such as irreversibility and psychological problems. One of the alternatives contraception is the combination of depot medroxyprogesterone acetate (DMPA and androgen. The minimum dosage of DMPA could suppress testosterone level that leads to reduced spermatogenesis and sperm viability. Nevertheless, until now it is not known whether minimum dosages of DMPA have an effect to body weight and blood chemistry. Therefore, this research aimed at determinate the effect of minimal dosages of DMPA to body mass and blood chemistry using male rats (Rattus norvegicus L. strain Sprague-Dawley as model. This research using completely randomized design, unequal size sample, castration treatments and several doses DMPA (1.25, 0.625, and 0.313 milligram. Injecting of DMPA conducted intramuscularly on week 0 and week 12. Normality/homogeneity Data normality were analyzed before ANOVA test. Then, abnormal data were tested using Kruskal-Wallis test. The result shows that injection of DMPA in various doses do not have an effect on body weight and blood chemistry such as erytrocytes, haemoglobin, hematocrite, HDL, LDL, total cholesterol, SGOT, SGPT and triglyseride (p>0,05. Furthermore, it is concluded that that no effect of minimal dosages of DMPA to body mass and blood chemistry of rat.

Limiting nitrogen and veterinary pharmaceutical input into groundwater: combining hydrogeophysics and soil science

Science.gov (United States)

Noell, Ursula; Stadler, Susanne

2017-04-01

The EU Interreg project TOPSOIL investigates opportunities to improve surface and groundwater quality as well as water management strategies under the consideration of climate adaptation challenges. Within the framework of the project, we investigate the transport behavior of percolation water in the unsaturated zone, the migration of nitrogen and veterinary pharmaceuticals in soils, and - together with different stakeholders (e.g. farmers, water supply companies) - develop common strategies to minimize the migration of these substances into the groundwater. In our study we focus on distinguishing preferential and diffuse flow using soil scientific and geophysical methods. During the first investigation campaign, we combined soil sampling with radiometry and electrical conductivity overview measurements on the typical sandy soil of the studied area south of Oldenburg, Germany. We used the CMD explorer for the electromagnetic mapping (horizontal and vertical dipoles, intercoil spacing of 1.48/2.82/4.49 m, investigations depths of appr. 0 - 6 m) and the radiometry detector comprised five sodium-iodide crystals each with a volume of 4 litres. The spectral data are evaluated for potassium (1.37 - 1.57 MeV), uranium (Bi-214) (1.66 - 1.86MeV) and thorium (T-208) (2.41 - 2.81MeV) and total counts (0.41-2.81MeV). A total of 292 soil samples were taken from 46 ram coring profiles (depth range: 0 to 3 m) and analyzed for soil chemical parameters and water content. The first evaluation showed a good correlation between conductivity and radiometry measurements. While the uranium and thorium values are generally low, the potassium values possibly reflect higher clay contents as do the higher conductivity values. The geophysical overview measurements were used to select the locations for soil sampling and we specifically targeted presumably clay-rich as well as clay-poor areas for sampling.

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.

[PICS: pharmaceutical inspection cooperation scheme].

Science.gov (United States)

Morénas, J

2009-01-01

The pharmaceutical inspection cooperation scheme (PICS) is a structure containing 34 participating authorities located worldwide (October 2008). It has been created in 1995 on the basis of the pharmaceutical inspection convention (PIC) settled by the European free trade association (EFTA) in1970. This scheme has different goals as to be an international recognised body in the field of good manufacturing practices (GMP), for training inspectors (by the way of an annual seminar and experts circles related notably to active pharmaceutical ingredients [API], quality risk management, computerized systems, useful for the writing of inspection's aide-memoires). PICS is also leading to high standards for GMP inspectorates (through regular crossed audits) and being a room for exchanges on technical matters between inspectors but also between inspectors and pharmaceutical industry.

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.

Evaluation of Fenton's Reagent and Activated Persulfate for Treatment of a Pharmaceutical Waste Mixture in Groundwater

DEFF Research Database (Denmark)

Bennedsen, Lars Rønn; Søgaard, Erik Gydesen; Kakarla, Prasad

2010-01-01

Soil and groundwater beneath the Kærgård Plantage megasite in Denmark are contaminated with a complex mixture of pharmaceutical wastes, including sulfonamides, barbiturates, aniline, pyridine chlorinated solvents (DNAPL), benzene, toluene, mercury, and cyanide. Regulatory agencies in Denmark...... capacity of the aquifer sediments, pH dropped to within the range of 1 to 3 for all tests. Due to the presence of significant quantities of mercury and cyanide in the target treatment zone and the lowering of pH, batch and continuous-flow column reactors were used to measure mobilization of the mercury......, cyanide, chromium and other metals both within the aqueous and vapour phases. Except the alkaline activation, all the investigated techniques for activating persulfate were able to remove more than 80% of the primary contaminants. Optimization and more dosages led to 98-99% destruction of primary...

Enhanced pharmaceutical removal from water in a three step bio-ozone-bio process.

Science.gov (United States)

de Wilt, Arnoud; van Gijn, Koen; Verhoek, Tom; Vergnes, Amber; Hoek, Mirit; Rijnaarts, Huub; Langenhoff, Alette

2018-07-01

Individual treatment processes like biological treatment or ozonation have their limitations for the removal of pharmaceuticals from secondary clarified effluents with high organic matter concentrations (i.e. 17 mg TOC/L). These limitations can be overcome by combining these two processes for a cost-effective pharmaceutical removal. A three-step biological-ozone-biological (BO 3 B) treatment process was therefore designed for the enhanced pharmaceutical removal from wastewater effluent. The first biological step removed 38% of ozone scavenging TOC, thus proportionally reducing the absolute ozone input for the subsequent ozonation. Complementariness between biological and ozone treatment, i.e. targeting different pharmaceuticals, resulted in cost-effective pharmaceutical removal by the overall BO 3 B process. At a low ozone dose of 0.2 g O 3 /g TOC and an HRT of 1.46 h in the biological reactors, the removal of 8 out of 9 pharmaceuticals exceeded 85%, except for metoprolol (60%). Testing various ozone doses and HRTs revealed that pharmaceuticals were ineffectively removed at 0.1 g O3/g TOC and an HRT of 0.3 h. At HRTs of 0.47 and 1.46 h easily and moderately biodegradable pharmaceuticals such as caffeine, gemfibrozil, ibuprofen, naproxen and sulfamethoxazole were over 95% removed by biological treatment. The biorecalcitrant carbamazepine was completely ozonated at a dose of 0.4 g O 3 /g TOC. Ozonation products are likely biodegraded in the last biological reactor as a 17% TOC removal was found. No appreciable acute toxicity towards D. magna, P. subcapitata and V. fischeri was found after exposure to the influents and effluents of the individual BO 3 B reactors. The BO 3 B process is estimated to increase the yearly wastewater treatment tariff per population equivalent in the Netherlands by less than 10%. Overall, the BO 3 B process is a cost-effective treatment process for the removal of pharmaceuticals from secondary clarified effluents. Copyright

Novel potentiometric application for the determination of pantoprazole sodium and itopride hydrochloride in their pure and combined dosage form.

Science.gov (United States)

Ragab, Mona T; Abd El-Rahman, Mohamed K; Ramadan, Nesrin K; El-Ragehy, Nariman A; El-Zeany, Badr A

2015-06-01

Three sensitive and selective polyvinyl chloride (PVC) matrix membrane electrodes were developed and investigated. Sensor I was developed using tetraheptylammonium bromide (THB) as an anion exchanger with 2-nitrophenyl octyl ether (2-NPOE) as a plasticizer for the determination of the anionic drug pantoprazole sodium sesquihydrate (PAN). To determine the cationic drug itopride hydrochloride (ITH), two electrodes (sensors II and III) were developed using potassium tetrakis(4-chlorophenyl) borate (KTCPB) as a cation exchanger with dioctyl phthalate (DOP) as a plasticizer. Selective molecular recognition components, 2-hydroxypropyl-β-cyclodextrin (2-HP βCD) and 4-tert-butylcalix[8]arene (tBC8), were used as ionophores to improve the selectivity of sensors II and III, respectively. The proposed sensors had a linear dynamic range of 1×10(-5) to 1×10(-2) mol L(-1) with Nernstian slopes of -54.83±0.451, 56.90±0.300, and 51.03±1.909 mV/decade for sensors I, II and III, respectively. The Nernstian slopes were also estimated over the pH ranges of 11-13, 3.5-8 and 4-7 for the three sensors, respectively. The proposed sensors displayed useful analytical characteristics for the determination of PAN and ITH in bulk powder, in laboratory prepared mixtures and in combined dosage forms with clear discrimination from several ions, sugars and some common drug excipients. The method was validated according to ICH guidelines. Statistical comparison between the results from the proposed method and the results from the reference methods showed no significant difference regarding accuracy and precision. Copyright © 2015 Elsevier B.V. All rights reserved.

