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Sample records for active pharmaceutical ingredients

  1. Optimised crystal morphologies for active pharmaceutical ingredients and related studies

    Horgan, Danielle E.

    2015-01-01

    The majority of active pharmaceutical ingredients (APIs) are crystalline solids in their pure forms. Crystalline solids have definable morphologies, i.e. shape and size. Crystal morphology is determined by both the internal structure of the crystals and external factors during growth from solution. The morphology of a crystal batch can affect key processes during manufacturing. Companies generally accept whatever morphology the manufacturing process provides and deal with any subsequent probl...

  2. Impurity profile tracking for active pharmaceutical ingredients: case reports.

    Zhou, Lili; Mao, Bing; Reamer, Robert; Novak, Tom; Ge, Zhihong

    2007-06-28

    Tracking the impurity profile of an active pharmaceutical ingredient (API) is a very important task for all stages of drug development. A systematic approach for tracking impurity profile of API is described. Various real pharmaceutical applications are presented through successful examples of impurity profile tracking for three different novel APIs. These include MK-0969, an M3 antagonist; MK-0677, an oral-active growth hormone secretagogue and API-A, a cathepsin K inhibitor. A general strategy including selection of a reversed phase high performance liquid chromatographic (RP-HPLC) impurity profile method based on screening various stationary phases and changing the pH of the mobile phase and elucidation of impurity structures through the utilization of LC-MS, preparative-LC and NMR is demonstrated. A series of studies were conducted on the peak purity check by using the LC-UV diode-array and LC-MS detections. The advantages and disadvantages of each technique in the evaluation of peak purity are discussed. PMID:17142001

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

    Sonali S. Bharate

    2010-12-01

    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 literaturereports of interaction and incompatibilities of commonly used pharmaceutical excipients with different active pharmaceutical ingredients in solid dosage forms. Examples of active drug/excipientinteractions, such as transacylation, the Maillard browning reaction, acid base reactions and physical changes are discussed for different active pharmaceutical ingredients belonging to different therapeuticcategories 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.

  4. Terahertz study on porosity and mass fraction of active pharmaceutical ingredient of pharmaceutical tablets.

    Bawuah, Prince; Tan, Nicholas; Tweneboah, Samuel Nana A; Ervasti, Tuomas; Axel Zeitler, J; Ketolainen, Jarkko; Peiponen, Kai-Erik

    2016-08-01

    In this study, terahertz time-domain spectroscopic (THz-TDS) technique has been used to ascertain the change in the optical properties, as a function of changing porosity and mass fraction of active pharmaceutical ingredient (API), of training sets of pharmaceutical tablets. Four training sets of pharmaceutical tablets were compressed with microcrystalline cellulose (MCC) excipient and indomethacin API by varying either the porosity, height, and API mass fraction or all three tablet parameters. It was observed, as far as we know, for the first time, that the THz time-domain and frequency-domain effective refractive index, as well as, the frequency-domain effective absorption coefficient both show linear correlations with the porosity and API mass fraction for training sets of real pharmaceutical tablets. We suggest that, the observed linear correlations can be useful in basic research and quality inspection of pharmaceutical tablets. Additionally, we propose a novel optical strain parameter, based on THz measurement, which yields information on the conventional strain parameter of a tablet as well as on the change of fill fraction of solid material during compression of porous pharmaceutical tablets. We suggest that the THz measurement and proposed method of data analysis, in addition to providing an efficient tool for basic research of porous media, can serve as one of the novel quality by design (QbD) implementation techniques to predict critical quality attributes (CQA) such as porosity, API mass fraction and strain of flat-faced pharmaceutical tablets before production. PMID:27288937

  5. Crystal solvates of active pharmaceutical ingredients actual for industry of Latvia

    Veldre, Kaspars

    2013-01-01

    Crystal solvates of active pharmaceutical ingredients actual for industry of Latvia ABSTRACT This doctoral thesis project is focused on investigation of active pharmaceutical ingredients (API), which are important for industry of Latvia. Crystal solvate search and screening was performed for compounds described and novel crystalline forms were obtained. Stability in acquisition, production and storage conditions was evaluated. Crystal structure determination was performed for selected A...

  6. Tregitope Peptides: The Active Pharmaceutical Ingredient of IVIG?

    Anne S. De Groot

    2013-01-01

    Full Text Available Five years ago, we reported the identification and characterization of several regulatory T-cell epitopes (now called Tregitopes that were discovered in the heavy and light chains of IgG (De Groot et al. Blood, 2008. When added ex vivo to human PBMCs, these Tregitopes activated regulatory T cells (Tregs, increased expression of the transcription factor FoxP3, and induced IL-10 expression in CD4+ T cells. We have now shown that coadministration of the Tregitopes in vivo, in a number of different murine models of autoimmune disease, can suppress immune responses to antigen in an antigen-specific manner, and that this response is mediated by Tregs. In addition we have shown that, although these are generally promiscuous epitopes, the activity of individual Tregitope peptides is restricted by HLA. In this brief report, we provide an overview of the effects of Tregitopes in vivo, discuss potential applications, and suggest that Tregitopes may represent one of the “active pharmaceutical ingredients” of IVIg. Tregitope applications may include any of the autoimmune diseases that are currently treated almost exclusively with intravenous immunoglobulin G (IVIG, such as Chronic Inflammatory Demyelinating Polyneuropathy (CIDP and Multifocal Motor Neuropathy (MMN, as well as gene therapy and allergy where Tregitopes may provide a means of inducing antigen-specific tolerance.

  7. Kinetics of the esterification of active pharmaceutical ingredients containing carboxylic Acid functionality in polyethylene glycol

    Schou-Pedersen, Anne Marie V; Hansen, Steen Honoré; Moesgaard, Birthe;

    2014-01-01

    reactions. In this study, kinetics of two active pharmaceutical ingredients, cetirizine and indomethacin possessing carboxylic acid functionality, has been studied in PEG 400 and PEG 1000 at 50°C, 60°C, 70°C, and 80°C. HPLC-UV was applied for the determination of concentrations in the kinetic studies...

  8. Oxidation of Mixed Active Pharmaceutical Ingredients in Biologically Treated Wastewater by ClO2

    Moradas, Gerly; Fick, Jerker; Ledin, Anna;

    2011-01-01

    Biologically treated wastewater containing a mixture of 53 active pharmaceutical ingredients (APIs)was treated with 0-20 mg/l chlorine dioxide (ClO2) solution. Wastewater effluents were taken from two wastewater treatment plants in Sweden, one with (low COD) and one without (high COD) extended...

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

    Bharate, Sonali S.; Bharate, Sandip B.; Bajaj, Amrita N.

    2010-01-01

    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 literaturereports of interaction and incompatibilities of commonly used pharmaceutical excipients with different...

  10. Determination of nickel in active pharmaceutical ingredients by electrothermal atomic absorption spectrometry.

    Bubnič, Zoran; Urleb, Uroš; Kreft, Katjuša; Veber, Marjan

    2010-03-01

    An electrothermal atomic absorption spectrometric procedure for the determination of nickel in active pharmaceutical ingredients was developed. Since the recoveries of nickel by the direct dissolution of samples in diluted nitric acid were low and caused errors in the determination of Ni in pharmaceutical samples, different approaches for sample pre-treatment were examined. It was found that the microwave digestion was the most suitable way for sample preparation. Various combinations of digestion agents and different microwave conditions were tested. The combination of nitric acid and hydrogen peroxide was found to be the most appropriate. The validity of the method was evaluated by recovery studies of spiked samples and by the comparison of the results obtained by inductively coupled plasma mass spectrometry (ICP-MS). The recovery ranged from 87.5 to 104.0% and a good agreement was achieved between both methods. The detection limit and the limit of quantification were 0.6 and 2.1 µg g-1 respectively. The precision of the method was confirmed by the determination of Ni in the spiked samples and was below 4%, expressed in terms of a relative standard deviation. The method was applied to the determination of nickel in production samples of active pharmaceutical ingredients and intermediates. PMID:24061653

  11. Integration of active pharmaceutical ingredient solid form selection and particle engineering into drug product design.

    Ticehurst, Martyn David; Marziano, Ivan

    2015-06-01

    This review seeks to offer a broad perspective that encompasses an understanding of the drug product attributes affected by active pharmaceutical ingredient (API) physical properties, their link to solid form selection and the role of particle engineering. While the crucial role of active pharmaceutical ingredient (API) solid form selection is universally acknowledged in the pharmaceutical industry, the value of increasing effort to understanding the link between solid form, API physical properties and drug product formulation and manufacture is now also being recognised. A truly holistic strategy for drug product development should focus on connecting solid form selection, particle engineering and formulation design to both exploit opportunities to access simpler manufacturing operations and prevent failures. Modelling and predictive tools that assist in establishing these links early in product development are discussed. In addition, the potential for differences between the ingoing API physical properties and those in the final product caused by drug product processing is considered. The focus of this review is on oral solid dosage forms and dry powder inhaler products for lung delivery. PMID:25677227

  12. Oxidation of Mixed Active Pharmaceutical Ingredients in Biologically Treated Wastewater by ClO2

    Moradas, Gerly; Fick, Jerker; Ledin, Anna; Jansen, Jes la Cour; Andersen, Henrik Rasmus

    2011-01-01

    Biologically treated wastewater containing a mixture of 53 active pharmaceutical ingredients (APIs)was treated with 0-20 mg/l chlorine dioxide (ClO2) solution. Wastewater effluents were taken from two wastewater treatment plants in Sweden, one with (low COD) and one without (high COD) extended nitrogen removal. The removal of the APIs varied from no significant removal at the highest dose of ClO2 (20 mg/l) to 90% removal at a dose of 0.5 mg/l of the oxidant. From the low COD effluent, only 4 ...

  13. Isolation and characterization of process related impurities in anastrozole active pharmaceutical ingredient

    Hiriyanna, S. G.; Basavaiah, K. [University of Mysore, Manasagangothri, Mysore (India). Dept. of Chemistry]. E-mail: hiriyannag@gmail.com

    2008-07-01

    Three impurities ranging from 0.08%-0.12% by peak area in anastrozole active pharmaceutical ingredient were detected by simple isocratic reverse-phase high performance liquid chromatography (HPLC). These impurities were isolated by prep-HPLC and were characterized by LC- MS/MS, GCMS and NMR experimental data. Based on the results obtained from different spectroscopic experiments, these impurities have been characterized as 2,2'-(5-((4H-1,2,4-triazol-4-yl)methyl)-1,3-phenylene)bis(2-methyl propanenitrile) (Impurity I), 2,2'-(5-methyl-1,3-phenylene)bis(2-methylpropanenitrile) (Impurity II) and 2,2'-(5-(bromomethyl)-1,3-phenylene)bis(2-methylpropanenitrile) (Impurity III). (author)

  14. Application of instrumented nanoindentation in preformulation studies of pharmaceutical active ingredients and excipients.

    Egart, Mateja; Janković, Biljana; Srčič, Stane

    2016-09-01

    Nanoindentation allows quantitative determination of a material's response to stress such as elastic and plastic deformation or fracture tendency. Key instruments that have enabled great advances in nanomechanical studies are the instrumented nanoindenter and atomic force microscopy. The versatility of these instruments lies in their capability to measure local mechanical response, in very small volumes and depths, while monitoring time, displacement and force with high accuracy and precision. This review highlights the application of nanoindentation for mechanical characterization of pharmaceutical materials in the preformulation phase (primary investigation of crystalline active ingredients and excipients). With nanoindentation, mechanical response can be assessed with respect to crystal structure. The technique is valuable for mechanical screening of a material at an early development phase in order to predict and better control the processes in which a material is exposed to stress such as milling and compression. PMID:27383883

  15. Active pharmaceutical ingredient (API) production involving continuous processes – A process system engineering (PSE)-assisted design framework

    Cervera Padrell, Albert Emili; Skovby, Tommy; Kiil, Søren;

    2012-01-01

    A systematic framework is proposed for the design of continuous pharmaceutical manufacturing processes. Specifically, the design framework focuses on organic chemistry based, active pharmaceutical ingredient (API) synthetic processes, but could potentially be extended to biocatalytic and fermenta......A systematic framework is proposed for the design of continuous pharmaceutical manufacturing processes. Specifically, the design framework focuses on organic chemistry based, active pharmaceutical ingredient (API) synthetic processes, but could potentially be extended to biocatalytic and...... for the selection of batch and continuous processes so that the whole design results in low capital and operational costs as well as low environmental footprint. The design framework has been applied to the retrofit of an existing batch-wise process used by H. Lundbeck A/S to produce an API...... exchange steps, and thus constitutes a good example of how the design framework can be useful to efficiently design novel or already existing API manufacturing processes taking advantage of continuous processes....

  16. Direct analysis of palladium in active pharmaceutical ingredients by anodic stripping voltammetry.

    Rosolina, Samuel M; Chambers, James Q; Xue, Zi-Ling

    2016-03-31

    Anodic stripping voltammetry, a classical electroanalytical method has been optimized to analyze trace Pd(II) in active pharmaceutical ingredient matrices. The electroanalytical approach with an unmodified glassy carbon electrode was performed in both aqueous and 95% DMSO/5% water (95/5 DMSO/H2O) solutions, without pretreatment such as acid digestion or dry ashing to remove the organics. Limits of detection (LODs) in the presence of caffeine and ketoprofen were determined to be 11 and 9.6 μg g(-1), with a relative standard deviation (RSD) of 5.7% and 2.3%, respectively. This method is simple, highly reproducible, sensitive, and robust. The instrumentation has the potential to be portable and the obviation of sample pretreatment makes it an ideal approach for determining lost catalytic metals in pharmaceutical-related industries. Furthermore, the simultaneous detection of Pd(II) with Cd(II) and Pb(II) in the low μg L(-1) range indicates that this system is capable of simultaneous multi-analyte analysis in a variety of matrices. PMID:26965326

  17. Core-Shell Composite Hydrogels for Controlled Nanocrystal Formation and Release of Hydrophobic Active Pharmaceutical Ingredients.

    Badruddoza, Abu Zayed Md; Godfrin, P Douglas; Myerson, Allan S; Trout, Bernhardt L; Doyle, Patrick S

    2016-08-01

    Although roughly 40% of pharmaceuticals being developed are poorly water soluble, this class of drugs lacks a formulation strategy capable of producing high loads, fast dissolution kinetics, and low energy input. In this work, a novel bottom-up approach is developed for producing and formulating nanocrystals of poorly water-soluble active pharmaceutical ingredients (APIs) using core-shell composite hydrogel beads. Organic phase nanoemulsion droplets stabilized by polyvinyl alcohol (PVA) and containing a model hydrophobic API (fenofibrate) are embedded in the alginate hydrogel matrix and subsequently act as crystallization reactors. Controlled evaporation of this composite material produces core-shell structured alginate-PVA hydrogels with drug nanocrystals (500-650 nm) embedded within the core. Adjustable loading of API nanocrystals up to 83% by weight is achieved with dissolution (of 80% of the drug) occurring in as little as 30 min. A quantitative model is also developed and experimentally validated that the drug release patterns of the fenofibrate nanocrystals can be modulated by controlling the thickness of the PVA shell and drug loading. Thus, these composite materials offer a "designer" drug delivery system. Overall, our approach enables a novel means of simultaneous controlled crystallization and formulation of hydrophobic drugs that circumvents energy intensive top-down processes in traditional manufacturing. PMID:27249402

  18. Estimation of active pharmaceutical ingredients content using locally weighted partial least squares and statistical wavelength selection.

    Kim, Sanghong; Kano, Manabu; Nakagawa, Hiroshi; Hasebe, Shinji

    2011-12-15

    Development of quality estimation models using near infrared spectroscopy (NIRS) and multivariate analysis has been accelerated as a process analytical technology (PAT) tool in the pharmaceutical industry. Although linear regression methods such as partial least squares (PLS) are widely used, they cannot always achieve high estimation accuracy because physical and chemical properties of a measuring object have a complex effect on NIR spectra. In this research, locally weighted PLS (LW-PLS) which utilizes a newly defined similarity between samples is proposed to estimate active pharmaceutical ingredient (API) content in granules for tableting. In addition, a statistical wavelength selection method which quantifies the effect of API content and other factors on NIR spectra is proposed. LW-PLS and the proposed wavelength selection method were applied to real process data provided by Daiichi Sankyo Co., Ltd., and the estimation accuracy was improved by 38.6% in root mean square error of prediction (RMSEP) compared to the conventional PLS using wavelengths selected on the basis of variable importance on the projection (VIP). The results clearly show that the proposed calibration modeling technique is useful for API content estimation and is superior to the conventional one. PMID:22001843

  19. Quantitative determination of residual active pharmaceutical ingredients and intermediates on equipment surfaces by ion mobility spectrometry.

    Qin, C; Granger, A; Papov, V; McCaffrey, J; Norwood, D L

    2010-01-01

    Ion mobility spectrometry (IMS) is an analytical technique that separates ions based on their gas phase mobility at atmospheric pressure. Since gas phase ion mobility is a function of the shape and structure of the ion, this technique has the potential to provide unique specificity and selectivity. Furthermore, IMS is very sensitive (subnanogram detection limits for many small molecules), and a single analysis is typically completed within 1 min. In principle, these features of IMS should make it an ideal choice for use in cleaning verification analysis of pharmaceutical manufacturing equipment. This report describes the successful development and validation of three different equipment cleaning verification methods using IMS. The methods were developed for a specific intermediate (Compound A) in the synthetic route for a drug substance as well as for final drug substances (active pharmaceutical ingredients Compounds B and C). The cleaning verification methods were validated with respect to specificity, linearity, precision, accuracy, stability, and limit-of-quantitation. In all cases, the limits-of-quantitation were determined to be at the nanogram or sub-nanogram level. Both swab and rinse samples collected from the equipment surfaces were successfully analyzed and manufacturing equipment down-time was significantly minimized due to the reduction in cleaning verification analysis time (for example, the total analysis time for more than 30 samples using IMS was reduced to less than 2h). PMID:19758781

  20. Consequences of New Approach to Chemical Stability Tests to Active Pharmaceutical Ingredients.

    Jamrógiewicz, Marzena

    2016-01-01

    There is a great need of broaden look on stability tests of active pharmaceutical ingredients (APIs) in comparison with current requirements contained in pharmacopeia. By usage of many modern analytical methods the conception of monitoring the changes of APIs during initial stage of their exposure to harmful factors has been developed. New knowledge must be acquired in terms of identification of each degradation products, especially volatile ones. Further research as toxicology prediction during in silico studies of determined and identified degradation products is necessary. In silico methods are known as computational toxicology or computer-assisted technologies which are used for predicting toxicology of pharmaceutical substances such as impurities or degradation products. This is a specialized software and databases intended to calculate probability of genotoxicity or mutagenicity of these substances through a chemical structure-based screening process and algorithm specific to a given software program. Applying of new analytical approach is proposed as the usage of PAT tools, XRD, HS-SPME GC-MS/MS, LC-MS/MS for stability testing. Described improvements should be taken into account in case of each drug existing already in the market as well as being implemented as new one. PMID:26955356

  1. Dissolution enhancement of active pharmaceutical ingredients by therapeutic deep eutectic systems.

    Aroso, Ivo M; Silva, João C; Mano, Francisca; Ferreira, Ana S D; Dionísio, Madalena; Sá-Nogueira, Isabel; Barreiros, Susana; Reis, Rui L; Paiva, Alexandre; Duarte, Ana Rita C

    2016-01-01

    A therapeutic deep eutectic system (THEDES) is here defined as a deep eutectic solvent (DES) having an active pharmaceutical ingredient (API) as one of the components. In this work, THEDESs are proposed as enhanced transporters and delivery vehicles for bioactive molecules. THEDESs based on choline chloride (ChCl) or menthol conjugated with three different APIs, namely acetylsalicylic acid (AA), benzoic acid (BA) and phenylacetic acid (PA), were synthesized and characterized for thermal behaviour, structural features, dissolution rate and antibacterial activity. Differential scanning calorimetry and polarized optical microscopy showed that ChCl:PA (1:1), ChCl:AA (1:1), menthol:AA (3:1), menthol:BA (3:1), menthol:PA (2:1) and menthol:PA (3:1) were liquid at room temperature. Dissolution studies in PBS led to increased dissolution rates for the APIs when in the form of THEDES, compared to the API alone. The increase in dissolution rate was particularly noticeable for menthol-based THEDES. Antibacterial activity was assessed using both Gram-positive and Gram-negative model organisms. The results show that all the THEDESs retain the antibacterial activity of the API. Overall, our results highlight the great potential of THEDES as dissolution enhancers in the development of novel and more effective drug delivery systems. PMID:26586342

  2. Microwave-assisted digestion using nitric acid for heavy metals and sulfated ash testing in active pharmaceutical ingredients.

    Pluhácek, T; Hanzal, J; Hendrych, J; Milde, D

    2016-04-01

    The monitoring of inorganic impurities in active pharmaceutical ingredients plays a crucial role in the quality control of the pharmaceutical production. The heavy metals and residue on ignition/sulfated ash methods employing microwave-assisted digestion with concentrated nitric acid have been demonstrated as alternatives to inappropriate compendial methods recommended in United States Pharmacopoeia (USP) and European Pharmacopoeia (Ph. Eur.). The recoveries using the heavy metals method ranged between 89% and 122% for nearly all USP and Ph. Eur. restricted elements as well as the recoveries of sodium sulfate spikes were around 100% in all tested matrices. The proposed microwave-assisted digestion method allowed simultaneous decomposition of 15 different active pharmaceutical ingredients with sample weigh up to 1 g. The heavy metals and sulfated ash procedures were successfully applied to the determination of heavy metals and residue on ignition/sulfated ash content in mycophenolate mofetil, nicergoline and silymarin. PMID:27209695

  3. Development of a solvate as an active pharmaceutical ingredient: Developability, crystallisation and isolation challenges

    Douillet, Julien; Stevenson, Neil; Lee, Mei; Mallet, Franck; Ward, Richard; Aspin, Peter; Dennehy, Daniel Robert; Camus, Laure

    2012-03-01

    The preclinical development of an active pharmaceutical ingredient (API) begins with the selection of a solid state form. A solvate may be selected for development if it is sufficiently stable and if the solvent quantity administered to the patient is lower than the tolerated potential daily exposure (PDE). The selection and process development of a solvate is presented here. The initial crystallisation process gave poor control over the particle size distribution (PSD) and inclusion of additional crystallisation solvent in the crystal lattice. These two API attributes were controlled using micronised seeds and optimising the crystallisation conditions. After filtration, slurry washing with a second solvent was used to replace the high boiling point crystallisation solvent to improve the drying efficiency. The slurry washing was modelled and studied in the laboratory to control the level of unbound crystallisation solvent in the API. The API desolvation during slurry washing was studied by considering thermodynamics, by construction of the ternary phase diagram, and kinetics aspects. This work provides useful approaches and considerations to assess the risks specific to the controlled production of a solvate that are rarely presented in the literature.

  4. Co-crystallization: An approach to improve the performance characteristics of active pharmaceutical ingredients

    Jignasa Ketan Savjani

    2015-01-01

    Full Text Available Co-crystal chemistry has recently attracted supramolecular scientists. Co-crystals are comprising of hydrogen boding assembly between different molecules. Many issues related to performance characteristics of an active pharmaceutical ingredient (API can be resolved using co-crystallization approach. Proper understanding of crystal structure of an API is required for successful formation of co-crystals with the selected co-former. This review article focus on explanation about co-crystals, intellectual property rights, their advantages and limitations. Co-crystallization can be achieved using different methods like co-grinding slurry based, solvent evaporation method, etc. Methods of co-crystallization are simple and increase the purity of the final product. Co-crystallization can be applied to the drugs prescribed in combination therapy. Stoichiometric composition of different drugs used in combination therapy can be co-crystallize to form one solid state form. Physicochemical properties of APIs such as solubility and stability can be improved using co-crystallization approach. With due regards co-crystallization should be used with caution because of some issues during manufacturing of final product.

  5. Adsorption chromatography to purify Spacer disaccharide of Active Pharmaceutical Ingredient of QuimiHib vaccine

    In this paper we study the conditions of adsorption chromatography on Silica gel 60 for purification of Spacer disaccharide a component of Active Pharmaceutical Ingredient (API) of QuimiHib vaccine. For that, we made a scale down on an analytical scale that represented at 1.8% of industrial process, indicating reproducibility between two procedures in terms of packing efficiency, purity and recovery. Dynamic binding capacity of the resin Silicagel 60 by the DSE was roughly 125±0.2 mg /mL, 3.4 times the base process. The elution profile obtained, showed the possibility of collecting a unique fraction at range 195±2 and 260±2 minutes, if it is maintained a proper packing of the chromatography resin determined by asymmetry factor from 0.8 to 1.2, which ensures a recovery of 58.9±4.5% and high purity analyzed by Thin Layer Chromatography. Adjusting the adsorption conditions increases the productivity of chromatographic operation up to 3.5 fold, indicating that it is feasible in economic terms

  6. Role of herbal bioactives as a potential bioavailability enhancer for Active Pharmaceutical Ingredients.

    Ajazuddin; Alexander, Amit; Qureshi, Azra; Kumari, Leena; Vaishnav, Pramudita; Sharma, Mukesh; Saraf, Swarnlata; Saraf, Shailendra

    2014-09-01

    The current review emphasizes on the herbal bioenhancers which themselves do not possess inherent pharmacological activity of their own but when co-administered with Active Pharmaceutical Ingredients (API), enhances their bioavailability and efficacy. Herbal bioenhancers play a crucial role in enhancing the bioavailability and bioefficacy of different classes of drugs, such as antihypertensives, anticancer, antiviral, antitubercular and antifungal drugs at low doses. This paper highlights various natural compounds that can be utilized as an efficient bioenhancer. Several herbal compounds including piperine, quercetin, genistein, naringin, sinomenine, curcumin, and glycyrrhizin have demonstrated capability to improve the pharmacokinetic parameters of several potent API. This article also focuses on various United States patents on herbal bioenhancers, which has proved to be beneficial in improving oral absorption of nutraceuticals like vitamins, minerals, amino acids and certain herbal compounds. The present paper also describes proposed mechanism of action, which mainly includes absorption process, drug metabolism, and action on drug target. The herbal bioenhancers are easily available, safe, free from side effects, minimizes drug toxicity, shortens the duration of treatment, lowers the drug resistance problems and minimizes the cost of treatment. Inspite of the fact that herbal bioenhancers provide an innovative concept for enhancing the bioavailability of several potent drugs, there are numerous bioenhancers of herbal origin that are yet to be explored in several vital areas. These bioenhancers must also be implied to enhance the bioavailability and bioefficacy through routes other than the oral route of drug delivery. There is a vast array of unexploited plants which can be investigated for their drug bioenhancing potency. The toxicity profiles of these herbal bioenhancers must not be overlooked. Researches must be carried out to solve these issues and to

  7. Continuous Hydrolysis and Liquid–Liquid Phase Separation of an Active Pharmaceutical Ingredient Intermediate Using a Miniscale Hydrophobic Membrane Separator

    Cervera Padrell, Albert Emili; Morthensen, Sofie Thage; Lewandowski, Daniel Jacob; Skovby, Tommy; Kiil, Søren; Gernaey, Krist V

    2012-01-01

    Continuous hydrolysis of an active pharmaceutical ingredient intermediate, and subsequent liquid–liquid (L-L) separation of the resulting organic and aqueous phases, have been achieved using a simple PTFE tube reactor connected to a miniscale hydrophobic membrane separator. An alkoxide product, obtained in continuous mode by a Grignard reaction in THF, reacted with acidic water to produce partially miscible organic and aqueous phases containing Mg salts. Despite the partial THF–water miscibil...

  8. Active pharmaceutical ingredients detected in herbal food supplements for weight loss samples on the Dutch market

    Reeuwijk, N.M.; Venhuis, B.J.; Kaste, de D.; Hoogenboom, L.A.P.; Rietjens, I.; Martena, M.J.

    2014-01-01

    Herbal food supplements claiming to reduce weight may contain active pharmacological ingredients (APIs) that can be used for the treatment of overweight and obesity. The aim of this study was to determine whether herbal food supplements for weight loss on the Dutch market contain APIs with weight lo

  9. Active pharmaceutical ingredients for antiretroviral treatment in low- and middle-income countries: a survey.

    Fortunak, Joseph M; de Souza, Rodrigo O M A; Kulkarni, Amol A; King, Christopher L; Ellison, Tiffany; Miranda, Leandro S M

    2014-01-01

    Active pharmaceutical ingredients (APIs) are the molecular entities that exert the therapeutic effects of medicines. This article provides an overview of the major APIs that are entered into antiretroviral therapy (ART), outlines how APIs are manufactured, and examines the regulatory and cost frameworks of manufacturing ART APIs used in low- and middle-income countries (LMICs). Almost all APIs for ART are prepared by chemical synthesis. Roughly 15 APIs account for essentially all of the ARTs used in LMICs. Nearly all of the ART APIs purchased through the Global Fund for AIDS, TB and Malaria (GFATM) or the United States President's Emergency Plan for AIDS Relief (PEPFAR) are produced by generic companies. API costs are very important because they are the largest contribution to the overall cost of ART. Efficient API production requires substantial investment in chemical manufacturing technologies and the ready availability of raw materials and energy at competitive prices. Generic API production is practiced in only a limited number of countries; the API market for ART is dominated by Indian companies. The quality of these APIs is ensured by manufacturing under good manufacturing practice (GMP), including process validation, testing against previously established specifications and the demonstration of clinical bioequivalence. The investment and personnel costs of a quality management system for GMP contribute significantly to the cost of API production. Chinese companies are the major suppliers for many advanced intermediates in API production. Improved chemistry of manufacturing, economies of scale and optimization of procurement have enabled drastic cost reductions for many ART APIs. The available capacity for global production of quality-assured APIs is likely adequate to meet forecasted demand for 2015. The increased use of ART for paediatric treatment, for second-line and salvage therapy, and the introduction of new APIs and combinations are important factors

  10. Determination of platinum group metal catalyst residues in active pharmaceutical ingredients by means of total reflection X-ray spectrometry

    Marguí, Eva; Queralt, Ignasi; Hidalgo, Manuela

    2013-08-01

    The control of metal catalyst residues (i.e., platinum group metals (PGMs)) in different stages of the manufacturing processes of the active pharmaceutical ingredients (APIs) and, especially, in the final product is crucial. For API specimens, there are strict guidelines to limit the levels of metal residues based on their individual levels of safety concern. For PGMs the concentration limit has been established at 10 mg/kg in the API. Therefore great effort is currently being devoted to the development of new and simple procedures to control metals in pharmaceuticals. In the present work, an analytical methodology based on benchtop total reflection X-ray fluorescence spectrometry (TXRF) has been developed for the rapid and simple determination of some PGM catalyst impurities (Rh, Pd, Ir and Pt) in different types of API samples. An evaluation of different sample treatments (dissolution and digestion of the solid pharmaceutical samples) has been carried out and the developed methodologies have been validated according to the analytical parameters to be considered and acceptance criteria for PGM determination according to the United States Pharmacopeia (USP). Limits of quantification obtained for PGM metals were in the range of 2-4 mg/kg which are satisfactory according to current legislation. From the obtained results it is shown that the developed TXRF method can be implemented in the pharmaceutical industries to increase productivity of the laboratory; offering an interesting and complementary analytical tool to other atomic spectroscopic methods.

  11. Characterizing Active Pharmaceutical Ingredient Binding to Human Serum Albumin by Spin-Labeling and EPR Spectroscopy.

    Hauenschild, Till; Reichenwallner, Jörg; Enkelmann, Volker; Hinderberger, Dariush

    2016-08-26

    Drug binding to human serum albumin (HSA) has been characterized by a spin-labeling and continuous-wave (CW) EPR spectroscopic approach. Specifically, the contribution of functional groups (FGs) in a compound on its albumin-binding capabilities is quantitatively described. Molecules from different drug classes are labeled with EPR-active nitroxide radicals (spin-labeled pharmaceuticals (SLPs)) and in a screening approach CW-EPR spectroscopy is used to investigate HSA binding under physiological conditions and at varying ratios of SLP to protein. Spectral simulations of the CW-EPR spectra allow extraction of association constants (KA ) and the maximum number (n) of binding sites per protein. By comparison of data from 23 SLPs, the mechanisms of drug-protein association and the impact of chemical modifications at individual positions on drug uptake can be rationalized. Furthermore, new drug modifications with predictable protein binding tendency may be envisaged. PMID:27460503

  12. Direct detection and identification of active pharmaceutical ingredients in intact tablets by helium plasma ionization (HePI) mass spectrometry

    Athula B. Attygalle; Freneil B. Jariwala; Julius Pavlov; Zhihua Yang; Jason A. Mahr; Mabel Oviedo

    2014-01-01

    A simple modification converts an electrospray ion source to an ambient-pressure helium plasma ionization source without the need of additional expensive hardware. Peaks for active ingredients were observed in the spectra recorded from intact pharmaceutical tablets placed in this source. A flow of heated nitrogen was used to thermally desorb analytes to gas phase. The desorption temperatures were sometimes as low as 50 1C. For example, negative-ion spectra recorded from an aspirin tablet showed peaks at m/z 137 (salicylate anion) and 179 (acetylsalicylate anion) which were absent in the background spectra. The overall ion intensity increased as the desorption gas temperature was elevated. Within the same acquisition experiment, both positive- and negative-ion signals for acetaminophen were recorded from volatiles emanating from Tylenol tablets by switching the polarity of the capillary back and forth. Moreover, different preparations of acetaminophen tablets could be distinguished by their ion-intensity thermograms.

  13. An Introduction to the Prequalification of Active Pharmaceutical Ingredients%WHO原料药预认证项目简介

    杜雯君; 梁毅

    2012-01-01

    Search the WHO website for guidanc e and technical documents for Prequalification of Active Pharmaceutical Ingredients,and translate and compile the program.Conclusion:Learn the relevant regulations of international organization and requirements of technology in depth,to form the system of drug management which meets the international standards,only in this way can we enter the international market as soon as possible.%检索WHO药品预认证项目技术指南,翻译并整理原料药预认证项目的工作程序。结论:只有深入学习国际组织相关法规和技术要求、建立符合国际标准的监管体系,才能有效推进我国制药产品早日进入国际市场。

  14. Optimization of HS-GC-FID-MS Method for Residual Solvent Profiling in Active Pharmaceutical Ingredients Using DoE.

    Poceva Panovska, Ana; Acevska, Jelena; Stefkov, Gjoshe; Brezovska, Katerina; Petkovska, Rumenka; Dimitrovska, Aneta

    2016-02-01

    Within this research, a headspace (HS) gas chromatography-flame ionization detector-mass spectrometry method was developed for profiling of residual solvents (RSs) in active pharmaceutical ingredients (APIs). Design of experiment was used for optimization of sample preparation, as well as for robustness testing of the method. HS equilibration temperature and dilution medium were detected as parameters with greater impact on the sensitivity, compared with the time used for equilibration of the samples. Regardless of the sample solubility, the use of water for sample preparation was found to be crucial for better sensitivity. The use of a well-designed strategy for method development and robustness testing, additional level of identification confidence, as well as use of internal standard provided a strong and reliable analytical tool for API fingerprinting, thus enabling the authentication of the substance based on the RS profile. PMID:26290585

  15. Determination of platinum group metal catalyst residues in active pharmaceutical ingredients by means of total reflection X-ray spectrometry

    Marguí, Eva, E-mail: eva.margui@udg.edu [Department of Chemistry, University of Girona, Campus Montilivi, 17071 Girona (Spain); Queralt, Ignasi, E-mail: iqueralt@ictja.csic.es [Laboratory of X-ray Analytical Applications, Institute of Earth Sciences “Jaume Almera”, CSIC, Solé Sabarís s/n, 08028 Barcelona (Spain); Hidalgo, Manuela, E-mail: manuela.hidalgo@udg.edu [Department of Chemistry, University of Girona, Campus Montilivi, 17071 Girona (Spain)

    2013-08-01

    The control of metal catalyst residues (i.e., platinum group metals (PGMs)) in different stages of the manufacturing processes of the active pharmaceutical ingredients (APIs) and, especially, in the final product is crucial. For API specimens, there are strict guidelines to limit the levels of metal residues based on their individual levels of safety concern. For PGMs the concentration limit has been established at 10 mg/kg in the API. Therefore great effort is currently being devoted to the development of new and simple procedures to control metals in pharmaceuticals. In the present work, an analytical methodology based on benchtop total reflection X-ray fluorescence spectrometry (TXRF) has been developed for the rapid and simple determination of some PGM catalyst impurities (Rh, Pd, Ir and Pt) in different types of API samples. An evaluation of different sample treatments (dissolution and digestion of the solid pharmaceutical samples) has been carried out and the developed methodologies have been validated according to the analytical parameters to be considered and acceptance criteria for PGM determination according to the United States Pharmacopeia (USP). Limits of quantification obtained for PGM metals were in the range of 2–4 mg/kg which are satisfactory according to current legislation. From the obtained results it is shown that the developed TXRF method can be implemented in the pharmaceutical industries to increase productivity of the laboratory; offering an interesting and complementary analytical tool to other atomic spectroscopic methods. - Highlights: • A TXRF method for PGM catalyst residue determination in API samples is presented. • Analysis can be performed using 10 μL of the internal standardized dissolved API. • The method is rapid, simple and suitable according to the USP requirements.

  16. Determination of platinum group metal catalyst residues in active pharmaceutical ingredients by means of total reflection X-ray spectrometry

    The control of metal catalyst residues (i.e., platinum group metals (PGMs)) in different stages of the manufacturing processes of the active pharmaceutical ingredients (APIs) and, especially, in the final product is crucial. For API specimens, there are strict guidelines to limit the levels of metal residues based on their individual levels of safety concern. For PGMs the concentration limit has been established at 10 mg/kg in the API. Therefore great effort is currently being devoted to the development of new and simple procedures to control metals in pharmaceuticals. In the present work, an analytical methodology based on benchtop total reflection X-ray fluorescence spectrometry (TXRF) has been developed for the rapid and simple determination of some PGM catalyst impurities (Rh, Pd, Ir and Pt) in different types of API samples. An evaluation of different sample treatments (dissolution and digestion of the solid pharmaceutical samples) has been carried out and the developed methodologies have been validated according to the analytical parameters to be considered and acceptance criteria for PGM determination according to the United States Pharmacopeia (USP). Limits of quantification obtained for PGM metals were in the range of 2–4 mg/kg which are satisfactory according to current legislation. From the obtained results it is shown that the developed TXRF method can be implemented in the pharmaceutical industries to increase productivity of the laboratory; offering an interesting and complementary analytical tool to other atomic spectroscopic methods. - Highlights: • A TXRF method for PGM catalyst residue determination in API samples is presented. • Analysis can be performed using 10 μL of the internal standardized dissolved API. • The method is rapid, simple and suitable according to the USP requirements

  17. Supramolecular hydrogen-bonding patterns of co-crystals containing the active pharmaceutical ingredient (API) phloroglucinol and N-heterocycles.

    Cvetkovski, Aleksandar; Bertolasi, Valerio; Ferretti, Valeria

    2016-06-01

    The active pharmaceutical ingredient phloroglucinol (PHL) has been taken as an illustrative molecule to explore the intermolecular interactions which can be established with other molecular entities to build PHL pharmaceutical co-crystals. The crystal structures of five newly synthesized co-crystals are reported, where PHL is crystallized with N-heterocycles, namely 2-hydroxy-6-methylpyridine (1), 2,4-dimethyl-6-hydroxypyrimidine (2), 4-phenylpyridine (3), 2-hydroxypyridine (4) and 2,3,5,6-tetramethylpyrazine (5). The structural characteristics of these co-crystals, as far as the hydrogen-bonding networks and the crystalline architectures are concerned, are strongly dependent on the chemical features of the coformer molecules, as well as on their size and shape. A detailed analysis of the intermolecular interactions established in all the PHL co-crystals of known structures has allowed the recognition of some regularities in the packing modes that can be useful in the design of new supramolecular adducts forming predictable structural motifs. PMID:27240764

  18. Direct Determination of ECD in ECD Kit: A Solid Sample Quantitation Method for Active Pharmaceutical Ingredient in Drug Product

    Ming-Yu Chao

    2011-01-01

    Full Text Available Technetium-99m ethyl cysteinate dimer (Tc-99m-ECD is an essential imaging agent used in evaluating the regional cerebral blood flow in patients with cerebrovascular diseases. Determination of active pharmaceutical ingredient, that is, L-Cysteine, N, N′-1,2-ethanediylbis-, diethyl ester, dihydrochloride (ECD in ECD Kit is a relevant requirement for the pharmaceutical quality control in processes of mass fabrication. We here presented a direct solid sample determination method of ECD in ECD Kit without sample dissolution to avoid the rapid degradation of ECD. An elemental analyzer equipped with a nondispersive infrared detector and a calibration curve of coal standard was used for the quantitation of sulfur in ECD Kit. No significant matrix effect was found. The peak area of coal standard against the amount of sulfur was linear over the range of 0.03–0.10 mg, with a correlation coefficient ( of 0.9993. Method validation parameters were achieved to demonstrate the potential of this method.

  19. A Tape Method for Fast Characterization and Identification of Active Pharmaceutical Ingredients in the 2-18 THz Spectral Range

    Kissi, Eric Ofosu; Bawuah, Prince; Silfsten, Pertti; Peiponen, Kai-Erik

    2015-03-01

    In order to find counterfeit drugs quickly and reliably, we have developed `tape method' a transmission spectroscopic terahertz (THz) measurement technique and compared it with a standard attenuated total reflection (ATR) THz spectroscopic measurement. We used well-known training samples, which include commercial paracetamol and aspirin tablets to check the validity of these two measurement techniques. In this study, the spectral features of some active pharmaceutical ingredients (APIs), such as aspirin and paracetamol are characterized for identification purpose. This work covers a wide THz spectral range namely, 2-18 THz. This proposed simple but novel technique, the tape method, was used for characterizing API and identifying their presence in their dosage forms. By comparing the spectra of the APIs to their dosage forms (powder samples), all distinct fingerprints present in the APIs are also present in their respective dosage forms. The positions of the spectral features obtained with the ATR techniques were akin to that obtained from the tape method. The ATR and the tape method therefore, complement each other. The presence of distinct fingerprints in this spectral range has highlighted the possibility of developing fast THz sensors for the screening of pharmaceuticals. It is worth noting that, the ATR method is applicable to flat faced tablets whereas the tape method is suitable for powders in general (e.g. curved surface tablets that require milling before measurement). Finally, we have demonstrated that ATR techniques can be used to screen counterfeit antimalarial tablets.

  20. A Hybrid MPC-PID Control System Design for the Continuous Purification and Processing of Active Pharmaceutical Ingredients

    Maitraye Sen

    2014-05-01

    Full Text Available In this work, a hybrid MPC (model predictive control-PID (proportional-integral-derivative control system has been designed for the continuous purification and processing framework of active pharmaceutical ingredients (APIs. The specific unit operations associated with the purification and processing of API have been developed from first-principles and connected in a continuous framework in the form of a flowsheet model. These integrated unit operations are highly interactive along with the presence of process delays. Therefore, a hybrid MPC-PID is a promising alternative to achieve the desired control loop performance as mandated by the regulatory authorities. The integrated flowsheet model has been simulated in gPROMSTM (Process System Enterprise, London, UK. This flowsheet model has been linearized in order to design the control scheme. The ability to track the set point and reject disturbances has been evaluated. A comparative study between the performance of the hybrid MPC-PID and a PID-only control scheme has been presented. The results show that an enhanced control loop performance can be obtained under the hybrid control scheme and demonstrate that such a scheme has high potential in improving the efficiency of pharmaceutical manufacturing operations.

  1. Acceleration of Anti-Markovnikov Hydroamination in the Synthesis of an Active Pharmaceutical Ingredient

    Mitic, Aleksandar; Skovby, Tommy; Dam-Johansen, Kim;

    2016-01-01

    Slow chemical reactions are a big challenge in the modern pharmaceutical industry. Their accelerations together with the introduction of continuous manufacturing modes are major drivers for future development. One example reaction is hydroamination, a reaction between unsaturated hydrocarbons and...... amines. Such a reaction type is the main focus of this work. More precisely, the anti-Markovnikov hydroamination reaction between cis/trans 9H-thioxanthene-2-chloro-9-(2-propenylidene)-(9CI) and 1-(2-hydroxyethyl)piperazine (HEP) is investigated in detail. It has been traditionally performed in toluene...

  2. Characterization of solid polymer dispersions of active pharmaceutical ingredients by 19F MAS NMR and factor analysis

    Urbanova, Martina; Brus, Jiri; Sedenkova, Ivana; Policianova, Olivia; Kobera, Libor

    In this contribution the ability of 19F MAS NMR spectroscopy to probe structural variability of poorly water-soluble drugs formulated as solid dispersions in polymer matrices is discussed. The application potentiality of the proposed approach is demonstrated on a moderately sized active pharmaceutical ingredient (API, Atorvastatin) exhibiting extensive polymorphism. In this respect, a range of model systems with the API incorporated in the matrix of polvinylpyrrolidone (PVP) was prepared. The extent of mixing of both components was determined by T1(1H) and T1ρ(1H) relaxation experiments, and it was found that the API forms nanosized domains. Subsequently it was found out that the polymer matrix induces two kinds of changes in 19F MAS NMR spectra. At first, this is a high-frequency shift reaching 2-3 ppm which is independent on molecular structure of the API and which results from the long-range polarization of the electron cloud around 19F nucleus induced by electrostatic fields of the polymer matrix. At second, this is broadening of the signals and formation of shoulders reflecting changes in molecular arrangement of the API. To avoid misleading in the interpretation of the recorded 19F MAS NMR spectra, because both the contributions act simultaneously, we applied chemometric approach based on multivariate analysis. It is demonstrated that factor analysis of the recorded spectra can separate both these spectral contributions, and the subtle structural differences in the molecular arrangement of the API in the nanosized domains can be traced. In this way 19F MAS NMR spectra of both pure APIs and APIs in solid dispersions can be directly compared. The proposed strategy thus provides a powerful tool for the analysis of new formulations of fluorinated pharmaceutical substances in polymer matrices.

  3. Measurement of low amounts of amorphous content in hydrophobic active pharmaceutical ingredients with dynamic organic vapor sorption.

    Müller, Thorsten; Schiewe, Jörg; Smal, Rüdiger; Weiler, Claudius; Wolkenhauer, Markus; Steckel, Hartwig

    2015-05-01

    Today, a variety of devices for dry powder inhalers (DPIs) is available and many different formulations for optimized deposition in the lung are developed. However, during the production of powder inhalers, processing steps may induce changes to both, the carrier and active pharmaceutical ingredients (APIs). It is well known that standard pharmaceutical operations may lead to structural changes, crystal defects and amorphous regions. Especially operations such as milling, blending and even sieving generate these effects. These disorders may induce re-crystallization and particle size changes post-production which have a huge influence on drug delivery and product stability. In this study, pilot tests with a polar solvent (water) and hydrophilic drug (Salbutamol sulfate) were performed to receive a first impression on further possible implementation of hydrophobic samples with organic solvents. Thereafter, a reliable method for the accurate detection of low amounts of amorphous content is described up to a limit of quantification (LOQ) of 0.5% for a hydrophobic model API (Ciclesonide). The organic vapor sorption method which is a gravimetric method quantifies exactly these low amounts of amorphous content in the hydrophobic powder once the suitable solvent (isopropanol), the correct p/p0 value (0.1) and the exact temperature (25°C) have been found. Afterward it was possible to quantitate low amorphous amounts in jet-milled powders (0.5-17.0%). In summary, the data of the study led to a clearer understanding in what quantity amorphous parts were generated in single production steps and how variable these parts behave to fully crystalline material. Nevertheless it showed how difficult it was to re-crystallize hydrophobic material with water vapor over a short period. For the individual samples it was possible to determine the single humidity at which the material starts to re-crystallize, the behavior against different nonpolar solvents and the calculation of the

  4. Quantitation of active pharmaceutical ingredients and excipients in powder blends using designed multivariate calibration models by near-infrared spectroscopy.

    Li, Weiyong; Worosila, Gregory D

    2005-05-13

    This research note demonstrates the simultaneous quantitation of a pharmaceutical active ingredient and three excipients in a simulated powder blend containing acetaminophen, Prosolv and Crospovidone. An experimental design approach was used in generating a 5-level (%, w/w) calibration sample set that included 125 samples. The samples were prepared by weighing suitable amount of powders into separate 20-mL scintillation vials and were mixed manually. Partial least squares (PLS) regression was used in calibration model development. The models generated accurate results for quantitation of Crospovidone (at 5%, w/w) and magnesium stearate (at 0.5%, w/w). Further testing of the models demonstrated that the 2-level models were as effective as the 5-level ones, which reduced the calibration sample number to 50. The models had a small bias for quantitation of acetaminophen (at 30%, w/w) and Prosolv (at 64.5%, w/w) in the blend. The implication of the bias is discussed. PMID:15848006

  5. Development and validation of a stability-indicating reverse phase ultra performance liquid chromatographic method for the estimation of nebivolol impurities in active pharmaceutical ingredients and pharmaceutical formulation.

    Thummala, Veera Raghava Raju; Lanka, Mohana Krishna

    2015-10-01

    A sensitive, stability-indicating gradient reverse phase ultra performance liquid chromatographic method has been developed for the quantitative estimation of nebivolol impurities in active pharmaceutical ingredient (API) and pharmaceutical formulation. Efficient chromatographic separation was achieved on an Acquity BEH C18 column (100 mm x 2.1 mm, 1.7 μm) with mobile phase of a gradient mixture. The flow rate of the mobile phase was 0.18 mL/min with column temperature of 30 degrees C and detection wavelength of 281 nm. The relative response factor values of (R*)-2-( benzylamino)-1-((S*)-6-fluorochroman-2-yl) ethanol ((R x S*) NBV-), (R)-1-((R)-6-fluorochroman-2-yl)-2-((S)-2-((S)-6-fluoro-chroman-2-yl)-2-hydroxyethyl-amino) ethanol ((RRSS) NBV-3), 1-(chroman-2-yl)-2-(2-(6-fluorochroman-2-yl)-2-hydroxyethyl amino) ethanol (monodesfluoro impurity), (S)-1-((R)-6-fluorochroman-2-yl)-2-((R)-2 (S*)-6-fluoro-chroman-2-yl)-2-hydroxyethylamino) ethanol hydrochloride ((RSRS) NBV-3) and (R*)-1-((S*)-6-fluorochroman-2-yl)-2-((S*)-2-((S*)-6-fluoro-chroman-2-yl)-2-hydroxyethylamino) ethanol ((R* S* S* S*) NBV-2) were 0.65, 0.91, 0.68, 0.92 and 0.91 respectively. Nebivolol formulation sample was subjected to the stress conditions of acid, base, oxidative, hydrolytic, thermal, humidity and photolytic degradation. Nebivolol was found to degrade significantly under peroxide stress condition. The degradation products were well resolved from nebivolol and its impurities. The peak purity test results confirmed that the nebivolol peak was homogenous and pure in all stress samples and the mass balance was found to be more than 98%, thus proving the stability-indicating power of the method. The developed method was validated according to International Conference on Hormonization (ICH) guidelines with respect to specificity, linearity, limits of detection and quantification, accuracy, precision and robustness. PMID:26930962

  6. Capillary-induced Homogenization of Matrix in Paper: A Powerful Approach for the Quantification of Active Pharmaceutical Ingredients Using Mass Spectrometry Imaging

    de Menezes, Maico; de Oliveira, Diogo Noin; Catharino, Rodrigo Ramos

    2016-01-01

    Herein we present a novel approach for the quantification of active pharmaceutical ingredients (APIs) using mass spectrometry imaging. This strategy uses a filter paper previously “eluted” with a MALDI matrix solution as a support for analyte application. Samples are submitted to mass spectrometry imaging (MSI) and quantification through characteristic fingerprints is ultimately performed. Results for the content of rosuvastatin from a known formulation are comparable to those obtained with a validated HPLC method. PMID:27439589

  7. Capillary-induced Homogenization of Matrix in Paper: A Powerful Approach for the Quantification of Active Pharmaceutical Ingredients Using Mass Spectrometry Imaging

    de Menezes, Maico; de Oliveira, Diogo Noin; Catharino, Rodrigo Ramos

    2016-07-01

    Herein we present a novel approach for the quantification of active pharmaceutical ingredients (APIs) using mass spectrometry imaging. This strategy uses a filter paper previously “eluted” with a MALDI matrix solution as a support for analyte application. Samples are submitted to mass spectrometry imaging (MSI) and quantification through characteristic fingerprints is ultimately performed. Results for the content of rosuvastatin from a known formulation are comparable to those obtained with a validated HPLC method.

  8. Impact of alternative solid state forms and specific surface area of high-dose, hydrophilic active pharmaceutical ingredients on tabletability.

    Paluch, Krzysztof J; Tajber, Lidia; Corrigan, Owen I; Healy, Anne Marie

    2013-10-01

    In order to investigate the effect of using different solid state forms and specific surface area (TBET) of active pharmaceutical ingredients on tabletability and dissolution performance, the mono- and dihydrated crystalline forms of chlorothiazide sodium and chlorothiazide potassium (CTZK) salts were compared to alternative anhydrous and amorphous forms, as well as to amorphous microparticles of chlorothiazide sodium and potassium which were produced by spray drying and had a large specific surface area. The tablet hardness and tensile strength, porosity, and specific surface area of single-component, convex tablets prepared at different compression pressures were characterized. Results confirmed the complexity of the compressibility mechanisms. In general it may be concluded that factors such as solid-state form (crystalline vs amorphous), type of hydration (presence of interstitial molecules of water, dehydrates), or specific surface area of the material have a direct impact on the tabletability of the powder. It was observed that, for powders of the same solid state form, those with a larger specific surface area compacted well, and better than powders of a lower surface area, even at relatively low compression pressures. Compacts prepared at lower compression pressures from high surface area porous microparticles presented the shortest times to dissolve, when compared with compacts made of equivalent materials, which had to be compressed at higher compression pressures in order to obtain satisfactory compacts. Therefore, materials composed of nanoparticulate microparticles (NPMPs) may be considered as suitable for direct compaction and possibly for inclusion in tablet formulations as bulking agents, APIs, carriers, or binders due to their good compactibility performance. PMID:23961942

  9. Thermal, mechanical and drug release characteristics of an acrylic film using active pharmaceutical ingredient as non-traditional plasticizer.

    Wiranidchapong, Chutima; Kieongarm, Waraporn; Managit, Chittima; Phrompittayarat, Watoo

    2016-04-01

    The objective of this study was to investigate thermal and mechanical properties as well as in vitro drug release of Eudragit® RL (ERL) film using chlorpheniramine maleate (CPM) as either active pharmaceutical ingredient or non-traditional plasticizer. Differential scanning calorimeter was used to measure the glass transition temperature (Tg) of 0-100% w/w CPM in ERL physical mixture. Instron testing machine was used to investigate Young's modulus, tensile stress and tensile strain (%) of ERL film containing 20-60% w/w CPM. Finally, a Franz diffusion cell was used to study drug release from ERL films obtained from four formulations, i.e. CRHP0/0, CRHP0/5, CRHP2/0 and CRHP2/5. The Tg of ERL was decreased when the weight percentage of CPM increased. The reduction of the Tg could be described by Kwei equation, indicating the interaction between CPM and ERL. Modulus and tensile stress decreased whereas tensile strain (%) increased when weight percentage of CPM increased. The change of mechanical properties was associated with the reduction of the Tg when weight percentage of CPM increased. ERL films obtained from four formulations could release the drug in no less than 10 h. Cumulative amount of drug release per unit area of ERL film containing only CPM (CRHP0/0) was lower than those obtained from the formulations containing traditional plasticizer (CRHP0/5), surfactant (CRHP2/0) or both of them (CRHP2/5). The increase of drug release was a result of the increase of drug permeability through ERL film and drug solubility based on traditional plasticizer and surfactant, respectively. PMID:26133082

  10. Encapsulation of active ingredients

    Soest, van, A.J.; Schijndel, van, AWM Jos; Gotlieb, K.F.

    2002-01-01

    Microspheres having a particle size of 50 nm to 1 nm and a polydispersity of less than 40%, consisting of a chemically cross-linked starch shell containing an active ingredient, are obtained by preparing an oil-in-water emulsion of the active ingredient in a hydrophobic phase and starch or a dispersion of a solid active ingredient and starch in water, incorporating the oil-in-water emulsion or solid dispersion in an outer hydrophobic phase, particles of the oil-in-water emulsion or solid disp...

  11. Encapsulation of active ingredients

    Gotlieb, K.F.; Schijndel, van, AWM Jos; Soest, van, A.J.

    1999-01-01

    Microspheres having a particle size of 50 nm to 1 nm and a polydispersity of less than 40%, consisting of a chemically cross-linked starch shell containing an active ingredient, are obtained by preparing an oil-in-water emulsion of the active ingredient in a hydrophobic phase and starch or a dispersion of a solid active ingredient and starch in water, incorporating the oil-in-water emulsion or solid dispersion in an outer hydrophobic phase, particles of the oil-in-water emulsion or solid disp...

  12. Encapsulation of active ingredients

    Soest, van, A.J.; Schijndel, van, AWM Jos; Gotlieb, K.F.

    2000-01-01

    Microspheres having a particle size of 50 nm to 1 nm and a polydispersity of less than 40%, consisting of a chemically cross-linked starch shell containing an active ingredient, are obtained by preparing an oil-in-water emulsion of the active ingredient in a hydrophobic phase and starch or a dispersion of a solid active ingredient and starch in water, incorporating the oil-in-water emulsion or solid dispersion in an outer hydrophobic phase, particles of the oil-in-water emulsion or solid disp...

  13. A survey of the syntheses of active pharmaceutical ingredients for antiretroviral drug combinations critical to access in emerging nations.

    Pinheiro, Eloan Dos Santos; Antunes, Octavio Augusto Ceva; Fortunak, Joseph M D

    2008-09-01

    irrelevant, except for "advanced salvage" drugs such as enfuvirtide. In resource-poor settings cost is a huge factor that limits drug access, resulting in high rates of new infection and subsequent mortality. IP coverage, where granted, can keep access prices for essential ARVs higher than would otherwise be the case. Large, innovator companies have made drugs available at prices very close to the cost of manufacturing for "lowest income" countries. Generic providers in India and elsewhere provide the largest supply of drugs for the developing world. The recent issuance of Voluntary and Compulsory Licenses (VLs, CLs) through the World Trade Organization's TRIP (Treaty Respecting Intellectual Property) provisions arguably contribute to bringing down access prices. The utilization of improved science, pooled purchasing and intelligent procurement practices all definitely contribute to access. This work surveys the production processes for several critical ARVs. These are discussed in terms of scale up, raw material/intermediates and active pharmaceutical ingredient (API) costs. In some cases new routes to APIs or critical intermediates are needed. Based on potential new chemistries, there are significant opportunities to reduce cost for a number of critical ARVs. PMID:18571246

  14. 离子液体在活性药物成分中的应用%The application of ionic liquids in active pharmaceutical ingredients

    孟坤燕; 齐明辉; 陈宜俍; 赵文杰; 任国宾

    2011-01-01

    离子液体具有独特的可调节的理化性能,近年来离子液体在活性药物成分中的应用成为国际上研究的前沿和热点.该文在介绍离子液体特性的基础上,综述了离子液体形式的活性药物成分的制备、表征和研究意义.%Ionic liquids (Ils) possess unique tunable physical and chemical properties. Recently, the application of Ils in active pharmaceutical ingredients (APIs) has become the frontier of international pharmaceutical research. The synthesis, characterization and significance of Ils-APIs are summarized based on the properties of Ils.

  15. Analytical method (HPLC, validation used for identification and assay of the pharmaceutical active ingredient, Tylosin tartrate for veterinary use and its finite product Tilodem 50, hydrosoluble powder

    Maria Neagu

    2010-12-01

    Full Text Available In SC DELOS IMPEX ’96 SRL the quality of the active pharmaceutical ingredient (API for the finite product Tilodem 50 - hydrosoluble powder was acomkplished in the respect of last European Pharmacopoeia.The method for analysis used in this purpose was the compendial method „Tylosin tartrate for veterinary use” in EurPh. in vigour edition and represent a variant developed and validation „in house”.The parameters which was included in the methodology validation for chromatographic method are the followings: Selectivity, Linearity, Linearity range, Detection and Quantification limits, Precision, Repeatability (intra day, Inter-Day Reproductibility, Accuracy, Robustness, Solutions’ stability and System suitability. According to the European Pharmacopoeia, the active pharmaceutical ingredient is consistent, in terms of quality, if it contains Tylosin A - minimum 80% and the amount of Tylosin A, B, C, D, at minimum 95%. Identification and determination of each component separately (Tylosin A, B, C, D is possible by chromatographic separation-HPLC. Validation of analytical methods is presented below.

  16. Continuous Hydrolysis and Liquid–Liquid Phase Separation of an Active Pharmaceutical Ingredient Intermediate Using a Miniscale Hydrophobic Membrane Separator

    Cervera Padrell, Albert Emili; Morthensen, Sofie Thage; Lewandowski, Daniel Jacob;

    2012-01-01

    capillary pressure (Laplace pressure) combined with a large number of pores per unit area offering low pressure drop. The separation device can easily be operated by means of a back-pressure regulator ensuring flow-independent separation efficiency. Simple monitoring and control strategies as well as...... scaling-up/out approaches are proposed, concluding that membrane-based L-L separation may become a standard unit operation for continuous pharmaceutical manufacturing....... a PTFE membrane with 28 cm2 of active area. A less challenging separation of water and toluene was achieved at total flow rates as high as 80 mL/min, with potential to achieve even higher flow rates. The operability and flexibility of the membrane separator and a plate coalescer were compared...

  17. Monitoring and Control of a Continuous Grignard Reaction for the Synthesis of an Active Pharmaceutical Ingredient Intermediate Using Inline NIR spectroscopy

    Cervera Padrell, Albert Emili; Nielsen, Jesper; Jønch Pedersen, Michael;

    2012-01-01

    the stoichiometric ratio, leading the path to full process automation. The feedback control loop relies on NIR transmission measurements performed in a flow cell where, in contrast to labor-intensive offline HPLC analytical methods, the whole reaction product can be scanned in real time without sample...... be used to obtain information about its dynamic behavior. This information is very useful for process control design, assessment of analytical tools and definition of sampling times. In this work, a systematic procedure for chemometric model building is followed, after which a discussion is made on......Inline near-infrared (NIR) spectroscopy has been used to monitor a continuous synthesis of an active pharmaceutical ingredient (API) intermediate by a Grignard alkylation reaction. The reaction between a ketone substrate and allylmagnesium chloride may form significant impurities with excess...

  18. Determination of everolimus in everolimus active pharmaceutical ingredient by HPLC%HPLC法测定依维莫司原料药中依维莫司

    孙莉君; 沈海梅; 马海霞; 董大伟; 王越; 杨静

    2015-01-01

    Objective To establish an HPLC method for determination of everolimus in everolimus active pharmaceutical ingredient. Methods The separation was performed on a Hypersil-ODS C18column with acetonitrile - water (70∶30) as mobile phases. The detection wavelength was set at 276 nm. The column temperature was 50℃. The flow rate was 0.8 mL/min with injection volume of 10μL.Results Everolimus had good linearity in the ranges of 63 — 1 008μg/mL (r= 0.999 7). The average recovery was 100.45% with RSD 0.64% (n=9).Conclusion The method is simple and specific, and can be used effectively for quality control of everolimus active pharmaceutical ingredient.%目的:建立HPLC法测定依维莫司原料药中依维莫司。方法采用Hypersil-ODS C18色谱柱(250 mm×4.6 mm,5μm);流动相:乙腈–水(70∶30);检测波长:276 nm;柱温:50℃;体积流量:0.8 mL/min;进样量:10μL。结果依维莫司在63~1008μg/mL线性关系良好(r=0.9997),平均回收率为100.45%,RSD值为0.64%(n=9)。结论所建立的操作简便,专属性强,可用于依维莫司原料药的质量控制。

  19. Study of molecular properties of specific pharmaceutical materials based on solid solutions and dispersions of active pharmaceutical ingredients in polymer matrix

    Policianová, Olivia; Brus, Jiří

    Chalkidiki : National Center for Scientific Research, 2010. s. 41. [International Workshop on "Structural and Functional Characterisation of Complex Materials" /2./. 03.06.2010-05.06.2010, Chalkidiki] R&D Projects: GA MŠk 2B08021 EU Projects: European Commission(XE) 204953 - RP-DEMATEN Institutional research plan: CEZ:AV0Z40500505 Keywords : bioavailability * NMR * pharmaceutical materials Subject RIV: CD - Macromolecular Chemistry

  20. Influence of Process Parameters on Content Uniformity of a Low Dose Active Pharmaceutical Ingredient in a Tablet Formulation According to GMP

    Muselík Jan

    2014-09-01

    Full Text Available The article describes the development and production of tablets using direct compression of powder mixtures. The aim was to describe the impact of filler particle size and the time of lubricant addition during mixing on content uniformity according to the Good Manufacturing Practice (GMP process validation requirements. Processes are regulated by complex directives, forcing the producers to validate, using sophisticated methods, the content uniformity of intermediates as well as final products. Cutting down of production time and material, shortening of analyses, and fast and reliable statistic evaluation of results can reduce the final price without affecting product quality. The manufacturing process of directly compressed tablets containing the low dose active pharmaceutical ingredient (API warfarin, with content uniformity passing validation criteria, is used as a model example. Statistic methods have proved that the manufacturing process is reproducible. Methods suitable for elucidation of various properties of the final blend, e.g., measurement of electrostatic charge by Faraday pail and evaluation of mutual influences of researched variables by partial least square (PLS regression, were used. Using these methods, it was proved that the filler with higher particle size increased the content uniformity of both blends and the ensuing tablets. Addition of the lubricant, magnesium stearate, during the blending process improved the content uniformity of blends containing the filler with larger particles. This seems to be caused by reduced sampling error due to the suppression of electrostatic charge.

  1. Development of Genotoxic Impurities Control in Active Pharmaceutical Ingredient%原料药中基因毒性杂质控制的研究进展

    王萍; 徐彩虹; 陈仙; 胡爱玲; 楼朝; 金秀芳; 龚俊强; 陈轶群

    2015-01-01

    目的 介绍原料药(active pharmaceutical ingredient,API)中基因毒性杂质控制的法规要求、评估方法和控制方法.方法 通过学习欧美法规发展历史,理解国际高端市场对基因毒性杂质控制的监管期望,提出原料药中基因毒性杂质风险评估方法.结果与结论 企业基于半定量评估,结合清除研究数据,建立科学的控制策略,使实际工艺中所有可能涉及的基因毒性杂质风险得到明确鉴别和控制,是达到监管期望的有效途径.

