Experimental and density functional theory studies on benzalkonium ibuprofenate, a double active pharmaceutical ingredient.

PubMed

Safna Hussan, K P; Thayyil, M Shahin; Rajan, Vijisha K; Muraleedharan, K

2018-02-01

Molecular aspects of a double active pharmaceutical ingredient in ionic liquid form, benzalkonium ibuprofenate (BaIb), were studied using density functional theory (DFT/B3LYP/6-31+G (d, p)). A detailed discussion on optimized geometry, energy, heat and the enthalpy of BaIb was carried out. The computed vibrational results agree well with the experimental results. The stability and biological activity were compared to the parent drugs on the basis of global descriptive parameters. The electrophilic and nucleophilic sites were pointed out in the MESP structures well evidently. NBO analysis was also done to predict the relative aromaticity, delocalization effects and the contribution towards stabilization energy of the title compound. The information about non-covalent, non-ionic weak interaction between the cation and anion was obtained from the list of Mulliken charges and NBO analysis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reliable and fast quantitative analysis of active ingredient in pharmaceutical suspension using Raman spectroscopy.

PubMed

Park, Seok Chan; Kim, Minjung; Noh, Jaegeun; Chung, Hoeil; Woo, Youngah; Lee, Jonghwa; Kemper, Mark S

2007-06-12

The concentration of acetaminophen in a turbid pharmaceutical suspension has been measured successfully using Raman spectroscopy. The spectrometer was equipped with a large spot probe which enabled the coverage of a representative area during sampling. This wide area illumination (WAI) scheme (coverage area 28.3 mm2) for Raman data collection proved to be more reliable for the compositional determination of these pharmaceutical suspensions, especially when the samples were turbid. The reproducibility of measurement using the WAI scheme was compared to that of using a conventional small-spot scheme which employed a much smaller illumination area (about 100 microm spot size). A layer of isobutyric anhydride was placed in front of the sample vials to correct the variation in the Raman intensity due to the fluctuation of laser power. Corrections were accomplished using the isolated carbonyl band of isobutyric anhydride. The acetaminophen concentrations of prediction samples were accurately estimated using a partial least squares (PLS) calibration model. The prediction accuracy was maintained even with changes in laser power. It was noted that the prediction performance was somewhat degraded for turbid suspensions with high acetaminophen contents. When comparing the results of reproducibility obtained with the WAI scheme and those obtained using the conventional scheme, it was concluded that the quantitative determination of the active pharmaceutical ingredient (API) in turbid suspensions is much improved when employing a larger laser coverage area. This is presumably due to the improvement in representative sampling.

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

Towards integrated drug substance and drug product design for an active pharmaceutical ingredient using particle engineering.

PubMed

Kougoulos, Eleftherios; Smales, Ian; Verrier, Hugh M

2011-03-01

A novel experimental approach describing the integration of drug substance and drug production design using particle engineering techniques such as sonocrystallization, high shear wet milling (HSWM) and dry impact (hammer) milling were used to manufacture samples of an active pharmaceutical ingredient (API) with diverse particle size and size distributions. The API instability was addressed using particle engineering and through judicious selection of excipients to reduce degradation reactions. API produced using a conventional batch cooling crystallization process resulted in content uniformity issues. Hammer milling increased fine particle formation resulting in reduced content uniformity and increased degradation compared to sonocrystallized and HSWM API in the formulation. To ensure at least a 2-year shelf life based on predictions using an Accelerated Stability Assessment Program, this API should have a D [v, 0.1] of 55 μm and a D [v, 0.5] of 140 μm. The particle size of the chief excipient in the drug product formulation needed to be close to that of the API to avoid content uniformity and stability issues but large enough to reduce lactam formation. The novel methodology described here has potential for application to other APIs. © 2011 American Association of Pharmaceutical Scientists

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

PubMed Central

Chao, Ming-Yu; Liu, Kung-Tien; Hsia, Yi-Chih; Liao, Mei-Hsiu; Shen, Lie-Hang

2011-01-01

Technetium-99m ethyl cysteinate dimer (Tc-99m-ECD) is an essential imaging agent used in evaluating the regional cerebral blood flow in patients with cerebrovascular diseases. Determination of active pharmaceutical ingredient, that is, L-Cysteine, N, N′-1,2-ethanediylbis-, diethyl ester, dihydrochloride (ECD) in ECD Kit is a relevant requirement for the pharmaceutical quality control in processes of mass fabrication. We here presented a direct solid sample determination method of ECD in ECD Kit without sample dissolution to avoid the rapid degradation of ECD. An elemental analyzer equipped with a nondispersive infrared detector and a calibration curve of coal standard was used for the quantitation of sulfur in ECD Kit. No significant matrix effect was found. The peak area of coal standard against the amount of sulfur was linear over the range of 0.03–0.10 mg, with a correlation coefficient (r) of 0.9993. Method validation parameters were achieved to demonstrate the potential of this method. PMID:21687539

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

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

PubMed

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

2018-06-01

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

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

PubMed

Veronin, Michael A; Nutan, Mohammad T; Dodla, Uday Krishna Reddy

2014-10-01

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. 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. 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. 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. 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 products compared with the US innovator product are not

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

Development and validation of an ICP-MS method for the determination of elemental impurities in TP-6076 active pharmaceutical ingredient (API) according to USP 〈232〉/〈233〉.

PubMed

Chahrour, Osama; Malone, John; Collins, Mark; Salmon, Vrushali; Greenan, Catherine; Bombardier, Amy; Ma, Zhongze; Dunwoody, Nick

2017-10-25

The new guidelines of the United States pharmacopeia (USP), European pharmacopeia (EP) and international conference on harmonization (ICH) regulating elemental impurities limits in pharmaceuticals signify the end of unspecific analysis of metals as outlined in USP 〈231〉. The new guidelines specify both daily doses and concentration/limits of elemental impurities in pharmaceutical final products, active pharmaceutical ingredients (API) and excipients. In chapter USP 〈233〉 method implementation, validation and quality control during the analytical process are described. We herein report the use of a stabilising matrix that overcomes low spike recovery problem encountered with Os and allows the determination of all USP required elemental impurities (As, Cd, Hg, Pb, V, Cr, Ni, Mo, Cu, Pt, Pd, Ru, Rh, Os and Ir) in a single analysis. The matrix was used in the validation of a method to determine elemental impurities in TP-6076 active pharmaceutical ingredient (API) by ICP-MS according to the procedures defined in USP〈233〉 and to GMP requirements. This validation will support the regulatory submission of TP-6076 which is a novel tetracycline analogue effective against the most urgent multidrug-resistant gram-negative bacteria. Evaluation of TP-6076 in IND-enabling toxicology studies has led to the initiation of a phase 1 clinical trial. Copyright © 2017 Elsevier B.V. All rights reserved.

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...

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-1010] Draft Guidance for Industry on Initial Completeness Assessments for Type II Active Pharmaceutical... certain drug master files, namely, Type II active pharmaceutical ingredient (API) drug master files (DMFs...

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.

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

Rapid Determination of Trace Palladium in Active Pharmaceutical Ingredients by Magnetic Solid-Phase Extraction and Flame Atomic Absorption Spectrometry

NASA Astrophysics Data System (ADS)

Yin, Q. H.; Zhu, D. M.; Yang, D. Z.; Hu, Q. F.; Yang, Y. L.

2018-01-01

Clutaraldehyde cross-linked magnetic chitosan nanoparticles were synthesized and used as an adsorbent for the dispersive solid-phase extraction of palladium in active pharmaceutical ingredients (APIs) prior to analysis by a flame atomic absorption spectrophotometer. FT-IR, X-ray diffraction, and TEM were used to characterize the adsorbent. Various parameters of experimental performance, such as adsorbent amount, pH, adsorption time, desorption solutions, coexisting ions, and adsorbent reusability, were investigated and optimized. Under the optimized conditions, good linearity was achieved in the 5.0-500 μg/L concentration range, with correlation coefficients of 0.9989. The limit of detection is 2.8 μg/L and the recoveries of spiked samples ranged from 91.7 to 97.6%. It was confirmed that the GMCNs nanocomposite was a promising adsorbing material for extraction and preconcentration of Pd in APIs.

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

PubMed

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

2014-09-01

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

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. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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 crossmore » 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.« less

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 crossmore » 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.« less

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

PubMed

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

2006-04-01

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

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

PubMed

Horkovics-Kovats, Stefan

2014-02-01

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

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

PubMed

Li, Weiyong; Worosila, Gregory D

2005-05-13

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

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.

