Science.gov

Sample records for active pharmaceutical ingredient

  1. Active Pharmaceutical Ingredients and Aquatic Organisms

    EPA Science Inventory

    The presence of active pharmaceuticals ingredients (APIs) in aquatic systems in recent years has led to a burgeoning literature examining environmental occurrence, fate, effects, risk assessment, and treatability of these compounds. Although APIs have received much attention as ...

  2. Ionic liquids as active pharmaceutical ingredients.

    PubMed

    Ferraz, Ricardo; Branco, Luís C; Prudêncio, Cristina; Noronha, João Paulo; Petrovski, Zeljko

    2011-06-06

    Ionic liquids (ILs) are ionic compounds that possess a melting temperature below 100 °C. Their physical and chemical properties are attractive for various applications. Several organic materials that are now classified as ionic liquids were described as far back as the mid-19th century. The search for new and different ILs has led to the progressive development and application of three generations of ILs: 1) The focus of the first generation was mainly on their unique intrinsic physical and chemical properties, such as density, viscosity, conductivity, solubility, and high thermal and chemical stability. 2) The second generation of ILs offered the potential to tune some of these physical and chemical properties, allowing the formation of "task-specific ionic liquids" which can have application as lubricants, energetic materials (in the case of selective separation and extraction processes), and as more environmentally friendly (greener) reaction solvents, among others. 3) The third and most recent generation of ILs involve active pharmaceutical ingredients (API), which are being used to produce ILs with biological activity. Herein we summarize recent developments in the area of third-generation ionic liquids that are being used as APIs, with a particular focus on efforts to overcome current hurdles encountered by APIs. We also offer some innovative solutions in new medical treatment and delivery options.

  3. Triboelectrification of active pharmaceutical ingredients: week acids and their salts.

    PubMed

    Fujinuma, Kenta; Ishii, Yuji; Yashihashi, Yasuo; Yonemochi, Estuo; Sugano, Kiyohiko; Tarada, Katsuhide

    2015-09-30

    The effect of salt formulation on the electrostatic property of active pharmaceutical ingredients was investigated. The electrostatic property of weak acids (carboxylic acids and amide-enole type acid) and their sodium salts was evaluated by a suction-type Faraday cage meter. Free carboxylic acids showed negative chargeability, whereas their sodium salts showed more positive chargeability than the free acids. However, no such trend was observed for amide-enole type acids.

  4. Heavy metals testing in active pharmaceutical ingredients: an alternate approach.

    PubMed

    Raghuram, P; Soma Raju, I V; Sriramulu, J

    2010-01-01

    The principle of the pharmacopoeial heavy metals test is detection and estimation of the metallic impurities colored by sulfide ion by comparison against lead standard. The test suffers from a loss of analytes upon ashing and from having varied responses for various metals. An inductively coupled plasma-optical emission spectroscopy (ICP-OES) for estimating 23 metals in active pharmaceutical ingredients is being proposed. The method covers the metals listed in USP, Ph. Eur and EMEA guidance on "Residues of Metal Catalysts or Metal Reagents".

  5. Source characterization of nervous system active pharmaceutical ingredients in healthcare wastewaters

    EPA Science Inventory

    Nervous system active pharmaceutical ingredients (APIs), including anti-depressants and opioids, are important clinically administered pharmaceuticals within healthcare facilities. Concentrations and mass loadings of ten nervous system APIs and three nervous system API metaboli...

  6. Impurities in Drug Products and Active Pharmaceutical Ingredients.

    PubMed

    Kątny, M; Frankowski, M

    2016-09-29

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

  7. Life cycle analysis within pharmaceutical process optimization and intensification: case study of active pharmaceutical ingredient production.

    PubMed

    Ott, Denise; Kralisch, Dana; Denčić, Ivana; Hessel, Volker; Laribi, Yosra; Perrichon, Philippe D; Berguerand, Charline; Kiwi-Minsker, Lioubov; Loeb, Patrick

    2014-12-01

    As the demand for new drugs is rising, the pharmaceutical industry faces the quest of shortening development time, and thus, reducing the time to market. Environmental aspects typically still play a minor role within the early phase of process development. Nevertheless, it is highly promising to rethink, redesign, and optimize process strategies as early as possible in active pharmaceutical ingredient (API) process development, rather than later at the stage of already established processes. The study presented herein deals with a holistic life-cycle-based process optimization and intensification of a pharmaceutical production process targeting a low-volume, high-value API. Striving for process intensification by transfer from batch to continuous processing, as well as an alternative catalytic system, different process options are evaluated with regard to their environmental impact to identify bottlenecks and improvement potentials for further process development activities.

  8. Quality investigation of hydroxyprogesterone caproate active pharmaceutical ingredient and injection

    PubMed Central

    Chollet, John L.; Jozwiakowski, Michael J.

    2012-01-01

    The purpose of this study was to investigate the quality of hydroxyprogesterone caproate (HPC) active pharmaceutical ingredient (API) sources that may be used by compounding pharmacies, compared to the FDA-approved source of the API; and to investigate the quality of HPC injection samples obtained from compounding pharmacies in the US, compared to the FDA-approved product (Makena®). Samples of API were obtained from every source confirmed to be an original manufacturer of the drug for human use, which were all companies in China that were not registered with FDA. Eight of the ten API samples (80%) did not meet the impurity specifications required by FDA for the API used in the approved product. One API sample was found to not be HPC at all; additional laboratory testing showed that it was glucose. Thirty samples of HPC injection obtained from com pounding pharmacies throughout the US were also tested, and eight of these samples (27%) failed to meet the potency requirement listed in the USP monograph for HPC injection and/or the HPLC assay. Sixteen of the thirty injection samples (53%) exceeded the impurity limit setforthe FDA-approved drug product. These results confirm the inconsistency of compounded HPC Injections and suggest that the risk-benefit ratio of using an unapproved compounded preparation, when an FDA-approved drug product is available, is not favorable. PMID:22329865

  9. Effects of active pharmaceutical ingredients mixtures in mussel Mytilus galloprovincialis.

    PubMed

    Gonzalez-Rey, M; Mattos, J J; Piazza, C E; Bainy, A C D; Bebianno, M J

    2014-08-01

    Active pharmaceutical ingredients (APIs) are emergent environmental contaminants widely detected in surface waters as result of incomplete waste water treatment plant (WWTP) removal processes and improper disposal. The assessment of potential effects of APIs on non-target organisms is still scarce since besides presenting multiple chemical structures, properties and modes of action, these compounds occur as complex mixtures. This study comprises a 15-day exposure of mussels Mytilus galloprovincialis to mixtures (at environmentally relevant nominal concentrations) of non-steroidal inflammatory drugs ibuprofen (IBU) and diclofenac (DCF) (250 ng L(-1) each) and selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLX) (75 ng L(-1)) (MIX 1) along with the addition of classical pro-oxidant copper (Cu) (5 μg L(-1)) (MIX 2). The goals included the assessment of oxidative stress, neurotoxic and endocrine effects on this sentinel species applying both a multibiomarker and gene expression (here and later gene expression is taken as synonym to gene transcription, although it is acknowledged that it is also affected by, e.g. translation, and mRNA and protein stability) analysis approaches. The results revealed a swifter antioxidant response in digestive glands than in gills induced by MIX 1, nevertheless the presence of Cu in MIX 2 promoted a higher lipid peroxidation (LPO) induction. Neither mixture altered acetylcholinesterase (AChE) activity, while both triggered the formation of vitellogenin-like proteins in females confirming the xenoestrogenic effect of mixtures. All these results varied with respect to those obtained in previous single exposure essays. Moreover, RT-PCR analysis revealed a catalase (CAT) and CYP4Y1 gene expression down- and upregulation, respectively, with no significant changes in mRNA levels of genes encoding superoxide dismutase (SOD) and glutathione-S-transferase (GST). Finally, this study highlights variable tissue and time-specific biomarker

  10. Potential Use of Cyclodextrins as Drug Carriers and Active Pharmaceutical Ingredients.

    PubMed

    Arima, Hidetoshi; Motoyama, Keiichi; Higashi, Taishi

    2017-01-01

    Cyclodextrins (CyDs) are extensively used in various fields, and especially have been widely utilized as pharmaceutical excipients and drug carriers in the pharmaceutical field. Owing to the multi-functional and biocompatible characteristics, CyDs can improve the undesirable properties of drug molecules. This review outlines the current application of CyDs in pharmaceutical formulations, focusing on their use as CyD-based drug carriers for several kinds of drugs. Additionally, CyDs have great potential as active pharmaceutical ingredients against various diseases with few side effects.

  11. 78 FR 3900 - Generic Drug User Fee-Active Pharmaceutical Ingredient and Finished Dosage Form Facility Fee...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-17

    ... HUMAN SERVICES Food and Drug Administration Generic Drug User Fee--Active Pharmaceutical Ingredient and... drug active pharmaceutical ingredient (API) and finished dosage form (FDF) facilities user fees for... applications in the backlog as of October 1, 2012, on finished dosage form (FDF) and active...

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

    PubMed Central

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

    2015-01-01

    Introduction Fixed-dose combinations (FDC) contain two or more active ingredients. The effective patent and exclusivity life of FDC compared to single active ingredient has not been assessed. Objectives Trends in FDA approved FDC in the period 1980–2012 and time lag between approval of FDC and single active ingredients in the combination were assessed, and the effective patent and exclusivity life of FDC was compared with their single active ingredients. Materials and Methods New molecular entities (NMEs), new therapeutic biologics license applications (BLAs) and FDC data were collected from the FDA Orange Book and Drugs@FDA. Analysis included FDC containing one or more NMEs or BLAs at first FDA approval (NMEs-FDC) and only already marketed drugs (Non-NMEs-FDC). Descriptive, Kruskal-Wallis and Wilcoxon Rank Sum analyses were performed. Results During the study period, the FDA approved 28 NMEs-FDC (3.5% of NMEs) and 117 non-NMEs-FDC. FDC approvals increased from 12 in the 1980s to 59 in the 2000s. Non-NMEs-FDC entered the market at a median of 5.43 years (interquartile range 1.74, 10.31) after first FDA approval of single active ingredients in the combination. The Non-NMEs-FDC entered the market at a median of 2.33 years (-7.55, 2.39) before approval of generic single active ingredient. Non-NME-FDC added a median of 9.70 (2.75, 16.24) years to the patent and exclusivity life of the single active ingredients in the combination. Conclusion FDC approvals significantly increased over the last twenty years. Pharmaceutical companies market FDC drugs shortly before the generic versions of the single ingredients enter the market extending the patent and exclusivity life of drugs included in the combination. PMID:26469277

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

    PubMed

    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.

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

    PubMed

    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.

  15. Peculiar surface behavior of some ionic liquids based on active pharmaceutical ingredients.

    PubMed

    Restolho, José; Mata, José Luis; Saramago, Benilde

    2011-02-21

    The ionic liquids based on biologically active cations and anions, commonly designated by ionic liquids based on active pharmaceutical ingredients (ILs-APIs), are interesting compounds for use in pharmaceutical applications. Lidocaine docusate, ranitidine docusate, and didecyldimethylammonium ibuprofen are examples of promising ILs-APIs that were recently synthesized. They were submitted to biological testing and calorimetric measurements, but nothing is known about their surface properties. In this work, we measured the surface tension and the contact angles on both hydrophilic and hydrophobic surfaces in a temperature range as wide as possible. Based on the wettability data, the polarity fractions were estimated using the Fowkes theory. The peculiar surface behavior observed was tentatively attributed to the presence of mesophases.

  16. Continuous Processing of Active Pharmaceutical Ingredients Suspensions via Dynamic Cross-Flow Filtration.

    PubMed

    Gursch, Johannes; Hohl, Roland; Toschkoff, Gregor; Dujmovic, Diana; Brozio, Jörg; Krumme, Markus; Rasenack, Norbert; Khinast, Johannes

    2015-10-01

    Over the last years, continuous manufacturing has created significant interest in the pharmaceutical industry. Continuous filtration at low flow rates and high solid loadings poses, however, a significant challenge. A commercially available, continuously operating, dynamic cross-flow filtration device (CFF) is tested and characterized. It is shown that the CFF is a highly suitable technology for continuous filtration. For all tested model active pharmaceutical ingredients, a material-specific strictly linear relationship between feed and permeate rate is identified. Moreover, for each tested substance, a constant concentration factor is reached. A one-parameter model based on a linear equation is suitable to fully describe the CFF filtration performance. This rather unexpected finding and the concentration polarization layer buildup is analyzed and a basic model to describe the observed filtration behavior is developed.

  17. Improving sensitivity in chiral supercritical fluid chromatography for analysis of active pharmaceutical ingredients.

    PubMed

    Helmy, Roy; Biba, Mirlinda; Zang, Jia; Mao, Bing; Fogelman, Kimber; Vlachos, Vaso; Hosek, Paul; Welch, Christopher J

    2007-11-01

    Despite its status as the preferred method for routine enantiopurity analysis in pharmaceutical research, supercritical fluid chromatography (SFC) has historically been unsuited for the accurate and precise measurements required for release testing of active pharmaceutical ingredients (APIs) under current good manufacturing processes (cGMPs). Insufficient signal to noise, as compared to HPLC, has heretofore been the major limitation of the chiral SFC approach. We herein describe an investigation into the fundamental limitations and sources of noise in the SFC approach, identifying thermal, electronic, and mechanical sources of noise within the flow cell as key parameters contributing to reduced sensitivity. A variety of instrument modifications are explored, ultimately leading to the development of a new and improved flow cell and other instrument modifications that allow suitable sensitivity and accuracy to carry out GMP release testing for enantiopurity analysis using SFC.

  18. Trends in active pharmaceutical ingredient salt selection based on analysis of the Orange Book database.

    PubMed

    Paulekuhn, G Steffen; Dressman, Jennifer B; Saal, Christoph

    2007-12-27

    The Orange Book database published by the U.S. Drug and Food Administration (FDA) was analyzed for the frequency of occurrence of different counterions used for the formation of pharmaceutical salts. The data obtained from the present analysis of the Orange Book are compared to reviews of the Cambridge Structural Database (CSD) and of the Martindale "The Extra Pharmacopoeia". As well as showing overall distributions of counterion usage, results are broken down into 5-year increments to identify trends in counterion selection. Chloride ions continue to be the most frequently utilized anionic counterions for the formation of salts as active pharmaceutical ingredients (APIs), while sodium ions are most widely utilized for the formation of salts starting from acidic molecules. A strong trend toward a wider variety of counterions over the past decade is observed. This trend can be explained by a stronger need to improve physical chemical properties of research and development compounds.

  19. Co-Crystals: A Novel Approach to Modify Physicochemical Properties of Active Pharmaceutical Ingredients

    PubMed Central

    Yadav, A. V.; Shete, A. S.; Dabke, A. P.; Kulkarni, P. V.; Sakhare, S. S.

    2009-01-01

    Crystal form can be crucial to the performance of a dosage form. This is especially true for compounds that have intrinsic barriers to drug delivery, such as low aqueous solubility, slow dissolution in gastrointestinal media, low permeability and first-pass metabolism. The nature of the physical form and formulation tends to exhibit the greatest effect on bioavailability parameters of water insoluble compounds that need to be given orally in high doses. An alternative approach available for the enhancement of drug solubility, dissolution and bioavailability is through the application of crystal engineering of co-crystals. The physicochemical properties of the active pharmaceutical ingredients and the bulk material properties can be modified, whilst maintaining the intrinsic activity of the drug molecule. This article covers the advantages of co-crystals over salts, solvates (hydrates), solid dispersions and polymorphs, mechanism of formation of co-crystals, methods of preparation of co-crystals and application of co-crystals to modify physicochemical characteristics of active pharmaceutical ingredients along with the case studies. The intellectual property implications of creating co-crystals are also highly relevant. PMID:20502540

  20. Electrochemical flow injection analysis of hydrazine in an excess of an active pharmaceutical ingredient: achieving pharmaceutical detection limits electrochemically.

    PubMed

    Channon, Robert B; Joseph, Maxim B; Bitziou, Eleni; Bristow, Anthony W T; Ray, Andrew D; Macpherson, Julie V

    2015-10-06

    The quantification of genotoxic impurities (GIs) such as hydrazine (HZ) is of critical importance in the pharmaceutical industry in order to uphold drug safety. HZ is a particularly intractable GI and its detection represents a significant technical challenge. Here, we present, for the first time, the use of electrochemical analysis to achieve the required detection limits by the pharmaceutical industry for the detection of HZ in the presence of a large excess of a common active pharmaceutical ingredient (API), acetaminophen (ACM) which itself is redox active, typical of many APIs. A flow injection analysis approach with electrochemical detection (FIA-EC) is utilized, in conjunction with a coplanar boron doped diamond (BDD) microband electrode, insulated in an insulating diamond platform for durability and integrated into a two piece flow cell. In order to separate the electrochemical signature for HZ such that it is not obscured by that of the ACM (present in excess), the BDD electrode is functionalized with Pt nanoparticles (NPs) to significantly shift the half wave potential for HZ oxidation to less positive potentials. Microstereolithography was used to fabricate flow cells with defined hydrodynamics which minimize dispersion of the analyte and optimize detection sensitivity. Importantly, the Pt NPs were shown to be stable under flow, and a limit of detection of 64.5 nM or 0.274 ppm for HZ with respect to the ACM, present in excess, was achieved. This represents the first electrochemical approach which surpasses the required detection limits set by the pharmaceutical industry for HZ detection in the presence of an API and paves the wave for online analysis and application to other GI and API systems.

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

    PubMed

    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.

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

    PubMed

    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.

  3. Charge density and optical properties of multicomponent crystals containing active pharmaceutical ingredients or their analogues.

    PubMed

    Gryl, Marlena

    2015-08-01

    Active pharmaceutical ingredients (APIs), through their favourable donor/acceptor spatial distribution and synthon formation flexibility, are attractive building blocks in modern materials crystallography. The optical properties of a crystal strongly depend on two factors, i.e. the spatial distribution of molecules in the crystal structure and the electronic properties of molecular building blocks (dipole moments, polarizabilities, hyperpolarizabilities). Although the latter are easy to predict through ab initio calculations, the former are not. Only a combination of experimental and theoretical charge density studies together with prediction and measurement of optical properties enable full analysis of the obtained functional material in terms of its usefulness in practical applications. This article presents design strategies of optical materials based on selected pharmaceutical molecules. Factors that contribute to molecular recognition in the four selected polar/chiral crystal phases (derived through charge density and Hirshfeld surfaces analysis) have been determined. Theoretically predicted optical properties of the molecular/ionic building blocks as well as bulk effects have been confirmed experimentally. This research is a first step in the design of novel optical materials based on push-pull molecules and APIs.

  4. Evaluation of the state of active ingredients in pharmaceutical preparations using fourier transform-Raman difference spectra.

    PubMed

    Mifune, Masaki; Iwasaki, Toshinobu; Kozaki, Yukari; Tsukamoto, Ikuko; Saito, Madoka; Kitamura, Youji; Yamaguchi, Toshikazu; Saito, Yutaka

    2006-12-01

    To examine the pharmaceutical application of Fourier transform (FT)-Raman spectroscopy, the state of active pharmaceutical ingredients (APIs) in a preparation of several forms was evaluated by investigating the Raman difference spectra between the preparation and excipient. The difference spectra indicated that APIs in alacepril tablets, caffeine sustained-release granules, and quinidine sulfate granules remained unchanged after the manufacturing process. However, the state of sparfloxacin in nanoparticles changed, although it remained unchanged in tablets or powders. These results show that the FT-Raman difference spectrum is expected to be utilized in the field of quality control of crystalline pharmaceutical preparations.

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

    PubMed

    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.

  6. Polymorph characterization of active pharmaceutical ingredients (APIs) using low-frequency Raman spectroscopy.

    PubMed

    Larkin, Peter J; Dabros, Marta; Sarsfield, Beth; Chan, Eric; Carriere, James T; Smith, Brian C

    2014-01-01

    Polymorph detection, identification, and quantitation in crystalline materials are of great importance to the pharmaceutical industry. Vibrational spectroscopic techniques used for this purpose include Fourier transform mid-infrared (FT-MIR) spectroscopy, Fourier transform near-infrared (FT-NIR) spectroscopy, Raman spectroscopy, and terahertz (THz) and far-infrared (FIR) spectroscopy. Typically, the fundamental molecular vibrations accessed using high-frequency Raman and MIR spectroscopy or the overtone and combination of bands in the NIR spectra are used to monitor the solid-state forms of active pharmaceutical ingredients (APIs). The local environmental sensitivity of the fundamental molecular vibrations provides an indirect probe of the long-range order in molecular crystals. However, low-frequency vibrational spectroscopy provides access to the lattice vibrations of molecular crystals and, hence, has the potential to more directly probe intermolecular interactions in the solid state. Recent advances in filter technology enable high-quality, low-frequency Raman spectra to be acquired using a single-stage spectrograph. This innovation enables the cost-effective collection of high-quality Raman spectra in the 200-10 cm(-1) region. In this study, we demonstrate the potential of low-frequency Raman spectroscopy for the polymorphic characterization of APIs. This approach provides several benefits over existing techniques, including ease of sampling and more intense, information-rich band structures that can potentially discriminate among crystalline forms. An improved understanding of the relationship between the crystalline structure and the low-frequency vibrational spectrum is needed for the more widespread use of the technique.

  7. Core-shell column Tanaka characterization and additional tests using active pharmaceutical ingredients.

    PubMed

    Ludvigsson, Jufang Wu; Karlsson, Anders; Kjellberg, Viktor

    2016-12-01

    In the last decade, core-shell particles have gained more and more attention in fast liquid chromatography separations due to their comparable performance with fully porous sub-2 μm particles and their significantly lower back pressure. Core-shell particles are made of a solid core surrounded by a shell of classic fully porous material. To embrace the developed core-shell column market and use these columns in pharmaceutical analytical applications, 17 core-shell C18 columns purchased from various vendors with various dimensions (50 mm × 2.1 mm to 100 mm × 3 mm) and particle sizes (1.6-2.7 μm) were characterized using Tanaka test protocols. Furthermore, four selected active pharmaceutical ingredients were chosen as test probes to investigate the batch to batch reproducibility for core-shell columns of particle size 2.6-2.7 μm, with dimension of 100 × 3 mm and columns of particle size 1.6 μm, with dimension 100 × 2.1 mm under isocratic elution. Columns of particle size 2.6-2.7 μm were also tested under gradient elution conditions. To confirm the claimed comparable efficiency of 2.6 μm core-shell particles as sub-2 μm fully porous particles, column performances of the selected core-shell columns were compared with BEH C18 , 1.7 μm, a fully porous column material as well.

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

    NASA Astrophysics Data System (ADS)

    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.

  9. Approaches to the Development of Human Health Toxicity Values for Active Pharmaceutical Ingredients in the Environment.

    PubMed

    Sorell, Tamara L

    2016-01-01

    Management of active pharmaceutical ingredients (API) in the environment is challenging because these substances represent a large and diverse group of compounds. Advanced wastewater treatment technologies that can remove API tend to be costly. Because of the potential resources required to address API in the environment, there is a need to establish environmental benchmarks that can serve as targets for treatment and release. To date, there are several different approaches that have been taken to derive human health toxicity values for API. These methods include traditional risk assessment approaches that calculate "safe" doses using experimental data and uncertainty (safety) factors; point of departure (POD), which starts from a therapeutic human dose and applies uncertainty factors; and threshold of toxicological concern (TTC), a generic approach that establishes threshold values across broad classes of chemicals based on chemical structure. To evaluate the use of these approaches, each of these methods was applied to three API commonly encountered in the environment: acetaminophen, caffeine, and chlorpromazine. The results indicate that the various methods of estimating toxicity values produce highly varying doses. Associated doses are well below typical intakes, or toxicity thresholds cannot be derived due to a lack of information. No uniform approach can be applied to establishing thresholds for multiple substances. Rather, an individualized approach will need to be applied to each target API.

  10. Active Pharmaceutical Ingredients: Prediction of Physical-Chemical Properties from First Principles

    NASA Astrophysics Data System (ADS)

    Valenzano, Loredana

    2013-03-01

    Polymorphism in active pharmaceutical ingredients (APIs) plays a crucial role both for medical and intellectual property concerns but despite ongoing efforts, experimental and computational investigations of the existence and the physical-chemical properties of the same compound in different forms is still an open question.While comparison between computed and experimental values for properties derived from differences between states is often promising (such as bulk modulus), results are disappointing for absolute values (such as density). Quantum mechanical computational methods describe the systems at 0K, experimentally properties are often evaluated at room temperature. Therefore it is not surprising that results determined from first principles dramatically differ from those obtained experimentally. By applying a quantum mechanical periodic approach that takes into account long range London dispersion forces fitted for solid materials, and by imposing different cell volumes corresponding to different thermodynamic conditions, we show how results from calculations at 0K (structures, vibrational spectra, elastic constants) may be compared to experimental values at higher temperatures, helping to foster a stronger linkage between computational and experimental work on systems such as APIs. Where experimental results are not available, our work represents an innovative approach in addressing the properties of APIs. Our results can also serve as foundation for the developing of new force fields to be adopted within a multi-scale computational approach.

  11. Prioritization methodology for the monitoring of active pharmaceutical ingredients in hospital effluents.

    PubMed

    Daouk, Silwan; Chèvre, Nathalie; Vernaz, Nathalie; Bonnabry, Pascal; Dayer, Pierre; Daali, Youssef; Fleury-Souverain, Sandrine

    2015-09-01

    The important number of active pharmaceutical ingredients (API) available on the market along with their potential adverse effects in the aquatic ecosystems, lead to the development of prioritization methods, which allow choosing priority molecules to monitor based on a set of selected criteria. Due to the large volumes of API used in hospitals, an increasing attention has been recently paid to their effluents as a source of environmental pollution. Based on the consumption data of a Swiss university hospital, about hundred of API has been prioritized following an OPBT approach (Occurrence, Persistence, Bioaccumulation and Toxicity). In addition, an Environmental Risk Assessment (ERA) allowed prioritizing API based on predicted concentrations and environmental toxicity data found in the literature for 71 compounds. Both prioritization approaches were compared. OPBT prioritization results highlight the high concern of some non steroidal anti-inflammatory drugs and antiviral drugs, whereas antibiotics are revealed by ERA as potentially problematic to the aquatic ecosystems. Nevertheless, according to the predicted risk quotient, only the hospital fraction of ciprofloxacin represents a risk to the aquatic organisms. Some compounds were highlighted as high-priority with both methods: ibuprofen, trimethoprim, sulfamethoxazole, ritonavir, gabapentin, amoxicillin, ciprofloxacin, raltegravir, propofol, etc. Analyzing consumption data and building prioritization lists helped choosing about 15 API to be monitored in hospital wastewaters. The API ranking approach adopted in this study can be easily transposed to any other hospitals, which have the will to look at the contamination of their effluents.

  12. Microwave-assisted extraction of active pharmaceutical ingredient from solid dosage forms.

    PubMed

    Hoang, T H; Sharma, R; Susanto, D; Di Maso, M; Kwong, E

    2007-07-13

    The microwave assisted extraction (MAE) technique has been evaluated for the extraction of active pharmaceutical ingredients (API) from various solid dosage forms. Using immediate release tablets of Compound A as a model, optimization of the extraction method with regards to extraction solvent composition, extraction time and temperature was briefly discussed. Complete recovery of Compound A was achieved when samples were extracted using acetonitrile as the extraction solvent under microwave heating at a constant cell temperature of 50 degrees C for 5 min. The optimized MAE method was applied for content uniformity (single tablet extraction) and potency (multiple tablets extraction) assays of release and stability samples of two products of Compound A (5 and 25mg dose strength) stored at various conditions. To further demonstrate the applicability of MAE, the instrumental extraction conditions (50 degrees C for 5 min) were adopted for the extraction of montelukast sodium (Singulair) from various solid dosage forms using methanol-water (75:25, v/v) as the extraction solvent. The MAE procedure demonstrated an extraction efficiency of 97.4-101.9% label claim with the greatest RSD at 1.4%. The results compare favorably with 97.6-102.3% label claim with the greatest RSD at 2.9% obtained with validated mechanical extraction procedures. The system is affordable, user-friendly and simple to operate and troubleshoot. Rapid extraction process (7 min/run) along with high throughput capacity (up to 23 samples simultaneously) would lead to reduced cycle time and thus increased productivity.

  13. Challenges in the analytical method development and validation for an unstable active pharmaceutical ingredient.

    PubMed

    Sajonz, Peter; Wu, Yan; Natishan, Theresa K; McGachy, Neil T; Detora, David

    2006-03-01

    A sensitive high-performance liquid chromatography (HPLC) impurity profile method for the antibiotic ertapenem is developed and subsequently validated. The method utilizes an Inertsil phenyl column at ambient temperature, gradient elution with aqueous sodium phosphate buffer at pH 8, and acetonitrile as the mobile phase. The linearity, method precision, method ruggedness, limit of quantitation, and limit of detection of the impurity profile HPLC method are found to be satisfactory. The method is determined to be specific, as judged by resolving ertapenem from in-process impurities in crude samples and degradation products that arise from solid state thermal and light stress, acid, base, and oxidative stressed solutions. In addition, evidence is obtained by photodiode array detection studies that no degradate or impurity having a different UV spectrum coeluted with the major component in stressed or unstressed samples. The challenges during the development and validation of the method are discussed. The difficulties of analyzing an unstable active pharmaceutical ingredient (API) are addressed. Several major impurities/degradates of the API have very different UV response factors from the API. These impurities/degradates are synthesized or prepared by controlled degradation and the relative response factors are determined.

  14. Quantification of active pharmaceutical ingredient and impurities in sildenafil citrate obtained from the Internet

    PubMed Central

    Nutan, Mohammad T.; Dodla, Uday Krishna Reddy

    2014-01-01

    Background: The accessibility of prescription drugs produced outside of the United States, most notably sildenafil citrate (innovator product, Viagra®), has been made much easier by the Internet. Of greatest concern to clinicians and policymakers is product quality and patient safety. The US Food and Drug Administration (FDA) has issued warnings to potential buyers that the safety of drugs purchased from the Internet cannot be guaranteed, and may present a health risk to consumers from substandard products. Objective: The objective of this study was to determine whether generic sildenafil citrate tablets from international markets obtained via the Internet are equivalent to the US innovator product regarding major aspects of pharmaceutical quality: potency, accuracy of labeling, and presence and level of impurities. This will help identify aspects of drug quality that may impact public health risks. Methods: A total of 15 sildenafil citrate tablets were obtained for pharmaceutical analysis: 14 generic samples from international Internet pharmacy websites and the US innovator product. According to US Pharmacopeial guidelines, tablet samples were tested using high-performance liquid chromatography for potency of active pharmaceutical ingredient (API) and levels of impurities (impurities A, B, C, and D). Impurity levels were compared with International Conference on Harmonisation (ICH) limits. Results: Among the 15 samples, 4 samples possessed higher impurity B levels than the ICH qualification threshold, 8 samples possessed higher impurity C levels than the ICH qualification threshold, and 4 samples possessed more than 1% impurity quantity of maximum daily dose (MDD). For API, 6 of the samples failed to fall within the 5% assay limit. Conclusions: Quality assurance tests are often used to detect formulation defects of drug products during the manufacturing and/or storage process. Results suggest that manufacturing standards for sildenafil citrate generic drug

  15. 35Cl dynamic nuclear polarization solid-state NMR of active pharmaceutical ingredients

    SciTech Connect

    Hirsh, David A.; Rossini, Aaron J.; Emsley, Lyndon; Schurko, Robert W.

    2016-08-24

    In this paper, we show how to obtain efficient dynamic nuclear polarization (DNP) enhanced 35Cl solid-state NMR (SSNMR) spectra at 9.4 T and demonstrate how they can be used to characterize the molecular-level structure of hydrochloride salts of active pharmaceutical ingredients (APIs) in both bulk and low wt% API dosage forms. 35Cl SSNMR central-transition powder patterns of chloride ions are typically tens to hundreds of kHz in breadth, and most cannot be excited uniformly with high-power rectangular pulses or acquired under conditions of magic-angle spinning (MAS). Herein, we demonstrate the combination of DNP and 1H–35Cl broadband adiabatic inversion cross polarization (BRAIN-CP) experiments for the acquisition of high quality wideline spectra of APIs under static sample conditions, and obtain signals up to 50 times greater than in spectra acquired without the use of DNP at 100 K. We report a new protocol, called spinning-on spinning-off (SOSO) acquisition, where MAS is applied during part of the polarization delay to increase the DNP enhancements and then the MAS rotation is stopped so that a wideline 35Cl NMR powder pattern free from the effects of spinning sidebands can be acquired under static conditions. This method provides an additional two-fold signal enhancement compared to DNP-enhanced SSNMR spectra acquired under purely static conditions. DNP-enhanced 35Cl experiments are used to characterize APIs in bulk and dosage forms with Cl contents as low as 0.45 wt%. These results are compared to DNP-enhanced 1H–13C CP/MAS spectra of APIs in dosage forms, which are often hindered by interfering signals arising from the binders, fillers and other excipient materials.

  16. Dissolution study of active pharmaceutical ingredients using molecular dynamics simulations with classical force fields

    NASA Astrophysics Data System (ADS)

    Greiner, Maximilian; Elts, Ekaterina; Schneider, Julian; Reuter, Karsten; Briesen, Heiko

    2014-11-01

    The CHARMM, general Amber and OPLS force fields are evaluated for their suitability in simulating the molecular dynamics of the dissolution of the hydrophobic, small-molecule active pharmaceutical ingredients aspirin, ibuprofen, and paracetamol in aqueous media. The force fields are evaluated by comparison with quantum chemical simulations or experimental references on the basis of the following capabilities: accurately representing intra- and intermolecular interactions, appropriately reproducing crystal lattice parameters, adequately describing thermodynamic properties, and the qualitative description of the dissolution behavior. To make this approach easily accessible for evaluating the dissolution properties of novel drug candidates in the early stage of drug development, the force field parameter files are generated using online resources such as the SWISS PARAM servers, and the software packages ACPYPE and Maestro. All force fields are found to reproduce the intermolecular interactions with a reasonable degree of accuracy, with the general Amber and CHARMM force fields showing the best agreement with quantum mechanical calculations. A stable crystal bulk structure is obtained for all model substances, except for ibuprofen, where the reproductions of the lattice parameters and observed crystal stability are considerably poor for all force fields. The heat of solution used to evaluate the solid-to-solution phase transitions is found to be in qualitative agreement with the experimental data for all combinations tested, with the results being quantitatively optimum for the general Amber and CHARMM force fields. For aspirin and paracetamol, stable crystal-water interfaces were obtained. The (100), (110), (011) and (001) interfaces of aspirin or paracetamol and water were simulated for each force field for 30 ns. Although generally expected as a rare event, in some of the simulations, dissolution is observed at 310 K and ambient pressure conditions.

  17. A comparison between pure active pharmaceutical ingredients and therapeutic deep eutectic solvents: Solubility and permeability studies.

    PubMed

    Duarte, Ana Rita C; Ferreira, Ana Sofia D; Barreiros, Susana; Cabrita, Eurico; Reis, Rui L; Paiva, Alexandre

    2017-05-01

    THEDES, so called therapeutic deep eutectic solvents are here defined as a mixture of two components, which at a particular molar composition become liquid at room temperature and in which one of them is an active pharmaceutical ingredient (API). In this work, THEDES based on menthol complexed with three different APIs, ibuprofen (ibu), BA (BA) and phenylacetic acid (PA), were prepared. The interactions between the components that constitute the THEDES were studied by NMR, confirming that the eutectic system is formed by H-bonds between menthol and the API. The mobility of the THEDES components was studied by PFGSE NMR spectroscopy. It was determined that the self-diffusion of the species followed the same behavior as observed previously for ionic liquids, in which the components migrate via jumping between voids in the suprastructure created by punctual thermal fluctuations. The solubility and permeability of the systems in an isotonic solution was evaluated and a comparison with the pure APIs was established through diffusion and permeability studies carried out in a Franz cell. The solubility of the APIs when in the THEDES system can be improved up to 12 fold, namely for the system containing ibu. Furthermore, for this system the permeability was calculated to be 14×10(-5)cm/s representing a 3 fold increase in comparison with the pure API. With the exception of the systems containing PA an increase in the solubility, coupled with an increase in permeability was observed. In this work, we hence demonstrate the efficiency of THEDES as a new formulation for the enhancement of the bioavailability of APIs by changing the physical state of the molecules from a solid dosage to a liquid system.

  18. 35Cl dynamic nuclear polarization solid-state NMR of active pharmaceutical ingredients

    DOE PAGES

    Hirsh, David A.; Rossini, Aaron J.; Emsley, Lyndon; ...

    2016-08-24

    In this paper, we show how to obtain efficient dynamic nuclear polarization (DNP) enhanced 35Cl solid-state NMR (SSNMR) spectra at 9.4 T and demonstrate how they can be used to characterize the molecular-level structure of hydrochloride salts of active pharmaceutical ingredients (APIs) in both bulk and low wt% API dosage forms. 35Cl SSNMR central-transition powder patterns of chloride ions are typically tens to hundreds of kHz in breadth, and most cannot be excited uniformly with high-power rectangular pulses or acquired under conditions of magic-angle spinning (MAS). Herein, we demonstrate the combination of DNP and 1H–35Cl broadband adiabatic inversion cross polarizationmore » (BRAIN-CP) experiments for the acquisition of high quality wideline spectra of APIs under static sample conditions, and obtain signals up to 50 times greater than in spectra acquired without the use of DNP at 100 K. We report a new protocol, called spinning-on spinning-off (SOSO) acquisition, where MAS is applied during part of the polarization delay to increase the DNP enhancements and then the MAS rotation is stopped so that a wideline 35Cl NMR powder pattern free from the effects of spinning sidebands can be acquired under static conditions. This method provides an additional two-fold signal enhancement compared to DNP-enhanced SSNMR spectra acquired under purely static conditions. DNP-enhanced 35Cl experiments are used to characterize APIs in bulk and dosage forms with Cl contents as low as 0.45 wt%. These results are compared to DNP-enhanced 1H–13C CP/MAS spectra of APIs in dosage forms, which are often hindered by interfering signals arising from the binders, fillers and other excipient materials.« less

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

    PubMed Central

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

    2015-01-01

    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

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

    PubMed

    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

  1. Evaluation of effects of pharmaceutical processing on structural disorders of active pharmaceutical ingredient crystals using nanoindentation and high-resolution total scattering pair distribution function analysis.

    PubMed

    Chen, Shuang; Sheikh, Ahmad Y; Ho, Raimundo

    2014-12-01

    Pharmaceutical unit operations such as milling and compaction can often generate disordered regions in crystals of active pharmaceutical ingredients (APIs). This may lead to changes in a number of important pharmaceutical properties including dissolution, stability, hygroscopicity, and so on. It is therefore important for pharmaceutical industry to evaluate the effects of pharmaceutical processing on API structural orders, and to investigate and develop analytical tools that are capable of accurately detecting and assessing subtle process-induced structural disorders in pharmaceutical crystals. In this study, nanoindentation was first used to determine the intrinsic mechanical properties including hardness and Young's modulus of two API crystals, compounds 1 and 2. These crystals of different mechanical properties were then milled and compacted under various conditions. The resulting structural disorders in these crystals were subsequently evaluated using synchrotron-based high-resolution total scattering pair distribution function (TS-PDF) analysis. Furthermore, principal component analysis was applied to the PDF data to assess the relative extents of disorders in the API crystals, which showed a good correlation with the process conditions. The study demonstrates that high-resolution TS-PDF analysis coupled with nanoindentation measurement is a valuable and effective tool for detecting and assessing process-induced subtle structural disorders in API crystals.

  2. Point of departure (PoD) selection for the derivation of acceptable daily exposures (ADEs) for active pharmaceutical ingredients (APIs).

    PubMed

    Bercu, Joel P; Morinello, Eric J; Sehner, Claudia; Shipp, Bryan K; Weideman, Patricia A

    2016-08-01

    The Acceptable Daily Exposure (ADE) derived for pharmaceutical manufacturing is a health-based limit used to ensure that medicines produced in multi-product facilities are safe and are used to validate quality processes. Core to ADE derivation is selecting appropriate point(s) of departure (PoD), i.e., the starting dose of a given dataset that is used in the calculation of the ADE. Selecting the PoD involves (1) data collection and hazard characterization, (2) identification of "critical effects", and (3) a dose-response assessment including the determination of the no-observed-adverse-effect-level (NOAEL) or lowest-observed-adverse-effect-level (LOAEL), or calculating a benchmark dose (BMD) level. Compared to other classes of chemicals, active pharmaceutical ingredients (APIs) are well-characterized and have unique, rich datasets that must be considered when selecting the PoD. Dataset considerations for an API include therapeutic/pharmacological effects, particularities of APIs for different indications and routes of administration, data gaps during drug development, and sensitive subpopulations. Thus, the PoD analysis must be performed by a qualified toxicologist or other expert who also understands the complexities of pharmaceutical datasets. In addition, as the pharmaceutical industry continues to evolve new therapeutic principles, the science behind PoD selection must also evolve to ensure state-of-the-science practices and resulting ADEs.

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

    NASA Astrophysics Data System (ADS)

    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.

  4. Spherical crystallization: A technique use to reform solubility and flow property of active pharmaceutical ingredients

    PubMed Central

    Chatterjee, Arindam; Gupta, Madan Mohan; Srivastava, Birendra

    2017-01-01

    Tablets have been choice of manufacturers over the years due to their comparatively low cost of manufacturing, packaging, shipping, and ease of administration; also have better stability and can be considered virtually tamper proof. A major challenge in formulation development of the tablets extends from lower solubility of the active agent to the elaborated manufacturing procedures for obtaining a compressible granular material. Moreover, the validation and documentation increases, as the numbers of steps increases for an industrially acceptable granulation process. Spherical crystallization (SC) is a promising technique, which encompass the crystallization, agglomeration, and spheronization phenomenon in a single step. Initially, two methods, spherical agglomeration, and emulsion solvent diffusion, were suggested to get a desired result. Later on, the introduction of modified methods such as crystallo-co-agglomeration, ammonia diffusion system, and neutralization techniques overcame the limitations of the older techniques. Under controlled conditions such as solvent composition, mixing rate and temperature, spherical dense agglomerates cluster from particles. Application of the SC technique includes production of compacted spherical particles of drug having improved uniformity in shape and size of particles, good bulk density, better flow properties as well as better solubility so SC when used on commercial scale will bring down the production costs of pharmaceutical tablet and will increase revenue for the pharmaceutical industries in the competitive market. This review summarizes the technologies available for SC and also suggests the parameters for evaluation of a viable product.