  2. Isotopic finger-printing of active pharmaceutical ingredients by 13C NMR and polarization transfer techniques as a tool to fight against counterfeiting.

    Bussy, Ugo; Thibaudeau, Christophe; Thomas, Freddy; Desmurs, Jean-Roger; Jamin, Eric; Remaud, Gérald S; Silvestre, Virginie; Akoka, Serge

    2011-09-30

    The robustness of adiabatic polarization transfer methods has been evaluated for determining the carbon isotopic finger-printing of active pharmaceutical ingredients. The short time stabilities of the adiabatic DEPT and INEPT sequences are very close to that observed with the one pulse sequence, but the DEPT long time stability is not sufficient for isotopic measurements at natural abundance or low enrichment. Using the INEPT sequence for (13)C isotopic measurements induces a dramatic reduction in the experimental time without deterioration in short time or long time stability. It appears, therefore, to be a method of choice for obtaining the isotopic finger-print of different ibuprofen samples in a minimum time. The results obtained on 13 commercial ibuprofen samples from different origins show that this strategy can be used effectively to determine (13)C distribution within a given molecule and to compare accurately differences in the isotopic distribution between different samples of the given molecule. The present methodology is proposed as a suitable tool to fight against counterfeiting. PMID:21872037

  3. Development Of New Visible Spectrophotometric Methods For Quantitative Determination Of Almotriptan Malate As An Active Pharmaceutical Ingredient In Formulations

    U. Viplava Prasad

    2012-06-01

    Full Text Available Purpose: The aim of the investigation was to see the simple and sensitive visible spectrophotometric methods for the determination of the almotriptan malate in bulk and tablet dosage forms. Methods: Two simple, sensitive and cost effective visible spectrophotometric methods (M1-M2 were developed for the estimation of almotriptan malate in bulk and dosage forms. The first method (M1 is based on the formation of blue reduced product by treating drug with Folin Ciocalteu (FC reagent in the presence of sodium carbonate solution with an absorption maximum of 770nm. The second method (M2 is based on the complex formation product by drug with 1, 10-phenanthroline in the presence of Fe (III as an oxidant in phosphoric acid medium with an absorption maximum of 510nm. Results: Beer’s law obeyed in the concentration range of 4-12μg/ml and 1-5 μg/ml for methodM1 and M2 respectively. No interference was observed from the usually existing additives in pharmaceutical formulations and the applicability of the methods was examined by analyzing AXERT tablets containing AM. Conclusion: The reported methods for its assay involve sophisticated equipment, which are very costly and pose problems of maintenance. To overcome these problems, the use of visible spectrophotometric technique is justifiable. The statistical data proved the accuracy, reproducibility and the precision of the proposed methods.

  4. Method for the determination of Pd-catalyst residues in active pharmaceutical ingredients by means of high-energy polarized-beam energy dispersive X-ray fluorescence.

    Marguí, E; Van Meel, K; Van Grieken, R; Buendía, A; Fontàs, C; Hidalgo, M; Queralt, I

    2009-02-15

    In medicinal chemistry, Pd is perhaps the most-widely utilized precious metal, as catalyst in reactions which represent key transformations toward the synthesis of new active pharmaceutical ingredients (APIs). The disadvantage of this metal-catalyzed chemistry is that expensive and toxic metal residues are invariably left bound to the desired product. Thus, stringent regulatory guidelines exist for the amount of residual Pd that a drug candidate is allowed to contain. In this work, a rapid and simple method for the determination of Pd in API samples by high-energy polarized-beam energy dispersive X-ray fluorescence spectrometry has been developed and validated according to the specification limits of current legislation (10 mg kg(-1) Pd) and the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH guidelines). Sample and calibration standards preparation includes a first step of homogenization and then, in a second step, the pressing of the powdered material into pellets without any chemical treatment. The use of several synthetic calibration standards made of cellulose to simulate the API matrix appears to be an effective means to obtain reliable calibration curves with a good spread of data points over the working range. With the use of the best measuring conditions, the limit of detection (0.11 mg kg(-1) Pd) as well as the limit of quantitation (0.37 mg kg(-1) Pd) achieved meet rigorous requirements. The repeatability of the XRF measurement appeared to be less than 2%, while the precision of the whole method was around 7%. Trueness was evaluated by analyzing spiked API samples at the level of the specification limit and calculating the recovery factor, which was better than 95%. To study the applicability of the developed methodology for the intended purpose, three batches of the studied API were analyzed for their Pd content, and the attained results were comparable to those obtained by the

  5. Identification, synthesis and characterization of an unknown process related impurity in eslicarbazepine acetate active pharmaceutical ingredient by LC/ESI–IT/MS, 1H, 13C and 1H–1H COSY NMR

    Saji Thomas; Saroj Kumar Paul; Subhash Chandra Joshi; Vineet Kumar; Ashutosh Agarwal; Dharam Vir

    2014-01-01

    A new impurity was detected during high performance liquid chromatographic (HPLC) analysis of eslicarbazepine acetate active pharmaceutical ingredient. The structure of unknown impurity was postulated based on liquid chromatography mass spectrometry using electrospray ionization and ion trap analyzer (LC/ESI–IT/MS) analysis. Proposed structure of impurity was unambiguously confirmed by synthesis followed by characterization using 1H, 13C nuclear magnetic resonance spectrometry (NMR), 1H–1H co...

  6. HPLC法测定达格列净原料药中有关物质%Determination of related substances in dapagliflozin active pharmaceutical ingredients by HPLC

    陈稳; 郑津津; 王晨

    2015-01-01

    Objective To establish a method for determination of related substances in dapagliflozin active pharmaceutical ingredients.Methods HPLC method was adopted. The determination was carried out on Diamonsil C18 column (250 mm × 4.6 mm, 5 µm). The mobile phase consisted of 0.02 mol/L sodium dihydrogen phosphate - methanol - tetrahydrofuran (60∶35∶5) at a flow rate of 1.0 mL/min. The detective wavelength was set at 220 nm, the column temperature was at 35℃, and the injection volume was 10μL.Results Dapagliflozin and its related substances had good separation. The LOQ of the related substances, such as Z1, Z2, F1, F2, and F3 were1.34, 1.54, 1.42, 1.71, and 2.11 ng, respectively. The average recoveries were 98.9%, 97.6%, 103.2%, 102.4%, and 102.8% with RSD values of 1.8%, 1.3%, 1.5%, 0.7%, and 1.7%, respectively.Conclusion The method is sensitive and accurate, and can be used for quality control of related substances in dapagliflozin active pharmaceutical ingredients.%目的:建立达格列净原料药中有关物质的测定方法。方法采用 HPLC法。Diamonsil C18色谱柱(250 mm×4.6 mm,5μm);以0.02 mol/L磷酸二氢钠水溶液–甲醇–四氢呋喃(60∶35∶5)为流动相;体积流量1.0 mL/min;检测波长220 nm;柱温35℃;进样量为10μL。结果达格列净与各杂质的分离度良好,杂质Z1、Z2、F1、F2、F3的定量限分别为3.22、3.83、3.65、4.33、4.92 ng,平均回收率分别为98.9%、97.6%、103.2%、102.4%、102.8%,RSD值分别为1.8%、1.3%、1.5%、0.7%、1.7%。结论本方法检测灵敏度高,精密度好,可以用于达格列净原料药中有关物质的质量控制。

  7. Determination of related substances in ambrisentan active pharmaceutical ingredients%HPLC法测定安立生坦原料药中有关物质

    陈保来; 李家春; 仲艳; 郭庆明; 沈旺; 王振中; 萧伟

    2015-01-01

    目的:建立安立生坦原料药中有关物质的测定方法。方法采用HPLC法。Waters Atlantis T3色谱柱(250 mm×4.6 mm,5μm);以0.02%三氟乙酸水溶液–0.01%三氟乙酸乙腈溶液为流动相,进行梯度洗脱;柱温30℃;体积流量1.0 mL/min;自动进样器控温5℃;检测波长220 nm。结果安立生坦与各杂质的分离度良好,杂质Z1、Z2、Z3、Z4、DP1的定量限分别为2.14、2.54、2.44、2.45、2.41 ng,平均回收率分别为102.9%、96.0%、93.1%、104.6%、115.2%,RSD值分别为2.1%、4.6%、2.9%、2.7%、4.9%(n=10)。结论该方法检测灵敏度高,精密度好,可以用于安立生坦原料药中有关物质的质量控制。%Objective To establish a method for determination of related substances in ambrisentan active pharmaceutical ingredients. Methods HPLC method was adopted. The determination was performed on Waters Atlantis T3 column (250 mm × 4.6 mm, 5μm) with mobile phase consisted of 0.02% trifluoroacetic acid - acetonitrile (containing 0.01% trifluoroacetic acid) with gradient elution. The temperature of column was set at 30℃. The flow rate was 1.0 mL/min with automatic injection volume of 5μL. The detective wavelength was set at 220 nm. Results Ambrisentan and its related substances could be separated completely. The LOQ of the related substances, such as Z1, Z2, Z3, Z4, and DP1 were 2.14, 2.54, 2.44, 2.45, and 2.41 ng, respectively. They all had good linearity. The average recovery were 102.9%, 96.0%, 93.1%, 104.6%, and 115.2%with RSD values of 2.1%, 4.6%, 2.9%, 2.7%, and 4.9%(n = 10), respectively. Conclusion The method is sensitive and accurate, and can be used for quality control of related substances in ambrisentan active pharmaceutical ingredients.

  8. Dynamics of active pharmaceutical ingredients loads in a Swiss university hospital wastewaters and prediction of the related environmental risk for the aquatic ecosystems.

    Daouk, Silwan; Chèvre, Nathalie; Vernaz, Nathalie; Widmer, Christèle; Daali, Youssef; Fleury-Souverain, Sandrine

    2016-03-15

    The wastewater contamination of a Swiss university hospital by active pharmaceutical ingredient (API) residues was evaluated with a three months monitoring campaign at the outlet of the main building. Flow-proportional samples were collected with an automatic refrigerated sampler and analyzed for 15 API, including antibiotics, analgesics, antiepileptic and anti-inflammatory drugs, by using a validated LC-MS/MS method. The metals Gd and Pt were also analyzed using ICP-MS. Measured concentrations were compared to the predicted ones calculated after the drug average consumption data obtained from the hospital pharmacy. The hospital contribution to the total urban load was calculated according to the consumption data obtained from city pharmacies. Lastly, the environmental hazard and risk quotients (RQ) related to the hospital fraction and the total urban consumption were calculated. Median concentrations of the 15 selected compounds were ranging from 0.04 to 675 μg/L, with a mean detection frequency of 84%. The ratio between predicted and measured environmental concentrations (PEC/MEC) has shown a good accuracy for 5 out of 15 compounds, revealing over- and under-estimations of the PEC model. Mean daily loads were ranging between 0.01 and 14.2g/d, with the exception of paracetamol (109.7 g/d). The hospital contribution to the total urban loads varied from 2.1 to 100% according to the compound. While taking into account dilution and removal efficiencies in wastewater treatment plant, only the hospital fraction of the antibiotics ciprofloxacin and sulfamethoxazole showed, respectively, a high (RQ>1) and moderate (RQ>0.1) risk for the aquatic ecosystems. Nevertheless, when considering the total urban consumption, 7 compounds showed potential deleterious effects on aquatic organisms (RQ>1): gabapentin, sulfamethoxazole, ciprofloxacin, piperacillin, ibuprofen, diclofenac and mefenamic acid. In order to reduce inputs of API residues originating from hospitals various

  9. Content of Active Pharmaceutical Ingredient with Somatostatin by UPLC Method%UPLC法测定生长抑素原料药的含量

    张承军; 王秀梅; 王建良; 贾长久; 李兰兰

    2012-01-01

    目的:建立快速、准确、灵敏的测定生长抑素原料药的方法.方法:采用沃特世ACQUITY超高液相色谱系统(UPLC),以磷酸(取磷酸11 mL,加水900 mL,用三乙胺调pH至2.3,用水稀释至刻度1 000 mL处)为流动相,(A)-乙腈 (B)梯度洗脱,流速:0.3 mL/min;检测波长为215 nm;柱温45℃;进样体积2μL.结果:生长抑素在0.005 149 2~0.128 73 mg / mL范围内有良好的线性关系(R2= 0.999 3),平均回收率(n=9)为99.1%.结论:UPLC法检测快速、准确、灵敏度高、重复性好,为生长抑素原料药的质量控制提供了一种快速准确的方法.%Objective: To establish a rapid, accurate and sensitive method to determine active pharmaceutical ingredient (API) with somatostatin. Method: Waters ACQUITY UPLC was adopted. Phosphoric acid-triethylamine buffer solution was as mobile phase A and acetonitrile as B, gradient elution was used with flow rate of 0.3 mL/min; detection wave length was 215 nm; column temperature was 45 ℃; injection volume was 2μL. Result: Somatostatin has a great linearity (R2 = 0.999 3) from 0.005 149 2 mg/mL to 0.128 73 mg/mL. Average recovery rate (n= 9) is 99.1%. Conclusion: UPLC method, which is rapid, accurate, sensitive and with good repeatability, could service for quality control of somatostatin (API).

  10. Identification, synthesis and characterization of an unknown process related impurity in eslicarbazepine acetate active pharmaceutical ingredient by LC/ESI-IT/MS, 1H, 13C and 1H-1H COSY NMR

    Saji Thomas; Saroj Kumar Paul; Subhash Chandra Joshi; Vineet Kumar; Ashutosh Agarwal; Dharam Vir

    2014-01-01

    A new impurity was detected during high performance liquid chromatographic (HPLC) analysis of eslicarbazepine acetate active pharmaceutical ingredient. The structure of unknown impurity was postulated based on liquid chromatography mass spectrometry using electrospray ionization and ion trap analyzer (LC/ESI-IT/MS) analysis. Proposed structure of impurity was unambiguously confirmed by synthesis followed by characterization using 1H, 13C nuclear magnetic resonance spectrometry (NMR), 1H-1H correlation spectro-scopy (COSY) and infrared spectroscopy (IR). Based on the spectroscopic and spectrometric data, unknown impurity was characterized as 5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl propionate.

  11. Identification, synthesis and characterization of an unknown process related impurity in eslicarbazepine acetate active pharmaceutical ingredient by LC/ESI–IT/MS, 1H, 13C and 1H–1H COSY NMR

    Saji Thomas

    2014-10-01

    Full Text Available A new impurity was detected during high performance liquid chromatographic (HPLC analysis of eslicarbazepine acetate active pharmaceutical ingredient. The structure of unknown impurity was postulated based on liquid chromatography mass spectrometry using electrospray ionization and ion trap analyzer (LC/ESI–IT/MS analysis. Proposed structure of impurity was unambiguously confirmed by synthesis followed by characterization using 1H, 13C nuclear magnetic resonance spectrometry (NMR, 1H–1H correlation spectroscopy (COSY and infrared spectroscopy (IR. Based on the spectroscopic and spectrometric data, unknown impurity was characterized as 5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl propionate.

  12. The validation of the analytical method (HPLC, use for identification and assay of the pharmaceutical active ingredient, colistine sulphate and the finished product Colidem 50 – hydrosoluble powder, in SC DELOS impex ‘96 SRL

    Maria Neagu,

    2011-06-01

    Full Text Available In SC DELOS IMPEX ’96 SRL the quality of the active pharmaceutical ingredient (API for the finished product Colidem 50 - hydrosoluble powder is make according to European Pharmacopoeia, curent edition. The method for analysis use in this purpose is the compendial method „Colistine sulphate” in E.P. in current edition and represent a optimized variant, developed and validated „in house”.The parameters which was included in the methodology validation for chromatographic method are the follow: Selectivity/Specificity, Linearity, Range of Linearity, Limit of Detection and Limit of Quantification, Precision (Repeatability - intra day, inter-Day Reproducibility, Accuracy, Robustness, Stability Solutions and System Suitability.

  13. Environmental Impact Assessment and Management for Active Pharmaceutical Ingredients from Pharmaceutical Wastewater%制药废水药物活性成分的环境影响评价与管理初探

    孟妮; 王峰; 周振

    2011-01-01

    The influence of active pharmaceutical ingredients(API) on the aquatic environment has been increasingly concerned in recent years.The main pathways of API into the environment are through waste discharge from pharmaceutical enterprises,excretion from the body and irrational disposal of unused or expired pharmaceuticals.The ratio between predicted environmental concentration(PEC) and predicted no effect concentration(PNEC) was introduced to evaluate the environmental risk of API in an API management practice,and the environmental risk includes both the effect of API on the aquatic environment and its disturbance to the biological wastewater treatment plant.The method can be applies to the environment management of API for both pharmaceutical enterprises and governmental authorities.%药物活性成分(API)对水环境的影响近年来日益引起关注。API可通过制药企业的废弃物排放、未完全被吸收利用的API排泄以及过期药物的不合理处置三种途径进入水体。通过具体案例分析介绍了制药企业采用预测环境浓度(PEC)和预测无效应浓度(PNEC)的比值对API的环境风险进行评估的方法,API的环境风险包括对自然水体的影响和对污水生物处理系统的干扰。该方法可作为API环境影响分析评价的有效工具用于制药企业的环境管理或者政府部门的监管工作中。

  14. Determination of palladium, platinum and rhodium in used automobile catalysts and active pharmaceutical ingredients using high-resolution continuum source graphite furnace atomic absorption spectrometry and direct solid sample analysis

    Resano, Martín, E-mail: mresano@unizar.es [Department of Analytical Chemistry, Aragón Institute of Engineering Research (I3A), University of Zaragoza, Pedro Cerbuna 12, 50009 Zaragoza (Spain); Flórez, María del Rosario [Department of Analytical Chemistry, Aragón Institute of Engineering Research (I3A), University of Zaragoza, Pedro Cerbuna 12, 50009 Zaragoza (Spain); Queralt, Ignasi [Institute of Earth Sciences Jaume Almera ICTJA-CSIC, Sole Sabarís s/n, 08028 Barcelona (Spain); Marguí, Eva [Department of Chemistry, Faculty of Sciences, Universitat de Girona, Campus Montilivi s/n, 17071 Girona (Spain)

    2015-03-01

    This work investigates the potential of high-resolution continuum source graphite furnace atomic absorption spectrometry for the direct determination of Pd, Pt and Rh in two samples of very different nature. While analysis of active pharmaceutical ingredients is straightforward and it is feasible to minimize matrix effects, to the point that calibration can be carried out against aqueous standard solutions, the analysis of used automobile catalysts is more challenging requiring the addition of a chemical modifier (NH{sub 4}F·HF) to help in releasing the analytes, a more vigorous temperature program and the use of a solid standard (CRM ERM®-EB504) for calibration. However, in both cases it was possible to obtain accurate results and precision values typically better than 10% RSD in a fast and simple way, while only two determinations are needed for the three analytes, since Pt and Rh can be simultaneously monitored in both types of samples. Overall, the methods proposed seem suited for the determination of these analytes in such types of samples, offering a greener and faster alternative that circumvents the traditional problems associated with sample digestion, requiring a small amount of sample only (0.05 mg per replicate for catalysts, and a few milligrams for the pharmaceuticals) and providing sufficient sensitivity to easily comply with regulations. The LODs achieved were 6.5 μg g{sup −1} (Pd), 8.3 μg g{sup −1} (Pt) and 9.3 μg g{sup −1} (Rh) for catalysts, which decreased to 0.08 μg g{sup −1} (Pd), 0.15 μg g{sup −1} (Pt) and 0.10 μg g{sup −1} (Rh) for pharmaceuticals. - Highlights: • Solid sampling HR CS GFAAS permits the fast and direct determination of Pd, Pt and Rh. • 2 determinations suffice for the 3 elements (2 of them can be measured simultaneously). • Samples as different as car catalysts and pharmaceuticals can be accurately analyzed. • Aqueous standards (pharmaceuticals) or a solid CRM (catalysts) is used for calibration.

  15. Determination of palladium, platinum and rhodium in used automobile catalysts and active pharmaceutical ingredients using high-resolution continuum source graphite furnace atomic absorption spectrometry and direct solid sample analysis

    This work investigates the potential of high-resolution continuum source graphite furnace atomic absorption spectrometry for the direct determination of Pd, Pt and Rh in two samples of very different nature. While analysis of active pharmaceutical ingredients is straightforward and it is feasible to minimize matrix effects, to the point that calibration can be carried out against aqueous standard solutions, the analysis of used automobile catalysts is more challenging requiring the addition of a chemical modifier (NH4F·HF) to help in releasing the analytes, a more vigorous temperature program and the use of a solid standard (CRM ERM®-EB504) for calibration. However, in both cases it was possible to obtain accurate results and precision values typically better than 10% RSD in a fast and simple way, while only two determinations are needed for the three analytes, since Pt and Rh can be simultaneously monitored in both types of samples. Overall, the methods proposed seem suited for the determination of these analytes in such types of samples, offering a greener and faster alternative that circumvents the traditional problems associated with sample digestion, requiring a small amount of sample only (0.05 mg per replicate for catalysts, and a few milligrams for the pharmaceuticals) and providing sufficient sensitivity to easily comply with regulations. The LODs achieved were 6.5 μg g−1 (Pd), 8.3 μg g−1 (Pt) and 9.3 μg g−1 (Rh) for catalysts, which decreased to 0.08 μg g−1 (Pd), 0.15 μg g−1 (Pt) and 0.10 μg g−1 (Rh) for pharmaceuticals. - Highlights: • Solid sampling HR CS GFAAS permits the fast and direct determination of Pd, Pt and Rh. • 2 determinations suffice for the 3 elements (2 of them can be measured simultaneously). • Samples as different as car catalysts and pharmaceuticals can be accurately analyzed. • Aqueous standards (pharmaceuticals) or a solid CRM (catalysts) is used for calibration. • 6–9 μg g−1 (catalysts) and 0.1–0

  16. Rapid Detection of Active Pharmaceutical Ingredients in Weak Active Pharmaceutical Ingredient Signal Drugs by Paper Substrate-Surface Enhanced Raman Scattering Spectrometry%纸基-表面增强拉曼光谱法快速检测弱主药信号药品中的主药成分

    李晓; 陈梦云; 王磊; 张倩倩; 方芳; 苗丽; 陆峰

    2015-01-01

    A rapid detection method of active pharmaceutical ingredients( API) in weak API signal drugs by surface enhanced Raman scattering ( SERS) technology combined with paper substrate was established in this work. By soaking the filter paper in silver nanoparticles solution ( Ag NPs) to synthesize Ag NPs-paper as the substrate, and then the sample solution was dropping on the substrate with SERS detection. On the basis of strengthen ability of Ag NPs-paper, result of SERS detection and optimal preparation conditions, the fast identification method of weak API signal drugs was established. In this case, the SERS spectra of weak API signal drugs and their standards SERS spectra were obtained, where the correlation coefficient of weak API signal drug SERS spectra and its standard was more than 0. 9. The result showed that by this method, the low content API in weak API signal drugs could be well investigated, and the deficiencies of the normal Raman spectroscopy efficiently was also overcome. In conclusion, the synthesize method of Ag NPs-paper was simple, and the strengthen effect of this Ag NPs-paper on the intensity was obviously observed. Paper substrate-SERS method was simple, rapid and sensitive, and could be used to detect weak API signal drugs, presenting broad application prospects in the rapid detection of weak API signal drugs.%建立了弱主药信号药品中主药成分的纸基-表面增强拉曼光谱( SERS)快速检测方法。采用浸泡法制备纳米银溶胶滤纸SERS基底(简称银胶纸),将待检样品滴加于银胶纸上进行SERS检测。通过考察银胶纸制备条件、银胶纸增强能力、SERS检测结果,建立用于弱主药信号药品中主药成分的快速检测方法。通过本方法获得弱主药信号药品中主药成分的SERS图谱,与其对应标准品图谱的相关系数大于0.9,较好地检测出弱主药信号药品中的主药成分,有效克服了常规拉曼光谱分析的不足之处。新型银胶纸制备简

  17. Determination of palladium, platinum and rhodium in used automobile catalysts and active pharmaceutical ingredients using high-resolution continuum source graphite furnace atomic absorption spectrometry and direct solid sample analysis

    Resano, Martín; Flórez, María del Rosario; Queralt, Ignasi; Marguí, Eva

    2015-03-01

    This work investigates the potential of high-resolution continuum source graphite furnace atomic absorption spectrometry for the direct determination of Pd, Pt and Rh in two samples of very different nature. While analysis of active pharmaceutical ingredients is straightforward and it is feasible to minimize matrix effects, to the point that calibration can be carried out against aqueous standard solutions, the analysis of used automobile catalysts is more challenging requiring the addition of a chemical modifier (NH4F·HF) to help in releasing the analytes, a more vigorous temperature program and the use of a solid standard (CRM ERM®-EB504) for calibration. However, in both cases it was possible to obtain accurate results and precision values typically better than 10% RSD in a fast and simple way, while only two determinations are needed for the three analytes, since Pt and Rh can be simultaneously monitored in both types of samples. Overall, the methods proposed seem suited for the determination of these analytes in such types of samples, offering a greener and faster alternative that circumvents the traditional problems associated with sample digestion, requiring a small amount of sample only (0.05 mg per replicate for catalysts, and a few milligrams for the pharmaceuticals) and providing sufficient sensitivity to easily comply with regulations. The LODs achieved were 6.5 μg g- 1 (Pd), 8.3 μg g- 1 (Pt) and 9.3 μg g- 1 (Rh) for catalysts, which decreased to 0.08 μg g- 1 (Pd), 0.15 μg g- 1 (Pt) and 0.10 μg g- 1 (Rh) for pharmaceuticals.

  18. 阿莫西林原料药中有关物质的UPLC-TOF-MS/MS鉴定%Identification of related substances in amoxicillin active pharmaceutical ingredients by UPLC-TOF-MS/MS

    雷勇胜; 宋丽明; 郝英魁; 王云; 李瑜; 蒋庆峰

    2015-01-01

    目的:快速鉴定阿莫西林原料药中的有关物质。方法采用UPLC-TOF-MS/MS法测定。Waters Acquity UPLCTM BEH色谱柱(100 mm×2.1 mm,1.7μm);流动相为乙酸铵体系;体积流量0.5 mL/min;检测波长254 nm;柱温30℃;进样量10μL。电喷雾电离源;正离子检测;毛细管电压3.0 kV;离子源温度120℃;雾化气温度500℃;雾化气体积流量700 L/h;锥孔气体积流量50 L/h。结果推测了阿莫西林原料药中6个杂质的化学结构及其裂解规律,同时与欧洲药典中的杂质进行了比对归属。结论建立的UPLC-TOF-MS/MS的方法和实验数据可为阿莫西林原料药的质量控制提供了重要依据。%Objective To establish a rapid identification method for related substances in amoxicillin active pharmaceutical ingredients. Methods UPLC-TOF-MS/MS method was used. HPLC was carried out on Waters Acquity UPLCTM BEH column (100 mm × 2.1 mm, 1.7μm) with ammonium acetate solution as mobile phase. The detection wavelength was 254 nm and injection volume was 10μL at the flow rate of 0.5 mL/min. The column temperature was set for 30℃. MS conditions were that a mass spectrometry equipped with electrospray ionization (ESI) (+) source for detection. Capillary voltage was 3.0 kV, and source temperature was 120℃. The desolvation temperature and flow rate of desolvation gas were 500℃ and 700 L/h. The flow rate of cone gas was 50 L/h. Results The structures and fragmentation regularities of six related substances in amoxicillin were elucidated according to their MS characteristics. At the same time, related substances were compared to the impurities from European Pharmacopoeia. Conclusion UPLC-TOF-MS/MS method and results can establish a basis for quality control and stability study of amoxicillin active pharmaceutical ingredients.

  19. Sterilization of pharmaceutical ingredients, adjuvants and packaging materials by gamma radiation

    Different antibiotics, pharmaceutical ingredients, adjuvants and packaging materials were treated with gamma radiation of 0.5-2.8x106 rad using 60Co source. The effect of 2.5-2.8x106 rad on antibiotics, carbohydrates, citiric acid is a discoloration in some degree. The change of colour was accompanied by a decrease of activity of oxytetracycline hydrochloride and tobramycin sulphate, a decrease of viscosity of starch, and an increase of the reducing rate of saccharose and lactose. The sterility of substances contaminated by 103 organisms per gram was obtained by a dose of 0.5x106 rad. There was no discoloration and no changes were observed in the examined parameter of these materials. The examined aluminium, rubber and plastic packaging materials suffered no changes. (author)

  20. PTSD: A Search for "Active Ingredients."

    Huber, Charles H.

    1997-01-01

    Family counselors working with individuals suffering the effects of trauma are encouraged to consider the "active ingredients" found by Charles Figley and Joyce Carbonell at Florida State University and reported in the two articles reviewed. (Author/MKA)

  1. STABILITY TESTING OF ACTIVE PHARMACEUTICAL INGREDIENT [API

    Agarwal Vipul

    2012-04-01

    Full Text Available Stability plays an important role in drug development process. It explains several factors that affect the quality of a drug substance or drug products varies with time under the influence of environmental factors such as temperature, humidity and light. Stability studies play a vital role to decide the re-test period and shelf life for the drug substance and recommended storage conditions of API. ICH and EMEA guidelines define stability data package for new drug substance or drug product that is sufficient for a registration application within the three regions of the EC, Japan and United States.

  2. Separation of Chiral Active Pharmaceutical Ingredients

    Chaaban, Joussef Hussein

    simulations were found to be in good agreement with the experimental data. The sensitivity analysis conducted suggests that the separation process can be improved by increasing the mean residence time of the liquid phase in the crystallizers, the crystallization temperature, and the mass of seeds supplied...... system of the amino acid asparagine monohydrate by crystal growth of seed crystals. The achievement of a racemic liquid phase composition consisting of nearly equal distribution of enantiomers in solution was also investigated. Finally, the performance of the CC-PC process and its potential for further...... products were influenced by the morphological differences in the seed crystals. Due to irregularly shaped seed crystals of L-asparagine mnohydrate (L-AsnH2O), increase in the productivities and yields were achieved in the L-Tank, i.e. the crystallizer in which L-AsnH2O crystals grow. Lower purities of...

  3. 21 CFR 341.12 - Antihistamine active ingredients.

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Antihistamine active ingredients. 341.12 Section 341.12 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...-COUNTER HUMAN USE Active Ingredients § 341.12 Antihistamine active ingredients. The active ingredient...

  4. The search for compounds that stimulate thermogenesis in obesity management: from pharmaceuticals to functional food ingredients

    Dulloo, Abdull G.

    2012-01-01

    The concept of managing obesity through the stimulation of thermogenesis is currently a focus of considerable attention by the pharmaceutical, nutraceutical and functional food industries. This paper first reviews the landmark discoveries that have fuelled the search for thermogenic anti-obesity products that range from single-target drugs to multi-target functional foods. It subsequently analyses the thermogenic and fat-oxidizing potentials of a wide array of bioactive food ingredients which...

  5. Research Progression of Anti-HIV Chinese Medicines and Their Natural Active Ingredients

    Jing Chen; Linchun Fu; Maoqing Li; Jiantao Chen

    2014-01-01

    Objective: To review the research progression of Chinese medicines for anti-human immunodeficiency virus (HIV) and their natural active ingredients at home and abroad so as to provide references for pharmaceutical research and clinical medication. Methods: Abundant representative literatures at home and abroad were classified to introduce the anti-HIV monomers, compounds and natural active ingredients of Chinese medicines. Results: The researches on anti-HIV natural medicines have obtained gr...

  6. Bioequivalence of Eslicarbazepine Acetate from Two Different Sources of its Active Product Ingredient in Healthy Subjects

    Falcão, Amílcar; Lima, Ricardo; Sousa, Rui; Nunes, Teresa; Soares-da-Silva, Patrício

    2013-01-01

    Purpose To compare the bioavailability (BA) and pharmacokinetic (PK) properties and to demonstrate the bioequivalence (BE) between two active product ingredient (API) sources of eslicarbazepine acetate (ESL) in healthy volunteers. Design, subjects and methods Forty healthy male and female subjects aged 18–40 years were randomized to treatment with 400 or 800 mg ESL marketed (MF) formulation [current active pharmaceutical ingredient (API) source] and 400 or 800 mg ESL to-be-marketed (TBM) form...

  7. Radiation sensitivity of fungal microflora isolated from some pharmaceutical ingredients

    The total number of fungal microflora of D-glucose, NaCl, KCl and their solutions was determined. The fungal isolates were identified as Aspergillus fumigatus. Aspergillus niger; Spicaria divaricate and Spicaria silvatica and their response to γ-radiation was determined, the most predominant isolate Asp. fumigatus was also the most irradiation resistant. The Dio and the lethal dose were determined for each isolate in a pure spore suspension as well as in the presence of the other isolates. The higher lethal dose values obtained for pure spore suspension as compared to that obtained for the natural fungal flora a D-glucose are discussed in terms of spore clumping. The activity of amylase, protease and L-asparaginase of Asp. fumigatus was examined prior to and after exposure to different doses of γ-radiation. Though all were inhibited at high doses, the effect was not as drastic as it was on cell viability

  8. Identification of uniformity in Pravastatin Sodium Tablets and crystallographic form in their active pharmaceutical ingredient by NIRS method%近红外光谱法鉴别普伐他汀钠片及其原料药晶型的一致性研究

    耿颖; 程奇蕾; 何兰

    2014-01-01

    目的:建立全覆盖抽样的普伐他汀钠片的近红外光谱法一致性检验模型,考察制剂工艺的差别和原料药晶型的差异,通过稳健、准确、代表性强的近红外光谱一致性模型实现普伐他汀钠片的快速检验和筛查。方法对评价性抽验抽取的5个企业中的4个共65批样品建立普伐他汀钠片近红外一致性检验模型,并对4个厂家的原料药的近红外光谱图进行比较。结果建立了4个厂家普伐他汀钠片剂的近红外一致性模型,预测成功率均为100%;4种原料药和1种无定型粉末的近红外光谱图显示不同晶型光谱图具有差异。结论近红外光谱法能够用于快速鉴别质量工艺稳定的普伐他汀钠片产品,对制剂工艺进行考察,并能够区分不同晶型的原料药。%Objective To develop near-infrared spectroscopy (NIRS) uniformity models for sampling of Pravastatin Sodium Tablets from overall manufactures in Chinese market, to evaluate the uniformity of Pravastatin Sodium Tablets and their active pharmaceutical ingredients, and provide robust, accurate, and representative uniformity models. Methods NIRS models for 65 batches of tablets were built for four individual manufactures from five manufactures. The active pharmaceutical ingredients form the four manufactures and an amorphous powder were investigated by comparing NIR spectrum. Results Uniformity Models for the four different manufactures were built with prediction rate 100%, respectively. The spectra of four active pharmaceutical ingredients and an amorphous powder showed differences in various crystallographic forms of NIRS. Conclusion It demonstrates the potential of NIRS being a rapid and highly effective method for the identification of Pravastatin Sodium Tablats, the investigation of their preparation process, and the discrimination of the active pharmaceutical ingredients from their various crystallographic forms.

  9. Expanding the analytical toolbox for identity testing of pharmaceutical ingredients: Spectroscopic screening of dextrose using portable Raman and near infrared spectrometers.

    Srivastava, Hirsch K; Wolfgang, Steven; Rodriguez, Jason D

    2016-03-31

    In the pharmaceutical industry, dextrose is used as an active ingredient in parenteral solutions and as an inactive ingredient (excipient) in tablets and capsules. In order to address the need for more sophisticated analytical techniques, we report our efforts to develop enhanced identification methods to screen pharmaceutical ingredients at risk for adulteration or substitution using field-deployable spectroscopic screening. In this paper, we report our results for a study designed to evaluate the performance of field-deployable Raman and near infrared (NIR) methods to identify dextrose samples. We report a comparison of the sensitivity of the spectroscopic screening methods against current compendial identification tests that rely largely on a colorimetric assay. Our findings indicate that NIR and Raman spectroscopy are both able to distinguish dextrose by hydration state and from other sugar substitutes with 100% accuracy for all methods tested including spectral correlation based library methods, principal component analysis and classification methods. PMID:26965331

  10. 21 CFR 333.310 - Acne active ingredients.

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Acne active ingredients. 333.310 Section 333.310... FOR HUMAN USE TOPICAL ANTIMICROBIAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Topical Acne Drug Products § 333.310 Acne active ingredients. The active ingredient of the product consists of any of...

  11. 21 CFR 333.210 - Antifungal active ingredients.

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Antifungal active ingredients. 333.210 Section 333.210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Antifungal Drug Products § 333.210 Antifungal active ingredients. The active ingredient of the...

  12. 21 CFR 344.12 - Ear drying aid active ingredient.

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Ear drying aid active ingredient. 344.12 Section 344.12 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED....12 Ear drying aid active ingredient. The active ingredient of the product consists of...

  13. Simple and direct determination of active ingredients in drugs by neutron activation analysis

    The increasing number of drugs in the market and the need for their control requires new, simple, fast and accurate analytical methods. Iodine, iron, manganese, silver and sodium were determined by INAA in various pharmaceutical formulations, representing capsules, injectables, powders for injection, solutions and tablets. From the results it appears that NAA could be used as an official method for the determination of iron, manganese and silver in pharmaceutical products, in which these elements are present as active ingredients, as well as for the control of the concentration limits for iodine and sodium. (author)

  14. NOVEL HYDROXAMIC ACIDS HAVING HISTONE DEACETYLASE INHIBITING ACTIVITY AND ANTI-CANCER COMPOSITION COMPRISING THE SAME AS AN ACTIVE INGREDIENT

    2013-01-01

    The present invention relates to a pharmaceutical composition for anticancer including novel hydroxamic acid with histone deacetylase inhibiting activity as an active ingredient. Hydroxamic acid compound of the present invention has inhibitory activity of histone deacetylase (HDAC) and shows...... cytotoxicity to a variety of cancer cells, being useful in strong anti-cancer drug....

  15. Active ingredients against human epidermal aging.

    Lorencini, Márcio; Brohem, Carla A; Dieamant, Gustavo C; Zanchin, Nilson I T; Maibach, Howard I

    2014-05-01

    The decisive role of the epidermis in maintaining body homeostasis prompted studies to evaluate the changes in epidermal structure and functionality over the lifetime. This development, along with the identification of molecular mechanisms of epidermal signaling, maintenance, and differentiation, points to a need for new therapeutic alternatives to treat and prevent skin aging. In addition to recovering age- and sun-compromised functions, proper treatment of the epidermis has important esthetic implications. This study reviews active ingredients capable of counteracting symptoms of epidermal aging, organized according to the regulation of specific age-affected epidermal functions: (1) several compounds, other than retinoids and derivatives, act on the proliferation and differentiation of keratinocytes, supporting the protective barrier against mechanical and chemical insults; (2) natural lipidic compounds, as well as glycerol and urea, are described as agents for maintaining water-ion balance; (3) regulation of immunological pathogen defense can be reinforced by natural extracts and compounds, such as resveratrol; and (4) antioxidant exogenous sources enriched with flavonoids and vitamin C, for example, improve solar radiation protection and epidermal antioxidant activity. The main objective is to provide a functional classification of active ingredients as regulatory elements of epidermal homeostasis, with potential cosmetic and/or dermatological applications. PMID:24675046

  16. Polyphenols as active ingredients for cosmetic products.

    Zillich, O V; Schweiggert-Weisz, U; Eisner, P; Kerscher, M

    2015-10-01

    Polyphenols are secondary plant metabolites with antioxidant, anti-inflammatory and anti-microbial activity. They are ubiquitously distributed in the plant kingdom; high amounts contain, for example, green tea and grape seeds. Polyphenolic extracts are attractive ingredients for cosmetics and pharmacy due to their beneficial biological properties. This review summarizes the effects of polyphenols in the context of anti-ageing activity. We have explored in vitro studies, which investigate antioxidant activity, inhibition of dermal proteases and photoprotective activity, mostly studied using dermal fibroblasts or epidermal keratinocytes cell lines. Possible negative effects of polyphenols were also discussed. Further, some physicochemical aspects, namely the possible interactions with emulsifiers and the influence of the cosmetic formulation on the skin delivery, were reported. Finally, few clinical studies, which cover the anti-ageing action of polyphenols on the skin after topical application, were reviewed. PMID:25712493

  17. Plant Cell Cultures as Source of Cosmetic Active Ingredients

    Ani Barbulova

    2014-04-01

    Full Text Available The last decades witnessed a great demand of natural remedies. As a result, medicinal plants have been increasingly cultivated on a commercial scale, but the yield, the productive quality and the safety have not always been satisfactory. Plant cell cultures provide useful alternatives for the production of active ingredients for biomedical and cosmetic uses, since they represent standardized, contaminant-free and biosustainable systems, which allow the production of desired compounds on an industrial scale. Moreover, thanks to their totipotency, plant cells grown as liquid suspension cultures can be used as “biofactories” for the production of commercially interesting secondary metabolites, which are in many cases synthesized in low amounts in plant tissues and differentially distributed in the plant organs, such as roots, leaves, flowers or fruits. Although it is very widespread in the pharmaceutical industry, plant cell culture technology is not yet very common in the cosmetic field. The aim of the present review is to focus on the successful research accomplishments in the development of plant cell cultures for the production of active ingredients for cosmetic applications.

  18. Tests Comparing of Benzylpenicillin Potassium Industry Salt and Benzylpenicillin Potassium Active Pharmaceutical Ingredient by Methods in Chinese Veterinary Pharmacopoeia%利用兽药典方法对青霉素钾工业盐和原料药的检测比较

    徐嫄; 于丽娜; 韩宁宁; 龚旭昊; 王静文; 郝利华; 赵晖

    2016-01-01

    In order to distinguish between benzylpenicillin potassium industry salt and benzylpenicillin potassium active pharmaceutical ingredient,4 bathes of industry salt samples and 4 bathes of active pharmaceutical ingredient samples offered by 4 different veterinary drug manufacturers respectively were identified according to quality standards in Chinese Veterinary Pharmacopoeia 2010 version.Results of those 8 batches of samples were all in compliance with the standards,however,finding no distinguish differences between industry salt and active pharmaceutical ingredient,which might indicate that quality standard of benzylpenicillin potassium need to be improved in order to enhance quality control of the finished drug -benzylpeninicillin potassium for injection.%为了辨别青霉素钾工业盐和青霉素钾原料药,依据《中国兽药典》中青霉素钾的质量标准,对四家青霉素原料药生产企业提供的4批青霉素钾工业盐和4批青霉素钾原料药进行了检测,项目包括性状、鉴别、吸光度、结晶性、溶液澄清度与颜色、青霉素聚合物、干燥失重、不溶性微粒、酸碱度、有关物质、细菌内毒素、可见异物、无菌和含量测定。结果表明,8批样品均符合现行兽药典青霉素钾标准中各项规定,但结果无法用以区分青霉素钾工业盐和青霉素钾原料药,提示青霉素钾的质量标准需进一步完善,以提高对成品药———注射用青霉素钾的质量控制。

  19. Registro de insumos farmacêuticos ativos: impactos e reflexos sobre as indústrias farmoquímica e farmacêutica instaladas no Brasil | Registration of active pharmaceutical Ingredients: impacts and repercussions on the pharmochemical and pharmaceutical industries in Brazil

    Diva Barrio Arrepia

    2015-05-01

    Full Text Available O presente estudo teve por objetivo investigar e avaliar a potencial contribuição que a obrigatoriedade do registro de Insumos Farmacêuticos Ativos (IFAs teve no estabelecimento da isonomia regulatória entre o fabricante de IFA no Brasil e o fabricante internacional e a efetividade que essa isonomia teve no restabelecimento da produção local desses produtos. A pesquisa levou à identificação dos registros dos 20 IFAs, definidos como prioritários pela Agência Nacional de Vigilância Sanitária (ANVISA, no período 2010-2012. A metodologia utilizada compreendeu o levantamento de dados de bases nacionais e internacionais, públicas e privadas, que possibilitaram a construção de tabelas e gráficos, levando às informações da pesquisa. Os resultados demonstraram que o registro do IFA é um importante instrumento de política pública na obtenção da isonomia regulatória. Porém, o tempo de análise não foi suficientemente longo para assegurar que a mesma, associada a outras ações do governo para o incentivo à produção local de IFAs, tenha sido capaz de promover o aumento da fabricação desses produtos, apesar de haver sinalizações de que isso acontecerá. ------------------------------------------------------------------------------------------ The aim of the study was to investigate the potential contribution that the obligatory registration of active pharmaceutical ingredients (APIs had on the establishment of regulatory isonomy between API producers in Brazil and international producers. In addition, this study aimed to evaluate the effect of this isonomy on the re-establishment of local production. The investigation identified the registration of 20 APIs, defined as priorities by the Brazilian National Agency for the Sanitary Surveillance (ANVISA, in the period 2010–2012. The methodology used included the collection of data from national and international, public and private, databases that allowed the construction of

  20. 21 CFR 333.110 - First aid antibiotic active ingredients.

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false First aid antibiotic active ingredients. 333.110... (CONTINUED) DRUGS FOR HUMAN USE TOPICAL ANTIMICROBIAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE First Aid Antibiotic Drug Products § 333.110 First aid antibiotic active ingredients. The product consists of any...

  1. 21 CFR 338.10 - Nighttime sleep-aid active ingredients.

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Nighttime sleep-aid active ingredients. 338.10... (CONTINUED) DRUGS FOR HUMAN USE NIGHTTIME SLEEP-AID DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 338.10 Nighttime sleep-aid active ingredients. The active ingredient of the product consists...

  2. Studies of Active Ingredients in Cough Syrup by Capillary Zone Electrophoresis with Amperometric Detection

    ZHOU Tian-shu; WANG Ai-fang; WU Fang; SHI Guo-yue; FANG Yu-zhi

    2003-01-01

    The present paper covers a simple, reliable and reproducible method, based on capillary zone electrophoresis(CZE) with amperometric detection(AD), for the separation and the determination of ephedrine hydrochloride, promethazine hydrochloride and codeine phosphate. Under the optimal conditions, the three analytes were base-line separated completely within 16 min. Good linear relationships between the peak heights and the concentrations of the three analytes were obtained with the correlation coefficients better than 0.9993. The method was directly applied to the determination of the active ingredients in pharmaceutical preparations and the assay results were satisfactory.

  3. 77 FR 60124 - Draft Guidance for Industry on Initial Completeness Assessments for Type II Active Pharmaceutical...

    2012-10-02

    ...The Food and Drug Administration (FDA or the Agency) is announcing the availability of a draft guidance for industry entitled ``Initial Completeness Assessments for Type II API DMFs Under GDUFA.'' Under the Generic Drug User Fee Amendments of 2012 (GDUFA), holders of certain drug master files, namely, Type II active pharmaceutical ingredient (API) drug master files (DMFs) that are referenced......

  4. 21 CFR 358.110 - Wart remover active ingredients.

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Wart remover active ingredients. 358.110 Section 358.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... collodion-like vehicle. (c) Salicylic acid 15 percent in a karaya gum, glycol plaster vehicle....

  5. Synthesis of cinacalcet: an enantiopure active pharmaceutical ingredient (API)

    Barniol-Xicota, Marta; Leiva Martínez, Rosana; Escolano Mirón, Carmen; Vázquez Cruz, Santiago

    2016-01-01

    Cinacalcet hydrochloride is the only approved drug acting as calcimimetic, a new class of compds. used in the therapy of secondary hyperparathyroidism and parathyroid carcinoma. Several generic drug manufacturers and research groups from academia have reported alternative approaches to this mol., mainly from (R)​-​(+)​-​1-​(1-​naphthyl)​ethylamine. There are mainly three strategies that have been used to couple this readily accessible enantiopure amine to the other part of the mol.: amide for...

  6. NMR crystallography of active pharmaceuticals ingredients for industrial applications

    Urbanová, Martina; Brus, Jiří; Kobera, Libor

    Herceg Novi : Materials Research Society, 2008. s. 165. [Annual Conference YUCOMAT 2008 /10./. 08.09.2008-12.09.2008, Herceg Novi] R&D Projects: GA MŠk 2B08021 Institutional research plan: CEZ:AV0Z40500505 Keywords : MAS NMR * atorvastatin * NMR crystallography Subject RIV: CF - Physical ; Theoretical Chemistry

  7. Solubility Prediction of Active Pharmaceutical Compounds with the UNIFAC Model

    Nouar, Abderrahim; Benmessaoud, Ibtissem; Koutchoukali, Ouahiba; Koutchoukali, Mohamed Salah

    2016-03-01

    The crystallization from solution of an active pharmaceutical ingredient requires the knowledge of the solubility in the entire temperature range investigated during the process. However, during the development of a new active ingredient, these data are missing. Its experimental determination is possible, but tedious. UNIFAC Group contribution method Fredenslund et al. (Vapor-liquid equilibria using UNIFAC: a group contribution method, 1977; AIChE J 21:1086, 1975) can be used to predict this physical property. Several modifications on this model have been proposed since its development in 1977, modified UNIFAC of Dortmund Weidlich et al. (Ind Eng Chem Res 26:1372, 1987), Gmehling et al. (Ind Eng Chem Res 32:178, 1993), Pharma-modified UNIFAC Diedrichs et al. (Evaluation und Erweiterung thermodynamischer Modelle zur Vorhersage von Wirkstofflöslichkeiten, PhD Thesis, 2010), KT-UNIFAC Kang et al. (Ind Eng Chem Res 41:3260, 2002), ldots In this study, we used UNIFAC model by considering the linear temperature dependence of interaction parameters as in Pharma-modified UNIFAC and structural groups as defined by KT-UNIFAC first-order model. More than 100 binary datasets were involved in the estimation of interaction parameters. These new parameters were then used to calculate activity coefficient and solubility of some molecules in various solvents at different temperatures. The model gives better results than those from the original UNIFAC and shows good agreement between the experimental solubility and the calculated one.

  8. Evaluation of P-Listed Pharmaceutical Residues in Empty Pharmaceutical Containers

    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...

  9. Lithium carbonate tablets. Preparation techniques influence over active ingredient liberation

    Lithium carbonate tablets, prepared using wet and dry granulation, were assessed in vitro so as to determine the active ingredient dissolution. In this study, standardized formulations were used and developed with usual adjuvants (lactose - maize starch). Parallel to the dissolution testing. The influence of the preparation process over some physical characteristics (hardness, friability and disintegration) was also analysed. Although a better performance was observed of tables prepared using dry granulation, the authors concluded that the wet process is more suitable in preparing tables with the mentioned drug. (author)

  10. Development and validation of stability indicating UPLC assay method for ziprasidone active pharma ingredient

    Sonam Mittal

    2012-01-01

    Full Text Available Background: Ziprasidone, a novel antipsychotic, exhibits a potent highly selective antagonistic activity on D2 and 5HT2A receptors. Literature survey for ziprasidone revealed several analytical methods based on different techniques but no UPLC method has been reported so far. Aim: Aim of this research paper is to present a simple and rapid stability indicating isocratic, ultra performance liquid chromatographic (UPLC method which was developed and validated for the determination of ziprasidone active pharmaceutical ingredient. Forced degradation studies of ziprasidone were studied under acid, base, oxidative hydrolysis, thermal stress and photo stress conditions. Materials and Methods: The quantitative determination of ziprasidone drug was performed on a Supelco analytical column (100×2.1 mm i.d., 2.7 ΅m with 10 mM ammonium acetate buffer (pH: 6.7 and acetonitrile (ACN as mobile phase with the ratio (55:45-Buffer:ACN at a flow rate of 0.35 ml/ min. For UPLC method, UV detection was made at 318 nm and the run time was 3 min. Developed UPLC method was validated as per ICH guidelines. Results and Conclusion: Mild degradation of the drug substance was observed during oxidative hydrolysis and considerable degradation observed during basic hydrolysis. During method validation, parameters such as precision, linearity, ruggedness, stability, robustness, and specificity were evaluated, which remained within acceptable limits. Developed UPLC method was successfully applied for evaluating assay of Ziprasidone active Pharma ingredient.

  11. Wisdom Pharmaceutical Co., Ltd.

    2003-01-01

    @@ Wisdom Pharmaceutical Co., Ltd. (Wisdom) headquartered in Haimen, Nantong, Jiangsu Province, China, is specialized in providing highly efficient production processes of active pharmaceutical ingredients (API) and intermediates. Currently, Wisdom is in the process of expanding GMP (Good Manufacturing Practice) capabilities, which is expected to be approved by the authorities before the end of September 2003.

  12. Validation of an assessment tool for evaluating the implementation of WHO GMP standards by Chinese manufacturers of active pharmaceutical ingredients (APIs)%我国原料药生产企业执行WHO GMP的评估工具验证

    黄宝斌; 孙新生; 许明哲; 白东亭; 武志昂; 吴春福

    2015-01-01

    目的:为客观评估我国活性原料药(active pharmaceutical ingredients,APIs)生产企业执行WHO GMP中的能力和现状,对评估工具进行验证,考察工具的信度(可靠性)和效度(准确性).方法:根据设定标准,筛选国内3家APIs生产企业和9名GMP专家参与验证.对于每家企业,先后应用评估工具进行自我评价和GMP专家独立评估,比较3种(严重、主要和次要)缺陷差异,考察信度.对参与评估的GMP专家进行问卷调查和访谈,评价工具对WHO GMP标准覆盖的全面性和代表性,考察效度.收集和整理企业和专家对于评估工具改进建议.结果:企业自评和专家独立评估结果均显示,3家企业均无“严重”缺陷项.在自评中,企业A,B,C的“主要”和“次要”缺陷项数量分别是(2;9),(22;36),(3;8);在独立评估中,企业A,B,C的“主要”和“次要”缺陷分别是(3;12),(26;41),(4;9).经统计学分析,企业自评和专家独立评估结果之间没有显著差异.专家访谈显示,9名专家均认为评估工具覆盖性良好,除4名专家认为4个评估指标有重复外,其余5名专家均认为代表性良好.企业和专家提出建议,对于指标重复、规定过细、缺乏操作性的情况进行改进.结论:经适宜企业和专家参与验证,认为该评估工具具有良好的信度和效度,能够测评我国APIs企业执行WHO GMP标准的差距和进度,在进行适当调整和完善后,可以在国内推广使用.

  13. Risks to aquatic organisms posed by human pharmaceutical use

    In order to help prioritize future research efforts within the US, risks associated with exposure to human prescription pharmaceutical residues in wastewater were estimated from marketing and pharmacological data. Masses of 371 active pharmaceutical ingredients (APIs) dispensed ...

  14. Aloe vera: a valuable ingredient for the food, pharmaceutical and cosmetic industries--a review.

    Eshun, Kojo; He, Qian

    2004-01-01

    Scientific investigations on Aloe vera have gained more attention over the last several decades due to its reputable medicinal properties. Some publications have appeared in reputable Scientific Journals that have made appreciable contributions to the discovery of the functions and utilizations of Aloe--"nature's gift." Chemical analysis reveals that Aloe vera contains various carbohydrate polymers, notably glucomannans, along with a range of other organic and inorganic components. Although many physiological properties of Aloe vera have been described, it still remains uncertain as to which of the component(s) is responsible for these physiological properties. Further research needs to be done to unravel the myth surrounding the biological activities and the functional properties of A. vera. Appropriate processing techniques should be employed during the stabilization of the gel in order to affect and extend its field of utilization. PMID:15116756

  15. 21 CFR 347.20 - Permitted combinations of active ingredients.

    2010-04-01

    ... ingredients to prepare an aluminum acetate solution. Aluminum sulfate tetradecahydrate may be combined with calcium acetate monohydrate in powder or tablet form to provide a 0.13 to 0.5 percent aluminum acetate..., antihistamines, or any permitted combination of these ingredients, but not with hydrocortisone, provided...

  16. Solid dosage forms comprising aliskiren and pharmaceutically acceptable salts thereof

    Škrabanja, Vida; Zajc, Natalija; Gojak, Urška; Vrečer, Franc

    2015-01-01

    The present invention relates to a pharmaceutical formulation comprising aliskiren or a pharmaceutically acceptable salt thereof as the active ingredient, wherein the pharmaceutical formulation is present in a solid dosage form suitable for oral administration based on a granulate obtained by a hot-melt and solvent-free granulation process, and to a process for manufacturing a pharmaceutical formulation.

  17. On the novel action of melanolysis by a leaf extract of Aloe vera and its active ingredient aloin, potent skin depigmenting agents.

    Ali, Sharique A; Galgut, Jyoti M; Choudhary, Ram K

    2012-05-01

    The present study was carried out to investigate the effects of an Aloe vera leaf extract, along with its standard active ingredient aloin, on the isolated tail melanophores of Bufo melanostictus tadpoles, which are a type of disguised smooth muscle cells offering excellent in vitro opportunities for studying the effects of pharmacological and pharmaceutical agents. It was found that the leaf extract of A. vera and its active ingredient aloin induced powerful, dose-dependent, physiologically significant melanin aggregating effects in the isolated tail melanophores of B. melanostictus similar to those of adrenaline per se. These preliminary findings clearly demonstrate that the extract of A. vera and its active ingredient aloin cause melanin aggregation leading to skin lightening via alpha adrenergic receptor stimulation. The present study opens new vistas for the use of A. vera regarding its clinical application as a new nontoxic melanolytic agent for the treatment of hyperpigmentation. PMID:22495441

  18. 21 CFR 341.14 - Antitussive active ingredients.

    2010-04-01

    ... and 21 CFR 1308.15(c). (i) Codeine. (ii) Codeine phosphate. (iii) Codeine sulfate. (3...) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR OVER-THE... established for each ingredient in § 341.74(d): (a) Oral antitussives. (1) Chlophedianol hydrochloride....

  19. Studies on Insecticidal Activities and Active Ingredients of Stephania kwangsiensis Lo.

    DENG Ye-cheng; XU Han-hong

    2005-01-01

    Insecticidal activities and active ingredients of Stephania kwangsiensis Lo. were studied for the first time. The results showed that all parts of S. kwangsiensis Lo. had contact activity against brown planthoppers, Nilaparvata lugens Stal,and the contact activity of methanol extract from root tubers was the highest, with a LD50 value being 1.5794 μg/female.l-roemerine was isolated from root tubers of S. kwangsiensis Lo. and identified, and it was the main active ingredient.l-roemerine had high contact toxicity to brown planthoppers, with a LD50 value being 0.0443 μg/female. Contact toxicity of l-roemerine to brown planthoppers was 7.48 times that of malathion, the convientional chemical insecticide used for controlling brown planthoppers.l-roemerine also had stomach poison activity against brown planthoppers.

  20. Internet as a Medium of Pharmaceutical Companies Promotional Activities

    Darko Pantelic

    2009-01-01

    Pharmaceuticals market is highly regulated, and it can be stated that prescription (legal or ethical) drugs have a status of substances in controlled circulation. Promotional activities are also under strict legislation, further burdened with ethical consideration and public scrutiny. Internet as liberal and hard to control medium brings entirely new sets of solutions and/or problems to pharmaceuticals market(ers).

  1. [Commercialization of results of intellectual activities in pharmaceutical industry].

    Posylkina, O V; Timaniuk, V N; Gladukh, E V

    2002-01-01

    An analysis has been done of those causes impending the development of innovative processes and commercialization of results of intellectual activities in the economics of Ukraine and its pharmaceutical sector. Possible ways for rectifying the prevailing situation are considered. A scheme is proposed of staged commercialization of developments involving creation of new pharmaceutical preparations. PMID:12669531

  2. Equivalence studies for complex active ingredients and dosage forms

    Bhattycharyya, Lokesh; Dabbah, Roger; Hauck, Walter; Sheinin, Eric; Yeoman, Lynn; Williams, Roger,

    2005-01-01

    This article examines the United States Pharmacopeia (USP) and its role in assessing the equivalence and inequivalence of biological and biotechnological drug substances and products—a role USP has played since its founding in 1820. A public monograph in theUnited States Pharmacopeia-National Formulary helps practitioners and other interested parties understand how an article’s strenght, quality, and purity should be controlled. Such a monograph is a standard to which all manufactured ingredi...

  3. Computer-aided tool for solvent selection in pharmaceutical processes: Solvent swap

    Papadakis, Emmanouil; K. Tula, Anjan; Gernaey, Krist V.;

    In the pharmaceutical processes, solvents have a multipurpose role since different solvents can be used in different stages (such as chemical reactions, separations and purification) in the multistage active pharmaceutical ingredients (APIs) production process. The solvent swap and selection tasks...

  4. Opinions expressed by Italian National Advisory Toxicological Committee on some active ingredients of pesticides

    Camoni, I. [Ist. Superiore di Sanita`, Rome (Italy). Lab. di Tossicologia Applicata

    1996-03-01

    The opinions expressed by the Italian National Advisory Toxicological Committee (CCTN) on some active ingredients of pesticides are presented. Carcinogenic and mutagenic effects of these substances have been examined and, on this basis, an evaluation and relative classification were expressed.

  5. Influence of environmental factors on the contents of active ingredients and radical scavenging property of potentilla fruticosa in the main production areas of China

    Extracts from Potentilla fruticosa have been applied in traditional medicine and exhibited antioxidant property, but little has been known about the diversity of phytochemicals and properties on this species from different growing environment. This study investigated the influence of environmental factors on the active ingredient contents and radical scavenging property of P. fruticosa from different production areas of China in order to discover a location could produce high-quality resources for pharmaceutical products. The contents of tannin, total flavonoids, and rutin were determined and varied within the range of 7.64 ± 0.43 ∼ 10.68 ± 0.67 percentage, 2.29 ± 0.34 ∼ 5.37 ± 0.36 percentage, and 0.19 ± 0.053 ∼ 0.79 ± 0.125 percentage, respectively. Radical scavenging property was quantified, with the IC /sub 50/ of 7.24 ± 0.423 to 17.23 ± 0.551 μ g mL-1. Principal component analysis, multiple linear stepwise regression analysis, and path analysis were conducted to further analysis the relationship between the variations of active ingredients and radical scavenging capacity and growth environment. The results showed dominant environmental factors for these variations were rapidly available nitrogen, rapidly available phosphorus, pH, July average temperature, and annual sunshine duration. Furthermore, a significant positive correlation was observed between pH, annual sunshine duration and active ingredients and radical scavenging property (p<0.05). Considering the high active ingredient contents and strong radical scavenging property, leaf extracts from P. fruticosa could become useful supplements for pharmaceutical products as a new antioxidant agent, and Huzhu Northern Mountain in Qinghai Province and E-mei Mountain in Sichuan Province were selected as favorable production locations. (author)

  6. Suspended biofilm carrier and activated sludge removal of acidic pharmaceuticals

    Falås, Per; Baillon-Dhumez, Aude; Andersen, Henrik Rasmus;

    2012-01-01

    Removal of seven active pharmaceutical substances (ibuprofen, ketoprofen, naproxen, diclofenac, clofibric acid, mefenamic acid, and gemfibrozil) was assessed by batch experiments, with suspended biofilm carriers and activated sludge from several full-scale wastewater treatment plants. A distinct...... difference between nitrifying activated sludge and suspended biofilm carrier removal of several pharmaceuticals was demonstrated. Biofilm carriers from full-scale nitrifying wastewater treatment plants, demonstrated considerably higher removal rates per unit biomass (i.e. suspended solids for the sludges and...... attached solids for the carriers) of diclofenac, ketoprofen, gemfibrozil, clofibric acid and mefenamic acid compared to the sludges. Among the target pharmaceuticals, only ibuprofen and naproxen showed similar removal rates per unit biomass for the sludges and biofilm carriers. In contrast to...

  7. Study on THz spectra of the active ingredients in the TCM

    Ma, ShiHua; Wang, WenFeng; Liu, GuiFeng; Ge, Min; Zhu, ZhiYong

    2008-03-01

    Terahertz spectroscopy has tremendous potential for applications to evaluate the quality of the drugs including the TCM. In this paper, the Terahertz Time-Domain Spectroscopy investigated two active ingredients: Andrographolide and Dehydroandrographoline, isolated from Andrographis paniculata (Burm. f.) Nees. We also measured the mixtures of two active ingredients at the different ratio and the quantitative analysis is also applied to determine the contents of compound. The Terahertz spectroscopy is a potential and promising technique in identifying the components, evaluating the drugs sanitation and inspecting the quality of medicine including TCM.

  8. Encapsulation of cosmetic active ingredients for topical application--a review.

    Casanova, Francisca; Santos, Lúcia

    2016-02-01

    Microencapsulation is finding increasing applications in cosmetics and personal care markets. This article provides an overall discussion on encapsulation of cosmetically active ingredients and encapsulation techniques for cosmetic and personal care products for topical applications. Some of the challenges are identified and critical aspects and future perspectives are addressed. Many cosmetics and personal care products contain biologically active substances that require encapsulation for increased stability of the active materials. The topical and transdermal delivery of active cosmetic ingredients requires effective, controlled and safe means of reaching the target site within the skin. Preservation of the active ingredients is also essential during formulation, storage and application of the final cosmetic product. Microencapsulation offers an ideal and unique carrier system for cosmetic active ingredients, as it has the potential to respond to all these requirements. The encapsulated agent can be released by several mechanisms, such as mechanical action, heat, diffusion, pH, biodegradation and dissolution. The selection of the encapsulation technique and shell material depends on the final application of the product, considering physical and chemical stability, concentration, required particle size, release mechanism and manufacturing costs. PMID:26612271

  9. ANTIMICROBIAL AND SYNERGISTIC ACTIVITY OF INGREDIENTS OF BETEL QUID ON ORAL AND ENTERIC PATHOGENS

    Niraj A Ghanwate

    2012-01-01

    Full Text Available In this study, antimicrobial and synergistic activity of ingredients of betel quid i.e. kattha, lime, betel leaf, betel nut, cardamom, clove and fennel seeds was tested against microbial population of oral cavity and four enteric pathogens namely Staphylococcus aureus, Salmonella typhi, Escherichia coli and Shigell flexneri. For this purpose two methods were used. Pour plate method was used for calculating the reduction in microbial population in oral cavity and disk diffusion method was used for detecting the effect of ingredients of betel quid on enteric pathogens. In the first method, microbial population of saliva before and after chewing above ingredients individually and in different combinations was compared. It was found that the each ingredient of betel quid separately and in different combination shows reduction in microbial population by different percentage. The highest percentage of reduction in microbial population was shown by the combination of betel leaf, lime and kattha (Blk followed by betel leaf, cardamom etc. In the second experiment it was found that the bacteria investigated showed most susceptibility against kattha followed by clove and then combination of betel leaf, lime and kattha. From the study it was concluded that chewing of betel quid after every meal reduces the population of oral micro flora which may be responsible for dental carries and bad breath. It was also seen that enteric pathogens like Staphylococcus aureus, Salmonella typhi, Escherichia coli and Shigell flexneri could be inhibited by ingredients of beetle quid.