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.

Selected pharmaceuticals entering an estuary: Concentrations, temporal trends, partitioning, and fluxes.

PubMed

Cantwell, Mark G; Katz, David R; Sullivan, Julia C; Ho, Kay; Burgess, Robert M; Cashman, Michaela

2016-11-01

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 were measured regularly over 1 yr in the dissolved and particulate phases as they entered Narragansett Bay from the Pawtuxet River in Cranston (Rhode Island, USA). Of the active pharmaceutical ingredients measured, 14 were consistently present in the dissolved phase, with concentrations ranging from below detection to >310 ng/L, whereas 8 were present in the particulate phase (0.2-18 ng/g). Partition coefficients (K d s and K OC s) were determined, and organic carbon normalization reduced variability associated with K d s for the active pharmaceutical ingredients evaluated. Flux estimates based on river flow were calculated for both dissolved and particulate-phase active pharmaceutical ingredients, with particulate fluxes being low (1-12 g/yr) and dissolved fluxes of active pharmaceutical ingredients being 155 g/yr to 11 600 g/yr. Results indicate that the pharmaceuticals measured in the present study reside primarily in the dissolved phase and thus are likely bioavailable on entering the estuarine waters of Narragansett Bay. This long-term temporal study provides important information on seasonal and annual dynamics of pharmaceuticals in an urban estuarine watershed. Environ Toxicol Chem 2016;35:2665-2673. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US Government work and, as such, is in the public domain in the United States of America. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US Government work and, as such, is in the public domain in the United States of America.

21 CFR 346.14 - Protectant active ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Protectant active ingredients. 346.14 Section 346...) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.14 Protectant active ingredients. (a) The following active ingredients may be used as the sole protectant active...

21 CFR 346.14 - Protectant active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Protectant active ingredients. 346.14 Section 346...) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.14 Protectant active ingredients. (a) The following active ingredients may be used as the sole protectant active...

21 CFR 346.14 - Protectant active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Protectant active ingredients. 346.14 Section 346...) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.14 Protectant active ingredients. (a) The following active ingredients may be used as the sole protectant active...

21 CFR 346.14 - Protectant active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Protectant active ingredients. 346.14 Section 346...) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.14 Protectant active ingredients. (a) The following active ingredients may be used as the sole protectant active...

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 341.14 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...-COUNTER HUMAN USE Active Ingredients § 341.14 Antitussive active ingredients. The active ingredients of...

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 341.12 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...-COUNTER HUMAN USE Active Ingredients § 341.12 Antihistamine active ingredients. The active ingredient of...

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...-COUNTER HUMAN USE Active Ingredients § 341.16 Bronchodilator active ingredients. The active ingredients of...

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 341.14 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...-COUNTER HUMAN USE Active Ingredients § 341.14 Antitussive active ingredients. The active ingredients of...

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...-COUNTER HUMAN USE Active Ingredients § 341.12 Antihistamine active ingredients. The active ingredient of...

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...-COUNTER HUMAN USE Active Ingredients § 341.16 Bronchodilator active ingredients. The active ingredients of...

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...-COUNTER HUMAN USE Active Ingredients § 341.12 Antihistamine active ingredients. The active ingredient of...

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...-COUNTER HUMAN USE Active Ingredients § 341.16 Bronchodilator active ingredients. The active ingredients of...

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 341.14 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...-COUNTER HUMAN USE Active Ingredients § 341.14 Antitussive active ingredients. The active ingredients of...

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 341.14 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...-COUNTER HUMAN USE Active Ingredients § 341.14 Antitussive active ingredients. The active ingredients of...

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...-COUNTER HUMAN USE Active Ingredients § 341.16 Bronchodilator active ingredients. The active ingredients of...

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...-COUNTER HUMAN USE Active Ingredients § 341.12 Antihistamine active ingredients. The active ingredient of...

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...-COUNTER HUMAN USE Active Ingredients § 341.18 Expectorant active ingredient. The active ingredient of the...

21 CFR 335.10 - Antidiarrheal active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Antidiarrheal active ingredients. 335.10 Section...) DRUGS FOR HUMAN USE ANTIDIARRHEAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 335.10 Antidiarrheal active ingredients. The active ingredient of the product consists of any one of the...

21 CFR 335.10 - Antidiarrheal active ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Antidiarrheal active ingredients. 335.10 Section...) DRUGS FOR HUMAN USE ANTIDIARRHEAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 335.10 Antidiarrheal active ingredients. The active ingredient of the product consists of any one of the...

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...-COUNTER HUMAN USE Active Ingredients § 341.18 Expectorant active ingredient. The active ingredient of the...

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...-COUNTER HUMAN USE Active Ingredients § 341.18 Expectorant active ingredient. The active ingredient of the...

21 CFR 335.10 - Antidiarrheal active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Antidiarrheal active ingredients. 335.10 Section...) DRUGS FOR HUMAN USE ANTIDIARRHEAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 335.10 Antidiarrheal active ingredients. The active ingredient of the product consists of any one of the...

21 CFR 335.10 - Antidiarrheal active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Antidiarrheal active ingredients. 335.10 Section...) DRUGS FOR HUMAN USE ANTIDIARRHEAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 335.10 Antidiarrheal active ingredients. The active ingredient of the product consists of any one of the...

21 CFR 335.10 - Antidiarrheal active ingredients.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Antidiarrheal active ingredients. 335.10 Section...) DRUGS FOR HUMAN USE ANTIDIARRHEAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 335.10 Antidiarrheal active ingredients. The active ingredient of the product consists of any one of the...

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...-COUNTER HUMAN USE Active Ingredients § 341.18 Expectorant active ingredient. The active ingredient of the...

21 CFR 350.10 - Antiperspirant active ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

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

21 CFR 350.10 - Antiperspirant active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

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

21 CFR 350.10 - Antiperspirant active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

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

21 CFR 350.10 - Antiperspirant active ingredients.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 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 the...

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 the...

21 CFR 336.10 - Antiemetic active ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Antiemetic active ingredients. 336.10 Section 336...) DRUGS FOR HUMAN USE ANTIEMETIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 336.10 Antiemetic active ingredients. The active ingredient of the product consists of any of the following when...

21 CFR 340.10 - Stimulant active ingredient.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Stimulant active ingredient. 340.10 Section 340.10... FOR HUMAN USE STIMULANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredient § 340.10 Stimulant active ingredient. The active ingredient of the product consists of caffeine when used within the...

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...) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 347.12 Astringent active ingredients. The active ingredient of the product consists of any one of the...

21 CFR 346.18 - 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. 346.18 Section 346...) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.18 Astringent active ingredients. The active ingredient of the product consists of any of the following when...

21 CFR 355.10 - Anticaries active ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

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

21 CFR 346.18 - 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. 346.18 Section 346...) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.18 Astringent active ingredients. The active ingredient of the product consists of any of the following when...

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 when...

21 CFR 346.20 - Keratolytic active ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Keratolytic active ingredients. 346.20 Section 346...) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.20 Keratolytic active ingredients. The active ingredient of the product consists of any of the following when...

21 CFR 346.12 - Vasoconstrictor active ingredients.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Vasoconstrictor active ingredients. 346.12 Section...) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.12 Vasoconstrictor active ingredients. The active ingredient of the product consists of any of the following when...

21 CFR 336.10 - Antiemetic active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Antiemetic active ingredients. 336.10 Section 336...) DRUGS FOR HUMAN USE ANTIEMETIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 336.10 Antiemetic active ingredients. The active ingredient of the product consists of any of the following when...

21 CFR 355.10 - Anticaries active ingredients.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 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 when...

21 CFR 346.20 - Keratolytic active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Keratolytic active ingredients. 346.20 Section 346...) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.20 Keratolytic active ingredients. The active ingredient of the product consists of any of the following when...

21 CFR 336.10 - Antiemetic active ingredients.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Antiemetic active ingredients. 336.10 Section 336...) DRUGS FOR HUMAN USE ANTIEMETIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 336.10 Antiemetic active ingredients. The active ingredient of the product consists of any of the following when...

21 CFR 355.10 - Anticaries active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

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

21 CFR 346.20 - Keratolytic active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Keratolytic active ingredients. 346.20 Section 346...) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.20 Keratolytic active ingredients. The active ingredient of the product consists of any of the following when...