  5. Enhancing crystalline properties of a cardiovascular active pharmaceutical ingredient using a process analytical technology based crystallization feedback control strategy.

    PubMed

    Saleemi, Ali N; Steele, Gerry; Pedge, Nicholas I; Freeman, Anthony; Nagy, Zoltan K

    2012-07-01

    Pharmaceutical regulatory bodies require minimal presence of solvent in an active pharmaceutical ingredient (API) after crystallization. From a processing point of view bigger crystals with minimal agglomeration and uniform size distribution are preferred to avoid solvent inclusion and for improved downstream processing. The current work addresses these issues encountered during the production of the potential anti-arrhythmic cardiovascular drug, AZD7009. This paper demonstrates that by applying the automated direct nucleation control (ADNC) approach problems with agglomeration and solvent inclusion were resolved. This model free approach automatically induces temperature cycles in the system, with the number of cycles, temperature range and adaptive heating and cooling rates determined to maintain the number of particles in the system, as measured by a focused beam reflectance measurement (FBRM) probe, within a constant range during the crystallization. The ADNC approach was able to produce larger and more uniform crystals and also removed the residual solvent trapped between the crystals compared to the typical crystallization operation using linear cooling profile. The results illustrate the application of process analytical technologies, such as FBRM and ATR-UV-vis spectroscopy, for the design of optimal crystallization operating conditions for the production of pharmaceuticals, and demonstrate that the ADNC approach can be used for rapid crystallization development for APIs exhibiting problems with agglomeration and solvent inclusion.

  6. The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

    PubMed Central

    2015-01-01

    Summary The implementation of continuous flow processing as a key enabling technology has transformed the way we conduct chemistry and has expanded our synthetic capabilities. As a result many new preparative routes have been designed towards commercially relevant drug compounds achieving more efficient and reproducible manufacture. This review article aims to illustrate the holistic systems approach and diverse applications of flow chemistry to the preparation of pharmaceutically active molecules, demonstrating the value of this strategy towards every aspect ranging from synthesis, in-line analysis and purification to final formulation and tableting. Although this review will primarily concentrate on large scale continuous processing, additional selected syntheses using micro or meso-scaled flow reactors will be exemplified for key transformations and process control. It is hoped that the reader will gain an appreciation of the innovative technology and transformational nature that flow chemistry can leverage to an overall process. PMID:26425178

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

    PubMed

    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.

  8. Quantification of potential impurities by a stability indicating UV-HPLC method in niacinamide active pharmaceutical ingredient.

    PubMed

    Thomas, Saji; Bharti, Amber; Tharpa, Kalsang; Agarwal, Ashutosh

    2012-02-23

    A sensitive, stability indicating reverse phase UV-HPLC method has been developed for the quantitative determination of potential impurities of niacinamide active pharmaceutical ingredient. Efficient chromatographic separation was achieved on C18 stationary phase in isocratic mode using simple mobile phase. Forced degradation study confirmed that the newly developed method was specific and selective to the degradation products. Major degradation of the drug substance was found to occur under oxidative stress conditions to form niacinamide N-oxide. The method was validated according to ICH guidelines with respect to specificity, precision, linearity and accuracy. Regression analysis showed correlation coefficient value greater than 0.999 for niacinamide and its six impurities. Detection limit of impurities was in the range of 0.003-0.005% indicating the high sensitivity of the newly developed method. Accuracy of the method was established based on the recovery obtained between 93.3% and 113.3% for all impurities.

  9. Use of near-infrared for quantitative measurement of viscosity and concentration of active ingredient in pharmaceutical gel.

    PubMed

    Donoso, M; Ghaly, E S

    2006-01-01

    Near infrared (NIR) spectroscopy is gaining worldwide interest as an analytical tool for quality control of raw materials, intermediate products, and final dosage forms. This technique can be used without sample preparation, therefore, avoiding the need for reagents and solvents. Quantitative NIR analyses involve calibration by sophisticated mathematical techniques that have been used extensively since the advent of microcomputing and chemometrics. The main objective of this investigation was to use transmission near-Infrared spectroscopy to measure the potency of an active ingredient in a topical gel preparation. A second objective was to evaluate the effect of gel viscosity on the NIR reflectance spectra. Four gel formulations with different ibuprofen concentrations were used for quantitative determination of the active ingredient, and five gel formulations with different viscosity values were used for the evaluation of the effect of viscosity change on the near-infrared reflectance spectra. The laboratory ibuprofen quantitative determination was compared to near-infrared transmission data using linear, quadratic, cubic and partial least square techniques to determine the relationship between ultraviolet (UV) determination and near-infrared spectra. For viscosity, the laboratory data were compared to near-infrared diffuse reflectance data using the same techniques used to determine the relationship between Brookfield viscometer determination and near-infrared spectra. The results demonstrated that an increase in ibuprofen concentration and viscosity produced an increase in near-infrared absorbance. Series of model equations were developed from the calibration of laboratory vs. the near-infrared data for each formulation. The near-infrared spectroscopy method is an alternative method that does not require sample pretreatment for quantitative measurement of active ingredient and viscosity of pharmaceutical gel.

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

    PubMed

    Reeuwijk, Noortje M; Venhuis, Bastiaan J; de Kaste, Dries; Hoogenboom, Ron L A P; Rietjens, Ivonne M C M; Martena, Martijn 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 loss properties. Herbal food supplements intended for weight loss (n = 50) were sampled from August 2004 to May 2013. An HPLC-DAD-MS/MS method was used to screen for the presence of the APIs in herbal supplements. In 24 samples the APIs sibutramine, desmethylsibutramine (DMS), didesmethylsibutramine (DDMS), rimonabant, sildenafil and/or the laxative phenolphthalein were identified 41 times. The presence of these APIs was, however, not stated on the label. The potential pharmacological effects of the detected APIs were estimated using data from reported effective doses of approved drugs. Use of 20 of the 24 herbal food supplements may result in potential pharmacological effects. Furthermore, risk assessment of phenolphthalein, a suspected carcinogen and found to be present in 10 supplements, based on the margin of exposure (MOE) approach, resulted in MOE values of 96-30,000. MOE values lower than 10,000 (96-220) were calculated for the daily intake levels of four out of these 10 supplements in which phenolphthalein was found. However, taking into account that weight loss preparations may be used for only a few weeks or months rather than during a lifetime, MOE values may be two to three orders of magnitude higher. The current study shows that the use of food supplements with sibutramine, DMS, DDMS and/or phenolphthalein could result in pharmacological effects.

  11. Effect of particle shape of active pharmaceutical ingredients prepared by fluidized-bed jet-milling on cohesiveness.

    PubMed

    Fukunaka, Tadashi; Sawaguchi, Kohta; Golman, Boris; Shinohara, Kunio

    2005-05-01

    Milling is a common procedure to improve bioavailability of many active pharmaceutical ingredients (APIs), which typically have low solubility in water. But such micronization can yield an increase in the cohesiveness of particles. Although particle cohesiveness is desirable for tablet strength in the subsequent formulation process, increased particle cohesiveness can lead to operational difficulties in a milling equipment due to compaction of particles inside. In this article, the impact of milling via a fluidized-bed jet-mill on the cohesive strength and interparticle force was studied using Ethenzamide as a pharmaceutical model compound. As a result, the particle shape was found to affect both the tensile strength of powder bed and the interparticle cohesive force. A powder bed, having relatively high void fraction by direct tensile test, shows a positive correlation between the cohesive force and the particle sphericity, while powders with low void fraction by diametral compression test show a positive correlation between the cohesive force and the angularity of the particle.

  12. Kinetics of the esterification of active pharmaceutical ingredients containing carboxylic acid functionality in polyethylene glycol: formulation implications.

    PubMed

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

    2014-08-01

    Polyethylene glycols (PEGs) are attractive as excipients in the manufacture of drug products because they are water soluble and poorly immunogenic. They are used in various pharmaceutical preparations. However, because of their terminal hydroxyl groups, PEGs can participate in esterification 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, whereas HPLC-MS was used to identify reaction products. The esterification reactions were observed to be reversible. A second-order reversible kinetic model was applied and rate constants were determined. The rate constants demonstrated that cetirizine was esterified about 240 times faster than indomethacin at 80 °C. The shelf-life for cetirizine in a PEG 400 formulation at 25 °C expressed as t(95%) was predicted to be only 30 h. Further, rate constants for esterification of cetirizine in PEG 1000 in relation to PEG 400 decreased by a factor of 10, probably related to increased viscosity. However, it is important to be aware of this drug-excipient interaction, as it can reduce the shelf-life of a low-average molecular weight PEG formulation considerably.

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

    NASA Astrophysics Data System (ADS)

    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.

  14. Comparison of the determination of a low-concentration active ingredient in pharmaceutical tablets by backscatter and transmission Raman spectrometry.

    PubMed

    Townshend, Nichola; Nordon, Alison; Littlejohn, David; Myrick, Michael; Andrews, John; Dallin, Paul

    2012-06-05

    A total of 383 tablets of a pharmaceutical product were analyzed by backscatter and transmission Raman spectrometry to determine the concentration of an active pharmaceutical ingredient (API), chlorpheniramine maleate, at the 2% m/m (4 mg) level. As the exact composition of the tablets was unknown, external calibration samples were prepared from chlorpheniramine maleate and microcrystalline cellulose (Avicel) of different particle size. The API peak at 1594 cm(-1) in the second derivative Raman spectra was used to generate linear calibration models. The API concentration predicted using backscatter Raman measurements was relatively insensitive to the particle size of Avicel. With transmission, however, particle size effects were greater and accurate prediction of the API content was only possible when the photon propagation properties of the calibration and sample tablets were matched. Good agreement was obtained with HPLC analysis when matched calibration tablets were used for both modes. When the calibration and sample tablets are not chemically matched, spectral normalization based on calculation of relative intensities cannot be used to reduce the effects of differences in physical properties. The main conclusion is that although better for whole tablet analysis, transmission Raman is more sensitive to differences in the photon propagation properties of the calibration and sample tablets.

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

    PubMed

    Cervera-Padrell, Albert E; Skovby, Tommy; Kiil, Søren; Gani, Rafiqul; Gernaey, Krist V

    2012-10-01

    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 fermentation-based products. The method exploits the synergic combination of continuous flow technologies (e.g., microfluidic techniques) and process systems engineering (PSE) methods and tools for faster process design and increased process understanding throughout the whole drug product and process development cycle. The design framework structures the many different and challenging design problems (e.g., solvent selection, reactor design, and design of separation and purification operations), driving the user from the initial drug discovery steps--where process knowledge is very limited--toward the detailed design and analysis. Examples from the literature of PSE methods and tools applied to pharmaceutical process design and novel pharmaceutical production technologies are provided along the text, assisting in the accumulation and interpretation of process knowledge. Different criteria are suggested 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: zuclopenthixol. Some of its batch operations were successfully converted into continuous mode, obtaining higher yields that allowed a significant simplification of the whole process. The material and environmental footprint of the process--evaluated through the process mass intensity index, that is, kg of material used per kg of product--was reduced to half of its initial value, with potential for further reduction. The case-study includes reaction steps typically used by the pharmaceutical

  16. Continuous-flow technology—a tool for the safe manufacturing of active pharmaceutical ingredients.

    PubMed

    Gutmann, Bernhard; Cantillo, David; Kappe, C Oliver

    2015-06-01

    In the past few years, continuous-flow reactors with channel dimensions in the micro- or millimeter region have found widespread application in organic synthesis. The characteristic properties of these reactors are their exceptionally fast heat and mass transfer. In microstructured devices of this type, virtually instantaneous mixing can be achieved for all but the fastest reactions. Similarly, the accumulation of heat, formation of hot spots, and dangers of thermal runaways can be prevented. As a result of the small reactor volumes, the overall safety of the process is significantly improved, even when harsh reaction conditions are used. Thus, microreactor technology offers a unique way to perform ultrafast, exothermic reactions, and allows the execution of reactions which proceed via highly unstable or even explosive intermediates. This Review discusses recent literature examples of continuous-flow organic synthesis where hazardous reactions or extreme process windows have been employed, with a focus on applications of relevance to the preparation of pharmaceuticals.

  17. Theoretical approaches to physical transformations of active pharmaceutical ingredients during manufacturing processes.

    PubMed

    Morris, K R; Griesser, U J; Eckhardt, C J; Stowell, J G

    2001-05-16

    Processing-induced transformations (PITs) during pharmaceutical manufacturing are well known but difficult to predict and often difficult to control. This review of the concepts of transformations is couched in terms of the issues associated with identifying rate-controlling events from the materials side and the processing side. Specifically, the approach is reconciling the characteristic time scale of the structural change(s) in the material with the time scale of the processing-induced stress. This is definitely a model (or rather a melding of a group of existing theories) in development. This overview is a 'snapshot' of the authors' attempts to identify the categories of existing theories needed to encompass all of the relevant events for each possible PIT. The ultimate goal is to establish a framework of concepts and theories for consideration, discussion, and modeling of PITs as well as to locate much of the relevant literature in the framework.

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

    PubMed

    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

  19. Assessment of active pharmaceutical ingredient particle size in tablets by Raman chemical imaging validated using polystyrene microsphere size standards.

    PubMed

    Kuriyama, Atsushi; Ozaki, Yukihiro

    2014-04-01

    Particle size is a critical parameter for controlling pharmaceutical quality. The aim of this study was to assess the size of the micrometer-scale active pharmaceutical ingredients (API) in tablets using Raman chemical imaging and to understand the effects of formulation on particle size. Model tablets containing National Institute of Standards and Technology traceable polystyrene microsphere size standards were developed to determine the binarization threshold value of Raman chemical images for API particle sizing in specific formulations and processes. Three sets of model tablets containing 5, 10, and 15 μm polystyrene microspheres, used to mimic API, were prepared using a commercial tablet formulation (Ebastel tablets, mean API particle size was about 5 μm). Raman mapping with a 50× objective (NA, 0.75) was applied to tablet cross-sections, and particle size of polystyrene microspheres was estimated from binary images using several binarization thresholds. Mean particle size for three sets of polystyrene microspheres showed good agreement between pre- and postformulation (the slope = 1.024, R = 1.000) at the specific threshold value ((mean + 0.5σ) of the polystyrene-specific peak intensity histogram), regardless of particle agglomeration, tablet surface roughness, and laser penetration depth. The binarization threshold value showed good applicability to Ebastel tablets, where the API-specific peak intensity histogram showed a pattern similar to that of polystyrene microspheres in model tablets. The model tablets enabled determination of an appropriate binarization threshold for assessing the mean particle size of micrometer-scale API in tablets by utilizing the unique physicochemical properties of polystyrene microspheres.

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

    PubMed

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

    2013-01-01

    In this contribution the ability of (19)F 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 T(1)((1)H) and T(1ρ)((1)H) 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 (19)F 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 (19)F 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 (19)F 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 (19)F 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.

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

    NASA Astrophysics Data System (ADS)

    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.

  2. Analysis of low active-pharmaceutical-ingredient signal drugs based on thin layer chromatography and surface-enhanced Raman spectroscopy.

    PubMed

    Li, Xiao; Chen, Hui; Zhu, Qingxia; Liu, Yan; Lu, Feng

    2016-11-30

    Active pharmaceutical ingredients (API) embedded in the excipients of the formula can usually be unravelled by normal Raman spectroscopy (NRS). However, more and more drugs with low API content and/or low Raman scattering coefficient were insensitive to NRS analysis, which was for the first time defined as Low API-Signal Drugs (LASIDs) in this paper. The NRS spectra of these LASIDs were similar to their dominant excipients' profiles, such as lactose, starch, microcrystalline cellulose (MCC), etc., and were classified into three types as such. 21 out of 100 kinds of drugs were screened as LASIDs and characterized further by Raman microscopic mapping. Accordingly, we proposed a tailored solution to the qualitation and quantitation problem of these LASIDs, using surface-enhanced Raman spectroscopic (SERS) detection on the thin layer chromatographic (TLC) plate both in situ and after-separation. Experimental conditions and parameters including TLC support matrix, SERS substrate, detection mode, similarity threshold, internal standard, etc., were optimized. All LASIDs were satisfactorily identified and the quantitation results agreed well with those of high performance liquid chromatography (HPLC). For some structural analogues of LASIDs, although they presented highly similar SERS spectra and were tough to distinguish even with Raman microscopic mapping, they could be successfully discriminated from each other by coupling SERS (with portable Raman spectrometer) with TLC. These results demonstrated that the proposed solution could be employed to detect the LASIDs with high accuracy and cost-effectiveness.

  3. The application of atomic absorption spectrometry for the determination of residual active pharmaceutical ingredients in cleaning validation samples.

    PubMed

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

    2011-03-01

    The objective of this work was the development and validation of atomic absorption spectrometric (AAS) methods for the determination of residual active pharmaceutical ingredients (API) in rinse samples for cleaning validation. AAS as an indirect method for the determination of API in rinse samples can be applied when it is in the form of salt with metal ions or when the metal ion is a part of the API's structure. The electrothermal AAS methods (aqueous and ethanol medium) for the determination of magnesium in esomeprazole magnesium and the flame AAS method for the determination of lithium in lithium carbonate in rinse samples were developed. Various combinations of solvents were tested and a combination of 1% aqueous or ethanol solution of nitric acid for esomeprazole magnesium and 0.1% aqueous solution of nitric acid for lithium carbonate were found to be the most suitable. The atomization conditions in the graphite furnace and in the flame were carefully studied to avoid losses of analyte and to achieve suitable sensitivity. The cleaning verification methods were validated with respect to accuracy, precision, linearity, limit of detection, and quantification. In all the cases, the limits of detection were at the microgram level. The methods were successfully applied for the determination of esomeprazole magnesium and lithium carbonate in rinse samples from cleaning procedures.

  4. Occurrence and behaviour of 105 active pharmaceutical ingredients in sewage waters of a municipal sewer collection system.

    PubMed

    Lindberg, Richard H; Östman, Marcus; Olofsson, Ulrika; Grabic, Roman; Fick, Jerker

    2014-07-01

    The concentrations and behaviour of 105 different active pharmaceutical ingredients (APIs) in the aqueous phase of sewage water within a municipal sewer collection system have been investigated. Sewage water samples were gathered from seven pump stations (one of which was located within a university hospital) and from sewage water treatment influent and effluent. The targeted APIs were quantified using a multi-residue method based on online solid phase extraction liquid chromatography tandem mass spectrometry. The method was thoroughly validated and complies with EU regulations on sample handling, limits of quantification, quality control and selectivity. 51 APIs, including antibiotics, antidepressants, hypertension drugs, analgesics, NSAIDs and psycholeptics, were found frequently within the sewer collection system. API concentrations and mass flows were evaluated in terms of their frequency of detection, daily variation, median/minimum/maximum/average concentrations, demographic dissimilarities, removal efficiencies, and mass flow profiles relative to municipal sales data. Our results suggest that some APIs are removed from, or introduced to, the aqueous phase of sewage waters within the studied municipal collection system.

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

    PubMed

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

    2011-09-01

    Various marine habitats sustain variety of bio-sources of ecological and biotech potentials. Pharmaceutical potential compound Cyclosporine A was reported from marine fungus Microdochium nivale associated with Porteresia coarctata, a marine salt marsh grass from mangrove environment distributed along the Central West Coast (CWC) of India. This study involves association of M. nivale with P. coarctata plant, fermentation conditions, purification of Cyclosporine A, chemical characterization etc. Its antifungal inhibition and MIC (Minimum inhibitory concentration) against Aspergillus strains (A. niger, A. japonicus, A. fresenii), yeasts and dermatophytes (Candida sp., Cryptococcus neoformans, Trichophyton mentagrophytes, T. tonsurans, T. violaceum, Microsporium gypsum and Fusarium sp.) were evaluated. However, the MIC against A. japonicus, C. neoformans, Candida sp. and T. tonsurans were confirmed to be as low as 12.5-25 mg disc(-1). The antifungal properties of Cyclosporine A against Aspergillus species, yeast and dermatophytes revealed that CyclosporineAwould be a potential compound for life threatening diseases caused by above fungi in both human and animals. Furthermore, we have reported herewith another source of Cyclosporin Aderived from filamentous fungus, M. nivale. occurring in marine environment.

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

    PubMed

    Kawakami, Kohsaku; Usui, Toshinori; Hattori, Mitsunari

    2012-09-01

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

  7. 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.

    PubMed

    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.

  8. Stability indicating LC method for rapid determination of related substances of O-desmethyl venlafaxine in active pharmaceutical ingredients and pharmaceutical formulations.

    PubMed

    Rao, Karri Visweswara; Reddy, Kesareddy Padmaja; Kumar, Yelavarthi Ravindra

    2014-01-01

    A simple, precise and accurate stability-indicating reversed phase-high performance liquid chromatography method was developed for the quantitative determination of O-desmethyl venlafaxine (ODV) and its related substances in active pharmaceutical ingredient and pharmaceutical formulation. The method was developed using YMC-pack ODS-A (150 × 4.6 mm, 3 μm) column with mobile phase containing a gradient mixture of solvents A and B. Solvent A contained a mixture of buffer and acetonitrile in the ratio of 85:15 (v/v). The buffer consisted of 10 mM potassium dihydrogen phosphate and 2 mM 1-octane sulfonic acid sodium salt (pH adjusted to 6.0 by using diluted potassium hydroxide solution). Solvent B contained a mixture of water and acetonitrile in the ratio of 20:80 (v/v). The eluted compounds were monitored at 230 nm. ODV and its six impurities were well separated within 14 min run time. It was subjected under the stress conditions of oxidative, acid, base, water, thermal and photolytic degradation. It was sensitive towards acidic, basic, oxidative and water stress conditions, stable in photolytic and thermal degradation conditions. The degradation products were well resolved from main peak and its impurities, the mass balance in each case was >99.0%, proving the stability-indicating power of the method. The developed method was validated as per International Conference on Harmonization (ICH) guidelines with respect to its specificity, linearity (correlation coefficient >0.9996), limit of detection, limit of quantification, accuracy (recovery range 97.1-103.2%), precision (% relative standard deviation ≤1.9%) and robustness.

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

    NASA Astrophysics Data System (ADS)

    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.

  10. Potential ecological footprints of active pharmaceutical ingredients: an examination of risk factors in low-, middle- and high-income countries.

    PubMed

    Kookana, Rai S; Williams, Mike; Boxall, Alistair B A; Larsson, D G Joakim; Gaw, Sally; Choi, Kyungho; Yamamoto, Hiroshi; Thatikonda, Shashidhar; Zhu, Yong-Guan; Carriquiriborde, Pedro

    2014-11-19

    Active pharmaceutical ingredients (APIs) can enter the natural environment during manufacture, use and/or disposal, and consequently public concern about their potential adverse impacts in the environment is growing. Despite the bulk of the human population living in Asia and Africa (mostly in low- or middle-income countries), limited work relating to research, development and regulations on APIs in the environment have so far been conducted in these regions. Also, the API manufacturing sector is gradually shifting to countries with lower production costs. This paper focuses mainly on APIs for human consumption and highlights key differences between the low-, middle- and high-income countries, covering factors such as population and demographics, manufacture, prescriptions, treatment, disposal and reuse of waste and wastewater. The striking differences in populations (both human and animal), urbanization, sewer connectivity and other factors have revealed that the environmental compartments receiving the bulk of API residues differ markedly between low- and high-income countries. High sewer connectivity in developed countries allows capture and treatment of the waste stream (point-source). However, in many low- or middle-income countries, sewerage connectivity is generally low and in some areas waste is collected predominantly in septic systems. Consequently, the diffuse-source impact, such as on groundwater from leaking septic systems or on land due to disposal of raw sewage or septage, may be of greater concern. A screening level assessment of potential burdens of APIs in urban and rural environments of countries representing low- and middle-income as well as high-income has been made. Implications for ecological risks of APIs used by humans in lower income countries are discussed.

  11. Potential ecological footprints of active pharmaceutical ingredients: an examination of risk factors in low-, middle- and high-income countries

    PubMed Central

    Kookana, Rai S.; Williams, Mike; Boxall, Alistair B. A.; Larsson, D. G. Joakim; Gaw, Sally; Choi, Kyungho; Yamamoto, Hiroshi; Thatikonda, Shashidhar; Zhu, Yong-Guan; Carriquiriborde, Pedro

    2014-01-01

    Active pharmaceutical ingredients (APIs) can enter the natural environment during manufacture, use and/or disposal, and consequently public concern about their potential adverse impacts in the environment is growing. Despite the bulk of the human population living in Asia and Africa (mostly in low- or middle-income countries), limited work relating to research, development and regulations on APIs in the environment have so far been conducted in these regions. Also, the API manufacturing sector is gradually shifting to countries with lower production costs. This paper focuses mainly on APIs for human consumption and highlights key differences between the low-, middle- and high-income countries, covering factors such as population and demographics, manufacture, prescriptions, treatment, disposal and reuse of waste and wastewater. The striking differences in populations (both human and animal), urbanization, sewer connectivity and other factors have revealed that the environmental compartments receiving the bulk of API residues differ markedly between low- and high-income countries. High sewer connectivity in developed countries allows capture and treatment of the waste stream (point-source). However, in many low- or middle-income countries, sewerage connectivity is generally low and in some areas waste is collected predominantly in septic systems. Consequently, the diffuse-source impact, such as on groundwater from leaking septic systems or on land due to disposal of raw sewage or septage, may be of greater concern. A screening level assessment of potential burdens of APIs in urban and rural environments of countries representing low- and middle-income as well as high-income has been made. Implications for ecological risks of APIs used by humans in lower income countries are discussed. PMID:25405973

  12. The effect of microcrystalline cellulose crystallinity on the hydrophilic property of tablets and the hydrolysis of acetylsalicylic acid as active pharmaceutical ingredient inside tablets.

    PubMed

    Awa, Kimie; Shinzawa, Hideyuki; Ozaki, Yukihiro

    2015-08-01

    The crystal structures of active pharmaceutical ingredients and excipients should be strictly controlled because they influence pharmaceutical properties of products which cause the change in the quality or the bioavailability of the products. In this study, we investigated the effects of microcrystalline cellulose (MCC) crystallinity on the hydrophilic properties of tablets and the hydrolysis of active pharmaceutical ingredient, acetylsalicylic acid (ASA), inside tablets by using tablets containing 20% MCC as an excipient. Different levels of grinding were applied to MCC prior to tablet formulation, to intentionally cause structural variation in the MCC. The water penetration and moisture absorbability of the tablets increased with decreasing the crystallinity of MCC through higher level of grinding. More importantly, the hydrolysis of ASA inside tablets was also accelerated. These results indicate that the crystallinity of MCC has crucial effects on the pharmaceutical properties of tablets even when the tablets contain a relatively small amount of MCC. Therefore, controlling the crystal structure of excipients is important for controlling product qualities.

  13. Active Ingredient - AZ

    EPA Pesticide Factsheets

    EPA Pesticide Chemical Search allows a user to easily find the pesticide chemical or active ingredient that they are interested in by using an array of simple to advanced search options. Chemical Search provides a single point of reference for easy access to information previously published in a variety of locations, including various EPA web pages and Regulations.gov.

  14. The slow relaxation dynamics in active pharmaceutical ingredients studied by DSC and TSDC: Voriconazole, miconazole and itraconazole.

    PubMed

    Ramos, Joaquim J Moura; Diogo, Hermínio P

    2016-03-30

    The slow molecular mobility of three active pharmaceutical drugs (voriconazole, miconazole and itraconazole) has been studied by differential scanning calorimetry (DSC) and thermally stimulated depolarization currents (TSDC). This study yielded the main kinetic features of the secondary relaxations and of the main (glass transition) relaxation, in particular their distribution of relaxation times. The dynamic fragility of the three glass formers was determined from DSC data (using two different procedures) and from TSDC data. According to our results voriconazole behaves as a relatively strong liquid, while miconazole is moderately fragile and itraconazole is a very fragile liquid. There are no studies in this area published in the literature relating to voriconazole. Also not available in the literature is a slow mobility study by dielectric relaxation spectroscopy in the amorphous miconazole. Apart from that, the results obtained are in reasonable agreement with published works using different experimental techniques.

  15. Isotopic 13C NMR spectrometry to assess counterfeiting of active pharmaceutical ingredients: site-specific 13C content of aspirin and paracetamol.

    PubMed

    Silvestre, Virginie; Mboula, Vanessa Maroga; Jouitteau, Catherine; Akoka, Serge; Robins, Richard J; Remaud, Gérald S

    2009-10-15

    Isotope profiling is a well-established technique to obtain information about the chemical history of a given compound. However, the current methodology using IRMS can only determine the global (13)C content, leading to the loss of much valuable data. The development of quantitative isotopic (13)C NMR spectrometry at natural abundance enables the measurement of the (13)C content of each carbon within a molecule, thus giving simultaneous access to a number of isotopic parameters. When it is applied to active pharmaceutical ingredients, each manufactured batch can be characterized better than by IRMS. Here, quantitative isotopic (13)C NMR is shown to be a very promising and effective tool for assessing the counterfeiting of medicines, as exemplified by an analysis of aspirin (acetylsalicylic acid) and paracetamol (acetaminophen) samples collected from pharmacies in different countries. It is proposed as an essential complement to (2)H NMR and IRMS.

  16. Quantitative HPLC analysis of active pharmaceutical ingredients in syrup vehicle using centrifugal filter devices and determination of xanthan gum in syrup vehicle using rheometry.

    PubMed

    Chen, Yong; Tadey, Tanya; Hu, Mougang; Carr, Geoff; Guo, Junan

    2010-02-01

    Using rapid centrifugal filtration (active pharmaceutical ingradients of interest. Two model active pharmaceutical ingredients, L-arginine and amphotericin B, were quantitatively recovered from the diluted syrup vehicle after centrifugation with the filter devices. The reproducibility [% relative standard deviation (RSD), peak area] of the filtered samples was less than 0.5%. For amphotericin B samples. The linear range was 0.28 microg/mL to 28.2 microg/mL. The limit of detection was 0.06 microg/mL. The limit of quantification was 0.28 microg/mL. The viscosity of a syrup vehicle changed linearly with the concentration of xanthan gum. A method was thus developed to determine xanthan gum in the syrup vehicle. The accuracy was within 95.0% to 105.0% at different concentration levels.

  17. Acoustic-resonance spectrometry as a process analytical technology for the quantification of active pharmaceutical ingredient in semi-solids.

    PubMed

    Medendorp, Joseph; Buice, Robert G; Lodder, Robert A

    2006-09-01

    The purpose of this study was to demonstrate acoustic resonance spectrometry (ARS) as an alternative process analytical technology to near infrared (NIR) spectroscopy for the quantification of active pharmaceutical ingradient (API) in semi-solids such as creams, gels, ointments, and lotions. The ARS used for this research was an inexpensive instrument constructed from readily available parts. Acoustic-resonance spectra were collected with a frequency spectrum from 0 to 22.05 KHz. NIR data were collected from 1100 to 2500 nm. Using 1-point net analyte signal (NAS) calibration, NIR for the API (colloidal oatmeal [CO]) gave anr (2) prediction accuracy of 0.971, and a standard error of performance (SEP) of 0.517%CO. ARS for the API resulted in anr (2) of 0.983 and SEP of 0.317%CO. NAS calibration is compared with principal component regression. This research demonstrates that ARS can sometimes outperform NIR spectrometry and can be an effective analytical method for the quantification of API in semi-solids. ARS requires no sample preparation, provides larger penetration depths into lotions than optical techniques, and measures API concentrations faster and more accurately. These results suggest that ARS is a useful process analytical technology (PAT).

  18. Monitoring the dissolution of Active Pharmaceutical Ingredient and TPGS in real time via IR spectroscopy during the manufacturing of liquid dosage formulation.

    PubMed

    Šašić, Slobodan; Palm, Andrew S; Tang, Degui

    2012-11-01

    Infrared spectroscopy is used to monitor the dissolution of the Active Pharmaceutical Ingredient (API) and an excipient (vitamin E - TPGS) during manufacturing of a liquid pharmaceutical formulation. The goal of the analysis is to explore options for real-time, on screen, and quantitative monitoring of these two components by using an iC10 instrument. As is common, the first step in the approach is to create respective calibration models for the two components and then apply those models on the spectra obtained from scale-up batches. Interestingly, while the API dissolves at the room temperature, TPGS dissolves at an acceptable rate at 50 °C so both temperatures have to be considered. It is shown that univariate models of sufficient accuracy can be developed with a straightforward applicability to the scale-up batches spectra and providing reasonably accurate estimates of the API and TPGS concentrations. Some limitations of the software on the employed instrument may diminish the prospect for the quantitative analysis of the components of interest in this formulation.

  19. Control and analysis of alkyl and benzyl halides and other related reactive organohalides as potential genotoxic impurities in active pharmaceutical ingredients (APIs).

    PubMed

    Elder, D P; Lipczynski, A M; Teasdale, A

    2008-11-04

    This paper continues the review of the relevant scientific literature associated with the control and analysis of potential genotoxic impurities (PGIs) in active pharmaceutical ingredients (APIs). The initial review [D.P. Elder, A. Teasdale, A.M. Lipczynski, J. Pharm. Biomed. Anal. 46 (2008) 1-8.] focused on the specific class of sulfonate esters but in this instance reference is made to the analysis of alkyl and benzyl halides and other related reactive organohalide alkylating agents. Such reactive materials are commonly employed in pharmaceutical research and development as raw materials, reagents and intermediates in the chemical synthesis of new drug substances. Consequently a great deal of attention and effort is extended by the innovative and ethical pharmaceutical industry to ensure that appropriate and practicable control strategies are established during drug development to ensure residues of such agents, as potential impurities in new drug substances, are either eliminated or minimized to such an extent so as to not present a significant safety risk to volunteers and patients in clinical trials and beyond. The reliable trace analysis of such reactive organohalides is central to such control strategies and invariably involves a state-of-the-art combination of high-resolution separation science techniques coupled to sensitive and selective modes of detection. This article reports on the most recent developments in the regulatory environment, overall strategies for the control of alkylating agents and the latest developments in analysis culminating in a literature review of analytical approaches. The literature is sub-categorized by separation technique (gas chromatography (GC), high-performance liquid chromatography (HPLC), thin layer chromatography (TLC) and capillary zone electrophoresis (CZE)) and further tabulated by API type and impurity with brief method details and references. As part of this exercise, a selection of relevant pharmacopoeial

  20. Application of mid-infrared spectroscopy to the development and transfer of a manufacturing process for an active pharmaceutical ingredient.

    PubMed

    Clegg, Ian M; Daly, Adrian M; Donnelly, Craig; Hardy, Ruth; Harris, Denise; Jackman, Hayley; Jones, Ricky; Luan, Amy; McAndrew, Douglas; McGauley, Pat; Pearce, John; Scotney, Gemma; Yeow, May-Ling

    2012-05-01

    The use of in situ mid-infrared spectroscopy to support the development of a pharmaceutical manufacturing process is disclosed. Data on this two-stage telescoped reaction from several reaction scales (<50 mL to 1600 liters) and at multiple manufacturing locations is shown. In addition to providing data on both reactions in the telescope, the mid-IR data has been used to monitor an intermediate distillation operation and therefore it has been possible to profile the whole process. Data is also shown on aliquot addition during the first chemical transformation, which is used to check the instrumentation.

  1. A new non-invasive, quantitative Raman technique for the determination of an active ingredient in pharmaceutical liquids by direct measurement through a plastic bottle.

    PubMed

    Kim, Minjung; Chung, Hoeil; Woo, Youngah; Kemper, Mark S

    2007-03-28

    The concentration of an active pharmaceutical ingredient (povidone) in a commercial eyewash solution has been measured directly through a plastic (low-density polyethylene: LDPE) container using a wide area illumination (WAI) Raman scheme. The WAI scheme allows excitation using a 6mm laser spot (focal length: 248 mm) that is designed to cover a wide sample area. As a result, it has the potential to improve the reliability Raman measurements by significantly enhancing representative sample interrogation, thus improving the reproducibility of sampling. It also decreases the sensitivity of sample placement with regard to the excitation focal plane. Simultaneously, isobutyric anhydride was placed in front of the bottles to use for a synchronous external standard configuration. This helps to correct the problematic variation of Raman intensity from the inherent fluctuation in laser power. Using the WAI Raman scheme combined with the synchronous standard method, the povidone concentration was successfully measured with spectral collection that was performed through a plastic barrier. The conventional Raman scheme was difficult to employ for the same purpose because of the degraded spectral reproducibility resulting from the smaller laser illumination area and the sensitivity of such an approach to the position of the sample bottle. The result from this study suggests that the WAI scheme exhibits a strong potential for the non-destructive quantitative analysis of pharmaceuticals measured directly in plastic containers. Preliminary work also shows that similar measurements can also be made in glass bottles. If implemented, this technique could be utilized as a simple and rugged method for quality assurance of final products in a manner consistent with Process analytical technology (PAT) requirements.

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

    PubMed

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

    2010-11-02

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

  3. Comparison of reversed-phase/cation-exchange/anion-exchange trimodal stationary phases and their use in active pharmaceutical ingredient and counterion determinations.

    PubMed

    Liu, Xiaodong; Pohl, Christopher A

    2012-04-06

    This study involved three commercial reversed-phase (RP)/anion-exchange (AEX)/cation-exchange (CEX) trimodal columns, namely Acclaim Trinity P1 (Thermo Fisher Scientific), Obelisc R (SIELC Technologies) and Scherzo SM-C18 (Imtakt). Their chromatographic properties were compared in details with respect to hydrophobicity, anion-exchange capacity, cation-exchange capacity, and selectivity, by studying retention behavior dependency on organic solvent, buffer concentration and pH. It was found that their remarkably different column chemistries resulted in distinctive chromatography properties. Trinity P1 exhibited strong anion-exchange and cation-exchange interactions but low RP retention while Scherzo SM-C18 showed strong reversed-phase retention with little cation-exchange and anion-exchange capacities. For Obelisc R, its reversed-phase capacity was weaker than Scherzo SM-C18 but slightly higher than Trinity P1, and its ion-exchange retentions were between Trinity P1 and Scherzo SM-C18. In addition, their difference in selectivity was demonstrated by examples of determining the active pharmaceutical ingredient (API) and counterion of drug products.

  4. Influence of process parameters on content uniformity of a low dose active pharmaceutical ingredient in a tablet formulation according to GMP.

    PubMed

    Muselík, Jan; Franc, Aleš; Doležel, Petr; Goněc, Roman; Krondlová, Anna; Lukášová, Ivana

    2014-09-01

    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.

  5. Completeness assessment of type II active pharmaceutical ingredient drug master files under generic drug user fee amendment: review metrics and common incomplete items.

    PubMed

    Zhang, Huyi; Li, Haitao; Song, Wei; Shen, Diandian; Skanchy, David; Shen, Kun; Lionberger, Robert A; Rosencrance, Susan M; Yu, Lawrence X

    2014-09-01

    Under the Generic Drug User Fee Amendments (GDUFA) of 2012, Type II active pharmaceutical ingredient (API) drug master files (DMFs) must pay a user fee and pass a Completeness Assessment (CA) before they can be referenced in an Abbreviated New Drug Application (ANDA), ANDA amendment, or ANDA prior approval supplement (PAS). During the first year of GDUFA implementation, from October 1, 2012 to September 30, 2013, approximately 1,500 Type II API DMFs received at least one cycle of CA review and more than 1,100 Type II DMFs were deemed complete and published on FDA's "Available for Reference List". The data from CA reviews were analyzed for factors that influenced the CA review process and metrics, as well as the areas of DMF submissions which most frequently led to an incomplete CA status. The metrics analysis revealed that electronic DMFs appear to improve the completeness of submission and shorten both the review and response times. Utilizing the CA checklist to compile and proactively update the DMFs improves the chance for the DMFs to pass the CA in the first cycle. However, given that the majority of DMFs require at least two cycles of CA before being deemed complete, it is recommended that DMF fees are paid 6 months in advance of the ANDA submissions in order to avoid negatively impacting the filling status of the ANDAs.

  6. Contribution of the physicochemical properties of active pharmaceutical ingredients to tablet properties identified by ensemble artificial neural networks and Kohonen's self-organizing maps.

    PubMed

    Onuki, Yoshinori; Kawai, Shota; Arai, Hiroaki; Maeda, Jin; Takagaki, Keisuke; Takayama, Kozo

    2012-07-01

    The aim of this study was to create a tablet database for use in designing tablet formulations. We focused on the contribution of active pharmaceutical ingredients (APIs) to tablet properties such as hardness and disintegration time (DT). Before we investigated the effects of the APIs, we optimized the tablet base formulation (placebo tablet) according to an expanded simplex search. The optimal placebo tablet showed sufficient hardness and rapid disintegration. We then tested 14 kinds of compounds as the model APIs. The APIs were characterized in terms of their physicochemical properties using Kohonen's self-organizing maps. We also prepared model tablets by incorporating the APIs into the optimal placebo tablet, and then examined the tablet properties, including tensile strength and DT. On the basis of the experimental data, an ensemble artificial neural network incorporating general regression analysis was conducted. A reliable model of the correlation between the physicochemical properties of the APIs and the tablet properties was thus constructed. From the correlation model, we clarified the detailed contributions of each physicochemical property to the tablet attributes.

  7. Investigation of solubilising effects of bile salts on an active pharmaceutical ingredient with unusual pH dependent solubility by NMR spectroscopy.