  10. Nano-microdelivery systems for oromucosal delivery of an active ingredient

    2014-01-01

    A composition for oromucosal delivery of at least one active ingredient, more particularly a lipid nano-microdelivery system comprising a nicotine component and/or a flavour component, wherein the nicotine component may be delivered to the oral cavity via absorption through the mucosal membranes...... thereof and/or wherein the flavour component may be delivered to the oral mucosa by controlled release....

  11. How active ingredient localisation in plant tissues determines the targeted pest spectrum of different chemistries

    Buchholz, Anke; Trapp, Stefan

    2016-01-01

    information sets revealed that the intracellular localisation of active ingredients determines the performance of test compounds against different target pests because of different feeding behaviours: mites feed on mesophyll, and aphids and whiteflies mostly in the vascular system. Polar compounds have a slow...

  12. 21 CFR 358.710 - Active ingredients for the control of dandruff, seborrheic dermatitis, or psoriasis.

    2010-04-01

    ..., seborrheic dermatitis, or psoriasis. 358.710 Section 358.710 Food and Drugs FOOD AND DRUG ADMINISTRATION... Psoriasis § 358.710 Active ingredients for the control of dandruff, seborrheic dermatitis, or psoriasis. The... psoriasis. (1) Coal tar, 0.5 to 5 percent. When a coal tar solution, derivative, or fraction is used as...

  13. Potential metal impurities in active pharmaceutical substances and finished medicinal products - A market surveillance study.

    Wollein, Uwe; Bauer, Bettina; Habernegg, Renate; Schramek, Nicholas

    2015-09-18

    A market surveillance study has been established by using different atomic spectrometric methods for the determination of selected elemental impurities of particular interest, to gain an overview about the quality of presently marketed drug products and their bulk drug substances. The limit tests were carried out with respect to the existing EMA guideline on the specification limits for residuals of metal catalysts or metal reagents. Also attention was given to the future implementation of two new chapters of the United States Pharmacopoeia (USP) stating limit concentrations of elemental impurities. The methods used for determination of metal residues were inductively coupled plasma-mass spectrometry (ICP-MS), inductively coupled plasma-optical emission spectrometry (ICP-OES), and atomic absorption spectrometry technologies (GFAAS, CVAAS, HGAAS). This article presents the development and validation of the methods used for the determination of 21 selected metals in 113 samples from drug products and their active pharmaceutical ingredients. PMID:26036232

  14. INFLUENCE OF SELECTED PHARMACEUTICALS ON ACTIVATED SLUDGE DEHYDROGENASE ACTIVITY

    Agnieszka Tomska

    2016-01-01

    Due to the increasing consumption of pharmaceuticals for the treatment of humans and animals as well as inadequate procedures for the disposal of pharmaceuticals into environmental, pollution caused by them is increasing. Generally these substances are introduced to the wastewater treatment plant with municipal wastewater. They are often resistant to biodegradation and can cause to the disruption in biological wastewater treatment processes. Traditional water treatment plants are not designed...

  15. A simple and fast method for the determination of active ingredient in antiperspirant cosmetics by neutron activation analysis

    Antiperspirant cosmetics are tested for their active ingredient (aluminium chlorohydroxide) by conventional analytical techniques. Aluminium has been determined by instrumental neutron activation analysis in all antiperspirant products and package forms available in the Greek market in order to develop a simple and fast method for quantization. The results show that neutron activation analysis could be established as an official method for the determination of active ingredient in antiperspirant cosmetics. The proposed method is compared with the existing official methods and an alternative sampling method for aerosol package is presented. (author)

  16. ANTIMICROBIAL ACTIVITY OF WATER EXTRACTS OF TRIKATU CHURNA AND ITS INDIVIDUAL INGREDIENT

    P.R. Malvankar* and M. M. Abhyankar

    2012-04-01

    Full Text Available Trikatu churna is one of the traditional poly herbal preparation, formed by mixing equal quantities of three important spicy materials such as Piper longum L. (Piperaceae, Piper nigrum L. (Piperaceae and Zingiber officinale Roscoe (Zingiberaceae. Trikatu is also known as “ Three Bitters”. The trikatu preparation was reported to contain alkaloids, phenols, tannins, flavanoids, steroids, lignin & saponins. The objective of study is to evaluate the antimicrobial activity of trikatu churna & its individual ingredients with their preliminary phytochemical study. The aqueous extracts of trikatu churna & its each ingredient were tested for antimicrobial activity against certain bacterial strains of Escherichia coli, Staphylococcus aureus by in vitro agar well diffusion method and the results are recorded as the zone of inhibition. Trikatu churna was found to possess higher extent of phytoconstituents with promising antimicrobial activity.

  17. A slow-release system of bacterial cellulose gel and nanoparticles for hydrophobic active ingredients.

    Numata, Yukari; Mazzarino, Leticia; Borsali, Redouane

    2015-01-01

    A combination of bacterial cellulose (BC) gel and amphiphilic block copolymer nanoparticles was investigated as a drug delivery system (DDS) for hydrophobic active ingredients. Poly(ethylene oxide)-b-poly(caprolactone) (PEO-b-PCL) and retinol were used as the block copolymer and hydrophobic active ingredient, respectively. The BC gel was capable of incorporating copolymer nanoparticles and releasing them in an acetic acid-sodium acetate buffer solution (pH 5.2) at 37 °C. The percentage of released copolymer reached a maximum value of approximately 60% after 6h and remained constant after 24h. The percentage of retinol released from the copolymer-containing BC gel reached a maximum value at 4h. These results show that the combination of BC gel and nanoparticles is a slow-release system that may be useful in the cosmetic and biomedical fields for skin treatment and preparation. PMID:25840273

  18. An active ingredient of Cat's Claw water extracts identification and efficacy of quinic acid.

    Sheng, Yezhou; Akesson, Christina; Holmgren, Kristin; Bryngelsson, Carl; Giamapa, Vincent; Pero, Ronald W

    2005-01-15

    Historic medicinal practice has defined Cat's Claw, also known as Una de Gato or Uncaria tomentosa, as an effective treatment for several health disorders including chronic inflammation, gastrointestinal dysfunction such as ulcers, tumors and infections. The efficacy of Cat's Claw was originally believed, as early as the 1960s, to be due to the presence of oxindole alkaloids. However, more recently water-soluble Cat's Claw extracts were shown not to contain significant amounts of alkaloids (<0.05%), and yet still were shown to be very efficacious. Here we characterize the active ingredients of a water-soluble Cat's Claw extract called C-Med-100 as inhibiting cell growth without cell death thus providing enhanced opportunities for DNA repair, and the consequences thereof, such as immune stimulation, anti-inflammation and cancer prevention. The active ingredients were chemically defined as quinic acid esters and could also be shown to be bioactive in vivo as quinic acid. PMID:15619581

  19. In vitro effects of buyang huanwu decoction and its ingredients on inhibiting the specific binding of 3H-platelet activating factor to its receptor in rabbits

    2007-01-01

    BACKGROUND: Pharmacologic action of traditional Chinese medicine compound is the comprehensive effect of various ingredients, and the interactions of various ingredients are closely correlated with the final effect. In order to reveal the compatibility mechanism of buyang huanwu decoction (BHD)'s prescription in treating and preventing ischemic cerebrovascular disease, we need to explore the effect and relation of ingredients in prescription except for considering the effect of each ingredient on the whole prescription.OBJECTIVE: To study the effect of BHD and its ingredients in the prescription on the specific binding of 3H-platelet activating factor (PAF) to its receptor (PAFR)in rabbits in vitro, and to analyze the action of each ingredient in the prescription.DESIGN: A decomposed recipe study based on orthogonal test.SETTING: Guangzhou University of Traditional Chinese Medicine.MATERIALS: Five healthy adult New Zealand rabbits of either gender were provided by the Experimental Animal Center of Guangzhou University of Traditional Chinese medicine. The prescription herbal pieces were purchased from Foshan Kangpu Pharmaceuticals Company and Jianmin Pharmaceuticals Company, and were appraised by Professor Yanchen Xu from College of Traditional Chinese Medicine, Guangzhou University of Traditional Chinese Medicine. 3H-PAF was supplied by Amersham Co.,Ltd.(Specific activity:6.475 TBq/mmol;batch number:200402); PAF standard by Biomol Co., Ltd.(batch number: P1318V).METHODS: This experiment was carried out in the Laboratory of Nuclear Medicine, Guangzhou University of Traditional Chinese Medicine between September and December 2004. ① The seven influencing factors were selected: such as Shenghuangqi , Dangguiwei, Chishao, Dilong, Taoren, Honghua, Chuanxiong. Each factor was divided into two levels, selected or not selected. The tests were arranged according to L8 (27) orthogonal test table. ②The specific binding of 3H-PAF to its receptors in rabbits was measured by

  20. Validation of the quality control methods for active ingredients of Fungirex cream

    Fungirex cream is a two-drug product, that is, undecylenic acid and zinc undecylenate over a suitable basis. Since this is a product not documented in the official monographs of the pharmacopoeia, simple analytical methods were suggested for quantitation of analytes of interest in the cream, which are useful for release of newly prepared cream batches. To validate two volumetric methods for the quality control of active ingredients in Fungirex cream

  1. Comparison of Active Ingredient Content of Nanwuweizi and Beiwuweizi Collected in Different Seasons Detected by HPLC-DAD

    YAO Feng; CHEN Da-shuai

    2015-01-01

    Objective:To compare the active ingredient content of Nanwuweizi (Kadsura longepedunculata) and Beiwuweizi (Fructus Schisandrae Chinensis) collected in different seasons. Methods:Microwave-assisted extraction was applied to extract the active ingredients in Nanwuweizi and Beiwuweizi, with methanol as the solvent. High performance liquid chromatography-diode array detection (HPLC-DAD) method was used to analyze the content of each ingredient, with chromatographic conditions as follows: Brava BDS C18 column (250 mm×4.6 mm, 5 μm); column temperature: 30℃; mobile phase: water (A) - acetonitrile (B); gradient elution: 0.8 mL/min; and detection wavelength: 225 nm. Results:All ingredients waiting for detection reached their peaks within 75 min, with excellent degree of separation and higher number of theoretical plates. Standard curves were drawn, and the mean value of phase relationship of each ingredient was >0.999. The content of active ingredients in lignans of Nanwuweizi and Beiwuweizi showed tendency of increase ifrst and then decreased. In addition, all ingredients in Beiwuweizi reached their peaks in September while those in Nanwuweizi in August. Conclusion:This method can be used to detect the content of multiple ingredients in Wuweizi (Schisandra chinensis) simultaneously because it is simple in operation, precise in results and excellent in repeatability.

  2. New Trends in Cosmetics: By-Products of Plant Origin and Their Potential Use as Cosmetic Active Ingredients

    Ani Barbulova

    2015-04-01

    Full Text Available In recent years, the amount of waste deriving from industrial processes has increased substantially. Many industries produce different types of disposable by-products, rich in valuable compounds. Their characterization and valorization could not only convert them into high value products with application in diverse biotechnological fields, such as Pharmaceutics, Food or Cosmetics, but would also reduce the waste environmental impact and the related treatment costs. There are many examples of cosmetic active ingredients deriving from fish, meat and dairy products, but in the present review we would like to focus on the potentialities and the current use of compounds and extracts deriving from agronomical disposable wastes in the cosmetic field. These types of products are effective, inexpensive and bio-sustainable, and thus represent a valid alternative to the regular plant derived extracts, more commonly adopted in cosmetic formulations. Moreover, if the waste products come from organic farming, they are certainly an even more valuable source of safe extracts for Cosmetics, since they lack any residual pesticide or potentially toxic chemical.

  3. Solubilization of active ingredients of different polarity in Pluronic® micellar solutions - Correlations between solubilizate polarity and solubilization site.

    Nguyen-Kim, Viet; Prévost, Sylvain; Seidel, Karsten; Maier, Walter; Marguerre, Ann-Kathrin; Oetter, Günter; Tadros, Tharwat; Gradzielski, Michael

    2016-09-01

    The solubilization of two pharmaceutically active ingredients (AI) with significantly different water solubility, namely carbamazepine and fenofibrate (solubility of 150ppm and 10ppm, respectively), has been investigated using a series of Pluronics® (Poloxamers) containing different ethylene oxide and propylene oxide (EO/PO) units in the molecule. The results show largely enhanced solubilization of fenofibrate by Pluronic® micelles that increases with the PPO chain length provided the temperature is above the critical micelle temperature (cmt). In contrast the more water-soluble carbamazepine only shows a moderate increase in solubilization upon addition of Pluronics®. Small angle neutron scattering (SANS) and pulsed field gradient (PFG) NMR experiments show that the solubilization of fenofibrate occurs in the core of the micelles, whereas carbamazepine shows no direct association with the micelles. These clearly different solubilization mechanisms for the two AIs were confirmed by Nuclear Overhauser Enhancement Spectroscopy (NOESY) experiments, which show that fenofibrate interacts only with the PPO core of the micelle, whereas carbamazepine interacts with both PPO and PEO similarly. Accordingly, the large enhancement of the solubilization of fenofibrate is related to the fact that it is solubilized within the PPO core of the Pluronic® micelles, while the much more moderate increase of carbamazepine solubility is attributed to the change of solvent quality due to the presence of the amphiphilic copolymer and the interaction with the EO and PO units in solution. PMID:27244594

  4. Active pharmaceutical ingredient (api) from an estuarine fungus, Microdochium nivale (Fr.)

    Bhosale, S.H.; Patil, K.B.; Parameswaran, P.S.; Jagtap, T.G.

    factor to the IL-2 enhacer. EMBO J., 9, 2529-2536 (1990). Rodriguez-Couto, S., E. Lopez and M.A. Sanroman: Utilisation of grape seed for laccase production in solid- state fermentation. J. Food Engineering, 74, 263-267 (2006). Rodriguez, M.A., G. Cabrera...

  5. A systematic methodology for the design of continuous active pharmaceutical ingredient production processes

    Cervera Padrell, Albert Emili; Gani, Rafiqul; Kiil, Søren;

    2011-01-01

    . However, the change from batch-wise production towards continuous operation and the definition of flexible design spaces requires a high degree of process knowledge. Process Systems Engineering (PSE) offers multiple methods and tools which can assist in efficient knowledge acquisition, structuring and...... representation, as well as on how to employ this knowledge for process (re-)design. The aim of this paper is to introduce a methodology that systematically identifies already existing PSE methods and tools which can assist in the design of CPM processes. This methodology has been applied to a process for the...

  6. Testing of the structure of macromolecular polymer films containing solid active pharmaceutical ingredient (API) particles

    Boelcskei, E. [Department of Pharmaceutical Technology, University of Szeged, H-6720 Szeged, Eoetvoes u. 6 (Hungary); Suevegh, K. [Laboratory of Nuclear Chemistry, Eoetvoes Lorand University, H-1518 Budapest 112, P.O. Box 32 (Hungary); Marek, T. [Hungarian Academy of Sciences, Research Group for Nuclear Techniques in Structural Chemistry, Eoetvoes Lorand University, H-1518 Budapest 112, P.O. Box 32 (Hungary); Regdon, G. [Department of Pharmaceutical Technology, University of Szeged, H-6720 Szeged, Eoetvoes u. 6 (Hungary); Pintye-Hodi, K., E-mail: klara.hodi@pharm.u-szeged.h [Department of Pharmaceutical Technology, University of Szeged, H-6720 Szeged, Eoetvoes u. 6 (Hungary)

    2011-07-15

    The aim of the present study was to investigate the structure of free films of Eudragit{sup L} 30D-55 containing different concentrations (0%, 1% or 5%) of diclofenac sodium by positron annihilation spectroscopy. The data revealed that the size of the free-volume holes and the lifetimes of ortho-positronium atoms decreased with increase of the API concentration. Films containing 5% of the API exhibited a different behavior during storage (17 {sup o}C, 65% relative humidity (RH)) in consequence of the uptake of water from the air. -- Highlights: {yields} The aim of the present study was to investigate the structure of free films of Eudragit{sup L} 30D-55 containing different concentrations (0%, 1% or 5%) of diclofenac sodium by positron annihilation spectroscopy. {yields} The data revealed that the size of the free-volume holes and the lifetimes of ortho-positronium atoms decreased with increase of the API concentration (). {yields} The API distorts the original polymer structure, but as time goes by, the metastable structure relaxes and it is almost totally restored after 3 weeks of storage (17 {sup o}C, 65% RH).

  7. Testing of the structure of macromolecular polymer films containing solid active pharmaceutical ingredient (API) particles

    Bölcskei, É.; Süvegh, K.; Marek, T.; Regdon, G.; Pintye-Hódi, K.

    2011-07-01

    The aim of the present study was to investigate the structure of free films of Eudragit ® L 30D-55 containing different concentrations (0%, 1% or 5%) of diclofenac sodium by positron annihilation spectroscopy. The data revealed that the size of the free-volume holes and the lifetimes of ortho-positronium atoms decreased with increase of the API concentration. Films containing 5% of the API exhibited a different behavior during storage (17 °C, 65% relative humidity (RH)) in consequence of the uptake of water from the air.

  8. Incorporation of acetaminophen as an active pharmaceutical ingredient into porous lactose.

    Ebrahimi, Amirali; Saffari, Morteza; Dehghani, Fariba; Langrish, Timothy

    2016-02-29

    A new formulation method for solid dosage forms with drug loadings from 0.65 ± 0.03% to 39 ± 1% (w/w) of acetaminophen (APAP) as a model drug has been presented. The proposed method involves the production of highly-porous lactose with a BET surface area of 20 ± 1 m(2)/g as an excipient using a templating method and the incorporation of drug into the porous structure by adsorption from a solution of the drug in ethanol. Drug deposition inside the carrier particles, rather than being physically distributed between them, eliminated the potential drug/carrier segregation, which resulted in excellent blend uniformities with relative standard deviations of less than 3.5% for all drug formulations. The results of DSC and XRD tests have shown deposition of nanocrystals of APAP inside the nanopores of lactose due the nanoconfinement phenomenon. FTIR spectroscopy has revealed no interaction between the adsorbed drug and the surface of lactose. The final loaded lactose particles had large BET surface areas and high porosities, which significantly increased the crushing strengths of the produced tablets. In vitro release studies in phosphate buffer (pH 5.8) have shown an acceptable delivery performance of 85% APAP release within 7 minutes for loaded powders filled in gelatin capsules. PMID:26768724

  9. WHO Prequalification of Active Pharmaceutical Ingredients%WHO原料药预认证项目

    吕修梅

    2014-01-01

    目的 帮助国内原料药厂家了解并通过WHO预认证项目.方法 全面论述WHO原料药预认证项目的背景、申请流程、文件要求和意义.结果与结论 通过加深对WHO原料药预认证项目的认识,可以提高生产厂家参与WHO原料药预认证的积极性,增强通过预认证的信心.

  10. Therapeutic deep eutectic solvents as solubility enhancers for different active pharmaceutical ingredients

    Silva, J. C.; Aroso, Ivo Manuel Ascensão; Mano, F.; Sá-Nogueira, I; Barreiros, S.; Reis, R.L.; Paiva, A; Duarte, Ana Rita C.

    2015-01-01

    In recent years, deep eutectic solvents (DES) have emerged as a sustainable alternative to ionic liquids mainly due to their lower production costs and higher biodegradability/ biocompatibility(1). DES are defined as a mixture of organic compounds with a melting point significantly lower than that of either individual component(2). When based in natural compounds such as aminoacids, organic acids, sugars or choline derivatives, DES are so called natural deep eutectic solvents (NADES) which fu...

  11. Classification of parasite eggs used as an active pharmaceutical ingredient (API)

    Bruun, J. M.; Carstensen, Jens Michael; Thamsborg, S.;

    2012-01-01

    The aim of the project is to describe the developmental stages of parasite eggs using digital image analysis of multispectral imagery. The primary focus is to identify and count eggs of different developmental stages and distinguish them from unrelated particles. This information is used to asses...

  12. Crystallization kinetics and molecular mobility of an amorphous active pharmaceutical ingredient: A case study with Biclotymol.

    Schammé, Benjamin; Couvrat, Nicolas; Malpeli, Pascal; Delbreilh, Laurent; Dupray, Valérie; Dargent, Éric; Coquerel, Gérard

    2015-07-25

    The present case study focuses on the crystallization kinetics and molecular mobility of an amorphous mouth and throat drug namely Biclotymol, through differential scanning calorimetry (DSC), temperature resolved X-ray powder diffraction (TR-XRPD) and hot stage microscopy (HSM). Kinetics of crystallization above the glass transition through isothermal and non-isothermal cold crystallization were considered. Avrami model was used for isothermal crystallization process. Non-isothermal cold crystallization was investigated through Augis and Bennett model. Differences between crystallization processes have been ascribed to a site-saturated nucleation mechanism of the metastable form, confirmed by optical microscopy images. Regarding molecular mobility, a feature of molecular dynamics in glass-forming liquids as thermodynamic fragility index m was determined through calorimetric measurements. It turned out to be around m=100, describing Biclotymol as a fragile glass-former for Angell's classification. Relatively long-term stability of amorphous Biclotymol above Tg was analyzed indirectly by calorimetric monitoring to evaluate thermodynamic parameters and crystallization behavior of glassy Biclotymol. Within eight months of storage above Tg (T=Tg+2°C), amorphous Biclotymol does not show a strong inclination to crystallize and forms a relatively stable glass. This case study, involving a multidisciplinary approach, points out the importance of continuing looking for stability predictors. PMID:26003417

  13. Active pharmaceutical ingredients in aqueous matrices : an integrated approach for assessing effects

    Vasquez, Marlen Ines; Βάσκες, Μάρλεν Ινές

    2012-01-01

    Η παρουσία ενεργών φαρμακευτικών συστατικών (ΕΦΣ) στο περιβάλλον είναι αποδεδειγμένη από τα μέσα της δεκαετίας του 90 και οφείλεται στη δυσκολία απομάκρυνσης τους στους βιολογικούς σταθμούς επεξεργασίας λυμάτων. Οι δυνητικές αρνητικές επιδράσεις λόγω της συμπτωματικής έκθεσης οργανισμών σε ΕΦΣ απασχολούν σήμερα την επιστημονική κοινότητα. Η πληθώρα ΕΦΣ που χρησιμοποιούνται ταυτοχρόνως και σε συνδυασμό με τη συνεχή βιοτική ή αβιοτική μετατροπή του κάθε ΕΦΣ στο περιβάλλον, οδηγεί στην παρουσία ...

  14. Testing of the structure of macromolecular polymer films containing solid active pharmaceutical ingredient (API) particles

    The aim of the present study was to investigate the structure of free films of EudragitL 30D-55 containing different concentrations (0%, 1% or 5%) of diclofenac sodium by positron annihilation spectroscopy. The data revealed that the size of the free-volume holes and the lifetimes of ortho-positronium atoms decreased with increase of the API concentration. Films containing 5% of the API exhibited a different behavior during storage (17 oC, 65% relative humidity (RH)) in consequence of the uptake of water from the air. -- Highlights: → The aim of the present study was to investigate the structure of free films of EudragitL 30D-55 containing different concentrations (0%, 1% or 5%) of diclofenac sodium by positron annihilation spectroscopy. → The data revealed that the size of the free-volume holes and the lifetimes of ortho-positronium atoms decreased with increase of the API concentration (). → The API distorts the original polymer structure, but as time goes by, the metastable structure relaxes and it is almost totally restored after 3 weeks of storage (17 oC, 65% RH).

  15. Oxidation of pharmaceutically active compounds by a ligninolytic fungal peroxidase.

    Eibes, Gemma; Debernardi, Gianfranco; Feijoo, Gumersindo; Moreira, M Teresa; Lema, Juan M

    2011-06-01

    Pharmaceuticals are an important group of emerging pollutants with increasing interest due to their rising consumption and the evidence for ecotoxicological effects associated to trace amounts in aquatic environments. In this paper, we assessed the potential degradation of a series of pharmaceuticals: antibiotics (sulfamethoxazole), antidepressives (citalopram hydrobromide and fluoxetine hydrochloride), antiepileptics (carbamazepine), anti-inflammatory drugs (diclofenac and naproxen) and estrogen hormones (estrone, 17β-estradiol, 17α-ethinylestradiol) by means of a versatile peroxidase (VP) from the ligninolytic fungus Bjerkandera adusta. The effects of the reaction conditions: VP activity, organic acid concentration and H(2)O(2) addition rate, on the kinetics of the VP based oxidation system were evaluated. Diclofenac and estrogens were completely degraded after only 5-25 min even with a very low VP activity (10 U l(-1)). High degradation percentages (80%) were achieved for sulfamethoxazole and naproxen. Low or undetectable removal yields were observed for citalopram (up to 18%), fluoxetine (lower than 10%) and carbamazepine (not degraded). PMID:20972884

  16. Demand Forecasting In Pharmaceutical Industry Using Neuro-Fuzzy Approach

    Taskin, M.Fatih; Candan, Gökçe; Yazgan, Harun Reşit

    2014-01-01

    Because of human healthcare, the pharmaceutical industry can be considered as one of the most significant industrial sector. For this reason, demand forecasting in pharmaceutical industry has more complex structure than other sectors. Human factors, seasonal and epidemic diseases, market shares of the competitive products and marketing conditions are considered as main external factors for forecasting pharmaceutical product. Additionally, active ingredients rate is also important factor for f...

  17. Identification and stability of calcipotriol pseudopolymorphs in pharmaceutical creams

    Kontoyannis, Christos; Orkoula, Malvina

    2012-01-01

    Calcipotriol is a vitamin D analogue and is used as active pharmaceutical ingredient in pharmaceutical formulations against psoriasis. It exists in two pseudopolymorphs, anhydrate and monohydrate, the latter of which, can be found in the commercially available cream Dovonex®. The percentage of the API in the cream is as low as 0.005 wt %. Methodologies were developed for monitoring calcipotriol’s hydrate state in creams exhibiting pharmaceutical strength considerably lower than the detec...

  18. Determination of active ingredients of Rhododendron dauricum L. by capillary electrophoresis with electrochemical detection.

    Cao, Yuhua; Lou, Changgang; Fang, Yuzhi; Ye, Jiannong

    2002-01-11

    High-performance capillary electrophoresis with electrochemical detection was employed to analyse active ingredients of Rhododendron dauricum L., an important crude herb frequently used in Chinese medicines. Farrerol, quercetin, syringic acid, vanillic acid, 4-hydroxybenzoic acid, protocatechuic acid are major important active ingredients. Operated in a wall-jet configuration, a 300-microm diameter carbon-disk electrode was used as the working electrode, which exhibits a good response at +950 mV (vs. saturated calomel electrodes) for six analytes. Under the optimum conditions, the analytes were baseline separated within 16 min in a borax buffer (pH 8.7). Notably, excellent linearity was obtained over two orders of magnitude with detection limits (S/N=3) ranged from 9 x 10(-7) to 3.0 x 10(-6) M for all analytes. This method was successfully used in the analysis of Rhododendron dauricum L. with relatively simple extraction procedures, and the assay results were satisfactory. PMID:11820277

  19. Curing Ingredients, Characteristics, Total Phenolic, and Antioxidant Activity of Commercial Indonesian Dried Meat Product (Dendeng

    T. Suryati

    2012-08-01

    Full Text Available Dendeng is Indonesian dried meat product that used spices rich in antioxidant component as ingredient. In addition, commercial dendeng usually use saltpeter (nitrate/nitrite salt as curing ingredient to inhibit rancidity and to produce stable red color. The aims of this study were to investigate composition of spices and saltpeter added, characteristic, total phenolic, and antioxidant activity of commercial dendeng. This research was conducted through interview with some dendeng producers to get information about saltpeter adding and spices composition used in their products. Then the interview results were verified by laboratory analysis. The results showed that spices and saltpeter adding from some producers varied. The saltpeter added in curing process produced inconsistent red color on commercial dendeng in this investigation. Total phenolic of dendeng from producers ranged from 42.47 to 102.0 mg GAE/100 g DM for raw dendeng, and 36.51 to 95.49 mg GAE/100 g DM for fried dendeng. Antioxidant capacity against DPPH ranged from 79.35 to 379.40 mg VCE/100 g DM for raw dendeng, and 94.30 to 559.40 mg VCE/100 g DM for fried dendeng. Antioxidant capacity of raw dendeng was influenced by phenolic content about 87.2%, but in fried dendeng was only 59.0%. In conclusion, dendeng has a significant antioxidant activity, even after frying, and saltpeter addition was not effective to maintain stable red color in dendeng products.

  20. Probabilistic Evaluation of Mammalian Pharmacology Data to Target Pharmaceuticals for Environmental Hazard Assessment

    Active Pharmaceutical Ingredients (APIs) are being detected with increasing frequency in aquatic systems associated with municipal effluent. APIs considered a Contaminant of Emerging Concern (CEC) -Little, if any, regulation considering aquatic systems -Effects on aquatic o...

  1. ANALYSIS OF PHARMACEUTICAL COMPANIES’ ACTIVITIES THAT ARE DIRECTED TO PHYSICIANS IN EGYPT

    M. M. Bahlol

    2016-01-01

    Full Text Available Purpose. Pharmaceutical market is one of the largest world markets with its own conditions. In Middle East, Egypt is a major pharmaceutical emerging market and has geographical, historical and political effective leading role among Arab countries. This research aims to investigate pharmaceutical companies’ activities in Egypt directed to physicians.Methodology. Urveying through simple random probability sampling is the approach appropriate for broad and representative overview of situation in research. Therefore, a survey of 1068 physicians was conducted through interviews and establishing structured data collection questionnaire.Originality. This is the first empirical paper to investigate pharmaceutical companies’ activities directed to physicians in pharmaceutical market of Egypt. These activities include identifying pharmaceutical companies through visits of medical representatives, analysis of those visits, frequency of medical representatives’ visits, characteristics of information introduced by medical representatives to physicians, physicians’ trust in provided information, spending of pharmaceutical companies on physicians, promotional techniques applied by medical representatives. These findings are useful for managers in pharmaceutical industry. They can be also useful in other industries such as medical equipment.Findings. Pharmaceutical companies are employing medical representatives widely, as the most effective and widely-applied promotion tool in Egypt.Practical Implications. Coordinate marketing management vision with pharmaceutical market real context will lead to synergism effect in utilizing medical representatives’ activities.

  2. Evaluation of teratogenic effects of crocin and safranal, active ingredients of saffron, in mice.

    Moallem, Seyed Adel; Afshar, Mohammad; Etemad, Leila; Razavi, Bibi Marjan; Hosseinzadeh, Hossein

    2016-02-01

    Saffron (Crocus sativus) is a widely used food additive for its color and taste. Crocin and safranal are two main components of this plant. Numerous studies are underway to introduce saffron and its active ingredients as pharmacological agents. Safety assessments of these compounds are important parts of this endeavor. In this study, the effects of crocin and safranal administrations during embryogenesis have been investigated in mice. A total of 75 BALB/c pregnant mice were divided into six experimental and control groups. Four experimental groups received intraperitoneal injection of crocin (200 mg/kg or 600 mg/kg) daily or safranal (0.075 ml/kg or 0.225 ml/kg) on gestational days (GDs) 6 to 15. Control groups received normal saline or paraffin as solvents of crocin and safranal. Dams were dissected on GD18 and embryos were collected. Routine maternal and fetal parameters were recorded. Macroscopic observation of external malformations was also performed. Fetuses were then selected for double skeletal staining with alizarin red and alcian blue. All experimental groups caused significant decrease in length and weight of fetuses when compared with the control groups and revealed malformations such as minor skeletal malformations, mandible and calvaria malformations, and growth retardation. Minor skeletal malformations were the most commonly observed abnormality, which were statistically significant when compared with the control groups (p saffron, further elaborate studies to understand the malformation mechanisms of these ingredients are recommended. PMID:24097366

  3. Comparative analysis of ciprofloxacin in different pharmaceutical products by high performance liquid chromatograph

    Pharmaceutical products with different trade names having ciprofloxacin as an active ingredient were collected from the market. The products were assayed under similar conditions for active ingredient applying HPLC technique. Results obtained from quantification of ciprofloxacin contents of each product were compared with their label claims. Comparative analysis of these products was performed based on the quantity of ciprofloxacin. (author)

  4. Activity and Stability Studies of Verbascoside, a Novel Antioxidant, in Dermo-Cosmetic and Pharmaceutical Topical Formulations

    Anna Baldisserotto

    2011-08-01

    Full Text Available We here report the results of our investigations carried out on verbascoside, a phenylpropanoid glycoside known for its antioxidant, anti-inflammatory and photoprotective actions. Verbascoside was obtained from Buddleia davidii meristematic cells, obtained in turn using a sustainable biotechnology platform which employs an in vitro plant cell culture technology. Verbascoside was first investigated to assess the behaviour of the active ingredient in solution or in finished preparations, in view of its potential topical use, especially in skin protection. Stability studies were performed by HPLC, and a PCL assay was adopted to determine the radical scavenging activity toward superoxide anion. The high hydrophilic character of verbascoside, suggested in a somewhat limited range of possible applications, leading us to explore its derivatization to obtain the semi-synthetic derivative VPP, an acyl derivative of verbascoside, with an improved range of applications due to its lower hydrophilic profile. Alone, VPP revealed increased antioxidant activity, both as an active ingredient and in dermocosmetic preparations. Stability studies showed a greater stability of VPP in lipophilic vehicles, whereas the parent verbascoside proved more stable in an O/W emulsions. Verbascoside was also stable in suppositories, an interesting pharmaceutical form for possible applications in treatment of inflammation of the intestinal mucosa.

  5. INFLUENCE OF SELECTED PHARMACEUTICALS ON ACTIVATED SLUDGE DEHYDROGENASE ACTIVITY

    Agnieszka Tomska

    2016-06-01

    The aim of this work was to evaluate the effect of selected antibiotics - sulfanilamide and erythromycin on activated sludge dehydrogenase activity with use of trifenyltetrazolinum chloride (TTC test. Dehydrogenases activity is an indicator of biochemical activity of microorganisms present in activated sludge or the ability to degrade organic compounds in waste water. TTC test is particularly useful for the regularity of the course of treatment, in which the presence of inhibitors of biochemical reactions and toxic compounds are present. It was observed that the dehydrogenase activity decreases with the increase of a antibiotics concentration. The lowest value of the dehydrogenase activity equal to 32.4 μmol TF / gMLSS obtained at sulfanilamide concentration 150mg / l. For this sample, an inhibition of dehydrogenase activity was 31%.

  6. Genotoxic effects of the herbicide Roundup Transorb and its active ingredient glyphosate on the fish Prochilodus lineatus.

    Moreno, Natália Cestari; Sofia, Silvia Helena; Martinez, Claudia B R

    2014-01-01

    Roundup Transorb (RT) is a glyphosate-based herbicide and despite its wide use around the world there are few studies comparing the effects of the active ingredient with the formulated product. In this context the purpose of this study was to compare the genotoxicity of the active ingredient glyphosate with the formulated product RT in order to clarify whether the active ingredient and the surfactant of the RT formula may exert toxic effects on the DNA molecule in juveniles of fish Prochilodus lineatus. Erythrocytes and gill cells of fish exposed to glyphosate and to RT showed DNA damage scores significantly higher than control animals. These results revealed that both glyphosate itself and RT were genotoxic to gill cells and erythrocytes of P. lineatus, suggesting that their use should be carefully monitored considering their potential impact on tropical aquatic biota. PMID:24448465

  7. 77 FR 15764 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

    2012-03-16

    ... process if it can be shown that the active pharmaceutical ingredient(s) (API) is the same as the pioneer... applications over the past 10 years. In the Federal Register of October 24, 2011 (76 FR 65733), FDA published...

  8. Synthesis, structure, antitumor activity of novel pharmaceutical co-crystals based on bispyridyl-substituted α, β-unsaturated ketones with gallic acid

    Liu, Lian-Dong; Liu, Shu-Lian; Liu, Zhi-Xian; Hou, Gui-Ge

    2016-05-01

    Three novel pharmaceutical co-crystals, (A)·(gallic acid) (1), (B)·(gallic acid) (2), and (C)·(gallic acid) (3) were generated based on 2,6-bis((pyridin-4-yl)methylene)cyclohexanone (A), N-methyl-3,5-bis((pyridin-3-yl)methylene)-4-piperidone (B), N-methyl-3,5-bis((pyridin-4-yl)methylene)-4-piperidone (C) with gallic acid, respectively. They are characterized by elemental analysis, FTIR spectroscopy, 1H NMR and single-crystal X-ray diffraction. Structural analysis reveals that two pharmaceutical ingredients link each other into H-bonding-driven 3D network in 1, 2, or 2D plane in 3. In addition, their antitumor activities against human neoplastic cell lines A549, SGC-7901, MCF-7, OVCA-433, HePG2 and cytotoxicity for HUVEC cell lines by CCK-8 method were evaluated primarily. Compared with gallic acid and free A, B and C, their antitumor activities have improved distinctly, while cytotoxicities have reduced markedly, especially for co-crystal 1. This is mainly because of the synergistic effect between pharmaceutical ingredients A, B, and C and gallic acid.

  9. Inter- and Intra-Manufacturer Variability in Pharmaceutical Grades and Lots of Xanthan Gum

    Thacker, Ankur; Fu, Shao; Boni, Riccardo L.; Block, Lawrence H.

    2010-01-01

    A pharmaceutical formulation typically contains one or more excipients in addition to the active pharmaceutical ingredient(s). Though excipients have been considered inert components of a formulation, variability in their properties has been shown to affect the performance of drug dosage forms and delivery systems. This study investigates the inter- and intra-manufacturer variability among different NF grades and lots of xanthan gum made by two manufacturers. As many formulators rely on compe...

  10. Analysis of ecologically relevant pharmaceuticals in wastewater and surface water using selective solid phase extraction and UPLC/MS/MS

    A rapid and sensitive method has been developed for the analysis of 48 human prescription active pharmaceutical ingredients (APIs) and 6 metabolites of interest, utilizing selective solid-phase extraction (SPE) and ultra performance liquid chromatography in combination with tripl...

  11. Defining the Active Ingredients of Interactive Computer Play Interventions for Children with Neuromotor Impairments: A Scoping Review

    Levac, Danielle; Rivard, Lisa; Missiuna, Cheryl

    2012-01-01

    Rehabilitation researchers who investigate complex interventions are challenged to describe the "active ingredients" of their interventions: the reason(s) why a treatment is expected to be effective. Interactive Computer Play (ICP) is an emerging complex intervention in rehabilitation practice and research. The purpose of this scoping review is to…

  12. Effects of ginsenosides, the active ingredients of Panax ginseng, on development, growth, and life span of Caenorhabditis elegans

    Ginsenosides, the active ingredients of Panax ginseng, are saponins derived from sterols. The free-living nematode Caenorhabditis elegans is a well-established model for biochemical and genetic studies in animals. Although cholesterol is an essential requirement for the growth and development of C. ...

  13. Collaborative Care for Patients With Severe Personality Disorders: Preliminary Results and Active Ingredients From a Pilot Study (Part I)

    Stringer, Barbara; Meijel, Berno van; Karman, Pieter; Koekkoek, Bauke; Hoogendoorn, Adriaan; Kerkhof, Ad; Beekman, Aartjan

    2014-01-01

    PURPOSE: To test if a collaborative care program (CCP) with nurses in a coordinating position is beneficial for patients with severe personality disorders. DESIGN AND METHODS: A pilot study with a comparative multiple case study design using mixed methods investigating active ingredients and prelimi

  14. Effects of rhubarb and the active ingredients of rhubarb on the cytoplasmic free calcium in INTMNC of rabbits

    Xiu Zhen Lin; De Lu Ma; Zhi Qing Cui; Yi Kang

    2000-01-01

    @@INTRODUCTION The recent studies have shown that rhubarb has not only the effect of removing stasis by purgation, but also intestinal barrier effects[1,2]. In order to further clarify the intestinal barrier mechanism of rhubarb, we studied the effects of rhubarb decoction and the active ingredients of rhubarb on the cytoplasmic free calcium in isolated intestinal mononuclear cells (INT-MNC)

  15. Quantifying Amphibian Pesticide Body Burdens for Active Ingredients Versus Formulations Through Dermal Exposure

    Widespread pesticide applications throughout agricultural landscapes pose a risk to post-metamorphic amphibians leaving or moving between breeding ponds in terrestrial habitats. Recent studies indicate that the inactive ingredients in pesticide formulations may be equally or more...

  16. MICROSPONGE DELIVERY SYSTEM (MDS: A UNIQUE TECHNOLOGY FOR DELIVERY OF ACTIVE INGREDIENTS

    Saurabh Kumar et al.

    2011-12-01

    Full Text Available In pharmaceutical industry, various controlled released dosage forms like solid formulation, semi solid formulation and topical preparation have more importance due to efficacy and patient compliance. Topical preparations have some disadvantages like unpleasant odour, greasiness and skin irritation and fail to reach the systemic circulation in sufficient amounts in few cases. This problem is overcome by microsponge delivery system. Microsponges are tiny sponge like spherical and highly porous micro-sized particles with a unique ability for entrapping actives. They offers programmable release active drug into the skin in order to reduce systemic exposure and minimize local cutaneous reactions to active. These MDS’s are closely related to microspheres, and used in the sun screens, creams, ointments, over- the-counter (OTC skin care preparations, recently used in oral drug as well as biopharmaceuticals (peptides, proteins and DNA-based therapeutics drug delivery. The present review introduces microsponge technology along with its synthesis, characterization, programmable parameters and release mechanism of MDS.

  17. Chitosonic® Acid as a Novel Cosmetic Ingredient: Evaluation of its Antimicrobial, Antioxidant and Hydration Activities

    Yi-Shyan Chen

    2013-03-01

    Full Text Available Chitosonic® Acid, carboxymethyl hexanoyl chitosan, is a novel chitosan material that has recently been accepted by the Personal Care Products Council as a new cosmetic ingredient with the INCI (International Nomenclature of Cosmetic Ingredients name Carboxymethyl Caprooyl Chitosan. In this study, we analyze several important cosmetic characteristics of Chitosonic® Acid. Our results demonstrate that Chitosonic® Acid is a water-soluble chitosan derivative with a high HLB value. Chitosonic® Acid can form a nano-network structure when its concentration is higher than 0.5% and can self-assemble into a nanosphere structure when its concentration is lower than 0.2%. Chitosonic® Acid has potent antimicrobial activities against gram-positive bacteria, gram-negative bacteria and fungus. Chitosonic® Acid also has moderate DPPH radical scavenging activity. Additionally, Chitosonic® Acid exhibits good hydration activity for absorbing and retaining water molecules with its hydrophilic groups. From a safety point of view, Chitosonic® Acid has no cytotoxicity to L-929 cells if its concentration is less than 0.5%. Moreover, Chitosonic® Acid has good compatibilities with various normal cosmetic ingredients. Therefore, we propose that Chitosonic® Acid has the potential to be a widely used ingredient in various types of cosmetic products.

  18. Pharmaceutical quality of nine generic orlistat products compared with Xenical(r).

    Taylor, P.W.; Arnet, I; Fischer, A; Simpson, I N

    2010-01-01

    OBJECTIVE: To compare the pharmaceutical quality of Xenical (chemically produced orlistat) with nine generic products, each produced by fermentation processes. METHODS: Xenical 120 mg capsules (Roche, Basel, Switzerland) were used as reference material. Generic products were from India, Malaysia, Argentina, Philippines, Uruguay, and Taiwan. Colour, melting temperature, crystalline form, particle size, capsule fill mass, active pharmaceutical ingredient content, amount of impurities, and disso...

  19. Inactive ingredient Search for Approved Drug Products

    U.S. Department of Health & Human Services — According to 21 CFR 210.3(b)(8), an inactive ingredient is any component of a drug product other than the active ingredient. Only inactive ingredients in the final...

  20. Study of Active Ingredients in Black Soybean Sprouts and Their Safety in Cosmetic Use

    Yinmao Dong

    2012-10-01

    Full Text Available Active ingredients in different lengths of black soybean sprouts were extracted with water. Concentrations of the main proteins and polysaccharides were determined by the Forint phenol assay and phenol-sulfuric acid assay, respectively. Anti-oxidizing capacities of the extracts were measured in vitro using the DPPH scavenging test and whitening capacity was measured in vitro using the tyrosinase inhibition test. The effects of the bean sprout extracts on human skin fibroblasts damnified by H2O2 were studied using an MTT colorimetric assay. The safety of the extracts was determined using the red blood cell (RBC test, chick chorioallantoic membrane (CAM assay and human patch test. Results show that DPPH radical scavenging rates at different shoot lengths were all greater than 95%, while the tyrosinase inhibition capacity of the extracts reached 98%. Hemolysis rate in all extracts were lower than 10%, below the 20% regulatory limit for the RBC test. No signs of allergic reactions were observed in the human patch tests. The optimum extract was obtained from bean sprouts grown to 0.5 cm. Extracts of black bean sprouts are safe and can be used as additives in anti-aging and whitening cosmetic products.

  1. Pharmacokinetics of hederacoside C, an active ingredient in AG NPP709, in rats.

    Kim, Ju Myung; Yoon, Ji Na; Jung, Ji Won; Choi, Hye Duck; Shin, Young June; Han, Chang Kyun; Lee, Hye Suk; Kang, Hee Eun

    2013-11-01

    1. Hederacoside C (HDC) is one of the active ingredients in Hedera helix leaf extract (Ivy Ex.) and AG NPP709, a new botanical drug to treat acute respiratory infection and chronic inflammatory bronchitis. However, information regarding its pharmacokinetic properties remains limited. 2. Here, we report the pharmacokinetics of HDC in rats after intravenous administration of HDC (3, 12.5, and 25 mg/kg) and after oral administration of HDC, Ivy Ex., and AG NPP709 (equivalent to 12.5, 25, and 50 mg/kg HDC). 3. Linear pharmacokinetics of HDC were identified upon its intravenous administration at doses of 3-25 mg/kg. Intravenous administration of HDC results in relatively slow clearance (1.46-2.08 mL/min/kg) and a small volume of distribution at steady state (138-222 mL/kg), while oral administration results in a low absolute oral bioavailability (F) of 0.118-0.250%. The extremely low F of HDC may be due to poor absorption of HDC from the gastrointestinal (GI) tract and/or its decomposition therein. 4. The oral pharmacokinetics of HDC did not differ significantly among pure HDC, Ivy Ex., and AG NPP709. PMID:23607546

  2. Determination of Four Active Ingredients in Vc Yinqiao Tablets by Capillary Zone Electrophoresis with Amperometric Detection

    L(U),Jin; WANG,Qing-Jiang; CHENG,Xi; LIU,Hai-Yan; HE,Pin-Gang; FANG,Yu-Zhi

    2006-01-01

    A simple, reliable and reproducible method, based on capillary zone electrophoresis with amperometric detection (CZE-AD), has been developed for simultaneous determination of four active ingredients in Vc Yinqiao tablets including paracetamol, vitamin C, caffeic acid and chlorogenic acid. A carbon-disk electrode was used as working electrode and 0.95 V (versus SCE) was selected as detection potential. The optimal conditions of CZE experiment were 30 mmol·L-1 borate solution (pH 9.5) as running buffer, 14 kV as separation voltage and 8 s (14 kV) as electro-kinetic sampling time. Under the selected optimum conditions, paracetamol, vitamin C, caffeic acid and chlorogenic acid could be perfectly separated within 22 min, and their detection limits (S/N=3) ranged from 5 × 10-7 to 1×10-6 mol·L-1. This proposed method demonstrated good reproducibility with relative standard deviations of less than 3% for both migration time and peak current (n=7). The utility of this method was demonstrated by monitoring a kind of compound medicine named Vc Yinqiao tablets and the assay results were satisfactory.

  3. Determination of sorption of seventy five pharmaceuticals in sewage sludge

    Hörsing, Maritha; Ledin, Anna; Grabic, Roman;

    2011-01-01

    Sorption of 75 active pharmaceutical ingredients (APIs) to three different types of sludge (primary sludge, secondary sludge with short and long sludge age respectively) were investigated. To obtain the sorption isotherms batch studies with the APIs mixture were performed in four nominal concentr......Sorption of 75 active pharmaceutical ingredients (APIs) to three different types of sludge (primary sludge, secondary sludge with short and long sludge age respectively) were investigated. To obtain the sorption isotherms batch studies with the APIs mixture were performed in four nominal...

  4. Patenting activity in biotechnology and pharmaceuticals: a comparative analysis of the Nordic Countries

    Enrico Sorisio

    2009-01-01

    The main aim of this paper is to study innovative activity, as measured by patent indicators, in pharmaceutical and biotechnological sectors in the Nordic Countries. The biotech sector in general and pharmaceutical in particular is one of the areas selected for strategic investments in every Nordic country. In terms of patents granted by country of inventors Denmark plays a leading role followed by Sweden, while patenting activity in Finland and Norway is lower. A concentration of patents tow...

  5. Oxygen species scavenging activity of phenolic extracts from hawthorn fresh plant organs and pharmaceutical preparations.

    Bahorun, T; Gressier, B; Trotin, F; Brunet, C; Dine, T; Luyckx, M; Vasseur, J; Cazin, M; Cazin, J C; Pinkas, M

    1996-11-01

    Different extracts of fresh vegetative and reproductive organs from Crataegus monogyna harvested during a whole season and from some pharmaceutical hawthorn preparations exhibit in vitro antioxidant activities using three different models of oxygen reactive species generation (superoxide anion, hydrogen peroxide and hypochlorous acid). All the tested samples show low IC50 values, the most efficient being fresh young leaves, fresh floral buds and pharmaceutical dried flowers. The activities seem to be especially bound to the total phenolic proanthocyanidin and flavonoid contents. PMID:8955870

  6. Biodegradation of pharmaceuticals in hospital wastewater by a hybrid biofilm and activated sludge system (Hybas)

    Escola Casas, Monica; Chhetri, Ravi Kumar; Ooi, Gordon Tze Hoong;

    2015-01-01

    hybrid process, based on the integrated fixed-film activated sludge technology, where plastic carriers for biofilm growth are suspended within activated sludge. To investigate the potential of a hybrid system for the removal of pharmaceuticals in hospital wastewater a pilot plant consisting of a series...... of one activated sludge reactor, two HybasTM reactors and one moving bed biofilm reactor (MBBR) has been operated for 10 months, where after batch and continuous flow tests were performed for the degradation of pharmaceuticals. Removal of organic matter and nitrification mainly occurred in the first...... reactor. Most pharmaceuticals were removed significantly. The removal of pharmaceuticals (including x-ray contrast media, ß-blockers, analgesics and antibiotics) were fitted to a single first-order kinetics degradation function, giving degradation rate constants from 0 to 1.49 h-1, from 0 to 7.78×10-1 h-1...

  7. Acaricidal activity against Panonychus citri and active ingredient of the mangrove plant Cerbera manghas.

    Deng, Yecheng; Yongmei Liao; Li, Jingjing; Yang, Linlin; Zhong, Hui; Zhou, Qiuyan; Qing, Zhen

    2014-09-01

    Cerbera manghas is a mangrove plant which possesses comprehensive biological activities. A great deal of research has been undertaken on the chemical constituents and medical functions of C. manghas; insecticidal and antifungal activities have also been reported, but the acaricidal activity has not been studied. In our study, the acaricidal activity and active substances of C. manghas were investigated using a spray method, which showed that the methanol extracts of the fruit, twigs and leaves exhibited contact activity against female adults of Panonychus citri, with LC50 values at 24 h of 3.39 g L(-1), 4.09 g L(-1) and 4.11 g L(-1), respectively. An acaricidal compound was isolated from C. manghas by an activity-guided isolation method, and identified as (-)-17β-neriifolin, which is a cardiac glycoside. (-)-17β-Neriifolin revealed high contact activity against female adults, nymphae, larvae and eggs of P. citri, with LC50 values at 24 h of 0.28 g L(-1), 0.29 g L(-1), 0.28 g L(-1) and 1.45 g L(-1), respectively. PMID:25918788

  8. Active ingredient-containing chitosan/polycaprolactone nonwoven mats: Characterizations and their functional assays

    Bai, Meng-Yi, E-mail: mybai@mail.ntust.edu.tw [Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei 10607, Taiwan, ROC (China); Adjunct appointment to the Department of Biomedical Engineering, National Defense Medical Center, Taipei 114, Taiwan, ROC (China); Chou, Tz-Chong, E-mail: tcchou@ms5.hinet.net [Department of Biomedical Engineering, National Defense Medical Center, Taipei 114, Taiwan, ROC (China); Tsai, Jie-Chang; Yang, Hui-Ching [Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei 10607, Taiwan, ROC (China)

    2013-01-01

    This study demonstrates a facile method developed to generate a chitosan/polycaprolactone (CS/PCL) nonwoven mat. All nonwoven mats are composed of microfibers with an average diameter of 2.51 {+-} 0.69 {mu}m. The X-ray photoelectron spectroscopy data indicate that positively charged nitrogen was generated on the surface of the mats after undergoing CS coating. By using a non-contacting electrostatic voltmeter, we determined that the nonwoven mats exhibited a positive potential and the charge density of the CS/PCL nonwoven mat was in proportion to the thickness of the CS overlayer. Moreover, platelet aggregation and anti-bacterial ability were enhanced by the CS/PCL nonwoven mat as compared to that of PCL nonwoven mat alone. The enhancements of the CS/PCL nonwoven mat on platelet aggregation are further promoted by incorporating a 1 mM calcium ion in its CS overlayer. We also find that the addition of tea tree oil in the CS overlayer significantly inhibited LPS-induced nitrite formation in Raw 264.7 macrophages. In conclusion, our CS/PCL nonwoven mat possesses pharmacological effects including an increase of platelet aggregation, anti-bacterial, anti-adhesive, and anti-inflammatory activities. The performance of this CS/PCL nonwoven mat can be further promoted by incorporating active compounds to exert therapeutic effects in wound healing. Highlights: Black-Right-Pointing-Pointer We develop a facile method to generate active ingredient-containing CS/PCLNM. Black-Right-Pointing-Pointer Our CS/PCLNM possesses superior mechanical strength, compared to CS-blended PCL nanofibers. Black-Right-Pointing-Pointer We prove that our prepared CS/PCLNM possesses several pharmacological properties Black-Right-Pointing-Pointer The functional performances of CS/PCLNM are enhanced by incorporation of active compounds. Black-Right-Pointing-Pointer Incorporation of 1 mM of calcium ions or 100 {mu}L of TTO into the CS overlayer of CS/PCLNM is the optimum dose.

  9. Active ingredient-containing chitosan/polycaprolactone nonwoven mats: Characterizations and their functional assays

    This study demonstrates a facile method developed to generate a chitosan/polycaprolactone (CS/PCL) nonwoven mat. All nonwoven mats are composed of microfibers with an average diameter of 2.51 ± 0.69 μm. The X-ray photoelectron spectroscopy data indicate that positively charged nitrogen was generated on the surface of the mats after undergoing CS coating. By using a non-contacting electrostatic voltmeter, we determined that the nonwoven mats exhibited a positive potential and the charge density of the CS/PCL nonwoven mat was in proportion to the thickness of the CS overlayer. Moreover, platelet aggregation and anti-bacterial ability were enhanced by the CS/PCL nonwoven mat as compared to that of PCL nonwoven mat alone. The enhancements of the CS/PCL nonwoven mat on platelet aggregation are further promoted by incorporating a 1 mM calcium ion in its CS overlayer. We also find that the addition of tea tree oil in the CS overlayer significantly inhibited LPS-induced nitrite formation in Raw 264.7 macrophages. In conclusion, our CS/PCL nonwoven mat possesses pharmacological effects including an increase of platelet aggregation, anti-bacterial, anti-adhesive, and anti-inflammatory activities. The performance of this CS/PCL nonwoven mat can be further promoted by incorporating active compounds to exert therapeutic effects in wound healing. Highlights: ► We develop a facile method to generate active ingredient-containing CS/PCLNM. ► Our CS/PCLNM possesses superior mechanical strength, compared to CS-blended PCL nanofibers. ► We prove that our prepared CS/PCLNM possesses several pharmacological properties ► The functional performances of CS/PCLNM are enhanced by incorporation of active compounds. ► Incorporation of 1 mM of calcium ions or 100 μL of TTO into the CS overlayer of CS/PCLNM is the optimum dose.

  10. Chitin-Hyaluronan Nanoparticles: A Multifunctional Carrier to Deliver Anti-Aging Active Ingredients through the Skin

    Pierfrancesco Morganti

    2014-07-01

    Full Text Available The paper describes the process to produce Chitin Nanofibril-Hyaluronan nanoparticles (CN-HA, showing their ability to easily load active ingredients, facilitate penetration through the skin layers, and increase their effectiveness and safety as an anti-aging agent. Size and characterization of CN-HA nanoparticles were determined by Scanning Electron Microscopy (SEM and Zetasizer, while encapsulation efficiency and loading capacity of the entrapped ingredients were controlled by chromatographic and spectrophotometric methods. Safeness was evidenced on fibroblasts and keratinocytes culture viability by the MTT (Methylthiazol assay; anti-aging activity was evaluated in vitro measuring antioxidant capacity, anti-collagenase activity, and metalloproteinase and pro-inflammatory release; efficacy was shown in vivo by a double-blind vehicle-controlled study for 60 days on 60 women affected by photo-aging. In addition, the CN-HA nanoparticles have shown interesting possibility to be used as active ingredients, for designing and making advanced medication by the electrospinning technology, as well as to produce transparent films for food packaging, by the casting method, and can be used also in their dry form as tissues or films without adding preservatives. These unusual CN-HA nanoparticles obtained from the use of raw materials of waste origin may offer an unprecedented occasion for making innovative products, ameliorating the quality of life, reducing pollution and safeguarding the environment’s integrity.

  11. 21 CFR 341.85 - Labeling of permitted combinations of active ingredients.

    2010-04-01

    ... ingredients in part 356 of this chapter should be used. (5) For permitted combinations containing camphor... camphor, menthol, and eucalyptus oil identified in § 341.40(u). The labeling states the warnings for... containing camphor, menthol, and eucalyptus oil identified in § 341.40(u). The labeling states the...

  12. 78 FR 23558 - Pesticide Products; Registration Applications for New Active Ingredients

    2013-04-19

    ... February 29, 2012 (77 FR 12295)(FRL- 9332-8), EPA announced receipt of two other applications to register... identifying information (subject heading, Federal Register date and page number). ii. Follow directions. The... Ingredient: Bacillus thuringiensis subsp. galleriae strain SDS-502 at 85.0%. Proposed Use: For control...

  13. Antifeedant Activity and Active Ingredients Against Plutella xylostella from Momordica charantia Leaves

    2008-01-01

    With the bioguided fractionation of the ethanol extracts from the leaves of Momordica charantia, we obtained two most active compounds against the feeding of the diamondback moth, Plutella xylostella larvae. The antifeedant activity of momordicine Ⅰ and momordicine Ⅱ against the second and the third instar larvae of Plutella xylostella were tested using leaf discs of cabbage in the laboratory. The results showed that momordicin Ⅰ and momordiein Ⅱ had significant antifeedant activity on the larvae of P. Xylostella, and momordicin Ⅱ was more active than momordicin Ⅰ. The concentrations for 50% antifeedant effects (AFC50) of momordicin Ⅱ against the second and the third instar larvae of P. Xylostella were 76.69 and 116.24 μg mL-1, whereas that of momordicin Ⅰ was 144.08 and 168.42 μg mL-1, respectively. In addition, momordicin Ⅰ and momordicin Ⅱ had significant inhibitive effect on the rate of weight gain and survival of P. Xylostella larvae.

  14. Active ingredients in sunscreens act as topical penetration enhancers for the herbicide 2,4-dichlorophenoxyacetic acid

    Agricultural workers are encouraged to use sunscreen to decrease the risk of UV-related skin cancer. Our previous studies have shown certain commercial sunscreens to be penetration enhancers. The focus of this project is to determine whether active ingredients in sunscreen formulations (i.e., the UV absorbing components and insect repellants for the sunscreen/bug repellant combinations) also act as dermal penetration enhancers for herbicides in vitro. The total percentages of 2,4-dichlorophenoxyacetic acid (2,4-D) penetrating through hairless mouse skin in 24 h ranged from 54.9 ± 4.7 for the no sunscreen control to 86.9 ± 2.5 for padimate-o. Of the active ingredients tested (7.5% octyl methoxycinnamate, 7% octocrylene, 0.6% oxybenzone, 5% homosalate, 5% octyl salicylate, 8% padimate-o, 10% sulisobenzone, and 9.5% and 19% N,N-diethyl-m-toluamide [DEET]), all but octocrylene led to a significant increase in total 2,4-D penetration as compared to the control (P 3H2O penetration across mouse skin, indicating physical damage to the stratum corneum. Additional studies demonstrated that the penetration enhancement seen across hairless mouse skin also occurred with human skin. Thus, the active ingredients of sunscreen formulations enhance dermal penetration of the moderately lipophilic herbicide 2,4-D

  15. Monitoring Blending of Pharmaceutical Powders with Multipoint NIR Spectroscopy

    SCHEIBELHOFER, OTTO; Balak, Nikolaus; Wahl, Patrick R.; Koller, Daniel M.; Glasser, Benjamin J; Khinast, Johannes G.

    2012-01-01

    Blending of powders is a crucial step in the production of pharmaceutical solid dosage forms. The active pharmaceutical ingredient (API) is often a powder that is blended with other powders (excipients) in order to produce tablets. The blending efficiency is influenced by several external factors, such as the desired degree of homogeneity and the required blending time, which mainly depend on the properties of the blended materials and on the geometry of the blender. This experimental study i...

  16. Content of Selected Minerals and Active Ingredients in Teas Containing Yerba Mate and Rooibos.

    Rusinek-Prystupa, Elżbieta; Marzec, Zbigniew; Sembratowicz, Iwona; Samolińska, Wioletta; Kiczorowska, Bożena; Kwiecień, Małgorzata

    2016-07-01

    The study aimed to determine the content of selected elements: sodium, potassium, copper, zinc, iron, manganese and active ingredients such as phenolic acids and tannins in teas containing Yerba Mate and Rooibos cultivated in various areas. The study material comprised six samples of Yerba Mate teas and of Rooibos teas, both tea bags and leaves, purchased in Puławy and online via Allegro. In total, 24 samples were tested. Yerba Mate was particularly abundant in Mn and Fe. The richest source of these elements was Yerba Mate Yer-Vita (2261.3 mg · kg(-1) d.m.) and (691.6 mg · kg(-1) d.m.). The highest content of zinc was determined in Yerba Mate Amanda with lime (106.0 mg · kg(-1) d.m.), while copper was most abundant in Yerba Mate Big-Active cocoa and vanilla (14.05 mg · kg(-1) d.m.). In Rooibos, the content of sodium was several times higher than in Yerba Mate. A clear difference was observed in the content of minerals in dry weight of the examined products, which could be a result of both the taxonomic distinctness and the origin of the raw material. Leaf teas turned out to be a better source of tannins; on the other hand, tea bags contained substantially more phenolic acids. The richest source of phenolic acids was Yer-Vita in bags (1.8 %), and the highest amount of tannins was recorded in the leaf tea Green Goucho caramel and dark chocolate (9.04 g · 100 g(-1) d.m.). In Rooibos products, the highest content of phenolic acids was recorded in tea bags (Savannah with honey and vanilla 0.96 %), and tannins in (Lord Nelson with strawberry and cream 7.99 g · 100 g (-1) d.m.). PMID:26686675

  17. Anti-cancer activities of Ganoderma lucidum: active ingredients and pathways

    Chi H.J. Kao; Jesuthasan, Amalini C; Karen S. Bishop; Marcus P. Glucina; Ferguson, Lynnette R

    2013-01-01

    ABSTRACTGanoderma lucidum, commonly referred to as Lingzhi, has been used in Asia for health promotion for centuries. The anti-cancer effects of G. lucidum have been demonstrated in both in vitro and in vivo studies. In addition, the observed anti-cancer activities of Ganoderma have prompted its usage by cancer patients alongside chemotherapy.The main two bioactive components of G. lucidum can be broadly grouped into triterpenes and polysaccharides. Despite triterpenes and polysaccharides bei...

  18. Special active ingredients and beauty-food%特种活性物及营养美容

    韩建英

    2012-01-01

    介绍了特种活性物及营养美容的理念。消费者目前对营养美容理念的兴趣越来越浓厚,使得营养美容产品逐渐成为市场营销的热点。配方师也热衷于将营养品与美容相结合,开发出营养美容产品,并将营养美容对身体的益处都囊括在产品配方中。介绍了几种最具潜力的营养美容成分以及特种活性物成分,并对其前景进行了展望。%The idea of special active ingredients and beauty-food are introduced briefly. Nowadays, the consumers become more and more interested in the concept of beauty-food, and the beauty-food product category has gradually become the hot topic of marketing. Formulators are eager to combine the benefits of nutrition with beauty in the formulations, and develop the beauty-food products. Some diet beauty ingredients with the greatest potential are introduced, and the future of the special active ingredients and the beauty-food are prospected here.

  19. Anti-inflammaging and antiglycation activity of a novel botanical ingredient from African biodiversity (Centevita™

    Maramaldi G

    2013-12-01

    Full Text Available Giada Maramaldi,1 Stefano Togni,1 Federico Franceschi,1 Elian Lati21Indena SpA, Milan, Italy; 2Laboratoire BIO-EC, Longjumeau, FrancePurpose: The aim of this study was to investigate the topical efficacy of a new purified extract from Madagascar, Gotu Kola (Centella asiatica [L.] Urban, both on human explants and on human volunteers, in relation to skin wrinkling and skin protection against ultraviolet light exposure. The extract, with a peculiar content of biologically active molecules, was investigated as a novel anti-inflammaging and antiglycation agent. Its typical terpenes, known as collagen synthesis promoters, represent at least 45% of the extract. It also contains a polyphenolic fraction cooperating to the observed properties.Methods: C. asiatica purified extract was assayed on human skin explants maintained alive, and several parameters were evaluated. Among the most relevant, the thymine dimerization was evaluated by immunostaining. Malondialdehyde formation was evaluated as free-radical scavenging marker by enzyme-linked immunosorbent assay. The expression of interleukin-1a was observed by enzyme-linked immunosorbent assay as well. The product was further evaluated as an antiglycation agent, being glycation quantified by the advanced glycation product carboxymethyl lysine. C. asiatica purified extract was also evaluated as an antiwrinkling agent in a single-blind, placebo-controlled study. Formulated in a simple oil-in-water emulsion, the extent of wrinkling was assessed by skin replicas, skin firmness, skin elasticity, and collagen density measurements.Results: C. asiatica purified extract could protect DNA from ultraviolet light-induced damage, decreasing the thymine photodimerization by over 28% (P<0.05. A reduced (26%, P<0.01 expression of interleukin-1α was also observed, supporting its anti-inflammatory potential. C. asiatica purified extract showed in vitro a total inhibition of carboxymethyl lysine formation induced by the

  20. Bioactive Ingredients and Antioxidant Activity of Austrian Wine and Grape Juice

    Pérez Navarro, Roser

    2008-01-01

    Wine has already been investigated for its potential nutritional quality, such as high amount of phenolic compounds. Phenolic compounds, well-known as natural antioxidants, are reported due their radical scavenging capacity. In the present work, the bioactive ingredients of nine Austrian wines (four red wines: Zweigelt, Blaufränkisch, Syrah and Cuvée; two white wines: Pinot Blanc and Chardonnay; one rosé Blaufränkisch; and two grape juice: red and white) have been quantified an...