Pharmaceutical care in Kuwait: hospital pharmacists' perspectives.

Science.gov (United States)

Katoue, Maram G; Awad, Abdelmoneim I; Schwinghammer, Terry L; Kombian, Samuel B

2014-12-01

Pharmaceutical care practice has been championed as the primary mission of the pharmacy profession, but its implementation has been suboptimal in many developing countries including Kuwait. Pharmacists must have sufficient knowledge, skills, and positive attitudes to practise pharmaceutical care, and barriers in the pharmacy practice model must be overcome before pharmaceutical care can be broadly implemented in a given healthcare system. To investigate hospital pharmacists' attitudes towards pharmaceutical care, perceptions of their preparedness to provide pharmaceutical care, and the barriers to its implementation in Kuwait. Six general hospitals, eight specialized hospitals and seven specialized health centers in Kuwait. A descriptive, cross-sectional survey was distributed to all pharmacists working in the governmental hospitals in Kuwait (385 pharmacists). Data were collected via a pre-tested self-administered questionnaire. Descriptive statistics including percentages, medians and means Likert scale rating (standard deviations) were calculated and compared using statistical package for social sciences, version 20. Statistical significance was accepted at a p value of Kuwait. Completed surveys were received from 250 (64.9%) of the 385 pharmacists. Pharmacists expressed overall positive attitudes towards pharmaceutical care. They felt well prepared to implement the various aspects of pharmaceutical care, with the least preparedness in the administrative/management aspects. Pharmacists with more practice experience expressed significantly more positive attitudes towards pharmaceutical care (p = 0.001) and they felt better prepared to provide pharmaceutical care competencies (p Kuwait advocate implementation of pharmaceutical care while also appreciating the organizational, technical and professional barriers to its widespread adoption. Collaborative efforts between health authorities and educational institutions, and the integration of innovative approaches in

Metabolism and elimination of methyl, iso- and n-butyl paraben in human urine after single oral dosage.

Science.gov (United States)

Moos, Rebecca K; Angerer, Jürgen; Dierkes, Georg; Brüning, Thomas; Koch, Holger M

2016-11-01

Parabens are used as preservatives in personal care and consumer products, food and pharmaceuticals. Their use is controversial because of possible endocrine disrupting properties. In this study, we investigated metabolism and urinary excretion of methyl paraben (MeP), iso-butyl paraben (iso-BuP) and n-butyl paraben (n-BuP) after oral dosage of deuterium-labeled analogs (10 mg). Each volunteer received one dosage per investigated paraben separately and at least 2 weeks apart. Consecutive urine samples were collected over 48 h. In addition to the parent parabens (free and conjugated) which are already used as biomarkers of internal exposure and the known but non-specific metabolites, p-hydroxybenzoic acid (PHBA) and p-hydroxyhippuric acid (PHHA), we identified new, oxidized metabolites with hydroxy groups on the alkyl side chain (3OH-n-BuP and 2OH-iso-BuP) and species with oxidative modifications on the aromatic ring. MeP represented 17.4 % of the dose excreted in urine, while iso-BuP represented only 6.8 % and n-BuP 5.6 %. Additionally, for iso-BuP, about 16 % was excreted as 2OH-iso-BuP and for n-BuP about 6 % as 3OH-n-BuP. Less than 1 % was excreted as ring-hydroxylated metabolites. In all cases, PHHA was identified as the major but non-specific metabolite (57.2-63.8 %). PHBA represented 3.0-7.2 %. For all parabens, the majority of the oral dose captured by the above metabolites was excreted in the first 24 h (80.5-85.3 %). Complementary to the parent parabens excreted in urine, alkyl-chain-oxidized metabolites of the butyl parabens are introduced as valuable and contamination-free biomarkers of exposure.

Low-dosage helical CT applications for chest medical checkup and lung cancer screening

International Nuclear Information System (INIS)

Wang Ping; Cui Fa; Liang Huanqing; Zheng Minfei

2005-01-01

Objective: A discussion on low-dosage helical CT applications on chest medical checkup and lung cancer screening. Methods: On the 100 chest medical check up with three different of protocols, including standard-dosage (the tube current was 230 mAs) were compared with low-dose (tube current was 50 mAs or 30 mAs). Results: Low-dosage helical CT scan provides excellent images. In 100 chest medical checkup, 39 nodules or masses were revealed, enlarged lymph node was noted in 1 case; emphysema or bullae was demonstrated in 3 segments; thickening of bronchial wall was shown in 2 cases; and localized pleural thickening was found in 1 case. Conclusion: In chest checkup or lung cancer screening low-dosage helical CT (tube current 30 mAs) will not only guarantee image quality but also reduce the radiation dose during the examination. (authors)

Application of ion chromatography in clinical studies and pharmaceutical industry.

Science.gov (United States)

Michalski, Rajmund

2014-01-01

Ion chromatography is a well-established regulatory method for analyzing anions and cations in environmental, food and many other samples. It offers an enormous range of possibilities for selecting stationary and mobile phases. Additionally, it usually helps to solve various separation problems, particularly when it is combined with different detection techniques. Ion chromatography can also be used to determine many ions and substances in clinical and pharmaceutical samples. It provides: availability of high capacity stationary phases and sensitive detectors; simple sample preparation; avoidance of hazardous chemicals; decreased sample volumes; flexible reaction options on a changing sample matrix to be analyzed; or the option to operate a fully-automated system. This paper provides a short review of the ion chromatography applications for determining different inorganic and organic substances in clinical and pharmaceutical samples.

Safety warnings and first aid instructions on consumer and pharmaceutical products in Nigeria: has there been an improvement?

Science.gov (United States)

Nonyelum, Stanley Catherine; Nkem, Nwachukwu; Ifeyinwa, Chijoke-Nwauche; Orisakwe, Orish Ebere

2010-10-01

To investigate the adequacy of safety warnings and first aid instructions on the labels of pharmaceutical and consumer products in Nigeria. A market basket method (total collection of all available samples) was used to investigate the adequacy of safety warnings and first aid instructions on the labels of 600 pharmaceutical and consumer products in Nigeria. The results showed that 69.8% of the products had adequate warnings whereas 385 (64.1%) of the products screened had legible product warnings. Only 52 (8.7%) of the total number of products had appropriate first aid instructions while only 25 (4.12%) of the products described symptoms and full treatment of poisoning by the product and 319 (53.2%) products surveyed recommended calling a health professional. A total of 31 (5.2%) products had labels that were considered too technical (non English). Of the 600 products, 386 (64.3%) had dosage instructions that were considered adequate while 538 (89.6%) had adequate storage instructions. About 68% of the products had partially correct warnings while 44 or 7.3% had partially correct first aid instructions. Some products had neither warnings nor first aid instructions. This study suggests a not too impressive improvement in the correctness and appropriateness of label information.

An understanding of modified release matrix tablets behavior during drug dissolution as the key for prediction of pharmaceutical product performance - case study of multimodal characterization of quetiapine fumarate tablets.

Science.gov (United States)

Kulinowski, Piotr; Woyna-Orlewicz, Krzysztof; Rappen, Gerd-Martin; Haznar-Garbacz, Dorota; Węglarz, Władysław P; Dorożyński, Przemysław P

2015-04-30

Motivation for the study was the lack of dedicated and effective research and development (R&D) in vitro methods for oral, generic, modified release formulations. The purpose of the research was to assess multimodal in vitro methodology for further bioequivalence study risk minimization. Principal results of the study are as follows: (i) Pharmaceutically equivalent quetiapine fumarate extended release dosage form of Seroquel XR was developed using a quality by design/design of experiment (QbD/DoE) paradigm. (ii) The developed formulation was then compared with originator using X-ray microtomography, magnetic resonance imaging and texture analysis. Despite similarity in terms of compendial dissolution test, developed and original dosage forms differed in micro/meso structure and consequently in mechanical properties. (iii) These differences were found to be the key factors of failure of biorelevant dissolution test using the stress dissolution apparatus. Major conclusions are as follows: (i) Imaging methods allow to assess internal features of the hydrating extended release matrix and together with the stress dissolution test allow to rationalize the design of generic formulations at the in vitro level. (ii) Technological impact on formulation properties e.g., on pore formation in hydrating matrices cannot be overlooked when designing modified release dosage forms. Copyright © 2015 Elsevier B.V. All rights reserved.