21 CFR 340.10 - Stimulant active ingredient.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Stimulant active ingredient. 340.10 Section 340.10... FOR HUMAN USE STIMULANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredient § 340.10 Stimulant active ingredient. The active ingredient of the product consists of caffeine when used within the...

21 CFR 346.18 - 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. 346.18 Section 346...) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.18 Astringent active ingredients. The active ingredient of the product consists of any of the following when...

21 CFR 346.12 - Vasoconstrictor active ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Vasoconstrictor active ingredients. 346.12 Section...) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.12 Vasoconstrictor active ingredients. The active ingredient of the product consists of any of the following when...

21 CFR 346.20 - Keratolytic active ingredients.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Keratolytic active ingredients. 346.20 Section 346...) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.20 Keratolytic active ingredients. The active ingredient of the product consists of any of the following when...

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...) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 347.12 Astringent active ingredients. The active ingredient of the product consists of any one of the...

21 CFR 346.18 - 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. 346.18 Section 346...) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.18 Astringent active ingredients. The active ingredient of the product consists of any of the following when...

21 CFR 346.12 - Vasoconstrictor active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Vasoconstrictor active ingredients. 346.12 Section...) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.12 Vasoconstrictor active ingredients. The active ingredient of the product consists of any of the following when...

21 CFR 346.12 - Vasoconstrictor active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Vasoconstrictor active ingredients. 346.12 Section...) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.12 Vasoconstrictor active ingredients. The active ingredient of the product consists of any of the following when...

21 CFR 346.18 - 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. 346.18 Section 346...) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.18 Astringent active ingredients. The active ingredient of the product consists of any of the following when...

21 CFR 346.20 - Keratolytic active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Keratolytic active ingredients. 346.20 Section 346...) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.20 Keratolytic active ingredients. The active ingredient of the product consists of any of the following when...

21 CFR 336.10 - Antiemetic active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Antiemetic active ingredients. 336.10 Section 336...) DRUGS FOR HUMAN USE ANTIEMETIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 336.10 Antiemetic active ingredients. The active ingredient of the product consists of any of the following when...

21 CFR 340.10 - Stimulant active ingredient.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Stimulant active ingredient. 340.10 Section 340.10... FOR HUMAN USE STIMULANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredient § 340.10 Stimulant active ingredient. The active ingredient of the product consists of caffeine when used within the...

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...) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 347.12 Astringent active ingredients. The active ingredient of the product consists of any one of the...

21 CFR 346.12 - Vasoconstrictor active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Vasoconstrictor active ingredients. 346.12 Section...) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.12 Vasoconstrictor active ingredients. The active ingredient of the product consists of any of the following when...

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...) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 347.12 Astringent active ingredients. The active ingredient of the product consists of any one of the...

21 CFR 355.10 - Anticaries active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

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

21 CFR 340.10 - Stimulant active ingredient.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Stimulant active ingredient. 340.10 Section 340.10... FOR HUMAN USE STIMULANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredient § 340.10 Stimulant active ingredient. The active ingredient of the product consists of caffeine when used within the...

21 CFR 336.10 - Antiemetic active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Antiemetic active ingredients. 336.10 Section 336...) DRUGS FOR HUMAN USE ANTIEMETIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 336.10 Antiemetic active ingredients. The active ingredient of the product consists of any of the following when...

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.

21 CFR 331.10 - Antacid active ingredients.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Antacid active ingredients. 331.10 Section 331.10... FOR HUMAN USE ANTACID PRODUCTS FOR OVER-THE-COUNTER (OTC) HUMAN USE Active Ingredients § 331.10 Antacid active ingredients. (a) The active antacid ingredients of the product consist of one or more of...

21 CFR 331.10 - Antacid active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Antacid active ingredients. 331.10 Section 331.10... FOR HUMAN USE ANTACID PRODUCTS FOR OVER-THE-COUNTER (OTC) HUMAN USE Active Ingredients § 331.10 Antacid active ingredients. (a) The active antacid ingredients of the product consist of one or more of...

21 CFR 331.10 - Antacid active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Antacid active ingredients. 331.10 Section 331.10... FOR HUMAN USE ANTACID PRODUCTS FOR OVER-THE-COUNTER (OTC) HUMAN USE Active Ingredients § 331.10 Antacid active ingredients. (a) The active antacid ingredients of the product consist of one or more of...

21 CFR 331.10 - Antacid active ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Antacid active ingredients. 331.10 Section 331.10... FOR HUMAN USE ANTACID PRODUCTS FOR OVER-THE-COUNTER (OTC) HUMAN USE Active Ingredients § 331.10 Antacid active ingredients. (a) The active antacid ingredients of the product consist of one or more of...

21 CFR 331.10 - Antacid active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Antacid active ingredients. 331.10 Section 331.10... FOR HUMAN USE ANTACID PRODUCTS FOR OVER-THE-COUNTER (OTC) HUMAN USE Active Ingredients § 331.10 Antacid active ingredients. (a) The active antacid ingredients of the product consist of one or more of...

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.

Modification of physicochemical characteristics of active pharmaceutical ingredients and application of supersaturatable dosage forms for improving bioavailability of poorly absorbed drugs.

PubMed

Kawakami, Kohsaku

2012-05-01

New chemical entities are required to possess physicochemical characteristics that result in acceptable oral absorption. However, many promising candidates need physicochemical modification or application of special formulation technology. This review discusses strategies for overcoming physicochemical problems during the development at the preformulation and formulation stages with emphasis on overcoming the most typical problem, low solubility. Solubility of active pharmaceutical ingredients can be improved by employing metastable states, salt forms, or cocrystals. Since the usefulness of salt forms is well recognized, it is the normal strategy to select the most suitable salt form through extensive screening in the current developmental study. Promising formulation technologies used to overcome the low solubility problem include liquid-filled capsules, self-emulsifying formulations, solid dispersions, and nanosuspensions. Current knowledge for each formulation is discussed from both theoretical and practical viewpoints, and their advantages and disadvantages are presented. Copyright © 2012 Elsevier B.V. All rights reserved.

[Screening of anti-aging active ingredients and mechanism analysis based on molecular docking technology].

PubMed

Du, Ran-Feng; Zhang, Xiao-Hua; Ye, Xiao-Tong; Yu, Wen-Kang; Wang, Yun

2016-07-01

Dampness evil is the source of all diseases, which is easy to cause disease and promote aging, while aging could also promote the occurence and development of diseases. In this paper, the relationship between the dampness evil and aging would be discussed, to find the anti-aging active ingredients in traditional Chinese medicine (TCM), and analyze the anti-aging mechanism of dampness eliminating drug. Molecular docking technology was used, with aging-related mammalian target of rapamycin as the docking receptors, and chemical components of Fuling, Sangzhi, Mugua, Yiyiren and Houpo as the docking molecules, to preliminarily screen the anti-aging active ingredients in dampness eliminating drug. Through the comparison with active drugs already on the market (temsirolimus and everolimus), 12 kinds of potential anti-aging active ingredients were found, but their drug gability still needs further study. The docking results showed that various components in the dampness eliminating drug can play anti-aging activities by acting on mammalian target of rapamycin. This result provides a new thought and direction for the method of delaying aging by eliminating dampness. Copyright© by the Chinese Pharmaceutical Association.

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 provided...

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 provided...

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 provided...

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 provided...

21 CFR 343.13 - Rheumatologic active ingredients.

Code of Federal Regulations, 2010 CFR

2010-04-01

...-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 provided...

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 provided...

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 provided...

21 CFR 343.12 - Cardiovascular active ingredients.

Code of Federal Regulations, 2010 CFR

2010-04-01

...-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 provided...

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 provided...

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 provided...

21 CFR 346.14 - Protectant active ingredients.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.14... ingredient in a product if the ingredient as identified constitutes 50 percent or more by weight of the final product. In addition, the following active ingredients may be used in concentrations of less than 50...

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

PubMed

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

2018-01-01

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

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... OVER-THE-COUNTER HUMAN USE Active Ingredients § 341.20 Nasal decongestant active ingredients. The active ingredient of the product consists of any of the following when used within the dosage limits and...

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... OVER-THE-COUNTER HUMAN USE Active Ingredients § 341.20 Nasal decongestant active ingredients. The active ingredient of the product consists of any of the following when used within the dosage limits and...

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... (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 of...