  1. Biodegradation of pharmaceuticals in hospital wastewater by a hybrid biofilm and activated sludge system (Hybas)

    Escolà Casas, Mònica [Environmental Science, Aarhus University, Frederiksborgsvej 399, 4000 Roskilde (Denmark); Chhetri, Ravi Kumar [Department of Environmental Engineering, Technical University of Denmark, Miljøvej 113, 2800 Kgs. Lyngby (Denmark); Ooi, Gordon [Environmental Science, Aarhus University, Frederiksborgsvej 399, 4000 Roskilde (Denmark); Hansen, Kamilla M.S. [Department of Environmental Engineering, Technical University of Denmark, Miljøvej 113, 2800 Kgs. Lyngby (Denmark); Litty, Klaus [Department of Chemistry and Biotechnology, Danish Technological Institute, Kongsvang Allé 29, 8000 Aarhus C (Denmark); Christensson, Magnus [AnoxKaldnes, Klosterängsvägen 11A, 226 47 Lund (Sweden); Kragelund, Caroline [Department of Chemistry and Biotechnology, Danish Technological Institute, Kongsvang Allé 29, 8000 Aarhus C (Denmark); Andersen, Henrik R. [Department of Environmental Engineering, Technical University of Denmark, Miljøvej 113, 2800 Kgs. Lyngby (Denmark); Bester, Kai, E-mail: kb@envs.au.dk [Environmental Science, Aarhus University, Frederiksborgsvej 399, 4000 Roskilde (Denmark)

    2015-10-15

    Hospital wastewater contributes a significant input of pharmaceuticals into municipal wastewater. The combination of suspended activated sludge and biofilm processes, as stand-alone or as hybrid process (hybrid biofilm and activated sludge system (Hybas™)) has been suggested as a possible solution for hospital wastewater treatment. To investigate the potential of such a hybrid system for the removal of pharmaceuticals in hospital wastewater a pilot plant consisting of a series of one activated sludge reactor, two Hybas™ reactors and one moving bed biofilm reactor (MBBR) has been established and adapted during 10 months of continuous operation. After this adaption phase batch and continuous experiments were performed for the determination of degradation of pharmaceuticals. Removal of organic matter and nitrification mainly occurred in the first reactor. Most pharmaceuticals were removed significantly. The removal of pharmaceuticals (including X-ray contrast media, β-blockers, analgesics and antibiotics) was fitted to a single first-order kinetics degradation function, giving degradation rate constants from 0 to 1.49 h{sup −1}, from 0 to 7.78 × 10{sup −1} h{sup −1}, from 0 to 7.86 × 10{sup −1} h{sup −1} and from 0 to 1.07 × 10{sup −1} h{sup −1} for first, second, third and fourth reactors respectively. Generally, the highest removal rate constants were found in the first and third reactors while the lowest were found in the second one. When the removal rate constants were normalized to biomass amount, the last reactor (biofilm only) appeared to have the most effective biomass in respect to removing pharmaceuticals. In the batch experiment, out of 26 compounds, 16 were assessed to degrade more than 20% of the respective pharmaceutical within the Hybas™ train. In the continuous flow experiments, the measured removals were similar to those estimated from the batch experiments, but the concentrations of a few pharmaceuticals appeared to increase

  2. Biodegradation of pharmaceuticals in hospital wastewater by a hybrid biofilm and activated sludge system (Hybas)

    Hospital wastewater contributes a significant input of pharmaceuticals into municipal wastewater. The combination of suspended activated sludge and biofilm processes, as stand-alone or as hybrid process (hybrid biofilm and activated sludge system (Hybas™)) has been suggested as a possible solution for hospital wastewater treatment. To investigate the potential of such a hybrid system for the removal of pharmaceuticals in hospital wastewater a pilot plant consisting of a series of one activated sludge reactor, two Hybas™ reactors and one moving bed biofilm reactor (MBBR) has been established and adapted during 10 months of continuous operation. After this adaption phase batch and continuous experiments were performed for the determination of degradation of pharmaceuticals. Removal of organic matter and nitrification mainly occurred in the first reactor. Most pharmaceuticals were removed significantly. The removal of pharmaceuticals (including X-ray contrast media, β-blockers, analgesics and antibiotics) was fitted to a single first-order kinetics degradation function, giving degradation rate constants from 0 to 1.49 h−1, from 0 to 7.78 × 10−1 h−1, from 0 to 7.86 × 10−1 h−1 and from 0 to 1.07 × 10−1 h−1 for first, second, third and fourth reactors respectively. Generally, the highest removal rate constants were found in the first and third reactors while the lowest were found in the second one. When the removal rate constants were normalized to biomass amount, the last reactor (biofilm only) appeared to have the most effective biomass in respect to removing pharmaceuticals. In the batch experiment, out of 26 compounds, 16 were assessed to degrade more than 20% of the respective pharmaceutical within the Hybas™ train. In the continuous flow experiments, the measured removals were similar to those estimated from the batch experiments, but the concentrations of a few pharmaceuticals appeared to increase during the first treatment step. Such

  3. Biodegradation of pharmaceuticals in hospital wastewater by a hybrid biofilm and activated sludge system (Hybas)

    Escola Casas, Monica; Chhetri, Ravi Kumar; Ooi, Gordon Tze Hoong;

    2015-01-01

    Hospital wastewater contributes a significant input of pharmaceuticals into municipal wastewater. The combination of suspended activated sludge and biofilm processes, as stand-alone or as hybrid process, has been suggested as a possible solution for hospital wastewater treatment. HybasTM is a...... hybrid process, based on the integrated fixed-film activated sludge technology, where plastic carriers for biofilm growth are suspended within activated sludge. To investigate the potential of a hybrid system for the removal of pharmaceuticals in hospital wastewater a pilot plant consisting of a series...

  4. Antibacterial Activities of Bacteriocins: Application in Foods and Pharmaceuticals

    Jia-YouFang

    2014-05-01

    Full Text Available Bacteriocins are a kind of ribosomal synthesized antimicrobial peptides produced by bacteria, which can kill or inhibit bacterial strains closely-related or non-related to produced bacteria, but will not harm the bacteria themselves by specific immunity proteins. Bacteriocins become one of the weapons against microorganisms due to the specific characteristics of large diversity of structure and function, natural resource, and being stable to heat. Many recent studies have purified and identified bacteriocins for application in food technology, which aims to extend food preservation time, treat pathogen disease and cancer therapy, and maintain human health. Therefore, bacteriocins may become a potential drug candidate for replacing antibiotics in order to treat multiple drugs resistance pathogens in the future. This review article summarizes different types of bacteriocins from bacteria. The latter half of this review focuses on the potential applications applications in food science and pharmaceutical industry.

  5. Required ozone doses for removing pharmaceuticals from wastewater effluents

    Antoniou, Maria; Hey, Gerly; Rodríguez Vega, Sergio;

    2013-01-01

    The aim of the this study was to investigate the ozone dosage required to remove active pharmaceutical ingredients (APIs) from biologically treated wastewater of varying quality, originated from different raw wastewater and wastewater treatment processes.Secondary effluents from six Swedish...

  6. An Integrated Approach to Thermal Analysis of Pharmaceutical Solids

    Riley, Shelley R. Rabel

    2015-01-01

    A three-tiered experiment for undergraduate Instrumental Analysis students is presented in which students characterize the solid-state thermal behavior of an active pharmaceutical ingredient (acetaminophen) and excipient (a-lactose hydrate) using differential scanning calorimetry, thermogravimetric analysis, and thermal microscopy. Students are…

  7. The interaction of a model active pharmaceutical with cationic surfactant and the subsequent design of drug based ionic liquid surfactants.

    Qamar, Sara; Brown, Paul; Ferguson, Steven; Khan, Rafaqat Ali; Ismail, Bushra; Khan, Abdur Rahman; Sayed, Murtaza; Khan, Asad Muhammad

    2016-11-01

    Interactions of active pharmaceutical ingredients (API) with surfactants remain an important research area due to the need to improve drug delivery systems. In this study, UV-Visible spectrophotometry was used to investigate the interactions between a model low molecular weight hydrophilic drug sodium valproate (SV) and cationic surfactant cetyltrimethylammonium bromide (CTAB). Changes in the spectra of SV were observed in pre- and post-micellar concentrations of CTAB. The binding constant (Kb) values and the number of drug molecules encapsulated per micelle were calculated, which posed the possibility of mixed micelle formation and strong complexation between SV and CTAB. These results were compared to those of a novel room temperature surface active ionic liquid, which was synthesized by the removal of inorganic counterions from a 1:1 mixture of CTAB and SV. In this new compound the drug now constitutes a building block of the carrier and, as such, has considerably different surfactant properties to its building blocks. In addition, enhanced solubility in a range of solvents, including simulated gastric fluid, was observed. The study provides valuable experimental evidence concerning the performance of drug based surfactant ionic liquids and how their chemical manipulation, without altering the architecture of the API, leads to control of surfactant behavior and physicochemical properties. In turn, this should feed through to improved and controlled drug release rates and delivery mechanisms, and the prevention of precipitation or formation of polymorphs typical of crystalline form APIs. PMID:27472069

  8. Examining pharmaceuticals using terahertz spectroscopy

    Sulovská, Kateřina; Křesálek, Vojtěch

    2015-10-01

    Pharmaceutical trafficking is common issue in countries where they are under stricter dispensing regime with monitoring of users. Most commonly smuggled pharmaceuticals include trade names Paralen Plus, Modafen, Clarinase repetabs, Aspirin complex, etc. These are transported mainly from Eastern Europe (e.g. Poland, Ukraine, Russia) to countries like Czech Republic, which is said to have one of the highest number of methamphetamine producers in Europe. The aim of this paper is to describe the possibility of terahertz spectroscopy utilization as an examining tool to distinguish between pharmaceuticals containing pseudoephedrine compounds and those without it. Selected medicaments for experimental part contain as an active ingredient pseudoephedrine hydrochloride or pseudoephedrine sulphate. Results show a possibility to find a pseudoephedrine compound spectra in samples according to previously computed and experimentally found ones, and point out that spectra of same brand names pills may vary according to their expiration date, batch, and amount of absorbed water vapours from ambience. Mislead spectrum also occurs during experimental work in a sample without chosen active ingredient, which shows persistent minor inconveniences of terahertz spectroscopy. All measurement were done on the TPS Spectra 3000 instrument.

  9. Preventive effects of Flos Perariae (Gehua water extract and its active ingredient puerarin in rodent alcoholism models

    Wang Yuqiang

    2010-10-01

    Full Text Available Abstract Background Radix Puerariae is used in Chinese medicine to treat alcohol addiction and intoxication. The present study investigates the effects of Flos puerariae lobatae water extract (FPE and its active ingredient puerarin on alcoholism using rodent models. Methods Alcoholic animals were given FPE or puerarin by oral intubation prior or after alcohol treatment. The loss of righting reflex (LORR assay was used to evaluate sedative/hypnotic effects. Changes of gama-aminobutyric acid type A receptor (GABAAR subunits induced by alcohol treatment in hippocampus were measured with western blot. In alcoholic mice, body weight gain was monitored throughout the experiments. Alcohol dehydrogenase (ADH levels in liver were measured. Results FPE and puerarin pretreatment significantly prolonged the time of LORR induced by diazepam in acute alcoholic rat. Puerarin increased expression of gama-aminobutyric acid type A receptor alpha1 subunit and decreased expression of alpha4 subunit. In chronic alcoholic mice, puerarin pretreatment significantly increased body weight and liver ADH activity in a dose-dependent manner. Puerarin pretreatment, but not post-treatment, can reverse the changes of gama-aminobutyric acid type A receptor subunit expression and increase ADH activity in alcoholism models. Conclusion The present study demonstrates that FPE and its active ingredient puerarin have preventive effects on alcoholism related disorders.

  10. BULK AND SURFACE PROPERTIES OF TIN BASED HERBAL DRUG DURING ITS PREPARATION: FINGERPRINTING OF THE ACTIVE PHARMACEUTICAL CONSTITUENT

    Asit Baran Mandal et al.

    2012-04-01

    Full Text Available The Tin based herbal drug (Vangaparpam - a Siddha system of Medicine has been widely used for the treatment of urinogenital infection and Arthritis. It was prepared by ten sequential stages of calcinations of the medicinally purified tin along with Aloe vera extract. In this study we analysed samples from various stages of preparation using analytical techniques viz., Fourier Transformed Infrared spectroscopy, Powder X ray Diffraction, X ray Photoelectron Spectroscopy, Energy Dispersive X- ray spectroscopy , Scanning Electron Microscopy, to create fingerprints required for the optimisation of the process parameters, detection of toxic impurities and crystal morphology of the Active Pharmaceutical ingredient during the formulation of drug for which reports are not available. Upon analysis of the samples of various stages of calcinations, we found that there was a programmed heating the medicinally purified tin metal was converted to crystalline tin oxide in the tetragonal phase at the first stage of calcinations itself along with a small percentage of therapeutically important elements of Calcium, Iron, and Potassium. Further calcinations steps brought interplay of nano and sub-micro sized particles for optimum bioavailability of the drug.

  11. Analysis of Three Penicillin Antibiotics (Ampicillin, Amoxicillin and Cloxacillin) of Several Iranian Pharmaceutical Companies by HPLC

    A. Ashnagar; N. Gharib Naseri

    2007-01-01

    Penicillin has been the most widely used antibiotic for many gram-positive bacterial infections. In this research the purity of the standard active ingredients of the various dosage forms of three penicillins (Amoxicillin, Cloxacillin and Ampicillin) imported and the purity percentage of the active ingredients in each of the various dosage forms of these drugs manufactured by several pharmaceutical companies of Iran (Kosar, Farabi and Jaber Ibn Hayan) were investigated and determined by HPLC ...

  12. Lubricants in Pharmaceutical Solid Dosage Forms

    Jinjiang Li

    2014-02-01

    Full Text Available Lubrication plays a key role in successful manufacturing of pharmaceutical solid dosage forms; lubricants are essential ingredients in robust formulations to achieve this. Although many failures in pharmaceutical manufacturing operations are caused by issues related to lubrication, in general, lubricants do not gain adequate attention in the development of pharmaceutical formulations. In this paper, the fundamental background on lubrication is introduced, in which the relationships between lubrication and friction/adhesion forces are discussed. Then, the application of lubrication in the development of pharmaceutical products and manufacturing processes is discussed with an emphasis on magnesium stearate. In particular, the effect of its hydration state (anhydrate, monohydrate, dihydrate, and trihydrate and its powder characteristics on lubrication efficiency, as well as product and process performance is summarized. In addition, the impact of lubrication on the dynamics of compaction/compression processes and on the mechanical properties of compacts/tablets is presented. Furthermore, the online monitoring of magnesium stearate in a blending process is briefly mentioned. Finally, the chemical compatibility of active pharmaceutical ingredient (API with magnesium stearate and its reactive impurities is reviewed with examples from the literature illustrating the various reaction mechanisms involved.

  13. Validation of a method by gas chromatography for the determination of fatty acids that comprise the active ingredient D-004

    D-004 is a new active ingredient obtained from the Cuban royal palm (Roystonea regia) fruits. This substance is mainly composed by a mixture of saturated and unsaturated free fatty acids, from 8 to 18 carbon atoms, and has shown to be effective in experimental model of prostate hyperplasia. A capillary gas chromatographic method for the determination of the fatty acids in D-004 was developed and validated. The acids were analyzed as methyl ester derivatives, which were obtained by reaction with 10 % acetyl chloride in methanol and separated in a BPX-5 wide-bore column using tridecanoic acid as internal standard. The specificity study showed no interferences regarding the determination of this mixture, once the samples were submitted to stress conditions. Determination of the total fatty acid content was linear (r > 0.999; CVs of the response factors and of the slopes lower than 5 and 2 %, respectively) and without bias in the studied concentration range, from 50 to 150 % of the nominal mass. In the accuracy study, over the range 80 to 120 % of the nominal fatty acid concentration, high recoveries (100.4 to 100.8 %) were reached. Good results were obtained in the repeatability and intermediate precision studies (CV < 2%), proving that the method is precise. These results support that this method is properly validated, being appropriate for the quality control and stability studies of this active ingredient

  14. The Contribution of Innovation Strategy Development and Implementation in Active Facilitation of Pharmaceutical Front End Innovation

    Aagaard, Annabeth

    2012-01-01

    research and FEI to produce more valid candidates and faster for drug development. This paper explores how pharmaceutical front end innovation can be actively supported through the development and implementation of an innovation strategy. The empirical field and applied methodology is an action......, Steven & Burly, 2003, and Vernorn et al., 2008) and that innovation strategies play a central role in optimization of innovation (Clark & Wheelwright, 1995; Cottam et al., 2001; Morgan & Berthon, 2008). Innovation strategies are suggested in literature (e.g. Page, 1993; Oke, 2002; Adams et al., 2006......; Igartua, 2010) as a facilitator of innovation and may therefore also be targeted at FEI support. The pharmaceutical industry has experienced a worldwide decline in the number of applications for new molecular entities to regulatory agencies since 1997. Therefore high pressures are put on pharmaceutical...

  15. Severe anaphylaxis: the secret ingredient.

    Buergi, Andreas; Jung, Barbara; Padevit, Christian; John, Hubert; Ganter, Michael T

    2014-02-01

    In this case report, we describe a healthy urological patient who suffered severe intraoperative anaphylaxis to chlorhexidine, an ingredient contained in frequently used lubricants (Instillagel, Endosgel). Chlorhexidine is a well-known skin disinfectant and antiseptic component in mouthwash or other over the counter antiseptic pharmaceuticals. There is little awareness that commonly used lubricants may contain hidden chlorhexidine. After severe intraoperative anaphylaxis, it is important to investigate all potential (including hidden) agents that might have caused this life-threatening reaction. PMID:25611155

  16. Biodegradation of pharmaceuticals in hospital wastewater by a hybrid biofilm and activated sludge system (Hybas).

    Escolà Casas, Mònica; Chhetri, Ravi Kumar; Ooi, Gordon; Hansen, Kamilla M S; Litty, Klaus; Christensson, Magnus; Kragelund, Caroline; Andersen, Henrik R; Bester, Kai

    2015-10-15

    Hospital wastewater contributes a significant input of pharmaceuticals into municipal wastewater. The combination of suspended activated sludge and biofilm processes, as stand-alone or as hybrid process (hybrid biofilm and activated sludge system (Hybas™)) has been suggested as a possible solution for hospital wastewater treatment. To investigate the potential of such a hybrid system for the removal of pharmaceuticals in hospital wastewater a pilot plant consisting of a series of one activated sludge reactor, two Hybas™ reactors and one moving bed biofilm reactor (MBBR) has been established and adapted during 10 months of continuous operation. After this adaption phase batch and continuous experiments were performed for the determination of degradation of pharmaceuticals. Removal of organic matter and nitrification mainly occurred in the first reactor. Most pharmaceuticals were removed significantly. The removal of pharmaceuticals (including X-ray contrast media, β-blockers, analgesics and antibiotics) was fitted to a single first-order kinetics degradation function, giving degradation rate constants from 0 to 1.49 h(-1), from 0 to 7.78 × 10(-1)h(-1), from 0 to 7.86 × 10(-1)h(-1) and from 0 to 1.07 × 10(-1)h(-1) for first, second, third and fourth reactors respectively. Generally, the highest removal rate constants were found in the first and third reactors while the lowest were found in the second one. When the removal rate constants were normalized to biomass amount, the last reactor (biofilm only) appeared to have the most effective biomass in respect to removing pharmaceuticals. In the batch experiment, out of 26 compounds, 16 were assessed to degrade more than 20% of the respective pharmaceutical within the Hybas™ train. In the continuous flow experiments, the measured removals were similar to those estimated from the batch experiments, but the concentrations of a few pharmaceuticals appeared to increase during the first treatment step. Such increase

  17. Situation analysis of R & d activities: an empirical study in Iranian pharmaceutical companies.

    Rasekh, Hamid Reza; Mehralian, Gholamhossein; Vatankhah-Mohammadabadi, Abbas Ali

    2012-01-01

    As global competition intensifies, research and development (R & D) organizations need to enhance their strategic management in order to become goal-directed communities for innovation and allocate their resources consistent with their overall R & D strategy. The world pharmaceutical market has undergone fast, unprecedented, tremendous and complex changes in the last several years. The pharmaceutical industry is today still one of the most inventive, innovative and lucrative of the so-called "high-tech" industries. This industry serves a dual role in modern society. On one hand, it is a growing industry, and its output makes a direct contribution to gross domestic product (GDP). On the other side, drugs, this industry's major output, are an input in the production of good health. The purpose of this study is to evaluate R & D activities of pharmaceutical companies, and also to highlight critical factors which have influential effect on results of these activities. To run this study a valid questionnaire based on literature review and experts' opinion was designed and delivered to 11 pharmaceutical companies. Empirical data show there is not acceptable situations considering of the factors that should be taken in to account by managers including; management commitment, human resource management, information technology and financial management. Furthermore, we concluded some interesting results related to different aspects of R & D management. In conclusion, managers must be aware about their performance in R & D activities, accordingly they will able to take a comprehensive policy in both national and within the company. PMID:24250532

  18. Behavior of selected pharmaceuticals in topsoil of Greyic Phaeozem

    Kodesova, Radka; Klement, Ales; Kocarek, Martin; Fer, Miroslav; Golovko, Oksana; Grabic, Roman; Jaksik, Ondrej

    2014-05-01

    It has been documented in several studies that soil may be contaminated by human or veterinary pharmaceuticals. Some of pharmaceutical ingredient may be retained in soils. The rest can be transported to the surface and groundwater through surface runoff and infiltration. Mobility of contaminants in soils is dependent on many soil and pharmaceutical properties (e.g. pharmaceutical adsorption on soil particles and pharmaceutical degradation). The goals of this study were: (1) to measure adsorption isotherms of selected pharmaceuticals in one soil; (2) to evaluate degradation of selected pharmaceuticals in this soil, and (3) to evaluate impact of applied pharmaceuticals on biological activity in soil, which influences pharmaceutical decomposition. Batch sorption tests were performed for 7 selected pharmaceuticals (beta blockers Atenolol and Metoprolol, anticonvulsant Carbamazepin, and antibiotics Clarithromycin, Clindamycin, Trimetoprim and Sulfamethoxazol) and one soil (topsoil of Greyic Phaeozem from Čáslav). The same concentrations (0.5, 1, 2.5, 5 and 10 mg/l) were used for almost all pharmaceuticals except Clarithromycin (0.033, 0.08, 0.165, 0.25, 0.33 mg/l). The Freundlich equations were used to describe adsorption isotherms. Degradation of all 7 pharmaceuticals was also studied. Solutes of different pharmaceuticals (concentration of 8.3 mg/l) were added into the plastic bottles (one pharmaceutical per bottle) with soil. Concentrations of pharmaceuticals remaining in soil 1, 2, 5, 12, 23, 40 and 61 days after the pharmaceutical application were analyzed. Colony forming unites were evaluated to describe microbial activity in time affected by different pharmaceuticals. Adsorption of studied pharmaceuticals on soil particles decreasing as follows: Clarithromycin, Trimetoprim, Metoprolol, Clindamycin, Atenolol, Carbamazepin, Sulfamethoxazol. Degradation rates in some degree reflected adsorption of studied pharmaceuticals on soil particles and increased with

  19. Evaluation of Essential Oil and its Three Main Active Ingredients of Chinese Chenopodium Ambrosioides (Family: Chenopodiaceae Against Blattella Germanica

    Wei Xiang Zhu

    2012-12-01

    Full Text Available Background: The efficacy of essential oil of Chenopodium ambrosioides flowering aerial parts and its three mainactive ingredients was evaluated against Blattella germanica male adults.Methods: Composition of essential oil was determined by GC-MS. Topical application bioassay was used to evaluatecontact toxicity of essential oil and three main components. Fumigant toxicity of essential oil and its main components was measured using a sealed space method.Results: Twenty-two components were identified in the essential oil and the main components were (Z-ascaridole(29.7%, isoascaridole (13.0%, ρ-cymene (12.7% and piperitone (5.0%. The essential oil and (Z-ascaridole,isoascaridole and -cymene possessed fumigant toxicity against male German cockroaches with LC50 values of 4.13,0.55, 2.07 and 6.92 mg/L air, respectively. Topical application bioassay showed that all the three compounds weretoxic to male German cockroaches and (Z-ascaridole was the strongest with a LD50 value of 22.02 g/adult while the crude oil with a LD50 value of 67.46 g/adult.Conclusion: The essential oil from Chinese C. ambrosioides and its three main active ingredients may be explored as natural potential insecticides in the control of cockroaches.

  20. The use of green tea extract in cosmetic formulations: not only an antioxidant active ingredient.

    Gianeti, Mirela D; Mercurio, Daiane G; Campos, Patricia M B G Maia

    2013-01-01

    Green tea (GT) extracts contain polyphenols, known to be effective free radical scavengers, and other ingredients that could also provide benefits to the skin. This is a report on clinical studies using objective, noninvasive methods to evaluate the effects of cosmetic formulations containing GT. Experimental formulations were supplemented or not (vehicle) with 6% Camellia sinensis glycolic leaf extracts (GT). These formulations were applied to the forearm skin of 24 volunteers, and their effects were evaluated before and after 2 hours, 15 and 30 days according to the following parameters: stratum corneum water content, transepidermal water loss, skin viscoelastic-to-elastic ratio (Uv/Ue), and microrelief. The volunteers were instructed not to apply any formulation in an area of the forearm (control area). Experimental formulations (GT) increased skin moisture in the long-term study, indicating that GT has a prolonged moisturizing effect. The Uv/Ue was significantly enhanced after 30 days of topical application of the experimental formulation when compared with vehicle and control. After 15-30 days, skin microrelief was significantly improved due to a reduction in skin roughness. The results suggest that GT-containing cosmetic formulations have pronounced moisturizing effects and improve skin microrelief. PMID:23742288

  1. 原料药清洁验证的程序%Cleaning Validation Procedure for Active Pharmaceutical Ingredient

    刘锋; 代兴华; 刘欢欢

    2015-01-01

    新版GMP实施后,为最大限度地降低药品生产过程中污染、交叉污染等风险,必须进行清洁验证。而在实际操作中,有一些人特别是新参加工作的人不清楚清洁验证将按照什么程序来进行。笔者在此根据本人工作经验和相关法规要求,对清洁验证的程序按照时间先后顺序一一列出,并对每一步应完成的工作进行总结。%After the implementation of new edition of GMP, to minimize the risk of contamination, cross-contamination etc. in the drug manufacturing course, conducting cleaning validation is necessary. But in actual operating practices, some people, especially new employee are not sure how to carry out cleaning validation. According to author’s experience and requirements of relevant regulations, this text lists cleaning validation procedure step by step, and provides details on how to complete each step.

  2. Analysis of China's active pharmaceutical ingredient export situation%中国原料药出口态势分析

    曹钢; 柳燕

    2014-01-01

    原料药是中国的传统优势产业,近年来政府的助力推动、竞争环境的变化和国际医药产业分工的调整,推动了中国原料药产业的转型升级.中国在全球医药供应体系中扮演着越来越重要的角色,特色原料药的品种越来越丰富,产业链不断向高端延伸.对中国原料药出口态势进行了分析.

  3. Transformation of an active pharmaceutical ingredient upon high-energy milling: A process-induced disorder in Biclotymol.

    Schammé, Benjamin; Couvrat, Nicolas; Malpeli, Pascal; Dudognon, Emeline; Delbreilh, Laurent; Dupray, Valérie; Dargent, Éric; Coquerel, Gérard

    2016-02-29

    This study investigates for the first time the thermodynamic changes of Biclotymol upon high-energy milling at various levels of temperature above and below its glass transition temperature (Tg). Investigations have been carried out by temperature modulated differential scanning calorimetry (TM-DSC) and X-ray powder diffraction (XRPD). Results indicate that Biclotymol undergoes a solid-state amorphization upon milling at Tg-45 °C. It is shown that recrystallization of amorphous milled Biclotymol occurs below the glass transition temperature of Biclotymol (Tg=20 °C). This displays molecular mobility differences between milled Biclotymol and quenched liquid. A systematic study at several milling temperatures is performed and the implication of Tg in the solid-state transformations generally observed upon milling is discussed. Influence of analysis temperature with respect to interpretation of results was investigated. Finally, it is shown that co-milling Biclotymol with only 20 wt% of amorphous PVP allows a stable amorphous dispersion during at least 5 months of storage. PMID:26707413

  4. Chemical constituents of active pharmaceutical ingredients of elemene%榄香烯原料药的化学成分

    孙敏鸽; 李淑斌; 周莉; 张青

    2009-01-01

    目的 对榄香烯原料药化学成分进行系统研究.方法 采用氧化铝柱色谱、硅胶柱色谱和制备型HPLC等分离方法从榄香烯原料药中分离化合物,采用NMR等光谱学手段对它们进行结构鉴定.结果 共分离得到4个化合物,分别鉴定为β -榄香烯(1)、γ -榄香烯(2)、β -石竹烯(3)和δ -榄香烯(4).结论 不仅对榄香烯原料药的3个主要活性成分进行了结构确证,而且对原料药中的1个主要杂质成分β -石竹烯进行了结构确证,并首次对文献中β -石竹烯碳谱数据中有误的归属进行了纠正.为榄香烯原料药质量控制和临床试验的研究提供了明确的物质基础.

  5. An investigation into the crystallization tendency/kinetics of amorphous active pharmaceutical ingredients: A case study with dipyridamole and cinnarizine.

    Baghel, Shrawan; Cathcart, Helen; Redington, Wynette; O'Reilly, Niall J

    2016-07-01

    Amorphous drug formulations have great potential to enhance solubility and thus bioavailability of BCS class II drugs. However, the higher free energy and molecular mobility of the amorphous form drive them towards the crystalline state which makes them unstable. Accurate determination of the crystallization tendency/kinetics is the key to the successful design and development of such systems. In this study, dipyridamole (DPM) and cinnarizine (CNZ) have been selected as model compounds. Thermodynamic fragility (mT) was measured from the heat capacity change at the glass transition temperature (Tg) whereas dynamic fragility (mD) was evaluated using methods based on extrapolation of configurational entropy to zero [Formula: see text] , and heating rate dependence of Tg [Formula: see text] . The mean relaxation time of amorphous drugs was calculated from the Vogel-Tammann-Fulcher (VTF) equation. Furthermore, the correlation between fragility and glass forming ability (GFA) of the model drugs has been established and the relevance of these parameters to crystallization of amorphous drugs is also assessed. Moreover, the crystallization kinetics of model drugs under isothermal conditions has been studied using Johnson-Mehl-Avrami (JMA) approach to determine the Avrami constant 'n' which provides an insight into the mechanism of crystallization. To further probe into the crystallization mechanism, the non-isothermal crystallization kinetics of model systems were also analysed by statistically fitting the crystallization data to 15 different kinetic models and the relevance of model-free kinetic approach has been established. The crystallization mechanism for DPM and CNZ at each extent of transformation has been predicted. The calculated fragility, glass forming ability (GFA) and crystallization kinetics are found to be in good correlation with the stability prediction of amorphous solid dispersions. Thus, this research work involves a multidisciplinary approach to establish fragility, GFA and crystallization kinetics as stability predictors for amorphous drug formulations. PMID:27108783

  6. Characterization of solid polymer dispersions of active pharmaceutical ingredients by 19F MAS NMR and factor analysis

    Urbanová, Martina; Brus, Jiří; Šeděnková, Ivana; Policianová, Olivia; Kobera, Libor

    2013-01-01

    Roč. 100, 1 January (2013), s. 59-66. ISSN 1386-1425 R&D Projects: GA ČR GPP106/11/P426; GA MŠk 2B08021 Institutional research plan: CEZ:AV0Z40500505 Institutional support: RVO:61389013 Keywords : solid-state NMR * factor analysis * 19F MAS NMR Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 2.129, year: 2013

  7. 78 FR 3900 - Generic Drug User Fee-Active Pharmaceutical Ingredient and Finished Dosage Form Facility Fee...

    2013-01-17

    ... Innovation Act, as further amended by the FDA User Fee Corrections Act of 2012, authorizes FDA to assess and... identified or intended to be identified, in at least one generic drug submission that is pending or approved... facility fee is owed by each person that owns a facility which produces, or which is pending review...

  8. On the direct characterization and quantification of active ingredients in commercial solid drugs using PIXE, PIGE and TOF-SIMS techniques

    The quantification of the active ingredient (AI) in drugs is a crucial and important step in the drug quality control process. This is usually performed by using wet chemical techniques like LC-MS, UV spectrophotometry and other appropriate organic analytical methods. In the case of an active ingredient contains specific heteroatoms (F, S, Cl, . . .), elemental IBA like PIXE and PIGE techniques, using small tandem accelerator of 1 - 2 MV, can be explored for molecular quantification. IBA techniques permit the analysis of the sample under solid form, without any laborious sample preparations. This is an advantage when the number of sample is relatively large. In this work, we demonstrate the ability of the Thick Target PIXE and PIGE technique for rapid and accurate quantification of low concentration of different fluorinated, sulfured and chlorinated active ingredients in several commercial anti-hyperlipidemic and anti-inflammatory commercial drugs. In this work we will demonstrate the ability of PIXE and PIGE techniques for rapid and accurate quantification of Celecoxib and Atorvastatin active ingredients contained in several solid commercial drugs. The experimental aspects related to the quantification validity are presented and discussed. In addition, the Time of Flight Secondary Ion Emission using multicharged Ar ions with ∼ 10 MeV energy, delivered by a 4 MV Vander Graaf single stage accelerator, was used for structural and chemical analysis for some cases of binary commercial drugs containing two different active ingredients. The aspect of sample preparation and the role of excipient will be highlighted and discussed. (author)

  9. Impact of solid retention time and nitrification capacity on the ability of activated sludge to remove pharmaceuticals

    Falås, Per; Andersen, Henrik Rasmus; Ledin, Anna;

    2012-01-01

    Removal of five acidic pharmaceuticals (ibuprofen, ketoprofen, naproxen, diclofenac and clofibric acid) by activated sludge from five municipal activated sludge treatment processes, with various sludge ages and nitrification capacities, was assessed through batch experiments. The increase in aero...

  10. Investigation of pharmaceutical drugs and caffeine-containing foods using Fourier and terahertz time-domain spectroscopy

    KaraliÅ«nas, Mindaugas; Venckevičius, Rimvydas; Kašalynas, Irmantas; Puc, Uroš; Abina, Andreja; Jeglič, Anton; Zidanšek, Aleksander; Valušis, Gintaras

    2015-08-01

    Several pharmaceutical drugs, such as alprazolam, ibuprofen, acetaminophen, activated carbon and others, and caffeine-containing foods were tested using terahertz (THz) time domain spectroscopy in the range from 0.3 to 2 THz. The dry powder of pharmaceutical drugs was mixed with HDPE and pressed into the pellets using hydraulic press. The coffee grounds were also pressed into the pellets after ball-milling and mixing with HDPE. The caffeine containing liquid foods were dried out on the paper strips of various stacking. Experiments allow one to determine characteristic spectral signatures of the investigated substances within THz range caused by active pharmaceutical ingredients, like in the case of caffeine, as well as supporting pharmaceutical ingredients. Spectroscopic THz imaging approach is considered as a possible option to identify packaged pharmaceutical drugs. The caffeine spectral features in the tested caffeine containing foods are difficult to observed due to the low caffeine concentration and complex caffeine chemical surrounding.

  11. Water and stability of pharmaceutical solids

    Shalaev, Evgenyi

    2007-03-01

    Solid pharmaceuticals are multi-component systems consisting of an active pharmaceutical ingredient (API) and inactive ingredients (excipients). Excipients may include inorganic salts (e.g., NaCl), carbohydrates (e.g., lactose), and polymers, to name a few, whereas APIs range from relatively simple molecules (e.g., aspirin) to proteins and olygonucleotides. Pharmaceutical solids could exist either as single-phase or heterophase systems. They also may have different extent of order, such as highly ordered crystalline phases, amorphous solids that are thermodynamically unstable but might be kinetically stable under the time frame of observation, and crystalline mesophases including liquid crystals. With all this diversity, there are common features for such systems, and two of them will be discussed in the presentation. (i) Requirements for chemical stability of pharmaceuticals are very strict. A very limited (e.g., less than 0.1%) extent of conversion is allowed in these materials over the shelf life, i.e., during several years of storage at ambient and (sometimes) not fully controlled (e.g., a medicine cabinet in one's bathroom) conditions. (ii) All pharmaceutical solids contain some water, although its amount and physical state are highly variable and may change during manufacturing and shelf life. There are many challenging questions and issues associated with the ``Water and stability of pharmaceutical solids'' subject; some of them will be considered in the presentation: (i) What are the features of chemical reactivity of crystalline vs disordered systems? (ii) What is the role of water in solid state chemical reactivity of amorphous solids, e.g., water as plasticizer vs reactant vs reaction media? (iii) How homogeneous are pharmaceutical amorphous solid solutions, e.g., carbohydrate-water systems? (iv) What is the optimal water content? With water being the most common destabilizing factor, is ``the drier - the better'' always the case?

  12. Determination of sodium in pharmaceuticals by neutron activation analysis

    A simple, fast and accurate neutron activation analysis method for determination of Na in drugs concerning either active compound or total content was developed. The examined dosage forms consisted of 10 injectable ampoules and 10 bottles of oral solutions. The irradiation of samples and standards was carried out in the rotation system of the Reactor of Nuclear Research Center Democritos with maximal neutron flux of 2,9.1013 n.cm-2.sec-1. Gamma-ray spectrometry of the irradiated samples and standards was accomplished with a coaxial Ge(Li) detector series Win 15 with an efficiency of 15% connected to an Ino-Tech 1024 channel analyser (Model IT 5200). The accuracy and precision of the method are found to be very high and therefore it could be established as an official one for the determination of sodium in parmaceuticals

  13. Simultaneous determination of active ingredients in Erigeron breviscapus (Vant.) Hand-Mazz. by capillary electrophoresis with electrochemical detection.

    Chu, Qingcui; Wu, Ting; Fu, Liang; Ye, Jiannong

    2005-03-01

    A high-performance capillary electrophoresis (CE) with electrochemical detection (ED) method was developed for the determination of the pharmacologically active ingredients in Erigeron breviscapus (Vant.) Hand-Mazz. and its extract phytopharmaceuticals in this work. Under the optimum conditions, nine analytes, baicalein, naringenin, scopoletin, kaempferol, apigenin, scutellarin, luteolin, caffeic acid and protocatechuic acid were separated within 24 min in a borax buffer (pH 8.7). Notably, excellent linearity was obtained over two orders of magnitude with detection limits (S/N=3) ranged from 1.0 x 10(-7) g/mL to 5.6 x 10(-7) g/mL for all nine analytes. This method was successfully used in the analysis of E. breviscapus (Vant.) Hand-Mazz. and its phytopharmaceuticals with a relatively simple extraction procedure, and the assay results were satisfactory. PMID:15740914

  14. Robust Market Launch Planning for a Multi- Echelon Pharmaceutical Supply Chain

    Hansen, Klaus Reinholdt Nyhuus; Grunow, Martin; Gani, Rafiqul

    2011-01-01

    launching activities after the drug has been approved. In this paper, we present a recourse-based stochastic model, which allows for time phasing the market entries to balance the fluctuating demand with the fixed and periodic production of the active pharmaceutical ingredient. The two major risk elements...

  15. Gross alpha and beta activities in potable waters used by pharmaceutical companies in India

    This paper presents the gross alpha and gross beta radioactivity present in potable waters used by pharmaceutical firms from different states of India. A three year analysis in more than 90 water samples indicated that the gross alpha activity was observed to be in the range of <1 to 42.9±2.5mBq/l while gross beta activity was in the range of <20 to 67.6±2 mBq/l. Higher level of activity was observed in Goa waters. However the activities were observed to be within the limits of drinking water regulations as per USEPA 40CFR.141 and WHO regulations. (author)

  16. Studies on free-radical scavenging activity and identification of active ingredients of different plant crude extracts of Mentha piperita collected from Sur, Sultanate of Oman

    Mohammad Amzad Hossain; Aqeela Said Hamed AL Orimi; Afaf Mohammed Weli; Qasim Al-Riyami; Jamal Nasser Al-Sabahi

    2014-01-01

    Objective: To determine free radical scavenging activity and active chemical ingredients of different plant crude extracts of Mentha piperita (M. piperita). Methods: The dried powder leaves of M. piperita were extracted with polar organic solvent by Soxhlet extractor. The crude extract and its fractions of hexane, chloroform, ethyl acetate and butanol crude extracts were prepared. The antioxidant activity of different crude extracts from M. piperita was carried out by DPPH method with minor modification, and the active chemical ingredients of different plant crude extracts of M. piperita were analyzed by gas chromatography-mass spectrometry (GC-MS). Results: Qualitative analysis of different polarities crude extracts by GC-MS found different types of active organic compounds. The antioxidant activity of different crude extracts were found to be in the order of chloroform extract> butanol extract> ethyl acetate extract> hexane extract>methanol extract. Majority identified compounds in the plant crude extracts by GC-MS were biologically active. Conclusions: Therefore, the isolation, purification, identification and characterization of bioactive compounds from various crude extracts of M. piperita might have ecological significance.

  17. Studies on free-radical scavenging activity and identification of active ingredients of different plant crude extracts of Mentha piperita collected from Sur, Sultanate of Oman

    Mohammad Amzad Hossain

    2014-10-01

    Full Text Available Objective: To determine free radical scavenging activity and active chemical ingredients of different plant crude extracts of Mentha piperita (M. piperita. Methods: The dried powder leaves of M. piperita were extracted with polar organic solvent by Soxhlet extractor. The crude extract and its fractions of hexane, chloroform, ethyl acetate and butanol crude extracts were prepared. The antioxidant activity of different crude extracts from M. piperita was carried out by DPPH method with minor modification, and the active chemical ingredients of different plant crude extracts of M. piperita were analyzed by gas chromatographymass spectrometry (GC-MS. Results: Qualitative analysis of different polarities crude extracts by GC-MS found different types of active organic compounds. The antioxidant activity of different crude extracts were found to be in the order of chloroform extract> butanol extract> ethyl acetate extract> hexane extract> methanol extract. Majority identified compounds in the plant crude extracts by GC-MS were biologically active. Conclusions: Therefore, the isolation, purification, identification and characterization of bioactive compounds from various crude extracts of M. piperita might have ecological significance.

  18. An Empirical Analysis of Primary and Secondary Pharmaceutical Patents in Chile

    Abud, MJ; Hall, B; Helmers, C

    2015-01-01

    We analyze the patent filing strategies of foreign pharmaceutical companies in Chile distinguishing between “primary” (active ingredient) and “secondary” patents (patents on modified compounds, formulations, dosages, particular medical uses, etc.). There is prior evidence that secondary patents are used by pharmaceutical originator companies in the U.S. and Europe to extend patent protection on drugs in length and breadth. Using a novel dataset that comprises all drugs registered in Chile bet...

  19. Application of chemical oxidation processes for the removal of pharmaceuticals in biologically treated wastewater

    Hey, Gerly

    2013-01-01

    The discharge of effluents from wastewater treatment plants (WWTPs) is considered to be the major source of residual pharmaceuticals frequently found in aquatic environments. The complex nature of such compounds tends to make conventional biological treatments aimed at their removal ineffective. The present thesis concerns the removal of 62 different active pharmaceutical ingredients commonly detected in Swedish wastewater effluents by means of chemical oxidation techniques. Techniques wit...

  20. Importance and globalization status of good manufacturing practice (GMP) requirements for pharmaceutical excipients

    Abdellah, Abubaker; Noordin, Mohamed Ibrahim; Wan Ismail, Wan Azman

    2013-01-01

    Pharmaceutical excipients are no longer inert materials but it is effective and able to improve the characteristics of the products’ quality, stability, functionality, safety, solubility and acceptance of patients. It can interact with the active ingredients and alter the medicament characteristics. The globalization of medicines’ supply enhances the importance of globalized good manufacturing practice (GMP) requirements for pharmaceutical excipients. This review was intended to assess the gl...

  1. A Stability Indicating U-HPLC Method for Milnacipran in Bulk Drugs and Pharmaceutical Dosage Forms

    K.V. Surendranath; Shakil S. Sait; Naresh Tondepu; Ravi Kiran Kaja; Suresh Kumar

    2012-01-01

    The objective of the current study was to develop a validated, specific and stability-indicating reverse phase UHPLC method for the quantitative determination of Milnacipran and its related substances. The determination was done for active pharmaceutical ingredient and its pharmaceutical dosage forms in the presence of degradation products, and its process-related impurities. The drug was subjected to stress conditions of hydrolysis (acid and base), oxidation, pho- tolysis and thermal degrada...

  2. Comparative activity of some veterinary pharmaceutical products in swine dysentery

    Cristina, T. Romeo

    2010-12-01

    after the treatment, no longer signs of illness being observed, all animals became normothermic. Weight gain recorded on our observation period was 29.3 kg/ lot which correspond to average daily gain of 162.7 g/day/animal.Group III, considered as control group, was at the beginning of the observation period, established with the average weight per lot, of 7.88 kg/head. In this series evolved enteritis with clear clinical manifestations (acute and subacute forms and during the experiment did not receive any treatment. Within this lot, in the studied period have died five piglets which represent 33.33% of the group. Consequently, to avoid the unnecessary losses, in the 21 day of experiment, the 10 remaining piglets were orally treated with tiamulin (60 mg/litre drinking water. Subsequent observations have shown gradual improvement and clinical remission to the remaining piglets. In the control group, practically can’t talk about a weight gain. After the 21 day average daily gain for animals remaining batch was 45.1 g/day/animal.Experiment IIThe groups were selected from age group 35-45 days, which are each, composed of 12 heads per group.Group I was treated with soluble granules tiamulin concentration of 45 mg of active substance per litre of drinking water. Treatment was performed over a period of 5 days. During the experiment, within this group there was one death case representing 8.33%. The remaining 12 piglets were cured within two weeks. Initial weight was of 92.9 kg/ group, and after 21 days of experiment, it reached at 98.9 kg, corresponding to an average daily gain of 101.5 g/head/day. Although, there was loss of a pig, average daily gain of piglets remaining was considered positive, the group recorded an increase of 6 kg in the 21 days of study.Group II received in drinking water, soluble tiamulin at concentration of 60 mg / litre for 5 consecutive days. In this group there was no mortality, all 12 piglets to heal within 10 days (cure rate 100%. The final

  3. [Effect of different nitrogen forms and ratio on growth and active ingredient content of Platycodon grandiflorum].

    Duan, Yun-jing; Wang, Kang-cai; Niu, Ling-hui; Li, Ke; Su, Yun-yun

    2015-10-01

    To providing evidence about nitrogen adequate application of Platycodon grandiflorum, the pot culture experiment was conducted to study the effect of nitrogen on the growth, physiological metabolism and the quality of P. grandiflorum. The activity of NR, GS and SOD, POD and CAT were determined. And the nitrate and ammonium nitrogen content, photosynthetic characteristics, active components of P. grandiflorum were determined. The results showed that the nitrate nitrogen content and P. biomass reached its maximum value, when NH4(+)-N/NO3(-) -N was 0: 100, the activity of NR. The activity of GS was the highest at the NH4(+) -N/NO3(-) -N ratio of 25:75 and ammonium nitrogen content was the highest at 75:25. The activity of SOD decreased and then increased with the increasing of NO3(-) -N. At the NH4(+) -N/NO3(-) -N ratio of 25: 75, the activity of CAT had its maximum value and the content of MDA had the minimum value. At the same time, the content of platycodon D was the highest at this treatment. The studies had shown that different nitrogen forms and ratio had a significant effect on the characteristics of photosynthetic physiology, nitrogen metabolism and resistance adjustment, growth and the quality of P. grandiflorum. The NH4(+) -N/NO3(-) -N ratio of 25: 75 was a suitable ratio of nitrogen forms for the growth of P. Grandiflorum and accumulating the content of platycodon D. PMID:26975097

  4. Effects of Two Endocrine-active Pharmaceuticals, Tamoxifen and Anastrozole, on Reproduction in a Marine Fish, Tautogolabrus adspersus

    Endocrine-active pharmaceuticals entering the aquatic environment through sewage effluent may have unintended, adverse impacts on the reproduction of aquatic organisms, which in turn may affect the sustainability of exposed populations. Laboratory experiments were conducted with ...

  5. Effects of Pharmaceuticals Used for Breast Cancer Treatment on Reproduction and Aromatase Activity in a Marine Fish

    Laboratory experiments were conducted with the marine fish cunner (Tautogolabrus adspersus) to evaluate whether four pharmaceuticals used in breast cancer treatment have an impact on reproduction or aromatase activity. Tamoxifen binds to estrogen receptors, while anastrozole, let...

  6. Anti-inflammatory, antioxidant and antitumor activities of ingredients of Curcuma phaeocaulis Val.

    Hou, Yan; Lu, Chuan-Li; Zeng, Qiao-Hui; Jiang, Jian-Guo

    2015-01-01

    Curcuma phaeocaulis Val. is used in Chinese Pharmacopoeia as health food and folk medicine for removing blood stasis, alleviating pain and tumor therapy. This research was aimed to explore and compare three main bioactivities including anti-oxidant, antitumor and anti-inflammatory activities between the ethanol extract of C. Phaeocaulis and its fractions using different in vitro models. Firstly, 70 % ethanol was used to extract C. Phaeocaulis, and then the crude extract was re-extracted, resulting in petroleum ether (EZ-PE), ethyl acetate (EZ-EA), and water fractions (EZ-W), respectively, and then a series of index was detected. Results showed that all the extracts had medium DPPH radical scavenging activity when the concentration was 200 μg/ml and their DPPH radical scavenging activity was in a concentration-dependent manner. The extracts except ethanol extract of C. Phaeocaulis had almost no cytotoxicity to the survival of RAW264.7 cell when the concentration reached 80 μg/ml, and all of them had medium inhibitory effect on nitrite release. Extracts of C. Phaeocaulis had medium intensity antitumor activity, EZ-PE and EZ-EA fractions significantly inhibited the proliferation of four tumor cells (SMMC-7721 cell lines, HepG-2 cell lines, A549 cell lines and Hela cell lines). C. Phaeocaulis had antioxidant and anti-inflammatory activities, which did not carry out centralized phenomenon when re-extracted. EZ-PE and EZ-EA were active antitumor sites of C. Phaeocaulis. PMID:26648822

  7. Active ingredients fatty acids as antibacterial agent from the brown algae Padina pavonica and Hormophysa triquetra

    Gihan Ahmed El Shoubaky; Essam Abd El Rahman Salem

    2014-01-01

    Objective: To estimate the fatty acids content in the brown algae Padina pavonica (P. pavonica) and Hormophysa triquetra (H. triquetra) and evaluate their potential antimicrobial activity as bioactive compounds.Methods:The fatty acid compositions of the examined species were analyzed using gas chromatography-mass spectrometry. The antimicrobial activity of crude and fatty acids was assessed using the agar plug technique.Results:The fatty acids profile ranged from C8:0 to C20:4. Concentration of saturated fatty acids in P. pavonica was in the order palmitic>myristic>stearic whereas concentration of the unsaturated fatty acids was oleic acid>palmitoleic>9-cis-hexadecenoic>linoleic acid>α-linolenic>arachidonic> elaidic acid. H. triquetra contained high concentration of saturated fatty acids than those of P. pavonica which was in the order as follows: palmitic>margaric>myristic>nonadecyclic>stearic>caprylic>tridecylic>pentadecylic>lauric while the unsaturated fatty acids consisted of oleic>nonadecenoic>non adecadienoate>margaroleic. The crude and fatty acid extracts of H. triquetra and P. pavonica were biologically active on the tested pathogens. H.triquetra exhibited a larger inhibitory zone than P. pavonica. Conclusions: The brown algae P. pavonica and H. triquetra have high efficient amount of fatty acids and showed strong antibacterial activity, especially H. triquetra.

  8. Intrinsic Motivation and Engagement as "Active Ingredients" in Garden-Based Education: Examining Models and Measures Derived from Self-Determination Theory

    Skinner, Ellen A.; Chi, Una

    2012-01-01

    Building on self-determination theory, this study presents a model of intrinsic motivation and engagement as "active ingredients" in garden-based education. The model was used to create reliable and valid measures of key constructs, and to guide the empirical exploration of motivational processes in garden-based learning. Teacher- and…

  9. Efficacy of attractive toxic sugar baits (ATSB) against Aedes albopictus with garlic oil encapsulated in beta-Cyclodextrin as the active ingredient

    We tested the efficacy of attractive toxic sugar bait (ATSB) with garlic oil microencapsulated in beta-cyclodextrin as active ingredient against Aedes albopictus in suburban Haifa, Israel. Two three-acre gardens with high numbers of Ae. albopictus were chosen for perimeter spray treatment with ATSB ...

  10. Attractive toxic sugar baits: Control of mosquitoes with the low risk active ingredient dinotefuran and potential impacts on non-target organisms in Morocco

    We evaluated the efficacy of ATSB in the laboratory and the field with the low risk active ingredient dinotefuran against mosquito populations. Assays indicated that dinotefuran in solution with the sugar baits was ingested and resulted in high mortality of female Culex quinquefasciatus and Aedes a...

  11. Anti-inflammatory, antioxidant and antitumor activities of ingredients of Curcuma phaeocaulis Val

    Hou, Yan; Lu, Chuan-li; Zeng, Qiao-Hui; Jiang, Jian-Guo

    2015-01-01

    Curcuma phaeocaulis Val. is used in Chinese Pharmacopoeia as health food and folk medicine for removing blood stasis, alleviating pain and tumor therapy. This research was aimed to explore and compare three main bioactivities including anti-oxidant, antitumor and anti-inflammatory activities between the ethanol extract of C. Phaeocaulis and its fractions using different in vitro models. Firstly, 70 % ethanol was used to extract C. Phaeocaulis, and then the crude extract was re-extracted, resu...

  12. The possibilities of using essential oils as an active ingredients or preservatives in cosmetic products

    Adaszy?ska, Michalina; Swarcewicz, Maria

    2011-01-01

    An important trend in the development of the cosmetics industry is searching for new biologically active, natural compounds and preservative systems, which will find application in the natural cosmetics production. Natural cosmetics are of considerable interest nowadays and essential oils could be employed in theirs production. The huge potential of essential oils indicates the possibility of applying them in practice because of theirs antibacterial, antiseptic, antifungal, and antioxidant...

  13. ANTIMICROBIAL ACTIVITY OF WATER EXTRACTS OF TRIKATU CHURNA AND ITS INDIVIDUAL INGREDIENT

    P.R. Malvankar* and M. M. Abhyankar

    2012-01-01

    Trikatu churna is one of the traditional poly herbal preparation, formed by mixing equal quantities of three important spicy materials such as Piper longum L. (Piperaceae), Piper nigrum L. (Piperaceae) and Zingiber officinale Roscoe (Zingiberaceae). Trikatu is also known as “ Three Bitters”. The trikatu preparation was reported to contain alkaloids, phenols, tannins, flavanoids, steroids, lignin & saponins. The objective of study is to evaluate the antimicrobial activity of trikatu churna & i...

  14. Diffusion of active ingredients in textiles: a three step multiscale model

    Goessens, Tineke; Malengier, Benny; Li, Pei; De Staelen, Rob H.

    2013-01-01

    Most practical textile models are based on a two scale approach: a one-dimensional fiber model and a fabric model. No meso-level is used in between, i.e. the yarn scale is neglected in this setup. For dense textile substrates this seems appropriate as the yarns connect everywhere, but for loose fabrics or scrims this approach cannot be kept. Specifically when one is interested in tracking an active component released by the fibers, the yarn level plays an important role. This is because the satu...

  15. Determination of antioxidant activity in herbal ingredients for foods using new methods of chemical analysis

    Katalina Muñoz

    2012-06-01

    Full Text Available A new procedure has been used to separate and quantify the free radical-scavenging activity of individual compounds 18 samples of Thymus vulgaris and 12 samples of Rosmarinus officinalis (both used as natural food preservatives, based on the combination of HPTLC (High Performance Thin Layer Chromatography and postchromatographic DPPH● radical derivatization. The compounds thymol and rosmarinic acid in T. vulgaris and R. officinalis, respectively, were identified by comparisons of their Rf values and UV spectra to standards analyzed under identical analytical conditions, while the quantitative data were calculated from their calibration curves. We found that not only that the biomass yield but also the metabolite content in herbs, depend on the ecotype (genetics and on the agro ecological conditions. The effect of the ambient on the metabolite content is extremely significant and also on their antioxidant activity (One-way ANOVA with Newman-Keuls Multiple Comparison post test was performed using GraphPad Prism version 4.00 for Windows, GraphPad Software. This work pretends to demonstrate the great importance of using new technologies for the selection of the best materials used as natural food preservatives.

  16. Piperine, an active ingredient of black pepper attenuates acetaminophen-induced hepatotoxicity in mice

    Evan Prince Sabina; Annie Deborah Harris Souriyan; Deborah Jackline; Mahaboob Khan Rasool

    2010-01-01

    Objective: To explore the hepatoprotective and antioxidant effects of piperine against acetaminophen-induced hepatotoxicity in mice. Methods: In mice, hepatotoxicity was induced by a single dose of acetaminophen (900 mg/kg b.w. i.p.). Piperine (25 mg/kg b.w. i.p.) and standard drug silymarin (25 mg/kg b.w. i.p.) were given to mice, 30 min after the single injection of acetaminophen. After 4 h, the mice were decapitated. Activities of liver marker enzymes [(aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP)] and inflammatory mediator tumour necrosis factor-alpha (TNF-α) were estimated in serum, while lipid peroxidation and antioxidant status (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-s-transferase and glutathione) were determined in liver homogenate of control and experimental mice. Results: Acetaminophen induction (900 mg/kg b.w. i.p.) significantly increased the levels of liver marker enzymes, TNF-α, and lipid peroxidation, and caused the depletion of antioxidant status. Piperine and silymarin treatment to acetaminophen challenged mice resulted in decreased liver marker enzymes activity, TNF-α and lipid peroxidation levels with increase in antioxidant status. Conclusions: The results clearly demonstrate that piperine shows promising hepatoprotective effect as comparable to standard drug silymarin.

  17. Ibuprofen-in-cyclodextrin-in-W/O/W emulsion - Improving the initial and long-term encapsulation efficiency of a model active ingredient.

    Hattrem, Magnus N; Kristiansen, Kåre A; Aachmann, Finn L; Dille, Morten J; Draget, Kurt I

    2015-06-20

    A challenge in formulating water-in-oil-in-water (W/O/W) emulsions is the uncontrolled release of the encapsulated compound prior to application. Pharmaceuticals and nutraceuticals usually have amphipathic nature, which may contribute to leakage of the active ingredient. In the present study, cyclodextrins (CyDs) were used to impart a change in the relative polarity and size of a model compound (ibuprofen) by the formation of inclusion complexes. Various inclusion complexes (2-hydroxypropyl (HP)-β-CyD-, α-CyD- and γ-CyD-ibuprofen) were prepared and presented within W/O/W emulsions, and the initial and long-term encapsulation efficiency was investigated. HP-β-CyD-ibuprofen provided the highest encapsulation of ibuprofen in comparison to a W/O/W emulsion with unassociated ibuprofen confined within the inner water phase, with a four-fold increase in the encapsulation efficiency. An improved, although lower, encapsulation efficiency was obtained for the inclusion complex γ-CyD-ibuprofen in comparison to HP-β-CyD-ibuprofen, whereas α-CyD-ibuprofen had a similar encapsulation efficiency to that of unassociated ibuprofen. The lower encapsulation efficiency of ibuprofen in combination with α-CyD and γ-CyD was attributed to a lower association constant for the γ-CyD-ibuprofen inclusion complex and the ability of α-CyD to form inclusion complexes with fatty acids. For the W/O/W emulsion prepared with HP-β-CyD-ibuprofen, the highest encapsulation of ibuprofen was obtained at hyper- and iso-osmotic conditions and by using an excess molar ratio of CyD to ibuprofen. In the last part of the study, it was suggested that the chemical modification of the HP-β-CyD molecule did not influence the encapsulation of ibuprofen, as a similar encapsulation efficiency was obtained for an inclusion complex prepared with mono-1-glucose-β-CyD. PMID:25839416

  18. Supply Network Planning for New Product Market Entry in the Pharmaceutical Industry

    Hansen, Klaus Reinholdt Nyhuus; Grunow, Martin

    2011-01-01

    planning before and during the market entry of the drug after the drug has been approved. Production of the active pharmaceutical ingredient [API] is characterized by long change-over times due to cleaning requirements. Production planning is long term, multiple batches of each drug are produced in...

  19. Removal of pharmaceuticals in biologically treated wastewater by chlorine dioxide or peracetic acid

    Hey, G.; Ledin, Anna; La Cour Jansen, Jes;

    2012-01-01

    Removal of six active pharmaceutical ingredients in wastewater was investigated using chlorine dioxide (ClO2) and peracetic acid (PAA) as chemical oxidants. Four non-steroidal anti -inflammatory drugs (ibuprofen, naproxen, diclofenac, and mefenamic acid) and two l ipid regulating agents (gemfibro...

  20. 槟榔十三味丸(高尤-13)对慢性应激抑郁大鼠行为学及海马神经元凋亡的影响%Effects of Mongolian Pharmaceutical Betel Shisanwei Ingredients Pill on Behavior and APoPtosis of HiPPocamPal Cells in DePressive Rats

    乌吉斯古冷; 佟海英; 斯日古楞; 白亮凤; 包伍叶; 胡日乐巴根; 李婧; 张月

    2014-01-01

    Objective:To study the effect of Mongolian Pharmaceutical Betel Shisanwei Ingredients Pill on behavior and apoptosis of hipp-ocampal cells in depressive rats and from the cell level to discuss antidepressant mechanism. Methods:48 male Wistar rats were random-ly divided into six groups according to the sugar consumption test and body weight(8 rats in each group):normal control group,model group,Fluoxetine group(3. 3 mg·kg - 1 )and high,medium and low dose group(0. 25,0. 5,1. 0 g·kg - 1 )of Betel Shisanwei ingredi-ents Pill. Except the normal control,the other groups were treated with the chronic unpredictable mild stress stimulation combined with lonely raising. Intragastric administration,once daily,continuously for 28 days. Behavior changes of rats were detected through open?field test,and sugar consumption test were also measured by AnnexinV - FITC/ PI double labeling. Flow Cytometer was used to detect the apoptotic rats in the hippocampus. Results:Compared with normal control group,the scores of horizontal activity and vertical activi-ty,weight and sugar consumption group decreased significantly(P < 0. 01);Compared with model group,Fluoxetine group and Betel Shisanwei Ingredients Pill medium,high dose group got significantly higher scores of horizontal activity and vertical activity,weight and sugar consumption(P < 0. 05). Flow Cytometer results show that compared with normal control group,model group rats hippocampal ap-optosis rate was significantly higher(P < 0. 05);Compared with model group,fluoxetine group,Betel Shisanwei ingredients pills medi-um,high dose group of rat hippocampal apoptosis rate is reduced,with decreased significantly(P < 0. 01). Conclusion:Chronic stress depression model rats exists abnormal behavior and hippocampus apoptosis phenomenon,Betel Shisanwei Ingredients pill can improve depression model rats abnormal behavior and inhibit apoptosis of rat hippocampal caused by chronic stress and play a role of antidepres-sant.%目的:观

  1. Application of the KeratinoSens™ assay for assessing the skin sensitization potential of agrochemical active ingredients and formulations.

    Settivari, Raja S; Gehen, Sean C; Amado, Ricardo Acosta; Visconti, Nicolo R; Boverhof, Darrell R; Carney, Edward W

    2015-07-01

    Assessment of skin sensitization potential is an important component of the safety evaluation process for agrochemical products. Recently, non-animal approaches including the KeratinoSens™ assay have been developed for predicting skin sensitization potential. Assessing the utility of the KeratinoSens™ assay for use with multi-component mixtures such as agrochemical formulations has not been previously evaluated and is a significant need. This study was undertaken to evaluate the KeratinoSens™ assay prediction potential for agrochemical formulations. The assay was conducted for 8 agrochemical active ingredients (AIs) including 3 sensitizers (acetochlor, meptyldinocap, triclopyr), 5 non-sensitizers (aminopyralid, clopyralid, florasulam, methoxyfenozide, oxyfluorfen) and 10 formulations for which in vivo sensitization data were available. The KeratinoSens™ correctly predicted the sensitization potential of all the AIs. For agrochemical formulations it was necessary to modify the standard assay procedure whereby the formulation was assumed to have a common molecular weight. The resultant approach correctly predicted the sensitization potential for 3 of 4 sensitizing formulations and all 6 non-sensitizing formulations when compared to in vivo data. Only the meptyldinocap-containing formulation was misclassified, as a result of high cytotoxicity. These results demonstrate the promising utility of the KeratinoSens™ assay for evaluating the skin sensitization potential of agrochemical AIs and formulations. PMID:25981449

  2. Elemental characterization of marijuana (cannabis sativa) as a stride in the isolation of its active ingredients

    Seed, stem and leaves samples of Marijuana (Cannabis sativa) popularly called Indian Hemp available in northern Nigeria were analyzed for trace amounts of Mg, Al, Ca, Ti, Mn, Na, Br, La, Yb, Cr, Fe, Zn, and Ba using Instrumental Neutron Activation Analysis. Sample sizes of roughly 300mg irradiated for five minutes (short irradiation) and six hours (long irradiation), with decay times of 7 minutes, 10,000 minutes and 26,000 minutes for short, medium and long-lived nuclides respectively. Counting times for ten minutes (short-lived nuclides), 1,800 minutes (medium-lived nuclides) and 36,000 minutes (long-lived nuclides) yielded detection limits between 0.05 - 0.09μg/g. For comparative study, refined tobacco produced by a tobacco company operating in northern Nigeria were characterized together with the marijuana-which is usually smoked raw with leaves stem and seed packed together. The results obtained shows that both the refined tobacco and the raw marijuana have high c oncentration of Ca, Mg, Al and Mn and low values of Na, Br and La. However, marijuana was found to have heavy elements in abundance compared to the refined tobacco, with Zn = 20.5 μg/g and Cr = 14.3μg/g recording the highest values among the heavy elements detected. This is a sharp difference between the two since the values of heavy elements obtained for the refined tobacco are even below detection limits. Quality Control and Quality Assurance was tested using certified reference material obtained from NIST (Tomato Leaves).