Enhanced pharmaceutical removal from water in a three step bio-ozone-bio process

NARCIS (Netherlands)

Wilt, de Arnoud; Gijn, van Koen; Verhoek, Tom; Vergnes, Amber; Hoek, Mirit; Rijnaarts, Huub; Langenhoff, Alette

2018-01-01

Individual treatment processes like biological treatment or ozonation have their limitations for the removal of pharmaceuticals from secondary clarified effluents with high organic matter concentrations (i.e. 17 mg TOC/L). These limitations can be overcome by combining these two processes for a

[Pharmaceutical preparations in the hospital. Analysis and in-house development of an automated system of management.

Science.gov (United States)

Barberini, Cinzia; Lavezzini, Enrica; Zoboli, Daniela; Busani, Corrado

2018-02-01

In the past couple of years, the demand of galenic compounds has risen sharply. In order to plan the activity, our team designed and set up a database which stores all the necessary information related to drugs and ingredients. This allows our internal Galenic Laboratory to better manage the pharmaceutical prescriptions for the hospital and the outpatients, optimizing the use of raw materials. The application is based on the interconnection of prescription-related aspects (patients' and prescriber's details and prescription information). The prescription name is linked to the list of substances, which allows to monitor the stock levels. Inserting the daily dosage into the system, our personnel can calculate the monthly supply of the medicine. Each prescription contains specific warnings on printable labels. A printed sheet, inclusive of label and checks on the final preparation, is produced for each prescription. After a testing phase, the application gradually replaced our traditional process of pharmaceutical activity management, allowing for a more accurate scheduling of the medicine requests. The worksheet and its specific label are automatically generated. Then a prediction scheme is generated for the ordinary programmable galenic activity. The project successfully achieved the following goals: 1) automate the information flow related to preparations; 2) improve the response time in terms of drug preparation and delivery; 3) minimize the number of emergencies.

Dosage-based parameters for characterization of puff dispersion results.

Science.gov (United States)

Berbekar, Eva; Harms, Frank; Leitl, Bernd

2015-01-01

A set of parameters is introduced to characterize the dispersion of puff releases based on the measured dosage. These parameters are the dosage, peak concentration, arrival time, peak time, leaving time, ascent time, descent time and duration. Dimensionless numbers for the scaling of the parameters are derived from dimensional analysis. The dimensionless numbers are tested and confirmed based on a statistically representative wind tunnel dataset. The measurements were carried out in a 1:300 scale model of the Central Business District in Oklahoma City. Additionally, the effect of the release duration on the puff parameters is investigated. Copyright © 2014 Elsevier B.V. All rights reserved.

Spectrophotometric Determination of Trimipramine in Tablet Dosage ...

African Journals Online (AJOL)

Purpose: To develop and validate simple, rapid and sensitive spectrophotometric procedures for determination of trimipramine in tablet dosage form. Methods: The methods were based on the interaction of trimipramine as n-electron donor with the ο-acceptor, iodine and various π-acceptors, namely: chloranil (CH), ...

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.

Entrepreneurial patent management in pharmaceutical startups.

Science.gov (United States)

Holgersson, Marcus; Phan, Tai; Hedner, Thomas

2016-07-01

Startups fill an increasingly important role as innovators in the pharmaceutical industry, and patenting is typically central to their success. This article aims to explore patent management in pharmaceutical startups. The results show that startups need to deal with several challenges related to patenting and an 'entrepreneurial' approach to patent management is called for. Resource constraints, venture capital provision, exits and other conditions and events must be readily considered in the patent management process to build a successful pharmaceutical venture, something that could benefit the pharmaceutical industry as a whole. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Sewage sludge disintegration by combined treatment of alkaline+high pressure homogenization.

Science.gov (United States)

Zhang, Yuxuan; Zhang, Panyue; Zhang, Guangming; Ma, Weifang; Wu, Hao; Ma, Boqiang

2012-11-01

Alkaline pretreatment combined with high pressure homogenization (HPH) was applied to promote sewage sludge disintegration. For sewage sludge with a total solid content of 1.82%, sludge disintegration degree (DD(COD)) with combined treatment was higher than the sum of DD(COD) with single alkaline and single HPH treatment. NaOH dosage ⩽0.04mol/L, homogenization pressure ⩽60MPa and a single homogenization cycle were the suitable conditions for combined sludge treatment. The combined sludge treatment showed a maximum DD(COD) of 59.26%. By regression analysis, the combined sludge disintegration model was established as 11-DD(COD)=0.713C(0.334)P(0.234)N(0.119), showing that the effect of operating parameters on sludge disintegration followed the order: NaOH dosage>homogenization pressure>number of homogenization cycle. The energy efficiency with combined sludge treatment significantly increased compared with that with single HPH treatment, and the high energy efficiency was achieved at low homogenization pressure with a single homogenization cycle. Copyright © 2012 Elsevier Ltd. All rights reserved.

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...

X chromosome dosage compensation via enhanced transcriptional elongation in Drosophila.

Science.gov (United States)

Larschan, Erica; Bishop, Eric P; Kharchenko, Peter V; Core, Leighton J; Lis, John T; Park, Peter J; Kuroda, Mitzi I

2011-03-03

The evolution of sex chromosomes has resulted in numerous species in which females inherit two X chromosomes but males have a single X, thus requiring dosage compensation. MSL (Male-specific lethal) complex increases transcription on the single X chromosome of Drosophila males to equalize expression of X-linked genes between the sexes. The biochemical mechanisms used for dosage compensation must function over a wide dynamic range of transcription levels and differential expression patterns. It has been proposed that the MSL complex regulates transcriptional elongation to control dosage compensation, a model subsequently supported by mapping of the MSL complex and MSL-dependent histone 4 lysine 16 acetylation to the bodies of X-linked genes in males, with a bias towards 3' ends. However, experimental analysis of MSL function at the mechanistic level has been challenging owing to the small magnitude of the chromosome-wide effect and the lack of an in vitro system for biochemical analysis. Here we use global run-on sequencing (GRO-seq) to examine the specific effect of the MSL complex on RNA Polymerase II (RNAP II) on a genome-wide level. Results indicate that the MSL complex enhances transcription by facilitating the progression of RNAP II across the bodies of active X-linked genes. Improving transcriptional output downstream of typical gene-specific controls may explain how dosage compensation can be imposed on the diverse set of genes along an entire chromosome.

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

ANALYSIS OF SCIENTIFIC RESEARCHES IN PHARMACEUTICAL PROMOTION GLOBALLY: TOWARDS INTERNATIONALLY DEVELOPING PRACTICALLY-ORIENTED GUIDELINES FOR PHARMACEUTICAL COMPANIES

Directory of Open Access Journals (Sweden)

M. M. Bahlol

2016-01-01

Full Text Available Purpose. Pharmaceutical industry is transnational and globally important. Many pharmaceutical companies operate their business in multinational and international forms in different countries. Diverse researches from different countries indicated and confirmed marketing promotion importance in pharmaceutical field. Therefore, marketing promotion and its effects are a very important issue that should be globally investigated in real life and evidence context. We oriented our research according to these scientific and practical values.Methodology. We reviewed pharmaceutical marketing promotion researches from more than 25 different countries, e.g., USA, Canada, Italy, France, Russia, India, Egypt and Syria where we employed our knowledge of three widely spread languages, i.e., English, Russian and Arabic. Such language variation supports us with large and variable amount of scientific knowledge, deep understanding and ability of analysis. Some studies investigated average response to pharmaceutical marketing promotion and few studies took into consideration heterogeneity in their effects with respect to advertising medium or drug characteristics.Originality. We investigated empirical evidences of pharmaceutical marketing promotion that can be directed to either consumer or healthcare professionals.Findings. We extracted, gathered and associated information of pharmaceutical promotion globally which oriented us to several evidence and practical facts with regard to employing promotion tools in different definite situations pertinent to main directions; their welfare and health enhancing effects and adverse effects. Practical Implications- Consequently, we developed practically-oriented guidelines for companies concerning pharmaceutical promotion globally ate the end of this paper.