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... OVER-THE-COUNTER HUMAN USE Active Ingredients § 341.20 Nasal decongestant active ingredients. The active ingredient of the product consists of any of the following when used within the dosage limits and...

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... (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 of...

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... OVER-THE-COUNTER HUMAN USE Active Ingredients § 341.20 Nasal decongestant active ingredients. The active ingredient of the product consists of any of the following when used within the dosage limits and...

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 of...

The binding of orally dosed hydrophobic active pharmaceutical ingredients to casein micelles in milk.

PubMed

Cheema, M; Hristov, A N; Harte, F M

2017-11-01

Casein proteins (α S1 -, α S2 -, β- and κ-casein) account for 80% of the total protein content in bovine milk and form casein micelles (average diameter = 130 nm, approximately 10 15 micelles/mL). The affinity of native casein micelles with the 3 hydrophobic active pharmaceutical ingredients (API), meloxicam [351.4 g/mol; log P = 3.43; acid dissociation constant (pK a ) = 4.08], flunixin (296.2 g/mol; log P = 4.1; pK a = 5.82), and thiabendazole (201.2 g/mol; log P = 2.92; pK a = 4.64), was evaluated in bovine milk collected from dosed Holstein cows. Native casein micelles were separated from raw bovine milk by mild techniques such as ultracentrifugation, diafiltration, isoelectric point precipitation (pH 4.6), and size exclusion chromatography. Acetonitrile extraction of hydrophobic API was then done, followed by quantification using HPLC-UV. For the API or metabolites meloxicam, 5-hyroxy flunixin and 5-hydroxy thiabendazole, 31 ± 3.90, 31 ± 1.3, and 28 ± 0.5% of the content in milk was associated with casein micelles, respectively. Less than ∼5.0% of the recovered hydrophobic API were found in the milk fat fraction, and the remaining ∼65% were associated with the whey/serum fraction. A separate in vitro study showed that 66 ± 6.4% of meloxicam, 29 ± 0.58% of flunixin, 34 ± 0.21% of the metabolite 5-hyroxy flunixin, 50 ± 4.5% of thiabendazole, and 33 ± 3.8% of metabolite 5-hydroxy thiabendazole was found partitioned into casein micelles. Our study supports the hypothesis that casein micelles are native carriers for hydrophobic compounds in bovine milk. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

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.

The significance of different health institutions and their respective contributions of active pharmaceutical ingredients to wastewater.

PubMed

Herrmann, Manuel; Olsson, Oliver; Fiehn, Rainer; Herrel, Markus; Kümmerer, Klaus

2015-12-01

Active pharmaceutical ingredients (APIs) have been frequently found in the environment. It is, however, still not quite clear who is mainly responsible for API emissions. Hospitals have been considered to be the main contributing point sources for wastewater (WW) discharge of APIs. However, recent studies have shown that the contribution of hospitals to the input of APIs into the aquatic environment is quite low. Due to demographic change and the increase of psychiatric diseases, health institutions (HIs) such as psychiatric hospitals and nursing homes are likely to be important sources as well, but no data is available in this respect. This study aims to assess the impact of HIs and to provide a methodology to measure their respective contributions. Drawing on pharmaceutical consumption data for the years 2010, 2011, and 2012, this study identified API usage patterns for a psychiatric hospital (146 beds), a nursing home (286 inhabitants), and a general hospital (741 beds), the latter of which comprises three separate locations. All the HIs are located in two sub-regions of a county district with about 400,000 citizens in southwestern Germany. A selection of neurological drugs was quantified in the sewer of these facilities to evaluate the correlation between consumption and emission. The API contribution of HIs was assessed by comparing the specific consumption in the facilities with the consumption in households, expressed as the emission potential (IEP). The study shows that the usage patterns of APIs in the psychiatric hospital and the nursing home were different from the general hospital. Neurological drugs such as anticonvulsants, psycholeptics, and psychoanaleptics were mainly consumed in the psychiatric hospital and the nursing home (74% and 65%, respectively). Predicted and average measured concentrations in the effluent of the investigated HIs differed mostly by less than one order of magnitude. Therefore, the consumption-based approach is a useful method

21 CFR 357.210 - Cholecystokinetic active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Cholecystokinetic active ingredients. 357.210 Section 357.210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Cholecystokinetic Drug Products § 357.210 Cholecystokinetic active ingredients. The active ingredient of the product...

21 CFR 333.210 - Antifungal active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Antifungal active ingredients. 333.210 Section 333.210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Antifungal Drug Products § 333.210 Antifungal active ingredients. The active ingredient of the product...

21 CFR 358.610 - Pediculicide active ingredients.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Pediculicide active ingredients. 358.610 Section 358.610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Pediculicide Drug Products § 358.610 Pediculicide active ingredients. The active ingredients of the product...

21 CFR 357.110 - Anthelmintic active ingredient.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Anthelmintic active ingredient. 357.110 Section 357.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Anthelmintic Drug Products § 357.110 Anthelmintic active ingredient. The active ingredient of the product is...

21 CFR 358.610 - Pediculicide active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Pediculicide active ingredients. 358.610 Section 358.610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Pediculicide Drug Products § 358.610 Pediculicide active ingredients. The active ingredients of the product...

21 CFR 357.110 - Anthelmintic active ingredient.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Anthelmintic active ingredient. 357.110 Section 357.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Anthelmintic Drug Products § 357.110 Anthelmintic active ingredient. The active ingredient of the product is...

21 CFR 333.210 - Antifungal active ingredients.

Code of Federal Regulations, 2010 CFR

2010-04-01

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

21 CFR 358.610 - Pediculicide active ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Pediculicide active ingredients. 358.610 Section 358.610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Pediculicide Drug Products § 358.610 Pediculicide active ingredients. The active ingredients of the product...

21 CFR 357.210 - Cholecystokinetic active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Cholecystokinetic active ingredients. 357.210 Section 357.210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Cholecystokinetic Drug Products § 357.210 Cholecystokinetic active ingredients. The active ingredient of the product...

21 CFR 358.610 - Pediculicide active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Pediculicide active ingredients. 358.610 Section 358.610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Pediculicide Drug Products § 358.610 Pediculicide active ingredients. The active ingredients of the product...

21 CFR 358.610 - Pediculicide active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Pediculicide active ingredients. 358.610 Section 358.610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Pediculicide Drug Products § 358.610 Pediculicide active ingredients. The active ingredients of the product...

21 CFR 357.110 - Anthelmintic active ingredient.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Anthelmintic active ingredient. 357.110 Section 357.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Anthelmintic Drug Products § 357.110 Anthelmintic active ingredient. The active ingredient of the product is...

21 CFR 333.210 - Antifungal active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Antifungal active ingredients. 333.210 Section 333.210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Antifungal Drug Products § 333.210 Antifungal active ingredients. The active ingredient of the product...

21 CFR 333.210 - Antifungal active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Antifungal active ingredients. 333.210 Section 333.210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Antifungal Drug Products § 333.210 Antifungal active ingredients. The active ingredient of the product...

21 CFR 357.110 - Anthelmintic active ingredient.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Anthelmintic active ingredient. 357.110 Section 357.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Anthelmintic Drug Products § 357.110 Anthelmintic active ingredient. The active ingredient of the product is...

21 CFR 357.110 - Anthelmintic active ingredient.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Anthelmintic active ingredient. 357.110 Section 357.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Anthelmintic Drug Products § 357.110 Anthelmintic active ingredient. The active ingredient of the product is...

21 CFR 357.210 - Cholecystokinetic active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Cholecystokinetic active ingredients. 357.210 Section 357.210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Cholecystokinetic Drug Products § 357.210 Cholecystokinetic active ingredients. The active ingredient of the product...

21 CFR 333.210 - Antifungal active ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Antifungal active ingredients. 333.210 Section 333.210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Antifungal Drug Products § 333.210 Antifungal active ingredients. The active ingredient of the product...

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.

21 CFR 332.10 - Antiflatulent active ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Antiflatulent active ingredients. 332.10 Section...) DRUGS FOR HUMAN USE ANTIFLATULENT PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 332.10 Antiflatulent active ingredients. Simethicone; maximum daily dose 500 mg. There is no dosage limitation at this...

21 CFR 332.10 - Antiflatulent active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Antiflatulent active ingredients. 332.10 Section...) DRUGS FOR HUMAN USE ANTIFLATULENT PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 332.10 Antiflatulent active ingredients. Simethicone; maximum daily dose 500 mg. There is no dosage limitation at this...