    PubMed

    Vogtherr, M; Marx, A; Mieden, A-C; Saal, C

    2015-05-01

    The interaction between an ampholytic and amphiphilic Active Pharmaceutical Ingredient (API) showing unusual pH dependent solubility and Fasted State Simulated Intestinal Fluid (FaSSIF) was studied by NMR spectroscopy. Solubility in FaSSIF was drastically increased, about 30 fold, compared to simulated gastrointestinal fluid without bile salts. Our studies aimed at understanding the mechanisms that lead to this drastic enhancement. All species present in solution at various concentrations of API were characterised by Diffusion Ordered Spectroscopy (DOSY) NMR measurements. These indicated the presence of mixed taurocholate-lecithin and pure taurocholate micelles in pure FaSSIF, and formation of mixed taurocholate-API micelles after addition of API. The formation of taurocholate-API micelles was also supported by Nuclear Overhauser Effect/Enhancement (NOE) contacts between taurocholate and the API. Formation of mixed taurocholate-API micelles took place at the expense of pure taurocholate micelles, whereas mixed taurocholate-lecithin micelles remained uninfluenced by the presence of API. Our results showed that the increase in solubility was due to similar amphiphilic properties of the API and taurocholate which enabled formation of mixed taurocholate-API micelles. From results of determination of solubility as well as NMR experiments a phase diagram comprising several micellar species was derived.

  8. Stability-indicating UPLC method for determination of Imatinib Mesylate and their degradation products in active pharmaceutical ingredient and pharmaceutical dosage forms.

    PubMed

    Nageswari, A; Reddy, K V S R Krishna; Mukkanti, K

    2012-07-01

    A simple, precise, accurate stability-indicating gradient reverse phase ultra-performance liquid chromatographic (RP-UPLC) method was developed for quantitative determination of purity of Imatinib Mesylate (IMM) drug substance and drug products in the presence of its process related impurities, and degradation products. The proposed RP-UPLC method utilizes Acquity UPLC BEH 50-mm, 2.1mm and 1.7 μm C-18 column at 30 °C, with a gradient program of 9.0 min at a flow rate of 0.3 mL/min. The compounds of interest were monitored at 237 nm. Resolution for Imatinib and eight related components was found to be greater than 1.5 for any pair of components. The correlation coefficients (r(2)>0.9990) obtained indicate clear correlations between the concentrations and their peak areas for the investigated compounds. RSD obtained for the repeatability and intermediate precision experiments, was less than 5.0%. Accuracy of the method was further ascertained by performing recovery studies through spiking experiments. The drug substance was subjected to hydrolytic, oxidative, photolytic and thermal stress conditions as per ICH. The developed method was validated according to the current ICH guidelines for specificity, limit of detection, limit of quantitation, linearity, accuracy, precision, ruggedness and robustness. The method is also suitable for the assay determination of IMM in pharmaceutical dosage forms.

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

    PubMed

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

    2011-03-25

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

  10. Encapsulation of new active ingredients.

    PubMed

    Onwulata, C I

    2012-01-01

    The organic construct consumed as food comes packaged in units that carry the active components and protect the entrapped active materials until delivered to targeted human organs. The packaging and delivery role is mimicked in the microencapsulation tools used to deliver active ingredients in processed foods. Microencapsulation efficiency is balanced against the need to access the entrapped nutrients in bioavailable forms. Encapsulated ingredients boosted with bioactive nutrients are intended for improved health and well-being and to prevent future health problems. Presently, active ingredients are delivered using new techniques, such as hydrogels, nanoemulsions, and nanoparticles. In the future, nutraceuticals and functional foods may be tailored to individual metabolic needs and tied to each person's genetic makeup. Bioactive ingredients provide health-enhancing nutrients and are protected through encapsulation processes that shield the active ingredients from deleterious environments.

  11. Synthetic oligosaccharides as active pharmaceutical ingredients: lessons learned from the full synthesis of one heparin derivative on a large scale.

    PubMed

    Driguez, Pierre-Alexandre; Potier, Pierre; Trouilleux, Patrick

    2014-08-01

    Covering: up to November 2013. Heparin and heparan sulfate are natural polysaccharides with strong structural variations, which are responsible for their numerous specific biological properties. One key target of heparin, among others, is antithrombin, a serine protease inhibitor that, upon activation, mainly targets anticoagulation factors IIa and Xa. It is well documented that inhibition of the latter is due to a specific pentasaccharidic sequence, its synthetic analog being the registered drug fondaparinux. The replacement of hydroxyls by methoxy groups, N-sulfates by O-sulfonates and the modulation of the sulfation pattern gave rise to both idraparinux and its neutralizable form, idrabiotaparinux, two pentasaccharides with a significantly increased half-life compared to fondaparinux. Although numerous efforts have been devoted to improving the chemoenzymatic preparation of heparin fragments, enzymes are usually selective for their natural substrates, which limits the generation of some specific non-natural structures. Up to now, total synthesis has proved to be a valuable approach for the preparation of tailor-made and pure saccharides in the milligram to gram scale. This highlight will focus on the synthesis and the technical challenges associated with the development and the production of complex carbohydrates which will be exemplified with idrabiotaparinux. Particular attention will be paid to the process improvements needed in order to implement the production in a pilot plant, achieving batch generation on a multi-kilogram scale with a purity higher than 99.5%, and with no unknown impurity over 0.1%.

  12. Development and validation of a sensitive GC-MS method for the determination of alkylating agent, 4-chloro-1-butanol, in active pharmaceutical ingredients.

    PubMed

    Harigaya, Koki; Yamada, Hiroyuki; Yaku, Koji; Nishi, Hiroyuki; Haginaka, Jun

    2014-01-01

    The analysis of genotoxic impurities (GTIs) in active pharmaceutical ingredients (APIs) is a challenging task. The target detection limit (DL) in an API is typically around 1 ppm (1 µg/g API). Therefore, a sensitive and selective analytical method is required for their analysis. 4-Chloro-1-butanol, an alkylating agent, is one of the GTIs. It is generated when tetrahydrofuran and hydrochloric acid are used during the synthesis of the APIs. In this study, a sensitive and robust gas chromatography-mass spectrometry (GC-MS) method was developed and validated for the identification of 4-chloro-1-butanol in APIs. In the GC-MS method, 3-chloro-1-butanol was employed as an internal standard to ensure accuracy and precision. Linearity was observed over the range 0.08 to 40 ppm (µg/g API), with a R(2) value of 0.9999. The DL and quantitation limit (QL) obtained were 0.05 ppm and 0.08 ppm (0.13 ng/mL and 0.20 ng/mL as the 4-chloro-1-butanol concentration), respectively. These DL and QL values are well over the threshold specified in the guidelines. The accuracy (recovery) of detection ranged from 90.5 to 108.7% between 0.4 ppm and 20 ppm of 4-chloro-1-butanol. The relative standard deviation in the repeatability of the spiked recovery test was 6.0%. These results indicate the validity of the GC-MS method developed in this study. The GC-MS method was applied for the determination of 4-chloro-1-butanol in the API (Compound A), which is under clinical trials. No 4-chloro-1-butanol was found in Compound A (below QL, 0.08 ppm).

  13. Pharmaceutical Ingredients in Drinking Water: Overview of Occurrence and Significance of Human Exposure

    EPA Science Inventory

    A comprehensive examination of the data published through most of 2009 on the active pharmaceutical ingredients (APIs) that have been reported in finished drinking water (FDW) is presented. A synoptic review reveals that published quantitative data for FDW exists for 61 APIs and ...

  14. Encapsulation of new active ingredients

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The organic construct consumed as food comes packaged in units that carry the active components, protects the entrapped active materials until delivered to targeted human organ. The packaging and delivery role is mimicked in the microencapsulation tools used to deliver active ingredients in process...

  15. A compatibility study of a secondary amine active pharmaceutical ingredient with starch: identification of a novel degradant formed between desloratadine and a starch impurity using LC-MS(n) and NMR spectroscopy.

    PubMed

    Yu, Xin; Buevich, Alexei V; Li, Min; Wang, Xin; Rustum, Abu M

    2013-02-01

    Active pharmaceutical ingredients (APIs) containing primary and secondary amine moieties have been extensively studied for their potential incompatibility with monosaccharides and disaccharides containing a reducing end such as glucose, lactose, and maltose because of the undesirable interaction between the amine and aldehyde functionalities. Compatibility studies of these APIs with olysaccharides such as starch are much less common. During a recent compatibility study between starch and desloratadine, an API that contains a secondary amine functional group, we observed a novel degradant formed between desloratadine and a previously unidentified starch impurity in addition to an Amadori degradant formed between desloratadine and maltose, a known starch impurity. An approach that combines liquid chromatography-tandem mass spectrometry (LC-MS(n)) analysis, stress studies, and comprehensive nuclear magnetic resonance (NMR) analyses was used to identify this novel degradant. On the basis of the structure determined by NMR spectroscopy and the results from the stress studies, a degradation mechanism is proposed to account for the formation of this novel degradant through the reaction of desloratadine with an isomer of acetylformoin, an impurity of polysaccharide origin. Because starch is a very common excipient used in solid dosage formulations, the results of this compatibility study should facilitate pharmaceutical development involving secondary amine APIs and starch.

  16. 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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    Horgos, József; Kóger, Péter; Zelkó, Romána

    2009-01-01

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

  18. Establishment of powder dustiness evaluation method by dustmeter with small amount of pharmaceutical ingredients.

    PubMed

    Ohta, Tomoaki; Maeda, Hiroyuki; Kubota, Ryuji; Koga, Akiko; Terada, Katsuhide

    2014-09-10

    The ratio of high potent materials in the new chemical entities has recently increased in the pharmaceutical industry. Generally, most of them are highly hazardous, but there is little toxicity information about the active pharmaceutical ingredients in the early development period. Even if their handling amount is quite small, the dustiness of high potent powder generated in the manufacturing process has an important impact on worker health; thus, it is important to understand the powder dustiness. The purpose of this study was to establish a method to evaluate the powder dustiness by the consumption of small amount of samples. The optimized measurement conditions for a commercially available dustmeter were confirmed using lactose monohydrate and naproxen sodium. The optimized test conditions were determined: the dustmeter mode, the flow rate, the drum rotation speed, the total measurement time, and sample loaded weight were type I mode, 4 L/min, 10 rpm, 1 min and 1-10 g , respectively. The setup conditions of the dustmeter are considerably valuable to pharmaceutical industries, especially, at the early development stage and especially for expensive materials, because the amount of air-borne dust can be evaluated with accuracy by the consumption of small amount of samples.

  19. Development of an LC-MS method for ultra trace-level determination of 2,2,6,6-tetramethylpiperidine-1-oxl (TEMPO), a potential genotoxic impurity within active pharmaceutical ingredients.

    PubMed

    Pennington, Justin; Cohen, Ryan D; Tian, Ye; Boulineau, Fabien

    2015-10-10

    TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) is a stable free radical which has been widely used for various research and industrial applications, including the manufacture of many active pharmaceutical ingredients. TEMPO has been identified as a potential genotoxic impurity resulting in the need for analytical methodology to accurately determine its level at several orders of magnitude less than typical impurity quantitation limits. TEMPO can undergo disproportionation to form both oxidized and reduced TEMPO, making individual determination unreliable. To overcome this challenge, all TEMPO related species were converted to the reduced form through reduction with sodium ascorbate. Given the ultra-trace (0.5 ppm) level requirements and the lack of UV response in the reduced form, a single quadrupole mass spectrometer (MS) was utilized. In order to implement a highly sensitive MS method in a GMP environment, several approaches were employed to optimize accuracy and robustness including: internal standard correction for drift elimination, six-level standard addition to reduce matrix effects, and weighted linear regression to cover a broad analytical range. The method was fully validated according to ICH guidelines. The method is specific, linear, accurate, precise, and robust within a range of 0.5-100 ppm.

  20. Solid-state characterization of novel active pharmaceutical ingredients: cocrystal of a salbutamol hemiadipate salt with adipic acid (2:1:1) and salbutamol hemisuccinate salt.

    PubMed

    Paluch, Krzysztof J; Tajber, Lidia; Elcoate, Curtis J; Corrigan, Owen I; Lawrence, Simon E; Healy, Anne Marie

    2011-08-01

    The production of salt or cocrystalline forms is a common approach to alter the physicochemical properties of pharmaceutical compounds. The goal of this work was to evaluate the impact of anion choice (succinate, adipate, and sulfate) on the physicochemical characteristics of salbutamol forms. Novel crystals of salbutamol were produced by solvent evaporation: a cocrystal of salbutamol hemiadipate with adipic acid (salbutamol adipate, SA), salbutamol hemisuccinate tetramethanolate (SSU.MeOH), and its desolvated form (SSU). The crystalline materials obtained were characterized using thermal, X-ray, nuclear magnetic resonance, Fourier transform infrared spectroscopy, dynamic vapor sorption (DVS), and elemental analysis. The crystal forms of SA and SSU.MeOH were determined to be triclinic, (Pī), and monoclinic, (P2(1) /n), respectively. DVS analysis confirmed that SSU and SA do not undergo hydration under increased relative humidity. Both thermal and elemental analyses confirmed the stoichiometry of the salt forms. The aqueous solubilities of SA and SSU were measured to be 82 ± 2 mg/mL (pH 4.5 ± 0.1) and 334 ± 13 mg/mL (pH 6.6 ± 0.1), respectively. Measured values corresponded well with the calculated pH solubility profiles. The intrinsic dissolution rate of cocrystallized SA was approximately four times lower than that of SSU, suggesting its use as an alternative to more rapidly dissolving salbutamol sulfate.

  1. 21 CFR 341.12 - Antihistamine active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Antihistamine active ingredients. 341.12 Section...-COUNTER HUMAN USE Active Ingredients § 341.12 Antihistamine active ingredients. The active ingredient of... ingredient: (a) Brompheniramine maleate. (b) Chlorcyclizine hydrochloride. (c) Chlorpheniramine maleate....

  2. Minimum Risk Pesticides - Inert Ingredient and Active Ingredient Eligibility under 40 CFR 152.25(f)

    EPA Pesticide Factsheets

    Ingredients found on both the Minimum Risk Active Ingredient and List 4A Inert Ingredients of Minimal Concern lists may be used either as an active or an inert ingredient. Otherwise, it can only be used based on the list it appears on.

  3. Chemically-related Groups of Active Ingredients

    EPA Pesticide Factsheets

    Many pesticide active ingredients affect pests in similar ways, and we re-evaluate them together as a group. Groups include carbamate insecticides, neonicotinoids, organochlorines, organophosphates, pyrethrins, and pyrethroids.

  4. 21 CFR 350.10 - Antiperspirant active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Antiperspirant active ingredients. 350.10 Section...) DRUGS FOR HUMAN USE ANTIPERSPIRANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 350.10 Antiperspirant active ingredients. The active ingredient of the product consists of any of...

  5. 21 CFR 346.10 - Local anesthetic active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Local anesthetic active ingredients. 346.10... (CONTINUED) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.10 Local anesthetic active ingredients. The active ingredient of the product consists of any...

  6. 21 CFR 352.20 - Permitted combinations of active ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... active ingredients. (1) Two or more sunscreen active ingredients identified in § 352.10(a), (c), (e), (f... multiplied by 2. (2) Two or more sunscreen active ingredients identified in § 352.10(b), (c), (e), (f), (i... active ingredients identified in § 347.10(a), (d), (e), (g), (h), (i), (k), (l), (m), and (r) of...

  7. 21 CFR 352.20 - Permitted combinations of active ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... active ingredients. (1) Two or more sunscreen active ingredients identified in § 352.10(a), (c), (e), (f... multiplied by 2. (2) Two or more sunscreen active ingredients identified in § 352.10(b), (c), (e), (f), (i... active ingredients identified in § 347.10(a), (d), (e), (g), (h), (i), (k), (l), (m), and (r) of...

  8. 21 CFR 347.10 - Skin protectant active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Skin protectant active ingredients. 347.10 Section...) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 347.10 Skin protectant active ingredients. The active ingredients of the product consist of any of...

  9. 21 CFR 352.10 - Sunscreen active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Sunscreen active ingredients. 352.10 Section 352...) DRUGS FOR HUMAN USE SUNSCREEN DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 352.10 Sunscreen active ingredients. The active ingredient of the product consists of any of the following,...

  10. 21 CFR 355.10 - Anticaries active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Anticaries active ingredients. 355.10 Section 355...) DRUGS FOR HUMAN USE ANTICARIES DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 355.10 Anticaries active ingredients. The active ingredient of the product consists of any of the following...

  11. 21 CFR 347.20 - Permitted combinations of active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... combination) or more of the skin protectant active ingredients identified in § 347.10(a), (d), (e), (g), (h... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Permitted combinations of active ingredients. 347... Active Ingredients § 347.20 Permitted combinations of active ingredients. (a) Combinations of...

  12. 21 CFR 352.20 - Permitted combinations of active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... active ingredients. (1) Two or more sunscreen active ingredients identified in § 352.10(a), (c), (e), (f... multiplied by 2. (2) Two or more sunscreen active ingredients identified in § 352.10(b), (c), (e), (f), (i... active ingredients identified in § 347.10(a), (d), (e), (g), (h), (i), (k), (l), (m), and (r) of...

  13. 21 CFR 352.10 - Sunscreen active ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Sunscreen active ingredients. 352.10 Section 352...) DRUGS FOR HUMAN USE SUNSCREEN DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 352.10 Sunscreen active ingredients. The active ingredient of the product consists of any of the following,...

  14. 21 CFR 347.10 - Skin protectant active ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Skin protectant active ingredients. 347.10 Section...) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 347.10 Skin protectant active ingredients. The active ingredients of the product consist of any of...

  15. 21 CFR 341.14 - Antitussive active ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Antitussive active ingredients. 341.14 Section 341...) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 341.14 Antitussive active ingredients. The active ingredients...

  16. 21 CFR 341.14 - Antitussive active ingredients.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Antitussive active ingredients. 341.14 Section 341...) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 341.14 Antitussive active ingredients. The active ingredients...

  17. 21 CFR 341.14 - Antitussive active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Antitussive active ingredients. 341.14 Section 341...) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 341.14 Antitussive active ingredients. The active ingredients...

  18. 21 CFR 341.14 - Antitussive active ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Antitussive active ingredients. 341.14 Section 341...) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 341.14 Antitussive active ingredients. The active ingredients...

  19. 21 CFR 347.10 - Skin protectant active ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Skin protectant active ingredients. 347.10 Section...) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 347.10 Skin protectant active ingredients. The active ingredients of the product consist of any of...

  20. 21 CFR 347.10 - Skin protectant active ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Skin protectant active ingredients. 347.10 Section...) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 347.10 Skin protectant active ingredients. The active ingredients of the product consist of any of...

  1. 21 CFR 347.10 - Skin protectant active ingredients.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Skin protectant active ingredients. 347.10 Section...) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 347.10 Skin protectant active ingredients. The active ingredients of the product consist of any of...

  2. "Inactive" ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics Committee on Drugs.

    PubMed

    1997-02-01

    Because of an increasing number of reports of adverse reactions associated with pharmaceutical excipients, in 1985 the Committee on Drugs issued a position statement recommending that the Food and Drug Administration mandate labeling of over-the-counter and prescription formulations to include a qualitative list of inactive ingredients. However, labeling of inactive ingredients remains voluntary. Adverse reactions continue to be reported, although some are no longer considered clinically significant, and other new reactions have emerged. The original statement, therefore, has been updated and its information expanded.

  3. Improved metabolites of pharmaceutical ingredient grade Ginkgo biloba and the correlated proteomics analysis.

    PubMed

    Zheng, Wen; Li, Ximin; Zhang, Lin; Zhang, Yanzhen; Lu, Xiaoping; Tian, Jingkui

    2015-06-01

    Ginkgo biloba is an attractive and traditional medicinal plant, and has been widely used as a phytomedicine in the prevention and treatment of cardiovascular and cerebrovascular diseases. Flavonoids and terpene lactones are the major bioactive components of Ginkgo, whereas the ginkgolic acids (GAs) with strong allergenic properties are strictly controlled. In this study, we tested the content of flavonoids and GAs under ultraviolet-B (UV-B) treatment and performed comparative proteomic analyses to determine the differential proteins that occur upon UV-B radiation. That might play a crucial role in producing flavonoids and GAs. Our phytochemical analyses demonstrated that UV-B irradiation significantly increased the content of active flavonoids, and decreased the content of toxic GAs. We conducted comparative proteomic analysis of both whole leaf and chloroplasts proteins. In total, 27 differential proteins in the whole leaf and 43 differential proteins in the chloroplast were positively identified and functionally annotated. The proteomic data suggested that enhanced UV-B radiation exposure activated antioxidants and stress-responsive proteins as well as reduced the rate of photosynthesis. We demonstrate that UV-B irradiation pharmaceutically improved the metabolic ingredients of Ginkgo, particularly in terms of reducing GAs. With high UV absorption properties, and antioxidant activities, the flavonoids were likely highly induced as protective molecules following UV-B irradiation.

  4. 21 CFR 343.13 - Rheumatologic active ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...-COUNTER HUMAN USE Active Ingredients § 343.13 Rheumatologic active ingredients. (a) Aspirin. (b) Buffered aspirin. Aspirin identified in paragraph (a) of this section may be buffered with any antacid ingredient(s... milliequivalents of acid-neutralizing capacity per 325 milligrams of aspirin as measured by the procedure...

  5. 21 CFR 343.12 - Cardiovascular active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...-COUNTER HUMAN USE Active Ingredients § 343.12 Cardiovascular active ingredients. (a) Aspirin. (b) Buffered aspirin. Aspirin identified in paragraph (a) of this section may be buffered with any antacid ingredient(s... milliequivalents of acid-neutralizing capacity per 325 milligrams of aspirin as measured by the procedure...

  6. 21 CFR 343.13 - Rheumatologic active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...-COUNTER HUMAN USE Active Ingredients § 343.13 Rheumatologic active ingredients. (a) Aspirin. (b) Buffered aspirin. Aspirin identified in paragraph (a) of this section may be buffered with any antacid ingredient(s... milliequivalents of acid-neutralizing capacity per 325 milligrams of aspirin as measured by the procedure...

  7. 21 CFR 343.12 - Cardiovascular active ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...-COUNTER HUMAN USE Active Ingredients § 343.12 Cardiovascular active ingredients. (a) Aspirin. (b) Buffered aspirin. Aspirin identified in paragraph (a) of this section may be buffered with any antacid ingredient(s... milliequivalents of acid-neutralizing capacity per 325 milligrams of aspirin as measured by the procedure...

  8. 21 CFR 343.13 - Rheumatologic active ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...-COUNTER HUMAN USE Active Ingredients § 343.13 Rheumatologic active ingredients. (a) Aspirin. (b) Buffered aspirin. Aspirin identified in paragraph (a) of this section may be buffered with any antacid ingredient(s... milliequivalents of acid-neutralizing capacity per 325 milligrams of aspirin as measured by the procedure...

  9. 21 CFR 343.12 - Cardiovascular active ingredients.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...-COUNTER HUMAN USE Active Ingredients § 343.12 Cardiovascular active ingredients. (a) Aspirin. (b) Buffered aspirin. Aspirin identified in paragraph (a) of this section may be buffered with any antacid ingredient(s... milliequivalents of acid-neutralizing capacity per 325 milligrams of aspirin as measured by the procedure...

  10. 21 CFR 343.12 - Cardiovascular active ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...-COUNTER HUMAN USE Active Ingredients § 343.12 Cardiovascular active ingredients. (a) Aspirin. (b) Buffered aspirin. Aspirin identified in paragraph (a) of this section may be buffered with any antacid ingredient(s... milliequivalents of acid-neutralizing capacity per 325 milligrams of aspirin as measured by the procedure...

  11. 21 CFR 343.13 - Rheumatologic active ingredients.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...-COUNTER HUMAN USE Active Ingredients § 343.13 Rheumatologic active ingredients. (a) Aspirin. (b) Buffered aspirin. Aspirin identified in paragraph (a) of this section may be buffered with any antacid ingredient(s... milliequivalents of acid-neutralizing capacity per 325 milligrams of aspirin as measured by the procedure...

  12. 77 FR 60124 - Draft Guidance for Industry on Initial Completeness Assessments for Type II Active Pharmaceutical...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-02

    ... Assessments for Type II Active Pharmaceutical Ingredient Drug Master Files Under the Generic Drug User Fee... Amendments of 2012 (GDUFA), holders of certain drug master files, namely, Type II active...

  13. 21 CFR 341.40 - Permitted combinations of active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... labeled according to § 341.85. (c) Any single antihistamine active ingredient identified in § 341.12 may...) Any single antihistamine active ingredient identified in § 341.12(a) through (e) and (h) through (m... according to § 341.70(a). (h) Any single oral antitussive active ingredient identified in §...

  14. 21 CFR 331.11 - Listing of specific active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... years or older. (c) Bismuth-containing active ingredients: (1) Bismuth aluminate. (2) Bismuth carbonate.... (8) Magnesium trisilicate. (h) Milk solids, dried. (i) Phosphate-containing active ingredients: (1... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Listing of specific active ingredients....

  15. 21 CFR 333.120 - Permitted combinations of active ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... First Aid Antibiotic Drug Products § 333.120 Permitted combinations of active ingredients. The following...) Combinations of antibiotic active ingredients. (1) Bacitracin-neomycin sulfate ointment containing, in each... with a suitable filler. (b) Combinations of first aid antibiotic active ingredients and...

  16. 21 CFR 333.120 - Permitted combinations of active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... First Aid Antibiotic Drug Products § 333.120 Permitted combinations of active ingredients. The following...) Combinations of antibiotic active ingredients. (1) Bacitracin-neomycin sulfate ointment containing, in each... with a suitable filler. (b) Combinations of first aid antibiotic active ingredients and...

  17. 21 CFR 333.120 - Permitted combinations of active ingredients.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... First Aid Antibiotic Drug Products § 333.120 Permitted combinations of active ingredients. The following...) Combinations of antibiotic active ingredients. (1) Bacitracin-neomycin sulfate ointment containing, in each... with a suitable filler. (b) Combinations of first aid antibiotic active ingredients and...

  18. 21 CFR 333.120 - Permitted combinations of active ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... First Aid Antibiotic Drug Products § 333.120 Permitted combinations of active ingredients. The following...) Combinations of antibiotic active ingredients. (1) Bacitracin-neomycin sulfate ointment containing, in each... with a suitable filler. (b) Combinations of first aid antibiotic active ingredients and...

  19. 21 CFR 333.120 - Permitted combinations of active ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... First Aid Antibiotic Drug Products § 333.120 Permitted combinations of active ingredients. The following...) Combinations of antibiotic active ingredients. (1) Bacitracin-neomycin sulfate ointment containing, in each... with a suitable filler. (b) Combinations of first aid antibiotic active ingredients and...

  20. 21 CFR 347.20 - Permitted combinations of active ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... SERVICES (CONTINUED) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 347.20 Permitted combinations of active ingredients. (a) Combinations of skin...) Combinations of skin protectant and external analgesic active ingredients. Any one (two when required to be...

  1. 21 CFR 333.310 - Acne active ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 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...

  2. 21 CFR 333.310 - Acne active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 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...

  3. 21 CFR 333.310 - Acne active ingredients.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 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...

  4. 21 CFR 333.310 - Acne active ingredients.

    Code of Federal Regulations, 2010 CFR

    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...

  5. 21 CFR 333.310 - Acne active ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 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...

  6. 21 CFR 346.10 - Local anesthetic active ingredients.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Local anesthetic active ingredients. 346.10 Section 346.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... § 346.10 Local anesthetic active ingredients. The active ingredient of the product consists of any...

  7. 21 CFR 346.10 - Local anesthetic active ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Local anesthetic active ingredients. 346.10 Section 346.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... § 346.10 Local anesthetic active ingredients. The active ingredient of the product consists of any...

  8. 21 CFR 347.20 - Permitted combinations of active ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... SERVICES (CONTINUED) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 347.20 Permitted combinations of active ingredients. (a) Combinations of skin...) Combinations of skin protectant and external analgesic active ingredients. Any one (two when required to be...

  9. 21 CFR 347.20 - Permitted combinations of active ingredients.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... SERVICES (CONTINUED) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 347.20 Permitted combinations of active ingredients. (a) Combinations of skin...) Combinations of skin protectant and external analgesic active ingredients. Any one (two when required to be...

  10. 21 CFR 347.20 - Permitted combinations of active ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... SERVICES (CONTINUED) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 347.20 Permitted combinations of active ingredients. (a) Combinations of skin...) Combinations of skin protectant and external analgesic active ingredients. Any one (two when required to be...

  11. 21 CFR 346.10 - Local anesthetic active ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Local anesthetic active ingredients. 346.10 Section 346.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... § 346.10 Local anesthetic active ingredients. The active ingredient of the product consists of any...

  12. 21 CFR 346.10 - Local anesthetic active ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Local anesthetic active ingredients. 346.10 Section 346.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... § 346.10 Local anesthetic active ingredients. The active ingredient of the product consists of any...

  13. 21 CFR 344.12 - Ear drying aid active ingredient.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 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...

  14. 21 CFR 344.12 - Ear drying aid active ingredient.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 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...

  15. 21 CFR 344.12 - Ear drying aid active ingredient.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 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...

  16. 21 CFR 344.12 - Ear drying aid active ingredient.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 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...

  17. 21 CFR 344.12 - Ear drying aid active ingredient.

    Code of Federal Regulations, 2010 CFR

    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...

  18. 21 CFR 358.720 - Permitted combinations of active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... solution, on a weight to volume basis, in combination with menthol, 1.5 percent, in a shampoo formulation... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Permitted combinations of active ingredients. 358... Permitted combinations of active ingredients. (a) Combination of active ingredients for the control...

  19. Electrochemical oxidation coupled with liquid chromatography and mass spectrometry to study the oxidative stability of active pharmaceutical ingredients in solution: A comparison of off-line and on-line approaches.

    PubMed

    Torres, Susana; Brown, Roland; Zelesky, Todd; Scrivens, Garry; Szucs, Roman; Hawkins, Joel M; Taylor, Mark R

    2016-11-30

    Stability studies of pharmaceutical drug products and pharmaceutical active substances are important to research and development in order to fully understand and maintain product quality and safety throughout its shelf-life. Oxidative forced degradation studies are among the different types of stability studies performed by the pharmaceutical industry in order to understand the intrinsic stability of drug molecules. We have been comparing the use of electrochemistry as an alternative oxidative forced degradation method to traditional forced degradation and accelerated stability studies. Using the electrochemical degradation approach the substrate oxidation takes place in a commercially available electrochemical cell and the effluent of the cell can be either a) directly infused into the mass spectrometer or b) injected in a chromatographic column for separation of the different products formed prior to the mass spectrometry analysis. To enable the study of large numbers of different experimental conditions and molecules we developed a new dual pump automated electrochemical screening platform. This system used a HPLC pump and autosampler to load and wash the electrochemical cell and deliver the oxidized sample plug to a second injection loop. This system enabled the automatic sequential analyses of large numbers of different solutions under varied experimental conditions without need for operator intervention during the run sequence. Here we describe the system and evaluate its performance using a test molecule with well characterized stability and compare results to those obtained using an off-line electrochemistry approach.

  20. 21 CFR 352.20 - Permitted combinations of active ingredients.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Ingredients § 352.20 Permitted combinations of active ingredients. The SPF of any combination product is... sufficient to contribute a minimum SPF of not less than 2 to the finished product. The finished product must have a minimum SPF of not less than the number of sunscreen active ingredients used in the...

  1. 21 CFR 352.20 - Permitted combinations of active ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Ingredients § 352.20 Permitted combinations of active ingredients. The SPF of any combination product is... sufficient to contribute a minimum SPF of not less than 2 to the finished product. The finished product must have a minimum SPF of not less than the number of sunscreen active ingredients used in the...

  2. Polyphenols as active ingredients for cosmetic products.

    PubMed

    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.

  3. Photocatalytic degradation of sunscreen active ingredients mediated by nanostructured materials

    NASA Astrophysics Data System (ADS)

    Soto-Vazquez, Loraine

    Water scarcity and pollution are environmental issues with terrible consequences. In recent years several pharmaceutical and personal care products, such as sunscreen active ingredients, have been detected in different water matrices. Its recalcitrant behavior in the environment has caused controversies and generated countless questions about its safety. During this research, we employed an advanced oxidation process (photocatalysis) to degrade sunscreen active ingredients. For this study, we used a 3x3 system, evaluating three photocatalysts and three different contaminants. From the three catalysts employed, two of them were synthesized. ZnO nanoparticles were obtained using zinc acetate dihydrated as the precursor, and TiO2 nanowires were synthesized from titanium tetrachloride precursor. The third catalyst employed (namely, P25) was obtained commercially. The synthesized photocatalysts were characterized in terms of the morphology, elemental composition, crystalline structure, elemental oxidation states, vibrational modes and surface area, using SEM-EDS, XRD, XPS, Raman spectroscopy and BET measurements, respectively. The photocatalysts were employed during the study of the degradation of p-aminobenzoic acid, phenylbenzimidazole sulfonic acid, and benzophenone-4. In all the cases, at least 50% degradation was achieved. P25 showed degradation efficiencies above 90%, and from the nine systems, 7 of them degraded at least 86%.

  4. APT drug R&D: the right active ingredient in the right presentation for the right therapeutic use.

    PubMed

    Cavalla, David

    2009-11-01

    Drug repurposing, in which an established active pharmaceutical ingredient is applied in a new way - for example, for a new indication, and often combined with an alternative method of presentation, such as a novel delivery route - is an evolving strategy for pharmaceutical R&D. This article discusses examples of the success of this strategy, and presents an analysis of sales of US pharmaceutical products that suggests that this low-risk approach to new product development retains substantial commercial value.

  5. Antibotulinal activity of process cheese ingredients.

    PubMed

    Glass, Kathleen A; Johnson, Eric A

    2004-08-01

    Ingredients used in the manufacture of reduced-fat process cheese products were screened for their ability to inhibit growth of Clostridium botulinum serotypes A and B in media. Reinforced clostridial medium (RCM) supplemented with 0, 0.5, 1, 2, 3, 5, or 10% (wt/vol) of various ingredients, including a carbohydrate-based fat replacer, an enzyme-modified cheese (EMC) derived from a Blue cheese, sweet whey, modified whey protein, or whey protein concentrate, did not inhibit botulinal growth and toxin production when stored at 30 degrees C for 1 week. In contrast, RCM supplemented with 10% soy-based flavor enhancer, 10% Parmesan EMC, or 5 or 10% Cheddar EMC inhibited botulinal toxin production in media for at least 6 weeks of storage at 30 degrees C. Subsequent trials revealed that the antibotulinal effect varied significantly among 13 lots of EMC and that the antimicrobial effect was not correlated with the pH or water activity of the EMC.

  6. Endocrine-Active Pharmaceuticals: An Environmental Concern?

    EPA Science Inventory

    Recently, there has been growing interest in pharmaceuticals that are specifically designed to have endocrine activity, such as the estrogens used in birth control pills, exerting unintended effects on fish and other aquatic organisms. These pharmaceuticals may not be persistent...

  7. 21 CFR 333.110 - First aid antibiotic active ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false First aid antibiotic active ingredients. 333.110 Section 333.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Antibiotic Drug Products § 333.110 First aid antibiotic active ingredients. The product consists of any...

  8. 21 CFR 333.110 - First aid antibiotic active ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false First aid antibiotic active ingredients. 333.110 Section 333.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Antibiotic Drug Products § 333.110 First aid antibiotic active ingredients. The product consists of any...

  9. 21 CFR 333.110 - First aid antibiotic active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false First aid antibiotic active ingredients. 333.110 Section 333.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Antibiotic Drug Products § 333.110 First aid antibiotic active ingredients. The product consists of any...

  10. 21 CFR 333.110 - First aid antibiotic active ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false First aid antibiotic active ingredients. 333.110 Section 333.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Antibiotic Drug Products § 333.110 First aid antibiotic active ingredients. The product consists of any...

  11. 21 CFR 333.110 - First aid antibiotic active ingredients.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false First aid antibiotic active ingredients. 333.110 Section 333.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Antibiotic Drug Products § 333.110 First aid antibiotic active ingredients. The product consists of any...

  12. 21 CFR 341.40 - Permitted combinations of active ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... with any generally recognized as safe and effective single oral anesthetic/analgesic active ingredient, or any combination of anesthetic/analgesic active ingredients provided that the product is available.... Menthol in § 341.14(b)(2) and part 356 of this chapter may be both the antitussive and the...

  13. 21 CFR 341.40 - Permitted combinations of active ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... with any generally recognized as safe and effective single oral anesthetic/analgesic active ingredient, or any combination of anesthetic/analgesic active ingredients provided that the product is available.... Menthol in § 341.14(b)(2) and part 356 of this chapter may be both the antitussive and the...

  14. Essential oils as active ingredients of lipid nanocarriers for chemotherapeutic use.

    PubMed

    Severino, Patricia; Andreani, Tatiana; Chaud, Marco V; Benites, Cibelem I; Pinho, Samantha C; Souto, Eliana B

    2015-01-01

    Essential oils have increased interest as promising ingredients for novel pharmaceutical dosage forms. These oils are reported to provide synergistic effects of their active ingredients, in parallel with their biodegradable properties. In addition, essential oils may also have therapeutic effects in diabetes, inflammation, cancer and to treat microbial infections. However, there are some physicochemical properties that may limit their use as active compounds in several formulations, such as high volatility, low-appealing organoleptic properties, low bioavailability and physicochemical instability, as result of exposure to light, oxygen and high temperatures. To overcome these limitations, lipid colloidal carriers (e.g. liposomes, solid lipid nanoparticles (SLN), self nanoemulsified drug delivery systems (SNEDDS)) have been pointed out as suitable carriers to improve bioavailability, low solubility, taste, flavor and long-term storage of sensitive compounds. This paper reviews the potential beneficial effects of formulating essential oils in pharmaceutical applications using colloidal carriers as delivery systems.

  15. Stability analysis for drugs with multiple active ingredients.

    PubMed

    Chow, Shein-Chung; Shao, Jun

    2007-03-30

    For every drug product on the market, the United States Food and Drug Administration (FDA) requires that an expiration dating period (shelf-life) must be indicated on the immediate container label. For determination of the expiration dating period of a drug product, regulatory requirements and statistical methodology are provided in the FDA and ICH Guidelines. However, this guideline is developed for drug products with a single active ingredient. There are many drug products consisting of multiple active ingredients, especially for most traditional Chinese medicine. In this article, we propose a statistical method for determining the shelf-life of a drug product with multiple active ingredients following similar idea as suggested by the FDA and assuming that these active ingredients are linear combinations of some factors. Stability data observed from a traditional Chinese medicine were analysed to illustrate the proposed method.

  16. A survey of Chinese herbal ingredients with liver protection activities

    PubMed Central

    Wang, Rubin; Kong, John; Wang, Dali; Lien, Linda Lin-min; Lien, Eric Jung-chi

    2007-01-01

    A literature survey was conducted on herbs, their preparations and ingredients with reported liver protection activities, in which a total of 274 different species and hundreds of active ingredients have been examined. These ingredients can be roughly classified into two categories according to their activities: (1) the main ingredients, such as silybin, osthole, coumarin, glycyrrhizin, saikosaponin A, schisandrin A, flavonoids; and (2) supporting substances, such as sugars, amino acids, resins, tannins and volatile oil. Among them, some active ingredients have hepatoprotective activities (e.g. anti-inflammatory, anticancer, antioxidant, immunomodulating and liver cirrhosis-regulating effects). Calculation of physicochemical parameters indicates that the main ingredients with negative and positive Elumo values possibly display their hepatoprotective effects through different mechanisms, such as antioxidative, anti-inflammatory and immunomodulating effects. As the combination of herbs may achieve some treatment effects synergistically and/or additively, it is common in Chinese medicine to use mixtures of various medicinal herbs with pharmacologically active compounds to have synergistic and/or additive effects, or to reduce harmful effects of some pharmacologically active compounds. In particular, the active compounds with Clog P around 2 are suitable for passive transport across membranes and accessible to the target sites. Thus, Elumo and Clog P values are good indicators among the calculated parameters. Seven different physicochemical parameters (MW, Clog P, CMR, μ, Ehomo, Elumo and Hf) and four major biological activities (antioxidant, anti-inflammatory, antiviral/antitumor and immunomodulating) are discussed in this review. It is hoped that the discussion may provide some leads in the development of new hepatoprotective drugs. PMID:17490493

  17. 21 CFR 338.10 - Nighttime sleep-aid active ingredients.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 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...

  18. 21 CFR 338.10 - Nighttime sleep-aid active ingredients.

    Code of Federal Regulations, 2010 CFR

    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...

  19. 21 CFR 338.10 - Nighttime sleep-aid active ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 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...

  20. 21 CFR 338.10 - Nighttime sleep-aid active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 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...

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

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 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. 21 CFR 347.12 - Astringent active ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Astringent active ingredients. 347.12 Section 347.12 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active...

  3. 21 CFR 347.12 - Astringent active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Astringent active ingredients. 347.12 Section 347.12 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active...

  4. 21 CFR 347.12 - Astringent active ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Astringent active ingredients. 347.12 Section 347.12 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active...

  5. 21 CFR 347.12 - Astringent active ingredients.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Astringent active ingredients. 347.12 Section 347.12 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active...

  6. 21 CFR 347.12 - Astringent active ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Astringent active ingredients. 347.12 Section 347.12 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active...

  7. Compaction properties of crystalline pharmaceutical ingredients according to the Walker model and nanomechanical attributes.

    PubMed

    Egart, M; Ilić, I; Janković, B; Lah, N; Srčič, S

    2014-09-10

    This study investigates the extent to which single-crystal mechanical properties of selected active ingredients (famotidine, nifedipine, olanzapine, piroxicam) influence their bulk compressibility and compactibility. Nanomechanical attributes of oriented single crystals were determined with instrumented nanoindentation, and bulk deformational properties were assessed with the Walker and Heckel models as well as the elastic relaxation index. Good correlations were established between bulk and single-crystal plasticity parameters: the Walker coefficient and indentation hardness. The Walker model showed more practical value for evaluating bulk deformational properties of the APIs investigated because their properties differed more distinctly compared to the Heckel model. In addition, it was possible to predict the elastic properties of the materials investigated at the bulk level because a correlation between the elastic relaxation index and compliance was established. The value of using indentation hardness for crystalline APIs was also confirmed because their compactibility at the bulk level was able to be predicted. Mechanically interlocked structures were characteristic of most polymorphic forms investigated, resulting in single crystals having isotropic mechanical properties. It was revealed that in such cases good correlations between single and bulk mechanical properties can be expected. The results imply that innate crystal deformational properties define their compressibility and compactibility properties to a great extent.