Guiding principles of value creation through collaborative innovation in pharmaceutical research.

Science.gov (United States)

Schweizer, Liang; He, Jeff

2018-02-01

Open innovation has become the main trend in pharmaceutical research. Potential obstacles and pitfalls of collaborations often lead to missed opportunities and/or poorly executed partnerships. This paper aims to provide a framework that facilitates the execution of successful collaborations. We start by mapping out three checkpoints onto early-stage collaborative partnerships: inception, ignition and implementation. Different value types and value drivers are then laid out for each phase of the partnership. We proceed to propose a ratio-driven approach and a value-adjustment mechanism, enhancing the probability of successes in pharmaceutical research collaborations. These guiding principles combined should help the partners either reach agreement more quickly or move on to the next potential project. Copyright © 2017 Elsevier Ltd. All rights reserved.

[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.

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.

PARTICULARITIES OF MODERN PHARMACEUTICAL PROMOTION

Directory of Open Access Journals (Sweden)

Юрий Владимирович Тарасов

2014-02-01

Full Text Available Pharmaceutical products market is one of the most saturated consumers’ markets. Characteristic features of it are: high competition, fierce struggle for the customer, specific technologies of promotion. In conditions of globalization and increase in competition both in world pharmaceutical market and in the market of medicines and goods of medical purpose in Russia modern marketing techniques of promotion of the products to the end consumers are the key tools for strengthening market positions – both of producers of pharmaceutical goods and their suppliers, distributors, big whole-sale companies. Among main tools of promotion are: advertising, public relations, stimulation of sales on the market of medicines, personal sales, computer technologies. The article describes different technologies of promotion of medicines: indoor-advertising, hot lines, pharmaceutical exhibitions, packing. DOI: http://dx.doi.org/10.12731/2218-7405-2013-12-1

National transparency assessment of Kuwait's pharmaceutical sector.

Science.gov (United States)

Badawi, Dalia A; Alkhamis, Yousif; Qaddoumi, Mohammad; Behbehani, Kazem

2015-09-01

Corruption is one of several factors that may hinder the access to pharmaceuticals. Since Kuwait has the highest per-capita spending on pharmaceuticals in the region, we wanted to evaluate the level of transparency in its pharmaceutical sector using an established assessment tool adapted by the World Health Organization. Standardized questionnaires were conducted via semi-structured interviews with key informants to measure the level of transparency in eight functions of the public pharmaceutical sector. The scores for the degree of vulnerability to corruption reflected marginal to moderate venerability to corruption for most pharmaceutical sectors. The perceived strengths included availability of appropriate laws, the presence of clear standard operating procedures, and the use of an efficient registration/distribution system. Weaknesses included lack of conflict of interest guidelines and written terms of reference, absence of pharmacoeconomic studies, and inconsistencies in law enforcement. Findings reveal that few functions of Kuwait pharmaceutical sector remain fairly vulnerable to corruption. However, the willingness of Kuwait Ministry of Health to adopt the assessment study and the acknowledgement of the weaknesses of current processes of the pharmaceutical sector may assist to achieve a transparent pharmaceutical system in the near future. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Strategic Management of Innovations at Pharmaceutical Enterprises

Directory of Open Access Journals (Sweden)

Honcharova Svіtlana Yu.

2014-01-01

Full Text Available The article is devoted to theoretical and practical issues of the use of the concept of strategic management of innovations at pharmaceutical enterprises. It studies main barriers, which restrict development of Ukrainian pharmaceutical enterprises. It analyses the state and tendencies of development of innovation activity of pharmaceutical enterprises and studies foreign experience of innovation activity. It marks out specific features of strategic management of innovation development in pharmaceutical industry. It specifies the role and advantages of methods of strategic analysis in the system of management of a pharmaceutical enterprise. It considers the essence of “innovation development” and “innovation model of development” notions and analyses their organisational and legal provision. It justifies strategic tasks of the pharmaceutical filed to focus on in order to achieve a breakthrough when building an innovation model of economic development. The article proves that the most important factors that ensure growth of efficiency of pharmaceutical production are: wide application of the concept of strategic management and creation of innovations.

[Chinese medicine industry 4.0：advancing digital pharmaceutical manufacture toward intelligent pharmaceutical manufacture].

Science.gov (United States)

Cheng, Yi-Yu; Qu, Hai-Bin; Zhang, Bo-Li

2016-01-01

A perspective analysis on the technological innovation in pharmaceutical engineering of Chinese medicine unveils a vision on "Future Factory" of Chinese medicine industry in mind. The strategy as well as the technical roadmap of "Chinese medicine industry 4.0" is proposed, with the projection of related core technology system. It is clarified that the technical development path of Chinese medicine industry from digital manufacture to intelligent manufacture. On the basis of precisely defining technical terms such as process control, on-line detection and process quality monitoring for Chinese medicine manufacture, the technical concepts and characteristics of intelligent pharmaceutical manufacture as well as digital pharmaceutical manufacture are elaborated. Promoting wide applications of digital manufacturing technology of Chinese medicine is strongly recommended. Through completely informationized manufacturing processes and multi-discipline cluster innovation, intelligent manufacturing technology of Chinese medicine should be developed, which would provide a new driving force for Chinese medicine industry in technology upgrade, product quality enhancement and efficiency improvement. Copyright© by the Chinese Pharmaceutical Association.

Dosage-dependent non-linear effect of L-dopa on human motor cortex plasticity.

Science.gov (United States)

Monte-Silva, Katia; Liebetanz, David; Grundey, Jessica; Paulus, Walter; Nitsche, Michael A

2010-09-15

The neuromodulator dopamine affects learning and memory formation and their likely physiological correlates, long-term depression and potentiation, in animals and humans. It is known from animal experiments that dopamine exerts a dosage-dependent, inverted U-shaped effect on these functions. However, this has not been explored in humans so far. In order to reveal a non-linear dose-dependent effect of dopamine on cortical plasticity in humans, we explored the impact of 25, 100 and 200 mg of L-dopa on transcranial direct current (tDCS)-induced plasticity in twelve healthy human subjects. The primary motor cortex served as a model system, and plasticity was monitored by motor evoked potential amplitudes elicited by transcranial magnetic stimulation. As compared to placebo medication, low and high dosages of L-dopa abolished facilitatory as well as inhibitory plasticity, whereas the medium dosage prolonged inhibitory plasticity, and turned facilitatory plasticity into inhibition. Thus the results show clear non-linear, dosage-dependent effects of dopamine on both facilitatory and inhibitory plasticity, and support the assumption of the importance of a specific dosage of dopamine optimally suited to improve plasticity. This might be important for the therapeutic application of dopaminergic agents, especially for rehabilitative purposes, and explain some opposing results in former studies.

Pharmaceutical Public-Private Partnerships

DEFF Research Database (Denmark)

Bagley, Constance; Tvarnø, Christina D.

2014-01-01

This article provides a game theory and law-and-management analysis of for- profit pharmaceutical public-private partnerships, a complex type of legal arrangement in the highly regulated pharmaceutical industry. A pharmaceutical public-private partnership (PPPP) agreement is a legally binding...... and a practical perspective on how properly crafted PPPP arrangements can promote innovation more efficiently than traditional self-optimizing contracts. In particular, a properly framed binding contract, coupled with respect for positive incentives, can move the parties away from an inefficient prisoners...... systems to build and share innovation. When coupled with appropriate attention to the difficult task of coordinating the actions of interdependent actors, a PPPP arrangement can enhance the likelihood of successful commercialization of pharmacological discoveries by flipping the par- ties’ incentives...