21 CFR 332.10 - Antiflatulent active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Antiflatulent active ingredients. 332.10 Section...) DRUGS FOR HUMAN USE ANTIFLATULENT PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 332.10 Antiflatulent active ingredients. Simethicone; maximum daily dose 500 mg. There is no dosage limitation at this...

21 CFR 332.10 - Antiflatulent active ingredients.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Antiflatulent active ingredients. 332.10 Section...) DRUGS FOR HUMAN USE ANTIFLATULENT PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 332.10 Antiflatulent active ingredients. Simethicone; maximum daily dose 500 mg. There is no dosage limitation at this...

21 CFR 332.10 - Antiflatulent active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Antiflatulent active ingredients. 332.10 Section...) DRUGS FOR HUMAN USE ANTIFLATULENT PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 332.10 Antiflatulent active ingredients. Simethicone; maximum daily dose 500 mg. There is no dosage limitation at this...

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...

21 CFR 352.20 - Permitted combinations of active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Permitted combinations of active ingredients. 352... INDEFINITELY] Active Ingredients § 352.20 Permitted combinations of active ingredients. The SPF of any...) Combinations of sunscreen active ingredients. (1) Two or more sunscreen active ingredients identified in § 352...

21 CFR 352.20 - Permitted combinations of active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Permitted combinations of active ingredients. 352... INDEFINITELY] Active Ingredients § 352.20 Permitted combinations of active ingredients. The SPF of any...) Combinations of sunscreen active ingredients. (1) Two or more sunscreen active ingredients identified in § 352...

21 CFR 352.20 - Permitted combinations of active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Permitted combinations of active ingredients. 352... INDEFINITELY] Active Ingredients § 352.20 Permitted combinations of active ingredients. The SPF of any...) Combinations of sunscreen active ingredients. (1) Two or more sunscreen active ingredients identified in § 352...

21 CFR 352.20 - Permitted combinations of active ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Permitted combinations of active ingredients. 352... INDEFINITELY] Active Ingredients § 352.20 Permitted combinations of active ingredients. The SPF of any...) Combinations of sunscreen active ingredients. (1) Two or more sunscreen active ingredients identified in § 352...

21 CFR 352.20 - Permitted combinations of active ingredients.

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. 352... INDEFINITELY] Active Ingredients § 352.20 Permitted combinations of active ingredients. The SPF of any...) Combinations of sunscreen active ingredients. (1) Two or more sunscreen active ingredients identified in § 352...

Presence of active pharmaceutical ingredients in the continuum of surface and ground water used in drinking water production.

PubMed

Ahkola, Heidi; Tuominen, Sirkku; Karlsson, Sanja; Perkola, Noora; Huttula, Timo; Saraperä, Sami; Artimo, Aki; Korpiharju, Taina; Äystö, Lauri; Fjäder, Päivi; Assmuth, Timo; Rosendahl, Kirsi; Nysten, Taina

2017-12-01

Anthropogenic chemicals in surface water and groundwater cause concern especially when the water is used in drinking water production. Due to their continuous release or spill-over at waste water treatment plants, active pharmaceutical ingredients (APIs) are constantly present in aquatic environment and despite their low concentrations, APIs can still cause effects on the organisms. In the present study, Chemcatcher passive sampling was applied in surface water, surface water intake site, and groundwater observation wells to estimate whether the selected APIs are able to end up in drinking water supply through an artificial groundwater recharge system. The API concentrations measured in conventional wastewater, surface water, and groundwater grab samples were assessed with the results obtained with passive samplers. Out of the 25 APIs studied with passive sampling, four were observed in groundwater and 21 in surface water. This suggests that many anthropogenic APIs released to waste water proceed downstream and can be detectable in groundwater recharge. Chemcatcher passive samplers have previously been used in monitoring several harmful chemicals in surface and wastewaters, but the path of chemicals to groundwater has not been studied. This study provides novel information on the suitability of the Chemcatcher passive samplers for detecting APIs in groundwater wells.

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 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS... Products § 333.310 Acne active ingredients. The active ingredient of the product consists of any of the...

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 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS... Products § 333.310 Acne active ingredients. The active ingredient of the product consists of any of the...

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 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS... Products § 333.310 Acne active ingredients. The active ingredient of the product consists of any of the...

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 the...

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 the...

21 CFR 347.20 - Permitted combinations of active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 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 skin protectant active ingredients. (1) Any two or more of the ingredients identified in § 347.10(a), (d), (e), (i...

21 CFR 347.20 - Permitted combinations of active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Permitted combinations of active ingredients. 347... Active Ingredients § 347.20 Permitted combinations of active ingredients. (a) Combinations of skin protectant active ingredients. (1) Any two or more of the ingredients identified in § 347.10(a), (d), (e), (i...

21 CFR 347.20 - Permitted combinations of active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Permitted combinations of active ingredients. 347... Active Ingredients § 347.20 Permitted combinations of active ingredients. (a) Combinations of skin protectant active ingredients. (1) Any two or more of the ingredients identified in § 347.10(a), (d), (e), (i...

21 CFR 347.20 - Permitted combinations of active ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Permitted combinations of active ingredients. 347... Active Ingredients § 347.20 Permitted combinations of active ingredients. (a) Combinations of skin protectant active ingredients. (1) Any two or more of the ingredients identified in § 347.10(a), (d), (e), (i...

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 ...

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

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.

Fast Determination of Ingredients in Solid Pharmaceuticals by Microwave-Enhanced In-Source Decay of Microwave Plasma Torch Mass Spectrometry.

PubMed

Su, Rui; Wang, Xinchen; Hou, Changming; Yang, Meiling; Huang, Keke; Chen, Huanwen

2017-09-01

Rapid qualitative and quantitative analysis of solid samples (e.g., pharmaceutical preparations) by using a small and low-resolution mass spectrometer without MS/MS function is still a challenge in ambient pressure ionization mass spectrometric analysis. Herein, a practically efficient method termed microwave-enhanced in-source decay (MEISD) using microwave plasma torch desorption ionization coupled with time-of-flight mass spectrometry (MPTDI-TOF MS) was developed for fast analysis of pharmaceutical tablets using a miniature TOF mass spectrometer without tandem mass function. The intensity of ISD fragmentation was evaluated under different microwave power values. Several factors, including desorption distance and time that might affect the signal intensity and fragmentation, were systematically investigated. It was observed that both the protonated molecular ions and major fragment ions from the active ingredients in tablets could be found in the full-scan mass spectra in positive ion mode, which were comparable to those obtained by a commercial LTQ-XL ion trap mass spectrometer. The structures of the ingredients could be elucidated in detail using the MEISD method, which promotes our understanding of the desorption/ionization processes in microwave plasma torch (MPT). Quantitative analysis of 10 tablets was achieved by full-scan MPTDI-TOF MS with low limit of detection (LOD, 0.763 mg/g), acceptable relative standard deviation (RSD < 7.33%, n =10), and 10 s for each tablet, showing promising applications in high throughput screening of counterfeit drugs. Graphical Abstract ᅟ.

Fast Determination of Ingredients in Solid Pharmaceuticals by Microwave-Enhanced In-Source Decay of Microwave Plasma Torch Mass Spectrometry

NASA Astrophysics Data System (ADS)

Su, Rui; Wang, Xinchen; Hou, Changming; Yang, Meiling; Huang, Keke; Chen, Huanwen

2017-09-01

Rapid qualitative and quantitative analysis of solid samples (e.g., pharmaceutical preparations) by using a small and low-resolution mass spectrometer without MS/MS function is still a challenge in ambient pressure ionization mass spectrometric analysis. Herein, a practically efficient method termed microwave-enhanced in-source decay (MEISD) using microwave plasma torch desorption ionization coupled with time-of-flight mass spectrometry (MPTDI-TOF MS) was developed for fast analysis of pharmaceutical tablets using a miniature TOF mass spectrometer without tandem mass function. The intensity of ISD fragmentation was evaluated under different microwave power values. Several factors, including desorption distance and time that might affect the signal intensity and fragmentation, were systematically investigated. It was observed that both the protonated molecular ions and major fragment ions from the active ingredients in tablets could be found in the full-scan mass spectra in positive ion mode, which were comparable to those obtained by a commercial LTQ-XL ion trap mass spectrometer. The structures of the ingredients could be elucidated in detail using the MEISD method, which promotes our understanding of the desorption/ionization processes in microwave plasma torch (MPT). Quantitative analysis of 10 tablets was achieved by full-scan MPTDI-TOF MS with low limit of detection (LOD, 0.763 mg/g), acceptable relative standard deviation (RSD < 7.33%, n =10), and 10 s for each tablet, showing promising applications in high throughput screening of counterfeit drugs. [Figure not available: see fulltext.