  8. Microbial Content of Nonsterile Therapeutic Agents Containing Natural or Seminatural Active Ingredients

    PubMed Central

    Schiller, I.; Kuntscher, H.; Wolff, A.; Nekola, M.

    1968-01-01

    The relationship was investigated between various chemical or pharmaceutical production processes and the extent of microbial contamination, of natural origin, of the resulting products. The products contained active ingredients of vegetable, enzymatic, or animal origin. It was concluded that (i) vegetable products practically free from microbes can be produced if the proper manufacturing steps are taken; (ii) sterilization of the media used to manufacture antibiotics, etc., produces products with little contamination; and (iii) products containing extracts of animal organs require careful refrigeration and addition of preservatives to produce acceptable levels of microbial contamination. PMID:5726165

  9. 21 CFR 346.16 - Analgesic, anesthetic, and antipruritic active ingredients.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Analgesic, anesthetic, and antipruritic active ingredients. 346.16 Section 346.16 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Ingredients § 346.16 Analgesic, anesthetic, and antipruritic active ingredients. The active ingredient of...

  10. 21 CFR 346.16 - Analgesic, anesthetic, and antipruritic active ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Analgesic, anesthetic, and antipruritic active ingredients. 346.16 Section 346.16 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Ingredients § 346.16 Analgesic, anesthetic, and antipruritic active ingredients. The active ingredient of...

  11. 21 CFR 346.16 - Analgesic, anesthetic, and antipruritic active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Analgesic, anesthetic, and antipruritic active ingredients. 346.16 Section 346.16 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Ingredients § 346.16 Analgesic, anesthetic, and antipruritic active ingredients. The active ingredient of...

  12. 21 CFR 346.16 - Analgesic, anesthetic, and antipruritic active ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Analgesic, anesthetic, and antipruritic active ingredients. 346.16 Section 346.16 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Ingredients § 346.16 Analgesic, anesthetic, and antipruritic active ingredients. The active ingredient of...

  13. 21 CFR 346.16 - Analgesic, anesthetic, and antipruritic active ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Analgesic, anesthetic, and antipruritic active ingredients. 346.16 Section 346.16 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Ingredients § 346.16 Analgesic, anesthetic, and antipruritic active ingredients. The active ingredient of...

  14. Metabolically active functional food ingredients for weight control.

    PubMed

    Kovacs, E M R; Mela, D J

    2006-02-01

    The scale of the obesity epidemic creates a pressing consumer need as well as an enormous business opportunity for successful development and marketing of food products with added benefits for weight control. A number of proposed functional food ingredients have been shown to act post-absorptively to influence substrate utilization or thermogenesis. Characteristics and supporting data on conjugated linoleic acid, diglycerides, medium-chain triglycerides, green tea, ephedrine, caffeine, capsaicin and calcium, are reviewed here, giving examples of how these could act to alter energy expenditure or appetite control. Consideration is also given to other factors, in addition to efficacy, which must be satisfied to get such ingredients into foods. We conclude that, for each of the safe, putatively metabolically active agents, there remain gaps in clinical evidence or knowledge of mechanisms, which need to be addressed in order to specify the dietary conditions and food product compositions where these ingredients could be of most benefit for weight control.

  15. 21 CFR 341.40 - Permitted combinations of active ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG... antitussive active ingredient identified in § 341.14(a)(1) through (a)(4) provided that the product is labeled... hydrochloride in §§ 341.12(g) and 341.14(a)(6) may be both the antihistamine and the antitussive...

  16. 21 CFR 341.18 - Expectorant active ingredient.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Expectorant active ingredient. 341.18 Section 341.18 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR...

  17. 21 CFR 341.18 - Expectorant active ingredient.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Expectorant active ingredient. 341.18 Section 341.18 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR...

  18. 21 CFR 341.16 - Bronchodilator active ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Bronchodilator active ingredients. 341.16 Section 341.16 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR...

  19. 21 CFR 341.18 - Expectorant active ingredient.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Expectorant active ingredient. 341.18 Section 341.18 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR...

  20. 21 CFR 341.16 - Bronchodilator active ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Bronchodilator active ingredients. 341.16 Section 341.16 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR...

  1. 21 CFR 341.12 - Antihistamine active ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Antihistamine active ingredients. 341.12 Section 341.12 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR...

  2. 21 CFR 341.18 - Expectorant active ingredient.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Expectorant active ingredient. 341.18 Section 341.18 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR...

  3. 21 CFR 341.20 - Nasal decongestant active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Nasal decongestant active ingredients. 341.20 Section 341.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS...

  4. 21 CFR 341.20 - Nasal decongestant active ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Nasal decongestant active ingredients. 341.20 Section 341.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS...

  5. 21 CFR 341.16 - Bronchodilator active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Bronchodilator active ingredients. 341.16 Section 341.16 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR...

  6. 21 CFR 341.40 - Permitted combinations of active ingredients.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG... antitussive active ingredient identified in § 341.14(a)(1) through (a)(4) provided that the product is labeled... hydrochloride in §§ 341.12(g) and 341.14(a)(6) may be both the antihistamine and the antitussive...

  7. 21 CFR 341.12 - Antihistamine active ingredients.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Antihistamine active ingredients. 341.12 Section 341.12 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR...

  8. 21 CFR 341.16 - Bronchodilator active ingredients.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Bronchodilator active ingredients. 341.16 Section 341.16 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR...

  9. 21 CFR 341.20 - Nasal decongestant active ingredients.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Nasal decongestant active ingredients. 341.20 Section 341.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS...

  10. 21 CFR 341.12 - Antihistamine active ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Antihistamine active ingredients. 341.12 Section 341.12 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR...

  11. 21 CFR 341.20 - Nasal decongestant active ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Nasal decongestant active ingredients. 341.20 Section 341.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS...

  12. 21 CFR 331.11 - Listing of specific active ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... ion; maximum daily dosage limit 200 mEq. for persons up to 60 years old and 100 mEq. for persons 60...., 8 grams calcium carbonate). (e) Citrate-containing active ingredients: Citrate ion, as citric acid... effervescent preparation); maximum daily dosage limit 200 mEq. of bicarbonate ion for persons up to 60...

  13. 21 CFR 331.11 - Listing of specific active ingredients.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... ion; maximum daily dosage limit 200 mEq. for persons up to 60 years old and 100 mEq. for persons 60...., 8 grams calcium carbonate). (e) Citrate-containing active ingredients: Citrate ion, as citric acid... effervescent preparation); maximum daily dosage limit 200 mEq. of bicarbonate ion for persons up to 60...

  14. 21 CFR 331.11 - Listing of specific active ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... ion; maximum daily dosage limit 200 mEq. for persons up to 60 years old and 100 mEq. for persons 60...., 8 grams calcium carbonate). (e) Citrate-containing active ingredients: Citrate ion, as citric acid... effervescent preparation); maximum daily dosage limit 200 mEq. of bicarbonate ion for persons up to 60...

  15. 21 CFR 331.11 - Listing of specific active ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... ion; maximum daily dosage limit 200 mEq. for persons up to 60 years old and 100 mEq. for persons 60...., 8 grams calcium carbonate). (e) Citrate-containing active ingredients: Citrate ion, as citric acid... effervescent preparation); maximum daily dosage limit 200 mEq. of bicarbonate ion for persons up to 60...

  16. 21 CFR 358.720 - Permitted combinations of active ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... dandruff. Salicylic acid identified in § 358.710(a)(4) may be combined with sulfur identified in § 358.710... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Permitted combinations of active ingredients. 358.720 Section 358.720 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND...

  17. 21 CFR 343.13 - Rheumatologic active ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Rheumatologic active ingredients. 343.13 Section 343.13 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE INTERNAL ANALGESIC, ANTIPYRETIC, AND ANTIRHEUMATIC DRUG PRODUCTS FOR...

  18. 21 CFR 343.12 - Cardiovascular active ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Cardiovascular active ingredients. 343.12 Section 343.12 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE INTERNAL ANALGESIC, ANTIPYRETIC, AND ANTIRHEUMATIC DRUG PRODUCTS FOR...

  19. 21 CFR 344.10 - Earwax removal aid active ingredient.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Earwax removal aid active ingredient. 344.10 Section 344.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... carbamide peroxide 6.5 percent formulated in an anhydrous glycerin vehicle....

  20. 21 CFR 341.20 - Nasal decongestant active ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Nasal decongestant active ingredients. 341.20 Section 341.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS...

  1. 21 CFR 341.16 - Bronchodilator active ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Bronchodilator active ingredients. 341.16 Section 341.16 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR...

  2. 21 CFR 341.14 - Antitussive active ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Antitussive active ingredients. 341.14 Section 341.14 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR...

  3. 21 CFR 341.12 - Antihistamine active ingredients.

    Code of Federal Regulations, 2010 CFR

    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) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR...

  4. 21 CFR 341.18 - Expectorant active ingredient.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Expectorant active ingredient. 341.18 Section 341.18 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR...

  5. 78 FR 64937 - Pesticide Products; Registration Applications for New Active Ingredients

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-30

    ....), Avda, Paret del Patriarca 11-B, Ap. 30, 46113 Moncada (Valencia) Spain. Active ingredient: Bacillus.... 30, 46113 Moncada (Valencia) Spain. Active ingredient: Bacillus subtilis strain IAB/BS03....

  6. 78 FR 75343 - Pesticide Products; Registration Applications for New Active Ingredients

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-11

    ... AGENCY Pesticide Products; Registration Applications for New Active Ingredients AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY: EPA has received several applications to register pesticide products containing active ingredients not included in any currently registered pesticide...

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

    NASA Astrophysics Data System (ADS)

    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. 21 CFR 348.10 - Analgesic, anesthetic, and antipruritic active ingredients.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Analgesic, anesthetic, and antipruritic active ingredients. 348.10 Section 348.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Active Ingredients § 348.10 Analgesic, anesthetic, and antipruritic active ingredients. The...

  9. 21 CFR 348.10 - Analgesic, anesthetic, and antipruritic active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Analgesic, anesthetic, and antipruritic active ingredients. 348.10 Section 348.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Active Ingredients § 348.10 Analgesic, anesthetic, and antipruritic active ingredients. The...

  10. 21 CFR 348.10 - Analgesic, anesthetic, and antipruritic active ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Analgesic, anesthetic, and antipruritic active ingredients. 348.10 Section 348.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Active Ingredients § 348.10 Analgesic, anesthetic, and antipruritic active ingredients. The...

  11. 21 CFR 348.10 - Analgesic, anesthetic, and antipruritic active ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Analgesic, anesthetic, and antipruritic active ingredients. 348.10 Section 348.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Active Ingredients § 348.10 Analgesic, anesthetic, and antipruritic active ingredients. The...

  12. 21 CFR 348.10 - Analgesic, anesthetic, and antipruritic active ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Analgesic, anesthetic, and antipruritic active ingredients. 348.10 Section 348.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Active Ingredients § 348.10 Analgesic, anesthetic, and antipruritic active ingredients. The...

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

    EPA Science Inventory

    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...

  14. 21 CFR 343.22 - Permitted combinations of active ingredients for cardiovascular-rheumatologic use.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... active ingredients for cardiovascular-rheumatologic use. Combinations containing aspirin must meet the... permitted: Aspirin identified in §§ 343.12 and 343.13 may be combined with any antacid ingredient...

  15. 21 CFR 343.22 - Permitted combinations of active ingredients for cardiovascular-rheumatologic use.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... active ingredients for cardiovascular-rheumatologic use. Combinations containing aspirin must meet the... permitted: Aspirin identified in §§ 343.12 and 343.13 may be combined with any antacid ingredient...

  16. 21 CFR 343.22 - Permitted combinations of active ingredients for cardiovascular-rheumatologic use.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... active ingredients for cardiovascular-rheumatologic use. Combinations containing aspirin must meet the... permitted: Aspirin identified in §§ 343.12 and 343.13 may be combined with any antacid ingredient...

  17. 21 CFR 343.22 - Permitted combinations of active ingredients for cardiovascular-rheumatologic use.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... active ingredients for cardiovascular-rheumatologic use. Combinations containing aspirin must meet the... permitted: Aspirin identified in §§ 343.12 and 343.13 may be combined with any antacid ingredient...

  18. Comparative Solid-State Stability of Perindopril Active Substance vs. Pharmaceutical Formulation

    PubMed Central

    Buda, Valentina; Andor, Minodora; Ledeti, Adriana; Ledeti, Ionut; Vlase, Gabriela; Vlase, Titus; Cristescu, Carmen; Voicu, Mirela; Suciu, Liana; Tomescu, Mirela Cleopatra

    2017-01-01

    This paper presents the results obtained after studying the thermal stability and decomposition kinetics of perindopril erbumine as a pure active pharmaceutical ingredient as well as a solid pharmaceutical formulation containing the same active pharmaceutical ingredient (API). Since no data were found in the literature regarding the spectroscopic description, thermal behavior, or decomposition kinetics of perindopril, our goal was the evaluation of the compatibility of this antihypertensive agent with the excipients in the tablet under ambient conditions and to study the effect of thermal treatment on the stability of perindopril erbumine. ATR-FTIR (Attenuated Total Reflectance Fourier Transform Infrared) spectroscopy, thermal analysis (thermogravimetric mass curve (TG—thermogravimetry), derivative thermogravimetric mass curve (DTG), and heat flow (HF)) and model-free kinetics were chosen as investigational tools. Since thermal behavior is a simplistic approach in evaluating the thermal stability of pharmaceuticals, in-depth kinetic studies were carried out by classical kinetic methods (Kissinger and ASTM E698) and later with the isoconversional methods of Friedman, Kissinger-Akahira-Sunose and Flynn-Wall-Ozawa. It was shown that the main thermal degradation step of perindopril erbumine is characterized by activation energy between 59 and 69 kJ/mol (depending on the method used), while for the tablet, the values were around 170 kJ/mol. The used excipients (anhydrous colloidal silica, microcrystalline cellulose, lactose, and magnesium stearate) should be used in newly-developed generic solid pharmaceutical formulations, since they contribute to an increased thermal stability of perindopril erbumine. PMID:28098840

  19. Risks to aquatic organisms posed by human pharmaceutical use

    EPA Science Inventory

    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 ...

  20. Predicting variability of aquatic concentrations of human pharmaceuticals

    EPA Science Inventory

    Potential exposure to active pharmaceutical ingredients (APIs) in the aquatic environment is a subject of ongoing concern. We recently estimated maximum likely potency-normalized exposure rates at the national level for several hundred commonly used human prescription pharmaceut...

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

    PubMed

    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.

  2. Prioritizing pharmaceuticals in municipal wastewater

    EPA Science Inventory

    Oral presentation at SETAC North America 32nd annual meeting, describing our prioritization of active pharmaceutical ingredients (APIs), based on estimates of risks posed by API residues originating from municipal wastewater. Goals of this project include prioritization of APIs f...

  3. Intestinal, portal, and peripheral profiles of daikenchuto (TU-100)'s active ingredients after oral administration

    PubMed Central

    Watanabe, Junko; Kaifuchi, Noriko; Kushida, Hirotaka; Matsumoto, Takashi; Fukutake, Miwako; Nishiyama, Mitsue; Yamamoto, Masahiro; Kono, Toru

    2015-01-01

    A pharmaceutical grade Japanese traditional medicine, daikenchuto (TU-100), consisting of Japanese pepper, processed ginger, and ginseng, has been widely used for various intestinal disorders in Japan and now under development as a new therapeutic drug in the US. It is suggested that TU-100 ingredients exert pharmacological effects on intestines via two routes, from the luminal side before absorption and the peripheral blood stream after absorption. Therefore, in order to fully understand the pharmacological actions of TU-100, it is critically important to know the intraluminal amounts and forms of ingested TU-100 ingredients. In the present study, after administrating TU-100 to rats, the concentrations of TU-100 ingredients and their conjugates in the peripheral and portal blood and ileal contents were determined by LC-MS/MS. Next, TU-100 was administered to patients with ileostomy bags, but whose small intestines are diagnosed as healthy, and the ingredients/conjugates in the ileal effluent were analyzed. The results suggest that: (1) Pepper ingredients hydroxysanshools are rapidly absorbed and enter systemic circulation, (2) Ginseng ingredients ginsenosides are transported to the colon with the least absorption, (3) Ginger ingredients gingerols are absorbed and some conjugated in the small intestine and transported via the portal vein. While only a small amount of gingerols/gingerol conjugates enter systemic circulation, considerable amounts reappear in the small intestine. Thus, the effect of TU-100 on the intestines is believed to be a composite of multiple actions by multiple compounds supplied via multiple routes. PMID:26516578

  4. Intestinal, portal, and peripheral profiles of daikenchuto (TU-100)'s active ingredients after oral administration.

    PubMed

    Watanabe, Junko; Kaifuchi, Noriko; Kushida, Hirotaka; Matsumoto, Takashi; Fukutake, Miwako; Nishiyama, Mitsue; Yamamoto, Masahiro; Kono, Toru

    2015-10-01

    A pharmaceutical grade Japanese traditional medicine, daikenchuto (TU-100), consisting of Japanese pepper, processed ginger, and ginseng, has been widely used for various intestinal disorders in Japan and now under development as a new therapeutic drug in the US. It is suggested that TU-100 ingredients exert pharmacological effects on intestines via two routes, from the luminal side before absorption and the peripheral blood stream after absorption. Therefore, in order to fully understand the pharmacological actions of TU-100, it is critically important to know the intraluminal amounts and forms of ingested TU-100 ingredients. In the present study, after administrating TU-100 to rats, the concentrations of TU-100 ingredients and their conjugates in the peripheral and portal blood and ileal contents were determined by LC-MS/MS. Next, TU-100 was administered to patients with ileostomy bags, but whose small intestines are diagnosed as healthy, and the ingredients/conjugates in the ileal effluent were analyzed. The results suggest that: (1) Pepper ingredients hydroxysanshools are rapidly absorbed and enter systemic circulation, (2) Ginseng ingredients ginsenosides are transported to the colon with the least absorption, (3) Ginger ingredients gingerols are absorbed and some conjugated in the small intestine and transported via the portal vein. While only a small amount of gingerols/gingerol conjugates enter systemic circulation, considerable amounts reappear in the small intestine. Thus, the effect of TU-100 on the intestines is believed to be a composite of multiple actions by multiple compounds supplied via multiple routes.

  5. STUDY ON THE DIFFERENCES OF MAJOR PHARMACEUTICAL INGREDIENTS IN DIFFERENT PARTS AND PROCESSED MEDICINAL MATERIAL OF EPIMEDIUM BREVICORNU MAXIM IN TAIHANG MOUNTAIN.

    PubMed

    Zai-you, Jian; Gui-fang, Xu; Hong-zhi, Chen; Hong-sheng, Wang; Xi-qiao, Hu

    2015-08-01

    The aim of this study is to evaluate the medicinal values of different parts of Epimedium brevicornu Maxim. and the effect of processing on major pharmaceutical ingredients in it. The contents of icariin and epimedin C in different parts and processed medicinal material of E. brevicornu in Taihang Mountain were determined with ultrasonic extraction and RP-HPLC. The results indicated that the contents of icariin and epimedin C, respectively 3.4524% and 0.5485%, in the leaf are higher than that in other parts. The contents of icariin and epimedin C, respectively 0.1942 % and 0.1342%, in the stem (include petiole) are the lowest. The contents of these ingredients in the root (include rhizome) are close to that in the leaf. The icariin and epimedin C in all parts of E. brevicornu reduced after processing. The content of icariin in the processed leaf is about 59.5% of that in unprocessed leaves. The effect of prossing on the content of icariin in the stem is unobvious. The content of epimedin C in the processed leaf is about 33.7% of that in unprocessed leaf. The content of epimedin C in the processed stem (include petiole) is about 36.9% of that in unprocessed stem. It is worth to exploit the stem and petiole of E. brevicornu because there are certain contents of pharmaceutical ingredients in them. The firepower should be paid attention to and the temperature should not be very high to avoid the damage on pharmaceutical ingredients in E. brevicornu when process it.

  6. The THz fingerprint spectra of the active ingredients of a TCM medicine: Herba Ephedrae

    NASA Astrophysics Data System (ADS)

    Ma, Shihua; Liu, Guifeng; Zhang, Peng; Song, Xiyu; Ji, Te; Wang, Wenfeng

    2008-12-01

    In this paper, THz-TDS has been used to measure the spectral properties of two active ingredients of Herba Ephedrae: ephedrine and pseudoephedrine, which exist in hydrochloride salts. The THz spectra of the sole-ingredient, twoingredient and three-ingredient compounds are studied. We obtained the finger-print spectra of the net active ingredients of the medicine, and also measured the mixtures of by two or three active ingredients at the different ratios. At the same time, theoretical analysis and quantitative analysis is applied to foretell the different THz spectra, identify the ingredients and infer the contents of principal components in samples. The THz spectroscopy is a potential and promising technique in evaluating and inspecting the quality of the drugs in the TCM field.

  7. 21 CFR 358.110 - Wart remover active ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... ingredient. (a) Salicylic acid 12 to 40 percent in a plaster vehicle. (b) Salicylic acid 5 to 17 percent in a collodion-like vehicle. (c) Salicylic acid 15 percent in a karaya gum, glycol plaster vehicle....

  8. 21 CFR 358.110 - Wart remover active ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... ingredient. (a) Salicylic acid 12 to 40 percent in a plaster vehicle. (b) Salicylic acid 5 to 17 percent in a collodion-like vehicle. (c) Salicylic acid 15 percent in a karaya gum, glycol plaster vehicle....

  9. 21 CFR 358.110 - Wart remover active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... ingredient. (a) Salicylic acid 12 to 40 percent in a plaster vehicle. (b) Salicylic acid 5 to 17 percent in a collodion-like vehicle. (c) Salicylic acid 15 percent in a karaya gum, glycol plaster vehicle....

  10. 21 CFR 358.110 - Wart remover active ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... ingredient. (a) Salicylic acid 12 to 40 percent in a plaster vehicle. (b) Salicylic acid 5 to 17 percent in a collodion-like vehicle. (c) Salicylic acid 15 percent in a karaya gum, glycol plaster vehicle....

  11. 21 CFR 358.110 - Wart remover active ingredients.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... ingredient. (a) Salicylic acid 12 to 40 percent in a plaster vehicle. (b) Salicylic acid 5 to 17 percent in a collodion-like vehicle. (c) Salicylic acid 15 percent in a karaya gum, glycol plaster vehicle....

  12. 21 CFR 331.15 - Combination with nonantacid active ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... solely for the concurrent symptoms involved, e.g., headache and acid indigestion, and is marketed in a... and effective antiflatulent ingredient if it is indicated for use solely for the concurrent...

  13. 21 CFR 358.510 - Corn and callus remover active ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Corn and callus remover active ingredients. 358.510 Section 358.510 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... USE Corn and Callus Remover Drug Products § 358.510 Corn and callus remover active ingredients....

  14. 21 CFR 358.510 - Corn and callus remover active ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Corn and callus remover active ingredients. 358.510 Section 358.510 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... USE Corn and Callus Remover Drug Products § 358.510 Corn and callus remover active ingredients....

  15. 21 CFR 358.510 - Corn and callus remover active ingredients.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Corn and callus remover active ingredients. 358.510 Section 358.510 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... USE Corn and Callus Remover Drug Products § 358.510 Corn and callus remover active ingredients....

  16. 21 CFR 358.510 - Corn and callus remover active ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Corn and callus remover active ingredients. 358.510 Section 358.510 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... USE Corn and Callus Remover Drug Products § 358.510 Corn and callus remover active ingredients....

  17. 21 CFR 358.510 - Corn and callus remover active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Corn and callus remover active ingredients. 358.510 Section 358.510 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... USE Corn and Callus Remover Drug Products § 358.510 Corn and callus remover active ingredients....

  18. 21 CFR 357.810 - Active ingredients for deodorant drug products for internal use.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Active ingredients for deodorant drug products for internal use. 357.810 Section 357.810 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... HUMAN USE Deodorant Drug Products for Internal Use § 357.810 Active ingredients for deodorant...

  19. 21 CFR 357.810 - Active ingredients for deodorant drug products for internal use.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Active ingredients for deodorant drug products for internal use. 357.810 Section 357.810 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... HUMAN USE Deodorant Drug Products for Internal Use § 357.810 Active ingredients for deodorant...

  20. 21 CFR 357.810 - Active ingredients for deodorant drug products for internal use.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Active ingredients for deodorant drug products for internal use. 357.810 Section 357.810 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... HUMAN USE Deodorant Drug Products for Internal Use § 357.810 Active ingredients for deodorant...

  1. 21 CFR 357.810 - Active ingredients for deodorant drug products for internal use.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Active ingredients for deodorant drug products for internal use. 357.810 Section 357.810 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... HUMAN USE Deodorant Drug Products for Internal Use § 357.810 Active ingredients for deodorant...

  2. 21 CFR 357.810 - Active ingredients for deodorant drug products for internal use.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Active ingredients for deodorant drug products for internal use. 357.810 Section 357.810 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... HUMAN USE Deodorant Drug Products for Internal Use § 357.810 Active ingredients for deodorant...

  3. Using Indices of Fidelity to Intervention Core Components to Identify Program Active Ingredients

    ERIC Educational Resources Information Center

    Abry, Tashia; Hulleman, Chris S.; Rimm-Kaufman, Sara E.

    2015-01-01

    Identifying the active ingredients of an intervention--intervention-specific components serving as key levers of change--is crucial for unpacking the intervention black box. Measures of intervention fidelity can be used to identify specific active ingredients, yet such applications are rare. We illustrate how fidelity measures can be used to…

  4. 40 CFR Table 1 to Part 455 - List of Organic Pesticide Active Ingredients

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 30 2014-07-01 2014-07-01 false List of Organic Pesticide Active Ingredients 1 Table 1 to Part 455 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... of Organic Pesticide Active Ingredients EPA census code Pesticide code Pesticide name CAS No. 1...

  5. 40 CFR Table 1 to Part 455 - List of Organic Pesticide Active Ingredients

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 31 2012-07-01 2012-07-01 false List of Organic Pesticide Active Ingredients 1 Table 1 to Part 455 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... of Organic Pesticide Active Ingredients EPA census code Pesticide code Pesticide name CAS No. 1...

  6. 40 CFR Table 1 to Part 455 - List of Organic Pesticide Active Ingredients

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 31 2013-07-01 2013-07-01 false List of Organic Pesticide Active Ingredients 1 Table 1 to Part 455 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... of Organic Pesticide Active Ingredients EPA census code Pesticide code Pesticide name CAS No. 1...

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

    PubMed

    Kalinkova, G N

    1999-09-30

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

  8. Pharmaceutically active secondary metabolites of marine actinobacteria.

    PubMed

    Manivasagan, Panchanathan; Venkatesan, Jayachandran; Sivakumar, Kannan; Kim, Se-Kwon

    2014-04-01

    Marine actinobacteria are one of the most efficient groups of secondary metabolite producers and are very important from an industrial point of view. Many representatives of the order Actinomycetales are prolific producers of thousands of biologically active secondary metabolites. Actinobacteria from terrestrial sources have been studied and screened since the 1950s, for many important antibiotics, anticancer, antitumor and immunosuppressive agents. However, frequent rediscovery of the same compounds from the terrestrial actinobacteria has made them less attractive for screening programs in the recent years. At the same time, actinobacteria isolated from the marine environment have currently received considerable attention due to the structural diversity and unique biological activities of their secondary metabolites. They are efficient producers of new secondary metabolites that show a range of biological activities including antibacterial, antifungal, anticancer, antitumor, cytotoxic, cytostatic, anti-inflammatory, anti-parasitic, anti-malaria, antiviral, antioxidant, anti-angiogenesis, etc. In this review, an evaluation is made on the current status of research on marine actinobacteria yielding pharmaceutically active secondary metabolites. Bioactive compounds from marine actinobacteria possess distinct chemical structures that may form the basis for synthesis of new drugs that could be used to combat resistant pathogens. With the increasing advancement in science and technology, there would be a greater demand for new bioactive compounds synthesized by actinobacteria from various marine sources in future.

  9. WHO Expert Committee on Specifications for Pharmaceutical Preparations.

    PubMed

    2009-01-01

    The Expert Committee on Specifications for Pharmaceutical Preparations works towards clear, independent and practical standards and guidelines for the quality assurance of medicines. Standards are developed by the Committee through worldwide consultation and an international consensus-building process. The following new standards and guidelines were adopted and recommended for use: the current list of available International Chemical Reference Substances and International Infrared Reference Spectra; guidelines on stability testing of active pharmaceutical ingredients and finished pharmaceutical products; procedure for prequalification of pharmaceutical products; and the procedure for assessing the acceptability, in principle, of active pharmaceutical ingredients for use in pharmaceutical products.

  10. Impact of active ingredients on the swelling properties of orally disintegrating tablets prepared by microwave treatment.

    PubMed

    Sano, Syusuke; Iwao, Yasunori; Kimura, Susumu; Noguchi, Shuji; Itai, Shigeru

    2014-07-01

    The impact of different active pharmaceutical ingredients (APIs) loading on the properties of orally disintegrating tablets (ODTs) prepared according to our previously reported microwave (MW) treatment process was evaluated using famotidine (FAM), acetaminophen (AAP), and ibuprofen (IBU). None of the APIs interrupted the tablet swelling during the MW treatment and the tablet hardness were improved by more than 20 N. MW treatment, however, led to a significant increase in the disintegration time of the ODTs containing IBU, but it had no impact on that of the ODTs containing FAM or AAP. This increased disintegration time of the ODTs containing IBU was attributed to the relatively low melting point of IBU (Tm=76 °C), with the IBU particles melting during the MW treatment to form agglomerates, which interrupted the penetration of water into the tablets and delayed their disintegration. The effects of the MW treatment on the chemical stability and dissolution properties of ODTs were also evaluated. The results revealed that MW treatment did not promote the degradations of FAM and AAP or delay their release from the ODTs, while dissolution of the ODTs containing IBU delayed by MW treatment. Based on these results, the MW method would be applicable to the preparation of ODTs containing APIs with melting points higher than 110 °C.

  11. Development of a topical suspension containing three active ingredients.

    PubMed

    Chang, H C; Li, L C; Toongsuwan, S; Stephens, D; Liu, R M; Plichta-Mahmoud, H

    2002-01-01

    The objective of this study was to develop a topical suspension that contains sarafloxacin hydrochloride (1 mg/mL), triamcinolone acetonide (1 mg/mL), and clotrimazole (10 mg/mL), and is stable at room temperature (15-28 degrees C) for clinical usage. Due to the difference in the physicochemical properties and chemical stability profiles of these three active ingredients, it is a challenge to develop a stable suspension formulation containing these three drugs. In this study, the stability of these drugs in different buffer solutions was determined under different accelerated isothermal conditions. The Arrhenius equation was subsequently utilized to predict the room-temperature stability of these three drugs in these buffer solutions. By knowing the room-temperature solubility of the drugs in the buffer solution, the stability of the drugs in suspension was predicted. As a result, a 0.02 M phosphate buffer (pH 7.0) containing 0.02% (w/v)polysorbate 20, 1% (w/v) NaCl, and 0.1% (w/v) EDTA was determined to be an acceptable medium. In addition, 0.35% (w/v) high-viscosity carboxymethylcellulose (HV-CMC) was first selected as the suspending agent to enhance the redispersibility of the suspension. Stability data further supported that all three drugs were stable in the suspension containing HV-CMC with less than 5% potency loss for at least 6 months at 40 degrees C and 12 months at 25 degrees C. However, the viscosity drop of this HV-CMC formulation at 25 degrees C and 40 degrees C became a product stability concern. To improve the viscosity stability of the suspension, the medium-viscosity carboxymethylcellulose (MV-CMC) was selected to replace the HV-CMC as the suspending agent. The optimal combination of MV-CMC and sodium chloride in achieving the most desirable dispersion properties for the formulation was determined through the use of a 32 factorial design. The optimal formulation containing 1% MV-CMC and 1% sodium chloride has shown improved viscosity stability

  12. Antiproliferative activities of Garcinia bracteata extract and its active ingredient, isobractatin, against human tumor cell lines.

    PubMed

    Shen, Tao; Li, Wei; Wang, Yan-Yan; Zhong, Qing-Qing; Wang, Shu-Qi; Wang, Xiao-Ning; Ren, Dong-Mei; Lou, Hong-Xiang

    2014-03-01

    In our cell based screening of antitumor ingredients from plants, the EtOH extract of Garcinia bracteata displayed antiproliferative effect against human lung adenocarcinoma A549 cells, human breast cancer MCF-7 cells, and human prostate cancer PC3 cells. Phytochemical investigation of this active extract produced nine ingredients, and their structures were established by analysis of MS and NMR spectra. Antiproliferative evaluation of isolated ingredients on A549, MCF-7 and PC3 cells indicated that a xanthone named isobractatin (1) exhibited potent antiproliferative activity against the above three human cancer cell lines with IC50 values ranging from 2.90 to 4.15 μM. Treatment of PC3 cells with 1 led to an enhancement of the cell apoptosis, and arrested cell cycle in the G0/G1 phase. The G0/G1 phase cycle-related proteins analysis showed that the expressions of cyclins D1 and E were reduced by 1, whereas the protein level of cyclin dependent kinase (CDK) inhibitor P21 was induced. Additionally, 1 enhanced PC3 cell apoptosis by activations of Bax, caspases 3 and 9, and by inhibition of Bcl-2. Our combined data illustrated that isobractatin (1) was the antiproliferative ingredient of G. bracteata against three human cancer cell lines, which exerted its antiproliferatrive effect via cell cycle arrest and induction of apoptosis.

  13. 21 CFR 358.760 - Labeling of permitted combinations of active ingredients for the control of dandruff.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... control of dandruff and external analgesic active ingredients in § 358.720(b). The label states “dandruff...) Combinations of control of dandruff and external analgesic active ingredients in § 358.720(b). The labeling... control of dandruff and external analgesic active ingredients in § 358.720(b). The labeling states “...

  14. Concentrations and mass loadings of cardiovascular pharmaceuticals in healthcare facility wastewaters

    EPA Science Inventory

    Healthcare facilities are an under-characterized source of pharmaceuticals to municipal wastewaters. In this study, the composition and magnitude of 16 cardiovascular active pharmaceutical ingredients (API) and two cardiovascular API metabolites in wastewater effluents from a ho...

  15. ENVIRONMENTAL FOOTPRINT OF PHARMACEUTICALS - THE SIGNIFICANCE OF FACTORS BEYOND DIRECT EXCRETION TO SEWERS

    EPA Science Inventory

    The combined excretion of active pharmaceutical ingredients (APIs) via urine and feces is considered the primary route by which APIs from human pharmaceuticals enter the environment. Disposal of unwanted, leftover medications by flushing into sewers has been considered a secondar...

  16. The Role of PharmEcovigilance in Reducing the Environmental Footprint of Pharmaceuticals

    EPA Science Inventory

    The prescribing and usage of medications have ramifications extending far beyond conventional medical care. The pharmaceutical and healthcare industries have an environmental footprint because the active pharmaceutical ingredients (APIs) can enter the environment as contaminants ...

  17. Leveraging a large scale mammalian pharmacological dataset to prioritize potential environmental hazard of pharmaceuticals

    EPA Science Inventory

    The potential for pharmaceuticals in the environment to cause adverse ecological effects is of increasing concern. Given the thousands of active pharmaceutical ingredients (APIs) which can enter the aquatic environment through various means, a current challenge in aquatic toxicol...

  18. Selected Pharmaceuticals Entering an Estuary: Concentrations, Temporal Trends, Partitioning and Fluxes

    EPA Science Inventory

    In many coastal watersheds and ecosystems, rivers discharging to estuaries receive waters from domestic wastewater-treatment plants resulting in the release and distribution of pharmaceuticals to the marine environment. In the present study, 15 active pharmaceutical ingredients w...

  19. 78 FR 76613 - Registration Applications for Pesticide Products Containing New Active Ingredients; Corrections

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-18

    ... in the Federal Register of August 14, 2012, concerning a new active ingredient (AI). The name of an AI was changed during the registration assessment process. This document corrects the name of the...

  20. 78 FR 70043 - Pesticide Product Registration; Receipt of an Application for a New Active Ingredient

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-22

    ... name: DAS-81419-2 Soybean. Active ingredients: Bacillus thuringiensis Cry1Ac protein expressed in soybean and Bacillus thuringiensis Cry1F protein expressed in soybean. Proposed classification/Use:...

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

    PubMed

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

    2017-01-26

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

  2. Direct determination of cadmium and lead in pharmaceutical ingredients using anodic stripping voltammetry in aqueous and DMSO/water solutions.

    PubMed

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

    2015-09-17

    A new electrochemical method has been developed to detect and quantify the elemental impurities, cadmium(II) (Cd(2+)) and lead(II) (Pb(2+)), either simultaneously or individually in pharmaceutical matrices. The electro-analytical approach, involving the use of anodic stripping voltammetry (ASV) on an unmodified glassy carbon electrode, was performed in both aqueous and in a 95/5 dimethyl sulfoxide (DMSO)/water solutions, without acid digestion or dry ashing to remove organic matrices. Limits of detection (LODs) in the μg L(-1) [or parts per billion (ppb), mass/volume] range were obtained for both heavy metals - in the presence and absence of representative pharmaceutical components. To the best of our knowledge, the work demonstrates the first analysis of heavy metals in DMSO/water solutions through ASV. The strong reproducibility and stability of the sensing platform, as well as obviation of sample pretreatment show the promise of utilizing ASV as a sensitive, robust, and inexpensive alternative to inductively-coupled-plasma (ICP)-based approaches for the analysis of elemental impurities in, e.g., pharmaceutical-related matrices.

  3. Consensus Modeling for Prediction of Estrogenic Activity of Ingredients Commonly Used in Sunscreen Products.

    PubMed

    Hong, Huixiao; Rua, Diego; Sakkiah, Sugunadevi; Selvaraj, Chandrabose; Ge, Weigong; Tong, Weida

    2016-09-29

    Sunscreen products are predominantly regulated as over-the-counter (OTC) drugs by the US FDA. The "active" ingredients function as ultraviolet filters. Once a sunscreen product is generally recognized as safe and effective (GRASE) via an OTC drug review process, new formulations using these ingredients do not require FDA review and approval, however, the majority of ingredients have never been tested to uncover any potential endocrine activity and their ability to interact with the estrogen receptor (ER) is unknown, despite the fact that this is a very extensively studied target related to endocrine activity. Consequently, we have developed an in silico model to prioritize single ingredient estrogen receptor activity for use when actual animal data are inadequate, equivocal, or absent. It relies on consensus modeling to qualitatively and quantitatively predict ER binding activity. As proof of concept, the model was applied to ingredients commonly used in sunscreen products worldwide and a few reference chemicals. Of the 32 chemicals with unknown ER binding activity that were evaluated, seven were predicted to be active estrogenic compounds. Five of the seven were confirmed by the published data. Further experimental data is needed to confirm the other two predictions.

  4. Consensus Modeling for Prediction of Estrogenic Activity of Ingredients Commonly Used in Sunscreen Products

    PubMed Central

    Hong, Huixiao; Rua, Diego; Sakkiah, Sugunadevi; Selvaraj, Chandrabose; Ge, Weigong; Tong, Weida

    2016-01-01

    Sunscreen products are predominantly regulated as over-the-counter (OTC) drugs by the US FDA. The “active” ingredients function as ultraviolet filters. Once a sunscreen product is generally recognized as safe and effective (GRASE) via an OTC drug review process, new formulations using these ingredients do not require FDA review and approval, however, the majority of ingredients have never been tested to uncover any potential endocrine activity and their ability to interact with the estrogen receptor (ER) is unknown, despite the fact that this is a very extensively studied target related to endocrine activity. Consequently, we have developed an in silico model to prioritize single ingredient estrogen receptor activity for use when actual animal data are inadequate, equivocal, or absent. It relies on consensus modeling to qualitatively and quantitatively predict ER binding activity. As proof of concept, the model was applied to ingredients commonly used in sunscreen products worldwide and a few reference chemicals. Of the 32 chemicals with unknown ER binding activity that were evaluated, seven were predicted to be active estrogenic compounds. Five of the seven were confirmed by the published data. Further experimental data is needed to confirm the other two predictions. PMID:27690075

  5. Terpinen-4-ol is the Most Active Ingredient of Tea Tree Oil to Kill Demodex Mites

    PubMed Central

    Tighe, Sean; Gao, Ying-Ying; Tseng, Scheffer C. G.

    2013-01-01

    Purpose To determine the active ingredient in tea tree oil (TTO) responsible for its reported killing effect on Demodex mites, the most common ectoparasite found in the human skin extending to the eye. Methods Using a reported in vitro killing assay to measure the survival time of adult Demodex folliculorum up to 150 minutes, we have screened serial concentrations of 13 of the 15 known ingredients of TTO (ISO4730:2004) that were soluble in mineral oil and examined their synergistic relationships in killing mites. The most potent ingredient was then tested for its efficacy in killing Demodex in vivo. Results All ingredients exhibited a dose-dependent killing effect. Besides Terpinen-4-ol, the order of relative potency did not correlate with the order of relative abundance in TTO for the remaining 12 ingredients. Terpinen-4-ol was the most potent ingredient followed by α-Terpineol, 1,8-Cineole and Sabinene. Terpinen-4-ol, the most abundant ingredient in TTO, was more potent than TTO at equivalent concentrations and its killing effect was even observable at a mere concentration of 1%. Terpinen-4-ol exhibited a significant synergistic effect with Terpinolene, but an antagonistic effect with α-Terpineol in killing mites (both P < 0.05). In vivo, Terpinen-4-ol was shown to eradicate mites. Conclusions The above finding suggests that deployment of Terpinen-4-ol alone should enhance its potency in killing Demodex mites by reducing the adverse and antagonistic effects from other ingredients in TTO. Translational Relevance Terpinen-4-ol can be adopted in future formulations of acaricides to treat a number of ocular and cutaneous diseases caused by demodicosis. PMID:24349880

  6. Possible Anticancer Mechanisms of Some Costus speciosus Active Ingredients Concerning Drug Discovery

    PubMed Central

    El-Far, Ali H.; Badria, Faried A.; Shaheen, Hazem M.