Relationship between chromosomal aberration of bone marrow cells and dosage of irradiation after 46Sc internal pollution and external low dose X-irradiation in mice

International Nuclear Information System (INIS)

Li Guofu; Li Zhang; Wu Yin

1989-01-01

The relationship between chromosomal aberration of bone marrow cells and dosage in mice 24 h after 46 Sc internal pollution combined with external low dose whole body X-irradiation was quantiatively studied. The results showed that the relationship between chromosomal aberration and dosage was expressed in a linear regression equation. The chromosomal aberration rate was lower in the combined exposure than that of the sum of internal and external exposures, but higher than that of either the internal or external exposure singly. The relationship between chromosomal aberration and time was expressed in the following three phase exponential function: Y(t) = 2.9078 exp 0.27668t + 2.9371 exp -0.0778t + 2.3786 -0.01788t . By means of fit test, there was no significant difference between the determined and the theoretical values. The 90% theoretical values got from all the equations distributed over the determined values

Combination strategies for pandemic influenza response - a systematic review of mathematical modeling studies

Directory of Open Access Journals (Sweden)

Lee Vernon J

2009-12-01

Full Text Available Abstract Background Individual strategies in pandemic preparedness plans may not reduce the impact of an influenza pandemic. Methods We searched modeling publications through PubMed and associated references from 1990 to 30 September 2009. Inclusion criteria were modeling papers quantifying the effectiveness of combination strategies, both pharmaceutical and non-pharmaceutical. Results Nineteen modeling papers on combination strategies were selected. Four studies examined combination strategies on a global scale, 14 on single countries, and one on a small community. Stochastic individual-based modeling was used in nine studies, stochastic meta-population modeling in five, and deterministic compartmental modeling in another five. As part of combination strategies, vaccination was explored in eight studies, antiviral prophylaxis and/or treatment in 16, area or household quarantine in eight, case isolation in six, social distancing measures in 10 and air travel restriction in six studies. Two studies suggested a high probability of successful influenza epicenter containment with combination strategies under favorable conditions. During a pandemic, combination strategies delayed spread, reduced overall number of cases, and delayed and reduced peak attack rate more than individual strategies. Combination strategies remained effective at high reproductive numbers compared with single strategy. Global cooperative strategies, including redistribution of antiviral drugs, were effective in reducing the global impact and attack rates of pandemic influenza. Conclusion Combination strategies increase the effectiveness of individual strategies. They include pharmaceutical (antiviral agents, antibiotics and vaccines and non-pharmaceutical interventions (case isolation, quarantine, personal hygiene measures, social distancing and travel restriction. Local epidemiological and modeling studies are needed to validate efficacy and feasibility.

Use of Activated Carbon in Packaging to Attenuate Formaldehyde-Induced and Formic Acid-Induced Degradation and Reduce Gelatin Cross-Linking in Solid Dosage Forms.

Science.gov (United States)

Colgan, Stephen T; Zelesky, Todd C; Chen, Raymond; Likar, Michael D; MacDonald, Bruce C; Hawkins, Joel M; Carroll, Sophia C; Johnson, Gail M; Space, J Sean; Jensen, James F; DeMatteo, Vincent A

2016-07-01

Formaldehyde and formic acid are reactive impurities found in commonly used excipients and can be responsible for limiting drug product shelf-life. Described here is the use of activated carbon in drug product packaging to attenuate formaldehyde-induced and formic acid-induced drug degradation in tablets and cross-linking in hard gelatin capsules. Several pharmaceutical products with known or potential vulnerabilities to formaldehyde-induced or formic acid-induced degradation or gelatin cross-linking were subjected to accelerated stability challenges in the presence and absence of activated carbon. The effects of time and storage conditions were determined. For all of the products studied, activated carbon attenuated drug degradation or gelatin cross-linking. This novel use of activated carbon in pharmaceutical packaging may be useful for enhancing the chemical stability of drug products or the dissolution stability of gelatin-containing dosage forms and may allow for the 1) extension of a drug product's shelf-life when the limiting attribute is a degradation product induced by a reactive impurity, 2) marketing of a drug product in hotter and more humid climatic zones than currently supported without the use of activated carbon, and 3) enhanced dissolution stability of products that are vulnerable to gelatin cross-linking. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Combination of electron beam irradiation and thermal treatment to enhance the shelf-life of traditional Indian fermented food (Idli)

International Nuclear Information System (INIS)

Mulmule, Manoj D.; Shimmy, Shankar M.; Bambole, Vaishali; Jamdar, Sahayog N.; Rawat, K.P.; Sarma, K.S.S.

2017-01-01

Idli, a steam-cooked breakfast food item consumed in India, is famous as a staple food for its spongy texture and unique fermented taste. Idli preparation is a time consuming process; although instant Idli pre-mixes as powder or batter are available in the market, they do not have the distinctive taste and aroma similar to the Idli prepared at home. Hence ready-to-eat (RTE) form of this food is in demand. Therefore, an attempt was made to prepare RTE Idli bearing similar taste as home-cooked Idli with an extended shelf-life of up to two months at an ambient temperature using Electron Beam Irradiation (EBI) at dosages 2.5 kGy, 5 kGy and 7.5 kGy and combination processing comprised of EBI dosage at 2.5 kGy and thermal treatment (80 °C for 20 min). The treated Idli's were microbiologically and sensorially evaluated at storage periods of zero day, 14 days, 30 days and 60 days. Idli's irradiated at 7.5 kGy and subjected to combination processing at 2.5 kGy and thermal treatment were shelf-stable for 60 days. 2.5 kGy and 5 kGy radiation dosages alone were not sufficient to preserve Idli samples for more than 14 days. Undesirable change in sensory properties of Idli was observed at an EBI dosage of 7.5 kGy. Sensory properties of combination processed Idli's were found to undergo minor change over the storage period. The present work suggests that lowest radiation dosage in combination with thermal treatment could be useful to achieve the extended shelf-life without considerably impairing the organoleptic quality of Ready-to-Eat Idli. - Highlights: • Idli (traditional Indian fermented food) was prepared in ready-to-eat (RTE) form. • Ready-to-eat Idli was then subjected to combination processing comprised of lowest irradiation dosage of 2.5 kGy with mild heat treatment to extend its shelf life. • Increase in hardness and decrease in brightness of combination processed Idli was observed. • Combination processed Idli was microbiologically safe and

Transmission FTIR derivative spectroscopy for estimation of furosemide in raw material and tablet dosage form

Directory of Open Access Journals (Sweden)

Máximo Gallignani

2014-10-01

Full Text Available A Fourier transform infrared derivative spectroscopy (FTIR-DS method has been developed for determining furosemide (FUR in pharmaceutical solid dosage form. The method involves the extraction of FUR from tablets with N,N-dimethylformamide by sonication and direct measurement in liquid phase mode using a reduced path length cell. In general, the spectra were measured in transmission mode and the equipment was configured to collect a spectrum at 4 cm−1 resolution and a 13 s collection time (10 scans co-added. The spectra were collected between 1400 cm−1 and 450 cm−1. Derivative spectroscopy was used for data processing and quantitative measurement using the peak area of the second order spectrum of the major spectral band found at 1165 cm−1 (SO2 stretching of FUR with baseline correction. The method fulfilled most validation requirements in the 2 mg/mL and 20 mg/mL range, with a 0.9998 coefficient of determination obtained by simple calibration model, and a general coefficient of variation <2%. The mean recovery for the proposed assay method resulted within the (100±3% over the 80%–120% range of the target concentration. The results agree with a pharmacopoeial method and, therefore, could be considered interchangeable.

Braving a faceless new world? Conceptualizing trust in the pharmaceutical industry and its products

NARCIS (Netherlands)

Brown, P.; Calnan, M.

2012-01-01

Pharmaceutical products are commonly relied upon by professionals, and correspondingly patients, within a wide range of healthcare contexts. This dependence, combined with the inherent risk and uncertainty surrounding both medical practice and the drugs it harnesses, points towards the importance of

On Identification of Critical Material Attributes for Compression Behaviour of Pharmaceutical Diluent Powders

Directory of Open Access Journals (Sweden)

Jianyi Zhang

2017-07-01

Full Text Available As one of the commonly-used solid dosage forms, pharmaceutical tablets have been widely used to deliver active drugs into the human body, satisfying patient’s therapeutic requirements. To manufacture tablets of good quality, diluent powders are generally used in formulation development to increase the bulk of formulations and to bind other inactive ingredients with the active pharmaceutical ingredients (APIs. For formulations of a low API dose, the drug products generally consist of a large fraction of diluent powders. Hence, the attributes of diluents become extremely important and can significantly influence the final product property. Therefore, it is essential to accurately characterise the mechanical properties of the diluents and to thoroughly understand how their mechanical properties affect the manufacturing performance and properties of the final products, which will build a sound scientific basis for formulation design and product development. In this study, a comprehensive evaluation of the mechanical properties of the widely-used pharmaceutical diluent powders, including microcrystalline cellulose (MCC powders with different grades (i.e., Avicel PH 101, Avicel PH 102, and DG, mannitol SD 100, lactose monohydrate, and dibasic calcium phosphate, were performed. The powder compressibility was assessed with Heckel and Kawakita analyses. The material elastic recovery during decompression and in storage was investigated through monitoring the change in the dimensions of the compressed tablets over time. The powder hygroscopicity was also evaluated to examine the water absorption ability of powders from the surroundings. It was shown that the MCC tablets exhibited continuous volume expansion after ejection, which is believed to be induced by (1 water absorption from the surrounding, and (2 elastic recovery. However, mannitol tablets showed volume expansion immediately after ejection, followed by the material shrinkage in storage. It is