21 CFR 331.11 - Listing of specific active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Listing of specific active ingredients. 331.11... (CONTINUED) DRUGS FOR HUMAN USE ANTACID PRODUCTS FOR OVER-THE-COUNTER (OTC) HUMAN USE Active Ingredients § 331.11 Listing of specific active ingredients. (a) Aluminum-containing active ingredients: (1) Basic...

21 CFR 331.11 - Listing of specific active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Listing of specific active ingredients. 331.11... (CONTINUED) DRUGS FOR HUMAN USE ANTACID PRODUCTS FOR OVER-THE-COUNTER (OTC) HUMAN USE Active Ingredients § 331.11 Listing of specific active ingredients. (a) Aluminum-containing active ingredients: (1) Basic...

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...) DRUGS FOR HUMAN USE TOPICAL OTIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 344.12 Ear drying aid active ingredient. The active ingredient of the product consists of isopropyl...

21 CFR 344.10 - Earwax removal aid active ingredient.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Earwax removal aid active ingredient. 344.10... (CONTINUED) DRUGS FOR HUMAN USE TOPICAL OTIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 344.10 Earwax removal aid active ingredient. The active ingredient of the product consists of...

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...) DRUGS FOR HUMAN USE TOPICAL OTIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 344.12 Ear drying aid active ingredient. The active ingredient of the product consists of isopropyl...

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...) DRUGS FOR HUMAN USE TOPICAL OTIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 344.12 Ear drying aid active ingredient. The active ingredient of the product consists of isopropyl...

21 CFR 344.10 - Earwax removal aid active ingredient.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Earwax removal aid active ingredient. 344.10... (CONTINUED) DRUGS FOR HUMAN USE TOPICAL OTIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 344.10 Earwax removal aid active ingredient. The active ingredient of the product consists of...

21 CFR 344.10 - Earwax removal aid active ingredient.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Earwax removal aid active ingredient. 344.10... (CONTINUED) DRUGS FOR HUMAN USE TOPICAL OTIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 344.10 Earwax removal aid active ingredient. The active ingredient of the product consists of...

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...) DRUGS FOR HUMAN USE TOPICAL OTIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 344.12 Ear drying aid active ingredient. The active ingredient of the product consists of isopropyl...

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...) DRUGS FOR HUMAN USE TOPICAL OTIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 344.12 Ear drying aid active ingredient. The active ingredient of the product consists of isopropyl...

21 CFR 344.10 - Earwax removal aid active ingredient.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Earwax removal aid active ingredient. 344.10... (CONTINUED) DRUGS FOR HUMAN USE TOPICAL OTIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 344.10 Earwax removal aid active ingredient. The active ingredient of the product consists of...

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... (CONTINUED) DRUGS FOR HUMAN USE TOPICAL OTIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 344.10 Earwax removal aid active ingredient. The active ingredient of the product consists of...

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 of...

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 of...

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 of...

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 of...

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 of...

21 CFR 358.110 - Wart remover active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Wart remover active ingredients. 358.110 Section... Remover Drug Products § 358.110 Wart remover active ingredients. The product consists of any of the following active ingredients within the specified concentration and in the dosage form established for each...

21 CFR 358.110 - Wart remover active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Wart remover active ingredients. 358.110 Section... Remover Drug Products § 358.110 Wart remover active ingredients. The product consists of any of the following active ingredients within the specified concentration and in the dosage form established for each...

21 CFR 358.110 - Wart remover active ingredients.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Wart remover active ingredients. 358.110 Section... Remover Drug Products § 358.110 Wart remover active ingredients. The product consists of any of the following active ingredients within the specified concentration and in the dosage form established for each...

21 CFR 358.110 - Wart remover active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Wart remover active ingredients. 358.110 Section... Remover Drug Products § 358.110 Wart remover active ingredients. The product consists of any of the following active ingredients within the specified concentration and in the dosage form established for each...

21 CFR 358.110 - Wart remover active ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Wart remover active ingredients. 358.110 Section... Remover Drug Products § 358.110 Wart remover active ingredients. The product consists of any of the following active ingredients within the specified concentration and in the dosage form established for each...

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 of...

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 of...

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%.

Characterization of low-abundance species in the active pharmaceutical ingredient of CIGB-300: A clinical-grade anticancer synthetic peptide.

PubMed

Garay, Hilda; Espinosa, Luis Ariel; Perera, Yasser; Sánchez, Aniel; Diago, David; Perea, Silvio E; Besada, Vladimir; Reyes, Osvaldo; González, Luis Javier

2018-04-20

CIGB-300 is a first-in-class synthetic peptide-based drug of 25 amino acids currently undergoing clinical trials in cancer patients. It contains an amidated disulfide cyclic undecapeptide fused to the TAT cell-penetrating peptide through a beta-alanine spacer. CIGB-300 inhibits the CK2-mediated phosphorylation leading to apoptosis of tumor cells in vitro, and in vivo in cancer patients. Despite the clinical development of CIGB-300, the characterization of peptide-related impurities present in the active pharmaceutical ingredient has not been reported earlier. In the decision tree of ICHQ3A(R2) guidelines, the daily doses intake, the abundance, and the identity of the peptide-related species are pivotal nodes that define actions to be taken (reporting, identification, and qualification). For this, purity was first assessed by reverse-phase chromatography (>97%) and low-abundance impurities (≤0.27%) were collected and identified by mass spectrometry. Most of the impurities were generated during peptide synthesis, the spontaneous air oxidation of the reduced peptide, and the lyophilization step. The most abundant impurity, with no biological activity, was the full-length peptide containing Met 17 transformed into a sulfoxide residue. Interestingly, parallel and antiparallel dimers of CIGB-300 linked by 2 intermolecular disulfide bonds exhibited a higher antiproliferative activity than the CIGB-300 monomer. Likewise, very low abundance trimers and tetramers of CIGB-300 linked by disulfide bonds (≤0.01%) were also detected. Here we describe for the first time the presence of active dimeric species whose feasibility as novel CIGB-300 derived entities merits further investigation. Copyright © 2018 European Peptide Society and John Wiley & Sons, Ltd.

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. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

21 CFR 347.10 - Skin protectant active ingredients.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) 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 the...) Aluminum hydroxide gel, 0.15 to 5 percent. (c) Calamine, 1 to 25 percent. (d) Cocoa butter, 50 to 100...

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

PubMed

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

2017-05-24

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

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...

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...

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...

21 CFR 358.720 - Permitted combinations of active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Permitted combinations of active ingredients. 358... Permitted combinations of active ingredients. (a) Combination of active ingredients for the control of... labeled according to § 358.750. (b) Combination of control of dandruff and external analgesic active...

21 CFR 358.720 - Permitted combinations of active ingredients.

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. 358... Permitted combinations of active ingredients. (a) Combination of active ingredients for the control of... labeled according to § 358.750. (b) Combination of control of dandruff and external analgesic active...

21 CFR 358.720 - Permitted combinations of active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Permitted combinations of active ingredients. 358... Permitted combinations of active ingredients. (a) Combination of active ingredients for the control of... labeled according to § 358.750. (b) Combination of control of dandruff and external analgesic active...

21 CFR 358.720 - Permitted combinations of active ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Permitted combinations of active ingredients. 358... Permitted combinations of active ingredients. (a) Combination of active ingredients for the control of... labeled according to § 358.750. (b) Combination of control of dandruff and external analgesic active...

21 CFR 358.720 - Permitted combinations of active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 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 of... labeled according to § 358.750. (b) Combination of control of dandruff and external analgesic active...

Active ingredients of substance use-focused self-help groups.