  3. Widespread occurrence of neuro-active pharmaceuticals and metabolites in 24 Minnesota rivers and wastewaters

    Writer, Jeffrey; Ferrer, Imma; Barber, Larry B.; Thurman, E. Michael

    2013-01-01

    Concentrations of 17 neuro-active pharmaceuticals and their major metabolites (bupropion, hydroxy-bupropion, erythro-hydrobupropion, threo-hydrobupropion, carbamazepine, 10,11,-dihydro-10,11,-dihydroxycarbamazepine, 10-hydroxy-carbamazepine, citalopram, N-desmethyl-citalopram, fluoxetine, norfluoxetine, gabapentin, lamotrigine, 2-N-glucuronide-lamotrigine, oxcarbazepine, venlafaxine and O-desmethyl-venlafaxine), were measured in treated wastewater and receiving surface waters from 24 locations across Minnesota, USA. The analysis of upstream and downstream sampling sites indicated that the wastewater treatment plants were the major source of the neuro-active pharmaceuticals and associated metabolites in surface waters of Minnesota. Concentrations of parent compound and the associated metabolite varied substantially between treatment plants (concentrations ± standard deviation of the parent compound relative to its major metabolite) as illustrated by the following examples; bupropion and hydrobupropion 700 ± 1000 ng L−1, 2100 ± 1700 ng L−1, carbamazepine and 10-hydroxy-carbamazepine 480 ± 380 ng L−1, 360 ± 400 ng L−1, venlafaxine and O-desmethyl-venlafaxine 1400 ± 1300 ng L−1, 1800 ± 2300 ng L−1. Metabolites of the neuro-active compounds were commonly found at higher or comparable concentrations to the parent compounds in wastewater effluent and the receiving surface water. Neuro-active pharmaceuticals and associated metabolites were detected only sporadically in samples upstream from the effluent outfall. Metabolite to parent ratios were used to evaluate transformation, and we determined that ratios in wastewater were much lower than those reported in urine, indicating that the metabolites are relatively more labile than the parent compounds in the treatment plants and in receiving waters. The widespread occurrence of neuro-active pharmaceuticals and metabolites in Minnesota effluents and surface waters indicate that

  4. Khaya grandifoliola C.DC: a potential source of active ingredients against hepatitis C virus in vitro.

    Galani, Borris Rosnay Tietcheu; Sahuc, Marie-Emmanuelle; Sass, Gabriele; Njayou, Frédéric Nico; Loscher, Christine; Mkounga, Pierre; Deloison, Gaspard; Brodin, Priscille; Rouillé, Yves; Tiegs, Gisa; Séron, Karin; Moundipa, Paul Fewou

    2016-05-01

    In this study, we examined the antiviral properties of Khaya grandifoliola C.DC (Meliaceae) on the hepatitis C virus (HCV) life cycle in vitro and identified some of the chemical constituents contained in the fraction with the most antiviral activity. Dried bark powder was extracted by maceration in a methylene chloride/methanol (MCM) system (50:50; v/v) and separated on silica gel by flash chromatography. Infection and replication rates in Huh-7 cells were investigated by luciferase reporter assay and indirect immunofluorescence assay using subgenomic replicons, HCV pseudotyped particles, and cell-culture-derived HCV (HCVcc), respectively. Cell viability was assessed by MTT assay, and cellular gene expression was analysed by qRT-PCR. The chemical composition of the fraction with the most antiviral activity was analysed by coupled gas chromatography and mass spectrometry (GC-MS). Five fractions of different polarities (F0-F100) were obtained from the MCM extract. One fraction (KgF25) showed the strongest antiviral effect on LucUbiNeoET replicons at nontoxic concentrations. Tested at 100 µg/mL, KgF25 had a high inhibitory effect on HCV replication, comparable to that of 0.01 µM daclatasvir or 1 µM telaprevir. This fraction also inhibited HCVcc infection by mostly targeting the entry step. KgF25 inhibited HCV entry in a pan-genotypic manner by directly inactivating free viral particles. Its antiviral effects were mediated by the transcriptional upregulation of the haem oxygenase-1 gene and interferon antiviral response. Three constituents, namely, benzene, 1,1'-(oxydiethylidene)bis (1), carbamic acid, (4-methylphenyl)-, 1-phenyl (2), and 6-phenyl, 4-(1'-oxyethylphenyl) hexene (3), were identified from the active fraction KgF25 by GC-MS. Khaya grandifoliola contains ingredients capable of acting on different steps of the HCV life cycle. PMID:26843184

  5. THE EFFECT OF DIFFERENT DOSES OF NITROGEN (N) APPLICATION ON THE ANTIOXIDANT ACTIVITY AND PHENOLIC MATERIAL INGREDIENT OF SORREL (RUMEX ACETOSA L.)

    Adiloğlu, Sevinç; Açıkgöz, Funda Eryılmaz; Dağlıoğlu, Figen; Barut Gök, Sıla; Altan, Deniz Damla

    2015-01-01

    In this study, The effect of different doses of nitrogen (N) application on the antioxidant activity and phenolic material ingredient of sorrel (Rumex acetosa L.) are investigated. In the test, four various doses of nitrogen NH4NO3 fertilizer have been applied to the plants. As a result, it has been determined that the antioxidant activity and phenolic compounds of Sorrel (Rumex acetosa L.) have parallels with the increase in the application of nitrogen.

  6. Pharmaceutical aerosols. Study of their gamma radiation sterilization

    The gamma radiation sterilization of pharmaceutical aerosols was studied. The following topics were investigated: radiosterilization of nitrogen protoxide used as a propellant; radiosterilization of packaging materials (aluminium containers, plastics valves); radio-sterilization of excipients and active ingredients. Most of the investigated materials proved to be stable to irradiation (2,5 Mrads) from pharmacopoeial aspect. Stability tests of the preparations packaged showed no change in the parameters investigated

  7. Rosmarinus officinalis L. extract and some of its active ingredients as potential emulsion stabilizers: a new approach to the formation of multiple (W/O/W) emulsion.

    Cizauskaite, Ugne; Ivanauskas, Liudas; Jakštas, Valdas; Marksiene, Ruta; Jonaitiene, Laimute; Bernatoniene, Jurga

    2016-09-01

    Nowadays, novel topical formulations loaded with natural functional actives are under intense investigations. Therefore, the aim of our study was to evaluate how the rosemary extract and some of its active ingredients [rosmarinic acid (RA), ursolic acid (UA) and oleanolic acid (OA)] affect technological characteristics of multiple emulsion. Formulation has been prepared by adding investigated solutions (10%) in water/oil/water (W/O/W) multiple emulsion consisting of different lipophilic phases: olive oil and liquid paraffin, with 0.5% emulsifying agent (complex of sodium polyacrylate and polysorbate 20) under constant stirring with mechanical stirrer at room temperature. The emulsion parameters were evaluated using centrifugation test, freeze-thaw cycle test, microscopical and texture analyses. Rosemary's triterpenic saponins UA and OA showed the highest emulsion stabilizing properties: they decreased CI from 3.26% to 10.23% (p rosemary active ingredients is not surfactant-like. Even though emulsifier itself at low concentration intends to form directly the multiple emulsion, the obtained results indicate that rosemary extract containing active ingredients does not only serve as functional cosmetic agent due to a number of biological activities, but also offer potential advantages as a stabilizer and an enhancer of W/O/W emulsions formation for dermopharmaceutical and cosmetic preparations. PMID:26000558

  8. Active heterotrophic biomass and sludge retention time (SRT) as determining factors for biodegradation kinetics of pharmaceuticals in activated sludge.

    Majewsky, Marius; Gallé, Tom; Yargeau, Viviane; Fischer, Klaus

    2011-08-01

    The present study investigates the biodegradation of pharmaceutically active compounds (PhACs) by active biomass in activated sludge. Active heterotrophs (X(bh)) which are known to govern COD removal are suggested as a determining factor for biological PhAC removal as well. Biodegradation kinetics of five polar PhACs were determined in activated sludge of two wastewater treatment plants which differed in size, layout and sludge retention time (SRT). Results showed that active fractions of the total suspended solids (TSS) differed significantly between the two sludges, indicating that TSS does not reveal information about heterotrophic activity. Furthermore, PhAC removal was significantly faster in the presence of high numbers of heterotrophs and a low SRT. Pseudo first-order kinetics were modified to include X(bh) and used to describe decreasing PhAC elimination with increasing SRT. PMID:21652206

  9. [Anti-counterfeit activities of pharmaceutical companies in Japan: for patient safety].

    Shofuda, Ken-ichi; Aragane, Katsumi; Igari, Yasutaka; Matsumoto, Kinya; Ito, Kazuya

    2014-01-01

    Global spread of counterfeit medicines is an imminent threat for the patients' safety. Although major targets of counterfeits are still erectile dysfunction (ED) drugs in the industrialized countries, including Japan, anti-cancer agents and some medicines for metabolic syndromes are also being counterfeited and circulated to the market mainly through the Internet. Due to the global expansion of the business, pharmaceutical companies based in Japan are suffering from the damage of counterfeits, illegal sales including diversion, and thefts, which have never been experienced in the conventional domestic market. We, pharmaceutical companies, must be responsible for the prevention of the prevalence because our mission is to deliver effective and safe medicine to patients. For this end, we are taking necessary actions including, 1. Forestalling counterfeit, falsification and illicit trade: Measures to prevent counterfeiting are taken by introducing anti-counterfeit technologies to the packaging and tablets on a risk basis. It is also important to establish supply chain security on a global scale. 2. Finding out counterfeits and cooperating crackdown: We are conducting market and internet surveillances when high risk products are sold in high risk markets. The outcome of the criminal investigation is reported to authorities and police if necessary. 3. Conducting educational campaign to medical staff or patients: For example, four companies which manufacture and sell ED drug in Japan are collaboratively continuing activities to raise the awareness of the danger of Internet purchase. To deliver effective and safe medicines stably and globally, pharmaceutical companies extend comprehensive measures against counterfeit and illicit trading. PMID:24492224

  10. A target analogue imprinted polymer for the recognition of antiplatelet active ingredients in Radix Salviae Miltiorrhizae by LC/MS/MS.

    Huang, Meixia; Pang, Wensheng; Zhang, Jing; Lin, Siding; Hu, Juan

    2012-01-25

    The purpose of this study was to prepare a propyl gallate (PrG) molecular imprinted polymer as a cartridge stuffing material to isolate antiplatelet active ingredients. A macroporous polymer was synthesized utilizing ethylene glycol dimethacrylate (EDMA) as the crosslinking agent, PrG as the template molecule and 4-vinylpyridine (4-Vpy) as the functional monomer. Subsequently, PrG was removed by washing with methanol-glacial acetic acid (9:1, v/v). The molecular imprinted polymer recognized an active ingredient, protocatechuic acid, from a crude extract of the Chinese herbal medicine, Radix Salviae Miltiorrhizae (Danshen), using an on-line column switching solid phase extraction process. Pharmacological experiments showed that protocatechuic acid inhibits arachidonic acid (10 mg/kg) induced aggregation of rat platelets in vivo. This study provides an example of an application of separation-analysis technique for screening potentially bioactive compounds. PMID:21978827

  11. On the direct characterization and quantification of active ingredients in commercial solid drugs using PIXE, PIGE and ToF-SIMS techniques

    The quantification of the active ingredient (AI) in drugs is a crucial and important step in the drug quality control process. This is usually performed by using wet chemical techniques like HPLC, LC-MS/MS, UV spectrophotometry and other appropriate organic analytical methods. In the case of an active ingredient contains specific heteroatoms (F, S, Cl, Br, ...), elemental IBA technique can be explored for molecular quantification. IBA techniques permit the analysis of the sample under solid form, without any laborious sample preparation. This is an advantage when the number of sample is relatively large. In this work, we demonstrate the ability of the Thick target PIXE (TT-PIXE) and the TT-PIGE techniques for rapid and accurate quantification of celecoxib and atorvastatin in commercial solid drugs. The experimental aspects related to the quantification validity are presented and discussed. (author)

  12. 77 FR 66620 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

    2012-11-06

    ...); fees for type II active pharmaceutical ingredient (API) and final dosage form (FDF) facilities; fees... (77 FR 43844), FDA published a 60-day notice requesting public comment on the proposed collection...

  13. 21 CFR 310.540 - Drug products containing active ingredients offered over-the-counter (OTC) for use as stomach...

    2010-04-01

    ... offered over-the-counter (OTC) for use as stomach acidifiers. 310.540 Section 310.540 Food and Drugs FOOD... ingredients offered over-the-counter (OTC) for use as stomach acidifiers. (a) Betaine hydrochloride, glutamic...-counter (OTC) drug products for use as stomach acidifiers. Because of the lack of adequate data...

  14. Altered Gene Expression in the Schistosome-Transmitting Snail Biomphalaria glabrata following Exposure to Niclosamide, the Active Ingredient in the Widely Used Molluscicide Bayluscide

    Zhang, Si-Ming; Buddenborg, Sarah K; Adema, Coen M.; Sullivan, John T.; Loker, Eric S

    2015-01-01

    In view of the call by the World Health Organization (WHO) for elimination of schistosomiasis as a public health problem by 2025, use of molluscicides in snail control to supplement chemotherapy–based control efforts is likely to increase in the coming years. The mechanisms of action of niclosamide, the active ingredient in the most widely used molluscicides, remain largely unknown. A better understanding of its toxicology at the molecular level will both improve our knowledge of snail biolog...

  15. Homeopathy – what are the active ingredients? An exploratory study using the UK Medical Research Council's framework for the evaluation of complex interventions

    Weiss Marjorie; Thompson Trevor DB

    2006-01-01

    Abstract Background Research in homeopathy has traditionally addressed itself to defining the effectiveness of homeopathic potencies in comparison to placebo medication. There is now increasing awareness that the homeopathic consultation is in itself a therapeutic intervention working independently or synergistically with the prescribed remedy. Our objective was to identify and evalute potential "active ingredients" of the homeopathic approach as a whole, in a prospective formal case series, ...

  16. Potential Upstream Strategies for the Mitigation of Pharmaceuticals in the Aquatic Environment: a Brief Review.

    Blair, Benjamin D

    2016-06-01

    Active pharmaceutical ingredients represent a class of pollutants of emerging concern, and there is growing evidence that these pollutants can cause damage to the aquatic environment. As regulations to address these concerns are expected in developed nations, decision-makers are looking to the scientific community for potential solutions. To inform these regulatory efforts, further information on the potential strategies to reduce the levels of pharmaceuticals entering the aquatic environment is needed. End-of-pipe (i.e., wastewater treatment) technologies that can remove pharmaceuticals exist; however, they are costly to install and operate. Thus, the goal of this brief review is to look beyond end-of-pipe solutions and present various upstream mitigation strategies discussed within the scientific literature. Programs such as pharmaceutical take-back programs currently exist to attempt to reduce pharmaceutical concentrations in the environment, although access and coverage are often limited for many programs. Other potential strategies include redesigning pharmaceuticals to minimize aquatic toxicity, increasing the percent of the pharmaceuticals metabolized in the body, selecting less harmful pharmaceuticals for use, starting new prescriptions at lower dosages, selecting pharmaceuticals with lower excretion rates, and implementing source treatment such as urine separating toilets. Overall, this brief review presents a summary of the upstream preventative recommendations to mitigate pharmaceuticals from entering the aquatic environment with an emphasis on regulatory efforts in the USA and concludes with priorities for further research. PMID:27068434

  17. The simultaneous determination of active ingredients in cough-cold mixtures by isocratic reversed-phase ion-pair high-performance liquid chromatography.

    Lau, O W; Chan, K; Lau, Y K; Wong, W C

    1989-01-01

    A simple, rapid and accurate method for the simultaneous determination of active ingredients in cough-cold mixtures using isocratic reversed-phase ion-pair high-performance liquid chromatography has been developed. It involves the use of an octadecylsilane column as the stationary phase with methanol, water, tetrahydrofuran, phosphoric acid mixtures as mobile phase including sodium dioctylsulphosuccinate as the ion-pair agent. The pH of the mobile phase was adjusted to 4.6 by means of phosphoric acid and ammonium hydroxide solutions. The proposed method involves the simple dilution of the samples with the mobile phase and the addition of metoclopramide hydrochloride as the internal standard. The active ingredients under investigation were chlorpheniramine, codeine, diphenhydramine, ephedrine, ethylmorphine, phenylephrine, phenylpropanolamine and pholcodine, which exist as various combinations in cough-cold mixtures. The optimum composition of the mobile phase and the optimum flow rate were determined and are reported. The method was applied to the determination of active ingredients in seven commercially available cough-cold mixtures. PMID:2577452

  18. Non-Hodgkin Lymphoma and Occupational Exposure to Agricultural Pesticide Chemical Groups and Active Ingredients: A Systematic Review and Meta-Analysis

    Leah Schinasi

    2014-04-01

    Full Text Available This paper describes results from a systematic review and a series of meta-analyses of nearly three decades worth of epidemiologic research on the relationship between non-Hodgkin lymphoma (NHL and occupational exposure to agricultural pesticide active ingredients and chemical groups. Estimates of associations of NHL with 21 pesticide chemical groups and 80 active ingredients were extracted from 44 papers, all of which reported results from analyses of studies conducted in high-income countries. Random effects meta-analyses showed that phenoxy herbicides, carbamate insecticides, organophosphorus insecticides and the active ingredient lindane, an organochlorine insecticide, were positively associated with NHL. In a handful of papers, associations between pesticides and NHL subtypes were reported; B cell lymphoma was positively associated with phenoxy herbicides and the organophosphorus herbicide glyphosate. Diffuse large B-cell lymphoma was positively associated with phenoxy herbicide exposure. Despite compelling evidence that NHL is associated with certain chemicals, this review indicates the need for investigations of a larger variety of pesticides in more geographic areas, especially in low- and middle-income countries, which, despite producing a large portion of the world’s agriculture, were missing in the literature that were reviewed.

  19. In-stream attenuation of neuro-active pharmaceuticals and their metabolites

    Writer, Jeffrey; Antweiler, Ronald C.; Ferrar, Imma; Ryan, Joseph N.; Thurman, Michael

    2013-01-01

    In-stream attenuation was determined for 14 neuro-active pharmaceuticals and associated metabolites. Lagrangian sampling, which follows a parcel of water as it moves downstream, was used to link hydrological and chemical transformation processes. Wastewater loading of neuro-active compounds varied considerably over a span of several hours, and thus a sampling regime was used to verify that the Lagrangian parcel was being sampled and a mechanism was developed to correct measured concentrations if it was not. In-stream attenuation over the 5.4-km evaluated reach could be modeled as pseudo-first-order decay for 11 of the 14 evaluated neuro-active pharmaceutical compounds, illustrating the capacity of streams to reduce conveyance of neuro-active compounds downstream. Fluoxetine and N-desmethyl citalopram were the most rapidly attenuated compounds (t1/2 = 3.6 ± 0.3 h, 4.0 ± 0.2 h, respectively). Lamotrigine, 10,11,-dihydro-10,11,-dihydroxy-carbamazepine, and carbamazepine were the most persistent (t1/2 = 12 ± 2.0 h, 12 ± 2.6 h, 21 ± 4.5 h, respectively). Parent compounds (e.g., buproprion, carbamazepine, lamotrigine) generally were more persistent relative to their metabolites. Several compounds (citalopram, venlafaxine, O-desmethyl-venlafaxine) were not attenuated. It was postulated that the primary mechanism of removal for these compounds was interaction with bed sediments and stream biofilms, based on measured concentrations in stream biofilms and a column experiment using stream sediments.

  20. On the Correlation of Effective Terahertz Refractive Index and Average Surface Roughness of Pharmaceutical Tablets

    Chakraborty, Mousumi; Bawuah, Prince; Tan, Nicholas; Ervasti, Tuomas; Pääkkönen, Pertti; Zeitler, J. Axel; Ketolainen, Jarkko; Peiponen, Kai-Erik

    2016-08-01

    In this paper, we have studied terahertz (THz) pulse time delay of porous pharmaceutical microcrystalline compacts and also pharmaceutical tablets that contain indomethacin (painkiller) as an active pharmaceutical ingredient (API) and microcrystalline cellulose as the matrix of the tablet. The porosity of a pharmaceutical tablet is important because it affects the release of drug substance. In addition, surface roughness of the tablet has much importance regarding dissolution of the tablet and hence the rate of drug release. Here, we show, using a training set of tablets containing API and with a priori known tablet's quality parameters, that the effective refractive index (obtained from THz time delay data) of such porous tablets correlates with the average surface roughness of a tablet. Hence, THz pulse time delay measurement in the transmission mode provides information on both porosity and the average surface roughness of a compact. This is demonstrated for two different sets of pharmaceutical tablets having different porosity and average surface roughness values.

  1. On the Correlation of Effective Terahertz Refractive Index and Average Surface Roughness of Pharmaceutical Tablets

    Chakraborty, Mousumi; Bawuah, Prince; Tan, Nicholas; Ervasti, Tuomas; Pääkkönen, Pertti; Zeitler, J. Axel; Ketolainen, Jarkko; Peiponen, Kai-Erik

    2016-03-01

    In this paper, we have studied terahertz (THz) pulse time delay of porous pharmaceutical microcrystalline compacts and also pharmaceutical tablets that contain indomethacin (painkiller) as an active pharmaceutical ingredient (API) and microcrystalline cellulose as the matrix of the tablet. The porosity of a pharmaceutical tablet is important because it affects the release of drug substance. In addition, surface roughness of the tablet has much importance regarding dissolution of the tablet and hence the rate of drug release. Here, we show, using a training set of tablets containing API and with a priori known tablet's quality parameters, that the effective refractive index (obtained from THz time delay data) of such porous tablets correlates with the average surface roughness of a tablet. Hence, THz pulse time delay measurement in the transmission mode provides information on both porosity and the average surface roughness of a compact. This is demonstrated for two different sets of pharmaceutical tablets having different porosity and average surface roughness values.

  2. Assessing the diurnal variability of pharmaceutical and personal care products in a full-scale activated sludge plant

    An intensive sampling campaign has been carried out in a municipal wastewater treatment plant (WWTP) to assess the dynamics of the influent pharmaceutical active compounds (PhAC) and musks. The mass loadings of these compounds in wastewater influents displayed contrasting diurnal variations depending on the compound. The musks and some groups of PhACs tended to follow a similar diurnal trend as compared to macropollutants, while the majority of PhACs followed either the opposite trend or no repeatable trend. The total musk loading to the WWTP was 0.74 ± 0.25 g d-1, whereas the total PhAC mass loading was 84.7 ± 63.8 g d-1. Unlike the PhACs, the musks displayed a high repeatability from one sampling day to the next. The range of PhAC loadings in the influent to WWTPs can vary several orders of magnitude from one day or week to the next, representing a challenge in obtaining data for steady-state modelling purposes. - Highlights: → Investigated the variations in influent wastewater pharmaceutical and musk loadings. → A high number of different pharmaceutical and musk compounds was analysed. → Many pharmaceutical groups displayed different characteristic patterns. → A representative steady-state pattern was observable for musks, not pharmaceuticals. → The results are relevant to the design of sampling campaigns for modelling purposes. - The diurnal variations of pharmaceuticals and musks were studied in an activated sludge plant, where the loadings of the musks were more repeatable than the pharmaceuticals.

  3. Assessing the diurnal variability of pharmaceutical and personal care products in a full-scale activated sludge plant

    Salgado, R. [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); ESTS-IPS, Escola Superior de Tecnologia de Setubal do Instituto Politecnico de Setubal, Rua Vale de Chaves, Campus do IPS, Estefanilha, 2910-761 Setubal (Portugal); Marques, R. [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Instituto de Biologia Experimental e Tecnologica (IBET), Av. da Republica (EAN), 2784-505 Oeiras (Portugal); Noronha, J.P. [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Mexia, J.T. [Center of Mathematic Applications, Mathematics Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Carvalho, G. [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Instituto de Biologia Experimental e Tecnologica (IBET), Av. da Republica (EAN), 2784-505 Oeiras (Portugal); Oehmen, A., E-mail: adriano@dq.fct.unl.pt [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Reis, M.A.M. [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal)

    2011-10-15

    An intensive sampling campaign has been carried out in a municipal wastewater treatment plant (WWTP) to assess the dynamics of the influent pharmaceutical active compounds (PhAC) and musks. The mass loadings of these compounds in wastewater influents displayed contrasting diurnal variations depending on the compound. The musks and some groups of PhACs tended to follow a similar diurnal trend as compared to macropollutants, while the majority of PhACs followed either the opposite trend or no repeatable trend. The total musk loading to the WWTP was 0.74 {+-} 0.25 g d{sup -1}, whereas the total PhAC mass loading was 84.7 {+-} 63.8 g d{sup -1}. Unlike the PhACs, the musks displayed a high repeatability from one sampling day to the next. The range of PhAC loadings in the influent to WWTPs can vary several orders of magnitude from one day or week to the next, representing a challenge in obtaining data for steady-state modelling purposes. - Highlights: > Investigated the variations in influent wastewater pharmaceutical and musk loadings. > A high number of different pharmaceutical and musk compounds was analysed. > Many pharmaceutical groups displayed different characteristic patterns. > A representative steady-state pattern was observable for musks, not pharmaceuticals. > The results are relevant to the design of sampling campaigns for modelling purposes. - The diurnal variations of pharmaceuticals and musks were studied in an activated sludge plant, where the loadings of the musks were more repeatable than the pharmaceuticals.

  4. Validation of quantitative 1H NMR method for the analysis of pharmaceutical formulations

    The need for effective and reliable quality control in products from pharmaceutical industries renders the analyses of their active ingredients and constituents of great importance. This study presents the theoretical basis of ¹H NMR for quantitative analyses and an example of the method validation according to Resolution RE N. 899 by the Brazilian National Health Surveillance Agency (ANVISA), in which the compound paracetamol was the active ingredient. All evaluated parameters (selectivity, linearity, accuracy, repeatability and robustness) showed satisfactory results. It was concluded that a single NMR measurement provides structural and quantitative information of active components and excipients in the sample. (author)

  5. 77 FR 63290 - Foreign-Trade Zone 121-Albany, NY; Notification of Proposed Production Activity; Albany Molecular...

    2012-10-16

    ... Rensselaer, New York, (Board Order 698, 7/20/1994, 59 FR 18318, 7/28/1994). AMRI is now requesting to produce an active pharmaceutical ingredient, dexpramipexole dihydrochloride monohydrate, under...

  6. Biotransformation and adsorption of pharmaceutical and personal care products by activated sludge after correcting matrix effects.

    Deng, Yu; Li, Bing; Yu, Ke; Zhang, Tong

    2016-02-15

    This study reported significant suppressive matrix effects in analyses of six pharmaceutical and personal care products (PPCPs) in activated sludge, sterilized activated sludge and untreated sewage by ultra-performance liquid chromatography-tandem mass spectrometry. Quantitative matrix evaluation on selected PPCPs supplemented the limited quantification data of matrix effects on mass spectrometric determination of PPCPs in complex environment samples. The observed matrix effects were chemical-specific and matrix-dependent, with the most pronounced average effect (-55%) was found on sulfadiazine in sterilized activated sludge. After correcting the matrix effects by post-spiking known amount of PPCPs, the removal mechanisms and biotransformation kinetics of selected PPCPs in activated sludge system were revealed by batch experiment. Experimental data elucidated that the removal of target PPCPs in the activated sludge process was mainly by biotransformation while contributions of adsorption, hydrolysis and volatilization could be neglected. High biotransformation efficiency (52%) was observed on diclofenac while other three compounds (sulfadiazine, sulfamethoxazole and roxithromycin) were partially biotransformed by ~40%. The other two compounds, trimethoprim and carbamazepine, showed recalcitrant to biotransformation of the activated sludge. PMID:26706769

  7. Pharmaceutical cocrystals: walking the talk.

    Bolla, Geetha; Nangia, Ashwini

    2016-06-28

    Pharmaceutical cocrystals belong to a sub-class of cocrystals wherein one of the components is a drug molecule (or an active pharmaceutical ingredient, API) and the second is a benign food or drug grade additive (generally regarded as safe, GRAS). The two components are hydrogen-bonded in a fixed stoichiometric ratio in the crystal lattice. In the past decade, pharmaceutical cocrystals have demonstrated significant promise in their ability to modify the physicochemical and pharmacokinetic properties of drug substances, such as the solubility and dissolution rate, bioavailability, particle morphology and size, tableting and compaction, melting point, physical form, biochemical and hydration stability, and permeability. In this feature review, we highlight some prominent examples of drug cocrystals which exhibit variable hardness/softness and elasticity/plasticity depending on coformer selection, improvement of solubility and permeability in the same cocrystal, increase of the melting point for solid formulation, enhanced color performance, photostability and hydration stability, and a longer half-life. Cocrystals of flavanoids and polyphenols can make improved pharmaceuticals and also extend to the larger class of nutraceuticals. The application of crystal engineering to assemble ternary cocrystals expands this field to drug-drug cocrystals which may be useful in multi-drug resistance, mitigating side effects of drugs, or attenuating/enhancing drug action synergistically by rational selection. The advent of new techniques for structural characterization beyond the standard X-ray diffraction will provide a better understanding of drug phases which are at the borderline of crystalline-amorphous nature and even newer opportunities in the future. PMID:27278109

  8. National rivers and streams assessment survey: evaluating the extent of selected human prescription pharmaceuticals in United States surface waters

    The Ecological Exposure Research Division (EERD) has prioritized a list of the most prescribed active pharmaceutical ingredients (API) in the U.S. based on the potential of their wastewater residues to cause biological effects. A method using selective solid phase extraction and...

  9. Effects of human pharmaceuticals on cytotoxicity, EROD activity and ROS production in fish hepatocytes

    Pharmaceuticals are found in the aquatic environment but their potential effects on non-target species like fish remain unknown. This in vitro study is a first approach in the toxicity assessment of human drugs on fish. Nine pharmaceuticals were tested on two fish hepatocyte models: primary cultures of rainbow trout hepatocytes (PRTH) and PLHC-1 fish cell line. Cell viability, interaction with cytochrome P450 1A (CYP1A) enzyme and oxidative stress were assessed by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrasodium bromide tetrazolium (MTT), 7-ethoxyresorufin-o-deethylase (EROD) and dichlorofluorescein (DCFH-DA) assays, respectively. The tested drugs were clofibrate (CF), fenofibrate (FF), carbamazepine (CBZ), fluoxetine (FX), diclofenac (DiCF), propranolol (POH), sulfamethoxazole (SFX), amoxicillin (AMX) and gadolinium chloride (GdCl3). All substances were cytotoxic, except AMX at concentration up to 500 μM. The calculated MTT EC50 values ranged from 2 μM (CF) to 651 μM (CBZ) in PLHC-1, and from 53 μM (FF) to 962 μM (GdCl3) in PRTH. CF, FF, and FX were the most cytotoxic drugs and induced oxidative stress before being cytotoxic. Compared to hepatocytes from human and dog, fish hepatocytes seemed to be more susceptible to the peroxisome proliferators (PPs) CF and FF. In PLHC-1 cells none of the tested drugs induced the EROD activity whereas POH appeared as a weak EROD inducer in PRTH. Moreover, in PRTH, SFX, DiCF, CBZ and to a lesser extend, FF and CF inhibited the basal EROD activity at clearly sublethal concentrations which may be of concern at the biological and chemical levels in a multipollution context

  10. Caveat medicus: consequences of federal investigations of marketing activities of pharmaceutical suppliers of prostate cancer drugs.

    McKoy, June M; Lyons, E Allison; Obadina, Eniola; Carson, Kenneth; Pickard, A Simon; Schellhammer, Paul; McLeod, David; Boyd, Cynthia E; McWilliams, Norene; Sartor, Oliver; Schumock, Glen T; McCaffery, Kathryn; Bennett, Charles L

    2005-12-01

    In the course of recent health care fraud investigations against TAP Pharmaceuticals (Lake Forest, IL) and AstraZeneca International (London, United Kingdom), each pled guilty to one violation of the Prescription Drug Marketing Act, settled claims related to alleged violations of the False Claims Act without admitting guilt, and paid fines, settlements for liabilities, and reimbursements of dollar 850 million and dollar 355 million, respectively. In a unique aspect of these cases, federal investigators brought criminal charges against 14 TAP employees and investigated the billing practices of several urologists. These investigations resulted in guilty pleas from both urologists and industry employees relative to the Prescription Drug Marketing Act or the False Claims Act and probationary sentences with payments of fines and restitution to the government for urologists who cooperated with federal investigations. One uncooperative urologist was found guilty of violating the Federal False Claims Act and sentenced to 6 months of home arrest, excluded from Medicare for 5 years, required to provide 600 hours of free medical care to indigent patients and patients covered by Medicare or Medicaid, and paid fines and restitution to the government. The cases against TAP and AstraZeneca have been followed by federal and state investigations of allegedly illegal marketing practices of other pharmaceutical firms and have resulted in negotiated settlements of dollar 3.8 billion and dollar 71.5 million, respectively. Believing that an Average Wholesale Price-based reimbursement system was an important driving factor for these marketing activities, Medicare has shifted to an Average Sales Price-based reimbursement system. This is expected to greatly impact the practice of outpatient oncology nationwide. PMID:16314650

  11. "Natural" ingredients in cosmetic dermatology.

    Baumann, Leslie; Woolery-Lloyd, Heather; Friedman, Adam

    2009-06-01

    Recently, both clinical and bench research has begun to provide scientific validation for the use of certain botanical ingredients. Related findings regarding proposed biological mechanisms of action have translated into clinical practice. Botanical compounds for which dermatologic and cosmetic applications have emerged include: olive oil, chamomile, colloidal oatmeal, oat kernal extract, feverfew, acai berry, coffee berry, curcumin, green tea, pomegranate, licorice, paper mulberry, arbutin, and soy. Many of these botanical sources offer biologically active components that require further in vitro and in vivo investigation in order for us to properly educate ourselves, and our patients, regarding over-the-counter products based on these ingredients. PMID:19562883

  12. How Chinese Pharmaceutical Companies to Become Successful API/Key Intermediate Outsourcing Suppliers from the Regulatory Perspective

    MinLi,Ph.D.

    2003-01-01

    With a record number of blockbuster drugs losing patent protection in recent years, major U.S. based multinational drug makers are finding ways to cut cost in order to keep their profit margin in the face of fierce generic competition. On the other hand, generic drug makers are looking for quality, yet inexpensive API/intermediate outsourcing suppliers in order to be profitable in a highly competitive industry. This has created an excellent opportunity for Chinese pharmaceutical companies to become active-pharmaceutical-ingredient (API, or drug substance) and/or pharmaceutical intermediate suppliers for the lucrative U.S.

  13. In Vitro Nail Penetration and Antifungal Activity of Tavaborole, a Boron-Based Pharmaceutical.

    Coronado, Dina; Merchant, Tejal; Chanda, Sanjay; Zane, Lee T

    2015-06-01

    An effective topical antifungal medication must penetrate through the nail plate at sufficient concentrations to eradicate the fungal infection. Tavaborole topical solution, 5% is a novel boron-based pharmaceutical approved for the treatment of toenail onychomycosis due to Trichophyton rubrum or T mentagrophytes. Four in vitro studies assessed the antifungal activity and nail penetration of tavaborole. In Study 1, tavaborole demonstrated minimum inhibitory concentration (MIC) values ranging from 0.25-2 μg/mL against all fungi tested; addition of 5% keratin powder did not affect the MIC against T rubrum. The minimum fungicidal concentration (MFC) values for tavaborole against T rubrum and T mentagrophytes were 8 and 16 μg/mL, respectively. In Study 2, tavaborole effectively penetrated through the nail plate; mean concentrations in the ventral/intermediate nail layer were significantly higher than ciclopirox at day 15. In Study 3, mean cumulative tavaborole penetration through ex vivo human nails was significantly higher than ciclopirox at day 15. In Study 4, tavaborole demonstrated superior nail penetration and fungicidal activity, as measured by zones of inhibition. These studies demonstrated the superior penetration of tavaborole through the nail plate vs ciclopirox. Tavaborole demonstrated robust antifungal activity, with low MIC and MFC values, even in the presence of keratin. PMID:26091387

  14. Hypoglycemic effects of clove (Syzygium aromaticum flower buds) on genetically diabetic KK-Ay mice and identification of the active ingredients.

    Kuroda, Minpei; Mimaki, Yoshihiro; Ohtomo, Takayuki; Yamada, Junji; Nishiyama, Tozo; Mae, Tatsumasa; Kishida, Hideyuki; Kawada, Teruo

    2012-04-01

    Clove (Syzygium aromaticum flower buds) EtOH extract significantly suppressed an increase in blood glucose level in type 2 diabetic KK-A(y) mice. In-vitro evaluation showed the extract had human peroxisome proliferator-activated receptor (PPAR)-γ ligand-binding activity in a GAL4-PPAR-γ chimera assay. Bioassay-guided fractionation of the EtOH extract resulted in the isolation of eight compounds, of which dehydrodieugenol (2) and dehydrodieugenol B (3) had potent PPAR-γ ligand-binding activities, whereas oleanolic acid (4), a major constituent in the EtOH extract, had moderate activity. Furthermore, 2 and 3 were shown to stimulate 3T3-L1 preadipocyte differentiation through PPAR-γ activation. These results indicate that clove has potential as a functional food ingredient for the prevention of type 2 diabetes and that 2-4 mainly contribute to its hypoglycemic effects via PPAR-γ activation. PMID:21987283

  15. Active Ingredient Analysis of Tibet Cultivated Ganoderma Lucidum%西藏人工栽培灵芝活性成分分析

    饶恩铭; 刘涛; 次仁德吉; 宋博文

    2015-01-01

    In order to understand the main active ingredient in Tibet cultivated Ganoderma Lucidum, this article collected the local cultivated Ganoderma Lucidum as the raw materials, used anthrone-sulfuric acid spectroscopy, spectrophotometry, pre-column derivatization RP-HPLC method to analyze the main active ingredient. The results showed that the contents of Ganoderma lucidum polysaccharides, triterpenoids, amino acids in Tibet cultivated Ganoderma Lucidum were:1.199g/100g, 1.63%, 8.898g/100g. Compared with national coverage, the active ingredient of cultivated Ganoderma Lucidum is richer, and the acid and triterpenoids content is higher than that in other regions.%为了解西藏人工栽培灵芝的主要活性成分,采集当地栽培的灵芝为原材料,分别采用蒽酮-硫酸分光法、紫外分光光度法、柱前衍生化RP-HPLC方法,分析其主要活性成分。结果表明,西藏人工栽培的灵芝中灵芝多糖、三萜类、氨基酸含量依次为:1.199g/100g、1.63%、8.898g/100g,经与国内报道相比较,西藏人工灵芝活性成分比较丰富,氨基酸和三萜类含量高于其他区域。

  16. Homeopathy – what are the active ingredients? An exploratory study using the UK Medical Research Council's framework for the evaluation of complex interventions

    Weiss Marjorie

    2006-11-01

    Full Text Available Abstract Background Research in homeopathy has traditionally addressed itself to defining the effectiveness of homeopathic potencies in comparison to placebo medication. There is now increasing awareness that the homeopathic consultation is in itself a therapeutic intervention working independently or synergistically with the prescribed remedy. Our objective was to identify and evalute potential "active ingredients" of the homeopathic approach as a whole, in a prospective formal case series, which draws on actual consultation data, and is based on the MRC framework for the evaluation of complex interventions. Methods Following on from a theoretical review of how homeopathic care might mediate its effects, 18 patients were prospectively recruited to a case series based at Bristol Homeopathic Hospital. Patients, who lived with one of three index conditions, were interviewed before and after a five visit "package of care". All consultations were recorded and transcribed verbatim. Additional data, including generic and condition-specific questionnaires, artwork and "significant other" reports were collected. Textual data was subject to thematic analysis and triangulated with other sources. Results We judged that around one third of patients had experienced a major improvement in their health over the study period, a third had some improvement and a third had no improvement. Putative active ingredients included the patients' "openness to the mind-body connection", consultational empathy, in-depth enquiry into bodily complaints, disclosure, the remedy matching process and, potentially, the homeopathic remedies themselves. Conclusion This study has has identified, using primary consultation and other data, a range of factors that might account for the effectiveness of homeopathic care. Some of these, such as empathy, are non-specific. Others, such as the remedy matching process, are specific to homeopathy. These findings counsel against the use of

  17. Genotoxicity evaluation of the herbicide Garlon(®) and its active ingredient (triclopyr) in fish (Anguilla anguilla L.) using the comet assay.

    Guilherme, Sofia; Santos, Maria A; Gaivão, Isabel; Pacheco, Mário

    2015-09-01

    Triclopyr-based herbicides are broadly used worldwide for site preparation and forest vegetation management. Thus, following application, these agrochemicals can inadvertently reach the aquatic ecosystems. Garlon(®) is one of the most popular commercial denominations of this group of herbicides, considered as highly toxic to fish, even by its manufacturer. Although DNA is frequently regarded as a target of pesticide toxicity, the genotoxic potential of Garlon(®) to fish remains completely unknown. Hence, the main goal of this study was to evaluate the genotoxicity of Garlon(®) and its active ingredient (triclopyr), clarifying the underlying mechanisms. Therefore, the comet assay, implemented as the standard procedure, with an extra step involving DNA lesion-specific repair enzymes (formamidopyrimidine DNA glycosylase and endonuclease III), was used to identify DNA damage in blood cells of Anguilla anguilla L. Short-term exposures (1 and 3 days) to Garlon(®) and triclopyr were carried out, adopting environmentally realistic concentrations (67.6 and 270.5 µg L(-1) Garlon(®) and 30 and 120 µg L(-1) triclopyr). The results concerning the nonspecific DNA damage proved the risk of the herbicide Garlon(®) and its active ingredient triclopyr in both tested concentrations and exposure lengths. In addition, the higher genotoxic potential of the formulation, in comparison with the active ingredient, was demonstrated. When the additional breaks corresponding to net enzyme-sensitive sites were considered, none of the conditions revealed significant levels of oxidative damage. This identification of the genotoxic properties of triclopyr-based herbicides to fish highlights the need to develop less hazardous formulations, as well as the adoption of mitigation measures related to the application of these agrochemicals in the framework of forestry and agriculture sustainable management. PMID:24623388

  18. Homeopathy – what are the active ingredients? An exploratory study using the UK Medical Research Council's framework for the evaluation of complex interventions

    Thompson, Trevor DB; Weiss, Marjorie

    2006-01-01

    Background Research in homeopathy has traditionally addressed itself to defining the effectiveness of homeopathic potencies in comparison to placebo medication. There is now increasing awareness that the homeopathic consultation is in itself a therapeutic intervention working independently or synergistically with the prescribed remedy. Our objective was to identify and evalute potential "active ingredients" of the homeopathic approach as a whole, in a prospective formal case series, which draws on actual consultation data, and is based on the MRC framework for the evaluation of complex interventions. Methods Following on from a theoretical review of how homeopathic care might mediate its effects, 18 patients were prospectively recruited to a case series based at Bristol Homeopathic Hospital. Patients, who lived with one of three index conditions, were interviewed before and after a five visit "package of care". All consultations were recorded and transcribed verbatim. Additional data, including generic and condition-specific questionnaires, artwork and "significant other" reports were collected. Textual data was subject to thematic analysis and triangulated with other sources. Results We judged that around one third of patients had experienced a major improvement in their health over the study period, a third had some improvement and a third had no improvement. Putative active ingredients included the patients' "openness to the mind-body connection", consultational empathy, in-depth enquiry into bodily complaints, disclosure, the remedy matching process and, potentially, the homeopathic remedies themselves. Conclusion This study has has identified, using primary consultation and other data, a range of factors that might account for the effectiveness of homeopathic care. Some of these, such as empathy, are non-specific. Others, such as the remedy matching process, are specific to homeopathy. These findings counsel against the use of placebo-controlled RCT designs in

  19. Genotoxic Potential of Two Herbicides and their Active Ingredients Assessed with Comet Assay on a Fish Cell Line, Epithelioma Papillosum Cyprini (EPC)

    Syberg, Kristian; Rank, Jette; Jensen, Klara;

    2013-01-01

    The aim of this study was to optimize the epithelioma papillosum cyprini (EPC) cell line handling procedure for the comet assay to investigate the genotoxic potential of widely used pesticides. The effects of various media and handling of the EPC cell line were examined. Results indicated...... that avoiding trypsin to detach cells led to lower level of DNA damage in the negative control. Further, two commonly used herbicides (Dezormon and Optica trio) and their four active ingredients (4-chloro-o-tolyloxyacetic acid, 2,4-dichlorophenoxyacetic acid, 2-(4-chloro-2-methylphenoxy)propionic acid, 2...

  20. Development of RP-HPLC method for Qualitative Analysis of Active Ingredient (Gallic acid) from Stem Bark of Dendrophthoe falcate Linn.

    Hafsa Deshmukh; Pradnya J. Prabhu

    2011-01-01

    A simple, precise and sensitive, RP-HPLC method with UV detection at 271nm was developed and validated for qualitative determination of active ingredient Gallic acid from stem bark of Dendrophthoe falcate Linn. Separation was performed on a ThermoMOS 2 HYPERSIL C18 column (250 cm × 4.6 mm, 5µm ODS 3) using mobile phase comprising of 0.1% Orthophosphoric acid : Acetonitrile (400 cm3 : 600 cm3) with a flow rate of 1 ml/minute with a short run time of 13 minute. The method was validated accordi...

  1. Membrane processes for removal of pharmaceutically active compounds (PhACs) from water and wastewaters.

    Taheran, Mehrdad; Brar, Satinder K; Verma, M; Surampalli, R Y; Zhang, T C; Valero, J R

    2016-03-15

    Pharmaceutically active compounds (PhACs), which find their way easily into the water sources, are emerging as a major concern for drinking water quality and aquatic species. Therefore, their removal from water sources is a priority from environmental point of view. During the past decade, different methods including membrane separation, adsorption systems and chemical transformation have been evaluated for removal of these compounds. This paper reviews different aspects of PhAC removal by using membrane separation processes, as they have been conventionally known to show high potential in the production of superior quality drinking and industrial water. In brief, osmosis membranes can efficiently remove almost all PhACs though its operational cost is relatively high and nanofiltration (NF) membranes are highly influenced by electrostatic and hydrophobic interaction. Moreover, the efficiency of membrane bioreactors (MBRs) is difficult to predict due to the complex interaction of compounds with microorganisms. To improve the performance and robustness of membrane technology, it is suggested to combine membranes with other systems, such as activated carbon and enzymatic degradation. PMID:26789358

  2. Nitrification activity and community structure of nitrite-oxidizing bacteria in the bioreactors operated with addition of pharmaceuticals

    Kraigher, Barbara, E-mail: barbara.kraigher@bf.uni-lj.si [University of Ljubljana, Biotechnical Faculty, Department of Food Science and Technology, Chair of Microbiology, Vecna pot 111, 1000 Ljubljana (Slovenia); Mandic-Mulec, Ines [University of Ljubljana, Biotechnical Faculty, Department of Food Science and Technology, Chair of Microbiology, Vecna pot 111, 1000 Ljubljana (Slovenia)

    2011-04-15

    Pharmaceuticals represent a group of the new emerging contaminants, which might influence microbial communities in the activated sludge. Nitrification activity and Nitrospira community structure in the small-scale reactors supplied with different concentrations (0, 50, 200, 500 {mu}g L{sup -1}) of the selected pharmaceuticals (ibuprofen, naproxen, ketoprofen, diclofenac and clofibric acid) were evaluated. Ammonia removal was not influenced by selected pharmaceuticals. However, in the two reactors operated with 50 {mu}g L{sup -1} of pharmaceuticals (R50 and R50P), the effluent concentration of N-(NO{sub 2}{sup -} + NO{sub 3}{sup -}) was significantly higher than in the other reactors. Nitrospira community structure was assessed by terminal restriction fragment length polymorphism (T-RFLP) and by cloning and sequencing of the partial genes for 16S rRNA. Nitrospira spp. were detected in all reactors. The two dominant T-RFs represented the sublineages I and II of the genus Nitrospira. Main shifts were observed in the reactors R50 and R50P, where the T-RF representing sublineage II was much higher as compared to the other reactors. Consistent with this, the Nitrospira sublineage II was detected only in the clone libraries from the reactors R50 and R50P. Our results suggest that the relative abundance of Nitrospira sublineage II could be related to the effluent N-(NO{sub 2}{sup -} + NO{sub 3}{sup -}) concentration.

  3. Nitrification activity and community structure of nitrite-oxidizing bacteria in the bioreactors operated with addition of pharmaceuticals

    Pharmaceuticals represent a group of the new emerging contaminants, which might influence microbial communities in the activated sludge. Nitrification activity and Nitrospira community structure in the small-scale reactors supplied with different concentrations (0, 50, 200, 500 μg L-1) of the selected pharmaceuticals (ibuprofen, naproxen, ketoprofen, diclofenac and clofibric acid) were evaluated. Ammonia removal was not influenced by selected pharmaceuticals. However, in the two reactors operated with 50 μg L-1 of pharmaceuticals (R50 and R50P), the effluent concentration of N-(NO2- + NO3-) was significantly higher than in the other reactors. Nitrospira community structure was assessed by terminal restriction fragment length polymorphism (T-RFLP) and by cloning and sequencing of the partial genes for 16S rRNA. Nitrospira spp. were detected in all reactors. The two dominant T-RFs represented the sublineages I and II of the genus Nitrospira. Main shifts were observed in the reactors R50 and R50P, where the T-RF representing sublineage II was much higher as compared to the other reactors. Consistent with this, the Nitrospira sublineage II was detected only in the clone libraries from the reactors R50 and R50P. Our results suggest that the relative abundance of Nitrospira sublineage II could be related to the effluent N-(NO2- + NO3-) concentration.

  4. Analysis of the pharmaceutical care activities practiced by private homeopathic pharmacies located in Rio de Janeiro North Zone

    Tereza Aguiar

    2011-09-01

    Full Text Available The complexity of homeopathic treatment delegates to the Pharmacist the need and the responsibility of pharmaceutical care. This paper had the objective of verifying the practices of pharmaceutical care in homeopathy. The study was conducted in homeopathic pharmacies situated in Rio de Janeiro North Zone, during March and April, 2011, where 15 pharmacists were interviewed, with the help of a semi-open questionary self-administered. For the survey were investigated variables related to pharmaceutical: sex, age, nature of the institution where he graduated, having completed post-graduate and working ties. Information professionals for the pharmaceutical care were collected in 14 questions grouped into three areas: attitudes, perceptions and satisfaction. Attending the ethical aspects, the study was submitted to and approved by the Ethics Committee of University Estácio de Sá. The results demonstrated that 33% of the pharmacists have less than 5 years of professional practice, and 53% are specialists graduated by the Hahnemann’s Institutite of Brasil. All Pharmacists claim to orient patients, mostly during dispensation and through phone contacts. Most pharmacists oriented patients passively and actively. The elderly were pointed as the ones, who most often sought orientation. During dispensation of homeopathic drugs, all patients elicit some orientation. 67% of the pharmacies keep material for pharmaceutical guidance to the patients, usually leaflets. The verbal and written orientation was predominanted on homeopathic pharmacist. Posology and instructions of use for the pharmaceutical form dispensed were described as the most common doubts of the patients. Of all pharmacists interviewed, 67% pointed to self-medication practices in the pharmacy. The questions which measure the position and perception of the pharmacists related to pharmaceutical assistance scored over 3. The question which scored higher was related to

  5. Comparative analysis of the effects of locally used herbicides and their active ingredients on a wild-type wine Saccharomyces cerevisiae strain.

    Braconi, Daniela; Sotgiu, Michele; Millucci, Lia; Paffetti, Alessandro; Tasso, Flavia; Alisi, Chiara; Martini, Silvia; Rappuoli, Roberto; Lusini, Paola; Sprocati, Anna Rosa; Rossi, Claudio; Santucci, Annalisa

    2006-04-19

    Herbicides are released to the environment with potential ecotoxicological risks for mammals. Yeast is a good model to elucidate toxicity mechanisms. We investigated how three commercial herbicides (Proper Energy, Pointer, and Silglif) and their active ingredients (respectively, fenoxaprop-P-ethyl, tribenuron methyl, and glyphosate) can affect biological activities of an oenological Saccharomyces cerevisiae strain, which may be resident on grape vineyards of the same geographical areas where herbicides are used. The use of commercial grade herbicides employed in Italy allowed us to reproduce the same conditions applied in crops; at the same time, assaying pure single active compounds made it possible to compare the effects obtained with commercial formulations. Interestingly, we found that while pure active compounds affect cell growth and metabolism at a lower extent, commercial preparations have a significant major negative influence on yeast biology. PMID:16608247

  6. Situation Analysis of R & D Activities: An Empirical Study in Iranian Pharmaceutical Companies

    Rasekh, Hamid Reza; Mehralian, Gholamhossein; Vatankhah-Mohammadabadi, Abbas Ali

    2012-01-01

    As global competition intensifies, research and development (R & D) organizations need to enhance their strategic management in order to become goal-directed communities for innovation and allocate their resources consistent with their overall R & D strategy. The world pharmaceutical market has undergone fast, unprecedented, tremendous and complex changes in the last several years. The pharmaceutical industry is today still one of the most inventive, innovative and lucrative of the so-called ...

  7. TASTE MASKING TECHNOLOGIES: A NOVEL APPROACH FOR THE IMPROVEMENT OF ORGANOLEPTIC PROPERTY OF PHARMACEUTICAL ACTIVE SUBSTANCE

    Sharma Deepak

    2012-04-01

    Full Text Available Acceptability of any dosage form are mainly depends over its taste i.e. mouth feel. Drug molecule interacts with taste receptor on the tongue to give bitter, sweet or salty taste sensation, when they dissolve in saliva. This sensation of the taste is the result of signal transduction from the receptor organs for taste, commonly known as taste buds. In market, there are numbers of pharmaceutical preparations available in which actives are bitter in taste. The improved palatability in these products has prompted the development of numerous formulations, which improved performance and acceptability. The bitterness of preparation also leads to patient incompliance. So masking of bitterness becomes essential. To overcome this problem, many techniques have been developed to mask the bitter taste of drugs. These techniques are not only mask the bitter taste of drug but also enhance the bioavailability and performance of drug dosage form. It includes adding sugars, flavors, sweeteners, use of lipoproteins, numbing taste buds, granulation, use of adsorbates ,coating drug, microencapsulation, multiple emulsion, viscosity modifier, vesicles and liposomes, prodrug and salt formation, inclusion and molecular complexes, solid dispersion and Ion Exchange Resins (IERs which have been tried by the formulators to mask the unpleasant taste of the bitter drugs. The present review article highlights different technologies of taste masking with respect to dosage form and novel methods of evaluation of taste masking effect.

  8. Adsorption of selected endocrine disrupting compounds and pharmaceuticals on activated biochars.

    Jung, Chanil; Park, Junyeong; Lim, Kwang Hun; Park, Sunkyu; Heo, Jiyong; Her, Namguk; Oh, Jeill; Yun, Soyoung; Yoon, Yeomin

    2013-12-15

    Chemically activated biochar produced under oxygenated (O-biochar) and oxygen-free (N-biochar) conditions were characterized and the adsorption of endocrine disrupting compounds (EDCs): bisphenol A (BPA), atrazine (ATR), 17 α-ethinylestradiol (EE2), and pharmaceutical active compounds (PhACs); sulfamethoxazole (SMX), carbamazepine (CBM), diclofenac (DCF), ibuprofen (IBP) on both biochars and commercialized powdered activated carbon (PAC) were investigated. Characteristic analysis of adsorbents by solid-state nuclear magnetic resonance (NMR) was conducted to determine better understanding about the EDCs/PhACs adsorption. N-biochar consisted of higher polarity moieties with more alkyl (0-45 ppm), methoxyl (45-63 ppm), O-alkyl (63-108 ppm), and carboxyl carbon (165-187 ppm) content than other adsorbents, while aromaticity of O-biochar was higher than that of N-biochar. O-biochar was composed mostly of aromatic moieties, with low H/C and O/C ratios compared to the highly polarized N-biochar that contained diverse polar functional groups. The higher surface area and pore volume of N-biochar resulted in higher adsorption capacity toward EDCs/PhACs along with atomic-level molecular structural property than O-biochar and PAC. N-biochar had a highest adsorption capacity of all chemicals, suggesting that N-biochar derived from loblolly pine chip is a promising sorbent for agricultural and environmental applications. The adsorption of pH-sensitive dissociable SMX, DCF, IBP, and BPA varied and the order of adsorption capacity was correlated with the hydrophobicity (Kow) of adsorbates throughout the all adsorbents, whereas adsorption of non-ionizable CBM, ATR, and EE2 in varied pH allowed adsorbents to interact with hydrophobic property of adsorbates steadily throughout the study. PMID:24231319

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

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

    2009-01-01

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

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

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

    2012-01-01

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

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

    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.

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

    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.

  13. Adsorption of pharmaceuticals onto activated carbon fiber cloths - Modeling and extrapolation of adsorption isotherms at very low concentrations

    Fallou, Hélène; Cimetiere, Nicolas; Giraudet, Sylvain; Wolbert, Dominique; Le Cloirec, Pierre

    2016-01-01

    International audience Activated carbon fiber cloths (ACFC) have shown promising results when applied to water treatment, especially for removing organic micropollutants such as pharmaceutical compounds. Nevertheless, further investigations are required, especially considering trace concentrations, which are found in current water treatment. Until now, most studies have been carried out at relatively high concentrations (mg L(-1)), since the experimental and analytical methodologies are mo...

  14. The Effect of Active Learning Methodologies on the Teaching of Pharmaceutical Care in a Brazilian Pharmacy Faculty

    Mesquita, Alessandra R.; Souza, Werlissandra M.; Boaventura, Thays C.; Barros, Izadora M. C.; Angelo R. Antoniolli; Silva, Wellington B.; Lyra Júnior, Divaldo P.

    2015-01-01

    Background In recent years, pharmacists have been involved in expanded patient care responsibilities, for example patient counseling in self-medication, medication review and pharmaceutical care, which require graduates to develop the necessary competences. Consequently, reorientation of pharmacy education has become necessary. As such, active learning strategies have been introduced into classrooms to increase problem-solving and critical thinking skills of students. The objective of this st...

  15. Changes in FDA enforcement activities following changes in federal administration: the case of regulatory letters released to pharmaceutical companies

    Nguyen Diane; Seoane-Vazquez Enrique; Rodriguez-Monguio Rosa; Montagne Michael

    2013-01-01

    Abstract Background The United States (US) Food and Drug Administration (FDA) is responsible for the protection of the public health by assuring the safety, effectiveness and security of human drugs and biological products through the enforcement of the Federal Food, Drug and Cosmetic Act (FDCA) and related regulations. These enforcement activities include regulatory letters (i.e. warning letters and notice of violation) to pharmaceutical companies. A regulatory letter represents the FDA’s fi...

  16. 圆孢蘑菇有效成分的定性分析%Qualitative Analysis of Active Ingredients of Agaricus gennadii

    白世俊; 包锦渊

    2012-01-01

    [Objective] The aim was to confirm the active ingredients of Agaricus gennadii. [Method] The water extraction method, alcohol extraction method and petroleum ether extraction method were used to extracted the chemical ingredients of Agaricus gennadii, and analyzed them. [Result]The results show that Agaricus gennadii contains protein,carbohydrates,organic acids,coumarin and lactones,etc. ,may also contains saponins and steroidal triterpenes,but does not contain alkaloids,cardiac glycosides,volatile oils,phenols and tannins,etc. [Conclusion] The study makes people to fully know Agaricus gennadii.%[目的]确定圆孢蘑菇(Agaricus gennadii)的有效成分.[方法]采用水提法、醇提法和石油醚提取法对圆孢蘑菇的有效成分进行定性提取和分析.[结果]圆孢蘑菇中含有蛋白质、糖类、有机酸、香豆素与内酯等物质,可能含有皂苷和甾体三萜类,不含生物碱、强心苷、挥发油、酚类和鞣质等.[结论]该研究可使人们更加清楚地了解圆孢蘑菇.

  17. Pharmacokinetics and tissue distribution of five active ingredients of Eucommiae cortex in normal and ovariectomized mice by UHPLC-MS/MS.

    An, Jing; Hu, Fangdi; Wang, Changhong; Zhang, Zijia; Yang, Li; Wang, Zhengtao

    2016-09-01

    1. Pinoresinol di-O-β-d-glucopyranoside (PDG), geniposide (GE), geniposidic acid (GA), aucubin (AN) and chlorogenic acid (CA) are the representative active ingredients in Eucommiae cortex (EC), which may be estrogenic. 2. The ultra high-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous determination of the five ingredients showed good linearity, low limits of quantification and high extraction recoveries, as well as acceptable precision, accuracy and stability in mice plasma and tissue samples (liver, spleen, kidney and uterus). It was successfully applied to the comparative study on pharmacokinetics and tissue distribution of PDG, GE, GA, AN and CA between normal and ovariectomized (OVX) mice. 3. The results indicated that except CA, the plasma and tissue concentrations of PDG, GE, GA in OVX mice were all greater than those in normal mice. AN could only be detected in the plasma and liver homogenate of normal mice, which was poorly absorbed in OVX mice and low in other measured tissues. PDG, GE and GA seem to be better absorbed in OVX mice than in normal mice proved by the remarkable increased value of AUC0-∞ and Cmax. It is beneficial that PDG, GE, GA have better plasma absorption and tissue distribution in pathological state. PMID:27232980

  18. Digestible energy requirement for females of Rhamdia quelen on reproductive activity fed with ration based on vegetal ingredients

    Robie A Bombardelli

    2015-07-01

    Full Text Available The present experiment was carried out to evaluate the growth and reproductive parameters of Rhamdia quelen females fed with pelleted ration containing different levels of digestible energy, and to evaluate the vigor of their offspring. The breeders were placed in tanks under conditions of photoperiod and natural temperature. The fishes were fed for 255 days with isoproteic rations pelleted containing 35% of crude protein (CP and five levels of the digestible energy (DE (2700, 2950, 3200, 3450, 3700 kcal kg-1. The fishes were distributed in a randomized experimental design compounded by five treatments and three repetitions. A 16-m² tank containing six females and three males was considered as one experimental unit. The weight and weight gain was evaluated. During the reproductive season the females were induced to breeding by hormonal manipulation and were evaluated the percentage of spawning females, the total fecundity, relative fecundity (number of oocytes per gram of spawning females, the fertilization ratio, the time to hatching and the vigor of larvae. The growth and reproductive parameters were not influenced (P > 0.05 by the increasing levels of digestible energy of the rations. The feeding of R. quelen females in breeding fit can be carried out with 2700 kcal kg-1 pelletized ration based on vegetal ingredients, without damage to reproductive performance.

  19. Organic Pesticide Ingredients

    ... Control a pest Integrated Pest Management What are pesticides? Herbicides Disinfectants Fungicides Insecticides Natural and Biological Pesticides ... Other types of pesticides Disponible en español Organic Pesticide Ingredients Organic foods are not necessarily pesticide-free. ...

  20. An Overview of Pharmaceutical Excipients: Safe or Not Safe?

    Abrantes, Cátia G; Duarte, Dinah; Reis, Catarina P

    2016-07-01

    A medicine consists of 2 fundamental parts: the active pharmaceutical ingredient and the excipient. Most, if not all, medicines could not be made without the use of excipients. In the early times, the safety of excipients was overlooked and no specific safety tests were generally conducted. This fact has been changed over times and is currently being recognized that the excipient's toxicity is not negligible, because its direct interaction with the active pharmaceutical ingredient or between other excipients may occur, leading to a potential change in the relationship between effectiveness and toxicity. This review is intended to address the general status of the pharmaceutical excipients and to describe the safety assessment. As a summary, this review suggests the interest of simplifying the formulations as much as possible and the interest of reducing the number of excipients necessary to strictly meet the required functions. The risk/benefit ratio of an excipient should be always evaluated on the basis of not only its production and quality but also of its safety. Further research according to Good Manufacturing Practices, Guiding Principles in Toxicology Assessment, Good Laboratory Practices, and Good Distribution Practices requirements are needed and are fundamental for health safety, contributing to a comprehensive picture of this matter. PMID:27262205

  1. Using a Mass Balance to Determine the Potency Loss during the Production of a Pharmaceutical Blend

    Mackaplow, Michael B.

    2010-01-01

    The manufacture of a blend containing the active pharmaceutical ingredient (API) and inert excipients is a precursor for the production of most pharmaceutical capsules and tablets. However, if there is a net water gain or preferential loss of API during production, the potency of the final drug product may be less than the target value. We use a mass balance to predict the mean potency loss during the production of a blend via wet granulation and fluidized bed drying. The result is an explici...