    2016-01-01

    Costus speciosus is native to South East Asia, especially found in India, Srilanka, Indonesia and Malaysia. C. speciosus have numerous therapeutic potentials against a wide variety of complains. The therapeutic properties of C. speciosus are attributed to the presence of various ingredients such as alkaloids, flavonoids, glycosides, phenols, saponins, sterols and sesquiterpenes. This review presented the past, present, and the future status of C. speciosus active ingredients to propose a future use as a potential anticancer agent. All possible up-regulation of cellular apoptotic molecules as p53, p21, p27, caspases, reactive oxygen species (ROS) generation and others attribute to the anticancer activity of C. speciosus along the down-regulation of anti-apoptotic agents such as Akt, Bcl2, NFκB, STAT3, JAK, MMPs, actin, surviving and vimentin. Eventually, we recommend further investigation of different C. speciosus extracts, using some active ingredients and evaluate the anticancer effect of these chemicals against different cancers. PMID:27515456

  7. Data-mining of potential antitubercular activities from molecular ingredients of traditional Chinese medicines

    PubMed Central

    Jamal, Salma

    2014-01-01

    Background. Traditional Chinese medicine encompasses a well established alternate system of medicine based on a broad range of herbal formulations and is practiced extensively in the region for the treatment of a wide variety of diseases. In recent years, several reports describe in depth studies of the molecular ingredients of traditional Chinese medicines on the biological activities including anti-bacterial activities. The availability of a well-curated dataset of molecular ingredients of traditional Chinese medicines and accurate in-silico cheminformatics models for data mining for antitubercular agents and computational filters to prioritize molecules has prompted us to search for potential hits from these datasets. Results. We used a consensus approach to predict molecules with potential antitubercular activities from a large dataset of molecular ingredients of traditional Chinese medicines available in the public domain. We further prioritized 160 molecules based on five computational filters (SMARTSfilter) so as to avoid potentially undesirable molecules. We further examined the molecules for permeability across Mycobacterial cell wall and for potential activities against non-replicating and drug tolerant Mycobacteria. Additional in-depth literature surveys for the reported antitubercular activities of the molecular ingredients and their sources were considered for drawing support to prioritization. Conclusions. Our analysis suggests that datasets of molecular ingredients of traditional Chinese medicines offer a new opportunity to mine for potential biological activities. In this report, we suggest a proof-of-concept methodology to prioritize molecules for further experimental assays using a variety of computational tools. We also additionally suggest that a subset of prioritized molecules could be used for evaluation for tuberculosis due to their additional effect against non-replicating tuberculosis as well as the additional hepato-protection offered by

  8. Laboratory evaluation of prallethrin as an active ingredient of DUET® against Aedes aegypti and Aedes albopictus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prallethrin, one of the two active ingredients in DUET®, has previously been shown to activate Culex quinquefasciatus females in the laboratory resulting in greater mortality. In this study, formulations of DUET® prepared with and without prallethrin were evaluated in a wind tunnel with unfed and b...

  9. 21 CFR 358.710 - Active ingredients for the control of dandruff, seborrheic dermatitis, or psoriasis.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... to be applied and left on the skin or scalp. (4) Salicylic acid, 1.8 to 3 percent. (5) Selenium sulfide, 1 percent. (6) Selenium sulfide, micronized, 0.6 percent. (7) Sulfur, 2 to 5 percent. (b) Active...) Salicylic acid, 1.8 to 3 percent. (5) Selenium sulfide, 1 percent. (c) Active ingredients for the control...

  10. 21 CFR 358.710 - Active ingredients for the control of dandruff, seborrheic dermatitis, or psoriasis.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... to be applied and left on the skin or scalp. (4) Salicylic acid, 1.8 to 3 percent. (5) Selenium sulfide, 1 percent. (6) Selenium sulfide, micronized, 0.6 percent. (7) Sulfur, 2 to 5 percent. (b) Active...) Salicylic acid, 1.8 to 3 percent. (5) Selenium sulfide, 1 percent. (c) Active ingredients for the control...

  11. 21 CFR 358.710 - Active ingredients for the control of dandruff, seborrheic dermatitis, or psoriasis.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... to be applied and left on the skin or scalp. (4) Salicylic acid, 1.8 to 3 percent. (5) Selenium sulfide, 1 percent. (6) Selenium sulfide, micronized, 0.6 percent. (7) Sulfur, 2 to 5 percent. (b) Active...) Salicylic acid, 1.8 to 3 percent. (5) Selenium sulfide, 1 percent. (c) Active ingredients for the control...

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

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... to be applied and left on the skin or scalp. (4) Salicylic acid, 1.8 to 3 percent. (5) Selenium sulfide, 1 percent. (6) Selenium sulfide, micronized, 0.6 percent. (7) Sulfur, 2 to 5 percent. (b) Active...) Salicylic acid, 1.8 to 3 percent. (5) Selenium sulfide, 1 percent. (c) Active ingredients for the control...

  13. 21 CFR 358.710 - Active ingredients for the control of dandruff, seborrheic dermatitis, or psoriasis.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... to be applied and left on the skin or scalp. (4) Salicylic acid, 1.8 to 3 percent. (5) Selenium sulfide, 1 percent. (6) Selenium sulfide, micronized, 0.6 percent. (7) Sulfur, 2 to 5 percent. (b) Active...) Salicylic acid, 1.8 to 3 percent. (5) Selenium sulfide, 1 percent. (c) Active ingredients for the control...

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

    NASA Astrophysics Data System (ADS)

    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.

  15. Effect of penetration modifiers on the dermal and transdermal delivery of drugs and cosmetic active ingredients.

    PubMed

    Otto, A; Wiechers, J W; Kelly, C L; Hadgraft, J; du Plessis, J

    2008-01-01

    In this study the effect of 2 penetration modifiers, dimethyl isosorbide (DMI) and diethylene glycol monoethyl ether (DGME) on the skin delivery of hydroquinone (HQ), salicylic acid (SA) and octadecenedioic acid (DIOIC) was investigated. Ten percent DMI and DGME were separately formulated into oil-in-water emulsions containing 1.8% HQ, SA and DIOIC, respectively. Skin delivery and the flux across split-thickness human skin of the active ingredients were determined using Franz diffusion cells. An emulsion with 10% water incorporated instead of the water-soluble penetration modifiers served as a control. The study showed that neither 10% DMI nor 10% DGME significantly enhanced the skin permeation of the various lipophilic active ingredients or the uptake into the skin. It was hypothesized that the addition of the penetration modifiers to the emulsions not only enhanced the solubility of the various active ingredients in the skin but also in the formulation, resulting in a reduced thermodynamic activity and hence a weaker driving force for penetration. Therefore, the effect of DMI and DGME on the solubility of the active ingredients in the skin was counteracted by a simultaneous reduction in the thermodynamic activity in the formulation.

  16. Guidance for the reregistration of pesticide products containing coal tar/creosote as the active ingredient

    SciTech Connect

    Not Available

    1988-04-01

    The document contains information regarding the registration of pesticide products containing the subject active ingredient. The document includes how to register under a registration standard, regulatory position and rationale, and summaries of date requirements and data gaps. Also included is a bibliography containing citations of all studies reviewed by EPA in arriving at the positions and conclusions contained in the standard.

  17. 21 CFR 347.60 - Labeling of permitted combinations of active ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... SERVICES (CONTINUED) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE.... (1) Combinations of skin protectant and external analgesic active ingredients in § 347.20(b). In addition to any or all of the indications for skin protectant drug products in § 347.50(b)(1), any or...

  18. 21 CFR 343.22 - Permitted combinations of active ingredients for cardiovascular-rheumatologic use.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Permitted combinations of active ingredients for cardiovascular-rheumatologic use. 343.22 Section 343.22 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE INTERNAL ANALGESIC, ANTIPYRETIC,...

  19. 40 CFR Table 1 to Part 455 - List of Organic Pesticide Active Ingredients

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false List of Organic Pesticide Active Ingredients 1 Table 1 to Part 455 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS PESTICIDE CHEMICALS Pt. 455, Table 1 Table 1 to Part 455—List of...

  20. 40 CFR Table 1 to Part 455 - List of Organic Pesticide Active Ingredients

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 30 2011-07-01 2011-07-01 false List of Organic Pesticide Active Ingredients 1 Table 1 to Part 455 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS PESTICIDE CHEMICALS Pt. 455, Table 1 Table 1 to Part 455—List of...

  1. 21 CFR 347.60 - Labeling of permitted combinations of active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... SERVICES (CONTINUED) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE.... (1) Combinations of skin protectant and external analgesic active ingredients in § 347.20(b). In addition to any or all of the indications for skin protectant drug products in § 347.50(b)(1), any or...

  2. 21 CFR 347.60 - Labeling of permitted combinations of active ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... SERVICES (CONTINUED) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE.... (1) Combinations of skin protectant and external analgesic active ingredients in § 347.20(b). In addition to any or all of the indications for skin protectant drug products in § 347.50(b)(1), any or...

  3. 21 CFR 347.60 - Labeling of permitted combinations of active ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... SERVICES (CONTINUED) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE.... (1) Combinations of skin protectant and external analgesic active ingredients in § 347.20(b). In addition to any or all of the indications for skin protectant drug products in § 347.50(b)(1), any or...

  4. 21 CFR 347.60 - Labeling of permitted combinations of active ingredients.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... SERVICES (CONTINUED) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE.... (1) Combinations of skin protectant and external analgesic active ingredients in § 347.20(b). In addition to any or all of the indications for skin protectant drug products in § 347.50(b)(1), any or...

  5. Fingerprints, Pharmaceutical and Radical Scavenging Activity Evaluation of an Alzheimer-Targeted Herbal Preparation

    PubMed Central

    Dabaghian, Farid; Khademian, Sedigheh; Azadi, Amir; Zarshenas, Mohammad

    2016-01-01

    Background: As the most common form of dementia, Alzheimer disease is characterized by progressive loss of memory and deterioration of cognitive functions. It is predicted that about 75.63 million people would suffer from dementia by 2030. Apart from conventional remedies, the application of herbal medicines is on the rise. There are numerous natural medicaments reported in the traditional manuscript of Persian medicine. Accordingly, in the present study, the intended remedy was selected and an appropriate pharmacognostical and pharmaceutical evaluations were performed. Methods: By searching through the traditional pharmaceutical manuscripts such as Qarabadeen-e-Salehi, Qarabadeen-e-Azam, Qarabadeen-e-Ghaderi and Canon of Medicine, a simple but proven compound remedy (frankincense and black pepper) was selected. A floating tablet was designed and formulated from those herbal components. Related pharmaceutical assessments such as weight variation, hardness, friability, and disintegration tests as well as pharmacognostical evaluations such as microscopic characterization, TLC, GC/MS, FT/IR fingerprints, and radical scavenging activity assessment (DPPH) were performed. Results: The resulting formulation, as a floating tablet, included 60% of frankincense gum and 15% of black pepper along with appropriate pharmaceutical ingredients (weight variation: 0.219±0.004 g, hardness: 6.50±0.67, friability: 0.45%, disintegration time >30 min). Microscopic characterization demonstrated stone cells, calcium oxalate crystals, sclereids of endocarp and pitted cells of mesocarp of pepper fruits as well as oil drops of frankincense gum. TLC fingerprinting showed classes of secondary metabolites related to both components. GC/MS analysis revealed Acetyl acetate and trans-Caryophyllene as the main constituent. Moderate radical scavenging activity (IC50 >100 µg/ml) was calculated for the methanol extract of tablets. Conclusion: Carrying out and validating a GC method for

  6. Fingerprints, Pharmaceutical and Radical Scavenging Activity Evaluation of an Alzheimer-Targeted Herbal Preparation

    PubMed Central

    Dabaghian, Farid; Khademian, Sedigheh; Azadi, Amir; Zarshenas, Mohammad

    2016-01-01

    Background: As the most common form of dementia, Alzheimer disease is characterized by progressive loss of memory and deterioration of cognitive functions. It is predicted that about 75.63 million people would suffer from dementia by 2030. Apart from conventional remedies, the application of herbal medicines is on the rise. There are numerous natural medicaments reported in the traditional manuscript of Persian medicine. Accordingly, in the present study, the intended remedy was selected and an appropriate pharmacognostical and pharmaceutical evaluations were performed. Methods: By searching through the traditional pharmaceutical manuscripts such as Qarabadeen-e-Salehi, Qarabadeen-e-Azam, Qarabadeen-e-Ghaderi and Canon of Medicine, a simple but proven compound remedy (frankincense and black pepper) was selected. A floating tablet was designed and formulated from those herbal components. Related pharmaceutical assessments such as weight variation, hardness, friability, and disintegration tests as well as pharmacognostical evaluations such as microscopic characterization, TLC, GC/MS, FT/IR fingerprints, and radical scavenging activity assessment (DPPH) were performed. Results: The resulting formulation, as a floating tablet, included 60% of frankincense gum and 15% of black pepper along with appropriate pharmaceutical ingredients (weight variation: 0.219±0.004 g, hardness: 6.50±0.67, friability: 0.45%, disintegration time >30 min). Microscopic characterization demonstrated stone cells, calcium oxalate crystals, sclereids of endocarp and pitted cells of mesocarp of pepper fruits as well as oil drops of frankincense gum. TLC fingerprinting showed classes of secondary metabolites related to both components. GC/MS analysis revealed Acetyl acetate and trans-Caryophyllene as the main constituent. Moderate radical scavenging activity (IC50 >100 µg/ml) was calculated for the methanol extract of tablets. Conclusion: Carrying out and validating a GC method for

  7. PharmEcovigilance and the Environmental Footprint of Pharmaceuticals

    EPA Science Inventory

    The prescribing and usage of medications have ramifications extending far beyond conventional medical care. The healthcare industry has an environmental footprint because the active ingredients from pharmaceuticals enter the environment as pollutants by a variety of routes, prima...

  8. Basic Information about Pesticide Ingredients

    EPA Pesticide Factsheets

    Pesticide products contain both active and inert ingredients. An “active ingredient” prevents, destroys, repels, or mitigates a pest. All other ingredients are called inert ingredients by federal law. They aid product performance and usability.

  9. 40 CFR Table 2 to Part 455 - Organic Pesticide Active Ingredient Effluent Limitations Best Available Technology Economically...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 30 2011-07-01 2011-07-01 false Organic Pesticide Active Ingredient... (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS PESTICIDE CHEMICALS Pt. 455, Table 2 Table 2 to Part 455—Organic Pesticide Active Ingredient Effluent Limitations Best Available Technology Economically...

  10. 40 CFR Table 2 to Part 455 - Organic Pesticide Active Ingredient Effluent Limitations Best Available Technology Economically...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 31 2012-07-01 2012-07-01 false Organic Pesticide Active Ingredient... (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) PESTICIDE CHEMICALS Pt. 455, Table 2 Table 2 to Part 455—Organic Pesticide Active Ingredient Effluent Limitations Best Available...

  11. 40 CFR Table 3 to Part 455 - Organic Pesticide Active Ingredient New Source Performance Standards (NSPS) and Pretreatment...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 30 2011-07-01 2011-07-01 false Organic Pesticide Active Ingredient... STANDARDS PESTICIDE CHEMICALS Pt. 455, Table 3 Table 3 to Part 455—Organic Pesticide Active Ingredient New Source Performance Standards (NSPS) and Pretreatment Standards for New Sources (PSNS) Pesticide...

  12. 40 CFR Table 3 to Part 455 - Organic Pesticide Active Ingredient New Source Performance Standards (NSPS) and Pretreatment...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Organic Pesticide Active Ingredient... STANDARDS PESTICIDE CHEMICALS Pt. 455, Table 3 Table 3 to Part 455—Organic Pesticide Active Ingredient New Source Performance Standards (NSPS) and Pretreatment Standards for New Sources (PSNS) Pesticide...

  13. 40 CFR Table 2 to Part 455 - Organic Pesticide Active Ingredient Effluent Limitations Best Available Technology Economically...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 30 2014-07-01 2014-07-01 false Organic Pesticide Active Ingredient... (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) PESTICIDE CHEMICALS Pt. 455, Table 2 Table 2 to Part 455—Organic Pesticide Active Ingredient Effluent Limitations Best Available...

  14. 40 CFR Table 2 to Part 455 - Organic Pesticide Active Ingredient Effluent Limitations Best Available Technology Economically...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Organic Pesticide Active Ingredient... (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS PESTICIDE CHEMICALS Pt. 455, Table 2 Table 2 to Part 455—Organic Pesticide Active Ingredient Effluent Limitations Best Available Technology Economically...

  15. 40 CFR Table 2 to Part 455 - Organic Pesticide Active Ingredient Effluent Limitations Best Available Technology Economically...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 31 2013-07-01 2013-07-01 false Organic Pesticide Active Ingredient... (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) PESTICIDE CHEMICALS Pt. 455, Table 2 Table 2 to Part 455—Organic Pesticide Active Ingredient Effluent Limitations Best Available...

  16. A brief review on anti diabetic plants: Global distribution, active ingredients, extraction techniques and acting mechanisms

    PubMed Central

    Chan, Chung-Hung; Ngoh, Gek-Cheng; Yusoff, Rozita

    2012-01-01

    A study has been conducted with the aim to provide researchers with general information on anti diabetic extracts based on relevant research articles collected from 34 reliable medical journals. The study showed that Asian and African continents have 56% and 17% share of the worldwide distribution of therapeutic herbal plants, respectively. In Asia, India and China are the leading countries in herbal plants research, and there has been an increase in medicinal research on plants extract for diabetes treatment since 1995 in these regions. The information collected shows that plant leaves are about 20% more favorable for storing active ingredients, as compared to other parts of herbal plants. A brief review on the extraction techniques for the mentioned parts is also included. Furthermore, the acting mechanisms for the anti diabetic activity were described, and the related active ingredients were identified. The findings reveal that most of the anti diabetic research is focused on the alteration of glucose metabolism to prevent diabetes. PMID:22654401

  17. Activation of a photosensitive pharmaceutical agent by a triboluminescent material

    SciTech Connect

    Yuen, Stacey; Schreyer, Magdalena; Finlay, W.H.; Loebenberg, R.; Moussa, W.

    2006-03-20

    Given the recent emphasis on applications of triboluminescent materials, we investigate the ability of a triboluminescent material to activate a photosensitive pharmaceutical agent. Using compressed sucrose doped with wintergreen, which luminesces when fractured, we demonstrate the activation of riboflavin (vitamin B2), a photosensitizer. A product of activation is the highly reactive singlet oxygen. We add ascorbic acid (vitamin C), an antioxidant, and measure the amount of ascorbic acid oxidation to correlate with the amount of riboflavin activation. Up to 17% ascorbic acid oxidation is observed, indicating triboluminescence is worth exploring as a mechanism for activation of photosensitizers in photodynamic therapy.

  18. 77 FR 63290 - Foreign-Trade Zone 121-Albany, NY; Notification of Proposed Production Activity; Albany Molecular...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-16

    ...; Albany Molecular Research, Inc., Subzone 121A, (Pharmaceutical Chemicals Production), Rensselaer, NY... originally approved by the Board in 1994 for the production of bulk pharmaceutical chemicals and... an active pharmaceutical ingredient, dexpramipexole dihydrochloride monohydrate, under...

  19. WHO Expert Committee on specifications for pharmaceutical preparations.

    PubMed

    2010-01-01

    The Expert Committee on Specifications for Pharmaceutical Preparations works towards clear, independent and practical standards and guidelines for the quality assurance of medicines. Standards are developed by the Committee through worldwide consultation and an international consensus-building process. The following new guidelines were adopted and recommended for use: good practices for pharmaceutical quality control laboratories; supplementary guidelines for active pharmaceutical ingredients; good manufacturing practices for pharmaceutical products containing hazardous substances; good manufacturing practices for sterile pharmaceutical products; good distribution practices for pharmaceutical products; guidelines on the requalification of prequalified dossiers: and guidelines for the preparation of a contract research organization master file.

  20. [Changed accumulation of active ingredient in different localities and growth period of Hemsleya zhejiangensis (Cucurbitaceae)].

    PubMed

    Yang, Wang-Wei; Lei, Zu-Pei; Wang, Wei-Min; Liang, Wei-qing; Zhou, Wei-Qing; Jin, Xiao-Feng

    2014-08-01

    In this paper, the content of moisture, ethanol-soluble extractives, total saponins and polysaccharide of different tuber samples of Hemsleya zhejiangensis, from different localities, years and seasons, were detected based upon Chinese Pharmacopoeia 2010 version. The samples of roots, stems and leaves in summer were detected as well. The results are mainly as follows. (1)With tuber quality increasing, the content of total saponins increased and then decreased. The individual quality of tubers getting 594.06 g, the content of total saponins reached the peak. (2) The content of active ingredients in different localities was significantly different, and the population of Wuyanling had the maximum content of total saponins and polysaccharide. (3) The content of active ingredients revealed stability between the years 2012 and 2013, but the content of polysaccharide was significantly different. The content in 2012 was higher than that of 2013. (4) The content of active ingredients reached the peak in autumn, which was the best harvest season. (5) Among different component content detection of nutritional organs, tubers had the maximum content of ethanol-soluble extractives, total saponins and polysaccharide. Leaves also contained higher content of ethanol-soluble extractives and total saponins than roots and stems. All of these provide theoretical basis for plant, harvest and production of H. zhejiangensis, which is an endemic, rare, and endangered medicinal plants.

  1. Development of new polysilsesquioxane spherical particles as stabilized active ingredients for sunscreens

    NASA Astrophysics Data System (ADS)

    Tolbert, Stephanie Helene

    Healthy skin is a sign of positive self-worth, attractiveness and vitality. Compromises to this are frequently caused by extended periods of recreation in the sun and in turn exposure to the harmful effects of UV radiation. To maintain strength and integrity, protection of the skin is paramount. This can be achieved by implementing skin-care products which contain sunscreen active ingredients that provide UV protection. Unfortunately, photo-degradation, toxicity, and photo-allergies limit the effectiveness of present day sunscreen ingredients. Currently, this is moderated by physically embedding within inert silica particles, but leaching of the active ingredient can occur, thereby negating protective efforts. Alternatively, this research details the preparation and investigation of bridged silsesquioxane analogues of commercial ingredients which can be chemically grafted to the silica matrix. Studies with bridged salicylate particles detail facile preparation, minimized leaching, and enhanced UV stability over physically encapsulated and pendant salicylate counterparts. In terms of UVB protective ability, the highest maintenance of sun protection factor (SPF) after extended UV exposure was achieved with bridged incorporation, and has been attributed to corollary UV stability. Additionally, bridged salicylate particles can be classified as broad-spectrum, and rate from moderate to good in terms of UVA protective ability. Particles incorporated with a bridged curcuminoid silsesquioxane were also prepared and displayed comparable results. As such, an attractive method for sunscreen isolation and stabilization has been developed to eliminate the problems associated with current sunscreens, all while maintaining the established UV absorbance profiles of the parent compound. To appreciate the technology utilized in this research, a thorough understanding of sol-gel science as it pertains to hybrid organic/silica particles, including methods of organic fragment

  2. The Role of Entrepreneurial Activities in Academic Pharmaceutical Science Research

    PubMed Central

    Stinchcomb, Audra L.

    2010-01-01

    Academic pharmaceutical science research is expanding further and further from the University setting to encompass the for-profit private company setting. This parallels the National Institutes of Health momentum to include multiple funding opportunities for University and private company collaboration. It has been recognized that the non-profit and for-profit combination research model can accelerate the commercialization of pharmaceutical products, and therefore more efficiently improve human health. Entrepreneurial activities require unique considerations in the University environment, but can be modeled after the commercialization expansion of the academic healthcare enterprise. Challenges and barriers exist to starting a company as an entrepreneurial faculty member, but the rewards to one's personal and professional lives are incomparable. PMID:20017206

  3. Soil sorption and leaching of active ingredients of Lumax® under mineral or organic fertilization.

    PubMed

    Pinna, Maria Vittoria; Roggero, Pier Paolo; Seddaiu, Giovanna; Pusino, Alba

    2014-09-01

    The study describes the soil sorption of the herbicide Lumax®, composed of S-metolachlor (MTC), terbuthylazine (TBZ), and mesotrione (MST), as influenced by mineral and organic fertilizers. The investigation was performed on a sandy soil of an agricultural area designated as a Nitrate Vulnerable Zone, where mineral and organic fertilizers were applied for many years. Two organic fertilizers, cattle manure and slurry, respectively, and a mineral fertilizer with a nitrification inhibitor, Entec®, were compared. According to the experiments, performed with a batch method, the sorption conformed to Freundlich model. The extent of sorption of Lumax® ingredients was closely related to their octanol-water partition coefficient Kow. The respective desorption was hysteretic. Leaching trials were carried out by using water or solutions of DOM or Entec® as the eluants. Only the elution with the mineral fertilizer promoted the leaching of Lumax® active ingredients.

  4. [Important application of intestinal transporters and metabolism enzymes on gastrointestinal disposal of active ingredients of Chinese materia medica].

    PubMed

    Bi, Xiaolin; Du, Qiu; Di, Liuqing

    2010-02-01

    Oral drug bioavailability depends on gastrointestinal absorption, intestinal transporters and metabolism enzymes are the important factors in drug gastrointestinal absorption and they can also be induced or inhibited by the active ingredients of Chinese materia medica. This article presents important application of intestinal transporters and metabolism enzymes on gastrointestinal disposal of the active ingredients of Chinese materia medica, and points out the importance of research on transport and metabolism of the active ingredients of Chinese materia medica in Chinese extract and Chinese medicinal formulae.

  5. Effects of active sunscreen ingredient combinations on the topical penetration of the herbicide 2,4-dichlorophenoxyacetic acid.

    PubMed

    Pont, Adam R; Charron, Anna R; Wilson, Roselyn M; Brand, Rhonda M

    2003-02-01

    Sunscreen use can reduce the incidence of certain skin cancers. However, a number of commercially available formulations have been shown to enhance the transdermal penetration of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). Most of the active ingredients used in these compounds can individually act as penetration enhancers. Commercial sunscreens frequently contain multiple active ingredients in order to provide broad sunscreen protection. The purpose of this study was therefore to examine the effect of these active ingredient combinations on the transdermal absorption of 2,4-D in vitro. All six of the combinations tested resulted in increased cumulative penetration (P <0.01) and faster lag times (P <0.05). The 2,4-D cumulative penetration in the presence of the OFF! Deepwoods combination was significantly greater than the absorption with either the individual ingredients or their average (P <0.05). A systematic study designed to isolate the chemicals responsible for this enhancement demonstrated that with UV absorbers DEET synergistically increased the 2,4-D penetration and that DEET's cumulative enhancement properties correlate with its concentration. By contrast, octocrylene significantly slowed the lag time when used in combinations and was the only active ingredient that showed any antagonistic effects on 2,4-D penetration. Because none of the active ingredient combinations were able to inhibit dermal uptake of 2,4-D, it seems that proper selection of inert ingredients may be the most feasible solution for reducing penetration enhancement.

  6. Prioritization of pharmaceuticals for potential environmental hazard through leveraging a large scale mammalian pharmacological dataset

    EPA Science Inventory

    To proceed in the investigation of potential effects of thousands of active pharmaceutical ingredients (API) which may enter the aquatic environment, a cohesive research strategy, specifically a prioritization is paramount. API are biologically active, with specific physiologica...

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

    PubMed

    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.

  8. Quantification and structural elucidation of potential impurities in agomelatine active pharmaceutical ingredient.

    PubMed

    Liu, Yaxuan; Chen, Lei; Ji, Yibing

    2013-01-01

    Seven impurities in agomelatine drug substance were determined by a newly developed RP-HPLC method. Structures of potential impurities were confirmed by NMR and IR analysis. Efficient chromatographic separation was achieved on Hypersil BDS C18 column (250 mm × 4.6 mm, 5 μm) in gradient mode by using a binary mixture of potassium dihydrogen phosphate (15 mM, pH adjusted to 3.0) and acetonitrile at a flow rate of 1.0 ml/min. A photodiode array detector set at 230 nm was used for detection. Forced degradation studies showed that the proposed method was specific, and agomelatine was found to be susceptible to acidic and alkaline conditions. The method was validated according to ICH guidelines with respect to specificity, sensitivity, precision, linearity, accuracy, robustness and system suitability. Detection limit of impurities was in the range of 0.0008-0.0047%. Regression analysis showed correlation coefficient value greater than 0.999 for agomelatine and its seven impurities. Accuracy of the method was established based on the recovery obtained between 94.4% and 106.7% for all impurities. The validation results demonstrated that the developed method was suitable for the quantitative determination of potential impurities in agomelatine. A possible mechanism for the formation of impurities was proposed.

  9. Interactions between active pharmaceutical ingredients and excipients affecting bioavailability: impact on bioequivalence.

    PubMed

    García-Arieta, Alfredo

    2014-12-18

    The aim of the present paper is to illustrate the impact that excipients may have on the bioavailability of drugs and to review existing US-FDA, WHO and EMA regulatory guidelines on this topic. The first examples illustrate that small amounts of sorbitol (7, 50 or 60mg) affect the bioavailability of risperidone, a class I drug, oral solution, in contrast to what is stated in the US-FDA guidance. Another example suggests, in contrast to what is stated in the US-FDA BCS biowaivers guideline, that a small amount of sodium lauryl sulphate (SLS) (3.64mg) affects the bioavailability of risperidone tablets, although the reference product also includes SLS in an amount within the normal range for that type of dosage form. These factors are considered sufficient to ensure that excipients do not affect bioavailability according to the WHO guideline. The alternative criterion, defined in the WHO guideline and used in the FIP BCS biowaivers monographs, that asserts that excipients present in generic products of the ICH countries do not affect bioavailability if used in normal amounts, is shown to be incorrect with an example of alendronate (a class III drug) tablets, where 4mg of SLS increases bioavailability more than 5-fold, although a generic product in the USA contains SLS. Finally, another example illustrates that a 2mg difference in SLS may affect bioavailability of a generic product of a class II drug, even if SLS is contained in the comparator product, and in all cases its amount was within the normal range. Therefore, waivers of in vivo bioequivalence studies (e.g., BCS biowaivers, waivers of certain dosage forms in solution at the time of administration and variations in the excipient composition) should be assessed more cautiously.

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

    NASA Astrophysics Data System (ADS)

    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.

  11. Neuroprotective effects of active ingredients isolated from Pegasus laternarius on cultured cerebral neurons.

    PubMed

    Li, Mengtao; Chen, Minhui; Huang, Hai; Tao, Wucheng; Cui, Jihong; Xiang, Hui

    2011-01-01

    Seamoth (Pegasus laternarius Cuvier) is extensively used to treat various diseases on the coastland of Guangdong Province in China, such as scrofula, cough, and diarrhea. The total extract of Pegasus laternarius (EP) was subjected to column chromatography to acquire three different constituents (EPC1, EPC2, and EPC3). Cerebral neuron injury was induced by glutamate, H₂O₂, and serum deprivation. After treating with or without different extracts, cell viability was assessed with the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, and cell apoptosis was analyzed with Hoechst 33258 staining and agarose gel electrophoresis. We also determined the levels of lactate dehydrogenase (LDH), maleic dialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). The results showed that both EP and EPC2 promoted the outgrowth of cultural neurons, increased antioxidant enzyme activity, and protected neurons from neuronal injury or apoptosis induced by glutamate, H₂O₂, and serum deprivation. EPC1 and EPC3 had little or no effect on neurons. These results suggest that the active ingredients obtained from Pegasus laternarius have potential neuroprotective effects on injured neurons by promoting the outgrowth of cultured neurons, increasing the activity of intracellular antioxidants, and exerting antiapoptotic effects. This neuroprotection may be attributable to specific active ingredients, such as taurine, novel ceramide, and cholesterol.

  12. Chromatography of crotamiton and its application to the determination of active ingredients in ointments.

    PubMed

    Izumoto, S; Machida, Y; Nishi, H; Nakamura, K; Nakai, H; Sato, T

    1997-06-01

    Crotamiton, which is a mixture of cis and trans isomers, was investigated by several separation techniques. One of the HPLC modes, in which crotamiton eluted as a single peak, was selected for the determination of five active ingredients (crotamiton, prednisolone, glycyrrhetinic acid, dibucaine and chlorhexidine hydrochloride) in an ointment. The simultaneous determination was performed using isocratic reversed-phase mode within 20 min by employing an octyl (C8) column and a mobile phase containing sodium dodecyl sulfate (SDS) and 2-propanol. The method was successfully applied to quality control and stability testing of the ointment.

  13. Active ingredients in Chinese medicines promoting blood circulation as Na+/K+-ATPase inhibitors

    PubMed Central

    Chen, Ronald JY; Jinn, Tzyy-rong; Chen, Yi-ching; Chung, Tse-yu; Yang, Wei-hung; Tzen, Jason TC

    2011-01-01

    The positive inotropic effect of cardiac glycosides lies in their reversible inhibition on the membrane-bound Na+/K+-ATPase in human myocardium. Steroid-like compounds containing a core structure similar to cardiac glycosides are found in many Chinese medicines conventionally used for promoting blood circulation. Some of them are demonstrated to be Na+/K+-ATPase inhibitors and thus putatively responsible for their therapeutic effects via the same molecular mechanism as cardiac glycosides. On the other hand, magnesium lithospermate B of danshen is also proposed to exert its cardiac therapeutic effect by effectively inhibiting Na+/K+-ATPase. Theoretical modeling suggests that the number of hydrogen bonds and the strength of hydrophobic interaction between the effective ingredients of various medicines and residues around the binding pocket of Na+/K+-ATPase are crucial for the inhibitory potency of these active ingredients. Ginsenosides, the active ingredients in ginseng and sanqi, substantially inhibit Na+/K+-ATPase when sugar moieties are attached only to the C-3 position of their steroid-like structure, equivalent to the sugar position in cardiac glycosides. Their inhibitory potency is abolished, however, when sugar moieties are linked to C-6 or C-20 position of the steroid nucleus; presumably, these sugar attachments lead to steric hindrance for the entrance of ginsenosides into the binding pocket of Na+/K+-ATPase. Neuroprotective effects of cardiac glycosides, several steroid-like compounds, and magnesium lithospermate B against ischemic stroke have been accordingly observed in a cortical brain slice-based assay model, and cumulative data support that effective inhibitors of Na+/K+-ATPase in the brain could be potential drugs for the treatment of ischemic stroke. PMID:21293466

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

    EPA Science Inventory

    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...

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

    PubMed

    Gadade, Dipak Dilip; Pekamwar, Sanjay Sudhakar

    2016-12-01

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

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

    PubMed Central

    Gadade, Dipak Dilip; Pekamwar, Sanjay Sudhakar

    2016-01-01

    Cocrystal is a concept of the supramolecular chemistry which is gaining the extensive interest of researchers from pharmaceutical and chemical sciences and of drug regulatory agencies. The prominent reason of which is its ability to modify physicochemical properties of active pharmaceutical ingredients. During the development of the pharmaceutical product, formulators have to optimize the physicochemical properties of active pharmaceutical ingredients. Pharmaceutical cocrystals can be employed to improve vital physicochemical characteristics of a drug, including solubility, dissolution, bioavailability and stability of pharmaceutical compounds while maintaining its therapeutic activity. It is advantageous being a green synthesis approach for production of pharmaceutical compounds. The formation polymorphic forms, solvates, hydrates and salts of cocrystals during the synthesis reported in the literature which can be a potential issue in the development of pharmaceutical cocrystals. The approaches like hydrogen bonding rules, solubility parameters, screening through the CSD database or thermodynamic characteristics can be utilized for the rational design of cocrystals and selection of coformers for synthesis multi-component cocrystals. Considering the significance of pharmaceutical cocrystals pharmaceutical regulatory authorities in the United States and Europe issued guidance documents which may be helpful for pharmaceutical product registration in these regions. In this article, we deal with the design, synthesis, strategic aspects and characteristics of cocrystals along perspectives on its regulatory and intellectual property considerations. PMID:28101455

  17. Transparent gels: study of their formation and assimilation of active ingredients through phase diagrams.

    PubMed

    Comelles, F; Caelles, J; Parra, J L; Leal, J S

    1992-08-01

    Synopsis Multicomponent gel formulations capable of assimilating, simultaneously, several active ingredients of potential application in the cosmetic field were studied. The possibility of formation of a transparent gel was determined using a method which consisted in the optimization of several lipophilic basic compositions, composed of oil, a mixture of surfactants, a sunscreen agent, several vitamins and antioxidants situated in the base of a regular tetrahedron that symbolized the considered system. To this, a polar phase made of water, a cosolvent and urea in appropriate proportions and situated in the fourth vertex, was progressively added. It may be concluded, that the use of phase diagrams on cosmetic systems, constitutes a useful way to select the components and their mutual ratios, allowing an adaptation to the specific requested conditions of formulation.

  18. Cotton defoliant runoff as a function of active ingredient and tillage.

    PubMed

    Potter, Thomas L; Truman, Clint C; Bosch, David D; Bednarz, Craig W

    2003-01-01

    Cotton (Gossypium hirsutum L.) defoliant runoff was recently identified as an ecological risk. However, assessments are not supported by field studies. Runoff potential of three defoliant active ingredients, dimethipin (2,3-dihydro-5,6-dimethyl-1,4-dithiin 1,1,4,4-tetraoxide), thidiazuron (N-phenyl-N-1,2,3-thidiazol-5-yl-urea), and tribufos (S,S,S-tributyl phosphorotrithioate) was investigated by rainfall simulation on strip (ST) and conventionally tilled (CT) cotton in south central Georgia. Simulated rainfall timing relative to defoliant application (1 h after) represented an extreme worst-case scenario; however, weather records indicate that it was not unrealistic for the region. Thidiazuron and tribufos losses were 12 to 15% of applied. Only 2 to 5% of the more water soluble dimethipin was lost. Although ST erosion rates were less, loss of tribufos, a strongly sorbing compound, was not affected. Higher sediment-water partition coefficients (kd) were measured in ST samples. This likely explains why no tillage related differences in loss rates were observed, but it is unknown whether this result can be generalized. The study was conducted in the first year following establishment of tillage treatments at the study site. As soil conditions stabilize, ST impacts may change. Data provide an estimate of the maximum amount of the defoliants that will run off during a single postapplication storm event. Use of these values in place of the default value in runoff simulation models used in pesticide risk assessments will likely improve risk estimate accuracy and enhance evaluation of comparative risk among these active ingredients.

  19. Review article: health benefits of some physiologically active ingredients and their suitability as yoghurt fortifiers.

    PubMed

    Fayed, A E

    2015-05-01

    The article is concerned with health benefits of two main physiologically active ingredients namely, Isoflavones and γ-Aminobutyric acid, with emphasis on their fitness for fortification of yoghurt to be consumed as a functional food. Isoflavones (ISO) are part of the diphenol compounds, called "phytoestrogens," which are structurally and functionally similar to estradiol, the human estrogen, but much less potent. Because of this similarity, ISO were suggested to have preventive effects for many kinds of hormone-dependent diseases. In nature, ISO usually occur as glycosides and, once deconjugated by the intestinal microflora, the ISO can be absorbed into the blood. At present, it seems convincing their possible protective actions against various cancers, osteoporosis and menopausal symptoms and high levels of blood cholesterol as well as the epidemiological evidence. Γ-Aminobutyric acid (GABA), it is an amino acid that has long been reported to lower blood pressure by intravenous administration in experimental animals and in human subjects. GABA is present in many vegetables and fruits but not in dairy products. GABA was reported to lower blood pressure in people with mild hypertension. It was suggested that low-dose oral GABA has a hypotensive effect in spontaneously hypertensive. Yoghurt beyond its ability to be probiotic food via its culturing with the gut strains, it could further carry more healthy benefits when it was fortified with physiological active ingredients, especially GABA versus ISO preferring, whether, bacteriologically or biochemically, a fortification level of 50 mg ISO/kg or 200 mg GABA/kg.

  20. 40 CFR Table 3 to Part 455 - Organic Pesticide Active Ingredient New Source Performance Standards (NSPS) and Pretreatment...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 30 2014-07-01 2014-07-01 false Organic Pesticide Active Ingredient... STANDARDS (CONTINUED) PESTICIDE CHEMICALS Pt. 455, Table 3 Table 3 to Part 455—Organic Pesticide Active...) Pesticide kg/kkg (lb/1,000 lb) pounds of pollutant per 1000 lbs product Daily maximum shall not...

  1. 40 CFR Table 3 to Part 455 - Organic Pesticide Active Ingredient New Source Performance Standards (NSPS) and Pretreatment...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 31 2012-07-01 2012-07-01 false Organic Pesticide Active Ingredient... STANDARDS (CONTINUED) PESTICIDE CHEMICALS Pt. 455, Table 3 Table 3 to Part 455—Organic Pesticide Active...) Pesticide kg/kkg (lb/1,000 lb) pounds of pollutant per 1000 lbs product Daily maximum shall not...

  2. 40 CFR Table 3 to Part 455 - Organic Pesticide Active Ingredient New Source Performance Standards (NSPS) and Pretreatment...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 31 2013-07-01 2013-07-01 false Organic Pesticide Active Ingredient... STANDARDS (CONTINUED) PESTICIDE CHEMICALS Pt. 455, Table 3 Table 3 to Part 455—Organic Pesticide Active...) Pesticide kg/kkg (lb/1,000 lb) pounds of pollutant per 1000 lbs product Daily maximum shall not...

  3. [PICS: pharmaceutical inspection cooperation scheme].

    PubMed

    Morénas, J

    2009-01-01

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

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

    PubMed

    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 < 0.05). The severities of malformations were comparable in the crocin- and safranal-treated groups. This study suggests that crocin or safranal can induce embryonic malformations when administered in pregnant mice. Due to the wide use of saffron, further elaborate studies to understand the malformation mechanisms of these ingredients are recommended.

  5. Identification of active ingredients in Wuzhuyu decoction improving migraine in mice by spectral efficiency association.