PubMed

Moos, Rudolf H

2008-03-01

This paper provides an overview of some of the probable active ingredients of self-help groups in light of four related theories that identify common social processes that appear to underlie effective psychosocial treatments for and continuing remission from these disorders. Social control theory specifies active ingredients such as bonding, goal direction and structure; social learning theory specifies the importance of norms and role models, behavioral economics and behavioral choice theory emphasizes involvement in rewarding activities other than substance use, and stress and coping theory highlights building self-efficacy and effective coping skills. A review of existing studies suggests that the emphasis on these active ingredients probably underlies some aspects of the effectiveness of self-help groups. Several issues that need to be addressed to enhance understanding of the active ingredients of action of self-help groups are discussed, including consideration of indices of Alcoholics Anonymous (AA) affiliation as active ingredients, identification of personal characteristics that may moderate the influence of active ingredients on substance use outcomes, examination of whether active ingredients of self-help groups, can amplify or compensate for treatment, identification of potential detrimental effects of involvement in self-help groups and focusing on the link between active ingredients of self-help groups and other aspects of the overall recovery milieu, such as the family and social networks.

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

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

PubMed

Baumann, Marcus; Baxendale, Ian R

2015-01-01

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.

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. Copyright © 2016 Elsevier B.V. All rights reserved.

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 ...

Modeling of quantitative relationships between physicochemical properties of active pharmaceutical ingredients and tensile strength of tablets using a boosted tree.

PubMed

Hayashi, Yoshihiro; Oishi, Takuya; Shirotori, Kaede; Marumo, Yuki; Kosugi, Atsushi; Kumada, Shungo; Hirai, Daijiro; Takayama, Kozo; Onuki, Yoshinori

2018-07-01

The aim of this study was to explore the potential of boosted tree (BT) to develop a correlation model between active pharmaceutical ingredient (API) characteristics and a tensile strength (TS) of tablets as critical quality attributes. First, we evaluated 81 kinds of API characteristics, such as particle size distribution, bulk density, tapped density, Hausner ratio, moisture content, elastic recovery, molecular weight, and partition coefficient. Next, we prepared tablets containing 50% API, 49% microcrystalline cellulose, and 1% magnesium stearate using direct compression at 6, 8, and 10 kN, and measured TS. Then, we applied BT to our dataset to develop a correlation model. Finally, the constructed BT model was validated using k-fold cross-validation. Results showed that the BT model achieved high-performance statistics, whereas multiple regression analysis resulted in poor estimations. Sensitivity analysis of the BT model revealed that diameter of powder particles at the 10th percentile of the cumulative percentage size distribution was the most crucial factor for TS. In addition, the influences of moisture content, partition coefficients, and modal diameter were appreciably meaningful factors. This study demonstrates that BT model could provide comprehensive understanding of the latent structure underlying APIs and TS of tablets.

The role of cocrystals in pharmaceutical science.

PubMed

Shan, Ning; Zaworotko, Michael J

2008-05-01

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

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.

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 in...

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.

21 CFR 331.15 - Combination with nonantacid active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Combination with nonantacid active ingredients... SERVICES (CONTINUED) DRUGS FOR HUMAN USE ANTACID PRODUCTS FOR OVER-THE-COUNTER (OTC) HUMAN USE Active Ingredients § 331.15 Combination with nonantacid active ingredients. (a) An antacid may contain any generally...

21 CFR 331.15 - Combination with nonantacid active ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Combination with nonantacid active ingredients... SERVICES (CONTINUED) DRUGS FOR HUMAN USE ANTACID PRODUCTS FOR OVER-THE-COUNTER (OTC) HUMAN USE Active Ingredients § 331.15 Combination with nonantacid active ingredients. (a) An antacid may contain any generally...

21 CFR 349.30 - Permitted combinations of active ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Permitted combinations of active ingredients. 349... SERVICES (CONTINUED) DRUGS FOR HUMAN USE OPHTHALMIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 349.30 Permitted combinations of active ingredients. The following combinations are permitted...

21 CFR 331.15 - Combination with nonantacid active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Combination with nonantacid active ingredients... SERVICES (CONTINUED) DRUGS FOR HUMAN USE ANTACID PRODUCTS FOR OVER-THE-COUNTER (OTC) HUMAN USE Active Ingredients § 331.15 Combination with nonantacid active ingredients. (a) An antacid may contain any generally...

21 CFR 331.15 - Combination with nonantacid active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Combination with nonantacid active ingredients... SERVICES (CONTINUED) DRUGS FOR HUMAN USE ANTACID PRODUCTS FOR OVER-THE-COUNTER (OTC) HUMAN USE Active Ingredients § 331.15 Combination with nonantacid active ingredients. (a) An antacid may contain any generally...

21 CFR 349.30 - Permitted combinations of active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Permitted combinations of active ingredients. 349... SERVICES (CONTINUED) DRUGS FOR HUMAN USE OPHTHALMIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 349.30 Permitted combinations of active ingredients. The following combinations are permitted...

21 CFR 349.30 - Permitted combinations of active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Permitted combinations of active ingredients. 349... SERVICES (CONTINUED) DRUGS FOR HUMAN USE OPHTHALMIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 349.30 Permitted combinations of active ingredients. The following combinations are permitted...

21 CFR 349.30 - Permitted combinations of active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Permitted combinations of active ingredients. 349... SERVICES (CONTINUED) DRUGS FOR HUMAN USE OPHTHALMIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 349.30 Permitted combinations of active ingredients. The following combinations are permitted...

21 CFR 349.30 - Permitted combinations of active ingredients.

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. 349... SERVICES (CONTINUED) DRUGS FOR HUMAN USE OPHTHALMIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 349.30 Permitted combinations of active ingredients. The following combinations are permitted...

21 CFR 331.15 - Combination with nonantacid active ingredients.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Combination with nonantacid active ingredients... SERVICES (CONTINUED) DRUGS FOR HUMAN USE ANTACID PRODUCTS FOR OVER-THE-COUNTER (OTC) HUMAN USE Active Ingredients § 331.15 Combination with nonantacid active ingredients. (a) An antacid may contain any generally...

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.

21 CFR 358.310 - Ingrown toenail relief active ingredient.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Ingrown toenail relief active ingredient. 358.310 Section 358.310 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Toenail Relief Drug Products § 358.310 Ingrown toenail relief active ingredient. The active ingredient of...

21 CFR 358.310 - Ingrown toenail relief active ingredient.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Ingrown toenail relief active ingredient. 358.310 Section 358.310 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Toenail Relief Drug Products § 358.310 Ingrown toenail relief active ingredient. The active ingredient of...

21 CFR 358.310 - Ingrown toenail relief active ingredient.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Ingrown toenail relief active ingredient. 358.310 Section 358.310 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Toenail Relief Drug Products § 358.310 Ingrown toenail relief active ingredient. The active ingredient of...

21 CFR 358.310 - Ingrown toenail relief active ingredient.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Ingrown toenail relief active ingredient. 358.310 Section 358.310 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Toenail Relief Drug Products § 358.310 Ingrown toenail relief active ingredient. The active ingredient of...

21 CFR 358.310 - Ingrown toenail relief active ingredient.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Ingrown toenail relief active ingredient. 358.310 Section 358.310 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Toenail Relief Drug Products § 358.310 Ingrown toenail relief active ingredient. The active ingredient of...

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 the...

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 the...

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 Ingredients...

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

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

21 CFR 340.10 - Stimulant active ingredient.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Stimulant active ingredient. 340.10 Section 340.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE STIMULANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredient § 340.10...

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.

Pharmaceutical Cocrystals and Their Physicochemical Properties

PubMed Central

2009-01-01

Over the last 20 years, the number of publications outlining the advances in design strategies, growing techniques, and characterization of cocrystals has continued to increase significantly within the crystal engineering field. However, only within the last decade have cocrystals found their place in pharmaceuticals, primarily due to their ability to alter physicochemical properties without compromising the structural integrity of the active pharmaceutical ingredient (API) and thus, possibly, the bioactivity. This review article will highlight and discuss the advances made over the last 10 years pertaining to physical and chemical property improvements through pharmaceutical cocrystalline materials and, hopefully, draw closer the fields of crystal engineering and pharmaceutical sciences. PMID:19503732

Accelerated aging: prediction of chemical stability of pharmaceuticals.

PubMed

Waterman, Kenneth C; Adami, Roger C

2005-04-11

Methods of rapidly and accurately assessing the chemical stability of pharmaceutical dosage forms are reviewed with respect to the major degradation mechanisms generally observed in pharmaceutical development. Methods are discussed, with the appropriate caveats, for accelerated aging of liquid and solid dosage forms, including small and large molecule active pharmaceutical ingredients. In particular, this review covers general thermal methods, as well as accelerated aging methods appropriate to oxidation, hydrolysis, reaction with reactive excipient impurities, photolysis and protein denaturation.