  2. Effects of Mongolian Pharmaceutical Betel Shisanwei Ingredient Pills on the Behavior and Different Cerebral Region Monoamine Neurotransmitters in the Rat Models with Depressive Chronic Stress%蒙药槟榔十三味丸(高尤-13)对抑郁模型大鼠行为学及不同脑区单胺类神经递质的影响

    佟海英; 王旭; 乌吉斯古冷; 白亮凤; 包伍叶; 胡日乐巴根; 李婧; 张月

    2014-01-01

    ingredient pills .Methods:Sixty male Wistar rats were randomly divided into six groups according to the sugar consumption test and body weight (10 rats in each group):Normal control group,Model group, Fluoxetine group and High dose,medium dose and low dose groups of Betel Shisanwei ingredient pills .Except the normal control group,other groups were treated with the chronic unpredictable mild stress stimulation combined with lonely rai -sing for 21days.10mL/kg drugs were given to the rats,once daily,continuously for 21 days.After 21 days,behavior chan-ges of rats were detected through Open -field test,and sugar consumption test and body weight were also measured . HPLC -ECD techniques were used to analyze the levels of prefrontal cortex and hippocampus NE and 5 -HT and DA and their metabolites.Results:Compared with normal control group ,the scores of horizontal activity and vertical activity , sugar consumption decreased significantly in the model group (P <0.01 or P <0.05);Compared with model group,Flu-oxetine group and Betel Shisanwei ingredient pills group got significantly higher scores of horizontal activity ,vertical ac-tivity and sugar consumption (P <0.05 or P <0.01).HPLC -ECD techniques showed that the model rats prefrontal cortex NE,5 -HT,DA,DOPAC,hippocampus 5 -HT,5HIAA,DA content decreased more significantly than those in normal control group(P <0.05 or P <0.01).Betel Shisanwei ingredient pills could increase model rat 's prefrontal cortex NE,5 -HT,DA,DOPAC and hippocampus 5 -HT,5HIAA,DA content, especially the medium and high dose groups were significant(P <0.05 or P <0.01).Conclusion: Betel Shisanwei ingredient pills can improve abnormal behavior of depressive model rats, improve the neurotransmitter NE, 5 -HT, DA and its metabolic product content in rats brain, and it could be one of the important antidepressant effect mechanisms of Betel Shisanwei ingredient pills .

  3. Applications of terahertz-pulsed technology in the pharmaceutical industry

    Taday, Philip F.

    2010-02-01

    Coatings are applied to pharmaceutical tablets (or pills) to for either cosmetic or release control reasons. Cosmetic coatings control the colour or to mask the taste of an active ingredient; the thickness of these coating is not critical to the performance of the product. On the other hand the thickness and uniformity of a controlled release coating has been found affect the release of the active ingredient. In this work we have obtained from a pharmacy single brand of pantoprazole tablet and mapped them using terahertz pulsed imaging (TPI) prior to additional dissolution testing. Three terahertz parameters were derived for univariate analysis for each layer: coating thickness, terahertz electric field peak strength and terahertz interface index. These parameters were then correlated dissolution tested. The best fit was found to be with combined coating layer thickness of the inert layer and enteric coating. The commercial tablets showed a large variation in coating thickness.

  4. Discovering novel ingredient pairings in molecular gastronomy using network analysis

    Ključevšek, Aleksander; Krapić, Luka

    2016-01-01

    Molecular gastronomy is a distinct sub-discipline of food science that takes an active role in examining chemical and physical properties of ingredients and as such lends itself to more scientific approaches to finding novel ingredient pairings. With thousands of ingredients and molecules, which participate in the creation of each ingredient's flavour, it can be difficult to find compatible flavours in an efficient manner. Existing literature is focused mainly on analysis of already establish...

  5. Simultaneous determination of some active ingredients in cough and cold preparations by gas chromatography, and method validation.

    Harsono, Thresiana; Yuwono, Mochammad; Indrayanto, Gunawan

    2005-01-01

    A simple and rapid gas chromatographic (GC) method has been developed for the simultaneous determination of combinations of acetaminophen, phenylpropanolamine hydrochloride, guaifenesin, pseudoephedrine hydrochloride, caffeine, chlorpheniramine maleate, and dextromethorphan hydrobromide in cough and cold tablets and syrups. After extraction of the analyte with alkaline ethyl acetate, 2 microL extract was injected (splitting ratio of 50:1) into a gas chromatograph equipped with a CBP1-M25-025 fused silica capillary column (25 m x 0.22 mm; film thickness, 0.25 microm). The column temperature was held at 150 degrees C for 5 min, increased to 175 degrees C at 3 degrees C/min, and increased to 270 degreesC at 10 degrees C/min. The temperatures of the flame ionization detector and injector were maintained at 300 degrees C. The GC method is inexpensive, rapid, accurate, and precise, and thus it can be used for routine analysis of tablet and syrup preparations in quality control laboratories of pharmaceutical companies. PMID:16152925

  6. Influence of activated carbon preloading by EfOM fractions from treated wastewater on adsorption of pharmaceutically active compounds.

    Hu, Jingyi; Shang, Ran; Heijman, Bas; Rietveld, Luuk

    2016-05-01

    In this study, the preloading effects of different fractions of wastewater effluent organic matter (EfOM) on the adsorption of trace-level pharmaceutically active compounds (PhACs) onto granular activated carbon (GAC) were investigated. A nanofiltration (NF) membrane was employed to separate the EfOM by size, and two GACs with distinct pore structures were chosen for comparison. The results showed that preloading with EfOM substantially decreased PhAC uptake of the GACs; however, comparable PhAC adsorption capacities were achieved on GACs preloaded by feed EfOM and the NF-permeating EfOM. This indicates that: (1) the NF-rejected, larger EfOM molecules with an expectation to block the PhAC adsorption pores exerted little impact on the adsorbability of PhACs; (2) the smaller EfOM molecules present in the NF permeate contributed mainly to the decrease in PhAC uptake, mostly due to site competition. Of the two examined GACs, the wide pore-size-distributed GAC was found to be more susceptible to EfOM preloading than the microporous GAC. Furthermore, among the fourteen investigated PhACs, the negatively charged hydrophilic PhACs were generally subjected to a greater EfOM preloading impact. PMID:26891356

  7. Ingredients for sustained excellence

    Point Lepreau, a 680MWe CANDU reactor, has, since startup, been one of the world's best performing reactors. Many of the ingredients for this success can be found at other plants, but Pt Lepreau has found a ''chemistry'' that has sustained its performance at a very high level. Our belief is that this is the result of two major influences: Pt Lepreau is the only nuclear unit in a small utility, all its nuclear expertise exists at the station, and all necessary disciplines can be readily galvanized to solve problems and get work done. The structure of the organization is simple, with station management involvement in day to day activities. This fosters accountability and a natural efficiency that does not need slogans to achieve its purpose. Turning to the factors that have contributed to the station's success, the IAEA's technical exchange visit in July 1990 identified four items ''which are particularly noteworthy since they can be developed and used widely in the nuclear industry to enhance safety and availability. These are: quality assurance applications; the degree to which system engineers are employed; the dedication of skilled resources to and thoroughness of outage planning; and the in-house development of computers to assist directly in the day to day, medium and long term management of the generating station''. (Author)

  8. Adsorption of selected endocrine disrupting compounds and pharmaceuticals on activated biochars

    Jung, Chanil [Department of Civil and Environmental Engineering, University of South Carolina, Columbia, SC 29208 (United States); Park, Junyeong [Department of Forest Biomaterials, North Carolina State University, Raleigh, NC 27695 (United States); Lim, Kwang Hun [Department of Chemistry, East Carolina University, Greenville, NC 27858 (United States); Park, Sunkyu [Department of Forest Biomaterials, North Carolina State University, Raleigh, NC 27695 (United States); Heo, Jiyong [Department of Civil and Environmental Engineering, Korea Army Academy at Young-Cheon, PO Box 135-1, Changhari, Gogyeongmeon, Young-cheon 770-849, Gyeongbuk (Korea, Republic of); Her, Namguk [Department of Chemistry and Environmental Sciences, Korea Army Academy at Young-Cheon, PO Box 135-1, Changhari, Gogyeongmeon, Young-cheon 770-849, Gyeongbuk (Korea, Republic of); Oh, Jeill; Yun, Soyoung [Department of Civil and Environmental Engineering, Chung-Ang University, Dongjak-Ku, Seoul 156-756 (Korea, Republic of); Yoon, Yeomin, E-mail: yoony@cec.sc.edu [Department of Civil and Environmental Engineering, University of South Carolina, Columbia, SC 29208 (United States)

    2013-12-15

    Highlights: • Biochars were prepared at different gas environments. • The competitive adsorption among EDCs/PhACs were investigated. • Aromaticity of adsorbent plays a significant role for EDCs/PhACs adsorption. -- Abstract: Chemically activated biochar produced under oxygenated (O-biochar) and oxygen-free (N-biochar) conditions were characterized and the adsorption of endocrine disrupting compounds (EDCs): bisphenol A (BPA), atrazine (ATR), 17 α-ethinylestradiol (EE2), and pharmaceutical active compounds (PhACs); sulfamethoxazole (SMX), carbamazepine (CBM), diclofenac (DCF), ibuprofen (IBP) on both biochars and commercialized powdered activated carbon (PAC) were investigated. Characteristic analysis of adsorbents by solid-state nuclear magnetic resonance (NMR) was conducted to determine better understanding about the EDCs/PhACs adsorption. N-biochar consisted of higher polarity moieties with more alkyl (0–45 ppm), methoxyl (45–63 ppm), O-alkyl (63–108 ppm), and carboxyl carbon (165–187 ppm) content than other adsorbents, while aromaticity of O-biochar was higher than that of N-biochar. O-biochar was composed mostly of aromatic moieties, with low H/C and O/C ratios compared to the highly polarized N-biochar that contained diverse polar functional groups. The higher surface area and pore volume of N-biochar resulted in higher adsorption capacity toward EDCs/PhACs along with atomic-level molecular structural property than O-biochar and PAC. N-biochar had a highest adsorption capacity of all chemicals, suggesting that N-biochar derived from loblolly pine chip is a promising sorbent for agricultural and environmental applications. The adsorption of pH-sensitive dissociable SMX, DCF, IBP, and BPA varied and the order of adsorption capacity was correlated with the hydrophobicity (K{sub ow}) of adsorbates throughout the all adsorbents, whereas adsorption of non-ionizable CBM, ATR, and EE2 in varied pH allowed adsorbents to interact with hydrophobic property

  9. Epithermal neutron activation analysis of blue-green algae Spirulina Platensis as a matrix for selenium-containing pharmaceuticals

    To evaluate the potentiality of the blue-green algae Spirulina Platensis as a matrix for the production of Se-containing pharmaceuticals, the background levels of 31 major, minor and trace elements (Na, Mg, Al, Cl, K, Ca, Sc, V, Cr, Mn, Fe, Co, Ni (using (n,p)-reaction), As, Br, Zn, Rb, Mo, Ag, Sb, I, Ba, Sm, Tb, Tm, Hf, Ta, W, Au, Hg, Th) in Spirulina Platensis biomass were determined by means of epithermal neutron activation analysis. The possibility of the purpose-oriented incorporation of Se into Spirulina Platensis biomass was demonstrated. The polynomial dependence of the Se accumulation on nutritional medium loading was revealed. The employed analytical technique allows one to reliably control the amount of toxic elements in algae Spirulina Platensis. Based on this study, a conclusion of the possibility to use Spirulina Platensis as a matrix for the production of Se-containing pharmaceuticals was drawn

  10. Epithermal neutron activation analysis of blue-green algae Spirulina platensis as a matrix for selenium-containing pharmaceuticals

    To evaluate the potentiality of the blue-green algae Spirulina platensis as a matrix for the production of Se-containing pharmaceuticals, the background levels of 31 major, minor and trace elements (Na, Mg, Al, Cl, K, Ca, Sc, V, Cr, Mn, Fe, Co, Ni using (n,p) reaction), As, Br, Zn, Rb, Mo, Ag, Sb, I, Ba, Sm, Tb, Tm, Hf, Ta, W, Au, Hg, Th were determined in Spirulina platensis biomass by means of epithermal neutron activation analysis. The possibility of the purpose-oriented incorporation of Se into Spirulina platensis biomass was demonstrated. The polynomial dependence of the Se accumulation on nutritional medium loading was revealed. The analytical technique used allows to control the amount of toxic elements in algae Spirulina platensis. Conclusion of the possibility to use Spirulina platensis as a matrix for the production of Se-containing pharmaceutical was drawn. (author)

  11. Application of chemical oxidation for removal of pharmaceuticals in wastewater effluents

    Hey, G.; Ledin, A.; la Cour Jansen, J; Hörsing, M.; Antoniou, Maria; Spiliotopoulou, Aikaterini; Andersen, Henrik Rasmus

    2012-01-01

    This study was conducted to evaluate the potential of the chemical oxidation processes chlorine dioxide (ClO2) and ozone (O3) as tertiary steps in wastewater to remove traces of active pharmaceutical ingredients (APIs). Wastewater effluents of varying organic content (COD ~ 30-90 mg/L) were collected from different wastewater treatment plants in Sweden to represent different types of biological treatment. Laboratory-scale batch experiments were carried out employing different doses of ClO2 (0...

  12. RECENT POTENTIAL USAGE OF SURFACTANT FROM MICROBIAL ORIGIN IN PHARMACEUTICAL AND BIOMEDICAL ARENA: A PERSPECTIVE

    Rath Kalyani; Mishra Bishwambhar; Vuppu Suneetha

    2011-01-01

    The use and potential commercial application of biosurfactant has increased during the past decade which can be used as emulsifiers, de-emulsifiers, wetting and foaming agents, functional food ingredients and as detergents in petroleum, petrochemicals, environmental management, agrochemicals, foods and beverages, cosmetics and pharmaceuticals and in the mining and metallurgical industries. Their antibacterial, antifungal and antiviral activities make them relevant molecules for applications i...

  13. Preparation and Characterization of Poly(Lactic Acid) Nanoparticles for Pharmaceutical Use

    HirsjÀrvi, Samuli

    2008-01-01

    Nanoparticles have versatile potential for efficient exploitation of different drug delivery formulations and routes because of the properties provided by their small size. These possible benefits include controlled release, protection of the active pharmaceutical ingredient and drug targeting. Nanoparticles are expected to offer new solutions e.g. for gene therapy and delivery of peptide drugs. Generally, nanoparticles are applied as an injectable or oral solution, but their use as dried mat...

  14. COMPRESSION PHYSICS OF PHARMACEUTICAL POWDERS: A REVIEW

    Shailender Mohan

    2012-06-01

    Full Text Available Due to various advantages such as high-precision dosing, manufacturing efficiency and patient compliance helped making tablets the most popular dosage forms among all available dosages forms. Compaction, which is an essential manufacturing step in the manufacture of tablets, mainly includes compression (i.e. reduction of volume of the powder under consideration and particle rearrangement and consolidation (i.e., formation of interparticulate bond to facilitate stable compaction. The success of the compaction process depends not only on the physico-technical properties of drugs and excipients, but also on the instrument settings with respect to rate and magnitude of force transfer. Tablet manufacturing speed and pre/main compression force profile also have an influence on the quality of the final tablet. Mechanical aspects of tablet formation can be studied using, instrumented punches/dies, instrumented tablet punching machines, and compaction simulators. These have potential application in pharmaceutical research and development, such as studying basic compaction mechanism, various process variables, scale-up parameters, trouble shooting problems, creating compaction data library, and fingerprinting of new active pharmaceutical ingredients (APIs or excipients. Mathematical models, force-time, force-distance, and die-wall force parameters of tablet manufacturing are used to describe work of compaction, elasticity/plasticity, and time dependent deformation behavior of pharmaceuticals powder under consideration.

  15. Changes in FDA enforcement activities following changes in federal administration: the case of regulatory letters released to pharmaceutical companies

    Nguyen Diane

    2013-01-01

    Full Text Available Abstract Background The United States (US Food and Drug Administration (FDA is responsible for the protection of the public health by assuring the safety, effectiveness and security of human drugs and biological products through the enforcement of the Federal Food, Drug and Cosmetic Act (FDCA and related regulations. These enforcement activities include regulatory letters (i.e. warning letters and notice of violation to pharmaceutical companies. A regulatory letter represents the FDA’s first official notification to a pharmaceutical company that the FDA has discovered a product or activity in violation of the FDCA. This study analyzed trends in the pharmaceutical-related regulatory letters released by the FDA during the period 1997–2011 and assessed differences in the average number and type of regulatory letters released during the last four federal administrations. Methods Data derived from the FDA webpage. Information about the FDA office releasing the letter, date, company, and drug-related violation was collected. Regulatory letters were classified by federal administration. Descriptive statistics were performed for the analysis. Results Between 1997 and 2011 the FDA released 2,467 regulatory letters related to pharmaceuticals. FDA headquarters offices released 50.6% and district offices 49.4% of the regulatory letters. The Office of Prescription Drug Promotion released the largest number of regulatory letters (850; 34.5% of the total, followed by the Office of Scientific Investigations (131; 5.3%, and the Office of Compliance (105; 4.3%. During the 2nd Clinton Administration (1997–2000 the average number of regulatory letters per year was 242.8 ± 45.6, during the Bush Administration (2001–2008 it was 120.4 ± 33.7, and during the first three years of the Obama administration (2009–2011 it was 177.7.0 ± 17.0. The average number of regulatory letters released by the Office of Prescription Drug Promotion also varied by

  16. Evaluation of Bioactive Compounds, Pharmaceutical Quality, and Anticancer Activity of Curry Leaf (Murraya koenigii L.

    Ali Ghasemzadeh

    2014-01-01

    Full Text Available In this study, we investigated some bioactive compounds and pharmaceutical qualities of curry leaf (Murraya koenigii L. extracts from three different locations in Malaysia. The highest TF and total phenolic (TP contents were observed in the extracts from Kelantan (3.771 and 14.371 mg/g DW, followed by Selangor (3.146 and 12.272 mg/g DW and Johor (2.801 and 12.02 mg/g DW, respectively. High quercetin (0.350 mg/g DW, catechin (0.325 mg/g DW, epicatechin (0.678 mg/g DW, naringin (0.203 mg/g DW, and myricetin (0.703 mg/g DW levels were observed in the extracts from Kelantan, while the highest rutin content (0.082 mg/g DW was detected in the leaves from Selangor. The curry leaf extract from Kelantan exhibited higher concentration of gallic acid (0.933 mg/g DW than that from Selangor (0.904 mg/g DW and Johor (0.813 mg/g DW. Among the studied samples, the ones from Kelantan exhibited the highest radical scavenging activity (DPPH, 66.41% and ferric reduction activity potential (FRAP, 644.25 μm of Fe(II/g followed by those from Selangor (60.237% and 598.37 μm of Fe(II/g and Johor (50.76% and 563.42 μm of Fe(II/g, respectively. A preliminary screening showed that the curry leaf extracts from all the locations exhibited significant anticarcinogenic effects inhibiting the growth of breast cancer cell line (MDA-MB-231 and maximum inhibition of MDA-MB-231 cell was observed with the curry leaf extract from Kelantan. Based on these results, it is concluded that Malaysian curry leaf collected from the North (Kelantan might be potential source of potent natural antioxidant and beneficial chemopreventive agents.

  17. Research Progress in the Active Ingredients of Rose & Rose Wine%玫瑰花有效成分及玫瑰花酒的研究进展

    胡晓燕; 沈才洪; 敖宗华; 杨学琴; 黄张君; 钟霞

    2014-01-01

    玫瑰花具有令人愉悦的香气,是一种适合开发保健酒的良好原料。主要对玫瑰花的有效成分、有效成分的提取方法、有效成分应用功能、玫瑰花酒生产等的研究进展作了简要的综述。%Rose has pleasant aroma and is suitable for the development of healthcare wine. In this paper, the research progress in the active ingre-dients of rose and their extraction and application, and the production of rose wine was reviewed.

  18. Highly sensitive solid forms discrimination on the whole tablet of the active ingredients in quercetin dietary supplements by NMR crystallography approaches.

    Miclaus, Maria O; Filip, Xenia; Filip, Claudiu; Martin, Flavia A; Grosu, Ioana G

    2016-05-30

    Similarly to synthetic drugs, the exact crystalline form of active ingredients in solid formulations of dietary supplements may directly influence the dissolution rate, bioavailability, and stability of the final product, but this information is usually not provided by manufacturers. Working on the examples of two commercial quercetin dietary supplements a quick, reliable, and sensitive method is introduced for quercetin solid forms discrimination directly on the marketed products, without the need for prior sample preparation. It exploits the complementarity between solid-state Nuclear Magnetic Resonance (ss-NMR) and Powder X-Ray Diffraction (PXRD), which proved essential for performing a complete and accurate solid-state characterization of the two commercial products, and for obtaining new insights into the complex quercetin solid-forms landscape. The method can be readily generalized also to other dietary supplements based on bio-flavonoids/polyphenols. PMID:26970982

  19. Review on active ingredients from Cannabis sativa leaves and its pharmacological characteristics%汉麻叶活性成分及其药理特性的研究概况

    杜军强; 何锦风; 何聪芬; 蒲彪; 李靖宇; 蒋勇

    2011-01-01

    Cannabis saliva leaves contains a variety of active ingredients, including cannabinoid and non -cannabinoid. Active ingredients from Cannahis saliva leaves have a high application value in the pharmacy and other fields. In this paper, the pharmacological characteristics of cannabinoid, non-cannabinoid and unknown active ingredients was summarized.%汉麻叶含有多种活性成分,包括大麻酚类化合物和非大麻酚类化合物.汉麻叶的活性成分在医药等领域有极高的应用价值.本文就大麻酚类化合物,非大麻酚类化合物和未知活性成分的药理特性展开综述.

  20. Oxidation of pharmaceuticals by chlorine dioxide in biologically treated wastewater

    Hey, G.; Grabic, R.; Ledin, A.; la Cour Jansen, J; Andersen, H R

    2012-01-01

    Biologically treated wastewater spiked with a mixture of 56 active pharmaceutical ingredients (APIs) was treated with 0–20mg/L chlorine dioxide (ClO2) solution in laboratory-scale experiments. Wastewater effluents were collected from two wastewater treatment plants in Sweden, one with extended nitrogen removal (low COD) and one without (high COD). About one third of the tested APIs resisted degradation even at the highest ClO2 dose (20mg/L), while others were reduced by more than 90% at the l...

  1. PBT assessment and prioritization of contaminants of emerging concern: Pharmaceuticals.

    Sangion, Alessandro; Gramatica, Paola

    2016-05-01

    The strong and widespread use of pharmaceuticals, together with incorrect disposal procedures, has recently made these products contaminants of emerging concern (CEC). Unfortunately, little is known about pharmaceuticals' environmental behaviour and ecotoxicity, so that EMEA (European Medicines Agency) released guidelines for the pharmaceuticals' environmental risk assessment. In particular, there is a severe lack of information about persistence, bioaccumulation and toxicity (PBT) of the majority of the thousands of substances on the market. Computational tools, like QSAR (Quantitative Structure Activity Relationship) models, are the only way to screen large sets of chemicals in short time, with the aim of ranking, highlighting and prioritizing the most environmentally hazardous for focusing further experimental studies. In this work we propose a screening method to assess the potential persistence, bioaccumulation and toxicity of more than 1200 pharmaceutical ingredients, based on the application of two different QSAR models. We applied the Insubria-PBT Index, a MLR (Multiple Linear Regression) QSAR model based on four simple molecular descriptors, implemented in QSARINS software, and able to synthesize the PBT potential in a unique cumulative value and the US-EPA PBT Profiler that assesses the PBT behaviour evaluating separately P, B and T. Particular attention was given to the study of Applicability Domain in order to provide reliable predictions. An agreement of 86% was found between the two models and a priority list of 35 pharmaceuticals, highlighted as potential PBTs by consensus, was proposed for further experimental validation. Moreover, the results of this computational screening are in agreement with preliminary experimental data in the literature. This study shows how in silico models can be applied in the hazard assessment to perform preliminary screening and prioritization of chemicals, and how the identification of the structural features, mainly

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

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

    2016-07-01

    Twenty commonly used pharmaceuticals including eight chiral drugs were investigated in Dongting Lake, China. The contamination level was relatively low on a global scale. Twelve pharmaceuticals were identified. The most abundant compound was caffeine followed by diclofenac, DEET, mefenamic acid, fluoxetine, ibuprofen and carbamazepine with mean concentrations from 2.0 to 80.8ngL(-1). Concentrations between East and West Dongting Lake showed spatial difference, with the West Dongting Lake less polluted. The relatively high ratio of caffeine versus carbamazepine (over 50) may indicate there was possible direct discharge of domestic wastewater into the lake. This is the first study presenting a survey allowing for comprehensive analysis of multiclass achiral and chiral pharmaceuticals including beta-blockers, antidepressants and anti-inflammatory drugs in freshwater lake. The enantiomeric compositions presented racemic to weakly enantioselective, with the highest enantiomeric fraction (EF) of 0.63 for fluoxetine. Meanwhile, venlafaxine was identified and evaluated the environment risk in surface water in China for the first time. The results of risk assessment suggested that fluoxetine, venlafaxine and diclofenac acid might pose a significant risk to aquatic organisms in Dongting Lake. The resulting data will be useful to enrich the research of emerging pollutants in freshwater lake and stereochemistry for environment investigations. PMID:27016674

  3. Suggestions on Improving Supervision of Active Pharmaceutical Ingredients in China%提高我国原料药监管水平的几点设想

    马云鹏; 叶桦

    2012-01-01

    目的 为加强原料药监管提出建议.方法 分析原料药产业监管现状和存在的问题.结果与结论 应结合中国的国情,完善监管法规与制度,建立以原料药目录为依据的管理模式,强化GMP对原料药的规范内容,加强流通与出口管理,积极参与国际联合监管.

  4. 山茱萸炮制前后药效成分含量的变化%Content Changes of Activated Pharmaceutical Ingredients from Cornus Officinalis during Processing

    赵玉丛; 杨卫华; 刘国际

    2007-01-01

    目的 对山茱萸炮制前后药效成分的含量进行比较研究.方法 分别采用高效液相色谱法和比色法对山茱萸生品和炮制品中的熊果酸和总皂苷的含量进行测定.结果 山茱萸酒蒸品与生品相比,熊果酸的含量增加,而总皂苷的含量却有所下降.结论 山茱萸的加工炮制对其有效成分含量的影响有所不同,临床入药应区别对待.

  5. 炮制对山茱萸中药效成分的影响%Effects of Processing on the Activated Pharmaceutical Ingredients from Cornus officinalis

    赵玉丛; 李存法; 刘国际

    2008-01-01

    [目的]系统考察了炮制对中药山茱萸药效成分的影响,并初步探讨了山茱萸炮制前后其药理作用发生变化的相关物质基础.[方法]结合试验研究与文献综述,分别对山茱萸生品、酒蒸品中各类药效成分的含量进行考察.[结果]山茱萸酒蒸后苷类成分的含量均有所下降,而有机酸类成分、多糖类成分、与肝肾有关的药用氨基酸及微量元素的含量均有所增加.[结论]山茱萸炮制前后药理作用的差异与其物质基础密切相关.山茱萸临床入药是否进行加工炮制应取决于其具体临床应用.

  6. 浅谈国外客户对原料药的质量审计%Quality Audit of Active Pharmaceutical Ingredients by Foreign Clients

    温耀明

    2012-01-01

    目的 浅析国外客户对原料药的质量审计.方法 介绍了质量审计的目的和特点,并针对客户审计的重点,按审计过程进行详细论述和分析.结果与结论 在准备和接受国外客户质量审计的活动中,完善了自身的质量管理体系,提高了企业的产品质量水平和国际市场竞争力.

  7. Analysis of FDA Inspection on GMP Conformance for the Manufacturing of Active Pharmaceutical Ingredients%谈谈FDA对原料药的GMP现场检查

    吕冬梅; 史玮

    2010-01-01

    目的浅析FDA对原料药的GMP现场检查.方法针对FDA关于原料药GMP现场检查的重点进行详细论述和分析.结果与结论 企业如果建立了有效的GMP制度,那么企业完全能够通过FDA的认证.

  8. 急需开发的原料药--头孢克肟%Cefixime:An Active Pharmaceutical Ingredient to be Development Urgently

    张诗海; 赵美法

    2003-01-01

    头孢克肟抗菌谱广、半衰期长、交叉耐药性小、用药剂量小、适应症广泛.该药专利已于2001年7月到期,是我国重点开发的第三代口服头孢菌素之一.头孢克肟的合成路线有两条:7-ACA工艺和脱乙酰头孢菌素C工艺.该药目前在欧洲的年销售额约2亿美元.

  9. Sterilization Process Validation of Aseptic Active Pharmaceutical Ingredient%无菌原料药生产的无菌工艺验证

    翟铁伟; 韩志伟

    2004-01-01

    介绍了无菌原料药无菌工艺验证的一般过程和注意事项,包括验证前准备、验证实施、最终报告和再验证,以及人员培训、操作时限、模拟介质的选择和灭菌、环境监测、取样和样品培养等.

  10. Developments of China's Active Pharmaceutical Ingredients Industry%国内原料药产业动态及发展建议

    汤方毅; 吴泉

    2003-01-01

    我国原料药年产量达56万t,是世界第二大原料药生产国.出口量占总产量的30%~40%,2001年出口额为19.2亿美元.产量大、劳动力成本低、技术水平不断提高成为我国原料药制造业的优势.在世界原料药生产中心向发展中国家转移的过程中,印度将成为我国的主要竞争对手,我国企业应通过技术创新来加强竞争力.

  11. 药品中遗传毒性杂质的评估和控制%Evaluation and Control of Genotoxic Impurities in Active Pharmaceutical Ingredients

    张慧敏; 林建群; 冯康彪; 杜有功; 王红; 孙渊

    2014-01-01

    目的 综述药品遗传毒性杂质控制相关指南和法规,为制药企业执行国际标准和准则提供一些建议和思路.方法 通过查找数据库如Pubmed、Medline及欧洲药品管理局(European Medicines Agency,EMA)、美国食品药品监督管理局(USFood and Drug Administratio,U.S.FDA)、人用药品注册技术要求国际协调会议(ICH)等网站,比较各指南法规关于遗传毒性控制限度和控制措施的异同点,为遗传毒性杂质的控制提供一个可行性步骤.结果 通过比较发现,EMA、U.S.FDA和即将出版的ICH M7指南在关键原则的应用方面如毒理学关注阈值(threshold of toxicological concern,TTC)、风险评估步骤、杂质5分类法等基本相同,但现行EMA和U.S.FDA法规存在分歧,不利于其有效执行,而ICH M7将为遗传毒性杂质的控制提供一个可行框架.结论 目前还缺乏完善有效的遗传毒性控制指南,ICH M7将解决U.S.FDA和EMA指南间分歧,更好地指导制药企业遗传毒性杂质的控制.

  12. 药用化工原料监管政策的研究%Discussion on Regulatory Policy for Active Pharmaceutical Ingredient

    王岩; 张启明; 孙磊

    2011-01-01

    目的 探讨药用化工原料的监管政策.方法 对比研究国内外原料药监管政策以及分析我国原料药的生产现状.结果与结论 应通过法律法规的完善、国际间的政府合作、提高技术准入标准等手段,加强对药用化工原料的监管.

  13. Pharmaceutical Economics

    2008-01-01

    Pharmaceutical Economics begins with an investigation of the structure of the industry and its three main components: the research firms which produce innovative products; the generic drug industry and its expanding role; and the biotech industry, which is regarded as the future for pharmaceuticals. Further sections discuss topics including demand and incentives, pricing and regulation.

  14. Aryl Hydrocarbon Receptor (AHR)-Active Pharmaceuticals Are Selective AHR Modulators in MDA-MB-468 and BT474 Breast Cancer Cells

    Jin, Un-Ho; Lee, Syng-Ook; Safe, Stephen

    2012-01-01

    Leflunomide, flutamide, nimodipine, mexiletine, sulindac, tranilast, 4-hydroxytamoxifen, and omeprazole are pharmaceuticals previously characterized as aryl hydrocarbon receptor (AHR) agonists in various cell lines and animal models. In this study, the eight AHR-active pharmaceuticals were investigated in highly aggressive aryl hydrocarbon (Ah)-responsive BT474 and MDA-MB-468 breast cancer cell lines, and their effects on AHR protein, CYP1A1 (protein and mRNA), CYP1B1 (mRNA), and cell migrati...

  15. Understanding the degree of awareness among medical professionals regarding the ethics of pharmaceutical marketing activities in context of revised medical council of India code of ethics

    Renuka H. Munshi; Kanchan R. Singh; Astha D. Thakkar

    2016-01-01

    Background: Pharmaceutical marketing activities are regarded as ethically challenging by most medical professionals. This study was planned to understand the extent of the interaction of pharmaceutical companies with healthcare providers and to determine the level of awareness about the and lsquo;Medical Council of India (MCI) Code of Ethics'. Methods: A questionnaire based survey was conducted among 100 consultants and residents. The questionnaire mainly dealt with ethical issues about...

  16. Functional ingredients from microalgae

    Buono, S.; Langellotti, A.L.; Martello, A.; Rinna, F.; Fogliano, V.

    2014-01-01

    A wide variety of natural sources are under investigation to evaluate their possible use for new functional ingredient formulation. Some records attested the traditional and ancient use of wild harvested microalgae as human food but their cultivation for different purposes started about 40 years ago

  17. Ingredients of supergravity

    Freedman, D. [Department of Mathematics and Center for Theoretical Physics, M.I.T., Cambridge, Massachusetts (United States); Proeyen, A. van [Instituut voor Theoretische Fysica, Katholieke Universiteit Leuven (Belgium)

    2011-11-15

    These notes give a summary of lectures given in Corfu in 2010 on basic ingredients in the study of supergravity. It also summarizes initial chapters of a forthcoming book 'Supergravity' by the same authors. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  18. Structural characterization of pharmaceutical heparins prepared from different animal tissues.

    Fu, Li; Li, Guoyun; Yang, Bo; Onishi, Akihiro; Li, Lingyun; Sun, Peilong; Zhang, Fuming; Linhardt, Robert J

    2013-05-01

    Although most pharmaceutical heparin used today is obtained from porcine intestine, heparin has historically been prepared from bovine lung and ovine intestine. There is some regulatory concern about establishing the species origin of heparin. This concern began with the outbreak of mad cow disease in the 1990s and was exacerbated during the heparin shortage in the 2000s and the heparin contamination crisis of 2007-2008. Three heparins from porcine, ovine, and bovine were characterized through state-of-the-art carbohydrate analysis methods with a view profiling their physicochemical properties. Differences in molecular weight, monosaccharide and disaccharide composition, oligosaccharide sequence, and antithrombin III-binding affinity were observed. These data provide some insight into the variability of heparins obtained from these three species and suggest some analytical approaches that may be useful in confirming the species origin of a heparin active pharmaceutical ingredient. PMID:23526651

  19. Compatibility and stability of valsartan in a solid pharmaceutical formulation

    Tamíris Amanda Júlio

    2013-12-01

    Full Text Available Valsartan (VAL is a highly selective blocker of the angiotensin II receptor that has been widely used in the treatment of hypertension. Active pharmaceutical ingredient compatibility with excipients (crospovidone, hypromellose, magnesium stearate, microcrystalline cellulose and titanium dioxide is usually evaluated in solid pharmaceutical development. Compatibility and stability can be evaluated by liquid chromatography. Studies were performed using binary mixtures of 1:1 (w/w VAL/excipient; samples were stored under accelerated stability test conditions (40 ºC at 75% relative humidity. The results indicate that VAL is incompatible with crospovidone and hypromellose, which reduced the VAL content and gave rise to new peaks in the chromatogram due to degradation products.

  20. Characterizing dense suspensions: two case studies from the pharmaceutical industry

    Goldfarb, David J.; Khawaja, Nazia; Kazakevich, Irina; Bhattacharjee, Himanshu; Heslinga, Michael; Dalton, Chad

    2015-11-01

    Liquid suspensions of Active Pharmaceutical Ingredient powders are present as pharmaceutical dosage forms in the form of oral suspensions and injectables. We present two case studies, both dense (~ 30-40%) suspensions, in which the physical characterization of the product, specifically, particle size & shape and rheology were key to understanding the key product attributes as pertaining to the manufacturing process and to patient administration. For the one case study, an oral suspension, identifying variations in particle morphology during the wet milling of the product was key to the product understanding necessary to modify the milling process. Rheological measurements were applied as well. For the second case study, an injectable, results from different particle size measurement techniques and rheological measurements indicated the possibility of flocculation in a formulation. Additionally, measurements were obtained to assess the ``injectability'' of the product via rheometer and texture analyzer measurements and Poiseuille flow modeling. As a result, the relevant shear rate regime for this drug product administration was identified.

  1. Whole-bowel irrigation versus activated charcoal in sorbitol for the ingestion of modified-release pharmaceuticals.

    Kirshenbaum, L A; Mathews, S C; Sitar, D S; Tenenbein, M

    1989-09-01

    Overdose with modified-release pharmaceuticals is an increasing phenomenon. This study examines whole-bowel irrigation as a potential decontamination strategy after overdose with enteric-coated acetylsalicylic acid and compares it with administration of activated charcoal in sorbitol, which is currently the recommended intervention. A three-phase randomized crossover protocol was used in 10 adult volunteers. Each volunteer ingested nine 325 mg doses of enteric-coated acetylsalicylic acid on three occasions, with at least 1 week between each administration period. Serum samples were analyzed for salicylic acid concentration by HPLC. Both interventions decreased peak salicylic acid concentration, time-to-zero salicylic acid concentration, and AUC when compared with control (p less than 0.01). Whole-bowel irrigation was superior to activated charcoal in sorbitol by all three criteria (p less than 0.05). Adverse effects were qualitatively and quantitatively greater during activated charcoal in sorbitol, and the volunteers preferred whole-bowel irrigation over charcoal in sorbitol. Our data suggest that whole-bowel irrigation should be considered for overdose of other modified-release pharmaceuticals. PMID:2673619

  2. Pharmaceutically active compounds and endocrine disrupting chemicals in water, sediments and mollusks in mangrove ecosystems from Singapore.

    Bayen, Stéphane; Estrada, Elvagris Segovia; Juhel, Guillaume; Kit, Lee Wei; Kelly, Barry C

    2016-08-30

    This study investigated the occurrence of bisphenol A (BPA), atrazine and selected pharmaceutically active compounds (PhACs) in mangrove habitats in Singapore in 2012-2013, using multiple tools (sediment sampling, POCIS and filter feeder molluscs). Using POCIS, the same suite of contaminants (atrazine, BPA and eleven PhACs) was detected in mangrove waters in 28-days deployments in both 2012 and 2013. POCIS concentrations ranged from pg/L to μg/L. Caffeine, BPA, carbamazepine, E1, triclosan, sulfamerazine, sulfamethazine, and lincomycin were also detected in mangrove sediments from the low pg/g dw (e.g. carbamazepine) to ng/g dw (e.g. BPA). The detection of caffeine, carbamazepine, BPA, sulfamethoxazole or lincomycin in bivalve tissues also showed that these chemicals are bioavailable in the mangrove habitat. Since there are some indications that some pharmaceutically active substances may be biologically active in the low ppb range in marine species, further assessment should be completed based on ecotoxicological data specific to mangrove species. PMID:27393211

  3. Rapid isolation and identification of active antioxidant ingredients from Gongju using HPLC-DAD-ESI-MS(n) and postcolumn derivatization.

    Cui, Gang; Niu, Yaru; Wang, Hong; Dong, Jing; Yuki, Hashi; Chen, Shizhong

    2012-05-30

    Flos Chrysanthemi (Gongju, GJ) is used to prepare a herbal tea that is commonly consumed as a health beverage in Asia and is believed to contain abundant beneficial antioxidants. To rapidly identify the chemical constituents and to obtain the profile related to antioxidant activity, an online analytical method combining high-performance liquid chromatography-diode-array detector-electrospray ionization-ion-trap time-of-flight mass spectrometry (HPLC-DAD-ESI-IT-TOF-MS(n)) and postcolumn derivatization (PCD) has been applied for a precise and thorough identification of the chemical constituents. Meanwhile, the antioxidant profile has also been characterized by directly measuring the scavenging activity of each compound for the free radical produced by DPPH. As a result, 13 compounds have been identified in GJ, 7 of which account for its antioxidant activity. The established LC-MS(n)-PCD system has proved to offer a useful strategy for correlating the chemical profile with the bioactivities of the components without their isolation and purification, and may be used for multicomponent analysis of active substances in other foods and herbs. PMID:22540938

  4. Field-scale monitoring of pharmaceutical compounds applied to active golf courses by recycled water.

    Young, M H; Green, R L; Conkle, J L; McCullough, M; Devitt, D A; Wright, L; Vanderford, B J; Snyder, S A

    2014-03-01

    The scarcity of potable water in arid and semiarid environments has led to the wider use of recycled water for irrigating agricultural fields, parks, golf courses, and other areas. One concern using recycled water as a source of irrigation has been the presence, fate, and transport of pharmaceutical compounds in water that percolates below the root zone of plants; however, very few multiyear field studies have been reported in the peer-reviewed literature. Here, we assessed compound mass flux of 13 pharmaceuticals in the fairways of four golf courses in the southwestern United States during a 2-yr field study. The sites varied by climate and soil type but were similar regarding turfgrass management. The results showed the presence of at least one pharmaceutical compound in nearly all samples collected, although concentrations were substantially lower after transport through the soil. Percent reduction in compound mass fluxes in drainage water was effectively 100% in 22 of 52 cases, 98 to 100% in 27 of 52 cases, and 73 to 94% in 3 of 52 cases (a case is defined as a specific compound measured at a specific site). Mass fluxes migrating below the root zone were calculated as 100 × 10 g ha in only two cases. For cases where the majority of the analyses were reportable, all fluxes were <8.80 × 10 g ha. Carbamazepine, meprobamate, and sulfamethoxazole were most commonly found in drainage water, representing nearly 80% of all reportable detections. This research demonstrates the potential of turfgrass/soil systems to reduce contaminant loading below the root zone and potentially toward groundwater. PMID:25602667

  5. Design of optimal solvent for extraction of bio–active ingredients from six varieties of Medicago sativa

    Caunii Angela

    2012-10-01

    Full Text Available Abstract Background Extensive research has been performed worldwide and important evidences were collected to show the immense potential of plants used in various traditional therapeutic systems. The aim of this work is to investigate the different extracting solvents in terms of the influence of their polarity on the extracting ability of bioactive molecules (phenolic compounds from the M. sativa flowers. Results The total phenolic content of samples was determined using the Folin Ciocalteu (FC procedure and their antioxidant activity was assayed through in vitro radical decomposing activity using the radical DPPH° assay (IUPAC name for DPPH is (phenyl–(2,4,6–trinitrophenyl iminoazanium. The results showed that water was better than methanol and acetic acid for extracting bioactive compounds, in particular for total phenolic compounds from the flowers of alfalfa. The average content of bioactive molecules in methanol extract was 263.5±1.02 mg GAE/100g of dry weight lyophilized extract. The total phenolic content of the tested plant extracts was highly correlated with the radical decomposing activity. However, all extracts were free–radical inhibitors, but the water extract was more potent than the acetic and the methanol ones. The order of inhibitor effectiveness (expressed by IC50 proved to be: water extract (0.924mg/mL > acetic acid extract (0.154mg/mL > methanol (0.079mg/mL. The profiles of each extract (fingerprint were characterized by FT–MIR spectroscopy. Conclusions The present study compares the fingerprint of different extracts of the M. sativa flowers, collected from the wild flora of Romania. The total phenolic content of the tested plant extracts was highly correlated with the radical decomposing activity. The dependence of the extract composition on the solvent polarity (acetic acid vs. methanol vs. water was revealed by UV–VIS spectrometry and Infrared fingerprint.

  6. Extraction and Separation of Active Ingredients in Schisandra chinensis (Turcz.) Baill and the Study of their Antifungal Effects

    Yi, Haijing; Yan CHEN; LIU Jun; Jie ZHANG; Wei GUO; Xiao, Weilie; Yao, Yuncong

    2016-01-01

    Schisandra chinensis extracts (SEs) have traditionally been used as an oriental medicine for the treatment of various human diseases, however, their further application in the biocontrol of plant disease remains poorly understood. This study was conducted to develop eco-friendly botanical pesticides from extracts of S. chinensis and assess whether they could play a key role in plant disease defense. Concentrated active fractions (SE-I, SE-II, and SE-III) were obtained from S. chinensis via sp...

  7. Antimicrobial activity of a traditionally used complex essential oil distillate (Olbas(®) Tropfen) in comparison to its individual essential oil ingredients.

    Hamoud, Razan; Sporer, Frank; Reichling, Jürgen; Wink, Michael

    2012-08-15

    Plant extracts and essential oils have been widely studied and used as antimicrobial agents in the last decades. In our study we investigated the antimicrobial activities of Olbas(®) Tropfen (in the following named Olbas), a traditionally used complex essential oil distillate, in comparison to its individual essential oil ingredients. Olbas (10 g) consists of three major components such as peppermint oil (5.3 g), eucalyptus oil (2.1 g), and cajuput oil (2.1 g) and of two minor constituents like juniper berry oil (0.3 g) and wintergreen oil (0.2 g). The composition of Olbas and the five individual essential oils were characterized by GLC-MS. According to GLC-MS analysis 1,8-cineol is the main component of the complex essential oil distillate followed by menthol and menthone. The minimum inhibitory and minimum microbicidal concentrations of Olbas and each of the single essential oils were evaluated in 17 species/strains of bacteria and fungi. Time-kill assay was performed to compare the microbicidal activity of Olbas and peppermint oil during several time intervals. Olbas displayed a high antimicrobial activity against all test strains used in this study, among them antibiotic resistant MRSA (methicillin-resistant Staphylococcus aureus) and VRE (vancomycin-resistant Enterococcus). Its antimicrobial activity was comparable to that of peppermint oil which was the most potent one of all individual essential oils tested. In the time kill assay Olbas as well as peppermint oil demonstrated similar microbicidal activities. Based on its wide antimicrobial properties Olbas can be a useful agent for the treatment of uncomplicated infections of skin and respiratory tract. PMID:22739414

  8. Extraction and Separation of Active Ingredients in Schisandra chinensis (Turcz.) Baill and the Study of their Antifungal Effects

    Liu, Jun; Zhang, Jie; Guo, Wei; Xiao, Weilie; Yao, Yuncong

    2016-01-01

    Schisandra chinensis extracts (SEs) have traditionally been used as an oriental medicine for the treatment of various human diseases, however, their further application in the biocontrol of plant disease remains poorly understood. This study was conducted to develop eco-friendly botanical pesticides from extracts of S. chinensis and assess whether they could play a key role in plant disease defense. Concentrated active fractions (SE-I, SE-II, and SE-III) were obtained from S. chinensis via specific extraction and separation. Then, lignan-like substances, such as Schisanhenol B, were detected via High-Performance Liquid Chromatography-ElectroSpray Ionization-Mass Spectrometry (HPLC-ESI-MS) analyses of the active fractions. Moreover, the results from biological tests on colony growth inhibition and spore germination indicated that SE-I, SE-II, and SE-III could inhibit hyphal growth and spore generation of three important plant pathogenic fungi (Monilinia fructicola, Fusarium oxysporum, and Botryosphaeria dothidea). The study of the mechanisms of resistant fungi revealed that the oxidation resistance system, including reactive oxygen species (ROS), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD), was activated. The expression of genes related to defense, such as pathogenesis-related protein (PR4), α-farnesene synthase (AFS), polyphenol oxidase (PPO), and phenylalanine ammonia lyase (PAL) were shown to be up-regulated after treatment with SEs, which suggested an increase in apple immunity and that fruits were induced to effectively defend against the infection of pathogenic fungi (B. dothidea). This study revealed that SEs and their lignans represent promising resources for the development of safe, effective, and multi-targeted agents against pathogenic fungi. PMID:27152614

  9. Preparation of ultrafine magnetic biochar and activated carbon for pharmaceutical adsorption and subsequent degradation by ball milling.

    Shan, Danna; Deng, Shubo; Zhao, Tianning; Wang, Bin; Wang, Yujue; Huang, Jun; Yu, Gang; Winglee, Judy; Wiesner, Mark R

    2016-03-15

    Ball milling was used to prepare two ultrafine magnetic biochar/Fe3O4 and activated carbon (AC)/Fe3O4 hybrid materials targeted for use in pharmaceutical removal by adsorption and mechanochemical degradation of pharmaceutical compounds. Both hybrid adsorbents prepared after 2h milling exhibited high removal of carbamazepine (CBZ), and were easily separated magnetically. These adsorbents exhibited fast adsorption of CBZ and tetracycline (TC) in the initial 1h. The biochar/Fe3O4 had a maximum adsorption capacity of 62.7mg/g for CBZ and 94.2mg/g for TC, while values obtained for AC/Fe3O4 were 135.1mg/g for CBZ and 45.3mg/g for TC respectively when data were fitted using the Langmuir expression. Solution pH values slightly affected the sorption of TC on the adsorbents, while CBZ sorption was almost pH-independent. The spent adsorbents with adsorbed CBZ and TC were milled to degrade the adsorbed pollutants. The adsorbed TC itself was over 97% degraded after 3h of milling, while about half of adsorbed CBZ were remained. The addition of quartz sand was found to improve the mechanochemical degradation of CBZ on biochar/Fe3O4, and its degradation percent was up to 98.4% at the dose of 0.3g quarts sand/g adsorbent. This research provided an easy method to prepare ultrafine magnetic adsorbents for the effective removal of typical pharmaceuticals from water or wastewater and degrade them using ball milling. PMID:26685062

  10. Bioassay-tracked temperature-stress-induced chemical degradation of bio-active wound healing antibacterial extract of Dissotis theifolia stem dispersed in a pharmaceutical cream and ointment

    D C Odimegwu

    2011-03-01

    Full Text Available Summary: Owing to the present upsurge in the utilization of medicinal herbal preparations, routine quality control assessment for their continued efficacy and safety is essential if the products are to continue to maintain their pharmacological usefulness under harsh use and storage temperature normally experienced, particularly in the tropics. As herbal medicinal products are complex mixtures which originate from biological sources and are therefore very variable and difficult to characterize, great efforts are necessary to guarantee a constant and adequate quality of potency and safety through selection of an appropriate analytical method for the monitoring of the active ingredient content of such products. Dissotis theifolia is a commonly used plant in traditional herbal medicine for the treatment of several medical ailments, including topical bacterial infections, among several communities in Nigeria. In this present study, the quality control monitoring of the content of active ingredient of pharmaceutical cream and ointment containing the methanol extract of the stem exposed to variegated temperatures was established using a specific microbiological assay method. Results showed reduction of potency of the formulated extracts due to chemical degradation through the first order reaction pathway. The ointment formulation demonstrated a longer half-life and shelf-life being more stable than the cream.   Industrial relevance: Herbal medicine, a form of complimentary and alternative medicine, is becoming increasingly popular in both developing and developed countries. However, there appear to be limited data on their temperature-induce chemical stability/instability profile which correspondingly impinges on their efficacy and safety. In view of this study involving stem extract of D. theifolia formulated as cream and ointment, appropriate bioassay-based techniques can be employed in monitoring the potency of herbal preparations and can serve as

  11. Pharmaceutical Frenzy

    LAN XINZHEN

    2010-01-01

    @@ When shares of Shanghai Pharmaceutical(Group)Co.Ltd.(Shanghai Pharma)resumed normal transactions on March9,2010,the biggest listed pharmaceutical company on China's stock market was born.By the time the closing bell rang at the end of the trading day,the market value of Shanghai Pharma had reached 32.28 billion yuan($4.73 billion).

  12. ICP-OES法快速检测药品中催化剂残留的14种重金属元素%Rapid Determination of 14 Heavy Metal Elements of Catalysts Residues in Pharmaceutical Ingredients by ICP- OES Method

    张玲帆; 王艳萍; 刘鑫; 陶卫; 张磊; 张文清

    2012-01-01

    采用有机溶剂二甲基亚砜和水(4∶1)的混合溶剂溶解药物样品,建立了电感耦合等离子体发射光谱法(ICP - OES)直接检测药物产品中金属催化剂残留的方法.在优化实验条件下,该法能快速检测欧洲药物评审委员会(EMEA)颁布指南中的14种重金属元素;方法检出限均小于0.30 mg/kg,加标回收率在90%~115%之间;对不同前处理方法的数据结果进行了对比.实验结果表明,该法操作简单、快速、准确度高,适合大批量药物产品中多元素的快速检测.%An inductively coupled plasma optical emission spectrometric (ICP - OES) method was developed for the determination of metallic impurities in pharmaceutical ingredients. The samples were directly dissolved with organic mixed solvent (DMSO : H2O =4 : 1). The conditions of instrument were optimized, and the 14 metal elements listed in EMEA guidance could be rapidly analyzed by the method. The detection limits were less than 0. 30 mg/kg, and the recoveries of the 14 metal elements ranged from 90% to 115% . The data was compared with those obtained from the different treatment methods. The results showed that the method, with the advantages of simplicity, easy operation and high accuracy, was suitable for the quick determination of multi-elements in large quantities of samples.

  13. 黄芪的有效成分提取与纳滤提取应用分析%Active Ingredients Extracted and Nanofiltration Application in Astragalus Extract

    郭立忠; 吴镝

    2015-01-01

    Objective To analyze the active ingredients of astragalus diarrhea extraction and nanofiltration extracted application,astragalus traditional extraction process improvements. Methods APS,saponins as subjects,the use of orthogonal experimental design and analysis of numerical range analysis by comparing the effects of different extraction temperature,time and number of ingredients,and the extraction process in boiling alcohol shen added effect of cel ulase,nanofiltration comparison,the evaporation method. Results The experimental results showed that the temperature < 80 ℃, extracting 2 times,and each time 60 min nanofiltration concentrated extract was the optimum water extraction of astragalus. Conclusion Compared to traditional boiling alcohol precipitation extraction,astragalus of nanofiltration extraction process in the economic,technical y strong advantages,it has some promotional value in guiding the preparation of manufacturing,clinical applications.%目的:分析黄芪的有效成分提取和纳滤提取的应用,对传统的黄芪提取工艺进行改进。方法将黄芪多糖、总皂甙作为实验对象,使用正交实验设计并用极差分析法分析数值,对比不同提取温度、时间和次数对成分含量的影响,并在水煮醇沉提取工艺中加入了纤维素酶,比较纳滤、蒸发方法的效果。结果实验表明温度<80℃、提取2次且每次60 min的纳滤浓缩提取是黄芪水提的最佳工艺。结论相比较传统水煮醇沉提取法,黄芪的纳滤浓缩提取工艺在经济、技术上有很强的优越性,在指导制剂生产、临床应用中具有一定的推广价值。

  14. Recent trends in the impurity profile of pharmaceuticals

    Kavita Pilaniya

    2010-01-01

    Full Text Available Various regulatory authorities such as the International Conference on Harmonization (ICH, the United States Food and Drug administration (FDA, and the Canadian Drug and Health Agency (CDHA are emphasizing on the purity requirements and the identification of impurities in Active Pharmaceutical Ingredients (APIs. The various sources of impurity in pharmaceutical products are - reagents, heavy metals, ligands, catalysts, other materials like filter aids, charcoal, and the like, degraded end products obtained during \\ after manufacturing of bulk drugs from hydrolysis, photolytic cleavage, oxidative degradation, decarboxylation, enantiomeric impurity, and so on. The different pharmacopoeias such as the British Pharmacopoeia, United State Pharmacopoeia, and Indian Pharmacopoeia are slowly incorporating limits to allowable levels of impurities present in APIs or formulations. Various methods are used to isolate and characterize impurities in pharmaceuticals, such as, capillary electrophoresis, electron paramagnetic resonance, gas-liquid chromatography, gravimetric analysis, high performance liquid chromatography, solid-phase extraction methods, liquid-liquid extraction method, Ultraviolet Spectrometry, infrared spectroscopy, supercritical fluid extraction column chromatography, mass spectrometry, Nuclear magnetic resonance (NMR spectroscopy, and RAMAN spectroscopy. Among all hyphenated techniques, the most exploited techniques for impurity profiling of drugs are Liquid Chromatography (LC-Mass Spectroscopy (MS, LC-NMR, LC-NMR-MS, GC-MS, and LC-MS. This reveals the need and scope of impurity profiling of drugs in pharmaceutical research.

  15. Development of RP-HPLC method for Qualitative Analysis of Active Ingredient (Gallic acid from Stem Bark of Dendrophthoe falcate Linn.

    Hafsa Deshmukh

    2011-04-01

    Full Text Available A simple, precise and sensitive, RP-HPLC method with UV detection at 271nm was developed and validated for qualitative determination of active ingredient Gallic acid from stem bark of Dendrophthoe falcate Linn. Separation was performed on a ThermoMOS 2 HYPERSIL C18 column (250 cm × 4.6 mm, 5µm ODS 3 using mobile phase comprising of 0.1% Orthophosphoric acid : Acetonitrile (400 cm3 : 600 cm3 with a flow rate of 1 ml/minute with a short run time of 13 minute. The method was validated according to the regulatory guidelines with respect to linearity, system suitability, precision, solution stability, accuracy, robustness, assay and recovery. Detector response was linear for HPLC in the range of 0.04 to 0.16 mg/cm3. The system suitability, precision, solution stability, accuracy, robustness, assay and recovery was assessed by calculating % COV for all these parameters which is less than two as expected. The recovery of the method for Gallic acid was found 98.94% which shows that method is accurate. The described method has the advantage of being rapid and easy hence it can be applied for routine quality control analysis of Gallic acid from Dendrophthoe falcate Linn.

  16. Study on cinnamon hypoglycemic active ingredient extraction method%肉桂降糖活性成分提取方法的研究

    卢春连; 陆志科

    2014-01-01

    用乙醇回流提取法、超声波提取法、新装置提取法提取肉桂降糖活性成分。结果表明,新装置提取法比回流提取法、超声波提取法提取效率高,且快速简便。新装置提取法提取肉桂降糖活性成分的最佳条件为:多功能提取器装置,提取溶剂为95%乙醇,提取时间2 h,产品粗提率达21.0%。%Three methods were compared of preparing cinnamon hypoglycemic active ingredients:the etha-nol refluxing extraction,ultrasonic extraction and the new device extraction. The results showed that the new device extraction was superior to ethanol refluxing extraction and ultrasonic extraction,and the meth-od was fast and simple. The best conditions of the method were:multi-extractor device,solvent of 95%ethanol,and the time of extraction was 2 h,the coarse product rate was 21. 0% .

  17. Action of the insect growth regulator fluazuron, the active ingredient of the acaricide Acatak®, in Rhipicephalus sanguineus nymphs (Latreille, 1806) (Acari: Ixodidae).

    Calligaris, Izabela Braggião; De Oliveira, Patricia Rosa; Roma, Gislaine Cristina; Bechara, Gervásio Henrique; Camargo-Mathias, Maria Izabel

    2013-11-01

    The present study evaluated the efficacy of fluazuron (active ingredient of the acaricide Acatak®) and its effects on Rhipicephalus sanguineus nymphs fed on rabbits exposed to different doses of this insect growth regulator. Three different doses of fluazuron (20 mg/kg, 40 mg/kg, and 80 mg/kg) were applied on the back of hosts (via "pour on"), while distilled water was applied to the Control group. On the first day of treatment with fluazuron (24 h), hosts were artificially infested with R. sanguineus nymphs. Once fully engorged, nymphs were removed and placed in identified Petri dishes in Biochemical Oxygen Demand (BOD) incubator for 7 days. After this period, engorged nymphs were processed for ultramorphological analysis. The results revealed alterations in the ultramorphology of many chitinous structures (smaller hypostome and chelicerae, less sclerotized scutum, fewer sensilla, fewer pores, absence of grooves, marginal and cervical strips and festoons in the body, even the anal plaque was damaged) that play essential roles for the survivor of ticks and that can compromise the total or partial development of nymphs and emergence of adults after periodic molting. Our findings confirm the efficacy of fluazuron, a more specific and less aggressive chemical to the environment and human health, and that does not induce resistance, in nymphs of the tick R. sanguineus in artificially infested rabbits treated with this arthropod growth regulator (AGR), indicating that it could be used in the control of this stage of the biological cycle of the tick R. sanguineus. PMID:24000046

  18. Simultaneous determination of active ingredients in ethnomedicine Gaultheria leucocarpa var. yunnanensis and its medicinal preparation by capillary electrophoresis with electrochemical detection.

    Zeng, Yikun; Tang, Zhuxing; Wang, Qingjiang; He, Pingang; Fang, Yuzhi

    2007-10-01

    A simple and rapid capillary electrophoresis (CE) with electrcochemical detection (ED) method has been established for the simultaneous determination of seven active ingredients in the stems and roots of Gaultheria leucocarpa var. yunnanensis and its medicinal preparation, including (+)-catechin, rutin, gentisic acid, vallinic acid, salicylic acid, quercetin, and protocatechuic acid. The effects of working potential, pH, and concentration of running buffer, separation voltage, and injection time on CE-ED are systematically investigated. Under the optimum conditions, the seven analytes could be completely separated within 23 min in a borax running buffer (pH 8.7). A good linear relationship is obtained over three orders of magnitude with detection limits (signal-to-noise ratio=3) ranging from 5x10(-8) g/mL to 3x10(-7) g/mL for the analytes. The proposed method is successfully used in the analysis of real samples after a relatively simple extraction procedure, and the assay results are satisfactory. PMID:17988450

  19. Component morphology, size, and compositional impact on pharmaceutical powder blend flowability

    Goldfarb, David; Nakagawa, Hirotaka; Conway, Stephen

    2014-11-01

    Through analysis of particle morphology, particle size, and compositional influences, we present experimental case studies revealing unexpected transitions in flowability and cohesion of pharmaceutical powder blends. We explore interactions between the needle-like API (Active Pharmaceutical Ingredient) and the more spherical remaining components (excipients) in the blend to explain these transitions, and optimal concentrations are identified. A range of particle sizes, aspect ratios (for API), and compositions were examined. Surprisingly, under certain conditions, a blend with a low API concentration exhibits less cohesive flowability properties than a placebo blend containing no API. Effective volume and coordination number models are tested by investigation of particle geometry, particle contact, and Van der Waals force factors. These results should translate both to the improved understanding of mixed component morphology systems and to a novel approach towards pharmaceutical product formulation optimization.

  20. SIMULTANEOUS ESTIMATION OF SAXAGLIPTIN HYDROCHLORIDE AND METFORMIN HYDROCHLORIDE IN ACTIVE PHARMACEUTICAL INGRIDENT BY RP-HPLC

    NYOLA NARENDRA, GOVINDASAMY JEYABALAN

    2013-09-01

    Full Text Available A new simple, accurate, precise and reproducible RP-HPLC method has been developed for the simultaneousestimation of Saxagliptin and Metformin in bulk drug form using C18 column (Phenomenex, 250 x 4.6 mm, 5 μm inisocratic mode. The mobile phase consisted of 0.02M Potassium dihydrogen phosphate (KH2PO4, Acetonitrile,Methanol in the ratio of 50:25:25 (v/v/v at pH 4.3. The detection wavelength was carried out at 240 nm. Themethod was linear over the concentration range for Saxagliptin 10-50μg/ml and for Metformin 5-25 μg/ml. Therecoveries of Saxagliptin and Metformin were found to be 100.48and 101.1% respectively. The validation of methodwas carried out utilizing ICH-guidelines. The described HPLC method was successfully employed for the analysisof pharmaceutical formulations containing combined dosage form.

  1. Synthesis and pharmaceutical properties of N-acyloxymethyl prodrugs of Allop with potential anti-trypanosomal activity.

    Gualdesi, M S; Ortiz, C S; Raviolo, M A

    2016-04-01

    We report herein the synthesis, and the physicochemical and pharmacokinetic properties of N-acyloxymethyl prodrugs of allopurinol (Allop) (2a-f). Allop is a compound with activity against Trypanosoma cruzi, a causative agent of Chagas disease. Its pathology leads to a huge number of infections and deaths per year, because in addition to many sufferers only having limited access to health services only an inefficient chemotherapy is available. Relevant pharmaceutical properties (pKa, stability, solubility, lipophilicity, in vitro permeability, binding protein, xanthine oxidase binding) were also determined. The results obtained showed that derivatives behave as prodrugs of Allop, since they exhibit improved physicochemical and pharmacokinetic properties relative to their precursor. This behavior turns these compounds into active reservoirs of Allop, and reduces its unfavorable characteristics, so 2a-f compounds are excellent candidates for the treatment of Chagas disease. This work is therefore an important contribution leading to the suppression of Chagas disease. PMID:26181622

  2. Ingredients of Huangqi decoction slow biliary fibrosis progression by inhibiting the activation of the transforming growth factor-beta signaling pathway

    Du Jin-Xing

    2012-04-01

    Full Text Available Abstract Background Huangqi decoction was first described in Prescriptions of the Bureau of Taiping People's Welfare Pharmacy in Song Dynasty (AD 1078, and it is an effective recipe that is usually used to treat consumptive disease, anorexia, and chronic liver diseases. Transforming growth factor beta 1 (TGFβ1 plays a key role in the progression of liver fibrosis, and Huangqi decoction and its ingredients (IHQD markedly ameliorated hepatic fibrotic lesions induced by ligation of the common bile duct (BDL. However, the mechanism of IHQD on hepatic fibrotic lesions is not yet clear. The purpose of the present study is to elucidate the roles of TGFβ1 activation, Smad-signaling pathway, and extracellular signal-regulated kinase (ERK in the pathogenesis of biliary fibrosis progression and the antifibrotic mechanism of IHQD. Methods A liver fibrosis model was induced by ligation of the common bile duct (BDL in rats. Sham-operation was performed in control rats. The BDL rats were randomly divided into two groups: the BDL group and the IHQD group. IHQD was administrated intragastrically for 4 weeks. At the end of the fifth week after BDL, animals were sacrificed for sampling of blood serum and liver tissue. The effect of IHQD on the TGFβ1 signaling pathway was evaluated by western blotting and laser confocal microscopy. Results Decreased content of hepatic hydroxyproline and improved liver function and histopathology were observed in IHQD rats. Hepatocytes, cholangiocytes, and myofibroblasts in the cholestatic liver injury released TGFβ1, and activated TGFβ1 receptors can accelerate liver fibrosis. IHQD markedly inhibited the protein expression of TGFβ1, TGFβ1 receptors, Smad3, and p-ERK1/2 expression with no change of Smad7 expression. Conclusion IHQD exert significant therapeutic effects on BDL-induced fibrosis in rats through inhibition of the activation of TGFβ1-Smad3 and TGFβ1-ERK1/2 signaling pathways.

  3. Sorption and toxicity reduction of pharmaceutically active compounds and endocrine disrupting chemicals in the presence of colloidal humic acid.