Conceptualizing Pharmaceutical Plants

DEFF Research Database (Denmark)

Larsen, Bent Dalgaard; Jensen, Klaes Ladeby; Gjøl, Mikkel

2006-01-01

In the conceptual design phase of pharmaceutical plants as much as 80%-90% of the total cost of a project is committed. It is therefore essential that the chosen concept is viable. In this design process configuration and 3D models can help validate the decisions made. Designing 3D models...... is a complex task and requires skilled users. We demonstrate that a simple 2D/3D configuration tool can support conceptualizing of pharmaceutical plants. Present paper reports on preliminary results from a full scale implementation project at a Danish engineering company....

PSE in Pharmaceutical Process Development

DEFF Research Database (Denmark)

Gernaey, Krist; Cervera Padrell, Albert Emili; Woodley, John

2011-01-01

The pharmaceutical industry is under growing pressure to increase efficiency, both in production and in process development. This paper will discuss the use of Process Systems Engineering (PSE) methods in pharmaceutical process development, and searches for answers to questions such as: Which PSE...

Degradation of Dye Wastewater by Pulsed High-Voltage Discharge Combined with Spent Tea Leaves

International Nuclear Information System (INIS)

Liu Yan; Yang Li; Yang Gang; Zhang Yanzong; Zhang Xiaohong; Deng Shihuai

2014-01-01

Degradation of methylene blue (MB) was performed using the pulsed discharge process (PDP) combined with spent tea leaves (STLs). The effects of STL dosage, concentration of initial solution, and pH were analyzed in the combined treatment. Results showed that the combined treatment was effective for dye wastewater degradation; when the dosage of STLs was 3.2 g/L, the degradation efficiency reached 90% after 15 min treatment, and STLs showed a good repeatability. The degradation rate decreased with increasing initial MB concentration but not related to the solution pH in the combined treatment. Fourier-transform infrared spectra and N 2 adsorption suggested that the number of acidic and basic groups in the STL surface increased after the treatment, but the surface area and pore volume remained unchanged. (plasma technology)

Study of Bokashi’s Type and Dosages to Growth and Harvest Yield Honey Dews (Cucumis Melo L. In Low Land

Directory of Open Access Journals (Sweden)

Ana Amiroh

2016-12-01

Full Text Available Recently, most cultivation and planting of Melon (Cucumis melo L. by farmers using inorganic fertilizers with an excessive dosage, and this causes the lowland productivity decrease with consequent. The soil organic matter decreased as low as time increasing. Application and using of mature organic matter are an alternative to solve these problems in order the lowland become more conducive and productive for growth of melon. But increasing pests and diseases attaching to the plants may caused by adding immature organic matters into soil. Sources to make bokashi like as paddy straw and water hyacinth is immense but it’s not yet used. This research was aimed to study, know and usage of paddy straw and water hyacinth bokashi’s on melon growing at lowland. Experiment was conducted at Lowland Experiment Station of Agricultural Faculty, Brawijaya, in Jatikerto Village, Kromengan Distric, Malang, from April-June 2015. Experiment was applied in a Randomized Block Design (RBD with double factors Types and Dosages of Bokashis. There is seven combinations of treatment with three replications, each treatment consisted four individual plants. Result showed there is significant difference between types and dosages of bokashi on plant length at 28, 35, 42 dan 49 days after planting (d,a,p respectively. The significant difference between treatment also shown by leaf area at 28 - 49 (d.a.p.. Application of paddy straw bokashi was better than hyacinth bokashi on melon growth. The best yield shows that by using paddy straw bokashi with 5 ton/ha of dosage gives melon with 2,56 kg /plant fresh weight.

Contribution of hospital effluents to the load of pharmaceuticals in urban wastewaters: identification of ecologically relevant pharmaceuticals.

Science.gov (United States)

Santos, Lúcia H M L M; Gros, Meritxell; Rodriguez-Mozaz, Sara; Delerue-Matos, Cristina; Pena, Angelina; Barceló, Damià; Montenegro, M Conceição B S M

2013-09-01

The impact of effluent wastewaters from four different hospitals: a university (1456 beds), a general (350 beds), a pediatric (110 beds) and a maternity hospital (96 beds), which are conveyed to the same wastewater treatment plant (WWTP), was evaluated in the receiving urban wastewaters. The occurrence of 78 pharmaceuticals belonging to several therapeutic classes was assessed in hospital effluents and WWTP wastewaters (influent and effluent) as well as the contribution of each hospital in WWTP influent in terms of pharmaceutical load. Results indicate that pharmaceuticals are widespread pollutants in both hospital and urban wastewaters. The contribution of hospitals to the input of pharmaceuticals in urban wastewaters widely varies, according to their dimension. The estimated total mass loadings were 306 g d(-1) for the university hospital, 155 g d(-1) for the general one, 14 g d(-1) for the pediatric hospital and 1.5 g d(-1) for the maternity hospital, showing that the biggest hospitals have a greater contribution to the total mass load of pharmaceuticals. Furthermore, analysis of individual contributions of each therapeutic group showed that NSAIDs, analgesics and antibiotics are among the groups with the highest inputs. Removal efficiency can go from over 90% for pharmaceuticals like acetaminophen and ibuprofen to not removal for β-blockers and salbutamol. Total mass load of pharmaceuticals into receiving surface waters was estimated between 5 and 14 g/d/1000 inhabitants. Finally, the environmental risk posed by pharmaceuticals detected in hospital and WWTP effluents was assessed by means of hazard quotients toward different trophic levels (algae, daphnids and fish). Several pharmaceuticals present in the different matrices were identified as potentially hazardous to aquatic organisms, showing that especial attention should be paid to antibiotics such as ciprofloxacin, ofloxacin, sulfamethoxazole, azithromycin and clarithromycin, since their hazard quotients

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...

Bioremediation Kinetics of Pharmaceutical Industrial Effluent

OpenAIRE

M. Šabić; M. Vuković Domanovac; Z. Findrik Blažević; E. Meštrović

2015-01-01

In recent years, concerns about the occurrence and fate of pharmaceuticals that could be present in water and wastewater has gained increasing attention. With the public’s enhanced awareness of eco-safety, environmentally benign methods based on microorganisms have become more accepted methods of removing pollutants from aquatic systems. This study investigates bioremediation of pharmaceutical wastewater from pharmaceutical company Pliva Hrvatska d.o.o., using activated sludge and bioaugmente...

Accelerated in vitro release testing methods for extended release parenteral dosage forms

Science.gov (United States)

Shen, Jie; Burgess, Diane J.

2012-01-01

Objectives This review highlights current methods and strategies for accelerated in vitro drug release testing of extended release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in situ depot-forming systems, and implants. Key findings Extended release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, “real-time” in vitro release tests for these dosage forms are often run over a long time period. Accelerated in vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in vitro release methods using United States Pharmacopoeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended release parenteral dosage forms, along with the accelerated in vitro release testing methods currently employed are discussed. Conclusions Accelerated in vitro release testing methods with good discriminatory ability are critical for quality control of extended release parenteral products. Methods that can be used in the development of in vitro-in vivo correlation (IVIVC) are desirable, however for complex parenteral products this may not always be achievable. PMID:22686344

Vulnerabilities to misinformation in online pharmaceutical marketing.