    PubMed

    Pan, Xueqiang; Wang, Manyuan; Wu, Yanchuan; Lu, Xuran; Shang, Yawen; Xu, Yongsong; Zhai, Yongsong; Li, Jing; Li, Zhaoxia; Gong, Muxin

    2015-07-01

    Wuzhuyu decoction is a traditional Chinese medicine used for the effective treatment of migraines, termed 'Jueyin headache', in China. However, there have been few investigations to clarify the composition of Wuzhuyu decoction for the treatment of migraines. In the present study, 10 types of Wuzhuyu decoction were analyzed by chromatograms. 5-hydroxytryptamine (5-HT)-depletion mouse models of migraine were prepared by subcutaneous injection of reserpine and placement of autologous blood clots in the cerebral cortex. The levels of 5-HT, noradrenaline (NE), dopamine (DA), nitric oxide (NO) and nitric oxide synthase (NOS) in the brain tissues and sera of the mice were determined. The ingredients and pharmacodynamic indices of the Wuzhuyu decoctions were analyzed using spectral efficiency association by partial least squares regression. The levels of 5-HT, NE and DA in the mouse brain tissues were reduced to 337.785 ± 84.504, 171.173 ± 65.172 and 242.075 ± 158.621 mg/g brain tissue, respectively. The level of NO in the brain tissues increased to 0.425 ± 0.184 µmol/g protein and the activities of NOS in the brain tissues and sera increased to 0.719 ± 0.477 U/mg and 50.688 ± 8.132 U/ml, respectively. Regarding the ingredients of the Wuzhuyu decoction, those with significant regression coefficients were ginsenoside-Rg1, Re, Rb1, rutaevine (Rv), limonin (Li), evodiamine (Ev), rutaecarpine (Ru) and substance X (awaiting identification). Rg1, Re, Rb1, Rv, Li, Ev, Ru and X in the Wuzhuyu decoction were observed to yield the pharmacological effects, whereas Rb1, Rv and Ev were important in index improvement.

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

    NASA Astrophysics Data System (ADS)

    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.

  7. Pharmaceutical salts: a summary on doses of salt formers from the Orange Book.

    PubMed

    Saal, C; Becker, A

    2013-07-16

    Over half of the active pharmaceutical ingredients currently approved within the US are pharmaceutical salts. Selection of suitable pharmaceutical salts is carried out during late research or early development phase. Therefore several properties of different pharmaceutical salts of a new chemical entity are assessed during salt screening and salt selection. This typically includes physico-chemical behavior, dissolution rate and pharmacokinetics of a pharmaceutical salt. Beyond these properties also toxicological aspects have to be taken into account. As a starting point for a toxicological assessment we present an overview of the usage of pharmaceutical salts as described in the FDA's Orange Book including maximum daily doses for the most important administration routes.

  8. Characterization and antimicrobial activity of a pharmaceutical microemulsion.

    PubMed

    Zhang, Hui; Cui, Yinan; Zhu, Songming; Feng, Fengqin; Zheng, Xiaodong

    2010-08-16

    The characterization of a pharmaceutical microemulsion system with glycerol monolaurate as oil, ethanol as cosurfactant, Tween 40 as surfactant, sodium diacetate and water, and the antimicrobial activities against Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Candida albicans, Aspergillus niger and Penicillium expansum have been studied. The influence of ethanol and sodium diacetate on oil solubilization capability was clearly reflected in the phase behavior of these systems. One microemulsion formulation was obtained and remained stable by physical stability studies. The antimicrobial assay using solid medium diffusion method showed that the prepared microemulsion was comparable to the commonly used antimicrobials as positive controls. The kinetics of killing experiments demonstrated that the microemulsion caused a complete loss of viability of bacterial cells (E. coli, S. aureus and B. subtilis) in 1 min, killed over 99% A. niger and P. expansum spores and 99.9% C. albicans cells rapidly within 2 min and resulted in a complete loss of fungal viability in 5 min. The fast killing kinetics of the microemulsion was in good agreement with the transmission electron microscopy observations, indicating the antimembrane activity of the microemulsion on bacterial and fungal cells due to the disruption and dysfunction of biological membranes and cell walls.

  9. Acetylcholinesterase inhibitory activity of Thai traditional nootropic remedy and its herbal ingredients.

    PubMed

    Tappayuthpijarn, Pimolvan; Itharat, Arunporn; Makchuchit, Sunita

    2011-12-01

    The incidence of Alzheimer disease (AD) is increasing every year in accordance with the increasing of elderly population and could pose significant health problems in the future. The use of medicinal plants as an alternative prevention or even for a possible treatment of the AD is, therefore, becoming an interesting research issue. Acetylcholinesterase (AChE) inhibitors are well-known drugs commonly used in the treatment of AD. The aim of the present study was to screen for AChE inhibitory activity of the Thai traditional nootropic recipe and its herbal ingredients. The results showed that ethanolic extracts of four out of twenty-five herbs i.e. Stephania pierrei Diels. Kaempfera parviflora Wall. ex Baker, Stephania venosa (Blume) Spreng, Piper nigrum L at 0.1 mg/mL showed % AChE inhibition of 89, 64, 59, 50; the IC50 were 6, 21, 29, 30 microg/mL respectively. The other herbs as well as combination of the whole recipe had no synergistic inhibitory effect on AChE activity. However some plants revealed antioxidant activity. More research should have be performed on this local wisdom remedy to verify the uses in scientific term.

  10. Fungicidal activities of commonly used disinfectants and antifungal pharmaceutical spray preparations against clinical strains of Aspergillus and Candida species.

    PubMed

    Gupta, A K; Ahmad, I; Summerbell, R C

    2002-04-01

    The antifungal efficacy of commercial chemical disinfectants and pharmaceutical antifungal agents against medically important moulds and yeast species was investigated. Chlorine, phenol, sodium dodecyl sulfate and quaternary ammonium salts were the chemical disinfectants, and bifonazole and terbinafine were the antifungal pharmaceutical products tested against clinical isolates of Aspergillus and Candida species. Fungal inocula were obtained from conidial preparations of two A. ochraceus strains and yeast cells of C. albicans, C. krusei and C. parapsilosis. The antifungal activities were evaluated either by determining the kill rate in a cell suspension media at different contact periods, or by examining the viability and growth on plates sprayed with the active ingredient. Chlorine (1%) was the only disinfectant with the ability to cause a rapid inactivation of all five strains. Phenol (5%) was equally effective against Candida species; however, a number of A. ochraceus conidia were able to survive this treatment for up to 1 h. Benzalkonium chloride (0.5%) and cetrimide (0.5%) were also able to disinfect the three Candida species rapidly; however, these two quaternary ammonium compounds were relatively ineffective against A. ochraceus. In spray experiments, quaternary ammonium compounds had a fungicidal activity against Candida species and were fungistatic against A. ochraceus conidia. All five fungal strains were able to resist 0.5% sodium dodecyl sulfate, present either in the suspension solution or on the sprayed plate. Of the two pharmaceutical antifungal products tested, bifonazole (1%) were essentially ineffective against all five strains. Terbinafine (1%) had a fungicidal activity against A. ochraceus and C. parapsilosis. In suspension experiments, an exposure to 0.01% terbinafine required a contact period of 1 h for a complete inactivation of A. ochraceus conidia and an onset of fungicidal effect on C. parapsilosis yeast cells. Terbinafine was only

  11. Approaches for predicting effects of unintended environmental exposure to an endocrine active pharmaceutical, tamoxifen

    EPA Science Inventory

    Tamoxifen is an endocrine-active pharmaceutical (EAP) that is used world-wide. Because tamoxifen is a ubiquitous pharmaceutical and interacts with estrogen receptors, a case study was conducted with this compound to (1) determine effects on reproductive endpoints in a nontarget s...

  12. Concentrations of prioritized pharmaceuticals in effluents from 50 large wastewater treatment plants in the US and implications for risk estimation

    EPA Science Inventory

    We measured the concentrations of 56 active pharmaceutical ingredients (APIs) and seven metabolites, including 50 prioritized APIs, in 24-hour composite effluent samples collected from 50 very large municipal wastewater treatment plants across the US. Hydrochlorothiazide was foun...

  13. Prioritizing and selecting pharmaceuticals to test the read-across approach: using human clearance rates to predict biotransformation in fish

    EPA Science Inventory

    Many active pharmaceutical ingredients (APIs) have been detected in aquatic systems around the world. These systems typically receive continual municipal sewage inputs, which results in pseudo-persistent exposures of aquatic animals to APIs, thus enhancing their bioaccumulative p...

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

    EPA Science Inventory

    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...

  15. Dampened neural activity and abolition of epileptic-like activity in cortical slices by active ingredients of spices

    PubMed Central

    Pezzoli, Maurizio; Elhamdani, Abdeladim; Camacho, Susana; Meystre, Julie; González, Stephanie Michlig; le Coutre, Johannes; Markram, Henry

    2014-01-01

    Active ingredients of spices (AIS) modulate neural response in the peripheral nervous system, mainly through interaction with TRP channel/receptors. The present study explores how different AIS modulate neural response in layer 5 pyramidal neurons of S1 neocortex. The AIS tested are agonists of TRPV1/3, TRPM8 or TRPA1. Our results demonstrate that capsaicin, eugenol, menthol, icilin and cinnamaldehyde, but not AITC dampen the generation of APs in a voltage- and time-dependent manner. This effect was further tested for the TRPM8 ligands in the presence of a TRPM8 blocker (BCTC) and on TRPM8 KO mice. The observable effect was still present. Finally, the influence of the selected AIS was tested on in vitro gabazine-induced seizures. Results coincide with the above observations: except for cinnamaldehyde, the same AIS were able to reduce the number, duration of the AP bursts and increase the concentration of gabazine needed to elicit them. In conclusion, our data suggests that some of these AIS can modulate glutamatergic neurons in the brain through a TRP-independent pathway, regardless of whether the neurons are stimulated intracellularly or by hyperactive microcircuitry. PMID:25359561

  16. Dampened neural activity and abolition of epileptic-like activity in cortical slices by active ingredients of spices.

    PubMed

    Pezzoli, Maurizio; Elhamdani, Abdeladim; Camacho, Susana; Meystre, Julie; González, Stephanie Michlig; le Coutre, Johannes; Markram, Henry

    2014-10-31

    Active ingredients of spices (AIS) modulate neural response in the peripheral nervous system, mainly through interaction with TRP channel/receptors. The present study explores how different AIS modulate neural response in layer 5 pyramidal neurons of S1 neocortex. The AIS tested are agonists of TRPV1/3, TRPM8 or TRPA1. Our results demonstrate that capsaicin, eugenol, menthol, icilin and cinnamaldehyde, but not AITC dampen the generation of APs in a voltage- and time-dependent manner. This effect was further tested for the TRPM8 ligands in the presence of a TRPM8 blocker (BCTC) and on TRPM8 KO mice. The observable effect was still present. Finally, the influence of the selected AIS was tested on in vitro gabazine-induced seizures. Results coincide with the above observations: except for cinnamaldehyde, the same AIS were able to reduce the number, duration of the AP bursts and increase the concentration of gabazine needed to elicit them. In conclusion, our data suggests that some of these AIS can modulate glutamatergic neurons in the brain through a TRP-independent pathway, regardless of whether the neurons are stimulated intracellularly or by hyperactive microcircuitry.

  17. 21 CFR 310.527 - Drug products containing active ingredients offered over-the-counter (OTC) for external use as...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... offered over-the-counter (OTC) for external use as hair growers or for hair loss prevention. 310.527... products containing active ingredients offered over-the-counter (OTC) for external use as hair growers or for hair loss prevention. (a) Amino acids, aminobenzoic acid, ascorbic acid, benzoic acid, biotin...

  18. 21 CFR 310.527 - Drug products containing active ingredients offered over-the-counter (OTC) for external use as...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... offered over-the-counter (OTC) for external use as hair growers or for hair loss prevention. 310.527... products containing active ingredients offered over-the-counter (OTC) for external use as hair growers or for hair loss prevention. (a) Amino acids, aminobenzoic acid, ascorbic acid, benzoic acid, biotin...

  19. Active Ingredients of Instructional Coaching: Developing a Conceptual Framework. R2Ed Working Paper 2015-3

    ERIC Educational Resources Information Center

    White, Andrew S.; Howell Smith, Michelle; Kunz, Gina M.; Nugent, Gwen C.

    2015-01-01

    Although researchers have explored the impact of instructional coaching and named possible elements believed essential to effective coaching, there has yet to emerge from the literature a coherent model of those essential elements ("active ingredients"). This qualitative study sought to identify those elements through a systematic…

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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. ...

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

    ERIC Educational Resources Information Center

    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…

  2. PRN 97-5: Use of Common Names for Active Ingredients on Pesticide Labeling

    EPA Pesticide Factsheets

    This notice announces EPA policy to expand the use of common names on pesticide labeling. EPA will permit the use of common names approved by ANSI in the label ingredients statement without the accompanying scientific chemical name.

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

    EPA Science Inventory

    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...

  4. Concentration evolution of pharmaceutically active compounds in raw urban and industrial wastewater.

    PubMed

    Camacho-Muñoz, Dolores; Martín, Julia; Santos, Juan Luis; Aparicio, Irene; Alonso, Esteban

    2014-09-01

    The distribution of pharmaceutically active compounds in the environment has been reported in several works in which wastewater treatment plants have been identified as the main source of these compounds to the environment. The concentrations of these compounds in influent wastewater can vary widely not only during the day but also along the year, because of the seasonal-consumption patterns of some pharmaceuticals. However, only few studies have attempted to assess the hourly variability of the concentrations of pharmaceutically active compounds in wastewater. In this work, the distribution and seasonal and hourly variability of twenty-one pharmaceuticals, belonging to seven therapeutic groups, have been investigated in urban and industrial wastewater. The highest concentrations of pharmaceutically active compounds, except salicylic acid, were found in urban wastewater, especially in the case of anti-inflammatory drugs and caffeine. The highest concentrations of salicylic acid were measured in industrial wastewater, reaching concentration levels up to 3295μgL(-)(1). The studied pharmaceutically active compounds showed different distribution patterns during winter and summer periods. Temporal variability of pharmaceutically active compounds during a 24-h period showed a distribution in concordance with their consumption and excretion patterns, in the case of urban wastewater, and with the schedule of industrial activities, in the case of industrial wastewater.

  5. Motivational Interviewing: A Pilot Test of Active Ingredients and Mechanisms of Change

    PubMed Central

    Morgenstern, Jon; Kuerbis, Alexis; Amrhein, Paul; Hail, Lisa; Lynch, Kevin; McKay, James

    2012-01-01

    Motivational Interviewing (MI) is an effective treatment for substance use disorders (SUD) that focuses on resolving ambivalence and increasing commitment to positive behavior change. While MI has a well developed clinical theory, research findings have been mixed in supporting its view of how change occurs. The primary aim of this pilot study was to test hypothesized MI active ingredients and mechanisms of change in reducing drinking during the initiation of a behavior change episode. Problem drinkers (N=89) seeking treatment were randomly assigned to MI, relational MI without directive elements (Spirit-Only MI, SOMI), or a self-change (SC) control condition. Participants were followed during an eight week treatment period. The first two of four treatment sessions were videotaped and coded for fidelity, discriminability, and change talk. Overall, conditions demonstrated high fidelity. As predicted, change talk significantly increased in MI relative to the SOMI condition. Drinking was significantly reduced at end treatment, but the reduction was equivalent across conditions. Post-hoc analyses found that MI reduced drinking more rapidly than SOMI and SC and that increased change talk mediated the effects of MI relative to SOMI during the week immediately following the first session. Findings are discussed in the context of the pilot nature of the study and the relative absence of experimental tests of mechanisms of behavior change in SUD treatment research. PMID:22905896

  6. Capturing the Active Ingredients of Multicomponent Participatory Organizational Stress Interventions Using an Adapted Study Design.

    PubMed

    Biron, Caroline; Ivers, Hans; Brun, Jean-Pierre

    2016-10-01

    Adapted study designs use process evaluation to incorporate a measure of intervention exposure and create an artificial control and intervention groups. Taking into account exposure levels to interventions combines process and outcome evaluation and strengthens the design of the study when exposure levels cannot be controlled. This study includes longitudinal data (two assessments) with added process measures at time 2 gathered from three complex participatory intervention projects in Canada in a hospital and a university. Structural equation modelling was used to explore the specific working mechanisms of particular interventions on stress outcomes. Results showed that higher exposure to interventions aiming to modify tasks and working conditions reduced demands and improved social support, but not job control, which in turn, reduced psychological distress. Exposure to interventions aiming to improve relationships was not related to psychosocial risks. Most studies cannot explain how interventions produce their effects on outcomes, especially when there are multiple concurrent interventions delivered in several contexts. This study advances knowledge on process evaluation by using an adapted study design to capture the active ingredients of multicomponent interventions and suggesting some mechanisms by which the interventions produce their effects on stress outcomes. It provides an illustration of how to conduct process evaluation and relate exposure levels to observed outcomes. Copyright © 2016 John Wiley & Sons, Ltd.

  7. A Hibiscus Abelmoschus seed extract as a protective active ingredient to favour FGF-2 activity in skin.

    PubMed

    Rival, D; Bonnet, S; Sohm, B; Perrier, E

    2009-12-01

    In the skin, heparin, heparan sulphate and heparan sulphate proteoglycans control the storage and release of growth factors and protect them from early degradation. We developed a cosmetic active ingredient containing Hibiscus Abelmoschus seed extract (trade name Linefactor) that can maintain the FGF-2 content in the skin by mimicking the protective effect of heparan sulphate proteoglycans. By preventing the natural degradation of FGF-2, Hibiscus Abelmoschus seed extract maintains the bioavailability of this growth factor for its target cells, i.e. skin fibroblasts. Our in vitro evaluations showed that this ingredient exhibited heparan sulphate-like properties and dose-dependently protected FGF-2 from thermal degradation. We could also show that, in turn, the protected FGF-2 could stimulate the synthesis of sulphated GAGs, the natural protective molecules for FGF-2, thus providing a double protection. Finally, the in vitro results were confirmed in vivo thanks to a clinical study in which skin biomechanical properties and reduction in wrinkles were assessed.

  8. The adsorption of pharmaceutically active compounds from aqueous solutions onto activated carbons.

    PubMed

    Rakić, Vesna; Rac, Vladislav; Krmar, Marija; Otman, Otman; Auroux, Aline

    2015-01-23

    In this study, the adsorption of pharmaceutically active compounds - salicylic acid, acetylsalicylic acid, atenolol and diclofenac-Na onto activated carbons has been studied. Three different commercial activated carbons, possessing ∼650, 900 or 1500m(2)g(-1) surface areas were used as solid adsorbents. These materials were fully characterized - their textural, surface features and points of zero charge have been determined. The adsorption was studied from aqueous solutions at 303K using batch adsorption experiments and titration microcalorimetry, which was employed in order to obtain the heats evolved as a result of adsorption. The maximal adsorption capacities of investigated solids for all target pharmaceuticals are in the range of 10(-4)molg(-1). The obtained maximal retention capacities are correlated with the textural properties of applied activated carbon. The roles of acid/base features of activated carbons and of molecular structures of adsorbate molecules have been discussed. The obtained results enabled to estimate the possibility to use the activated carbons in the removal of pharmaceuticals by adsorption.

  9. Bacteriological Effects of Dentifrices with and without Active Ingredients of Natural Origin

    PubMed Central

    Latimer, Joe; Humphreys, Gavin J.; Sreenivasan, Prem K.; McBain, Andrew J.

    2014-01-01

    Compounds of natural origin are increasingly used as adjuncts to oral hygiene. We have adopted four distinct approaches to assess the antibacterial activity of dentifrices containing natural active ingredients against oral bacteria in several test systems. Corsodyl Daily (CD), Kingfisher Mint (KM), and Parodontax fluoride (PF) were compared to a dentifrice containing fluoride (Colgate Cavity Protection [CCP]) and one containing triclosan (Colgate Total [CT]). The growth inhibitory and bactericidal potency of the formulations were determined for 10 isolated oral bacteria. Effects of single exposures of simulated supragingival plaques were then determined by epifluorescence and confocal microscopy, while the effects of repeated exposures were quantified by viable counting. Additionally, dense plaques, maintained in continuous culture, were repeatedly dosed, and the outcome was assessed by viable counting and eubacterial DNA profiling. The test dentifrices exhibited variable specificity and potency against oral bacteria in axenic culture. Of the herbal formulations, KM caused the largest viability reductions in simulated supragingival plaques, with CT causing the greatest reductions overall. Following single exposures, CD caused moderate reductions, while PF had no effect. After multiple dosing, all formulations significantly reduced numbers of total, facultative, and Gram-negative anaerobes, but only KM and CT caused greater reductions than the fluoride control. KM also reduced counts of streptococci (rank order of effectiveness: CT > KM > CCP > PF > CD). Marked changes in eubacterial DNA profiles were not detected for any herbal formulation in dense plaques, although KM markedly reduced viable counts of streptococci, in agreement with supragingival data. While both nonherbal comparators displayed antibacterial activity, the triclosan-containing formulation caused greater viability reductions than the herbal and nonherbal formulations. PMID:25107974

  10. Identification of aroma active compounds of cereal coffee brew and its roasted ingredients.

    PubMed

    Majcher, Małgorzata A; Klensporf-Pawlik, Dorota; Dziadas, Mariusz; Jeleń, Henryk H

    2013-03-20

    Cereal coffee is a coffee substitute made mainly from roasted cereals such as barley and rye (60-70%), chicory (15-20%), and sugar beets (6-10%). It is perceived by consumers as a healthy, caffeine free, non-irritating beverage suitable for those who cannot drink regular coffee made from coffee beans. In presented studies, typical Polish cereal coffee brew has been subjected to the key odorants analysis with the application of gas chromatography-olfactometry (GC-O) and aroma extract dilution analysis (AEDA). In the analyzed cereal coffee extract, 30 aroma-active volatiles have been identified with FD factors ranging from 16 to 4096. This approach was also used for characterization of key odorants in ingredients used for the cereal coffee production. Comparing the main odors detected in GC-O analysis of roasted cereals brew to the odor notes of cereal coffee brew, it was evident that the aroma of cereal coffee brew is mainly influenced by roasted barley. Flavor compound identification and quantitation has been performed with application of comprehensive multidimentional gas chromatography and time-of-flight mass spectrometry (GCxGC-ToFMS). The results of the quantitative measurements followed by calculation of the odor activity values (OAV) revealed 17 aroma active compounds of the cereal coffee brew with OAV ranging from 12.5 and 2000. The most potent odorant was 2-furfurylthiol followed by the 3-mercapto-3-methylbutyl formate, 3-isobutyl-2-methoxypyrazine and 2-ethyl-3,5-dimethylpyrazine, 2-thenylthiol, 2,3-butanedione, 2-methoxy phenol and 2-methoxy-4-vinyl phenol, 3(sec-butyl)-2-methoxypyrazine, 2-acetyl-1-pyrroline, 3-(methylthio)-propanal, 2,3-pentanedione, 4-hydroxy-2,5-dimethyl-3-(2H)-furanone, (E,E)-2,4-decadienal, (Z)-4-heptenal, phenylacetaldehyde, and 1-octen-3-one.

  11. 40 CFR 152.114 - Approval of registration under FIFRA sec. 3(c)(7)-Products that contain a new active ingredient.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... sec. 3(c)(7)-Products that contain a new active ingredient. 152.114 Section 152.114 Protection of... CLASSIFICATION PROCEDURES Agency Review of Applications § 152.114 Approval of registration under FIFRA sec. 3(c)(7)—Products that contain a new active ingredient. An application for registration of a...

  12. 40 CFR 152.114 - Approval of registration under FIFRA sec. 3(c)(7)-Products that contain a new active ingredient.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... sec. 3(c)(7)-Products that contain a new active ingredient. 152.114 Section 152.114 Protection of... CLASSIFICATION PROCEDURES Agency Review of Applications § 152.114 Approval of registration under FIFRA sec. 3(c)(7)—Products that contain a new active ingredient. An application for registration of a...

  13. 40 CFR 152.114 - Approval of registration under FIFRA sec. 3(c)(7)-Products that contain a new active ingredient.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... sec. 3(c)(7)-Products that contain a new active ingredient. 152.114 Section 152.114 Protection of... CLASSIFICATION PROCEDURES Agency Review of Applications § 152.114 Approval of registration under FIFRA sec. 3(c)(7)—Products that contain a new active ingredient. An application for registration of a...

  14. 40 CFR 152.114 - Approval of registration under FIFRA sec. 3(c)(7)-Products that contain a new active ingredient.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... sec. 3(c)(7)-Products that contain a new active ingredient. 152.114 Section 152.114 Protection of... CLASSIFICATION PROCEDURES Agency Review of Applications § 152.114 Approval of registration under FIFRA sec. 3(c)(7)—Products that contain a new active ingredient. An application for registration of a...

  15. Human Health Relevance of Pharmaceutically Active Compounds in Drinking Water.

    PubMed

    Khan, Usman; Nicell, Jim

    2015-05-01

    In Canada, as many as 20 pharmaceutically active compounds (PhACs) have been detected in samples of treated drinking water. The presence of these PhACs in drinking water raises important questions as to the human health risk posed by their potential appearance in drinking water supplies and the extent to which they indicate that other PhACs are present but have not been detected using current analytical methods. Therefore, the goal of the current investigation was to conduct a screening-level assessment of the human health risks posed by the aquatic release of an evaluation set of 335 selected PhACs. Predicted and measured concentrations were used to estimate the exposure of Canadians to each PhAC in the evaluation set. Risk evaluations based on measurements could only be performed for 17 PhACs and, of these, all were found to pose a negligible risk to human health when considered individually. The same approach to risk evaluation, but based on predicted rather than measured environmental concentrations, suggested that 322 PhACs of the evaluation set, when considered individually, are expected to pose a negligible risk to human health due to their potential presence in drinking waters. However, the following 14 PhACs should be prioritized for further study: triiodothyronine, thyroxine, ramipril and its metabolite ramiprilat, candesartan, lisinopril, atorvastatin, lorazepam, fentanyl, atenolol, metformin, enalaprilat, morphine, and irbesartan. Finally, the currently available monitoring data for PhACs in Canadian surface and drinking waters was found to be lacking, irrespective of whether their suitability was assessed based on risk posed, predicted exposure concentrations, or potency.

  16. Types of Pesticide Ingredients

    EPA Pesticide Factsheets

    Pesticide active ingredients are described by the types of pests they control or how they work. For example, algicides kill algae, biopesticides are derived from natural materials, and insecticides kill insects.

  17. [Influence of stir-baked with sand on active ingredients, diarrhea and hepatoprotection of Herpetospermum caudigerum].

    PubMed

    Li, Juan-juan; Shen, Gang; Yin, Rong-li; Shen, Cheng-ying; Cheng, Ling; Qiu, Ling; Han, Jin; Yuan, Hai-long

    2015-01-01

    To study the influence of stir-baked with sand on active ingredients, diarrhea and hepatoprotection of Herpetospermum caudigerum, the contents of herperione and herpetin in H. caudigerum before and after stir-baking with sand were analyzed by HPLC. The effect of stir-baked with sand on diarrhea of H. caudigerum TL was evaluated using the mean stool rate (MSR) and mean diarrheal index ( MDI) and the influence of stir-baked with sand on hepatoprotective effect of H. caudigerum TL was examined using a mouse model of CCl4-induced liver injury based on the analysis of serum ALT and AST activities. The results of HPLC analysis showed the content of herperione in H. caudigerum after stir-baking with sand decreased by 40.9% (P < 0.01) and the content of herpetin had no change. Pharmacodynamic results showed that the MSR and MDI of high-dose and middle-dose group of H. caudigerum TL after stir-baking with sand were significantly lower than that of high-dose and middle-dose group of H. caudigerum TL without stir-baking with sand; The high-dose and middle-dose of H. caudigerum TL with/without stir-baking with sand significantly alleviated liver injury as indicated by the decreased levels of serum ALT and AST, but the ALT and AST levels of high-dose and middle-dose group of H. caudigerum TL after stir-baking with sand were higher than that of H. caudigerum TL without stir-baking with sand. The results revealed that the stir-baking with sand could effectively relieve diarrhea effect of H. caudigerum TL, while it also reduces the hepatoprotection of H. caudigerum TL.

  18. PHARMACEUTICALS AND PERSONAL CARE PRODUCTS AS UBIQUITOUS POLLUTANTS FROM PERSONAL USE AND ACTIVITIES

    EPA Science Inventory

    Perhaps more so than with any other class of pollutants, the occurrence of pharmaceuticals and personal care products (PPCPS) in the environment highlights the immediate, intimate, and inseparable connection between the individual activities of consumers and their environment. In...

  19. POLLUTION FROM PERSONAL ACTIONS, ACTIVITIES, AND BEHAVIORS: PHARMACEUTICALS AND PERSONAL CARE PRODUCTS IN THE ENVIRONMENT

    EPA Science Inventory

    Perhaps more so than with any other class of pollutants, the occurrence of pharmaceuticals and personal care products (PPCPs) in the environment highlights the immediate, intimate, and inseparable connection between the personal activities of individual citizens and their environ...

  20. POLLUTION FROM PERSONAL ACTIONS, ACTIVITIES, AND BEHAVIORS: PHARMACEUTICALS AND PERSONAL CARE PRODUCTS IN THE ENVIRONMENT

    EPA Science Inventory

    Perhaps more so than with any other class of pollutants, the occurrence of pharmaceuticals and personal care products (PPCPS) in the environment highlights the immediate, intimate, and inseparable connection between the personal activities of individual citizens and their environ...

  1. PHARMACEUTICAL AND PERSONAL CARE PRODUCTS AS UBIQUITOUS POLLUTANTS FROM PERSONAL USE AND ACTIVITIES

    EPA Science Inventory

    Perhaps more so than with any other class of pollutants, the occurrence of pharmaceuticals and personal care products (PPCPS) in the environment highlights the immediate, intimate, and inseparable connection between the individual activities of consumers and their environment. In...

  2. MICROWAVE-ASSISTED GREENER SYNTHESIS OF PHARMACEUTICALLY ACTIVE HETEROCYCLES UNDER BENIGN CONDITIONS

    EPA Science Inventory

    Green chemistry is a rapidly developing new field that provides us a proactive avenue for the sustainable development of future science and technologies. Environmentally benign protocols have been developed for the synthesis of various pharmaceutically active heterocycles namely ...

  3. Activities of the Federal Interagency Workgroup on Pharmaceuticals in Water

    EPA Science Inventory

    In 2012, four federal agencies signed a Memorandum of Understanding (MOU) establishing a formal mechanism to improve and sustain federal coordination and collaboration on issues related to pharmaceuticals in water. The MOU is in response to the Government Accountability Office re...

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

    PubMed

    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.

  5. 78 FR 23558 - Pesticide Products; Registration Applications for New Active Ingredients

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-19

    .... Proposed Uses: For use only in California: Post-flooding rice paddy fields. Contact: Emily Hartman, (RD.... Pursuant to the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), EPA is hereby providing notice... ingredient: Streptomyces microflavus strain AQ 6121. Product Type: e.g., Insecticide/Miticide. Proposed...

  6. Analysis of molecular interactions in solid dosage forms; challenge to molecular pharmaceutics.

    PubMed

    Yamamoto, Keiji; Limwikrant, Waree; Moribe, Kunikazu

    2011-01-01

    The molecular states of active pharmaceutical ingredients (APIs) in pharmaceutical dosage forms strongly affect the properties and quality of a drug. Various important fundamental physicochemical studies were reviewed from the standpoint of molecular pharmaceutics. Mechanochemical effects were evaluated in mixtures of APIs and pharmaceutical additives. Amorphization, complex formation and nanoparticle formation are observed after grinding process depending on the combination of APIs and pharmaceutical additives. Sealed-heating method and mesoporous materials have been used to investigate drug molecular interactions in dosage forms. Molecular states have been investigated using powder X-ray diffraction, thermal analysis, IR, solid state fluorometry, and NMR.

  7. Effects of surfactants and thermodynamic activity of model active ingredient on transport over plant leaf cuticle.

    PubMed

    Fagerström, Anton; Kocherbitov, Vitaly; Ruzgas, Tautgirdas; Westbye, Peter; Bergström, Karin; Engblom, Johan

    2013-03-01

    The main objective of this study was to investigate the mechanism of molecular transport across the cuticle of Clivia leaves. In vitro diffusion methodology was used to investigate the transport of a systemic fungicide, tebuconazole, over a model silicone membrane, enzymatically isolated cuticle membranes, and dermatomed leaves. It was shown that dermatomed leaves may replace enzymatically isolated cuticles. Furthermore, the effects of two surfactants, C(10)EO(7) and C(8)G(1.6), on the fungicide transport were investigated. Tebuconazole cuticle permeation was described using Fick's first law of diffusion, expressed by the thermodynamic activity of the solute in the membrane. A new method for calculation of diffusion coefficients in the membrane is proposed. To access the thermodynamic activity of the fungicide in the membranes, sorption isotherms of tebuconazole in the membrane materials studied were recorded. The thermodynamic activity of the fungicide in aqueous solutions was calculated from solubility data. For that purpose, the effect of surfactants on tebuconazole solubility was studied. The results show that addition of surfactants allows for higher concentrations of tebuconazole available for penetration. Nonetheless, at a fixed fungicide thermodynamic activity, all formulations produced the same flux over the silicone membrane independently on the fungicide concentration. This shows that the driving force across non-responding membranes is the gradient of thermodynamic activity, rather than the gradient of the fungicide concentration. In case of leaves, surfactants induced the same quantitative increase in both flux and diffusion coefficient of solute in the cuticle, while the cuticle-water partition coefficient was unaffected.

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

    PubMed

    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.).

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

    PubMed Central

    Maramaldi, Giada; Togni, Stefano; Franceschi, Federico; Lati, Elian

    2014-01-01

    Purpose 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-1α 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 glycating agent methylglyoxal. A clear epidermal densification of collagen network in the papillary dermis was observed. These in vitro data have been

  10. 21 CFR 341.85 - Labeling of permitted combinations of active ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... ingredient identified in § 341.40(a), (c), (f), (g), (m), (q), and (r) when labeled for relief of hay fever... general cough-cold symptoms and/or the common cold and for relief of hay fever/allergic rhinitis and/or... “pain reliever” or “analgesic (pain reliever).” If the product is also labeled to relieve fever,...

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

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... ingredient identified in § 341.40(a), (c), (f), (g), (m), (q), and (r) when labeled for relief of hay fever... general cough-cold symptoms and/or the common cold and for relief of hay fever/allergic rhinitis and/or... “pain reliever” or “analgesic (pain reliever).” If the product is also labeled to relieve fever,...

  12. 21 CFR 341.85 - Labeling of permitted combinations of active ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... ingredient identified in § 341.40(a), (c), (f), (g), (m), (q), and (r) when labeled for relief of hay fever... general cough-cold symptoms and/or the common cold and for relief of hay fever/allergic rhinitis and/or... “pain reliever” or “analgesic (pain reliever).” If the product is also labeled to relieve fever,...

  13. 21 CFR 341.85 - Labeling of permitted combinations of active ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... ingredient identified in § 341.40(a), (c), (f), (g), (m), (q), and (r) when labeled for relief of hay fever... general cough-cold symptoms and/or the common cold and for relief of hay fever/allergic rhinitis and/or... “pain reliever” or “analgesic (pain reliever).” If the product is also labeled to relieve fever,...

  14. WHO Expert Committee on Specifications for Pharmaceutical Preparations.

    PubMed

    2012-01-01

    The Expert Committee on Specifications for Pharmaceutical Preparations works towards clear, independent and practical standards and guidelines for the quality assurance of medicines. Standards are developed by the Committee through worldwide consultation and an international consensus-building process. The following new guidelines were adopted and recommended for use: Development of monographs for The International Pharmacopoeia; WHO good manufacturing practices: water for pharmaceutical use; Pharmaceutical development of multisource (generic) pharmaceutical products--points to consider; Guidelines on submission of documentation for a multisource (generic) finished pharmaceutical product for the WHO Prequalification of Medicines Programme: quality part; Development of paediatric medicines: points to consider in formulation; Recommendations for quality requirements for artemisinin as a starting material in the production of antimalarial active pharmaceutical ingredients.

  15. Artepillin C, a major ingredient of Brazilian propolis, induces a pungent taste by activating TRPA1 channels.

    PubMed

    Hata, Taketoshi; Tazawa, Shigemi; Ohta, Shozo; Rhyu, Mee-Ra; Misaka, Takumi; Ichihara, Kenji

    2012-01-01

    Brazilian green propolis is a popular health supplement because of its various biological properties. The ethanol extract of Brazilian green propolis (EEBP) is characteristic for its herb-like smell and unique pungent taste. However, the ingredients responsible for its pungency have not yet been identified. This study provides the first evidence that artepillin C is the main pungent ingredient in EEBP and that it potently activates human transient receptor potential ankyrin 1 (TRPA1) channels. EEBP was fractionated using column chromatography with a step gradient elution of an ethanol-water solution, and the fractions having the pungent taste were determined by sensory tests. HPLC analysis revealed that the pungent fraction was composed primarily of artepillin C, a prenylated derivative of cinnamic acid. Artepillin C was also identified as the pungent compound of EEBP by organoleptic examiners. Furthermore, the effects of artepillin C and other cinnamic acids found in EEBP on TRPA1 channels were examined by calcium imaging and plate reader-based assays in human TRPA1-expressing cells to investigate the molecular mechanisms underlying their pungent tastes. Artepillin C and baccharin activated the TRPA1 channel strongly, whereas drupanin caused a slight activation and p-coumaric acid showed no activation. Because the EC(50) values of artepillin C, baccharin, and allyl isothiocyanate were 1.8 µM, 15.5 µM, and 6.2 µM, respectively, artepillin C was more potent than the typical TRPA1 agonist allyl isothiocyanate. These findings strongly indicate that artepillin C is the main pungent ingredient in EEBP and stimulates a pungent taste by activating TRPA1 channels.

  16. Antibacterial activities of bacteriocins: application in foods and pharmaceuticals

    PubMed Central

    Yang, Shih-Chun; Lin, Chih-Hung; Sung, Calvin T.; Fang, Jia-You

    2014-01-01

    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 in food science and pharmaceutical industry. PMID:24904554

  17. THE EFFECTS OF DISINFECTION ON PHARMACEUTICALS IN DRINKING WATER SUPPLIES

    EPA Science Inventory

    Pharmaceuticals are intended to be applied to or ingested by humans and animals, metabolized and excreted through urine or feces. However it has been estimated that 30-90% of administered active ingredients pass through humans and animals unchanged. While sewage treatment plants ...

  18. An Integrated Approach to Thermal Analysis of Pharmaceutical Solids

    ERIC Educational Resources Information Center

    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…

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

    PubMed

    Pont, Adam R; Charron, Anna R; Brand, Rhonda M

    2004-03-15

    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 < 0.05), and only octocrylene and oxybenzone did not significantly decrease the corresponding lag time. Octyl salicylate (P < 0.01) and octyl methoxycinnimate (P < 0.05) significantly increased the 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.

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

    PubMed Central

    2010-01-01

    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. PMID:20974012

  1. Examining pharmaceuticals using terahertz spectroscopy

    NASA Astrophysics Data System (ADS)

    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.

  2. Characterization and Quality Control of Pharmaceutical Cocrystals.

    PubMed

    Izutsu, Ken-Ichi; Koide, Tatsuo; Takata, Noriyuki; Ikeda, Yukihiro; Ono, Makoto; Inoue, Motoki; Fukami, Toshiro; Yonemochi, Etsuo

    2016-10-01

    Recent active research and new regulatory guidance on pharmaceutical cocrystals have increased the rate of their development as promising approaches to improve handling, storage stability, and bioavailability of poorly soluble active pharmaceutical ingredients (APIs). However, their complex structure and the limited amount of available information related to their performance may require development strategies that differ from those of single-component crystals to ensure their clinical safety and efficacy. This article highlights current methods of characterizing pharmaceutical cocrystals and approaches to controlling their quality. Different cocrystal regulatory approaches between regions are also discussed. The physical characterization of cocrystals should include elucidating the structure of their objective crystal form as well as their possible variations (e.g., polymorphs, hydrates). Some solids may also contain crystals of individual components. Multiple processes to prepare pharmaceutical cocrystals (e.g., crystallization from solutions, grinding) vary in their applicable ingredients, scalability, and characteristics of resulting solids. The choice of the manufacturing method affects the quality control of particular cocrystals and their formulations. In vitro evaluation of the properties that govern clinical performance is attracting increasing attention in the development of pharmaceutical cocrystals. Understanding and mitigating possible factors perturbing the dissolution and/or dissolved states, including solution-mediated phase transformation (SMPT) and precipitation from supersaturated solutions, are important to ensure the bioavailability of orally administrated lower-solubility APIs. The effect of polymer excipients on the performance of APIs emphasizes the relevance of formulation design for appropriate use.

  3. Corporate colonization of health activism? Irish health advocacy organizations' modes of engagement with pharmaceutical corporations.

    PubMed

    O'Donovan, Orla

    2007-01-01

    This article is based on a study that aimed to shed light on the "cultures of action" of Irish health advocacy organizations, and particularly their modes of engagement with pharmaceutical corporations. Debates about what some interpret as the "corporate colonization" of health activism provide the backdrop for the analysis. The empirical dimension of the study involved a survey of 112 organizations and in-depth study of a small number of organizations that manifest diverse modes of engagement with the pharmaceutical industry. The varying modes of interaction are plotted along a continuum and characterized as corporatist, cautious cooperation, and confrontational. Evidence is presented of a strong and growing cultural tendency in Irish health advocacy organizations to frame pharmaceutical corporations as allies in their quests for better health. The analysis of four constitutive dimensions of organizations' cultures of action can reveal the legitimating logics underlying their diverging positions around pharmaceutical industry sponsorship. While the research shows that pharmaceutical corporations have largely succeeded in defining themselves as a philanthropic force and rightful players in Irish health activism, it cautions against a simplistic conclusion that this is evidence of corporate colonization.

  4. Towards improved therapies using nanopharmaceuticals: recent patents on pharmaceutical nanoformulations.

    PubMed

    Horstkotte, Elke; Odoerfer, Kathrin I

    2012-12-01

    Pharmaceutical formulations that contain nanosized drugs are perceived as "Nanopharmaceuticals" and offer significant benefit for the patient compared to the conventional formulated drugs. There are several advantages of nanoparticular drug formulations such as enhanced solubility and dissolution rate, enhanced oral bioavailability, improved dose proportionality, reduced food effects, suitability for administration by all routes and possibility of sterile filtration due to decreased particle size range. Several nanopharmaceuticals are successfully marketed. Different patented techniques are commercialized to prepare nanopharmaceuticals such as milling, homogenization and precipitation. The focus of the underlying review is to give an overview of those technologies for nanosizing active pharmaceutical ingredients and recently published patents in the field of nanosized pharmaceutics.