    Kim, Injeong; Kim, Hyo-Dong; Jeong, Tae-Yong; Kim, Sang Don

    2016-01-01

    This study investigated the toxicity changes and sorption of pharmaceuticals and endocrine disrupters in the presence of humic acid (HA). For the sorption experiment, a dead end filtration (DEF) system was used to separate bound and free-form target compounds. An algae growth inhibition test and E-screen assay were conducted to estimate the toxic effect of pharmaceutically active compounds (PhACs) and endocrine disrupting chemicals (EDCs), respectively. The permeate concentration was confirmed using liquid chromatography-mass spectrometry. In the sorption test, we observed significant sorption of PhACs and EDCs on colloidal HA, except for sulfamethoxazole (SMX). The values of log KCOC derived from DEF determinations ranged from 4.40 to 5.03. The removal efficiency varied with the HA concentration and the target chemical properties. Tetracycline and 4-octylphenol showed the highest sorption or removal efficiency (≈50%), even at 5 mg C/L HA. The algal growth inhibition of PhACs and the estrogenic effects of EDCs were significantly decreased in proportion to HA concentrations, except for SMX. In addition, the chemical analysis results showed a positive relationship with the bioassay results. Consequently, the sorption of PhACs and EDCs onto colloidal HA should be emphasized in natural environments because it significantly reduces bioavailable concentrations and toxicity to aquatic organisms. PMID:27533865

  4. Automated evaluation of pharmaceutically active ionic liquids’ (eco)toxicity through the inhibition of human carboxylesterase and Vibrio fischeri

    Costa, Susana P.F.; Justina, Vanessa D. [REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira, n° 228, 4050-313 Porto (Portugal); Bica, Katharina; Vasiloiu, Maria [Vienna University of Technology, Institute of Applied and Synthetic Chemistry, A-1060 Vienna (Austria); Pinto, Paula C.A.G., E-mail: ppinto@ff.up.pt [REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira, n° 228, 4050-313 Porto (Portugal); Saraiva, M. Lúcia M.F.S., E-mail: lsaraiva@ff.up.pt [REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira, n° 228, 4050-313 Porto (Portugal)

    2014-01-30

    Highlights: • IL-APIs toxicity on humans and aquatic environment was evaluated by inhibition assays. • The inhibition assays were implemented through automated screening bioassays. • Automation of bioassays enabled a rigorous control of the reaction conditions. • EC{sub 50} obtained provide vital information on IL-APIs safety and potential use as drugs. -- Abstract: The toxicity of 16 pharmaceutical active ionic liquids (IL-APIs) was evaluated by automated approaches based on sequential injection analysis (SIA). The implemented bioassays were centered on the inhibition of human carboxylesterase 2 and Vibrio fischeri, in the presence of the tested compounds. The inhibitory effects were quantified by calculating the inhibitor concentration required to cause 50% of inhibition (EC{sub 50}). The EC{sub 50} values demonstrated that the cetylpyridinium group was one of the most toxic cations and that the imidazolium group was the less toxic. The obtained results provide important information about the safety of the studied IL-APIs and their possible use as pharmaceutical drugs. The developed automated SIA methodologies are robust screening bioassays, and can be used as a generic tools to identify the (eco)toxicity of the structural elements of ILs, contributing to a sustainable development of drugs.

  5. Automated evaluation of pharmaceutically active ionic liquids’ (eco)toxicity through the inhibition of human carboxylesterase and Vibrio fischeri

    Highlights: • IL-APIs toxicity on humans and aquatic environment was evaluated by inhibition assays. • The inhibition assays were implemented through automated screening bioassays. • Automation of bioassays enabled a rigorous control of the reaction conditions. • EC50 obtained provide vital information on IL-APIs safety and potential use as drugs. -- Abstract: The toxicity of 16 pharmaceutical active ionic liquids (IL-APIs) was evaluated by automated approaches based on sequential injection analysis (SIA). The implemented bioassays were centered on the inhibition of human carboxylesterase 2 and Vibrio fischeri, in the presence of the tested compounds. The inhibitory effects were quantified by calculating the inhibitor concentration required to cause 50% of inhibition (EC50). The EC50 values demonstrated that the cetylpyridinium group was one of the most toxic cations and that the imidazolium group was the less toxic. The obtained results provide important information about the safety of the studied IL-APIs and their possible use as pharmaceutical drugs. The developed automated SIA methodologies are robust screening bioassays, and can be used as a generic tools to identify the (eco)toxicity of the structural elements of ILs, contributing to a sustainable development of drugs

  6. Removal of Trace Pharmaceuticals from Water using coagulation and powdered activated carbon as pretreatment to ultrafiltration membrane system.

    Sheng, Chenguang; Nnanna, A G Agwu; Liu, Yanghe; Vargo, John D

    2016-04-15

    In this study, the efficacy of water treatment technologies: ultra-filtration (UF), powdered activated carbon (PAC), coagulation (COA) and a combination of these technologies (PAC/UF and COA/UF) to remove target pharmaceuticals (Acetaminophen, Bezafibrate, Caffeine, Carbamazepine, Cotinine, Diclofenac, Gemfibrozil, Ibuprofen, Metoprolol, Naproxen, Sulfadimethoxine, Sulfamethazine, Sulfamethoxazole, Sulfathiazole, Triclosan and Trimethoprim) was investigated. Samples of wastewater from municipal WWTPs were analyzed using direct aqueous injection High Performance Liquid Chromatography with Tandem Quadrupole Mass Spectrometric (LC/MS/MS) detection. On concentration basis, results showed an average removal efficiency of 29%, 50%, and 7%, respectively, for the UF, PAC dosage of 50ppm, and COA dosage of 10ppm. When PAC dosage of 100ppm was used as pretreatment to the combined PAC and UF in-line membrane system, a 90.3% removal efficiency was achieved. The removal efficiency of UF in tandem with COA was 33%, an increase of 4% compared with the single UF treatment. The adsorption effect of PAC combined with the physical separation process of UF revealed the best treatment strategy for removing pharmaceutical contaminant from water. PMID:26867086

  7. Electrochemical biosensors in pharmaceutical analysis

    Eric de Souza Gil; Giselle Rodrigues de Melo

    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...

  8. Dropwise additive manufacturing of pharmaceutical products for melt-based dosage forms.

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

    2015-05-01

    The US Food and Drug Administration introduced the quality by design approach and process analytical technology guidance to encourage innovation and efficiency in pharmaceutical development, manufacturing, and quality assurance. As part of this renewed emphasis on the improvement of manufacturing, the pharmaceutical industry has begun to develop more efficient production processes with more intensive use of online measurement and sensing, real-time quality control, and process control tools. Here, we present dropwise additive manufacturing of pharmaceutical products (DAMPP) as an alternative to conventional pharmaceutical manufacturing methods. This mini-manufacturing process for the production of pharmaceuticals utilizes drop on demand printing technology for automated and controlled deposition of melt-based formulations onto edible substrates. The advantages of drop-on-demand technology, including reproducible production of small droplets, adjustable drop sizing, high placement accuracy, and flexible use of different formulations, enable production of individualized dosing even for low-dose and high-potency drugs. In this work, DAMPP is used to produce solid oral dosage forms from hot melts of an active pharmaceutical ingredient and a polymer. The dosage forms are analyzed to show the reproducibility of dosing and the dissolution behavior of different formulations. PMID:25639605

  9. Altered Gene Expression in the Schistosome-Transmitting Snail Biomphalaria glabrata following Exposure to Niclosamide, the Active Ingredient in the Widely Used Molluscicide Bayluscide.

    Zhang, Si-Ming; Buddenborg, Sarah K; Adema, Coen M; Sullivan, John T; Loker, Eric S

    2015-01-01

    In view of the call by the World Health Organization (WHO) for elimination of schistosomiasis as a public health problem by 2025, use of molluscicides in snail control to supplement chemotherapy-based control efforts is likely to increase in the coming years. The mechanisms of action of niclosamide, the active ingredient in the most widely used molluscicides, remain largely unknown. A better understanding of its toxicology at the molecular level will both improve our knowledge of snail biology and may offer valuable insights into the development of better chemical control methods for snails. We used a recently developed Biomphalaria glabrata oligonucleotide microarray (31K features) to investigate the effect of sublethal exposure to niclosamide on the transcriptional responses of the snail B. glabrata relative to untreated snails. Most of the genes highly upregulated following exposure of snails to niclosamide are involved in biotransformation of xenobiotics, including genes encoding cytochrome P450s (CYP), glutathione S-transferases (GST), and drug transporters, notably multi-drug resistance protein (efflux transporter) and solute linked carrier (influx transporter). Niclosamide also induced stress responses. Specifically, six heat shock protein (HSP) genes from three super-families (HSP20, HSP40 and HSP70) were upregulated. Genes encoding ADP-ribosylation factor (ARF), cAMP response element-binding protein (CREB) and coatomer, all of which are involved in vesicle trafficking in the Golgi of mammalian cells, were also upregulated. Lastly, a hemoglobin gene was downregulated, suggesting niclosamide may affect oxygen transport. Our results show that snails mount substantial responses to sublethal concentrations of niclosamide, at least some of which appear to be protective. The topic of how niclosamide's lethality at higher concentrations is determined requires further study. Given that niclosamide has also been used as an anthelmintic drug for decades and has been

  10. Transcriptome analysis of buds and leaves using 454 pyrosequencing to discover genes associated with the biosynthesis of active ingredients in Lonicera japonica Thunb.

    Liu He

    Full Text Available BACKGROUND: Lonicera japonica Thunb. is a plant used in traditional Chinese medicine known for its anti-inflammatory, anti-oxidative, anti-carcinogenic, and antiviral pharmacological properties. The major active secondary metabolites of this plant are chlorogenic acid (CGA and luteoloside. While the biosynthetic pathways of these metabolites are relatively well known, the genetic information available for this species, especially the biosynthetic pathways of its active ingredients, is limited. METHODOLOGY/PRINCIPAL FINDINGS: We obtained one million reads (average length of 400 bp in a whole sequence run using a Roche/454 GS FLX titanium platform. Altogether, 85.69% of the unigenes covering the entire life cycle of the plant were annotated and 325 unigenes were assigned to secondary metabolic pathways. Moreover, 2039 unigenes were predicted as transcription factors. Nearly all of the possible enzymes involved in the biosynthesis of CGA and luteoloside were discovered in L. japonica. Three hydroxycinnamoyl transferase genes, including two hydroxycinnamoyl-CoA quinate hydroxycinnamoyl transferase genes and one hydroxycinnamoyl-CoA shikimate/quinate hydroxycinnamoyl transferase (HCT gene featuring high similarity to known genes from other species, were cloned. The HCT gene was discovered for the first time in L. japonica. In addition, 188 candidate cytochrome P450 unigenes and 245 glycosyltransferase unigenes were found in the expressed sequence tag (EST dataset. CONCLUSION: This study provides a high quality EST database for L. japonica by 454 pyrosequencing. Based on the EST annotation, a set of putative genes involved in CGA and luteoloside biosynthetic pathways were discovered. The database serves as an important source of public information on genetic markers, gene expression, genomics, and functional genomics in L. japonica.

  11. Altered Gene Expression in the Schistosome-Transmitting Snail Biomphalaria glabrata following Exposure to Niclosamide, the Active Ingredient in the Widely Used Molluscicide Bayluscide.

    Si-Ming Zhang

    Full Text Available In view of the call by the World Health Organization (WHO for elimination of schistosomiasis as a public health problem by 2025, use of molluscicides in snail control to supplement chemotherapy-based control efforts is likely to increase in the coming years. The mechanisms of action of niclosamide, the active ingredient in the most widely used molluscicides, remain largely unknown. A better understanding of its toxicology at the molecular level will both improve our knowledge of snail biology and may offer valuable insights into the development of better chemical control methods for snails. We used a recently developed Biomphalaria glabrata oligonucleotide microarray (31K features to investigate the effect of sublethal exposure to niclosamide on the transcriptional responses of the snail B. glabrata relative to untreated snails. Most of the genes highly upregulated following exposure of snails to niclosamide are involved in biotransformation of xenobiotics, including genes encoding cytochrome P450s (CYP, glutathione S-transferases (GST, and drug transporters, notably multi-drug resistance protein (efflux transporter and solute linked carrier (influx transporter. Niclosamide also induced stress responses. Specifically, six heat shock protein (HSP genes from three super-families (HSP20, HSP40 and HSP70 were upregulated. Genes encoding ADP-ribosylation factor (ARF, cAMP response element-binding protein (CREB and coatomer, all of which are involved in vesicle trafficking in the Golgi of mammalian cells, were also upregulated. Lastly, a hemoglobin gene was downregulated, suggesting niclosamide may affect oxygen transport. Our results show that snails mount substantial responses to sublethal concentrations of niclosamide, at least some of which appear to be protective. The topic of how niclosamide's lethality at higher concentrations is determined requires further study. Given that niclosamide has also been used as an anthelmintic drug for decades and

  12. Analysis on the active ingredients of lavender honey from Xinjiang province%新疆薰衣草蜜活性成分的分析

    潘柳; 张琦; 毛秀丽; 黄俊逸

    2012-01-01

    The reduced sugar, amylase value, total protein, total phenolic acid and anti-oxidative activities (DPPH radical scavenging activity test) of lavender honey, black locust honey and linden honey were determined and compared. The results showed that the content of amylase value, total phenolic acid and total protein in lavender honey are 14.8 mL/g.h, (200.8+6.9) IJg/g and (25.35+2.74) mg/100 g, respectively, all of which are higher than that of the other two kinds of honey, but the content of reduced sugar is lower, which is 74%. Three kinds of bee honeys have anti-oxidative activity. The scavenging capacities of lavender honey and linden honey don't exhibit an obvious difference, which are stronger than that of black locust honey. In addition, total phenolic acid content have no obvious correlation with anti-oxidative activities. It suggests that there are other active ingredients contributing to the anti-oxidative activities in honey.%以薰衣草蜜、洋槐蜜和椴树蜜3种蜂蜜为材料,对蜂蜜中的还原糖含量、淀粉酶值、蛋白质含量、总酚酸含量和它们清除DPPH自由基的能力进行分析。结果表明:薰衣草蜜中的淀粉酶值、总酚酸含量、蛋白质的含量分别为14.8mL/g·h、(200.8±6.9)μg/g和(25.35±2.74)mg/100g,均高于其他2种蜜,但还原糖含量比其他2种蜂蜜略低,为74%。3种蜂蜜均具有抗氧化的作用,薰衣草蜜与椴树蜜对DPPH自由基的清除能力相当,均高于洋槐蜜。总酚酸含量与抗氧化能力之间无明显相关性,说明蜂蜜中还含有其他的抗氧化活性成分。

  13. Nanoscale Concentration Quantification of Pharmaceutical Actives in Amorphous Polymer Matrices by Electron Energy-Loss Spectroscopy.

    Ricarte, Ralm G; Lodge, Timothy P; Hillmyer, Marc A

    2016-07-26

    We demonstrated the use of electron energy-loss spectroscopy (EELS) to evaluate the composition of phenytoin:hydroxypropyl methylcellulose acetate succinate (HPMCAS) spin-coated solid dispersions (SDs). To overcome the inability of bright-field and high-angle annular dark-field TEM imaging to distinguish between glassy drug and polymer, we used the π-π* transition peak in the EELS spectrum to detect phenytoin within the HPMCAS matrix of the SD. The concentration of phenytoin within SDs of 10, 25, and 50 wt % drug loading was quantified by a multiple least-squares analysis. Evaluating the concentration of 50 different regions in each SD, we determined that phenytoin and HPMCAS are intimately mixed at a length scale of 200 nm, even for drug loadings up to 50 wt %. At length scales below 100 nm, the variance of the measured phenytoin concentration increases; we speculate that this increase is due to statistical fluctuations in local concentration and chemical changes induced by electron irradiation. We also performed EELS analysis of an annealed 25 wt % phenytoin SD and showed that the technique can resolve concentration differences between regions that are less than 50 nm apart. Our findings indicate that EELS is a useful tool for quantifying, with high accuracy and sub-100 nm spatial resolution, the composition of many pharmaceutical and soft matter systems. PMID:27419264

  14. Multipoint-NIR-measurements in pharmaceutical powder applications

    In this paper, multipoint near-infrared (NIR) spectroscopy is used in studying particulate pharmaceutical ingredients and their mixing and granulation processes. Homogeneous mixing of active pharmaceutical ingredients with excipients is essential in getting the correct dosage in the tableting phase. The basic principles of NIR spectroscopy and the associated molecular vibrations are briefly reviewed in the beginning of the work, followed by a summary of typical applications of NIR spectroscopy. A multipoint NIR measurement system developed at VTT is presented in this work. It consists of a spectral camera with fiber-optic inputs, a fiber-optic light source and twelve fiber-optic probes. The performance of the system in the laboratory is thoroughly reported, including signal-to-noise ratio, stability and probe-to-probe variability. The system was also tested in a fluidized bed granulator at Helsinki University. Eight probes were attached in two rows into the granulator, and several granulations were run. The mixing period in the beginning of the granulation process was clearly visible, as well as the changes in the moisture level during liquid spraying and final drying. The study shows that multipoint NIR spectroscopy is a valuable tool in monitoring the granulation process. In particular, it gives information about the macroscopic homogeneity of the fluidized bed. (orig.)

  15. Fucoxanthin: A Promising Medicinal and Nutritional Ingredient

    Hui Zhang; Yibo Tang; Ying Zhang; Shuofeng Zhang; Jing Qu; Xu Wang; Ran Kong; Chunchao Han; Zhenquan Liu

    2015-01-01

    Fucoxanthin, an allenic carotenoid, can be isolated from edible brown seaweeds. Recent studies have reported that fucoxanthin has many physiological functions and biological properties, such as antiobesity, antitumor, antidiabetes, antioxidant, anti-inflammatory, and hepatoprotective activities, as well as cardiovascular and cerebrovascular protective effects. Therefore, fucoxanthin can be used as both medicinal and nutritional ingredient to prevent and treat chronic diseases. Although fucoxa...

  16. Validation of quantitative {sup 1}H NMR method for the analysis of pharmaceutical formulations; Validacao de metodo quantitativo por RMN de {sup 1}H para analises de formulacoes farmaceuticas

    Santos, Maiara da S. [Universidade de Sao Paulo (USP), Sao Carlos, SP (Brazil). Instituto de Quimica; Colnago, Luiz Alberto, E-mail: luiz.colnago@embrapa.br [Embrapa Instrumentacao, Sao Carlos, SP (Brazil)

    2013-09-01

    The need for effective and reliable quality control in products from pharmaceutical industries renders the analyses of their active ingredients and constituents of great importance. This study presents the theoretical basis of Superscript-One H NMR for quantitative analyses and an example of the method validation according to Resolution RE N. 899 by the Brazilian National Health Surveillance Agency (ANVISA), in which the compound paracetamol was the active ingredient. All evaluated parameters (selectivity, linearity, accuracy, repeatability and robustness) showed satisfactory results. It was concluded that a single NMR measurement provides structural and quantitative information of active components and excipients in the sample. (author)

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

    Maeng, Sungkyu

    2011-05-01

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

  18. Detoxification of alpha- and beta-Thujones (the active ingredients of absinthe): site specificity and species differences in cytochrome P450 oxidation in vitro and in vivo.

    Höld, K M; Sirisoma, N S; Casida, J E

    2001-05-01

    Alpha- and beta-Thujones are active ingredients in the liqueur absinthe and in herbal medicines and seasonings for food and drinks. Our earlier study established that they are convulsants and have insecticidal activity, acting as noncompetitive blockers of the gamma-aminobutyric acid (GABA)-gated chloride channel, and identified 7-hydroxy-alpha-thujone as the major metabolite and 4-hydroxy-alpha- and -beta-thujones and 7,8-dehydro-alpha-thujone as minor metabolites in the mouse liver microsome-NADPH system. We report here unexpected site specificity and species differences in the metabolism of the thujone diastereomers in mouse, rat, and human liver microsomes and human recombinant P450 (P450 3A4), in orally treated mice and rats, and in Drosophila melanogaster. Major differences are apparent on comparing in vitro microsome-NADPH systems and in vivo urinary metabolites. Hydroxylation at the 2-position is observed only in mice where conjugated 2R-hydroxy-alpha-thujone is the major urinary metabolite of alpha-thujone. Hydroxylation at the 4-position gives one or both of 4-hydroxy-alpha- and -beta-thujones depending on the diastereomer and species studied with conjugated 4-hydroxy-alpha-thujone as the major urinary metabolite of alpha- and beta-thujones in rats. Hydroxylation at the 7-position of alpha- and beta-thujones is always a major pathway, but the conjugated urinary metabolite is minor except with beta-thujone in the mouse. Site specificity in glucuronidation favors excretion of 2R-hydroxy- and 4-hydroxy-alpha-thujone glucuronides rather than those of three other hydroxythujones. Two dehydro metabolites are observed from both alpha- and beta-thujones, the 7,8 in the P450 systems and the 4,10 in urine. Two types of evidence establish that P450-dependent oxidations of alpha- and beta-thujones are detoxification reactions: three P450 inhibitors block the metabolism of alpha- and beta-thujones and strongly synergize their toxicity in Drosophila; six metabolites

  19. 超分子化学在药物共晶中的应用%Application of Supramolecular Chemistry on Pharmaceutical Cocrystals

    陈嘉媚; 吴传斌; 鲁统部

    2011-01-01

    药物共晶是一种新兴的药物晶型,一个给定的活性药物分子通过形成共晶,一方面可以大大丰富其结晶形式,另一方面可以改善其物化性质及临床疗效.本文从超分子化学的角度对药物共晶进行了综述,列举了一系列通过氢键超分子合成子进行药物共晶设计和制备的研究实例,旨在促进超分子化学和药学的交叉融合.%Pharmaceutical cocrystal is a new type of pharmaceutical crystalline state. It is attractive to pharmaceutical scientists because it can provide a number of crystalline states for a given active pharmaceutical ingredient ( API) , in which the physical and chemical properties of the API can be adjusted by pharmaceutical cocrystal. In this review, we address pharmaceutical cocrystals from the perspective of supramolecular chemistry , and present a series of structures of pharmaceutical cocrystals constructed through hydrogen bonding supramolecular synthons, in which the physical and chemical properties(solubility, dissolution, bioavailability, melting point, stability, etc. ) of APIs can be changed by pharmaceutical cocrystal.

  20. Reversible anti-settlement activity against Amphibalanus (= Balanus ) amphitrite, Bugula neritina , and Hydroides elegans by a nontoxic pharmaceutical compound, mizolastine

    Zhou, Xiaojian

    2009-11-01

    Mizolastine, an antihistamine pharmaceutical, was found to significantly inhibit larval settlement of the barnacle Amphibalanus (=Balanus) amphitrite, the bryozoan Bugula neritina, and the polychaete Hydroides elegans with EC50 values of 4.2, 11.2, and 4.1 mg ml-1, respectively. No toxicity against the larvae of these three species was observed at the concentration range tested during incubations with mizolastine. To determine whether the anti-settlement activity of mizolastine is reversible, recovery bioassays using these three species were conducted. More than 70% of the larvae that had been exposed for 4 h to mizolastine at concentrations four-fold greater than their respective EC50 values completed normal metamorphosis. The results of the recovery bioassay provide evidence that the antisettlement effect of mizolastine is reversible in addition to being nontoxic. The anti-settlement activities of several intermediates of the synthesis process of mizolastine were also examined. One of the intermediates, 2-chloro-1-(4- fluorobenzyl)-1H-benzo[d]imidazole, inhibited larval settlement and metamorphosis with low toxicity. These results may improve the understanding of the key functional group responsible for the anti-settlement activity of mizolastine. © 2009 Taylor & Francis.

  1. Development and application of reversed phase liquid chromatography based techniques for automated purification of biologically active ingredients from plant extracts and for characterization of plant extracts and environmental pollutants

    Mahsunah, Anis H.

    2006-01-01

    Automated preparative HPLC purification systems are an important and useful technology in pharmaceutical and chemical development. The systems have been applied to high-throughput purification of products from combinatorial compound synthesis for drug discovery, single compound isolation for further structure elucidation and activity screening, as well as fractionation of active compounds from plant extracts. Fraction collection in automated HPLC purification system can be triggered by le...

  2. Product Quality Review in Pharmaceutical Manufacturers%药品生产企业产品质量回顾分析的研究

    丁越; 梁毅

    2011-01-01

    介绍了产品质量回顾分析,将其与欧盟GMP、ICHQ7A中的内容进行了对比,并介绍了质量回顾分析的编写方法。%This article introduced product quality review in pharmaceutical manufacturers,compared the content in GMP with it in Good Manufacturing Practice for Active Pharmaceutical Ingredients and in EU GMP.The method of writing product quality review was also included.

  3. Comparative study of the effect of pharmaceutical additives on the elimination of antibiotic activity during the treatment of oxacillin in water by the photo-Fenton, TiO2-photocatalysis and electrochemical processes.

    Serna-Galvis, Efraim A; Silva-Agredo, Javier; Giraldo, Ana L; Flórez-Acosta, Oscar A; Torres-Palma, Ricardo A

    2016-01-15

    Synthetic pharmaceutical effluents loaded with the β-lactam antibiotic oxacillin were treated using advanced oxidation processes (the photo-Fenton system and TiO2 photocatalysis) and chloride mediated electrochemical oxidation (with Ti/IrO2 anodes). Combinations of the antibiotic with excipients (mannitol or tartaric acid), an active ingredient (calcium carbonate, i.e. bicarbonate ions due to the pH) and a cleaning agent (sodium lauryl ether sulfate) were considered. Additionally, urban wastewater that had undergone biological treatment was doped with oxacillin and treated with the tested systems. The evolution of antimicrobial activity was monitored as a parameter of processes efficiency. Although the two advanced oxidation processes (AOPs) differ only in the way they produce OH, marked differences were observed between them. There were also differences between the AOPs and the electrochemical system. Interestingly, each additive had a different effect on each treatment. For water loaded with mannitol, electrochemical treatment was the most suitable option because the additive did not significantly affect the efficiency of the system. Due to the formation of a complex with Fe(3+), tartaric acid accelerated the elimination of antibiotic activity during the photo-Fenton process. For TiO2 photocatalysis, the presence of bicarbonate ions contributed to antibiotic activity elimination through the possible formation of carbonate and bicarbonate radicals. Sodium lauryl ether sulfate negatively affected all of the processes. However, due to the higher selectivity of HOCl compared with OH, electrochemical oxidation showed the least inhibited efficiency. For the urban wastewater doped with oxacillin, TiO2 photocatalysis was the most efficient process. These results will help select the most suitable technology for the treatment of water polluted with β-lactam antibiotics. PMID:26479916

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

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

    2010-01-01

    , 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...... technology or series of technologies for a future full-scale remediation system. The bench tests investigated oxidant stability, oxidation efficiency, toxicity reduction, metal mobilization and, for the persulfate, different activating agents, including NaOH, chelated iron, and modified Fenton's reagent. 126...

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

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

    -going bench tests evaluating treatment of site groundwater and soil using modified Fenton's reagent and activated persulfate. These tests are investigating oxidant stability, oxidation efficiency, metals mobilization and, for the persulfate, different activating agents, including NaOH, chelated iron, and...... modified Fenton's reagent. The stability of the oxidants will be determined under simulated aquifer conditions, with and without catalyst or activating agents. Once an optimal activation technique has been determined, oxidation efficiency towards the complex mix of contaminants will be measured in terms of...... contaminant loss. The treatment efficiency will also be evaluated on the basis of pre- and post-treatment toxicity tests. Due to the presence of significant quantities of mercury and cyanide in the target treatment zone (up to 1500 kg and 2500 kg, respectively), a key of objective of these tests is to...

  6. Development of LC-MS/MS Methods for the Analysis of Chiral and Achiral Pharmaceuticals and Metabolites in Aqueous Environmental Matrices

    Barclay, Victoria K.H.

    2012-01-01

    This thesis describes the development of liquid chromatography tandem mass spectrometry (LC-MS/MS) methods for the trace analysis of active pharmaceutical ingredients (APIs) and their metabolites in aqueous environmental matrices. The research was focused on the development of chiral LC-MS/MS methods for the analysis of fluoxetine and metoprolol, as well as their chiral metabolites in environmental water samples. A method was also developed for the achiral compounds, diazepam and nordiazepam....

  7. Thiomers: A Blessing to Evaluating Era of Pharmaceuticals

    Muhammad Hanif

    2015-01-01

    Full Text Available Thiomers are the polymers modified for the mucoadhesive properties and other additive properties by incorporating thiol moieties in the backbone of the unmodified polymeric chain by substitution reactions or simple oxidation reactions. Drugs that are less soluble and permeable can be complexed with thiomers for their increased absorption through the mucosal membranes by increase in contact time and prolonged stay in body due to mucoadhesion. Immobilization of thiol group therefore increases the mucoadhesive properties of the modified polymer by 2–140-folds. The prepared thiomers are characterized and made stable by different techniques. Thiomers also give the controlled delivery of the active pharmaceutical ingredients in the body. Different polymers that are modified by thiolation are chitosan, polyacrylic acid, sodium alginate, sodium carboxy methyl cellulose, guar gum, and so forth. Thiomeric formulations are a challenge to deliver drugs with low therapeutic compatibility. Micro- and nanopreparations containing thiomers can be prepared by different techniques such as covalent crosslinking, in situ gelation, radical emulsion polymerization, and emulsification. Nowadays thiomers have wide range of applications as a promising pharmaceutical excipient in the evaluating era of pharmaceutical technology.

  8. Recent patents and patented technology platforms for pharmaceutical taste masking.

    Kaushik, Deepak; Dureja, Harish

    2014-04-01

    Taste masking is an important factor in the development of oral dosage forms containing bitter active pharmaceutical ingredients. Currently numerous techniques are being applied to overcome this problem. Realizing this, several researchers and pharmaceutical companies are now engaged in developing novel techniques to address the problem of taste masking evident by numerous patents filed in this area in recent times. In this review the most recent patents for taste masking are discussed and how these patents overcome the limitations of conventional approaches of taste masking is also highlighted. Novel techniques based on some recent patents such as nanohybrid, melt extrusion, non-complex cyclodextrin compositions and off taste masking are providing new realms to taste masking of bitter drugs. The present article also provides an overview of various patented platform technologies based on different techniques/mechanisms employed for taste masking. The unique features and principles of taste-masking approaches used in various patented technologies are also discussed. A better understanding of these new patents and patented technologies will help researchers and pharmaceutical industries to select the appropriate platform, or to develop innovative products with improved taste masking properties. PMID:24499438

  9. Manufacturing capability as a technological development indicator in the pharmaceutical industry

    John Jairo Gallo Castro

    2010-05-01

    Full Text Available The pharmaceutical industrial has five subsectors: medicines, cosmetics, phytotherapeutics, cleaning products and medical devices. The medicine subsector consists of organisations producing, importing and selling these products. Most studies about this industry have been guided by economic interests without assessing technological aspects of production. This article was aimed at proposing a methodology for assessing and describing the medicine sector according to its technological development by using the manufacturing capability concept. The main information was taken from the Colombian Medicaments and Food Surveillance Institute’s (Instituto Nacional de Vigilancia de Medicamentos y Alimentos - INVIMA databases related to pharmaceutical plant production in Bogotá, including material transformation facilities. This study led to three characteristics being identified for defining the pharmaceutical industry’s manufacturing capability: that related to the pharmacological group to which active pharmaceutical ingredients belong, that linked to specifications regarding medicines’ sterility and that related to the technology required for manufacturing each pharmaceutical product. An analysis of these features has thus been presented and some technologies have been identified which have not been transferred or assimilated by the organisations being studied. It was found that manufacturing capability should be considered as being an indicator of the degree of technological development in these subsectors in Colombia.

  10. Influence of excipients in comilling on mitigating milling-induced amorphization or structural disorder of crystalline pharmaceutical actives.

    Balani, Prashant N; Ng, Wai Kiong; Tan, Reginald B H; Chan, Sui Yung

    2010-05-01

    The feasibility of using excipients to suppress the amorphization or structural disorder of crystalline salbutamol sulphate (SS) during milling was investigated. SS was subjected to ball-milling in the presence of alpha-lactose monohydrate (LAC), adipic acid (AA), magnesium stearate (MgSt), or polyvinyl pyrrolidone (PVP). X-ray powder diffraction, dynamic vapor sorption (DVS), high sensitivity differential scanning calorimetry (HSDSC) were used to analyze the crystallinity of the milled mixtures. Comilling with crystalline excipients, LAC, AA, and MgSt proved effective in reducing the amorphization of SS. LAC, AA, or MgSt acting as seed crystals to induce recrystallization of amorphous SS formed by milling. During comilling, both SS and LAC turned predominantly amorphous after 45 min but transformed back to a highly crystalline state after 60 min. Amorphous content was below the detection limits of DVS (0.5%) and HSDSC (5%). Comilled and physical mixtures of SS and ALM were stored under normal and elevated humidity conditions. This was found to prevent subsequent changes in crystallinity and morphology of comilled SS:LAC as compared to significant changes in milled SS and physical mixture. These results demonstrate a promising application of comilling with crystalline excipients in mitigating milling induced amorphization of pharmaceutical actives. PMID:19902526

  11. Improving the performance of an aerobic membrane bioreactor (MBR) treating pharmaceutical wastewater with powdered activated carbon (PAC) addition.

    Kaya, Yasemin; Bacaksiz, A Murat; Golebatmaz, Ugur; Vergili, Ilda; Gönder, Z Beril; Yilmaz, Gulsum

    2016-04-01

    In this study, the effects of organic loading rate (OLR) and the addition of powdered activated carbon (PAC) on the performance and membrane fouling of MBR were conducted to treat real pharmaceutical process wastewater. Over 145 days of operation, the MBR system was operated at OLRs ranging from 1 to 2 kg COD m(-3) day(-1) without sludge wasting. The addition of PAC provided an improvement in the flux, despite an increase in the OLR:PAC ratio. The results demonstrated that the hybrid PAC-MBR system maintained a reduced amount of membrane fouling and steadily increased the removal performance of etodolac. PAC addition reduced the deposition of extracellular polymeric substance and organic matter on the membrane surface and resulted an increase in COD removal even at higher OLRs with low PAC addition. Membrane fouling mechanisms were investigated using combined adsorption fouling models. Modified fouling index values and normalized mass transfer coefficient values indicated that predominant fouling mechanism was cake adsorption. PMID:26846538

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

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

    2005-07-15

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

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

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

  14. Multi-residue enantiomeric analysis of pharmaceuticals and their active metabolites in the Guadalquivir River basin (South Spain) by chiral liquid chromatography coupled with tandem mass spectrometry.

    López-Serna, Rebeca; Kasprzyk-Hordern, Barbara; Petrović, Mira; Barceló, Damià

    2013-07-01

    This paper describes the development and application of a multi-residue chiral liquid chromatography coupled with tandem mass spectrometry method for simultaneous enantiomeric profiling of 18 chiral pharmaceuticals and their active metabolites (belonging to several therapeutic classes including analgesics, psychiatric drugs, antibiotics, cardiovascular drugs and β-agonists) in surface water and wastewater. To the authors' knowledge, this is the first time an enantiomeric method including such a high number of pharmaceuticals and their metabolites has been reported. Some of the pharmaceuticals have never been studied before in environmental matrices. Among them are timolol, betaxolol, carazolol and clenbuterol. A monitoring programme of the Guadalquivir River basin (South Spain), including 24 sampling sites and five wastewater treatment plants along the basin, revealed that enantiomeric composition of studied pharmaceuticals is dependent on compound and sampling site. Several compounds such as ibuprofen, atenolol, sotalol and metoprolol were frequently found as racemic mixtures. On the other hand, fluoxetine, propranolol and albuterol were found to be enriched with one enantiomer. Such an outcome might be of significant environmental relevance as two enantiomers of the same chiral compound might reveal different ecotoxicity. For example, propranolol was enriched with S(-)-enantiomer, which is known to be more toxic to Pimephales promelas than R(+)-propranolol. Fluoxetine was found to be enriched with S(+)-enantiomer, which is more toxic to P. promelas than R(-)-fluoxetine. PMID:23579471

  15. 226Ra and 228Ra activity levels in potable drinking water supplied to pharmaceutical companies in India

    The low level 226Ra and 228Ra activities were measured in Potable water samples received by pharmaceutical companies located in Maharashtra, Goa, Gujarat, Madhya Pradesh and Himachal Pradesh through private Borewell Supply and Municipal water Supply units. Radium in drinking water and food enhances the ingestion dose due to its long radiological and biological half-life. The Radium activity level in the fresh water was supposed to be within the limits prescribed by USEPA Guideline for Drinking Water Quality, 40 CFR 141,a Code of Federal Regulation. Higher concentration of Radium can be easily measured by Gamma spectrometry. The paper gives the low levels of radium isotopes present in the water samples which are not detectable successfully by simple gamma spectrometry. A separation chemistry considering Radium isotopes decay scheme and chemical similarity to Calcium was adapted to measure the activity with sequential chemical separation method followed by determining the alpha and beta activity of individual radium isotopes. In bore well water 226Ra activity level was in the range of 0.21 to 60±3.7 mBq/l and 228Ra level was in the range of 5.48 to 111.9±12.2 mBq/l while in Municipal water supply 226Ra and 228Ra was observed to be in the range of 0.32 to 28.89 mBq/l and 2.19 to 117.43 mBq/l respectively. A combined 226Ra+228Ra activity was observed to be in the range of 2.63 to 171.9±12.75 mBq/l which is very much within the prescribed limits. The investigation indicated that 228Ra activity is comparatively more than 226Ra indicating the water source to be from Thorium rich locations.The expected dose assessed was in the range of 13.18 to 0.04 μSv/y which is well within the limit of 0.1 mSv/y. (author)

  16. Hepatoprotective activity of Clerodendron Inerme against Paracetamol induced Hepatic injury in Rats for Pharmaceutical Product

    Haque Rabiul

    2011-03-01

    Full Text Available Hepatitis is one of the major health problems in human which sometimes may lead to even death. Natural products may be the best source of remedies for the treatment of liver diseases. Thus identification of a potential therapeutic agent for the protection of liver from the hepatotoxins will provide a useful way for the prevention of these liver related illnesses. Our studies identified a plant with potential hepatoprotective activity. The etanolic extract of Clerodendron inerme leaves were screened for its hepatoprotective activity in paracetamol induced liver damage in Swiss albino rats at a dose of 200 mg/kg bw. The etanolic extract exhibited a significant protective effect by lowering serum levels of glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, alkaline phosphatase and total bilirubin. Liv.52 was used as positive control. The effects of the drug was judged by changes in serum marker ALT, AST, ALP, Protein and bilirubin levels. The extract did not show any mortality up to a dose of 2000g/kg bw.

  17. Recent developments in the Raman and infrared investigations of amorphous pharmaceuticals and protein formulations: A review.

    Hédoux, Alain

    2016-05-01

    The success rate for drug discovery and the development of innovative therapeutic strategies are intimately related to the physical properties of the solid-state condensed matter, which have direct influence on the bioavailability of Active Pharmaceutical Ingredients. In order to transform a new molecule in efficient drug, the material is brought into an amorphous state using various manufacturing processes including freeze drying, spray drying, hot melt extrusion and loading in different delivery devices. The infrared and Raman spectroscopic analyses used for exploring disordered and amorphous states, for the monitoring of the drug physical stability in drug delivery systems are described in this review. PMID:26686831

  18. Life cycle analysis of solvent reduction in pharmaceutical synthesis using continuous adsorption for palladium removal.

    Slater, C Stewart; Savelski, Mariano J; Ruiz-Felix, Marie Nydia

    2013-01-01

    The life cycle emissions associated with the reduction of wastes from an adsorption process to remove palladium complexes in drug manufacture have been evaluated. The study assessed a green improvement to a process step in an active pharmaceutical ingredient synthesis where palladium catalyst is removed from a reaction mixture. The greener process uses a continuous adsorption system, composed of a more efficient adsorbent, consuming less organic solvent and rinse water, which results in less waste disposal. The newer process is also more energy and cost efficient from an operational perspective. There is a 94% reduction in the carbon footprint of the new process when compared to the current operation. PMID:23947697

  19. Risk-based prioritization of pharmaceuticals in the natural environment in Iraq.

    Al-Khazrajy, Omar S A; Boxall, Alistair B A

    2016-08-01

    Numerous studies have demonstrated the occurrence of pharmaceuticals in the natural environment, raising concerns about their impact on non-target organisms or human health. One region where little is known about the exposure and effects of pharmaceuticals in the environment is Iraq. Due to the high number of pharmaceuticals used by the public health sector in Iraq (hospitals and care centres) and distributed over the counter, there is a need for a systematic approach for identifying substances that should be monitored in the environment in Iraq and assessed in terms of environmental risk. In this study, a risk-based prioritization approach was applied to 99 of the most dispensed pharmaceuticals in three Iraqi cities, Baghdad, Mosul and Basrah. Initially, information on the amounts of pharmaceuticals used in Iraq was obtained. The top used medicines were found to be paracetamol, amoxicillin and metformin with total annual consumption exceeding 1000 tonnes per year. Predicted environmental concentrations (PECs) and predicted no-effect concentrations (PNECs), derived from ecotoxicological end-points and effects related to the therapeutic mode of action, were then used to rank the pharmaceuticals in terms of risks to different environmental compartments. Active pharmaceutical ingredients used as antibiotics, antidepressants and analgesics were identified as the highest priority in surface water, sediment and the terrestrial environment. Antibiotics were also prioritized according to their susceptibility to kill or inhibit the growth of bacteria or to accelerate the evolution and dissemination of antibiotic-resistant genes in water. Future work will focus on understanding the occurrence, fate and effects of some of highly prioritized substances in the environment. PMID:27137195

  20. Evaluation of new pharmaceuticals using in vivo neutron inelastic scattering and neutron activation analysis

    Nutritional status of patients can be evaluated by monitoring changes in body composition, including depletion of protein and muscle, adipose tissue distribution and changes in hydration status, bone or cell mass. Fast neutron activation (for N and P) and neutron inelastic scattering (for C and O) are used to assess in vivo elements characteristic of specific body compartments. The fast neutrons are produced with a sealed deuterium-tritium (D-T) neutron generator. This method provides the most direct assessment of body composition. Non-bone phosphorus for muscle is measured by the 31P(n,α)28Al reaction, and nitrogen for protein via the (n,2n) fast neutron reaction. Inelastic neutron scattering is used for the measurement of total body carbon and oxygen. Carbon is used to derive body fat, after subtracting carbon contributions due to protein, bone and glycogen. Carbon-to-oxygen (C/O) ratio is used to measure distribution of fat and lean tissue in the body and to monitor small changes of lean mass and its quality. In addition to evaluating the efficacy of new treatments, the system is used to study the mechanisms of lean tissue depletion with aging and to investigate methods for preserving function and quality of life in the elderly. (author)

  1. 21 CFR 212.50 - What production and process controls must I have?

    2010-04-01

    ..., the name and radioactivity or other measurement of each active pharmaceutical ingredient and each... active pharmaceutical ingredient and each inactive ingredient per batch or per unit of radioactivity...

  2. Design of cost controller based on activity based costing for pharmaceutical enterprises%基于ABC的药业企业成本控制系统设计

    王晓艳; 吴锋

    2012-01-01

    精确的企业成本信息是企业进行生产管理、实施生产控制、乃至生产决策的重要依据.然而传统作业成本法扭曲成本信息的现象很可能导致成本失控,经营决策失败.本文引入了新的作业成本法(Activity Based Costing,ABC),探讨了ABC在药业企业成本核算中的基本原理,针对药业企业的运作模式、流程和特点,构建了基于作业成本法的药业企业成本控制系统模型,该模型对药业企业市场营销及竞争战略制定提供了重要的决策依据.%The precise cost information is an important basis for production management, production control, and even production decisions of enterprises. However, the phenomenon that the traditional activity-based costing methods distort cost information often lead to cost out of control and the failure of management decision. This paper introduces the new operating cost method (Activity Based Costing, ABC), and discusses the basic principle of ABC in cost accounting of pharmaceutical enterprise, in allusion to pharmaceutical enterprise operation mode, process and characteristics, it constructs the cost control system model about pharmaceutical enterprise Based on the activity-based Costing method. The model provides an important basis for decision-making on the marketing and competition strategy formulation of pharmaceutical enterprise.

  3. Changes in Phytochemical Synthesis, Chalcone Synthase Activity and Pharmaceutical Qualities of Sabah Snake Grass (Clinacanthus nutans L.) in Relation to Plant Age

    Ali Ghasemzadeh; Alireza Nasiri; Jaafar, Hawa Z. E.; Ali Baghdadi; Izham Ahmad

    2014-01-01

    In the current study, changes in secondary metabolite synthesis and the pharmaceutical quality of sabah snake grass leaves and buds were considered in relation to plant age (1 month, 6 months, and 1 year old). The activity of the enzyme chalcone synthase (CHS, EC 2.3.1.74) was measured, as it is a key enzyme for flavonoid production. Significant differences in total flavonoid (TF) production were observed between the three plant growth periods and the different plant parts. The highest conten...

  4. Phlorizin, an Active Ingredient of Eleutherococcus senticosus, Increases Proliferative Potential of Keratinocytes with Inhibition of MiR135b and Increased Expression of Type IV Collagen.

    Choi, Hye-Ryung; Nam, Kyung-Mi; Lee, Hyun-Sun; Yang, Seung-Hye; Kim, Young-Soo; Lee, Jongsung; Date, Akira; Toyama, Kazumi; Park, Kyoung-Chan

    2016-01-01

    E. senticosus extract (ESE), known as antioxidant, has diverse pharmacologic effects. It is also used as an antiaging agent for the skin and phlorizin (PZ) is identified as a main ingredient. In this study, the effects of PZ on epidermal stem cells were investigated. Cultured normal human keratinocytes and skin equivalents are used to test whether PZ affects proliferative potential of keratinocytes and how it regulates these effects. Skin equivalents (SEs) were treated with ESE and the results showed that the epidermis became slightly thickened on addition of 0.002% ESE. The staining intensity of p63 as well as proliferating cell nuclear antigen (PCNA) is increased, and integrin α6 was upregulated. Analysis of ESE confirmed that PZ is the main ingredient. When SEs were treated with PZ, similar findings were observed. In particular, the expression of integrin α6, integrin β1, and type IV collagen was increased. Levels of mRNA for type IV collagen were increased and levels of miR135b were downregulated. All these findings suggested that PZ can affect the proliferative potential of epidermal cells in part by microenvironment changes via miR135b downregulation and following increased expression of type IV collagen. PMID:27042261

  5. Phlorizin, an Active Ingredient of Eleutherococcus senticosus, Increases Proliferative Potential of Keratinocytes with Inhibition of MiR135b and Increased Expression of Type IV Collagen

    Hye-Ryung Choi

    2016-01-01

    Full Text Available E. senticosus extract (ESE, known as antioxidant, has diverse pharmacologic effects. It is also used as an antiaging agent for the skin and phlorizin (PZ is identified as a main ingredient. In this study, the effects of PZ on epidermal stem cells were investigated. Cultured normal human keratinocytes and skin equivalents are used to test whether PZ affects proliferative potential of keratinocytes and how it regulates these effects. Skin equivalents (SEs were treated with ESE and the results showed that the epidermis became slightly thickened on addition of 0.002% ESE. The staining intensity of p63 as well as proliferating cell nuclear antigen (PCNA is increased, and integrin α6 was upregulated. Analysis of ESE confirmed that PZ is the main ingredient. When SEs were treated with PZ, similar findings were observed. In particular, the expression of integrin α6, integrin β1, and type IV collagen was increased. Levels of mRNA for type IV collagen were increased and levels of miR135b were downregulated. All these findings suggested that PZ can affect the proliferative potential of epidermal cells in part by microenvironment changes via miR135b downregulation and following increased expression of type IV collagen.

  6. Food Ingredients as Anti-Obesity Agents.

    Saito, Masayuki; Yoneshiro, Takeshi; Matsushita, Mami

    2015-11-01

    Brown adipose tissue (BAT) is a site of adaptive non-shivering thermogenesis after cold exposure, and is involved in the regulation of energy expenditure and body fatness. BAT can be activated and recruited by not only cold exposure but also by various food ingredients including capsaicin in chili pepper and catechins in green tea, which would be easily and safely applicable to our daily life for preventing obesity. PMID:26421678

  7. 复方卡力孜然凝胶剂主要活性成分体外经皮渗透%In vitro Percutaneous Penetration of Main Active Ingredient from Fufang Kali Ziran Gel

    邢建国; 王新春; 赵媛; 马建红; 薛桂蓬; 刘桂花

    2012-01-01

    目的:研究不同透皮促进剂对复方卡力孜然凝胶剂3种有效成分体外经皮渗透的影响,筛选有效的透皮吸收促进剂.方法:采用改良Franz扩散池法、离体鼠皮进行体外透皮试验,HPLC测定透皮吸收促进剂对3种有效成分补骨脂素、异补骨脂素及蛇床子素的累积透过量及透皮速率的影响.结果:不同促透剂对复方卡力孜然凝胶剂中补骨脂素、异补骨脂素及蛇床子素体外透皮吸收产生不同的影响,确定2%氮酮为促进剂时3种有效成分的促透效果最好.结论:2%氮酮能够促进复方卡力孜然凝胶剂3种有效成分的有效渗透,透皮吸收过程符合Higuchi方程.%Objective: To study on effects of in vitro percutaneous penetration of different penetration enhancers for three active ingredients from Fufang Kali Ziran gel, and to screen out effective transdermal absorption enhancers. Method;In vitro transdermal test was used by modified Franz diffusion cell method and in vitro rat skin, effect of cumulative penetration volume and penetration rate from transdermal absorption enhancers for three active ingredients ( psoralen, isopsoralen and osthole) was determined by HPLC. Result; Different enhancers were found to have different degree in vitro penetration enhancing effect on psoralen, isopsoralen and osthole in Fufang Kali Ziran gel,determined 2% azone had optimum promoting effect as enhancers to three active ingredients. Conclusion;2% azone could promote effective penetration of three active ingredients from Fufang Kali Ziran gel. This process of penetration absorption could be in line with Higuchi equation.

  8. Pharmaceutical Advertisements in Indian Scientific Journals: Analysis of Completeness of Information Content

    Dr. Jignesh K Ved,

    2010-10-01

    Full Text Available Purpose: In India, pharmaceutical advertising is governed by ‘The Drugs and Magic Remedies (Objectionable Advertisements Act, 1954’, and ‘The Drugs and Cosmetics Rules, 1945’. These acts do not specify the ‘minimum essential information requirements’ for an dvertisement, keeping this area ill-defined. The ‘Organization ofPharmaceutical Producers of India (OPPI’, in its ‘Code of Pharmaceutical Marketing Practices’, provides a guideline for the information requirements in advertisements. Our study is intended to analyze the ‘completeness of information content’, in pharmaceutical advertisements, published in 2009-10 in Indian Scientific journals, in the context of OPPI code. Method: Indian Scientific Journals (2009-10 issues were surveyed for pharmaceutical advertisements.Advertisements were classified as ‘Full’ or ‘Reminder’ advertisements and were separately analyzed for the presence of information on ‘Brand name’; ‘Active ingredient(s’; ‘Marketer’s Name and Address’; ‘Date of Production of advertisement’; ‘Abbreviated Prescribing Information (only for Full advertisements’ and ‘Overall completeness’. Data was expressed as absolute numbers and percentage.Results: Full advertisements (n=34 demonstrated 41.2% of ‘Overall completeness’. ‘Date’ was missing in 52.9%, while ‘Marketer’s Name and Address’ in 17.6% of advertisements. ‘Active ingredient’ was mentioned in all, while ‘Abbreviated Prescribing Information’ was complete in 97.1% of Full advertisements. Reminder advertisements (n=134 demonstrated 10.4% of ‘Overall completeness’. ‘Date’ was issing in 88.1%, ‘Marketer’s Name and Address’ in 29.1% and ‘Active ingredient’ in 8.2% of Reminder advertisements.Conclusion: Low percentage of completeness, as observed in our study, indicates a lack of adherence to OPPI code and need for mandatory regulations, to ensure information completeness in

  9. RECENT POTENTIAL USAGE OF SURFACTANT FROM MICROBIAL ORIGIN IN PHARMACEUTICAL AND BIOMEDICAL ARENA: A PERSPECTIVE

    Rath Kalyani

    2011-08-01

    Full Text Available The use and potential commercial application of biosurfactant has increased during the past decade which can be used as emulsifiers, de-emulsifiers, wetting and foaming agents, functional food ingredients and as detergents in petroleum, petrochemicals, environmental management, agrochemicals, foods and beverages, cosmetics and pharmaceuticals and in the mining and metallurgical industries. Their antibacterial, antifungal and antiviral activities make them relevant molecules for applications in combating many diseases and as therapeutic agents. In addition to this their role as antiadhesive agents against several disease causing pathogens makes their utility as suitable antiadhesive coating agents for medical insertional materials which helps in the reduction in a large number of hospital infections without the use of synthetic drugs and chemicals. This review looks at the various pharmaceutical, biomedical and therapeutic perspectives on biosurfactant applications.

  10. On-demand continuous-flow production of pharmaceuticals in a compact, reconfigurable system.

    Adamo, Andrea; Beingessner, Rachel L; Behnam, Mohsen; Chen, Jie; Jamison, Timothy F; Jensen, Klavs F; Monbaliu, Jean-Christophe M; Myerson, Allan S; Revalor, Eve M; Snead, David R; Stelzer, Torsten; Weeranoppanant, Nopphon; Wong, Shin Yee; Zhang, Ping

    2016-04-01

    Pharmaceutical manufacturing typically uses batch processing at multiple locations. Disadvantages of this approach include long production times and the potential for supply chain disruptions. As a preliminary demonstration of an alternative approach, we report here the continuous-flow synthesis and formulation of active pharmaceutical ingredients in a compact, reconfigurable manufacturing platform. Continuous end-to-end synthesis in the refrigerator-sized [1.0 meter (width) × 0.7 meter (length) × 1.8 meter (height)] system produces sufficient quantities per day to supply hundreds to thousands of oral or topical liquid doses of diphenhydramine hydrochloride, lidocaine hydrochloride, diazepam, and fluoxetine hydrochloride that meet U.S. Pharmacopeia standards. Underlying this flexible plug-and-play approach are substantial enabling advances in continuous-flow synthesis, complex multistep sequence telescoping, reaction engineering equipment, and real-time formulation. PMID:27034366

  11. 药用辅料对药品安全性的影响%The impact of pharmaceutical excipients on the drug safety

    杨锐; 孙会敏; 于丽娜; 袁松

    2012-01-01

    药用辅料和药物活性成分共同组成了我们日常使用的药品,药用辅料同药物活性成分一样全程参与了体内的吸收、分布、代谢、排泄过程,所以药用辅料的安全性直接影响到了药物制剂的安全性,本文从药用辅料本身的毒副作用、药用辅料同药物活性物质(API)的配伍禁忌、药用辅料有毒副作用的杂质以及其他引起的药品安全性问题的辅料因素等四个方面阐述了药用辅料同药品安全性的关系.%Our daily used medicines were composed of pharmaceutical excipients and active pharmaceutical ingredients (API). The pharmaceutical excipients also involved in the whole process of absorption,distribution,metabolism and excretion in vivo as well as API. Therefore,the safety of pharmaceutical excipients was closely related to that of the pharmaceutical preparations. This review explained the relationship between the pharmaceutical excipients and medicines from the four aspects as below;the toxicity and side effects of pharmaceutical excipients itself,incompatibility of pharmaceutical excipients and API,the toxic impurity of pharmaceutical excipients and the other influencing factors of pharmaceutical excipients to the drug safety.

  12. Toxicological and ecotoxicological risk-based prioritization of pharmaceuticals in the natural environment.

    Guo, Jiahua; Sinclair, Chris J; Selby, Katherine; Boxall, Alistair B A

    2016-06-01

    Approximately 1500 active pharmaceutical ingredients are currently in use; however, the environmental occurrence and impacts of only a small proportion of these have been investigated. Recognizing that it would be impractical to monitor and assess all pharmaceuticals that are in use, several previous studies have proposed the use of prioritization approaches to identify substances of most concern so that resources can be focused on these. All of these previous approaches suffer from limitations. In the present study, the authors draw on experience from previous prioritization exercises and present a holistic approach for prioritizing pharmaceuticals in the environment in terms of risks to aquatic and soil organisms, avian and mammalian wildlife, and humans. The approach considers both apical ecotoxicological endpoints as well as potential nonapical effects related to the therapeutic mode of action. Application of the approach is illustrated for 146 active pharmaceuticals that are used either in the community or in hospital settings in the United Kingdom. Using the approach, 16 compounds were identified as a potential priority. These substances include compounds belonging to the antibiotic, antidepressant, anti-inflammatory, antidiabetic, antiobesity, and estrogen classes as well as associated metabolites. In the future, the prioritization approach should be applied more broadly around the different regions of the world. Environ Toxicol Chem 2016;35:1550-1559. © 2016 SETAC. PMID:26799673

  13. Stimuli-sensitive hydrogels for pharmaceutical and medical applications

    Ilić-Stojanović Snežana

    2011-01-01

    Full Text Available Hydrogels are three-dimensional cross-linked hydrophilic polymers that swell in water and aqueous solutions without dissolving in them. They are very sensitive to environmental stimulus, which is manifested by a sharp phase transition. This feature is important for their application in the pharmaceutical field, especially for making formulations with controlled release of active ingredients, with the correction of the solubility, degradation and their toxicity reducing. Because of the compatibility with living tissues, hydrogels can be used in different medical purposes (for making contact lenses, stents, balloon catheters, artificial muscles, substitutes for arteries and veins, trachea, oviduct. This work presents methods (chemical and physical for obtaining hydrogels, their properties and sensitivity to environmental stimuli (temperature, pH, magnetic field, as well as their potential application in medicine and pharmacy.

  14. Effects of Manufacturing Conditions on Pharmaceutical Properties of Petrolatum Ointment.

    Ashizuka, Yuki; Horisawa, Eijiro

    2016-08-01

    Oleaginous white petrolatum ointment (WP ointment) is one of the most commonly used dosage forms in the preparation of topical products. In general, WP ointments containing medium chain fatty acid triglycerides (MCT) are manufactured through a process of melting, mixing, agitating, and cooling. To investigate the pharmaceutical properties of WP ointments in greater detail, we examined manufacturing factors which could potentially influence the pharmaceutical properties of the finished product. WP ointment samples containing 10% MCT were stirred with a homogenizer and a paddle mixer at 65°C, then the homogenizer was stopped. Next, the paddle-mixer was stopped at several planned temperature points at which different samples were taken. Each sample was then cooled under the following planned conditions: rapid-cooling [-50°C/h] and slow-cooling [-7.5°C/h]. The pharmaceutical properties of each WP ointment sample, along with the appearance (Optical/digital microscope), hardness (Rheometer), and bleeding ability (100 Mesh wire-net cone) were measured. Then, release profiles were performed with a WP ointment using the model active ingredient Vitamin D. As a result, high hardness, low bleeding ability and low release profile were observed in the WP ointment samples that were manufactured under the condition of stopping the paddle-mixer at 40°C. However, the influence of cooling speed was observed to affect only hardness. Through optical microscopic observation, it was found that the appearance of WP ointment samples differed depending on the conditions under which they were manufactured. In this study, it was clear that the pharmaceutical properties of WP ointment samples were particularly influenced by the paddle-mixer stopping temperature. PMID:27193304

  15. An analysis of ingredient and nutritional labeling for wine

    Battaglene Tony

    2014-01-01

    Full Text Available Ingredient and nutritional information are currently mandatory in many countries for food labeling. Although wine is generally exempt from this requirement, regulatory changes are being actively considered by authorities across the globe. In this paper, a review of the current international requirements for the presentation of ingredient and nutritional information is undertaken. A literature review of studies into consumer's requirements and understanding of such information is undertaken and the potential costs to producers analysed. The study makes a number of conclusions on whether ingredient and nutritional labeling is appropriate for wine and investigates the effectiveness, usefulness and impact of such a labeling regime.

  16. On the relationship of inter-particle cohesiveness and bulk powder behavior: Flowability of pharmaceutical powders.

    Capece, Maxx; Silva, Karina Ruiz; Sunkara, Divya; Strong, John; Gao, Ping

    2016-09-10

    This study investigates the relationship between particle interactions dominated by the cohesive van der Waals force and powder flowability for materials commonly used by the pharmaceutical industry in oral solid dosage formulation. This study first sought to correlate the granular Bond number, defined as the ratio of the inter-particle cohesion force to particle weight, to the flow function coefficient, a metric commonly used to assess powder flowability. However, the granular Bond number which strictly quantifies inter-particle cohesiveness was found to correlate poorly with powder flowability due to the complexity associated with particle assemblies. To account for the multitude of interactions between particles of different sizes within a powder and to more precisely predict bulk powder behavior, a population-dependent granular Bond number was proposed. The population-dependent granular Bond number which explicitly accounts for particle size distribution and described herein as a quantification of powder cohesiveness (instead of inter-particle cohesiveness) was shown to correlate well with the flow function coefficient for a wide variety of materials including four active pharmaceutical ingredients (APIs) and fourteen common pharmaceutical excipients. Due to the success of the population-dependent granular Bond number, it was extended to predict the flowability of powder blends. This so-called population-dependent multi-component granular Bond number takes into account relevant material properties and particle interactions and was used to predict the flowability of 6-component powder blends containing acetaminophen as a model cohesive active pharmaceutical ingredient. Prediction of bulk powder behavior from individual material properties as accomplished here may be highly useful in formulation development. PMID:27353729

  17. Strategic Management of Innovations at Pharmaceutical Enterprises

    Honcharova Svіtlana Yu.; Honcharov Andrіy B.

    2014-01-01

    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 phar...

  18. Anti-Phytopthora capsici Activities and Potential Use as Antifungal in Agriculture of Alpinia galanga Swartz, Curcuma longa Linn, Boesenbergia pandurata Schut and Chromolaena odorata: Bioactivities Guided Isolation of Active Ingredients

    Wilart Pompimon

    2009-01-01

    Full Text Available Problem statement: Plant derived fungicides are now being subjects of many research groups. These secondary metabolites have enormous potential to inspire and influence modern agrochemical research. The study aimed to investigate the antifungal activity and their potential use as fungicides in the agriculture of crude extracts and purified compounds derived from plants used in traditional medicines. Approach: Four medicinal plants including A. galanga, C. longa, B. pandurata and C. odorata were selected and percolated with hexane, ethyl acetate, acetone or methanol. The extracts were purified and elucidated their chemical structures. Disc mycelial growth inhibition was applied in order to determine their anti P. capsici activity and the field study was performed to determine their potential use in controlling fungal infection in chili plants compared with commercial fungicides such as captan and bio-control Trichoderma virens. Results: All crude extract inhibited mycelial growth of the fungus performed with similar efficacy. ED90 was equal to 300 ppm. Among plants studied B. pandurata was the most potent against P. capsici. The proposed active ingredients were pinostrobin and pinocembrin. In the field study, pinocembrin mediated the same anti P. capsici activity as captan. B. pandurata can protect chili from infection, thus increasing crop yield of chili comparable to Trichoderma virens. Conclusion: The results clearly showed that the extracts of the four plants studied could be considered as potential sources of novel fungicides. Particularly, B. pandurata has a very high potential as raw material for developing the antifungal molecule of non-petrochemical, naturally eco-friendly, easily obtainable and not toxic to human beings and environment, at least for use in chili growing.

  19. Pharmaceutical market in Serbia

    Veselin Tima Dickov

    2012-02-01

    Full Text Available Marketing concept formed around the focus on the consumers, their needs, wants and demands, evolves in the case of pharmaceutical into a care of the complex interest of constituents generating demand on this market and #8211; pres scribers whose role is to select therapies, pharmacists who dispense drugs within a specialized distribution channel to the final consumer -patient, alongside the payers and #8211; the state and or insurance companies refund a part of or total costs of the pharmaceutical product. A special challenge that the subject raises is the existence of controversy generated from two sources. Marketing controversy stems from criticism leveled at the effectiveness and efficiency of marketing activities and the debatable ethical code of conduct. [J Intercult Ethnopharmacol 2012; 1(1.000: 44-51

  20. Ecotoxicological assessment using six pharmaceuticals commonly found in wastewaters

    Taipale, Paula; Ursin, Sisko

    2011-01-01

    Pharmaceutical residues in wastewaters are relatively new concern in environment protection. The usage of pharmaceuticals has increased a lot and their impact on the environment is unknown. Low levels of pharmaceuticals have been detected in many countries in sewage treatment plant effluents, surface waters, seawaters, groundwater and some drinking waters. Pharmaceutically-active compounds until recently have not been studied however even small residues of pharmaceuticals can have an effect o...

  1. The removal of endocrine disrupting compounds, pharmaceutically activated compounds and cyanobacterial toxins during drinking water preparation using activated carbon--a review.

    Delgado, Luis F; Charles, Philippe; Glucina, Karl; Morlay, Catherine

    2012-10-01

    This paper provides a review of recent scientific research on the removal by activated carbon (AC) in drinking water (DW) treatment of 1) two classes of currently unregulated trace level contaminants with potential chronic toxicity-pharmaceutically activate compounds (PhACs) and endocrine disrupting compounds (EDCs); 2) cyanobacterial toxins (CyBTs), which are a group of highly toxic and regulated compounds (as microcystin-LR); and 3) the above mentioned compounds by the hybrid system powdered AC/membrane filtration. The influence of solute and AC properties, as well as the competitive effect from background natural organic matter on the adsorption of such trace contaminants, are also considered. In addition, a number of adsorption isotherm parameters reported for PhACs, EDCs and CyBTs are presented herein. AC adsorption has proven to be an effective removal process for such trace contaminants without generating transformation products. This process appears to be a crucial step in order to minimize PhACs, EDCs and CyBTs in finished DW, hence calling for further studies on AC adsorption removal of these compounds. Finally, a priority chart of PhACs and EDCs warranting further study for the removal by AC adsorption is proposed based on the compounds' structural characteristics and their low removal by AC compared to the other compounds. PMID:22885596

  2. 77 FR 17484 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

    2012-03-26

    ... submission of listing. Note that unfinished products and active pharmaceutical ingredient listings will not... Register of August 29, 2006 (the 2006 proposed rule) (71 FR 51276), FDA proposed to revise part 207. The... Register of June 1, 2009 (74 FR 26248), FDA announced the availability of a guidance for industry...

  3. An analysis of ingredient and nutritional labeling for wine

    Battaglene Tony

    2014-01-01

    Ingredient and nutritional information are currently mandatory in many countries for food labeling. Although wine is generally exempt from this requirement, regulatory changes are being actively considered by authorities across the globe. In this paper, a review of the current international requirements for the presentation of ingredient and nutritional information is undertaken. A literature review of studies into consumer's requirements and understanding of such information is undertaken an...

  4. Pharmaceutically active compounds: Their removal during slow sand filtration and their impact on slow sand filtration bacterial removal.