Science.gov (United States)

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

2013-05-01

Given the large percentage of Internet users who search for health information online, pharmaceutical companies have invested significantly in online marketing of their products. Although online pharmaceutical marketing can potentially benefit both physicians and patients, it can also harm these groups by misleading them. Indeed, some pharmaceutical companies have been guilty of undue influence, which has threatened public health and trust. We conducted a review of the available literature on online pharmaceutical marketing, undue influence and the psychology of decision-making, in order to identify factors that contribute to Internet users' vulnerability to online pharmaceutical misinformation. We find five converging factors: Internet dependence, excessive trust in the veracity of online information, unawareness of pharmaceutical company influence, social isolation and detail fixation. As the Internet continues to change, it is important that regulators keep in mind not only misinformation that surrounds new web technologies and their contents, but also the factors that make Internet users vulnerable to misinformation in the first place. Psychological components are a critical, although often neglected, risk factor for Internet users becoming misinformed upon exposure to online pharmaceutical marketing. Awareness of these psychological factors may help Internet users attentively and safely navigate an evolving web terrain.

Pharmaceutical policies in European countries.

Science.gov (United States)

Barros, Pedro Pita

2010-01-01

Pharmaceutical expenditures have an important role in Europe. The attempts to control expenditure have used a wide range of policy measures. We reviewed the main measures adopted by the European Union countries, especially in countries where governments are the largest third-party payers. To complement a literature review on the topic, data was gathered from national reviews of health systems and direct inquiries to several government bodies. Almost all countries regulate prices of pharmaceutical products. Popular policy measures include international referencing to set prices (using as benchmark countries that have set lower prices), internal reference pricing systems to promote price competition in domestic markets, and positive lists for reimbursement to promote consumption of generics (including in some cases substitution by pharmacists of drugs prescribed by physicians). Despite the wide range of policy measures, it is not possible to identify a "silver bullet" to control pharmaceutical expenditures. We also identified two main policy challenges: policy coordination among countries within the European Union to maintain incentives for R&D at the global level, and the development of new relationships with the pharmaceutical industry; namely, the so-called risk-sharing agreements between the pharmaceutical industry and governments/regulators (or large third-party payers).

Combined effects of pharmaceuticals, personal care products, biocides and organic contaminants on the growth of Skeletonema pseudocostatum.

Science.gov (United States)

Petersen, Karina; Heiaas, Harald Hasle; Tollefsen, Knut Erik

2014-05-01

Organisms in the environment are exposed to a number of pollutants from different compound groups. In addition to the classic pollutants like the polychlorinated biphenyls, polyaromatic hydrocarbons (PAHs), alkylphenols, biocides, etc. other compound groups of concern are constantly emerging. Pharmaceuticals and personal care products (PPCPs) can be expected to co-occur with other organic contaminants like biocides, PAHs and alkylphenols in areas affected by wastewater, industrial effluents and intensive recreational activity. In this study, representatives from these four different compound groups were tested individually and in mixtures in a growth inhibition assay with the marine algae Skeletonema pseudocostatum (formerly Skeletonema costatum) to determine whether the combined effects could be predicted by models for additive effects; the concentration addition (CA) and independent action (IA) prediction model. The eleven tested compounds reduced the growth of S. pseudocostatum in the microplate test in a concentration-dependent manner. The order of toxicity of these chemicals were irgarol>fluoxetine>diuron>benzo(a)pyrene>thioguanine>triclosan>propranolol>benzophenone 3>cetrimonium bromide>4-tert-octylphenol>endosulfan. Several binary mixtures and a mixture of eight compounds from the four different compound groups were tested. All tested mixtures were additive as model deviation ratios, the deviation between experimental and predicted effect concentrations, were within a factor of 2 from one or both prediction models (e.g. CA and IA). Interestingly, a concentration dependent shift from IA to CA, potentially due to activation of similar toxicity pathways at higher concentrations, was observed for the mixture of eight compounds. The combined effects of the multi-compound mixture were clearly additive and it should therefore be expected that PPCPs, biocides, PAHs and alkylphenols will collectively contribute to the risk in areas contaminated by such complex

EU pharmaceutical expenditure forecast

OpenAIRE

Urbinati, Duccio; Rémuzat, Cécile; Kornfeld, Åsa; Vataire, Anne-Lise; Cetinsoy, Laurent; Aballéa, Samuel; Mzoughi, Olfa; Toumi, Mondher

2014-01-01

Background and Objectives: 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’ ph...

Nanotechnology tools in pharmaceutical R&D

OpenAIRE

Challa S.S.R. Kumar

2010-01-01

Nanotechnology is a new approach to problem solving and can be considered as a collection of tools and ideas which can be applied in pharmaceutical industry. Application of nanotechnology tools in pharmaceutical R&D is likely to result in moving the industry from ‘blockbuster drug’ model to ‘personalized medicine’. There are compelling applications in pharmaceutical industry where inexpensive nanotechnology tools can be utilized. The review explores the possibility of categorizing various nan...

The effect of chlorine and combined chlorine/UV treatment on coliphages in drinking water disinfection.

Science.gov (United States)

Zyara, Alyaa M; Torvinen, Eila; Veijalainen, Anna-Maria; Heinonen-Tanski, Helvi

2016-08-01

Chlorine disinfection is a globally used method to ensure the safety of drinking water. However, it has not always been successful against viruses and, therefore, it is important to find new methods to disinfect water. Seventeen different coliphages were isolated from the treated municipal wastewater. These coliphages and MS2 were treated with different dosages of chlorine in drinking water, and a combined chlorine/ultraviolet irradiation treatment for the chlorine-resistant coliphages. Chlorine disinfection with 0.3-0.5 mg/L total chlorine (free Cl-dosage 0.12-0.21 mg/L) for 10 min achieved 2.5-5.7 Log10-reductions for 11 sensitive coliphages. The six most resistant coliphages showed no reduction with these chlorine concentrations. MS2 was intermediate in chlorine resistance, and thus it is not a good indicator for viruses in chlorine disinfection. In the combined treatment total chlorine of 0.05-0.25 mg/L (free Cl-dosage 0.02-0.08 mg/L) and ultraviolet irradiation (14-22 mWs/cm(2)) were more effective than chlorine alone, and 3-5 Log10-reductions were achieved for the chlorine-resistant strains. The chlorination efficiency could be increased by higher dosages and longer contact times, but this could increase the formation of disinfection by-products. Therefore, the combination treatment is a recommended disinfection method.

Intrathecal baclofen in multiple sclerosis and spinal cord injury: complications and long-term dosage evolution.

Science.gov (United States)

Draulans, Nathalie; Vermeersch, Kristof; Degraeuwe, Bart; Meurrens, Tom; Peers, Koen; Nuttin, Bart; Kiekens, Carlotte

2013-12-01

To investigate the long-term dosage evolution and complication rate of intrathecal baclofen use in multiple sclerosis and spinal cord injury patients, based on a large population with a long follow-up. Retrospective data analysis. Academic hospital. Patients with multiple sclerosis (n = 81) or spinal cord injury (n = 49) having an intrathecal baclofen pump implanted at the University Hospitals Leuven between 1988 and 2009. Medical records review of included patients in August 2010. Complications linked to intrathecal baclofen therapy. Daily baclofen dosage after 3 and 6 months, and yearly thereafter. Data on dosage evolution were analysed using a mixed-effect linear model. In 130 patients with a mean follow-up of 63 months, comprising 797 pump years, 104 complications were recorded. This corresponds to a complication rate of 0.011 per month, equally divided among both groups. Seventy-eight of these complications were catheter related. The mean dosage of baclofen stabilizes two years after implantation at 323 µg/day in the multiple sclerosis population. In spinal cord injury patients the daily dose only stabilizes after five years at a significantly higher dosage (504 µg/day). No significant increase in dosage is seen in the long term. In multiple sclerosis and spinal cord injury patients, intrathecal baclofen therapy has a complication rate of 1% per month. Complications are mainly due to catheter-related problems (74%). The intrathecal baclofen dosage stabilizes in the long term, indicating that long-term tolerance, defined as progressive diminution of the susceptibility to the effects of a drug, is not present.

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.

Archives: Tropical Journal of Pharmaceutical Research

African Journals Online (AJOL)

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Archives: Nigerian Journal of Pharmaceutical Research

African Journals Online (AJOL)

Items 1 - 9 of 9 ... Archives: Nigerian Journal of Pharmaceutical Research. Journal Home > Archives: Nigerian Journal of Pharmaceutical Research. Log in or Register to get access to full text downloads.

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.

Pharmaceutical care education in Kuwait: pharmacy students’ perspectives

OpenAIRE

Katoue, Maram G.; Awad, Abdelmoneim I.; Schwinghammer, Terry L.; Kombian, Samuel B.