  5. 21 CFR 310.545 - Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... (as single ingredient) Resorcinol monoacetate (as single ingredient) Salicylic acid (over 2 up to 5... stearate Zinc sulfide (2) Anticaries drug products—(i) Approved as of May 7, 1991. Hydrogen fluoride Sodium... hydrochloride (B) Ingredients. Phenyltoloxamine dihydrogen citrate Methapyrilene hydrochloride...

  6. 21 CFR 310.545 - Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... (as single ingredient) Resorcinol monoacetate (as single ingredient) Salicylic acid (over 2 up to 5... stearate Zinc sulfide (2) Anticaries drug products—(i) Approved as of May 7, 1991. Hydrogen fluoride Sodium... hydrochloride (B) Ingredients. Phenyltoloxamine dihydrogen citrate Methapyrilene hydrochloride...

  7. 21 CFR 310.545 - Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... (as single ingredient) Resorcinol monoacetate (as single ingredient) Salicylic acid (over 2 up to 5... stearate Zinc sulfide (2) Anticaries drug products—(i) Approved as of May 7, 1991. Hydrogen fluoride Sodium... hydrochloride (B) Ingredients. Phenyltoloxamine dihydrogen citrate Methapyrilene hydrochloride...

  8. 21 CFR 310.545 - Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (as single ingredient) Resorcinol monoacetate (as single ingredient) Salicylic acid (over 2 up to 5... stearate Zinc sulfide (2) Anticaries drug products—(i) Approved as of May 7, 1991. Hydrogen fluoride Sodium... hydrochloride (B) Ingredients. Phenyltoloxamine dihydrogen citrate Methapyrilene hydrochloride...

  9. Evaluation of Essential Oil and its Three Main Active Ingredients of Chinese Chenopodium ambrosioides (Family: Chenopodiaceae) against Blattella germanica

    PubMed Central

    Zhu, Wei Xiang; Zhao, Kun; Chu, Sha Sha; Liu, Zhi Long

    2012-01-01

    Background: The efficacy of essential oil of Chenopodium ambrosioides flowering aerial parts and its three main active ingredients was evaluated against Blattella germanica male adults. Methods: Composition of essential oil was determined by GC-MS. Topical application bioassay was used to evaluate contact 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 ρ-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 were toxic to male German cockroaches and (Z)-ascaridole was the strongest with a LD50 value of 22.02 μg/adult while the crude oil with a LD50 value of 67.46 μg/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. PMID:23378965

  10. PHARMACEUTICALS AND PERSONAL CARE PRODUCTS IN THE ENVIRONMENT: POLLUTION FROM PERSONAL ACTIONS, ACTIVITIES, AND BEHAVIORS

    EPA Science Inventory



    Perhaps more so than with any other class of pollutants, the occurrence of pharmaceuticals and personal care products (PPCPS) in the environment highlights the immediate, intimate, and inseparable connection between the individual activities of consumers and their environ...

  11. Organic Pesticide Ingredients

    MedlinePlus

    ... W X Y Z A-Z Index Health & Environment Human Health Animal Health Safe Use Practices Food Safety ... Low-Risk Pesticides Organic Pesticide Ingredients Pesticide Incidents Human Exposure Pet Exposure Environmental Incident Illegal Pesticide Activity Problem With Labels or ...

  12. Cichorium intybus root extract: A "vitamin D-like" active ingredient to improve skin barrier function.

    PubMed

    Maia Campos, P M B G; G Mercurio, D; O Melo, M; Closs-Gonthier, B

    2017-02-01

    During the aging process, the human skin suffers many alterations including dryness, skin barrier function damage. The skin barrier function is important to the prevention of skin alterations and maintenance of homeostasis. So, the objective of this study was to assess the clinical efficacy on skin barrier function of Cichorium intybus root extract in cosmetic formulations with or without UV filters. Fifty women, aged between 45 and 60 years, were divided into two groups. One group received vehicle formulations containing UV filters, and the other group received formulations without UV filters. Both groups received a formulation containing the extract and the vehicle. The formulations were applied twice daily to the upper arms after washing with sodium lauryl sulphate. Transepidermal water loss (TEWL) and skin microrelief were evaluated before and after a 14- and 28-day period of treatment. The control regions and regions where the vehicles were applied showed an increase in the TEWL. For the formulations containing the extract, decreased TEWL and improved microrelief were observed when compared to the vehicle and control areas after a 28-day period. In conclusion, Cichorium intybus root extract showed protective and restructuring effects on the skin and stands out as an innovative ingredient to improve skin barrier function.

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

    PubMed

    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.

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

    PubMed Central

    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

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

    PubMed

    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.

  16. Self-assembled sorbitol-derived supramolecular hydrogels for the controlled encapsulation and release of active pharmaceutical ingredients.

    PubMed

    Howe, Edward J; Okesola, Babatunde O; Smith, David K

    2015-05-01

    A simple supramolecular hydrogel based on 1,3:2,4-di(4-acylhydrazide)benzylidene sorbitol (DBS-CONHNH2), is able to extract acid-functionalised anti-inflammatory drugs via directed interactions with the self-assembled gel nanofibres. Two-component hydrogel-drug hybrid materials can be easily formed by mixing and exhibit pH-controlled drug release.

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

    PubMed

    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.

  18. A stability-indicating HPLC method for the determination of bazedoxifene acetate and its related substances in active pharmaceutical ingredient.

    PubMed

    Visweswara Rao, Karri; Reddy, Kesareddy Padmaja; Kumari, Kondapaturu Siva; Srinivas, Mudigonda

    2013-03-01

    A simple, cost effective, stability-indicating reversed-phase high-performance liquid chromatography method was developed for the quantitative determination of bazedoxifene acetate (BAZ) drug substance in the presence of its impurities and degradation products. The method was developed using an X-terra RP-18, 150 × 4.6 mm, 3.5 μm column with a mobile phase containing solvent A, a mixture of 10 mM K(2)HPO(4) (pH 8.3) and acetonitrile in the ratio of 70:30 (v/v); and solvent B, a mixture of water and acetonitrile in the ratio 10:90 (v/v). The eluted compounds were monitored at 220 nm, and within a short run time of 18 min, BAZ and its impurities were satisfactorily separated with resolution more than 2.0. BAZ was subjected to stress degradation and found to be sensitive towards acidic, basic, oxidative, thermal and hydrolytic stress conditions and stable in photo degradation conditions. The degradation products were well resolved from BAZ peak and its impurities; the mass balance in each case was more than 99.5%, proving the stability-indicating power of the method. The developed method was validated as per International Conference on Harmonization guidelines with respect to specificity, linearity (correlation coefficient > 0.9994), limit of detection, limit of quantification, accuracy (recovery range 96.3 to 102.1%), precision (relative standard deviation < 2.8%) and robustness.

  19. Raman Spectroscopy: A Sensitive and Specific Technique for Determining the Accuracy of Compounded Pharmaceutical Formulations.

    PubMed

    Meek, Claudia; Hoe, Jihye; Evans, Jason; Thurman, Rosanne; Ashworth, Lisa; Leff, Richard

    2016-01-01

    OBJECTIVES: Raman spectroscopy is a widely used technology to identify chemical unknowns or confirm chemical identity. We have tested Raman spectrometry to identify compounded pharmaceutical formulations. In contrast to the commonly used application mentioned above, compounded pharmaceutical formulations contain a mixture of ingredients, and the Raman spectrometer is being used to correctly identify the composition of the complete pharmaceutical formulation, including the active pharmaceutical ingredient(s). The objective of this pilot study was to document the potential use of Raman spectroscopy as a tool to provide quality control to compounded pharmaceutical formulations. METHODS: "Testing a test" study design was used to prospectively determine whether Raman spectroscopy could verify the accuracy of compounded pharmaceutical formulations. A total of 9 formulations that are commonly compounded at Cook Children's Health Center were selected for testing. Each of the 9 formulations and 2 blank controls were randomly tested for compounding accuracy in replicate. A total of 110 tests were conducted. RESULTS: Raman spectroscopy was found to be a reliable test to determine the accuracy of compounded pharmaceutical formulations with a 100% positive predictive value. CONCLUSIONS: Raman spectroscopy promises to be an excellent tool for compounding pharmacies to provide an objective measure of compounding accuracy to their unique, compounded pharmaceutical formulations.

  20. Raman Spectroscopy: A Sensitive and Specific Technique for Determining the Accuracy of Compounded Pharmaceutical Formulations

    PubMed Central

    Meek, Claudia; Hoe, Jihye; Evans, Jason; Thurman, Rosanne; Ashworth, Lisa

    2016-01-01

    OBJECTIVES: Raman spectroscopy is a widely used technology to identify chemical unknowns or confirm chemical identity. We have tested Raman spectrometry to identify compounded pharmaceutical formulations. In contrast to the commonly used application mentioned above, compounded pharmaceutical formulations contain a mixture of ingredients, and the Raman spectrometer is being used to correctly identify the composition of the complete pharmaceutical formulation, including the active pharmaceutical ingredient(s). The objective of this pilot study was to document the potential use of Raman spectroscopy as a tool to provide quality control to compounded pharmaceutical formulations. METHODS: “Testing a test” study design was used to prospectively determine whether Raman spectroscopy could verify the accuracy of compounded pharmaceutical formulations. A total of 9 formulations that are commonly compounded at Cook Children's Health Center were selected for testing. Each of the 9 formulations and 2 blank controls were randomly tested for compounding accuracy in replicate. A total of 110 tests were conducted. RESULTS: Raman spectroscopy was found to be a reliable test to determine the accuracy of compounded pharmaceutical formulations with a 100% positive predictive value. CONCLUSIONS: Raman spectroscopy promises to be an excellent tool for compounding pharmacies to provide an objective measure of compounding accuracy to their unique, compounded pharmaceutical formulations. PMID:27877094

  1. Behavior of selected pharmaceuticals in topsoil of Greyic Phaeozem

    NASA Astrophysics Data System (ADS)

    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

  2. In silico dissolution rates of pharmaceutical ingredients

    NASA Astrophysics Data System (ADS)

    Dogan, Berna; Schneider, Julian; Reuter, Karsten

    2016-10-01

    The correlation between in vitro dissolution rates and the efficiency of drug formulations establishes an opportunity for accelerated drug development. Using in silico methods to predict the dissolution rates bears the prospect of further efficiency gains by avoiding the actual synthesis of candidate formulations. Here, we present a computational protocol that achieves such prediction for molecular crystals at low undersaturation. The protocol exploits the classic spiral dissolution model to minimize the number of material parameters that require explicit molecular simulations. Comparison to available data for acetylsalicylic acid and alpha lactose monohydrate indicates a tunable accuracy within one order of magnitude.

  3. Validation of an in-line Raman spectroscopic method for continuous active pharmaceutical ingredient quantification during pharmaceutical hot-melt extrusion.

    PubMed

    Saerens, L; Segher, N; Vervaet, C; Remon, J P; De Beer, T

    2014-01-02

    A calibration model for in-line API determination was developed based on Raman spectra collected during hot-melt extrusion. This predictive model was validated by calculating the accuracy profile based on the analysis results of validation experiments. Furthermore, based on the data of the accuracy profile, the measurement uncertainty was determined. Finally, the robustness of the model was evaluated. A Raman probe was implemented in the die of a twin-screw extruder, to monitor the drug concentration during extrusion of physical mixtures containing 15, 20, 25, 30 and 35% (w/w) metoprolol tartrate (MPT) in Eudragit(®) RS PO, an amorphous copolymer of acrylic and methacrylic acid esters with a low content of quaternary ammonium groups, which are present as salts. Several different calibration models for the prediction of the MPT content were developed, based on the use of single spectra or averaged spectra, and using partial least squares (PLS) regression or multivariate curve resolution (MCR). These predictive models were validated by extruding and monitoring mixtures containing 17.5, 22.5, 25.0, 27.5 and 32.5% (w/w) MPT. Each validated concentration was monitored on three different days, by two different operators. The β-expectation tolerance intervals were calculated for each model and for each of the validated MPT concentration levels (β was set at 95%), and acceptance limits were set at 10% (relative bias), indicating that at least 95% of future measurements should not deviate more than 10% from the true value. The only model where these acceptance limits were not exceeded was the MCR model based on averaged Raman spectra. The uncertainty measurements for this model showed that the unknown true value can be found at a maximum of ±7.00% around the measured result, with a confidence level of 95%. The robustness of this model was evaluated via an experimental design varying throughput, screw speed and barrel temperature. The robustness designs showed no significant influence of any of the process settings on the predicted concentration values. Raman spectroscopy proved to be a fast, non-destructive and reliable method for the quantification of MPT during hot-melt extrusion. From the accuracy profile of the MCR model based on averaged spectra, it was concluded that for each MPT concentration in the validated concentration range, 95 out 100 future routine measurements will be included within the acceptance limits (10%).

  4. A comparative toxicologic and genotoxic study of the herbicide arsenal, its active ingredient imazapyr, and the surfactant nonylphenol ethoxylate.

    PubMed

    Grisolia, Cesar Koppe; Bilich, Marina Rolim; Formigli, Lia Menezes

    2004-09-01

    The herbicide arsenal 250 NA, its technical-grade active ingredient imazapyr, and the surfactant nonylphenol ethoxylate (NP) were evaluated through genotoxicity and toxicity studies in different organisms. A comparative study of these three compounds was carried out to assess how the addition of surfactant components may pose the highest toxicological risk to pesticide formulations. The results showed that arsenal, imazapyr, and NP did not cause chromosome aberration in Allium cepa nor increase the frequency of micronuclei in mice. However, toxicological evaluations showed that NP was the most toxic compound to mice, A. cepa, Drosophila melanogaster, and Biomphalaria tenagophila. In this evaluation, it was observed that the adverse effects were produced by the surfactant additive of the pesticide formulation.

  5. [Chemical diversity of the biological active ingredients of salvia officinalis and some closely related species].

    PubMed

    Máthé, Imre; Hohmann, Judit; Janicsák, Gábor; Nagy, Gábor; Dora, Rédei

    2007-01-01

    Comparative studies on the volatile and non-volatile fractions of 6 species. i.e. Salvia officinalis, S. tomentosa, S. fruticosa, S. candelabrum, S. ringens, S. lavandulifolia of the Section Salvia (Lamiaceae) have been carried out. Both fractions provide the chemical pattern matches to the chemotaxonomic character of Subfamily Nepetoideae in Erdtmanr two subfamiliar system. S. lavandulifolia had the highest essential oil content, followed by S. fruticosa, S. tomentosa, S. officinalis and S. candelabrum. S. ringens contains volatile oil only in traces. The neurotoxin thujone content was the highest in the S. officinalis oils and in that of S. fruticosa. No thujone was detected in S. lavandulifolia. The other species, e.g.: S. tomentosa contain this compound only in moderate concentrations (less than 10%). Among the non-volatile fractions of the plant ingredients the triterpene ursolic and oleanolic acids had the highest concentration in the leaves. Despite some rare cases, ursolic acid dominates the tritepene fraction. Rosmarinic and caffeic acids were measured in similar concentrations, in all species. As the case of S. officinalis shows, these compounds vary significantly in all organs during the vegetation period. Caffeic acid is also ubiquitous in the genus Salvia but as our data suggest it occurs in an order of magnitude lower concentration than rosmarinic acid. The isolation of phenylethanolid martynoside, though obtained in a rather small concentration, is of great chemotaxonomic significance, as this is the first phenylethanolid type glycoside isolated not only from the Salvia genus but also from the entire Subfamily Nepetoideae. As pheylethanolids are rather common and accumulate in significant concentrations in plants of the Subfamily Lamioideae, our opinion that the chemical differences between the two subfamilies are less qualititative than quantitative, is confirmed. This holds true of other chemical markers like monoterpenes, ursolic and oleanolic

  6. Active Ingredients of Treatment and Client Mechanisms of Change in Behavioral Treatments for Alcohol Use Disorders: Progress 10 Years Later

    PubMed Central

    Magill, M.; Kiluk, B.D.; McCrady, B.; Tonigan, J.S.; Longabaugh, R.

    2015-01-01

    Background The current review revisits the article entitled: Active Ingredients of Behavioral Treatments for Alcohol Use Disorders (AUDs) published in Alcoholism: Clinical and Experimental Research. This work summarized proceedings from a 2004 Symposium of the same name that was held at the Annual Meeting of the Research Society on Alcoholism (RSA). A decade has passed, which provides occasion for an evaluation of progress. In 2014, an RSA symposium titled Active Treatment Ingredients and Client Mechanisms of Change in Behavioral Treatments for Alcohol Use Disorders: Progress 10 Years Later did just that. Overview The current review revisits state-of-the-art research on the three treatments examined 10 years ago: Cognitive Behavioral Therapy (CBT), Alcohol Behavior Couples Therapy (ABCT), and Twelve Step Facilitation (TSF). Because of its empirically-validated effectiveness and robust research agenda on the study of process-outcome, Motivational Interviewing (MI) has been selected as the fourth treatment modality to be discussed. For each of these four treatments, the reviewers provide a critical assessment of current theory and research with a special emphasis on key recommendations for the future. Conclusions Noteworthy progress has been made in identifying AITs and MOBCs in these four behavioral interventions for alcohol and other drug use disorders. Not only have we established some of the mechanisms through which these evidence-based treatments work, but we have also uncovered some of the limitations in our existing frameworks and methods. Further progress in this area will require a broader view with respect to conceptual frameworks, analytic methods, and measurement instrumentation. PMID:26344200

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

    NASA Astrophysics Data System (ADS)

    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.

  8. Water and stability of pharmaceutical solids

    NASA Astrophysics Data System (ADS)

    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?

  9. [Effect of exogenous sucrose on growth and active ingredient content of licorice seedlings under salt stress conditions].

    PubMed

    Liu, Fu-zhi; Yang, Jun

    2015-11-01

    Licorice seedlings were taken as experimental materials, an experiment was conducted to study the effects of exogenous sucrose on growth and active ingredient content of licorice seedlings under NaCl stress conditions. The results of this study showed that under salt stress conditions, after adding a certain concentration of exogenous sucrose, the licorice seedlings day of relative growth rate was increasing, and this stress can be a significant weakening effect, indicating that exogenous sucrose salt stress-relieving effect. The total flavonoids and phenylalanine ammonia lyase (PAL) activity were significantly increased, the exogenous sucrose can mitigated the seedling roots under salt stress, the licorice flavonoid content in the enhanced growth was largely due to the activity of PAL an increased, when the concentration of exogenous sucrose wae 10 mmol x L(-1), PAL activity reaching a maximum, when the concentration of exogenous sucrose was 15 mmol x L(-1), PAL activity turned into a downward trend, the results indicating that this mitigation has concentration effect. After applying different concentrations of exogenous sugar, the contents of liquiritin changes with the change of flavonoids content was similar. After applying different concentrations of exogenous sucrose, the content of licorice acid under salt stress was higher than the levels were not reached during salt stress, the impact of exogenous sucrose concentration gradient of licorice acid accumulation was not obvious.

  10. Perceptions and Attitudes of Egyptian Health Professionals and Policy-Makers towards Pharmaceutical Sales Representatives and Other Promotional Activities

    PubMed Central

    Kamal, Susan; Holmberg, Christine; Russell, Jean; Bochenek, Tomasz; Tobiasz-Adamczyk, Beata; Fischer, Christiane; Tinnemann, Peter

    2015-01-01

    Background Pharmaceutical promotion activities in low and middle-income countries are often neither regulated nor monitored. While Egypt has the highest population and per capita use of medicines in the Arab world, we know very little about pharmaceutical companies promotional activities in the country. Aim To explore and analyze the perceptions of physicians towards promotional and marketing activities of pharmaceutical companies among physicians and pharmacists in Egypt. Methodology Perspectives of different healthcare system stakeholders were explored through semi-structured, in-depth interviews conducted in 2014 in Cairo, Egypt. Interviewees were chosen via purposive sampling and snowball technique. Each interview was recorded and transcribed. Then qualitative, thematic analysis was conducted with the help of NVIVO software. Findings The majority of physicians and pharmacists acknowledged exposure to pharmaceutical promotion. It was commonly believed that interaction with the pharmaceutical industry is necessary and both associated risks and benefits were acknowledged. The interviewed physicians considered themselves competent enough to minimize risks and maximize benefits to their prescribing habits. Views diverged on the extent and magnitude of the risks and benefits of pharmaceutical promotion, especially in regard to the influence on patients’ health. Conclusions Pharmaceutical promotion in Egypt is intensely directed at prescribers and dispensers. Physicians, pharmacists and policymakers expressed little skepticism to the influence of promotion towards their individual prescribing. Raising awareness of the pitfalls of pharmaceutical promotion is necessary, especially among the less experienced physicians. PMID:26473484

  11. Activated carbon for the removal of pharmaceutical residues from treated wastewater.

    PubMed

    Ek, Mats; Baresel, Christian; Magnér, Jörgen; Bergström, Rune; Harding, Mila

    2014-01-01

    Pharmaceutical residues, which pass naturally through the human body into sewage, are in many cases virtually unaffected by conventional wastewater treatment. Accumulated in the environment, however, they can significantly impact aquatic life. The present study indicates that many pharmaceutical residues found in wastewater can be removed with activated carbon in a cost-efficient system that delivers higher resource utilisation and security than other carbon systems. The experiment revealed a substantial separation of the analysed compounds, notwithstanding their relatively high solubility in water and dissimilar chemical structures. This implies that beds of activated carbon may be a competitive alternative to treatment with ozone. The effluent water used for the tests, performed over 20 months, originated from Stockholm's largest sewage treatment plant. Passing through a number of different filters with activated carbon removed 90-98% of the pharmaceutical residues from the water. This paper describes pilot-scale tests performed by IVL and the implications for an actual treatment plant that has to treat up to several thousand litres of wastewater per second. In addition, the advantages, disadvantages and costs of the method are discussed. This includes, for example, the clogging of carbon filters and the associated hydraulic capacity limits of the activated carbon.

  12. Bactericidal active ingredient in cryopreserved plasma-treated water with the reduced-pH method for plasma disinfection

    NASA Astrophysics Data System (ADS)

    Kitano, Katsuhisa; Ikawa, Satoshi; Nakashima, Yoichi; Tani, Atsushi; Yokoyama, Takashi; Ohshima, Tomoko

    2016-09-01

    For the plasma disinfection of human body, plasma sterilization in liquid is crucial. We found that the plasma-treated water (PTW) has strong bactericidal activity under low pH condition. Physicochemical properties of PTW is discussed based on chemical kinetics. Lower temperature brings longer half-life and the bactericidal activity of PTW can be kept by cryopreservation. High performance PTW, corresponding to the disinfection power of 22 log reduction (B. subtilis spore), can be obtained by special plasma system equipped with cooling device. This is equivalent to 65% H2O2, 14% sodium hypochlorite and 0.33% peracetic acid, which are deadly poison for human. But, it is deactivated soon at higher temperature (4 sec. at body temperature), and toxicity to human body seems low. For dental application, PTW was effective on infected models of human extracted tooth. Although PTW has many chemical components, respective chemical components in PTW were isolated by ion chromatography. In addition to peaks of H2O2, NO2- and NO3-, a specific peak was detected. and only this fraction had bactericidal activity. Purified active ingredient of PTW is the precursor of HOO, and further details will be discussed in the presentation. MEXT (15H03583, 23340176, 25108505). NCCE (23-A-15).

  13. A Comprehensive and System Review for the Pharmacological Mechanism of Action of Rhein, an Active Anthraquinone Ingredient.

    PubMed

    Sun, Hao; Luo, Guangwen; Chen, Dahui; Xiang, Zheng

    2016-01-01

    Rhein is a major medicinal ingredient isolated from several traditional Chinese medicines, including Rheum palmatum L., Aloe barbadensis Miller, Cassia angustifolia Vahl., and Polygonum multiflorum Thunb. Rhein has various pharmacological activities, such as anti-inflammatory, antitumor, antioxidant, antifibrosis, hepatoprotective, and nephroprotective activities. Although more than 100 articles in PubMed are involved in the pharmacological mechanism of action of rhein, only a few focus on the relationship of crosstalk among multiple pharmacological mechanisms. The mechanism of rhein involves multiple pathways which contain close interactions. From the overall perspective, the pathways which are related to the targets of rhein, are initiated by the membrane receptor. Then, MAPK and PI3K-AKT parallel signaling pathways are activated, and several downstream pathways are affected, thereby eventually regulating cell cycle and apoptosis. The therapeutic effect of rhein, as a multitarget molecule, is the synergistic and comprehensive result of the involvement of multiple pathways rather than the blocking or activation of a single signaling pathway. We review the pharmacological mechanisms of action of rhein by consulting literature published in the last 100 years in PubMed. We then summarize these pharmacological mechanisms from a comprehensive, interactive, and crosstalk perspective. In general, the molecular mechanism of action of drug must be understood from a systematic and holistic perspective, which can provide a theoretical basis for precise treatment and rational drug use.

  14. A Comprehensive and System Review for the Pharmacological Mechanism of Action of Rhein, an Active Anthraquinone Ingredient

    PubMed Central

    Sun, Hao; Luo, Guangwen; Chen, Dahui; Xiang, Zheng

    2016-01-01

    Rhein is a major medicinal ingredient isolated from several traditional Chinese medicines, including Rheum palmatum L., Aloe barbadensis Miller, Cassia angustifolia Vahl., and Polygonum multiflorum Thunb. Rhein has various pharmacological activities, such as anti-inflammatory, antitumor, antioxidant, antifibrosis, hepatoprotective, and nephroprotective activities. Although more than 100 articles in PubMed are involved in the pharmacological mechanism of action of rhein, only a few focus on the relationship of crosstalk among multiple pharmacological mechanisms. The mechanism of rhein involves multiple pathways which contain close interactions. From the overall perspective, the pathways which are related to the targets of rhein, are initiated by the membrane receptor. Then, MAPK and PI3K-AKT parallel signaling pathways are activated, and several downstream pathways are affected, thereby eventually regulating cell cycle and apoptosis. The therapeutic effect of rhein, as a multitarget molecule, is the synergistic and comprehensive result of the involvement of multiple pathways rather than the blocking or activation of a single signaling pathway. We review the pharmacological mechanisms of action of rhein by consulting literature published in the last 100 years in PubMed. We then summarize these pharmacological mechanisms from a comprehensive, interactive, and crosstalk perspective. In general, the molecular mechanism of action of drug must be understood from a systematic and holistic perspective, which can provide a theoretical basis for precise treatment and rational drug use. PMID:27582705

  15. 21 CFR 333.160 - Labeling of permitted combinations of active ingredients.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... HUMAN USE First Aid Antibiotic Drug Products § 333.160 Labeling of permitted combinations of active... product may state, under the heading “Indications,” the following additional indication: “First aid...

  16. 21 CFR 333.160 - Labeling of permitted combinations of active ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... HUMAN USE First Aid Antibiotic Drug Products § 333.160 Labeling of permitted combinations of active... product may state, under the heading “Indications,” the following additional indication: “First aid...

  17. 21 CFR 333.160 - Labeling of permitted combinations of active ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... HUMAN USE First Aid Antibiotic Drug Products § 333.160 Labeling of permitted combinations of active... product may state, under the heading “Indications,” the following additional indication: “First aid...

  18. Skin-Applied Repellent Ingredients

    EPA Pesticide Factsheets

    Active ingredients in EPA-registered insect repellents include catnip oil, oil of citronella, DEET, IR 3535, picaridin, oil of lemon eucalyptus, and 2-undecanone. Find fact sheets and pesticide regulatory information.

  19. Developing a Passive Time-Activity Triage System In support of Consumer Ingredient Exposure Prioritization

    EPA Science Inventory

    Chemical Hazard/toxicity assessment of chemicals relies on droves of chemical-biological data at the organism, tissue, cell, and biomolecular level of resolution. Big data in the context of exposure science relies on a comprehensive knowledge of societies’ and community activity ...

  20. Quantitative structure property relationships for the adsorption of pharmaceuticals onto activated carbon.

    PubMed

    Dickenson, E R V; Drewes, J E

    2010-01-01

    Isotherms were determined for the adsorption of five pharmaceutical residues, primidone, carbamazepine, ibuprofen, naproxen and diclofenac, to Calgon Filtrasorb 300 powdered activated carbon (PAC). The sorption behavior was examined in ultra-pure and wastewater effluent organic matter (EfOM) matrices, where more sorption was observed in the ultra-pure water for PAC doses greater than 10 mg/L suggesting the presence of EfOM hinders the sorption of the pharmaceuticals to the PAC. Adsorption behaviors were described by the Freundlich isotherm model. Quantitative structure property relationships (QSPRs) in the form of polyparameter linear solvation energy relationships were developed for simulating the Freundlich adsorption capacity in both ultra-pure and EfOM matrices. The significant 3D-based descriptors for the QSPRs were the molar volume, polarizability and hydrogen-bond donor parameters.

  1. Deliquescence of pharmaceutical systems.

    PubMed

    Mauer, Lisa J; Taylor, Lynne S

    2010-12-01

    Deliquescence is a first order phase transition from solid to solution that occurs at a relative humidity (RH) that is characteristic to the crystalline compound. Such dissolution of active pharmaceutical ingredients and excipients can lead to detrimental physical and chemical instabilities. Furthermore, in systems containing more than one deliquescent component, the RH of the solid-solution transition will be lowered, leading to some level of dissolution at unexpectedly low RH conditions. Deliquescence lowering is independent of the ratio of the deliquescent components and therefore is of concern for any formulation containing two or more deliquescent compounds. Because chemical reactions occur much more readily in solution, deliquescence will enhance the degradation of labile APIs. RH fluctuations will lead to cycles of deliquescence and efflorescence (crystallization), which will contribute to particle agglomeration and caking. This review will address the phenomenon of deliquescence, the significance of deliquescence to pharmaceutical systems, measurement techniques, the kinetics and thermodynamics of deliquescence, the behavior of mixtures of deliquescent compounds (including phase diagrams and thermodynamics of binary systems), and consequences of deliquescence on chemical and physical stability.

  2. PHARMACEUTICALS AND PERSONAL CARE PRODUCTS IN THE ENVIRONMENT: AN OVERVIEW - POLLUTION FROM PERSONAL ACTIONS, ACTIVITIES, AND BEHAVIORS

    EPA Science Inventory

    Perhaps more so than with any other class of pollutants, the occurrence of pharmaceuticals and personal care products (PPCPS) in the environment highlights the immediate, intimate, and inseparable connection between the individual activities of consumers and their environment. I...

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

    EPA Science Inventory

    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...

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

    EPA Science Inventory

    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. Antifungal activity of sourdough fermented wheat germ used as an ingredient for bread making.

    PubMed

    Rizzello, Carlo Giuseppe; Cassone, Angela; Coda, Rossana; Gobbetti, Marco

    2011-08-01

    This study aimed at investigating the antifungal activity of sourdough fermented (Lactobacillus plantarum LB1 and Lactobacillus rossiae LB5) wheat germ (SFWG). Preliminarily, methanol and water/salt-soluble extracts from SFWG were assayed by agar diffusion towards Penicillium roqueforti DPPMAF1. As shown by hyphal radial growth rate, the water/salt-soluble extract showed the inhibition of various fungi isolated from bakeries. The antifungal activity was attributed to a mixture of organic acids and peptides which were synthesized during fermentation. Formic (24.7mM) acid showed the highest antifungal activity. Four peptides, having similarities with well known antifungal sequences, were identified and chemically synthesized. The minimal inhibitory concentration was 2.5-15.2mg/ml. Slices of bread made by addition of 4% (wt/wt) of freeze dried SFWG were packed in polyethylene bags and stored at room temperature. Slices did not show contamination by fungi until at least 28days of storage and behaved as the calcium propionate (0.3%, wt/wt).

  6. 40 CFR 152.114 - Approval of registration under FIFRA sec. 3(c)(7)-Products that contain a new active ingredient.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS PESTICIDE REGISTRATION AND...)(7)—Products that contain a new active ingredient. An application for registration of a pesticide... § 152.112(a), (b), (d), and (f) through (h) have been satisfied; (d) The use of the pesticide...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  9. 21 CFR 310.534 - Drug products containing active ingredients offered over-the-counter (OTC) for human use as oral...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... offered over-the-counter (OTC) for human use as oral wound healing agents. 310.534 Section 310.534 Food... active ingredients offered over-the-counter (OTC) for human use as oral wound healing agents. (a... aqueous solution have been present in oral mucosal injury drug products for use as oral wound...

  10. 21 CFR 310.534 - Drug products containing active ingredients offered over-the-counter (OTC) for human use as oral...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... offered over-the-counter (OTC) for human use as oral wound healing agents. 310.534 Section 310.534 Food... active ingredients offered over-the-counter (OTC) for human use as oral wound healing agents. (a... aqueous solution have been present in oral mucosal injury drug products for use as oral wound...

  11. 21 CFR 310.534 - Drug products containing active ingredients offered over-the-counter (OTC) for human use as oral...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... offered over-the-counter (OTC) for human use as oral wound healing agents. 310.534 Section 310.534 Food... active ingredients offered over-the-counter (OTC) for human use as oral wound healing agents. (a... aqueous solution have been present in oral mucosal injury drug products for use as oral wound...

  12. 21 CFR 310.534 - Drug products containing active ingredients offered over-the-counter (OTC) for human use as oral...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... offered over-the-counter (OTC) for human use as oral wound healing agents. 310.534 Section 310.534 Food... active ingredients offered over-the-counter (OTC) for human use as oral wound healing agents. (a... aqueous solution have been present in oral mucosal injury drug products for use as oral wound...

  13. 21 CFR 310.534 - Drug products containing active ingredients offered over-the-counter (OTC) for human use as oral...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... offered over-the-counter (OTC) for human use as oral wound healing agents. 310.534 Section 310.534 Food... active ingredients offered over-the-counter (OTC) for human use as oral wound healing agents. (a... aqueous solution have been present in oral mucosal injury drug products for use as oral wound...

  14. Understanding the Active Ingredients in an Effective Preschool Vocabulary Intervention: An Exploratory Study of Teacher and Child Talk during Book Reading

    ERIC Educational Resources Information Center

    Wasik, Barbara A.; Hindman, Annemarie H.

    2014-01-01

    Research Findings: In order to identify the active ingredients in an effective professional development intervention focused on enhancing preschool vocabulary instruction, this study examines the frequency with which teachers and children discussed theme-related vocabulary words during shared book reading. Head Start teachers received 1 year of…

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

    ERIC Educational Resources Information Center

    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…

  16. The hallucinogenic herb Salvia divinorum and its active ingredient salvinorin A reduce inflammation-induced hypermotility in mice.

    PubMed

    Capasso, R; Borrelli, F; Zjawiony, J; Kutrzeba, L; Aviello, G; Sarnelli, G; Capasso, F; Izzo, A A

    2008-02-01

    The hallucinogenic plant Salvia divinorum has been used for medical treatments of gastrointestinal disorders. Here, we evaluated the effect of a standardized extract from the leaves of Salvia divinorum (SDE) and of its active ingredient salvinorin A on motility in vivo, both in physiological states and during croton oil-induced intestinal inflammation. SDE (1-100 mg kg(-1)) significantly inhibited motility only in inflamed, but not in control, mice. In control mice, salvinorin A (0.01-10 mg kg(-1)) significantly inhibited motility only at the highest doses tested (3 and 10 mg kg(-1)) and this effect was not counteracted by naloxone or by the kappa-opioid receptor (KOR) antagonist nor-binaltorphimine. Inflammation significantly increased the potency of salvinorin A (but not of the KOR agonist U-50488) in reducing motility. The inhibitory effects of both salvinorin A and U-50488 in inflamed mice were counteracted by naloxone or by nor-binaltorphimine. We conclude that salvinorin A may reduce motility through activation of different targets. In physiological states, salvinorin A, at high doses, inhibited motility through a non-KOR mediated mechanism. Gut inflammation increased the potency of salvinorin A; this effect was mediated by KOR, but it was not shared by U-50488, thus suggesting that salvinorin A may have target(s) other than KOR in the inflamed gut.

  17. Evaluation of cytogenetic and DNA damage induced by the antidepressant drug-active ingredients, trazodone and milnacipran, in vitro.

    PubMed

    Avuloglu Yilmaz, Ece; Unal, Fatma; Yuzbasioglu, Deniz

    2017-01-01

    Trazodone and milnacipran are the active antidepressant drugs that are being used in the treatment of psychiatric disorders. In this study, the in vitro genotoxic effects of trazodone and milnacipran have been determined in human peripheral blood lymphocytes by using chromosomal aberrations (CAs), sister chromatid exchanges (SCEs), micronuclei (MN), and comet assays. 3.13; 6.25; 12.50; 25.00; 50.00; and 75.00 μg/mL concentrations of trazodone and 2.50; 5.00; 10.00; 20.00; 30.00; and 40.00 μg/mL concentrations of milnacipran were used. Trazodone and milnacipran significantly increased the frequency of CAs and SCEs compared with the control. Both of the active ingredients raised the MN frequency in a dose-dependent manner. Mitotic index was significantly decreased, but replication and nuclear division indices were not affected at all treatments. Trazodone was statistically increased the mean comet tail intensity, tail length, and tail moment at three concentrations (6.25; 12.50; and 25.00 μg/mL) compared with control. Two highest concentrations (50 and 75 μg/mL) of trazodone were toxic in the comet assay. Milnacipran increased the comet tail intensity, tail length, and tail moment at all concentrations. It is concluded that trazodone and milnacipran have clastogenic, mutagenic, and cytotoxic effects on human lymphocytes in vitro.

  18. Identification of Major Active Ingredients Responsible for Burn Wound Healing of Centella asiatica Herbs.

    PubMed

    Wu, Fang; Bian, Difei; Xia, Yufeng; Gong, Zhunan; Tan, Qian; Chen, Jiaojiao; Dai, Yue

    2012-01-01

    Centella asiatica herbs have been prescribed as a traditional medicine for wound healing in China and Southeast Asia for a long time. They contain many kinds of triterpenoid compounds, mainly including glycosides (asiaticoside and madecassoside) and corresponding aglycones (asiatic acid and madecassic acid). To identify which is the major active constituent, a comprehensive and comparative study of these compounds was performed. In vitro, primary human skin fibroblasts, originating from healthy human foreskin samples, were treated with various concentrations of asiaticoside, madecassoside, asiatic acid, and madecassic acid, respectively. Cell proliferation, collagen synthesis, MMP-1/TIMP-1 balance, and TGF-β/Smad signaling pathway were investigated. In vivo, mice were orally administered with the four compounds mentioned above for two weeks after burn injury. The speed and quality of wound healing, as well as TGF-β(1) levels in skin tissues, were examined. Interestingly, in contrast to prevalent postulations, asiaticoside and madecassoside themselves, rather than their corresponding metabolites asiatic acid and madecassic acid, are recognized as the main active constituents of C. asiatica herbs responsible for burn wound healing. Furthermore, madecassoside is more effective than asiaticoside (P = 0.0446 for procollagen type III synthesis in vitro, P = 0.0057 for wound healing speed, and P = 0.0491 for wound healing pattern in vivo, correspondingly).

  19. Active ingredient-containing chitosan/polycaprolactone nonwoven mats: characterizations and their functional assays.

    PubMed

    Bai, Meng-Yi; Chou, Tz-Chong; Tsai, Jie-Chang; Yang, Hui-Ching

    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 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 1mM 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.

  20. Recognition of pharmaceuticals with compact mini-Raman-spectrometer and automized pattern recognition algorithms

    NASA Astrophysics Data System (ADS)

    Jähme, Hendrik; Di Florio, Giuseppe; Conti Nibali, Valeria; Esen, Cemal; Ostendorf, Andreas; Grafen, Markus; Henke, Erich; Soetebier, Jens; Brenner, Carsten; Havenith, Martina; Hofmann, Martin R.

    2016-04-01

    Robust classification of pharmaceuticals in an industrial process is an important step for validation of the final product. Especially for pharmaceuticals with similar visual appearance a quality control is only possible if a reliable algorithm based on easily obtainable spectroscopic data is available. We used Principal Component Analysis (PCA) and Support Vector Machines (SVM) on Raman spectroscopy data from a compact Raman system to classify several look-alike pharmaceuticals. This paper describes the data gathering and analysis process to robustly discriminate 19 different pharmaceuticals with similar visual appearance. With the described process we successfully identified all given pharmaceuticals which had a significant amount of active ingredients. Thus automatic validation of these pharmaceuticals in a process can be used to prevent wrong administration of look-alike drugs in an industrial setting, e.g. patient individual blistering.

  1. [The intervention of the Royal College of Medicine in Nancy in the regulation of pharmaceutical activity].

    PubMed

    Labrude, Pierre

    2011-01-01

    Created in 1752 the Royal College of Medicine in Nancy constituted an institution with extended powers, particularly in sanitary policy and pharmaceutical activity. After explaining the rules of the College, the paper describes with examples its participation to the examinations of pharmacy pupils and their sustaining of "Conclusions de pharmacie et de chymie", to the delivery of drugs and to the fight against charlatanry and prohibited activity of pharmacy. From its creating to its disparition in 1793 by order of the government, the Royal College of Medicine worked remarkably, and the rules worked up during the forty years of its life appear to be of a great modernity.

  2. [Studies on cardiac ingredients of plants. X. Preparation of nitrates of tetrahydroproscillaridin and their pharmacological activities].

    PubMed

    Tanase, T; Murakami, N; Nagatsu, A; Nagai, S; Sakakibara, J; Ando, H; Hotta, Y; Takeya, K; Asano, M

    1992-11-01

    To reduce the vascular contracting effect of the hydrogenated cardiac glycosides, 20-(R)- and 20-(S)-tetrahydroproscillaridins (THPs, 1a, 1b), and to extend the concentration-dependent range, mono- and dinitrates of THPs were prepared. The pharmacological activities of the nitrates of THP were evaluated by use of isolated guinea-pig papillary muscle preparations and Na+,K(+)-adenosine triphosphatase preparations from dog kidney. Furthermore, the effect for smooth muscle was examined using the helical strips isolated from 13-week-old spontaneously hypertensive rat. The positive inotropic effects of mononitrates (11a, 11b, 2a, 2b, 8a, and 8b) were more potent than those of THPs. Nitration of the sugar moiety in THPs resulted in a vascular relaxing effect unobserved in the case of THPs.