    D'Alessio, Matteo; Yoneyama, Bunnie; Kirs, Marek; Kisand, Veljo; Ray, Chittaranjan

    2015-08-15

    Slow sand filtration (SSF) has been widely used as a means of providing potable water due to its efficacy, low cost, and minimal maintenance. Advances in analytical instrumentation have revealed the occurrence of pharmaceutically active compounds (PhACs) in surface water as well as in groundwater. It is unclear if the presence of these compounds in the feed water can interfere with the performances of an SSF unit. The aim of this work was to examine i) the ability of two SSF units to remove six PhACs (caffeine, carbamazepine, 17-β estradiol [E2], estrone [E1], gemfibrozil, and phenazone), and ii) the impact of these PhACs on the removal of bacteria by two SSF units. The presence of PhACs in feed water for SSF can occur in surface waters impacted by wastewater or leakage from sewers and septic tanks, as well as in developing countries where unregulated use and improper disposal are prevalent. Two pilot-scale SSF units were used during the study. Unit B1 was fed with stream water with 1% of primary effluent added, while unit B2 was fed with stream water alone. Although limited removal (gemfibrozil, and phenazone occurred, the complete removal of caffeine, and the partial removal (11-92%) of E2 and E1 were observed in the two SSF units. The results of this study suggest that the occurrence of the selected PhACs, probably estrogens and caffeine, in the feed water at 50 μg L(-1) affected the ability of the schmutzdecke to remove total coliform and Escherichia coli. The bacterial removal achieved within the schmutzdecke dropped from 95% to less than 20% by the end of the study. This decrease in removal may be related to the change in the microbial community within the schmutzdecke. A diverse microbial community, including Bacteroidetes and several classes of Proteobacteria, was replaced by a microbial community in which Gammaproteobacteria was the predominant phylum (99%). Despite the low removal achieved within the schmutzdecke, removal of total coliform and E. coli

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

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

    2016-02-01

    Hot-melt extrusion (HME) is a promising technology for the production of new chemical entities in the developmental pipeline and for improving products already on the market. In drug discovery and development, industry estimates that more than 50% of active pharmaceutical ingredients currently used belong to the biopharmaceutical classification system II (BCS class II), which are characterized as poorly water-soluble compounds and result in formulations with low bioavailability. Therefore, there is a critical need for the pharmaceutical industry to develop formulations that will enhance the solubility and ultimately the bioavailability of these compounds. HME technology also offers an opportunity to earn intellectual property, which is evident from an increasing number of patents and publications that have included it as a novel pharmaceutical formulation technology over the past decades. This review had a threefold objective. First, it sought to provide an overview of HME principles and present detailed engineered extrusion equipment designs. Second, it included a number of published reports on the application of HME techniques that covered the fields of solid dispersions, microencapsulation, taste masking, targeted drug delivery systems, sustained release, films, nanotechnology, floating drug delivery systems, implants, and continuous manufacturing using the wet granulation process. Lastly, this review discussed the importance of using the quality by design approach in drug development, evaluated the process analytical technology used in pharmaceutical HME monitoring and control, discussed techniques used in HME, and emphasized the potential for monitoring and controlling hot-melt technology. PMID:26159653

  6. 药物共晶研究进展及应用%Pharmaceutical cocrystal research progress and application

    弋东旭; 洪鸣凰; 徐军; 赵文杰; 任国宾

    2011-01-01

    Pharmaceutical cocrystal could be obtained by combining active pharmaceutical ingredient (API) and cocrystal former (CCF) in one crystal lattice through noncovalent interaction.It is a new pharmaceutical physical form which can improve the physicochemical properties, such as solubility, stability and bioavailability of API.It has becoming a novel hot spot in pharmaceutical research and development field.This paper mainly introduces the pharmaceutical cocrystal on its application, design, preparation and analysis method.%药物共晶是活性药物成分通过非共价键和共晶形成物结合在一个晶格中形成的.它是一种新的药物固体型态,可以改善药物的理化性质,比如改善溶解度、增加稳定性、提高生物利用度等,是目前药物研发的一个新的热点.本文主要介绍了药物共晶在药物研发中的应用及其设计、制备以及分析方法.

  7. Alkaloids in the pharmaceutical industry: Structure, isolation and application

    Nikolić Milan

    2003-01-01

    Full Text Available By the end of the 18th and the beginning of the 19th century a new era began in medicine, pharmaceutics and chemistry that was strongly connected with alkaloids and alkaloid drugs. Even before that it was known that certain drugs administered in limited doses were medicines, and toxic if taken in larger doses (opium, coke leaves, belladonna roots, monkshood tubers crocus or hemlock seeds. However, the identification, isolation and structural characterization of the active ingredients of the alkaloid drugs was only possible in the mid 20th century by the use of modern extraction equipment and instrumental methods (NMR, X-ray diffraction and others.In spite of continuing use over a long time, there is still great interest in investigating new drugs, potential raw materials for the pharmaceutical industry, as well as the more detailed investigation and definition of bio-active components and the indication of their activity range, and the partial synthesis of new alkaloid molecules based on natural alkaloids. The scope of these investigations, especially in the field of semi-synthesis is to make better use of the bio-active ingredients of alkaloid drugs, i.e. to improve the pharmacological effect (stronger and prolonged effect of the medicine, decreased toxicity and side effects, or to extend or change the applications. A combined classification of alkaloids was used, based on the chemical structure and origin, i.e. the source of their isolation to study alkaloid structure. For practical reasons, the following classification of alkaloids was used: ergot alkaloids, poppy alkaloids, tropanic alkaloids purine derivative alkaloids, carbon-cyclic alkaloids, and other alkaloids. The second part of this report presents a table of general procedures for alkaloid isolation from plant drugs (extraction by water non-miscible solvents, extraction by water-miscible solvents and extraction by diluted acid solutions. Also, methods for obtaining chelidonine and

  8. A simple and sensitive method to analyze genotoxic impurity hydrazine in pharmaceutical materials.

    Wang, Jenny; Yang, Samuel; Zhang, Kelly

    2016-07-15

    Hydrazine (N2H4) is a known genotoxic impurity that typically needs to be controlled down to low ppm level in pharmaceutical development. Hydrazine, however, is a challenging molecule to analyze using conventional analytical techniques due to its physical and chemical properties (e.g. lack of chromophore, absence of any carbon atom, low molecular weight, high polarity and volatility). Additionally, analysis in pharmaceutical samples commonly encounters significant interference from matrix components that greatly overshadow the response of hydrazine. This work describes a simple, accurate and sensitive reversed-phase liquid chromatography-UV derivatization method for determination of trace amount hydrazine in pharmaceutical materials featuring three prominent strategies to address the problems associated with hydrazine analysis. First, the derivatization reaction attaches chromophores to hydrazine, which greatly increases its sensitivity by UV-vis detection. Secondly, the derivatization reaction generates a lambda max that is well-shifted away from the absorption wavelengths of pharmaceutical matrix interferences. Thirdly, from a separation standpoint, the derivatization further removes matrix interference effects through chromatography by achieving higher resolution of the derivative product from the active pharmaceutical ingredient (API) and its related impurities for accurate quantitation for trace level of genotoxic impurities (GTIs). 2-Hydroxy-1-Naphthalaldehyde (HNA) was chosen as the derivatizing reagent, and the resulting hydrazone product has a maximum UV absorbance at wavelength of 406/424nm which is in the visible range. Since most drug substance and impurities have UV absorbance ranging from 190 to 380nm, interference from the matrix was minimized and the appropriate selectivity was obtained, the detection limit is 0.25ppm (0.25μg/g API). This method was validated and applied as a generic method to determine hydrazine for pharmaceutical process control

  9. ''Old labels in new clothes'' - Optimisation of pharmaceutical formulations using radionuclide imaging

    The use of gamma-emitting radiopharmaceuticals is confined mainly to nuclear medicine applications. The technique of gamma scintigraphy, however, can provide the biological scientist with a powerful tool with which to monitor the in vivo behaviour of radiolabelled substances (Hardy and Wilson, 1981). Radionuclide imaging is proving to be a valuable technique in pharmaceutical research, where it is used for the optimisation of drug formulations (Wilson and colleagues 1981). Several approaches can be adopted for radiolabelling of drug preparations. The obvious approach is to replace a stable atom with a gamma-emitting isotope. Unfortunately this is rarely practicable, since the majority of drug molecules do not comprise elements having suitable radioisotopes. The second possibility is to add to the preparation a tracer amount of a radiopharmaceutical having similar physicochemical properties to the active ingredient. The efficacy of many pharmaceutical products is influenced by the nature of the dosage form, and the physical characteristics of the active ingredients such as particle size, solubility and viscosity. Often these parameters can be investigated using appropriately radiolabelled model systems. As an alternative to radiolabelling the drug preparation it may be possible to observe the effect of the drug by monitoring changes in the distribution of conventionally administered radiopharmaceuticals. Examples illustrate the diversity of the applications of radiopharmaceuticals in drug formulation studies

  10. Bioremediation Kinetics of Pharmaceutical Industrial Effluent

    Šabić, M.; Vuković Domanovac, M.; Findrik Blažević, Z.; Meštrović, E.

    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...

  11. Application of Refractometry in Purification Technology of Active Ingredients from Citrus aurantium by Macroporous Resin%折光法在树脂精制枳实中有效成分的应用

    曾文雪; 姚珍珍; 涂瑶生; 陈银芳; 宋小玲; 王跃生

    2013-01-01

    目的:探讨折光法在大孔树脂纯化工艺中应用的可行性.方法:选取枳实提取物为研究对象,经AB-8型大孔吸附树脂精制有效部位,用水与50%乙醇洗脱,间隔取样,在线监测洗脱液的折光率并分析其变化规律,同时以HPLC和UV检测作为参比,判断洗脱过程中始点和终点.结果:枳实有效部位精制过程中水洗终点为第4 BV(折光率0),亦即50%乙醇洗脱始点,50%乙醇洗脱终点为第9 BV(折光率16).结论:折光法准确可靠、便捷快速,具有较强的实践指导意义.%Objective: To explore application feasibility of refractometry in purification technology of macroporous resin. Method: Taking extract of Citrus aurantium as research object, active ingredients in it was refined by AB-8 macroporous resin, washed with water and 50% ethanol, interval sampled, refractive ratio of eluent was monitored on line and analyzed its regularity. At the same time, HPLC and UV spectrophotometric method was used to determine hesperidin as references, and to judge initiation point and terminal point during elution. Result: In purification process of active ingredients from C. aurantium, water elution terminal point 4 BV ( refractive index 0) of which was the initiation point by 50% ethanol, 9 BV (refractive index 16) of 50% ethanol elution was the terminal point. Conclusion: Refractometry was accurate, reliable, convenient, quickly in purification technology of active ingredients of TCM, it had a strong practical significance.

  12. BREAKTHROUGH POSITIONING STRATEGY: USAGE AT THE ENTERPRISE LEVEL RUSSIAN PHARMACEUTICAL CLUSTER

    Pashkus V.Y.; Pashkus N.A

    2015-01-01

    The article deals with the development of pharmaceutical clusters. We study the development of the Russian pharmaceutical market, highlighted areas where there are promising pharmaceutical companies engaged in innovative activities and using modern marketing strategies, including breakthrough positioning strategy. The aim is to develop a tool positioning regional pharmaceutical cluster region-specific manufacturers and features segments of the pharmaceutical market, including: formulations, d...

  13. Pharmaceutical cocrystals: a comparison of sulfamerazine with sulfamethazine

    Lu, Jie; Li, Yi-Ping; Wang, Jing; Li, Zhen; Rohani, Sohrab; Ching, Chi-Bun

    2011-11-01

    Although there has been much debate about its definition among scientists, a cocrystal may be defined as a crystalline material that consists of two or more electrically neutral molecular species held together by non-covalent forces, and meanwhile all components are solids at room temperature. Obviously it is great to introduce predictable structural motifs to an active pharmaceutical ingredient (API) by design. One widely used approach to cocrystal design is based on the consideration of Δp Ka, which can represent the propensity of molecular species to form a cocrystal or a salt. In this work, p-aminobenzoic acid (PABA) was mixed with sulfamerazine (SMZ) or sulfamethazine (STH) by use of neat cogrinding and solvent-drop cogrinding. It was found that PABA and SMZ with a Δp Ka of 2.13 would form a binary eutectic, while PABA and STH with a larger Δp Ka of 2.59 can form a cocrystal in the ratio of 1:1. The phenomenon indicates that not only the Δp Ka but also the stereo-hindrance effect (geometric fit) should be considered during the design of pharmaceutical cocrystals.

  14. Multiscale modelling of pharmaceutical powders: Macroscopic behaviour prediction

    Loh, Jonathan; Ketterhagen, William; Elliott, James

    2013-06-01

    The pharmaceutical industry uses computer models at many stages during drug development. Quantum and molecular models are used to predict the crystal structures of potential active pharmaceutical ingredients (APIs), whereas discrete element models are used to optimise the mechanical properties of mixtures of APIs and excipient powders. The present work combines the strengths of modelling from all of the mentioned length scales to predict the behaviour of macroscopic powder granules from first principles using the molecular and crystal structures of acetazolamide as an example API. Starting with a single molecule of acetazolamide, ab initio self-consistent field calculations were used to calculate the equilibrium gas phase structure, vibrational spectra, interaction energy with water molecules and perform potential energy scans. By using these results and following the CHARMM General Force Field parameterisation process, all of the parameters required to perform a molecular dynamics simulation were iteratively determined using the CHARMM program. Next, by using crystallographic data from literature, the monoclinic and triclinic forms of the acetazolamide crystal were simulated. Material properties like the Young's modulus and Poisson ratio, and surface energies have been calculated. These material properties are then used as input parameters in a discrete element model containing Thornton's plastic model and the JKR cohesive force to predict the behaviour of macroscopic acetazolamide powder in angle of repose tests and tabletting simulations. Similar methodologies can be employed in the future to evaluate at an early stage the performance of novel APIs and excipients for tabletting applications.

  15. Development of a comprehensive spectral library of sildenafil and related active analogues using LC-QTOF-MS and its application for screening counterfeit pharmaceuticals.

    Lee, Sooyeun; Ji, Dajeong; Park, Meejung; Chung, Kyu Hyuck

    2015-12-01

    The abuse or misuse of forged erectile-dysfunction drugs, containing phosphodiesterase type 5 inhibitors (e.g. sildenafil), is a serious issue globally. Therefore, the detection of sildenafil and related active analogues in counterfeit pharmaceuticals or the differentiation between counterfeit and authentic drugs has been performed with a variety of analytical techniques. Recently, a liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-QTOF-MS)-based in-house library, consisting of accurate mass ion fragmentation information and retention times, was effectively applied to screen a large number of compounds in field of forensic toxicology. However, a comprehensive LC-QTOF-MS spectral library of sildenafil and related active analogues has not yet been reported. In the present study, a spectral library of 40 compounds of sildenafil and related analogues was developed with accurate mass spectra and retention times using LC-QTOF-MS, and applied to screen nine marketed counterfeit products. The in-house library successfully identified sildenafil, dimethylsildenafil, hydroxyhomosildenafil, demethylhongdenafil, pseudovardenafil and vardenafil in the samples. Our LC-QTOF-MS-based spectral library search is considered a powerful approach for identifying sildenafil and related active analogues in counterfeit pharmaceuticals. PMID:26363440

  16. A preliminary analysis of the active ingredients from the seeds of Polygonum orientale against Mythimna separata%红蓼种子中杀黏虫活性成分的初步分析

    姚赛群; 胡冠芳; 刘敏艳; 张新瑞

    2011-01-01

    [目的]对红蓼种子乙酸乙酯萃取物中具有潜在杀虫活性的化合物进行初步分析,为指导开发利用杀虫植物资源提供依据.[方法]采用硅胶柱层析和气相色谱-质谱(GC-MS)联用法,以5龄黏虫为试虫;对红蓼种子萃取物的有效杀虫活性成分进行分析,应用色谱峰面积归一法测定各组分的相对百分含量.[结果]极性(甲醇)组分共分离出37个色谱峰,鉴定了其中的35个组分,占总含量的94.46%.弱极性(二氯甲烷)组分共分离出39个色谱峰,鉴定出39个组分.[结论]从成分的化学结构推断,红蓼种子的杀虫活性可能存在于14种成分中,主要成分为酮、醇、开环萜和五环三萜烷类化合物.%[Objective] Active ingredients of the ethyl acetate fraction from seeds of Polygonum orientale Linn, were analyzed to provide the basis for the exploitation of the insecticidal plant resources. [Method] Insecticidal ingredients from the seeds of P. orientale fractions were analyzed against the 5th instar larvae of Mythimna separata Walker by using silica gel colurnn-chromatographer (CO and gas chromatography-mass spectrometry (GC-MS). The relative percentage of each composition was determined by area normalization. [Result] Thirty-seven peaks were found, 35 of which were identified, representing 94.46% of the total contents in polar fraction. Thirty-nine peaks were found, all of which were identified in low polar fraction. [Conclusion] It was deduced that the insecticidal active ingredients in P. orientale seeds were 14 chemical compounds, belonging to ketone, alcohol, terpene with open-ring and pentacyclic triterpene classes.

  17. Removal of selected pharmaceuticals from domestic wastewater in an activated sludge system followed by a horizontal subsurface flow bed - analysis of their respective contributions.

    Verlicchi, P; Galletti, A; Petrovic, M; Barceló, D; Al Aukidy, M; Zambello, E

    2013-06-01

    Seventy-three commonly administered pharmaceuticals from twelve different therapeutic classes were investigated at a municipal wastewater treatment plant in northern Italy featuring a conventional activated sludge system (full-scale) and a polishing horizontal subsurface flow bed (pilot plant). Removal of these micro-pollutants by the two systems was assessed in order to evaluate their respective contributions. Mean concentrations and standard deviations were calculated and found to differ for the compounds detected, ranging from few ng/L to over 1,165 ng/L in the secondary effluent and from 11 to 533 in the polished effluent. Eighteen compounds were consistently below the detection limit and the remaining 55 compounds were found at a minimum of one sampling point. Average removal efficiencies of both treatment steps and in treatment train as a whole are evaluated and discussed, highlighting the difficulties in predicting the fate of pharmaceuticals in both an activated sludge system and a horizontal subsurface flow bed. Comparison between the observed average removal efficiencies and those reported in the literature was also carried out for the pharmaceuticals of interest, and the discrepancies that emerged are discussed. The investigated constructed wetland did show efficacy in removing some of these compounds, and it contributed to the overall removal efficiency of each therapeutic class. Indeed, evaluation of the specific mass loadings of each class of PhC detected in the raw wastewaters, secondary and polished effluent evidences that the investigated constructed wetland is able to further reduce the load of micropollutants, which could become a necessity, especially where the receiving water body is an effluent-dominant river and mitigation measures of the discharge impact are required to protect and safeguard the aquatic environment. PMID:23563255

  18. Modulation of steroidogenic gene expression and hormone production of H295R cells by pharmaceuticals and other environmentally active compounds

    The H295R cell bioassay was used to evaluate the potential endocrine disrupting effects of 18 of the most commonly used pharmaceuticals in the United States. Exposures for 48 h with single pharmaceuticals and binary mixtures were conducted; the expression of five steroidogenic genes, 3βHSD2, CYP11β1, CYP11β2, CYP17 and CYP19, was quantified by Q-RT-PCR. Production of the steroid hormones estradiol (E2), testosterone (T) and progesterone (P) was also evaluated. Antibiotics were shown to modulate gene expression and hormone production. Amoxicillin up-regulated the expression of CYP11β2 and CYP19 by more than 2-fold and induced estradiol production up to almost 3-fold. Erythromycin significantly increased CYP11β2 expression and the production of P and E2 by 3.5- and 2.4-fold, respectively, while production of T was significantly decreased. The β-blocker salbutamol caused the greatest induction of CYP17, more than 13-fold, and significantly decreased E2 production. The binary mixture of cyproterone and salbutamol significantly down-regulated expression of CYP19, while a mixture of ethynylestradiol and trenbolone, increased E2 production 3.7-fold. Estradiol production was significantly affected by changes in concentrations of trenbolone, cyproterone, and ethynylestradiol. Exposures with individual pharmaceuticals showed the possible secondary effects that drugs may exert on steroid production. Results from binary mixture exposures suggested the possible type of interactions that may occur between drugs and the joint effects product of such interactions. Dose-response results indicated that although two chemicals may share a common mechanism of action the concentration effects observed may be significantly different

  19. Intravenous microemulsion of docetaxel containing an anti-tumor synergistic ingredient (Brucea javanica oil): formulation and pharmacokinetics

    Ma S; Chen F; Ye X; Dong Y.; Xue Y; Xu H; Zhang W; Song S.; Ai L; Zhang N; Pan W

    2013-01-01

    Shilin Ma,1 Fen Chen,1 Xiaohui Ye,2 Yingjie Dong,2 Yingna Xue,1 Heming Xu,1 Wenji Zhang,1 Shuangshuang Song,1 Li Ai,2 Naixian Zhang,2 Weisan Pan1 1School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 2Liaoning Institute of Pharmaceutical Industry, Liaoning, The People's Republic of China Abstract: The purpose of this study was to develop a docetaxel microemulsion containing an anti-tumor synergistic ingredient (Brucea javanica oil) and to investigate the characteristics of th...

  20. Thermal stability of synthetic thyroid hormone l-thyroxine and l-thyroxine sodium salt hydrate both pure and in pharmaceutical formulations.

    Ledeţi, Ionuţ; Ledeţi, Adriana; Vlase, Gabriela; Vlase, Titus; Matusz, Petru; Bercean, Vasile; Şuta, Lenuţa-Maria; Piciu, Doina

    2016-06-01

    In this paper, the thermal stability of pure l-thyroxine (THY) and l-thyroxine sodium salt hydrate (THYSS) vs. two pharmaceutical solid formulations commercialized on both Romanian and European market (with a content of 100μg, respectively 200μg THYSS per tablet) were investigated. In order to determine whether the presence of excipients affects the thermal stability of the active pharmaceutical ingredient (API), the preliminary study of thermal stability in air atmosphere was completed with an in-depth solid-state kinetic study. By kinetic analysis, the non-isothermal degradation of the selected active pharmaceutical ingredients vs. the solid formulation with strength of 200μg THYSS per tablet was investigated. Isoconversional methods (Kissinger-Akahira-Sunose, Flynn-Wall-Ozawa and Friedman) were employed for the estimation of activation energies values, at five different heating rates, β=5, 7, 10, 12 and 15°Cmin(-1). Also, a fourth method was applied in the processing of data, namely NPK, allowing an objective separation in the physical and chemical processes that contribute to the thermal degradation of the selected compounds. A discussion of thermal stability from the kinetic point of view is also presented. PMID:26999320

  1. Development of a simple, rapid and validated spectrophotometric method for nitazoxanide in pharmaceutical formulations and comparison with HPLC

    Marcelo Donadel Malesuik

    2010-01-01

    Full Text Available A rapid, economical, reproducible, and simple direct spectrophotometric method was developed and validated for the assay of nitazoxanide in pharmaceutical formulations. Nitazoxanide concentration was estimated in water at 345 nm and pH 4.5. The method was suitable and validated for specificity, linearity, precision, and accuracy. There was no interference of the excipients in the determination of the active pharmaceutical ingredient. The proposed method was successfully applied in the determination of nitazoxanide in coated tablets and in powders for oral suspension. This method was compared to a previously developed and validated method for liquid chromatography to the same drug. There was no significative difference between these methods for nitazoxanide quantitation.

  2. A PHARMACEUTICAL COMPARISON OF GUDUCHI GHRITA PREPARED FROM MALE AND FEMALE PLANTS OF TINOSPORA CORDIFOLIA (WILLD. MIERS.

    BK Ashok

    2011-04-01

    Full Text Available Pharmaceutical study appreciates the importance of formulation preparation which ultimately determines the nature and magnitude of pharmacological activity expressed. Guduchi is one among the most important medicinal plants of India and various formulations of Guduchi ghrita are mentioned in different Ayurvedic classical texts. In the present study, a simple formulation of Guduchi ghrita which is used for treatment of chronic fever wherein no other ingredient except Guduchi was selected and a comparative pharmaceutical study of Guduchi ghrita prepared from male and female plants was carried out. The preparation of Guduchi ghrita formulations were carried out by adopting standard operative procedure. The result of this study shows that ghrita prepared from male plant yielded more quantity of finished product than that of female plant.

  3. 羽裂蟹甲草对家蝇和白纹伊蚊的杀虫活性和活性成分%Insecticidal activities and active ingredients of Cacalia tangutica against Musca domestica and Aedes albopictus

    黄继光; 赵欢欢; 苗辉; 徐汉虹

    2012-01-01

    To study the insecticidal activities and active ingredients of Cacalia tangutica,the methanol extracts of C.tangutica against Musca domestica and Aedes albopictus were bioassayed with feeding method and dipping method.The active ingredients of C.tangutica were isolated and identified.Results indicated that the methanol extracts from different parts of C.tangutica showed highly insecticidal activities against adult M.domestica and the 4th instar larvae of A.albopictus.Nine compounds (stigmasterol,friedelin,7-hydroxy-8-methoxycoumarin,umbelliferone,daphnetin,daphnetin-8-O-β-D-glucopyranoside,quercetin,kaempferol and β-daucosterol) were isolated and identified from extracts of leaves and flowers of C.tangutica.Among them,friedelin,quercetin and kaempferol were firstly isolated from this plant.At 48 h after treatment,the corrected mortalities of adult M.domestica caused by friedelin,quercetin and kaempferol at the dosage of 500 μg/g were 88.33%,69.90% and 77.04%,respectively.At 72 h after treatment,the corrected mortalities of the 4th instar larvae of A.albopictus caused by friedelin,quercetin and kaempferol at the concentration of 50 μg/g were 88.49%,72.22%and 71.06%,respectively.The studies suggest that C.tangutica would be a promising control agent on medical insects and deserves a further study.%为探明羽裂蟹甲草Cacalia tangutica的杀虫活性及其活性成分,通过拌糖饲喂法和浸渍法测定了羽裂蟹甲草甲醇提取物对家蝇Musca domestica成虫和白纹伊蚊Aedes albopictus 4龄幼虫的毒杀活性,并采用色谱分离技术和现代波谱技术对羽裂蟹甲草中的化学成分进行了分离鉴定.结果表明:该植物不同部位甲醇提取物对家蝇成虫和白纹伊蚊4龄幼虫均具有较高的生物活性.从该植物叶和花甲醇提取物中分离鉴定了豆甾醇、无羁萜、7-羟基-8-甲氧基香豆素、7-羟基香豆素、7,8-二羟基香豆素、瑞香素-8-O-β-D-葡萄糖苷、槲皮素

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

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

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

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

    2007-02-15

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

  6. Radiation sterilization of pharmaceuticals

    Ionizing radiation for sterilization of medical products has been widely used throughout the world, but application of pharmaceuticals has not yet gain popularity due their complex nature. Radiation sterilization especially gamma radiation is a promising method for those pharmaceuticals which are sensitive to heat and ethylene oxide. This article compare various methods of sterilization and their shortcomings, radiation sterilization and its advantages over conventional methods, various radiation sources, effect of gamma irradiation on solid and aqueous pharmaceuticals and the methods of evaluation of irradiated products. Different pharmaceuticals approved for radiation treatment in different parts of the world and pharmaceuticals and radiopharmaceutical kits sterilized in Pakistan have also been described. (author)

  7. Ba-Wei-Di-Huang-Wan through its active ingredient loganin counteracts substance P-enhanced NF-κB/ICAM-1 signaling in rats with bladder hyperactivity.

    Tsai, Wen-Hsin; Wu, Chung-Hsin; Cheng, Chen-Hung; Chien, Chiang-Ting

    2016-09-01

    Overt bladder afferent activation may exacerbate endogenous substance P (SP) release to induce intercellular adhesion molecule-1 (ICAM-1)-mediated inflammation and reactive oxygen species (ROS) production leading to hyperactive bladder. Ba-Wei-Die-Huang-Wan (BWDHW), a traditional Chinese medicine, has been used to treat lower urinary tract symptoms in patients by undefined mechanisms. We explored the possible mechanisms and the active components of BWDHW on exogenous SP-induced bladder hyperactivity. BWDHW contained six major components: loganin, paeoniflorin, 5-hydroxymethylfurfural, cinnamic acid, cinnamaldehyde, and paeonol by high-performance liquid chromatography. In urethane-anesthetized female Wistar rats, we evaluated transcystometrogram, pelvic afferent nerve activity by electrophysiologic recording techniques, ICAM-1 expression by Western blot and immunohistochemistry, ROS amount by an ultrasensitive chemiluminescence method and possible ROS sources from the different leukocytes by specific stains in SP-treated bladder. BWDHW and its major component loganin dose-dependently inhibited H2 O2 and HOCl activity in vitro. Intragastrical BWDHW (250 mg/kg) and loganin (5 mg/kg) twice daily for 2 weeks did not affect the baseline micturition parameters. Intra-arterial SP (20 µg/rat) through neurokinin-1 receptor activation increased voiding frequency (shortened intercontraction intervals), pelvic afferent nerve activity, bladder NF-κB/ICAM-1 expression, bladder ROS amount, neutrophils adhesion to venous endothelium, CD68 (monocyte/macrophage), and mast cell infiltration in the inflamed bladder. BWDHW and loganin pretreatment significantly depressed SP-enhanced pelvic afferent nerve activity, bladder NF-κB/ICAM-1 expression, leukocyte infiltration, and ROS amount, and subsequently improved bladder hyperactivity. In conclusion, our results suggest that BWDHW and its active component loganin improves bladder hyperactivity via inhibiting SP/neurokinin-1

  8. Development and Validation of a Stability Indicating RP-HPLC Method for Hydrocortisone Acetate Active Ingredient, Propyl Parahydroxybenzoate and Methyl Parahydroxybenzoate Preservatives, Butylhydroxyanisole Antioxidant, and Their Degradation Products in a Rectal Gel Formulation.

    Ascaso, Magda; Pérez-Lozano, Pilar; García, Mireia; García-Montoya, Encarna; Miñarro, Montse; Ticó, Josep R; Fàbregas, Anna; Carrillo, Carolina; Sarrate, Rocío; Suñé-Negre, Josep M

    2015-01-01

    A stability indicating method was established through a stress study, wherein different methods of degradation (oxidation, hydrolysis, photolysis, and temperature) were studied simultaneously to determine the active ingredient hydrocortisone acetate, preservatives propyl parahydroxybenzoate, and methyl parahydroxybenzoate, antioxidant butylhydroxyanisole (BHA), and their degradation products in a semisolid dosage gel form. The proposed method was suitably validated using a Zorbax SB-Phenyl column and gradient elution. The mobile phase consisted of a mixture of methanol, acetonitrile, and water in different proportions according to a planned program at a flow rate of 1.5 mL/min. The diode array detector was set at 240 nm for the active substance and two preservatives, and 290 nm for BHA. The validation study was conducted according to International Conference on Harmonization guidelines for specificity, linearity, repeatability, precision, and accuracy. The method was used for QC of hydrocortisone acetate gel and for the stability studies with the aim of quantifying the active substance, preservatives, antioxidant, and degradation products. It has proved to be suitable as a fast and reliable method for QC. PMID:25857875

  9. Lactose in dairy ingredients: Effect on processing and storage stability.

    Huppertz, Thom; Gazi, Inge

    2016-08-01

    Lactose is the main carbohydrate in the milk of most species. It is present in virtually all dry dairy ingredients, with levels ranging from lactose powders. The presence of lactose has a strong effect on ingredient processing and stability. Lactose can negatively influence powder properties and lead to undesirable effects, such as the stickiness of powder resulting in fouling during drying, or caking and related phenomena during storage. In addition, being a reducing carbohydrate, lactose can also participate in the Maillard reaction with free amino groups of proteins, peptides, and free AA. In this review, the influence of the presence (or absence) of lactose on physiochemical properties of dairy ingredients is reviewed, with particular emphasis on behavior during processing and storage. Particularly important features in this respect are whether lactose is in the (glassy) amorphous phase or in the crystalline phase, which is strongly affected by precrystallization conditions (e.g., in lactose, permeate, and whey powders) and by drying conditions. Furthermore, the moisture content and water activity of the ingredients are important parameters to consider, as they determine both mobility and reactivity, influencing Maillard reactions and concomitant browning, the crystallization of amorphous lactose during storage of dairy ingredients, glass transitions temperatures, and associated stickiness and caking phenomena. For the stickiness and caking, a crucial aspect to take into account is powder particle surface composition in relation to the bulk powder. Lactose is typically underrepresented at the powder surface, as a result of which deviations between observed lactose-induced caking and stickiness temperatures, and determined glass transition temperatures arise. By considering lactose as an integral part of ingredient composition along with all other compositional and environmental properties, lactose behavior in dairy ingredients can be understood, controlled, and

  10. 美白活性原料的筛选及其特性研究%Study of selection and properties of active ingredients in whitening cosmetics

    王鹏; 王勇刚; 李素霞; 韩福森; 吴巧玲; 王素英

    2009-01-01

    Tyrosinase inhibiting activity and anti-oxidizing capacity (scavenging activity against hydroxyl free radicals and super-oxidizing anionic free radicals in vitro) of extracts of twenty kinds of plant material, including green tea, grape seed and Brazil cherry were investigated. Experimental results showed that, all the extracts of twenty kinds of plant material display tyrosinase inhibiting activity and anti-oxidizing capacity in vitro with different extent;while the extracts from green tea, grape seed and Brazil cherry display very strong ty-rosinase inhibiting activity,which are much higher than that of arbutin. Further,the above-mentioned three extracts display significant scavenging activity against hydroxyl free radicals and super-oxdizing anionic free radicals in vitro. Thus the three kinds of plant material have the potential to be used in whitening cosmetics.%对绿茶、葡萄籽和巴西大樱桃等23种植物提取物对酪氨酸酶的抑制作用以及其抗氧化能力(清除羟基自由基和超氧阴离子自由基的能力)进行了研究.实验结果表明,20种样品均表现出不同程度的酪氨酸酶抑制作用和抗氧化能力,其中绿茶、巴西大樱桃和葡萄籽提取物表现出极强的酪氨酸酶活性抑制率,且抑制活性远高于熊果苷;同时这3种植物提取物也表现出显著的清除羟基自由基和超氧阴离子自由基的能力,具有应用于美白化妆品的潜力.

  11. Near infra red spectroscopy as a multivariate process analytical tool for predicting pharmaceutical co-crystal concentration.

    Wood, Clive; Alwati, Abdolati; Halsey, Sheelagh; Gough, Tim; Brown, Elaine; Kelly, Adrian; Paradkar, Anant

    2016-09-10

    The use of near infra red spectroscopy to predict the concentration of two pharmaceutical co-crystals; 1:1 ibuprofen-nicotinamide (IBU-NIC) and 1:1 carbamazepine-nicotinamide (CBZ-NIC) has been evaluated. A partial least squares (PLS) regression model was developed for both co-crystal pairs using sets of standard samples to create calibration and validation data sets with which to build and validate the models. Parameters such as the root mean square error of calibration (RMSEC), root mean square error of prediction (RMSEP) and correlation coefficient were used to assess the accuracy and linearity of the models. Accurate PLS regression models were created for both co-crystal pairs which can be used to predict the co-crystal concentration in a powder mixture of the co-crystal and the active pharmaceutical ingredient (API). The IBU-NIC model had smaller errors than the CBZ-NIC model, possibly due to the complex CBZ-NIC spectra which could reflect the different arrangement of hydrogen bonding associated with the co-crystal compared to the IBU-NIC co-crystal. These results suggest that NIR spectroscopy can be used as a PAT tool during a variety of pharmaceutical co-crystal manufacturing methods and the presented data will facilitate future offline and in-line NIR studies involving pharmaceutical co-crystals. PMID:27429366

  12. Laser-induced breakdown spectroscopy-based investigation and classification of pharmaceutical tablets using multivariate chemometric analysis.

    Myakalwar, Ashwin Kumar; Sreedhar, S; Barman, Ishan; Dingari, Narahara Chari; Venugopal Rao, S; Prem Kiran, P; Tewari, Surya P; Manoj Kumar, G

    2011-12-15

    We report the effectiveness of laser-induced breakdown spectroscopy (LIBS) in probing the content of pharmaceutical tablets and also investigate its feasibility for routine classification. This method is particularly beneficial in applications where its exquisite chemical specificity and suitability for remote and on site characterization significantly improves the speed and accuracy of quality control and assurance process. Our experiments reveal that in addition to the presence of carbon, hydrogen, nitrogen and oxygen, which can be primarily attributed to the active pharmaceutical ingredients, specific inorganic atoms were also present in all the tablets. Initial attempts at classification by a ratiometric approach using oxygen (∼777 nm) to nitrogen (742.36 nm, 744.23 nm and 746.83 nm) compositional values yielded an optimal value at 746.83 nm with the least relative standard deviation but nevertheless failed to provide an acceptable classification. To overcome this bottleneck in the detection process, two chemometric algorithms, i.e. principal component analysis (PCA) and soft independent modeling of class analogy (SIMCA), were implemented to exploit the multivariate nature of the LIBS data demonstrating that LIBS has the potential to differentiate and discriminate among pharmaceutical tablets. We report excellent prospective classification accuracy using supervised classification via the SIMCA algorithm, demonstrating its potential for future applications in process analytical technology, especially for fast on-line process control monitoring applications in the pharmaceutical industry. PMID:22099648

  13. Molecular ingredients of heterogeneous catalysis

    The purpose of this paper is to present a review and status report to those in theoretical chemistry of the rapidly developing surface science of heterogeneous catalysis. The art of catalysis is developing into science. This profound change provides one with opportunities not only to understand the molecular ingredients of important catalytic systems but also to develop new and improved catalyst. The participation of theorists to find answers to important questions is sorely needed for the sound development of the field. It is the authors hope that some of the outstanding problems of heterogeneous catalysis that are identified in this paper will be investigated. For this purpose the paper is divided into several sections. The brief Introduction to the methodology and recent results of the surface science of heterogeneous catalysis is followed by a review of the concepts of heterogeneous catalysis. Then, the experimental results that identified the three molecular ingredients of catalysis, structure, carbonaceous deposit and the oxidation state of surface atoms are described. Each section is closed with a summary and a list of problems that require theoretical and experimental scrutiny. Finally attempts to build new catalyst systems and the theoretical and experimental problems that appeared in the course of this research are described

  14. Fate of bulk organic matter, nitrogen, and pharmaceutically active compounds in batch experiments simulating soil aquifer treatment (SAT) using primary effluent

    Abel, Chol D T

    2013-06-30

    Reduction of bulk organic matter, nitrogen, and pharmaceutically active compounds from primary effluent during managed aquifer recharge was investigated using laboratory-scale batch reactors. Biologically stable batch reactors were spiked with different concentrations of sodium azide to inhibit biological activity and probe the effect of microbial activity on attenuation of various pollutants of concern. The experimental results obtained revealed that removal of dissolved organic carbon correlated with active microbial biomass. Furthermore, addition of 2 mM of sodium azide affected nitrite-oxidizing bacteria leading to accumulation of nitrite-nitrogen in the reactors while an ammonium-nitrogen reduction of 95.5 % was achieved. Removal efficiencies of the hydrophilic neutral compounds phenacetin, paracetamol, and caffeine were independent of the extent of the active microbial biomass and were >90 % in all reactors, whereas removal of pentoxifylline was dependent on the biological stability of the reactor. However, hydrophobic ionic compounds exhibited removal efficiency >80 % in batch reactors with the highest biological activity as evidenced by high concentration of adenosine triphosphate. © 2013 Springer Science+Business Media Dordrecht.

  15. Bioactive potential of Rosa micrantha Borrer ex Sm. and Castanea sativa Mill. flowers as functional food ingredients: antioxidant and antifungal activity

    Barros, Lillian; Ferreira, Isabel C. F. R.

    2014-01-01

    Natural products represent a rich source of biologically active compounds and are an example of molecular diversity, with recognized potential in drug discovery and development. Particularly, the plant kingdom offers a wide range of natural antioxidants, recognized by having remarkable medicinal properties [1,2]. These beneficial effects could be related to the high content in phenolic compounds, known for being strong scavengers of free radicals, which have key roles in ageing...

  16. Bioavailability & Bioequivalence Studies ? Pharmaceutical Importance

    Pratibha Muntha

    2015-01-01

    Pharmacokinetics has now emerged as an important part of drug development especially in the development of new drugs. The combined studies of Pharmacodynamics and pharmacokinetics present a thorough understanding on how the drug affects the body and how the body affects the drug.Bioavailability is the study of the rate and extent to which the active ingredient is absorbed from a dosage form and it is available at the required action site. Bioequivalence is that the...

  17. 石榴籽油冷榨技术及活性成分生理作用研究%Pomegranate Seed Oil Cold Pressing and Physiological Role of Its Active Ingredient

    李勇

    2011-01-01

    石榴籽油冷榨技术采用低温62℃,使脂肪氧化酶灭活,既可提高出油率,又可防止挥发油、多酚、维生素等活性物质的损失.冷榨技术与莘取法相比,出油率仅低3%-5%,但没有萃取溶剂有害物质的残留.本文介绍了冷榨技术工艺流程及操作要点,分析了石榴籽油的活性成分及其生理作用.%Pomegranate seed oil cold pressing technology inactives lipoxygenase at low temperature 62℃ ,which can increase oil yield and prevent the loss of volatile oils, polyphenols, vitamins and other active substances. Compared with extraction technology,oil yield of cold pressing technology is 3%-5% lower, but no harmful substances residues in extraction solvent. Process and operating points of cold pressing technology were introduced and physiological role of active ingredients in pomegranate seed oil was analyzed.

  18. Physical and Chemical Aspects of Pharmaceutical Solids: Fundamentals of Polymorphs, Hydrates and Solvates

    Reutzel-Edens, Susan

    2007-03-01

    Crystal polymorphs are solid phases of a given compound resulting from the possibility of at least two different arrangements of the molecules of that compound in the solid state. Solvates form when the solvent is incorporated in the crystal structure of a compound; hydrates form when water is the solvent of crystallization. The potential effects of crystal polymorphism and hydration on the quality and performance of drug products is widely recognized by the pharmaceutical industry. Investigations of crystal polymorphism and hydration are usually conducted early in drug development to optimize the physical properties of a pharmaceutical solid. Although the thermodynamically most stable crystal form is generally selected for commercial development to mitigate the risk of undesired phase transformations, form selection oftentimes involves a compromise among different physical properties of various drug crystal forms. Controlling polymorph (or hydrate) appearance must be accomplished through careful evaluation of both thermodynamic (tendency toward the formation of more stable crystal forms) and kinetic parameters (which lead to the formation of metastable forms) in the crystallization process. In this presentation, fundamental aspects of polymorphs and solvates (hydrates) will be explored. Particular attention will be given to the structure and stability relationships between polymorphs and hydrates, kinetic vs. thermodynamic transitions, and the impact of polymorphism and hydration on the chemical and physical stability of an active pharmaceutical ingredient.

  19. Validation of a liquid chromatographic method for the pharmaceutical quality control of products containing elacridar

    Emilia Sawicki

    2016-08-01

    Full Text Available Many anticancer drugs have an impaired bioavailability and poor brain penetration because they are substrates to drug efflux pumps such as P-glycoprotein and Breast Cancer Resistance Protein. Elacridar is a strong inhibitor of these two drug efflux pumps and therefore has great potential to improve oral absorption and brain penetration of many anticancer drugs. Currently, a clinical formulation of elacridar is unavailable and therefore the pharmaceutical development of a drug product is highly warranted. This also necessitates the availability of an analytical method for its quality control. A reverse-phase high-performance liquid chromatographic method with ultraviolet detection was developed for the pharmaceutical quality control of products containing elacridar as the active pharmaceutical ingredient. The analytical method was validated for linearity, accuracy, precision, selectivity, carry-over, stability of stock and reference solutions, stability of the final extract, stability-indicating capability and impurity testing. We found that elacridar is unstable in aqueous solutions that are exposed to light because a hydroxylation product of elacridar is formed. Therefore, sample solutions with elacridar must be protected from light.

  20. Prioritization of pharmaceuticals for potential environmental hazard through leveraging a large-scale mammalian pharmacological dataset.

    Berninger, Jason P; LaLone, Carlie A; Villeneuve, Daniel L; Ankley, Gerald T

    2016-04-01

    The potential for pharmaceuticals in the environment to cause adverse ecological effects is of increasing concern. Given the thousands of active pharmaceutical ingredients (APIs) that can enter the aquatic environment through human and/or animal (e.g., livestock) waste, a current challenge in aquatic toxicology is identifying those that pose the greatest risk. Because empirical toxicity information for aquatic species is generally lacking for pharmaceuticals, an important data source for prioritization is that generated during the mammalian drug development process. Applying concepts of species read-across, mammalian pharmacokinetic data were used to systematically prioritize APIs by estimating their potential to cause adverse biological consequences to aquatic organisms, using fish as an example. Mammalian absorption, distribution, metabolism, and excretion (ADME) data (e.g., peak plasma concentration, apparent volume of distribution, clearance rate, and half-life) were collected and curated, creating the Mammalian Pharmacokinetic Prioritization For Aquatic Species Targeting (MaPPFAST) database representing 1070 APIs. From these data, a probabilistic model and scoring system were developed and evaluated. Individual APIs and therapeutic classes were ranked based on clearly defined read-across assumptions for translating mammalian-derived ADME parameters to estimate potential hazard in fish (i.e., greatest predicted hazard associated with lowest mammalian peak plasma concentrations, total clearance and highest volume of distribution, half-life). It is anticipated that the MaPPFAST database and the associated API prioritization approach will help guide research and/or inform ecological risk assessment. PMID:25772004

  1. A harmonization effort for acceptable daily exposure application to pharmaceutical manufacturing - Operational considerations.

    Hayes, Eileen P; Jolly, Robert A; Faria, Ellen C; Barle, Ester Lovsin; Bercu, Joel P; Molnar, Lance R; Naumann, Bruce D; Olson, Michael J; Pecquet, Alison M; Sandhu, Reena; Shipp, Bryan K; Sussman, Robert G; Weideman, Patricia A

    2016-08-01

    A European Union (EU) regulatory guideline came into effect for all new pharmaceutical products on June 1st, 2015, and for all existing pharmaceutical products on December 1st, 2015. This guideline centers around the use of the Acceptable Daily Exposure (ADE) [synonymous with the Permitted Daily Exposure (PDE)] and operational considerations associated with implementation are outlined here. The EU guidance states that all active pharmaceutical ingredients (API) require an ADE; however, other substances such as starting materials, process intermediates, and cleaning agents may benefit from an ADE. Problems in setting ADEs for these additional substances typically relate to toxicological data limitations precluding the ability to establish a formal ADE. Established methodologies such as occupational exposure limits or bands (OELs or OEBs) and the threshold of toxicological concern (TTC) can be used or adjusted for use as interim ADEs when only limited data are available and until a more formal ADE can be established. Once formal ADEs are derived, it is important that the documents are routinely updated and that these updates are communicated to appropriate stakeholders. Another key operational consideration related to data-poor substances includes the use of maximum daily dose (MDD) in setting cross-contamination limits. The MDD is an important part of the maximum allowable/safe concentration (MAC/MSC) calculation and there are important considerations for its use and definition. Finally, other considerations discussed include operational aspects of setting ADEs for pediatrics, considerations for large molecules, and risk management in shared facilities. PMID:27267172

  2. Dropwise additive manufacturing of pharmaceutical products for solvent-based dosage forms.

    Hirshfield, Laura; Giridhar, Arun; Taylor, Lynne S; Harris, Michael T; Reklaitis, Gintaras V

    2014-02-01

    In recent years, the US Food and Drug Administration has encouraged pharmaceutical companies to develop more innovative and efficient manufacturing methods with improved online monitoring and control. Mini-manufacturing of medicine is one such method enabling the creation of individualized product forms for each patient. This work presents dropwise additive manufacturing of pharmaceutical products (DAMPP), an automated, controlled mini-manufacturing method that deposits active pharmaceutical ingredients (APIs) directly onto edible substrates using drop-on-demand (DoD) inkjet printing technology. The use of DoD technology allows for precise control over the material properties, drug solid state form, drop size, and drop dynamics and can be beneficial in the creation of high-potency drug forms, combination drugs with multiple APIs or individualized medicine products tailored to a specific patient. In this work, DAMPP was used to create dosage forms from solvent-based formulations consisting of API, polymer, and solvent carrier. The forms were then analyzed to determine the reproducibility of creating an on-target dosage form, the morphology of the API of the final form and the dissolution behavior of the drug over time. DAMPP is found to be a viable alternative to traditional mass-manufacturing methods for solvent-based oral dosage forms. PMID:24311373

  3. Recent Advances in Lipase-Mediated Preparation of Pharmaceuticals and Their Intermediates.

    Carvalho, Ana Caroline Lustosa de Melo; Fonseca, Thiago de Sousa; de Mattos, Marcos Carlos; de Oliveira, Maria da Conceição Ferreira; de Lemos, Telma Leda Gomes; Molinari, Francesco; Romano, Diego; Serra, Immacolata

    2015-01-01

    Biocatalysis offers an alternative approach to conventional chemical processes for the production of single-isomer chiral drugs. Lipases are one of the most used enzymes in the synthesis of enantiomerically pure intermediates. The use of this type of enzyme is mainly due to the characteristics of their regio-, chemo- and enantioselectivity in the resolution process of racemates, without the use of cofactors. Moreover, this class of enzymes has generally excellent stability in the presence of organic solvents, facilitating the solubility of the organic substrate to be modified. Further improvements and new applications have been achieved in the syntheses of biologically active compounds catalyzed by lipases. This review critically reports and discusses examples from recent literature (2007 to mid-2015), concerning the synthesis of enantiomerically pure active pharmaceutical ingredients (APIs) and their intermediates in which the key step involves the action of a lipase. PMID:26690428

  4. Novel botanical ingredients for beverages.

    Gruenwald, Joerg

    2009-01-01

    Natural substances are generally preferred over chemical ones and are generally seen as healthy. The increasing demand for natural ingredients, improving health and appearance, is also attracting beverages as the fastest growing segment on the functional food market. Functional beverages are launched as fortified water, tea, diary or juices claiming overall nutrition, energy, anti-aging or relaxing effects. The substitution of so called superfruits, such as berries, grapes, or pomegranate delivers an effective range of beneficial compounds, including vitamins, fatty acids, minerals, and anti-oxidants. In this context, new exotic and African fruits could be useful sources in the near future. Teas and green botanicals, such as algae or aloe vera are also rich in effective bioactives and have been used traditionally. The botanical kingdom offers endless possibilities. PMID:19168002

  5. Qualitative Confirmation of Active Ingredient of Arbutin in Pear Leaves and Quantitative Determination by HPLC%梨树叶中有效成分熊果苷的确证及HPLC检测

    赵洁; 何强; 姚秉华; 孔祥虹

    2011-01-01

    目的 确证梨树叶中含有熊果苷,并建立高效液相色谱法测定梨树叶中熊果苷的含量.方法 将充分粉碎的梨树叶样品用甲醇提取,蒸去甲醇后用ENVITM- 18固相萃取柱净化,采用在线获取的紫外光谱及扫描质谱对熊果苷进行确证.高效液相色谱分析时用Inertsil ODS-3色谱柱分离,甲醇-水(1:9)洗脱,282 nm检测.结果 梨树叶样品中目标物的紫外吸收光谱及子离子扫描质谱图与熊果苷标准品相同.高效液相色谱法定量分析时线性关系良好,熊果苷的回收率>93%,RSD<2.1%.结论 梨树叶中含有熊果苷有效成分,高效液相色谱法检测梨树叶中熊果苷的含量简便、快速、准确.%OBJECTIVE To confirm arbutin as an ingredient in pear leaves, and develop a method for the determination of arbutin content in pear leaves by HPLC. METHODS The full powdered pear leaves were extracted with methanol, then cleanup was performed on ENVI-18 SPE columns after methanol boiled off. Qualitative confirmation using the UV spectrum and mass spectra was acquired on-line. HPLC was performed on Inertsil ODS-3 column with DAD detection wavelength of 282 nm using methanol-water( 1: 9) as mobile phase. RESULTS The UV spectrum and mass spectra of the target chromatographic peak were the same as arbutin standard. The HPLC method showed good linear relationship, the recoveries of arbutin were all more than 93% and RSD was less than 2.1%. CONCLUSION Arbutin is an active ingredient in pear leaves, and HPLC as the content analysis method is simple, rapid and accurate.

  6. Biological and Pharmaceutical Nanomaterials

    Kumar, Challa S. S. R.

    2006-01-01

    This first comprehensive yet concise overview of all important classes of biological and pharmaceutical nanomaterials presents in one volume the different kinds of natural biological compounds that form nanomaterials or that may be used to purposefully create them. This unique single source of information brings together the many articles published in specialized journals, which often remain unseen by members of other, related disciplines. Covering pharmaceutical, nucleic acid, peptide and DNA-Chitosan nanoparticles, the book focuses on those innovative materials and technologies needed for the continued growth of medicine, healthcare, pharmaceuticals and human wellness. For chemists, biochemists, cell biologists, materials scientists, biologists, and those working in the pharmaceutical and chemical industries.

  7. Research advances in garlic's main active ingredients and their pharmacological effects%大蒜主要活性成分及药理作用研究进展

    马丽娜; 李峰杰; 陈坚; 李贻奎

    2014-01-01

    大蒜为广义百合科植物大蒜( Allium sativum L.)的鳞茎,具有防治心血管疾病、抗肿瘤及抗病原微生物等多方面的作用。该文通过查阅国内外文献,对大蒜的主要活性成分及药理作用进行综述,并针对国内大蒜研究中存在的问题和研究进展进行了初步的分析,为大蒜的进一步研究及新药开发提供一定的参考。%Garlic is a bulb from generalized liliaceous plant Alli-um sativum, it plays an essential role in the prevention and treat-ment of cardiovascular diseases, tumors and pathogenic microor-ganisms. Through consulting domestic and foreign references, the main active ingredients of garlic and their pharmacological effects are reviewed, the problems and achievement in Chinese research are also discussed. It can provide a certain reference for the further study of garlic and new drug development.

  8. 抗肝纤维化的中药有效成分及其作用机制研究进展%Advances in active ingredients and action mechanism of TCM in treatment of hepatic fibrosis

    孙蕾; 邓华平; 席忠新; 李霞; 孙连娜

    2012-01-01

    肝纤维化是多数慢性肝病所共有的病理特征,肝纤维化逐步发展形成肝硬化,最终导致肝癌.本文将近年报道的具有抗HF作用的中药有效成分作简单综述,归纳为黄酮类、生物碱类、萜类、酚类化合物,并总结了各类有效成分抗HF的作用机制,为深入开展中药抗HF的研究提供一定的参考.%Hepatic fibrosis was the common feature of pathology in almost all patients with chronic liver injury, which led to cirrhosis gradually and liver cancer ultimately. The anti-hepatic fibrosis active ingredients from TCM, including flavones, alkaloids, terpenes and phenols compounds were reviewed with the action mechanism in this paper, which could provide some references for the further study about the anti-hepatic fibrosis of TCM.

  9. Ionic Liquids in Pharmaceuticals%具有药物活性的离子液体

    杨亭亭; 高国华

    2012-01-01

    In order to solve the problems associated with the solid form of conventional pharmaceuticals including polymorphic conversion, low solubility, low bioavailability, and the tendency of amorphous forms to spontaneously crystallize, the liquid form pharmaceuticals have attracted much attention. Recent developments of ionic liquids (ionic liquids are loosely defined as salts with melting points below 100℃) might prove beneficial. Ionic liquids exhibit controlled solubility, unique surface activity, high thermostability and enhancement in bioavailability or bioactivity, which make ionic liquids have the advantage of elimination of polymorphism, new delivery options, or having customized pharmaceutical cocktails. In some cases, an active cation and an active anion can be combined to produce a liquid possessing dual functionality. These make ionic liquids have the possibility of being used in the pharmaceutical industry. The aim of this mini-review is to summarize the recent development of ionic liquids as active pharmaceutical ingredients, antimicrobial agents and agricuhure chemicals, and discuss the existing problems and the future research of ionic liquids in pharmaceuticals.%离子液体阴阳离子的可设计性使其具有可控溶解性、独特表面活性、高热稳定性、增强的生物利用率和生物活性,这些特点使离子液体在消除同质多晶现象、改变药物传输模式及可包含传统药物组分等方面具有优势,成为当前离子液体研究领域的热点之一。本文对离子液体在医药领域的应用做了全面的阐述,主要介绍了近十年来离子液体在活性药物组分、抗菌剂及除草剂方面的成果,探讨了当前存在的问题及研究方向,并对其应用做了展望。

  10. Pharmaceutical care in smoking cessation.

    Marín Armero, Alicia; Calleja Hernandez, Miguel A; Perez-Vicente, Sabina; Martinez-Martinez, Fernando

    2015-01-01

    As a determining factor in various diseases and the leading known cause of preventable mortality and morbidity, tobacco use is the number one public health problem in developed countries. Facing this health problem requires authorities and health professionals to promote, via specific programs, health campaigns that improve patients' access to smoking cessation services. Pharmaceutical care has a number of specific characteristics that enable the pharmacist, as a health professional, to play an active role in dealing with smoking and deliver positive smoking cessation interventions. The objectives of the study were to assess the efficacy of a smoking cessation campaign carried out at a pharmaceutical care center and to evaluate the effects of pharmaceutical care on patients who decide to try to stop smoking. The methodology was an open, analytical, pre-post intervention, quasi-experimental clinical study performed with one patient cohort. The results of the study were that the promotional campaign for the smoking cessation program increased the number of patients from one to 22, and after 12 months into the study, 43.48% of the total number of patients achieved total smoking cessation. We can conclude that advertising of a smoking cessation program in a pharmacy increases the number of patients who use the pharmacy's smoking cessation services, and pharmaceutical care is an effective means of achieving smoking cessation. PMID:25678779

  11. Challenging near infrared spectroscopy discriminating ability for counterfeit pharmaceuticals detection.

    Storme-Paris, I; Rebiere, H; Matoga, M; Civade, C; Bonnet, P-A; Tissier, M H; Chaminade, P

    2010-01-25

    This study was initiated by the laboratories and control department of the French Health Products Safety Agency (AFSSAPS) as part of the fight against the public health problem of rising counterfeit and imitation medicines. To test the discriminating ability of Near InfraRed Spectroscopy (NIRS), worse cases scenarios were first considered for the discrimination of various pharmaceutical final products containing the same Active Pharmaceutical Ingredient (API) with different excipients, such as generics of proprietary medicinal products (PMP). Two generic databases were explored: low active strength hard capsules of Fluoxetine and high strength tablets of Ciprofloxacin. Then 4 other cases involving suspicious samples, counterfeits and imitations products were treated. In all these cases, spectral differences between samples were studied, giving access to API or excipient contents information, and eventually allowing manufacturing site identification. A chemometric background is developed to explain the optimisation methodology, consisting in the choices of appropriate pretreatments, algorithms for data exploratory analyses (unsupervised Principal Component Analysis), and data classification (supervised cluster analysis, and Soft Independent Modelling of Class Analogy). Results demonstrate the high performance of NIRS, highlighting slight differences in formulations, such as 2.5% (w/w) in API strength, 1.0% (w/w) in excipient and even coating variations (<1%, w/w) with identical contents, approaching the theoretical limits of NIRS sensitivity. All the different generic formulations were correctly discriminated and foreign PMP, constituted of formulations slightly different from the calibration ones, were also all discriminated. This publication addresses the ability of NIRS to detect counterfeits and imitations and presents the NIRS as an ideal tool to master the global threat of counterfeit drugs. PMID:20103090

  12. Strategic Management of Innovations at Pharmaceutical Enterprises

    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.

  13. Process and technical requirement for the development of the active pharmaceutical ingredient (API) generic drugs%仿制原料药研究开发流程及技术要求

    刘旭亮; 张立颖; 臧恒昌

    2009-01-01

    本文针对国家食品药品监督管理局对仿制原料药研究开发出台的一些新法规和技术指导原则,研究确定了仿制药研发流程及技术要求,以期对仿制原料药的研发具有一定的指导意义.

  14. Determination of the Content of Gefitinib Active Pharmaceutical Ingredients and Related Substances by HPLC%HPLC法测定吉非替尼原料药的含量和有关物质

    梁晓东; 马小涛; 和龙; 赵卫红

    2015-01-01

    目的:建立测定吉非替尼原料药含量和有关物质的方法.方法:采用高效液相色谱法.色谱柱为SunfireC18,流动相A为醋酸铵溶液、流动相B为乙腈,流速为1.0 ml/min;有关物质测定采用梯度洗脱,进样量为10 μl,检测波长为240 nm,柱温为40℃;含量测定采用等度洗脱,进样量为5 μl,检测波长为247 nm,柱温为30℃.结果:有关物质测定方法中各杂质及主成分之间能够很好地分离;吉非替尼及杂质A、B、C、D、E和F质量浓度分别在0.280 8~28.08(r=0.999 5)、0.042 24~28.16(r=0.999 9)、0.355~28.40(r=0.999 9)、0.283~28.30(r=0.999 9)、0.286 4~28.64(r=0.999 9)、0.098 28~28.08(r=0.999 9)和0.724~28.96μg/ml(r=0.999 9)范围内与各自峰面积呈良好的线性关系;有关物质和含量测定仪器精密度、中间精密度、稳定性试验的RSD不超过5.97%和0.90%;各杂质测定平均回收率在100.6%~106.9%,RSD在0.82%~6.86%(n=9);含量测定平均加样回收率为100.5%,RSD为0.15%(n=9).结论:本方法专属性强,精密度、准确度和耐用性良好,可用于吉非替尼原料药的质量控制.

  15. 化药原料药当前药学审评技术要求初探%Thoughts on current chemistry, manufacturing & control (CMC) technical review requirement of chemical active pharmaceutical ingredients

    操锋; 马玉楠

    2014-01-01

    回顾近十年来我国药品研发和审评的历程,分析目前我国医药行业形势及国家食品药品监督管理总局药品审评中心(CDE)对化药原料药审评理念和技术要求的变化.结合CDE审评现状详细分析了原料药研发要点,从合成工艺、起始原料和中间体的控制、关键步骤及工艺参数、晶型、批量、结构确证、质量研究、质量标准以及稳定性等多个方面介绍了药品研发中应该注意的问题,供我国新药研发人员参考.

  16. 失效模式和影响分析在原料药工艺验证中的应用%Application of Failure Mode and Effects Analysis in Active Pharmaceutical Ingredient(API) Process Validation

    孟铮; 黄文锋

    2015-01-01

    目的 探索风险管理工具在原料药工艺验证中的应用,使用失效模式和影响分析(failure mode and effects analysis,FMEA)评估关键工艺参数,降低验证风险.方法 将FMEA应用于原料药的工艺验证,根据风险优先数(risk priority number,RPN)值的大小,确定关键工艺参数和风险控制措施.结果 通过实施和跟踪工艺操作控制措施,再次计算RPN值,较验证前减小,降低发生工艺偏差的风险.结论 质量风险管理应用于原料药工艺验证,可有效地提高针对性,降低生产质量的系统风险,将有利于日常商业化生产的平稳运行,提高生产效率.

  17. HPLC法测定盐酸阿扎司琼原料药中主药含量%Determination of Main Component in Active Pharmaceutical Ingredient of Azasetron Hydrochloride by HPLC

    董晓琴

    2013-01-01

    目的:建立HPLC法测定盐酸阿扎司琼原料药中的主药含量.方法:采用外标法,使用Phenomenex Luna 5u C18(2)100A色谱柱(250mm×4.6 mm,5μn),磷酸盐缓冲液-乙腈(82∶ 18)为流动相,流速为1.0 mL·min-1,检测波长为305 nm,柱温为35℃.结果:盐酸阿扎司琼进样质量在2.01 ~20.08 μg范围内,与色谱峰面积的线性关系良好(r =0.999 9).测得3批原料药中盐酸阿扎司琼质量分数分别为99.6%、99.9%和99.5%,与非水滴定法的测定结果相近.结论:该法准确、便捷、低污染,可用于盐酸阿扎司琼原料药中主药含量的测定.

  18. 原料药发酵车间工程设计关键要素分析%Analysis of Key Factors in Engineering Design of Active Pharmaceutical Ingredient Fermentation Plant

    李向科; 姚雪坤

    2013-01-01

    对采用传统发酵工艺生产的原料药发酵车间,在工程设计过程中需要着重考虑的一些关键要素,如:车间布局、种子制备、发酵罐、接种方式、补料、压缩空气系统及排气系统等分别进行了阐述和分析.总结出原料药发酵车间的一般特点,用于工程设计参考.

  19. 茯苓药物成分提取分离及其药用价值研究进展%A Review on Separation and Medicinal Value of Active Pharmaceutical Ingredients from Poria cocos

    刘惠知; 吴胜莲; 张德元; 詹少军; 邵晨霞; 谭明辉

    2015-01-01

    茯苓(Poria cocos)是一类寄生在松树根上的多孔菌科真菌.茯苓作为传统的食(药)用菌,在中医药领域具有重要的应用价值,茯苓的主要药物成分为茯苓多糖和茯苓三萜类物质.对茯苓多糖和茯苓三萜类物质的提取分离,及其抗肿瘤作用、免疫调节功能、抗炎症作用、对泌尿系统的保护作用进行了综述,为茯苓的药理学研究以及应用提供参考.

  20. HPLC法测定复方愈酚麻黄糖浆中四种成分的含量%Quantitative Determination of Four Active Pharmaceutical Ingredients in Compound Guaifenensin Diclofenac and Ephedrine Syrup by HPLC

    冯国

    2014-01-01

    目的 建立测定复方愈酚麻黄糖浆中盐酸麻黄碱、愈创甘油醚、马来酸氯苯那敏、双氯芬酸含量的HPLC方法.方法 采用Insteril ODS-3 C18色谱柱,梯度洗脱,流速:1.0 mL·min-1,柱温:30℃,检测波长:257 nm.结果 盐酸麻黄碱、愈创甘油醚、马来酸氯苯那敏、双氯芬酸分别在0.4018~6.4287 μg(r=0.9999)、3.1836~50.9379 μg(r=0.9999)、0.1610~2.5762 μg(r=1.0000)、0.1485~2.3759 μg (r=0.9999)范围内线性关系良好,平均回收率分别为99.58% (RSD=0.39%)、99.58%(RSD=0.30%)、99.36% (RSD=0.29%)、99.40% (RSD=0.46%)(n=9).结论 本方法经方法学验证可用于复方愈酚麻黄糖浆中盐酸麻黄碱、愈创甘油醚、马来酸氯苯那敏、双氯芬酸的含量检测.