2014-01-01

Background: Pharmaceutical care is defined as the responsible provision of medication therapy to achieve definite outcomes that improve patients’ quality of life. Pharmacy education should equip students with the knowledge, skills, and attitudes they need to practise pharmaceutical care competently. Objective: To investigate pharmacy students’ attitudes towards pharmaceutical care, perceptions of their preparedness to perform pharmaceutical care competencies, opinions about the importance...

Spectrophotometric Determination of Cilostazol in Tablet Dosage Form

African Journals Online (AJOL)

Purpose: To develop simple, rapid and selective spectrophotometric methods for the determination of cilostazol in tablet dosage form. Methods: Cilostazol was dissolved in 50 % methanol and its absorbance was scanned by ultraviolet (UV) spectrophotometry. Both linear regression equation and standard absorptivity were ...

Validated stability-indicating spectrofluorimetric methods for the determination of ebastine in pharmaceutical preparations

Directory of Open Access Journals (Sweden)

Eid Manal

2011-03-01

Full Text Available Abstract Two sensitive, selective, economic, and validated spectrofluorimetric methods were developed for the determination of ebastine (EBS in pharmaceutical preparations depending on reaction with its tertiary amino group. Method I involves condensation of the drug with mixed anhydrides (citric and acetic anhydrides producing a product with intense fluorescence, which was measured at 496 nm after excitation at 388 nm. Method (IIA describes quantitative fluorescence quenching of eosin upon addition of the studied drug where the decrease in the fluorescence intensity was directly proportional to the concentration of ebastine; the fluorescence quenching was measured at 553 nm after excitation at 457 nm. This method was extended to (Method IIB to apply first and second derivative synchronous spectrofluorimetric method (FDSFS & SDSFS for the simultaneous analysis of EBS in presence of its alkaline, acidic, and UV degradation products. The proposed methods were successfully applied for the determination of the studied compound in its dosage forms. The results obtained were in good agreement with those obtained by a comparison method. Both methods were utilized to investigate the kinetics of the degradation of the drug.

Vulnerabilities to misinformation in online pharmaceutical marketing

Science.gov (United States)

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

2013-01-01

Given the large percentage of Internet users who search for health information online, pharmaceutical companies have invested significantly in online marketing of their products. Although online pharmaceutical marketing can potentially benefit both physicians and patients, it can also harm these groups by misleading them. Indeed, some pharmaceutical companies have been guilty of undue influence, which has threatened public health and trust. We conducted a review of the available literature on online pharmaceutical marketing, undue influence and the psychology of decision-making, in order to identify factors that contribute to Internet users’ vulnerability to online pharmaceutical misinformation. We find five converging factors: Internet dependence, excessive trust in the veracity of online information, unawareness of pharmaceutical company influence, social isolation and detail fixation. As the Internet continues to change, it is important that regulators keep in mind not only misinformation that surrounds new web technologies and their contents, but also the factors that make Internet users vulnerable to misinformation in the first place. Psychological components are a critical, although often neglected, risk factor for Internet users becoming misinformed upon exposure to online pharmaceutical marketing. Awareness of these psychological factors may help Internet users attentively and safely navigate an evolving web terrain. PMID:23761527

Stability indicating high performance thin layer chromatographic method for quantitation of venlafaxine in bulk and pharmaceutical dosage form

Directory of Open Access Journals (Sweden)

Sunil K Dubey

2015-01-01

Full Text Available Background: Venlafaxine (VEN is a phenethylamine bicyclic compound, chemically, 1-(2-[dimethyl amino]-1-[4-methoxy phenyl] ethyl cyclo-hexan-1ol hydrochloride. It is a antidepressant. It inhibits the reuptake of serotonin, nor adrenaline and dopamine to a lesser extent at the presynaptic membrane. Aim: A simple, rapid, precise, accurate, and economical high performance thin layer chromatographic (HPTLC method has been developed and validated for the determination of VEN both as a bulk drug and in formulation. Materials and Methods: The method uses aluminum plates precoated with silica gel 60 F254 as the stationary phase and dichloromethane:acetonitrile:N-hexane:triethylamine: 0.5:0.5:4:0.7 (v/v/v/v as mobile phase. Results: This system gave compact spots for VEN (R f = 0.46 ± 0.05. Forced degradation studies were done by subjecting VEN to acid and alkali hydrolysis, oxidation, and reduction. The peak of the degradation product was well resolved from that of the pure drug and had significant different R f values. Analysis of VEN was performed in the absorbance mode at 225 nm. The limit of detection and quantification were 12.48 and 37.81 ng/spot respectively. Conclusions: The developed method was validated and found to be simple, specific, accurate and precise and can be used for routine quality control analysis of VEN in bulk and pharmaceutical formulation.

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.

Fourteen days oral administration of therapeutic dosage of some ...

African Journals Online (AJOL)

Fourteen days oral administration of therapeutic dosage of some antibiotics reduced serum testosterone in male rats. FO Awobajo, Y Raji, II Olatunji-Bello, FT Kunle-Alabi, AO Adesanya, TO Awobajo ...

Optimizing the dosage of stabilizing chemical

OpenAIRE

Harjula, Tomi

2013-01-01

A chemical company provides chemical treatment at customer mill in paper industry. This thesis work was done to determine the optimum dosage of stabilizing chemical. The theoretical framework explains the basics of paper brightness and bleaching and how these topics are connected to each other. The knowledge gained is very valuable and can possibly be used in the future in other similar applications as well. This thesis work contains confidential back ground information. Key ...

Pharmaceutical policy and the pharmacy profession

DEFF Research Database (Denmark)

Traulsen, Janine Marie; Almarsdóttir, Anna Birna

2005-01-01

In this article, the authors look at the relationship between pharmaceutical policy and the pharmacy profession with focus on pharmacy practice and pharmacists in the health care sector. Pharmaceutical policy encompasses three major policy inputs: public health policy, health care policy and indu......In this article, the authors look at the relationship between pharmaceutical policy and the pharmacy profession with focus on pharmacy practice and pharmacists in the health care sector. Pharmaceutical policy encompasses three major policy inputs: public health policy, health care policy...... and industrial policy. In order to analyse and understand pharmaceutical policy, it is important to know how policymakers view pharmacy and pharmacists. The authors look at the issues that arise when policy regulates pharmacy as a business, and what this means for the profession. The perspective of pharmacy...... in managerialism, and how the division of labour with other health professionals such as physicians and pharmacy assistants is affecting the pharmacy profession's position in the labour market. Next the authors look at ways in which the pharmacy profession has affected policy. Pharmacists have been instrumental...

Methotrexate Dosage Reduction Upon Adalimumab Initiation: Clinical and Ultrasonographic Outcomes from the Randomized Noninferiority MUSICA Trial.

Science.gov (United States)

Kaeley, Gurjit S; Evangelisto, Amy M; Nishio, Midori J; Goss, Sandra L; Liu, Shufang; Kalabic, Jasmina; Kupper, Hartmut

2016-08-01

To examine the clinical and ultrasonographic (US) outcomes of reducing methotrexate (MTX) dosage upon initiating adalimumab (ADA) in MTX-inadequate responders with moderately to severely active rheumatoid arthritis (RA). MUSICA (NCT01185288) was a double-blind, randomized, parallel-arm study of 309 patients with RA receiving MTX ≥ 15 mg/week for ≥ 12 weeks before screening. Patients were randomized to high dosage (20 mg/week) or low dosage (7.5 mg/week) MTX; all patients received 40 mg open-label ADA every other week for 24 weeks. The primary endpoint was Week 24 mean 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) to test for noninferiority of low-dosage MTX using a 15% margin. US images were scored using a 10-joint semiquantitative system incorporating OMERACT definitions for pathology, assessing synovial hypertrophy, vascularity, and bony erosions. Rapid improvement in clinical indices was observed in both groups after addition of ADA. The difference in mean DAS28-CRP (0.37, 95% CI 0.07-0.66) comparing low-dosage (4.12, 95% CI 3.88-4.34) versus high-dosage MTX (3.75, 95% CI 3.52-3.97) was statistically significant and non-inferiority was not met. Statistically significant differences were not detected for most clinical, functional, and US outcomes. Pharmacokinetic and safety profiles were similar. In MUSICA, Week 24 mean DAS28-CRP, the primary endpoint, did not meet non-inferiority for the low-dosage MTX group. Although the differences between the 2 MTX dosage groups were small, our study findings did not support routine MTX reduction in MTX inadequate responders initiating ADA.