  3. Formulation ingredients for toothpastes and mouthwashes.

    PubMed

    Vranić, Edina; Lacević, Amela; Mehmedagić, Aida; Uzunović, Alija

    2004-10-01

    In order to achieve the multi-claim products required for the dental care category, it is necessary for the formulator to use a variety of different ingredients. This places a number of demands on the development process. Innovations in the areas of pharmaceutical technology have contributed to the formulation of the products having superior efficacy as well as other attributes that may contribute to clinical response and patient acceptability. Improved clinical efficacy and tolerability, along with conditioning signals, should encourage patient compliance with oral hygiene further complementing professional efforts directed at disease prevention. The most effective way of preventing the development of dental disease is in controlling the production of dental plaque. It is formed by microbial action. The removal of plaque from the teeth and related areas is essential for the maintenance of a healthy mouth. In this paper we have presented the main components of toothpastes and mouthwashes. For the active ingredients, their supposed effect as therapeutic agents is also explained.

  4. Identification and molecular docking analysis of active ingredients with medicinal properties from edible Baccaurea sapida

    PubMed Central

    Mann, Sonia; Sharma, Ankita; Biswas, Sagarika; Gupta, Rajinder K

    2015-01-01

    Underutilized plant species has started changing the conception of plants by expanding the use well beyond from foods and fibers to rich source of medicinally important secondary metabolites. Bioactive compounds from natural sources are gaining importance as potential drug candidates towards many inflammatory conditions like Rheumatoid Arthritis (RA). The focus of the present study has been centred to reveal the anti-inflammatory potential of an underutilized fruits of B. sapida. Further efforts towards its medicinal significance may provide relieve from symptoms of RA by reducing the side effects that are observed in available medications. Total 10 compounds in fruit crude methanol extract were identified and quantified by LC-MS/MS analysis followed by the agar well diffusion method for their anti microbial activity. Among all studied micro organism S. aureus was found to surmount the inflammation in RA through domain B of surface protein A (Staphylococcal surface protein A). Identified compounds (having anti-inflammatory properties) were scrutinized for their toxicity and quantitative structure–activity relationship (QSAR) using lazer toxicity and Molinspiration servers respectively. Further, docking studies have been carried out between domain B and studied compounds using AutoDock. Out of 6 anti-inflammtory compounds, quercetin has been identified as the most potent compound in reference to its inhibitory constant (47.01) and binding energy (-5.90 kcal/mol) to bacterial protein. Our data suggest that methanol extract of B. sapida fruit posses medicinally significant anti-inflammatory compounds and thus justifies the use of this fruit as folklore medicine for preventing inflammation related diseases. PMID:26527853

  5. Identification and molecular docking analysis of active ingredients with medicinal properties from edible Baccaurea sapida.

    PubMed

    Mann, Sonia; Sharma, Ankita; Biswas, Sagarika; Gupta, Rajinder K

    2015-01-01

    Underutilized plant species has started changing the conception of plants by expanding the use well beyond from foods and fibers to rich source of medicinally important secondary metabolites. Bioactive compounds from natural sources are gaining importance as potential drug candidates towards many inflammatory conditions like Rheumatoid Arthritis (RA). The focus of the present study has been centred to reveal the anti-inflammatory potential of an underutilized fruits of B. sapida. Further efforts towards its medicinal significance may provide relieve from symptoms of RA by reducing the side effects that are observed in available medications. Total 10 compounds in fruit crude methanol extract were identified and quantified by LC-MS/MS analysis followed by the agar well diffusion method for their anti microbial activity. Among all studied micro organism S. aureus was found to surmount the inflammation in RA through domain B of surface protein A (Staphylococcal surface protein A). Identified compounds (having anti-inflammatory properties) were scrutinized for their toxicity and quantitative structure-activity relationship (QSAR) using lazer toxicity and Molinspiration servers respectively. Further, docking studies have been carried out between domain B and studied compounds using AutoDock. Out of 6 anti-inflammtory compounds, quercetin has been identified as the most potent compound in reference to its inhibitory constant (47.01) and binding energy (-5.90 kcal/mol) to bacterial protein. Our data suggest that methanol extract of B. sapida fruit posses medicinally significant anti-inflammatory compounds and thus justifies the use of this fruit as folklore medicine for preventing inflammation related diseases.

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

    PubMed

    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.

  7. Iron chelators in medicinal applications - chemical equilibrium considerations in pharmaceutical activity.

    PubMed

    Manning, Thomas; Kean, Greg; Thomas, Jessica; Thomas, Khaleh; Corbitt, Michael; Gosnell, Donna; Ware, Ronald; Fulp, Sonya; Jarrard, Joey; Phillips, Dennis

    2009-01-01

    Iron chelators are being examined as a potential class of pharmaceutical agents to battle different types of cancer as well as iron overload diseases. In recent studies, iron binding species such as desferrioxamine, triapine, tachpyridine, Dp44Mt, and PIH have been tested in cell line tests and clinical trials. Using published chemical equilibrium values (stability constants, equilibrium constants), it is argued that an iron chelator cannot competitively remove iron from a heme-containing biomolecule (i.e. hemoglobin (Hb), myoglobin) causing a cancerous cell to die. This type of reaction (DFO(aq) + [Fe(2+,3+)-Hb] --> [Fe(2+,3+)-DFO] + Hb) has been proposed in a number of published studies using circumstantial evidence. It is argued that iron chelators can potentially interact with iron from ferritin or iron that has precipitated or flocculated as oxyhydroxide under physiological pH's. It is argued that chelators can interfere with various physiological processes by binding cations such as Ca(2+), Zn(2+) or K(+). A number of siderophores and natural products that have the ability to bind Fe(3+)/Fe(2+) as well as other cations are discussed in terms of their potential pharmaceutical activity as chelators. Chemical equilibria between cations and pharmaceutical agents, which are rarely quantitated in explaining medicinal mechanisms, are used to show that chelators can bind and remove iron and other cations from physiologically important systems required for cell survival and propagation.

  8. Lack of sustained efficacy for alcohol-based surgical hand rubs containing 'residual active ingredients' according to EN 12791.

    PubMed

    Kampf, G; Kramer, A; Suchomel, M

    2017-02-01

    The World Health Organization recommends the use of hand rubs with 'sustained activity' for surgical hand preparation. This review aims to verify whether any of the alcohol-based hand rubs containing non-volatile 'active ingredients' such as chlorhexidine digluconate (CHG), mecetronium ethylsulphate (MES), or ortho-phenylphenol (OPP) provides such sustained efficacy for surgical hand disinfection. Literature was searched to find studies according to EN 12791. Published data sets were analysed to verify whether any of the formulations has a superior efficacy (P<0.01) after 3h in comparison to the reference procedure. Formulations with 0.5 and 1% CHG in 70% iso-propanol or 61% ethanol were not superior after 3h. Formulations with 0.2% MES in 45% iso-propanol and 30% n-propanol were also not superior when applied for 1min (one data set), 1.5min as currently recommended for use (14 data sets), and 2min (one data set). When applied for 3min the formulations were superior in three out of seven data sets. The hand rub with 0.1% OPP in 78.2% ethanol was also not superior to the reference treatment when applied as recommended for 1.5min. It appears reasonable and responsible to limit the dermal exposure and environmental input to biocidal agents with a clear benefit such as the alcohols. In analogy to avoiding dyes and fragrances in hand rubs, formulations containing 'active' substances without a clear benefit but with potential risks should be avoided when alternative formulations with the same level of antimicrobial activity, dermal tolerance, and user acceptability are available.

  9. Risks of hormonally active pharmaceuticals to amphibians: a growing concern regarding progestagens.

    PubMed

    Säfholm, Moa; Ribbenstedt, Anton; Fick, Jerker; Berg, Cecilia

    2014-11-19

    Most amphibians breed in water, including the terrestrial species, and may therefore be exposed to water-borne pharmaceuticals during critical phases of the reproductive cycle, i.e. sex differentiation and gamete maturation. The objectives of this paper were to (i) review available literature regarding adverse effects of hormonally active pharmaceuticals on amphibians, with special reference to environmentally relevant exposure levels and (ii) expand the knowledge on toxicity of progestagens in amphibians by determining effects of norethindrone (NET) and progesterone (P) exposure to 0, 1, 10 or 100 ng l(-1) (nominal) on oogenesis in the test species Xenopus tropicalis. Very little information was found on toxicity of environmentally relevant concentrations of pharmaceuticals on amphibians. Research has shown that environmental concentrations (1.8 ng l(-1)) of the pharmaceutical oestrogen ethinylestradiol (EE2) cause developmental reproductive toxicity involving impaired spermatogenesis in frogs. Recently, it was found that the progestagen levonorgestrel (LNG) inhibited oogenesis in frogs by interrupting the formation of vitellogenic oocytes at an environmentally relevant concentration (1.3 ng l(-1)). Results from the present study revealed that 1 ng NET l(-1) and 10 ng P l(-1) caused reduced proportions of vitellogenic oocytes and increased proportions of previtellogenic oocytes compared with the controls, thereby indicating inhibited vitellogenesis. Hence, the available literature shows that the oestrogen EE2 and the progestagens LNG, NET and P impair reproductive functions in amphibians at environmentally relevant exposure concentrations. The progestagens are of particular concern given their prevalence, the range of compounds and that several of them (LNG, NET and P) share the same target (oogenesis) at environmental exposure concentrations, indicating a risk for adverse effects on fertility in exposed wild amphibians.

  10. Risks of hormonally active pharmaceuticals to amphibians: a growing concern regarding progestagens

    PubMed Central

    Säfholm, Moa; Ribbenstedt, Anton; Fick, Jerker; Berg, Cecilia

    2014-01-01

    Most amphibians breed in water, including the terrestrial species, and may therefore be exposed to water-borne pharmaceuticals during critical phases of the reproductive cycle, i.e. sex differentiation and gamete maturation. The objectives of this paper were to (i) review available literature regarding adverse effects of hormonally active pharmaceuticals on amphibians, with special reference to environmentally relevant exposure levels and (ii) expand the knowledge on toxicity of progestagens in amphibians by determining effects of norethindrone (NET) and progesterone (P) exposure to 0, 1, 10 or 100 ng l−1 (nominal) on oogenesis in the test species Xenopus tropicalis. Very little information was found on toxicity of environmentally relevant concentrations of pharmaceuticals on amphibians. Research has shown that environmental concentrations (1.8 ng l−1) of the pharmaceutical oestrogen ethinylestradiol (EE2) cause developmental reproductive toxicity involving impaired spermatogenesis in frogs. Recently, it was found that the progestagen levonorgestrel (LNG) inhibited oogenesis in frogs by interrupting the formation of vitellogenic oocytes at an environmentally relevant concentration (1.3 ng l−1). Results from the present study revealed that 1 ng NET l−1 and 10 ng P l−1 caused reduced proportions of vitellogenic oocytes and increased proportions of previtellogenic oocytes compared with the controls, thereby indicating inhibited vitellogenesis. Hence, the available literature shows that the oestrogen EE2 and the progestagens LNG, NET and P impair reproductive functions in amphibians at environmentally relevant exposure concentrations. The progestagens are of particular concern given their prevalence, the range of compounds and that several of them (LNG, NET and P) share the same target (oogenesis) at environmental exposure concentrations, indicating a risk for adverse effects on fertility in exposed wild amphibians. PMID:25405966

  11. Ginkgo biloba extracts: a review of the pharmacokinetics of the active ingredients.

    PubMed

    Ude, Christian; Schubert-Zsilavecz, Manfred; Wurglics, Mario

    2013-09-01

    Ginkgo biloba is among the most favourite and best explored herbal drugs. Standardized extracts of Ginkgo biloba represent the only herbal alternative to synthetic antidementia drugs in the therapy of cognitive decline and Alzheimer's diseases. The clinical efficiency of such standardized Ginkgo biloba extracts (GBE) is still controversial, but authors of numerous international clinical studies recommended the use of GBE in the described therapies.Extracts of Ginkgo biloba are a mixture of substances with a wide variety of physical and chemical properties and activities. Numerous pharmacological investigations lead to the conclusion that the terpene trilactones (TTL) and the flavonoids of GBE are responsible for the main pharmacological effects of the extract in the therapy of cognitive decline. Therefore, the quality of GBE products must be oriented on a defined quantity of TTL and flavonoids. Furthermore, because of their toxic potential the amount of ginkgolic acid should be less than 5 ppm.However, data on pharmacokinetics and bioavailability, especially related to the central nervous system (CNS), which is the target tissue, are relatively rare. A few investigations characterize the TTL and flavonoids of Ginkgo biloba pharmacokinetically in plasma and in the brain. Recent investigations show that significant levels of TTL and Ginkgo biloba flavonoids cross the blood-brain barrier and enter the CNS of rats after oral application of GBE. Knowledge about the pharmacokinetic behaviour of these substances is necessary to discuss the pharmacological results on a more realistic basis.

  12. Novel Methods to Generate Active Ingredients-Enriched Ashwagandha Leaves and Extracts

    PubMed Central

    Kaul, Sunil C.; Ishida, Yoshiyuki; Tamura, Kazuya; Wada, Teruo; Iitsuka, Tomoko; Garg, Sukant; Kim, Mijung; Gao, Ran; Nakai, Shoichi; Okamoto, Youji; Terao, Keiji; Wadhwa, Renu

    2016-01-01

    Ashwagandha (Withania somnifera) is an Ayurvedic herb commonly used in world-renowned traditional Indian home medicine system. Roots of Ashwagandha have been traditionally known to possess a variety of therapeutic and health promoting potentials that have not been sufficiently supported by laboratory studies. Nevertheless, most, if not all, of the preventive and therapeutic potentials have been assigned to its bioactive components, steroidal alkaloids and lactones. In contrast to the traditional use of roots, we have been exploring bioactivities in leaves of Ashwagandha. Here, we report that the leaves possess higher content of active Withanolides, Withaferin-A (Wi-A) and Withanone (Wi-N), as compared to the roots. We also established, for the first time, hydroponic cultivation of Ashwagandha and investigated the effect of various cultivation conditions on the content of Wi-A and Wi-N by chemical analysis and bioassays. We report that the Withanone/Withaferin A-rich leaves could be obtained by manipulating light condition during hydroponic cultivation. Furthermore, we recruited cyclodextrins to prepare extracts with desired ratio of Wi-N and Wi-A. Hydroponically grown Ashwagandha and its extracts with high ratio of withanolides are valuable for cancer treatment. PMID:27936030

  13. Study and description of hydrogels and organogels as vehicles for cosmetic active ingredients.

    PubMed

    Morales, M E; Gallardo, V; Clarés, B; García, M B; Ruiz, M A

    2009-01-01

    Cellulite, a clinical syndrome mainly affecting women, involves specific changes in conjunctive dermic and subcutaneous tissue, leading to vascular and hypertrophic alterations in adipose tissues and the consequent alteration of tissue structure. This paper describes the design of hydrogels and pluronic-lecithin organogels elaborated as vehicles of Aloe vera (Aloe vera linné) and Hydrocotyle asiatica (Centella asiatica) for the treatment of cellulite. The objective of this work was to carry out a complete evaluation of the proposed formulae through the study of the organoleptic and rheological properties of the formulae. Our work revealed that, in appearance, hydrogels show better organoleptic characteristics than organogels. On the other hand, from a rheological point of view, both hydrogels and organogels display a plastic behavior. However, the main difference between the two is that the more complex internal structure of the organogel bestows it with more viscosity. Finally, in vitro tests with Franz-type diffusion cells revealed that the release of cosmetic active principle from the tested excipients was appropriate, both in terms of magnitude and velocity.

  14. Contact Lenses Wettability In Vitro: Effect of Surface-Active Ingredients

    PubMed Central

    Lin, Meng C.; Svitova, Tatyana F.

    2010-01-01

    Purpose To investigate the release of surface-active agents (surfactants) from unworn soft contact lenses and their influence on the lens surface wettability in vitro. Methods Surface tension (ST) of blister pack solutions was measured by pendant-drop technique. STs at the air-aqueous interface and contact angles (CAs) of four conventional and seven silicone hydrogel (SiH) soft contact lenses (SCLs) were evaluated in a dynamic-cycling regime using a modified captive-bubble tensiometer-goniometer. Measurements were performed immediately after removal from blister packs, and after soaking in a glass vial filled with a surfactant-free solution, which was replaced daily for one week. Lens surface wettability was expressed as adhesion energy (AE) according to Young’s equation. Results STs of all blister pack solutions were lower than the reference ST of pure water (72.5 mN/m), indicating the presence of surfactants. When lenses were depleted of surfactants by soaking, the STs of all studied lenses and advancing CAs of selected lenses increased (p < 0.001). Receding CAs of all studied lenses were 12° ± 5° and were not affected by the presence of surfactants. For most of the conventional lenses, the surface wettability was largely dependent on surfactants, and reduced significantly after surfactant depletion. In contrast, most SiH lenses exhibited stable and self-sustained surface wettability in vitro. Conclusions The manufacturer-added surfactants affected wetting properties of all studied SCLs, although to different degrees. PMID:20400924

  15. Mathematical Modeling of the Release of Active Ingredients from a Contraceptive Patch: Ortho Evra® as a Case Study

    PubMed Central

    Trujillo-de Santiago, Grissel; Patricio Sáenz-Collins, Carlos; García-Arellano, Lizette; Moisés Álvarez, Mario

    2014-01-01

    Contraceptive patches have become a frequently used contraceptive method. We present a mathematical model that describes the serum concentration profiles of Norelgestromin (NGMN) and Ethinylestradiol (EE) released from the contraceptive patch Ortho Evra®. We propose a simple one-compartment model based on pharmacokinetics data reported in previous studies. The model assumes a time-dependent release rate and a first order elimination rate for each of the active ingredients contained in the patch. The model was applied to noncompliance scenarios, such as total and partial detachment of the patch or prolonged use without patch replacement. The proposed model adequately describes the clinically observed evolution of NGMN and EE in serum. Predictions from the model were successfully validated using reported experimental data of serum concentrations of NGMN and EE. This simple model can be a valuable tool to predict pharmacokinetic profiles in diverse scenarios such us non-compliance situations. Alternatively, the model can be conveniently adapted to anticipate the effect of variations on patch characteristics such as differences in contact area, doses, materials, among others. PMID:24734055

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

    PubMed

    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.

  17. Negatively charged silver nanoparticles with potent antibacterial activity and reduced toxicity for pharmaceutical preparations

    PubMed Central

    Salvioni, Lucia; Galbiati, Elisabetta; Collico, Veronica; Alessio, Giulia; Avvakumova, Svetlana; Corsi, Fabio; Tortora, Paolo; Prosperi, Davide; Colombo, Miriam

    2017-01-01

    Background The discovery of new solutions with antibacterial activity as efficient and safe alternatives to common preservatives (such as parabens) and to combat emerging infections and drug-resistant bacterial pathogens is highly expected in cosmetics and pharmaceutics. Colloidal silver nanoparticles (NPs) are attracting interest as novel effective antimicrobial agents for the prevention of several infectious diseases. Methods Water-soluble, negatively charged silver nanoparticles (AgNPs) were synthesized by reduction with citric and tannic acid and characterized by transmission electron microscopy, dynamic light scattering, zeta potential, differential centrifuge sedimentation, and ultraviolet–visible spectroscopy. AgNPs were tested with model Gram-negative and Gram-positive bacteria in comparison to two different kinds of commercially available AgNPs. Results In this work, AgNPs with higher antibacterial activity compared to the commercially available colloidal silver solutions were prepared and investigated. Bacteria were plated and the antibacterial activity was tested at the same concentration of silver ions in all samples. The AgNPs did not show any significant reduction in the antibacterial activity for an acceptable time period. In addition, AgNPs were transferred to organic phase and retained their antibacterial efficacy in both aqueous and nonaqueous media and exhibited no toxicity in eukaryotic cells. Conclusion We developed AgNPs with a 20 nm diameter and negative zeta potential with powerful antibacterial activity and low toxicity compared to currently available colloidal silver, suitable for cosmetic preservatives and pharmaceutical preparations administrable to humans and/or animals as needed.

  18. Disk-driven hydromagnetic winds as a key ingredient of active galactic nuclei unification schemes

    NASA Technical Reports Server (NTRS)

    Konigl, Arieh; Kartje, John F.

    1994-01-01

    Centrifugally driven winds from the surfaces of magnetized accretion disks have been recognized as an attractive mechanism of removing the angular momentum of the accreted matter and of producing the bipolar outflows and jets that are often associated with compact astronomical objects. As previously suggested in the context of young stellar objects, such winds have unique observational manifestations stemming from their highly stratified density and velocity structure and from their exposure to the strong continuum radiation field of the compact object. We have applied this scenario to active galactic nuclei (AGNs) and investigated the properties of hydromagnetic outflows that originate within approximately 10(M(sub 8)) pc of the central 10(exp 8)(M(sub 8)) solar mass black hole. On the basis of our results, we propose that hydromagnetic disk-driven winds may underlie the classification of broad-line and narrow-line AGNs (e.g., the Seyfert 1/Seyfert 2 dichotomy) as well as the apparent dearth of luminous Seyfert 2 galaxies. More generally, we demonstrate that such winds could strongly influence the spectral characteristics of Seyfert galaxies, QSOs, and BL Lac objects (BLOs). In our picture, the torus is identified with the outer regions of the wind where dust uplifted from the disk surfaces by gas-grain collisions is embedded in the outflow. Using an efficient radiative transfer code, we show that the infrared emission of Seyfert galaxies and QSOs can be attributed to the reprocessing of the UV/soft X-ray AGN continuum by the dust in the wind and the disk. We demonstrate that the radiation pressure force flattens the dust distribution in objects with comparatively high (but possibly sub-Eddington) bolometric luminosities, and we propose this as one likely reason for the apparent paucity of narrow-line objects among certain high-luminosity AGNs. Using the XSTAR photoionization code, we show that the inner regions of the wind could naturally account for the warm

  19. Potential anxiolytic- and antidepressant-like effects of salvinorin A, the main active ingredient of Salvia divinorum, in rodents

    PubMed Central

    Braida, Daniela; Capurro, Valeria; Zani, Alessia; Rubino, Tiziana; Viganò, Daniela; Parolaro, Daniela; Sala, Mariaelvina

    2009-01-01

    Background and purpose: Drugs targeting brain κ-opioid receptors produce profound alterations in mood. In the present study we investigated the possible anxiolytic- and antidepressant-like effects of the κ-opioid receptor agonist salvinorin A, the main active ingredient of Salvia divinorum, in rats and mice. Experimental approach: Experiments were performed on male Sprague-Dawley rats or male Albino Swiss mice. The anxiolytic-like effects were tested by using the elevated plus maze, in rats. The antidepressant-like effect was estimated through the forced swim (rats) and the tail suspension (mice) test. κ-Opioid receptor involvement was investigated pretreating animals with the κ-opioid receptor antagonist, nor-binaltorphimine (1 or 10 mg·kg−1), while direct or indirect activity at CB1 cannabinoid receptors was evaluated with the CB1 cannabinoid receptor antagonist, N-(piperidin-1-yl) -5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251, 0.5 or 3 mg·kg−1), binding to striatal membranes of naïve rats and assay of fatty acid amide hydrolase in prefrontal cortex, hippocampus and amygdala. Key results: Salvinorin A, given s.c. (0.001–1000 µg·kg−1), exhibited both anxiolytic- and antidepressant-like effects that were prevented by nor-binaltorphimine or AM251 (0.5 or 3 mg·kg−1). Salvinorin A reduced fatty acid amide hydrolase activity in amygdala but had very weak affinity for cannabinoid CB1 receptors. Conclusions and implications: The anxiolytic- and antidepressant-like effects of Salvinorin A are mediated by both κ-opioid and endocannabinoid systems and may partly explain the subjective symptoms reported by recreational users of S. divinorum. PMID:19422370

  20. Temporal and spatial behavior of pharmaceuticals in Narragansett Bay, Rhode Island, United States

    EPA Science Inventory

    The behavior of active pharmaceutical ingredients (APIs) in urban estuaries is not well understood. In this study, 15 high volume usage APIs were measured over a one year period throughout Narragansett Bay, RI, USA to determine factors controlling their concentration and distrib...

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

    PubMed Central

    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 study was to evaluate the performance and perceptions of competency of students in a new pharmaceutical care course that uses active learning methodologies. Methods This pharmaceutical care course was conducted in the first semester of 2014, in the Federal University of Sergipe. In the pharmaceutical care course, active learning methods were used, consisting of dialogic classroom expository, simulation and case studies. Student learning was evaluated using classroom tests and instruments that evaluated the perception of competency in pharmaceutical care practice. Furthermore, students' satisfaction with the course was evaluated. Results Thirty-three students completed the four evaluations used in the course (i.e., a discursive written exam, seminars, OSCE, and virtual patient); 25 were female (75.75%), and the median age was 23.43 (SD 2.82) years. The overall mean of student scores, in all evaluation methods was 7.97 (SD 0.59) on a scale of 0 to 10 points, and student performance on the virtual patient method was statistically superior to other methods. With respect to the perception of competency in pharmaceutical care practice, a comparison of pre- and post-test scores revealed statistically significant improvement for all evaluated competences. At the end of the semester, the students presented positive opinions of the pharmaceutical care course. Conclusions The results suggest that an active learning course can enhance the learning of pharmaceutical care competences. In

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

    USGS Publications Warehouse

    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

  3. Complement activation by polyethoxylated pharmaceutical surfactants: Cremophor-EL, Tween-80 and Tween-20.

    PubMed

    Weiszhár, Zsóka; Czúcz, Judit; Révész, Csaba; Rosivall, László; Szebeni, János; Rozsnyay, Zoltán

    2012-03-12

    Immunosafety analysis of pharmaceutical surfactants is an important step in understanding the complex mechanisms by which they induce side effects in susceptible patients. This paper provides experimental evidences that polyethoxylated surfactants, Cremophor-EL and Tween-80, also known as Polysorbate-80, activate the complement system in vitro, in normal human serum and plasma. They appeared to be more efficient reactogens than their structural homolog, Tween-20. Cremophor-EL and Tween-80 promoted the generation of biologically active complement products, C3a, C5a and C5b-9. Consistently, Paclitaxel and Taxotere (Docetaxel), pharmaceuticals formulated in Cremophor-EL and Tween-80, activated the complement system in similar extent. Moreover, comparison of serum reactivity against the drug-loaded and drug-free formulations exhibited a significant linear correlation. Taken together, these results are consistent with the hypothesis that therapeutic side effects, such as acute hypersensitivity and systemic immunostimulation, caused by intravenous nanomedicines containing polyethoxylated detergents such as Cremophor-EL and Tween-80, can be attributed to complement activation-derived inflammatory mediators.

  4. Modulation of chemokine expression on intestinal epithelial cells by Kampo (traditional Japanese herbal) medicine, Hochuekkito, and its active ingredients.

    PubMed

    Sekiya, Michiko; Kiyohara, Hiroaki; Maruyama, Hiroko; Yabe, Takeshi; Yamada, Haruki

    2013-07-01

    The intestinal epithelial cells sit at the interface between a lumen and a lamina propria or lymph nodes such as Peyer's patches, where they play important roles in maintaining intestinal homeostasis through chemokine secretion. This study investigated the effect of Hochuekkito (TJ-41)-a traditional Japanese herbal (Kampo) formula used as a tonic for weakness-on chemokine expression in intestinal epithelial cells in order to explore the mechanism of its modulating effect against mucosal immunity. When cells from the rat normal small intestinal epithelial cell-line IEC-6 were stimulated with TJ-41, mRNA expression of CC chemokine ligand (CCL) 11 (eotaxin), CCL20 (MIP-3α) and CCL25 (TECK) was enhanced. Oral administration of TJ-41 to methotrexate-treated mice enhanced mRNA expression of CCL25 and keratinocyte growth factor in the jejunum with, decreasing mRNA expression of the inflammatory marker tumor necrosis factor (TNF)-α. Although oral administration of TJ-41 did not affect CCL20 mRNA expression in villus epithelium of methotrexate-treated mice, enhancement of CCL20 mRNA expression was observed in Peyer's patches. Immunohistochemical analysis detected dense staining with anti-CCL20 antibody in the follicle-associated epithelium region of Peyer's patches in mice administered TJ-41. Analysis of active ingredients indicates that polysaccharide-containing macromolecules in TJ-41 contribute to the enhancement of CCL20 mRNA expression through an intracellular signal cascade via nuclear factor kappa B (NF-κB) activation.

  5. SoSoSo or its active ingredient chrysophanol regulates production of inflammatory cytokines & adipokine in both macrophages & adipocytes

    PubMed Central

    Hong-Kun, Rim; Phil-Dong, Moon; In-Hwa, Choi; Eun-Hee, Lee; Hyung-Min, Kim; Hyun-Ja, Jeong

    2013-01-01

    Background & objectives: Obesity is now considered as a major risk factor for the development of fatty liver diseases, cardiovascular diseases, and atherosclerosis. SoSoSo is a newly developed dietary supplement made of seven medicinal herbs. This study was aimed at examining the anti-obesity effect of SoSoSo or its active ingredient chrysophanol on the production of inflammatory cytokines and adipokine in macrophyage cell line RAW264 and 3T3-L1 adipocytes. Methods: No release was measured as a form of nitrite by Griess method. The production of inflammatory cytokines and adipokine were measured with the ELISA method. The m-RNA expression of each cytokine and adipokine were measured using RT-PCR. The nuclear proteins for NF-κB were analyzed with western blotting. Results: SoSoSo or chrysophanol significantly inhibited the nitric oxide production in lipopolysaccharide-stimulated RAW264 cells as well as in RAW264 cells-conditioned medium (CM)-treated 3T3-L1 cells. The production of interleukin (IL)-6 and tumour necrosis factor (TNF)-α were inhibited by SoSoSo or chrysophanol. In addition, SoSoSo or chrysophanol inhibited the activation of nuclear factor-κB in RAW264 cells. SoSoSo or chrysophanol inhibited the productions of IL-6, TNF-α, and monocyte chemoattractant protein-1 as well as the reduction of adiponectin production in CM-treated 3T3-L1 cells. Interpretation & conclusions: These results suggest a potential of SoSoSo or chrysophanol as a source of anti-inflammatory agent for obesity. Further in vivo studies would be required to confirm these findings. PMID:23481064

  6. The effects of UV-B radiation intensity on biochemical parameters and active ingredients in flowers of Qi chrysanthemum and Huai chrysanthemum.

    PubMed

    Yao, Xiao-Qin; Chu, Jian-Zhou; He, Xue-Li; Si, Chao

    2014-01-01

    The article studied UV-B effects on biochemical parameters and active ingredients in flowers of Qi chrysanthemum and Huai chrysanthemum during the bud stage. The experiment included four UV-B radiation levels (CK, ambient UV-B; T1, T2 and T3 indicated a 5%, 10% and 15% increase in ambient UV-BBE, respectively) to determine the optimal UV-B radiation intensity in regulating active ingredients level in flowers of two chrysanthemum varieties. Flower dry weight of two cultivars was not affected by UV-B radiation under experimental conditions reported here. UV-B treatments significantly increased the rate of superoxide radical production, hydrogen peroxide (H2O2) (except for T1) and malondialdehyde concentration in flowers of Huai chrysanthemum and H2O2 concentration in flowers of Qi chrysanthemum. T2 and T3 treatments induced a significant increase in phenylalanine ammonia lyase enzyme (PAL) activity, anthocyanins, proline, ascorbic acid, chlorogenic acid and flavone content in flowers of two chrysanthemum varieties, and there were no significant differences in PAL activity, ascorbic acid, flavone and chlorogenic acid content between the two treatments. These results indicated that appropriate UV-B radiation intensity did not result in the decrease in flower yield, and could regulate PAL activity and increase active ingredients content in flowers of two chrysanthemum varieties.

  7. Adsorption of pharmaceuticals to microporous activated carbon treated with potassium hydroxide, carbon dioxide, and steam.

    PubMed

    Fu, Heyun; Yang, Liuyan; Wan, Yuqiu; Xu, Zhaoyi; Zhu, Dongqiang

    2011-01-01

    Adsorption of sulfapyridine, tetracycline, and tylosin to a commercial microporous activated carbon (AC) and its potassium hydroxide (KOH)-, CO-, and steam-treated counterparts (prepared by heating at 850°C) was studied to explore efficient adsorbents for the removal of selected pharmaceuticals from water. Phenol and nitrobenzene were included as additional adsorbates, and nonporous graphite was included as a model adsorbent. The activation treatments markedly increased the specific surface area and enlarged the pore sizes of the mesopores of AC (with the strongest effects shown on the KOH-treated AC). Adsorption of large-size tetracycline and tylosin was greatly enhanced, especially for the KOH-treated AC (more than one order of magnitude), probably due to the alleviated size-exclusion effect. However, the treatments had little effect on adsorption of low-size phenol and nitrobenzene due to the predominance of micropore-filling effect in adsorption and the nearly unaffected content of small micropores causative to such effect. These hypothesized mechanisms on pore-size dependent adsorption were further tested by comparing surface area-normalized adsorption data and adsorbent pore size distributions with and without the presence of adsorbed antibiotics. The findings indicate that efficient adsorption of bulky pharmaceuticals to AC can be achieved by enlarging the adsorbent pore size through suitable activation treatments.

  8. Pharmaceutically active compounds in sludge stabilization treatments: anaerobic and aerobic digestion, wastewater stabilization ponds and composting.

    PubMed

    Martín, Julia; Santos, Juan Luis; Aparicio, Irene; Alonso, Esteban

    2015-01-15

    Sewage sludge disposal onto lands has been stabilized previously but still many pollutants are not efficiently removed. Special interest has been focused on pharmaceutical compounds due to their potential ecotoxicological effects. Nowadays, there is scarce information about their occurrence in different sludge stabilization treatments. In this work, the occurrence of twenty-two pharmaceutically active compounds has been studied in sludge from four sludge stabilization treatments: anaerobic digestion, aerobic digestion, composting and lagooning. The types of sludge evaluated were primary, secondary, anaerobically-digested and dehydrated, composted, mixed, aerobically-digested and dehydrated and lagoon sludge. Nineteen of the twenty-two pharmaceutically active compounds monitored were detected in sewage sludge. The most contaminated samples were primary sludge, secondary sludge and mixed sludge (the average concentrations of studied compounds in these sludges were 179, 310 and 142 μg/kg dm, respectively) while the mean concentrations found in the other types of sewage sludge were 70 μg/kg dm (aerobically-digested sludge), 63 μg/kg dm (lagoon sludge), 12 μg/kg dm (composted sludge) and 8 μg/kg dm (anaerobically-digested sludge). The antibiotics ciprofloxacin and norfloxacin were found at the highest concentration levels in most of the analyzed sludge samples (up to 2660 and 4328 μg/kg dm, respectively). Anaerobic-digestion treatment reduced more considerably the concentration of most of the studied compounds than aerobic-digestion (especially in the case of bezafibrate and fluoroquinolones) and more than anaerobic stabilization ponds (in the case of acetaminophen, atenolol, bezafibrate, carbamazepine, 17α-ethinylestradiol, naproxen and salicylic acid). Ecotoxicological risk assessment, of sludge application onto soils, has also been evaluated. Risk quotients, expressed as the ratio between the predicted environmental concentration and the predicted non

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

    PubMed Central

    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 globalization status of good manufacturing practice (GMP) requirements for pharmaceutical excipients. The review outcomes demonstrate that there is a lack of accurately defined methods to evaluate and measure excipients’ safety. Furthermore good manufacturing practice requirements for excipients are not effectively globalized. PMID:25685037

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

    PubMed

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

    2015-01-01

    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 globalization status of good manufacturing practice (GMP) requirements for pharmaceutical excipients. The review outcomes demonstrate that there is a lack of accurately defined methods to evaluate and measure excipients' safety. Furthermore good manufacturing practice requirements for excipients are not effectively globalized.

  11. Fusion production of solid dispersions containing a heat-sensitive active ingredient by hot melt extrusion and Kinetisol dispersing.

    PubMed

    Dinunzio, James C; Brough, Chris; Hughey, Justin R; Miller, Dave A; Williams, Robert O; McGinity, James W

    2010-02-01

    Many techniques for the production of solid dispersions rely on elevated temperatures and prolonged material residence times, which can result in decomposition of temperature-sensitive components. In this study, hydrocortisone was used as a model temperature-sensitive active ingredient to study the effect of formulation and processing techniques as well as to characterize the benefits of KinetiSol Dispersing for the production of solid dispersions. Preformulation studies were conducted using differential scanning calorimetry and hot stage microscopy to identify optimum carriers for the production of amorphous solid dispersions. After identification, solid dispersions were prepared by hot melt extrusion and KinetiSol Dispersing, with material characterized by X-ray diffraction, dissolution and potency testing to evaluate physicochemical properties. Results from the preformulation studies showed that vinylacetate:vinylpyrrolidone (PVPVA) copolymer allowed for hydrocortisone dissolution within the carrier at temperatures as low as 160 degrees C, while hydroxypropyl methylcellulose required temperatures upward of 180 degrees C to facilitate solubilization. Low substituted hydroxypropyl cellulose, a high glass transition temperature control, showed that the material was unable to solubilize hydrocortisone. Manufacturing process control studies using hot melt extruded compositions of hydrocortisone and PVPVA showed that increased temperatures and residence times negatively impacted product potency due to decomposition. Using KinetiSol Dispersing to reduce residence time and to facilitate lower temperature processing, it was possible to produce solid dispersions with improved product potency. This study clearly demonstrated the importance of carrier selection to facilitate lower temperature processing, as well as the effect of residence time on product potency. Furthermore, KinetiSol Dispersing provided significant advantages over hot melt extrusion due to the reduced

  12. Adsorption of active ingredients of surface disinfectants depends on the type of fabric used for surface treatment.

    PubMed

    Bloss, R; Meyer, S; Kampf, G

    2010-05-01

    The disinfection of surfaces in the immediate surrounding of a hospitalised patient is considered to be an important element for prevention of nosocomial infection. The type of fabric in a mop, however, has to our knowledge never been regarded as relevant for an effective disinfection of surfaces. We have therefore studied the adsorption of benzalkonium chloride (BAC), glutardialdehyde and propan-1-ol from working solutions of three surface disinfectants to four different types of fabric (A: white pulp and polyester; B: viscose rayon; C: polyester; D: mixture of viscose, cellulose and polyester). The working solutions of each disinfectant were exposed to each fabric for up to 24h. Before and after exposure, tissues were removed and squeezed in a standardised way. The eluate was used for determination of the concentration of the active ingredient in quadruplicate. The analysis of glutardialdehyde and BAC was performed using high performance liquid chromatography; the analysis of propan-1-ol was done using gas chromatography. BAC was strongly adsorbed to the tissues based on white pulp (up to 61% after 30 min), followed by the viscose rayon tissues (up to 70% after 30 min) and the mixed tissues (up to 54% after 7h). The polyester fibre tissue adsorbed the smallest amounts of BAC with up to 17% after 15 min. Only with the polyester fibre tissue were BAC concentrations found in the range of the calculated BAC concentrations. Glutardialdehyde and propan-1-ol did not adsorb to any of the fibres. Effective surface disinfection also includes selection of an appropriate fabric.

  13. Molecular structure activity on pharmaceutical applications of Phenacetin using spectroscopic investigation

    NASA Astrophysics Data System (ADS)

    Madanagopal, A.; Periandy, S.; Gayathri, P.; Ramalingam, S.; Xavier, S.

    2017-01-01

    The pharmaceutical compound; Phenacetin was investigated by analyzing FT-IR, FT-Raman and 1H &13C NMR spectra. The hybrid efficient computational calculations performed for computing physical and chemical parameters. The cause of pharmaceutical activity due to the substitutions; carboxylic, methyl and amine groups in appropriate positions on the pedestal compound was deeply investigated. Moreover, 13C NMR and 1H NMR chemical shifts correlated with TMS standard to explain the truth of compositional ratio of base and ligand groups. The bathochromic shift due to chromophores over the energy levels in UV-Visible region was strongly emphasized the Anti-inflammatory chemical properties. The chemical stability was pronounced by the strong kubo gap which showed the occurring of charge transformation within the molecule. The occurrence of the chemical reaction was feasibly interpreted by Gibbs free energy profile. The standard vibrational analysis stressed the active participation of composed ligand groups for the existence of the analgesic as well as antipyretic properties of the Phenacetin compound. The strong dipole interaction energy utilization for the transition among non-vanishing donor and acceptor for composition of the molecular structure was interpreted.

  14. 40 CFR 180.940 - Tolerance exemptions for active and inert ingredients for use in antimicrobial formulations (Food...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... mixture) generated either (i) by directly metering a concentrated chlorine dioxide solution prepared just... inert ingredients for use in antimicrobial formulations (Food-contact surface sanitizing solutions). 180...-contact surface sanitizing solutions). Residues of the following chemical substances are exempted from...

  15. 40 CFR 180.940 - Tolerance exemptions for active and inert ingredients for use in antimicrobial formulations (Food...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... mixture) generated either (i) by directly metering a concentrated chlorine dioxide solution prepared just... inert ingredients for use in antimicrobial formulations (Food-contact surface sanitizing solutions). 180...-contact surface sanitizing solutions). Residues of the following chemical substances are exempted from...

  16. 21 CFR 310.540 - Drug products containing active ingredients offered over-the-counter (OTC) for use as stomach...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 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...

  17. 21 CFR 310.540 - Drug products containing active ingredients offered over-the-counter (OTC) for use as stomach...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 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...

  18. 21 CFR 310.540 - Drug products containing active ingredients offered over-the-counter (OTC) for use as stomach...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 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...

  19. 21 CFR 310.540 - Drug products containing active ingredients offered over-the-counter (OTC) for use as stomach...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 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...

  20. 21 CFR 310.540 - Drug products containing active ingredients offered over-the-counter (OTC) for use as stomach...

    Code of Federal Regulations, 2010 CFR

    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...