21 CFR 341.40 - Permitted combinations of active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... ingredients, or any aspirin and antacid combination provided that the product is labeled according to § 341.85... combination of acetaminophen with other analgesic-antipyretic active ingredients, or any aspirin and antacid... other analgesic-antipyretic active ingredients, or any aspirin and antacid combination provided that the...

21 CFR 341.40 - Permitted combinations of active ingredients.

Code of Federal Regulations, 2010 CFR

2010-04-01

... ingredients, or any aspirin and antacid combination provided that the product is labeled according to § 341.85... combination of acetaminophen with other analgesic-antipyretic active ingredients, or any aspirin and antacid... other analgesic-antipyretic active ingredients, or any aspirin and antacid combination provided that the...

21 CFR 341.40 - Permitted combinations of active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

... ingredients, or any aspirin and antacid combination provided that the product is labeled according to § 341.85... combination of acetaminophen with other analgesic-antipyretic active ingredients, or any aspirin and antacid... other analgesic-antipyretic active ingredients, or any aspirin and antacid combination provided that the...

21 CFR 341.40 - Permitted combinations of active ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

... ingredients, or any aspirin and antacid combination provided that the product is labeled according to § 341.85... combination of acetaminophen with other analgesic-antipyretic active ingredients, or any aspirin and antacid... other analgesic-antipyretic active ingredients, or any aspirin and antacid combination provided that the...

21 CFR 341.40 - Permitted combinations of active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

... ingredients, or any aspirin and antacid combination provided that the product is labeled according to § 341.85... combination of acetaminophen with other analgesic-antipyretic active ingredients, or any aspirin and antacid... other analgesic-antipyretic active ingredients, or any aspirin and antacid combination provided that the...

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 active...

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... SERVICES (CONTINUED) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.16 Analgesic, anesthetic, and antipruritic active ingredients. The active ingredient of the...

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 active...

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... SERVICES (CONTINUED) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.16 Analgesic, anesthetic, and antipruritic active ingredients. The active ingredient of the...

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 active...

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... SERVICES (CONTINUED) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.16 Analgesic, anesthetic, and antipruritic active ingredients. The active ingredient of the...

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 active...

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 active...

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...

[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.

In-line UV spectroscopy for the quantification of low-dose active ingredients during the manufacturing of pharmaceutical semi-solid and liquid formulations.

PubMed

Bostijn, N; Hellings, M; Van Der Veen, M; Vervaet, C; De Beer, T

2018-07-12

UltraViolet (UV) spectroscopy was evaluated as an innovative Process Analytical Technology (PAT) - tool for the in-line and real-time quantitative determination of low-dosed active pharmaceutical ingredients (APIs) in a semi-solid (gel) and a liquid (suspension) pharmaceutical formulation during their batch production process. The performance of this new PAT-tool (i.e., UV spectroscopy) was compared with an already more established PAT-method based on Raman spectroscopy. In-line UV measurements were carried out with an immersion probe while for the Raman measurements a non-contact PhAT probe was used. For both studied formulations, an in-line API quantification model was developed and validated per spectroscopic technique. The known API concentrations (Y) were correlated with the corresponding in-line collected preprocessed spectra (X) through a Partial Least Squares (PLS) regression. Each developed quantification method was validated by calculating the accuracy profile on the basis of the validation experiments. Furthermore, the measurement uncertainty was determined based on the data generated for the determination of the accuracy profiles. From the accuracy profile of the UV- and Raman-based quantification method for the gel, it was concluded that at the target API concentration of 2% (w/w), 95 out of 100 future routine measurements given by the Raman method will not deviate more than 10% (relative error) from the true API concentration, whereas for the UV method the acceptance limits of 10% were exceeded. For the liquid formulation, the Raman method was not able to quantify the API in the low-dosed suspension (0.09% (w/w) API). In contrast, the in-line UV method was able to adequately quantify the API in the suspension. This study demonstrated that UV spectroscopy can be adopted as a novel in-line PAT-technique for low-dose quantification purposes in pharmaceutical processes. Important is that none of the two spectroscopic techniques was superior to the other

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... USE Corn and Callus Remover Drug Products § 358.510 Corn and callus remover active ingredients. The product consists of any of the following active ingredients within the specified concentrations and in the...

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... USE Corn and Callus Remover Drug Products § 358.510 Corn and callus remover active ingredients. The product consists of any of the following active ingredients within the specified concentrations and in the...

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... USE Corn and Callus Remover Drug Products § 358.510 Corn and callus remover active ingredients. The product consists of any of the following active ingredients within the specified concentrations and in the...

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... USE Corn and Callus Remover Drug Products § 358.510 Corn and callus remover active ingredients. The product consists of any of the following active ingredients within the specified concentrations and in the...

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...

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...

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

PubMed

Balk, Anja; Holzgrabe, Ulrike; Meinel, Lorenz

2015-08-01

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

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

PubMed

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

2009-02-15

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

Improved properties of fine active pharmaceutical ingredient powder blends and tablets at high drug loading via dry particle coating.

PubMed

Kunnath, Kuriakose; Huang, Zhonghui; Chen, Liang; Zheng, Kai; Davé, Rajesh

2018-05-30

It has been shown that dry coating cohesive active pharmaceutical ingredients (APIs) with nano-silica can improve packing and flow of their blends, facilitating high speed direct compression tableting. This paper examines the broader scope and generality of previous work by examining three fine APIs; micronized Acetaminophen (mAPAP), coarse Acetaminophen (cAPAP) and micronized Ibuprofen (mIBU), and considers dry coating with both hydrophobic or hydrophilic nano-silica to examine the effect not only on packing density and flow of their blends, but also dissolution and tensile strength of their tablets. The impact of the excipient size on blend and tablet properties are also investigated, indicating blend flow is most improved when matching API particle size with excipient particle size. In all cases where the API is dry coated, the blend packing and flow improve, so as to suggest such high drug loaded blends could enable direct compression. Using dry coated API along with finer excipients in blends lead to improved hardness of the corresponding tablets. Interestingly, dissolution profiles show dry coated API tablets generally have faster dissolution rates, regardless of silica hydrophilicity, suggesting API powder deagglomeration via nano-silica coating plays a crucial role. The most significant conclusion is that, although there are differences in properties of blends that depend on the API, hydrophobic or hydrophilic nano-silica coating, as well as large or fine excipients, in all cases, dry coating of APIs significantly improves the possibility of using the specific blend at high drug loading in direct compression tableting. Copyright © 2018 Elsevier B.V. All rights reserved.

[Recent advances of synthetic biology for production of functional ingredients in Chinese materia medica].

PubMed

Su, Xin-Yao; Xue, Jian-Ping; Wang, Cai-Xia

2016-11-01

The functional ingredients in Chinese materia medica are the main active substance for traditional Chinese medicine and most of them are secondary metabolites derivatives. Until now,the main method to obtain those functional ingredients is through direct extraction from the Chinese materia medica. However, the income is very low because of the high extraction costs and the decreased medicinal plants. Synthetic biology technology, as a new and microbial approach, can be able to carry out large-scale production of functional ingredients and greatly ease the shortage of traditional Chinese medicine ingredients. This review mainly focused on the recent advances in synthetic biology for the functional ingredients production. Copyright© by the Chinese Pharmaceutical Association.

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.

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.

21 CFR 333.320 - Permitted combinations of active ingredients.

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. 333... Topical Acne Drug Products § 333.320 Permitted combinations of active ingredients. (a) Resorcinol... of the user, the revised text is set forth as follows: § 333.320 Permitted combinations of active...

[Several changes of Indocalamus leaf active ingredients contents].

PubMed

Su, Chun-hua; Liu, Guo-hua; Wang, Fu-sheng; Ding, Yu-long; Xue, Jian-hui

2011-09-01

In this paper, the leaves of Indocalamus herklotsii, Indocalamus decorus, and Indocalamus latifolius were collected from Nanjing in different seasons to study the seasonal changes of the total flavonoids, tea polyphenols, and soluble sugar contents in the leaves. There existed significant differences in the test active ingredients contents among the leaves of the three Indocalamus species. The leaf total flavonoids content of the three Indocalamus species in different seasons ranged in 1.7%-2.7%, being the highest for I. herklotsii and I. decorus in spring and for I. latifolius in winter. The leaf tea polyphenols content varied from 5.5% to 7.6%; and the leaf soluble sugar content was 1.0%-8.5%, with the maximum in spring. Within the three months after leaf unfolding, the active ingredients contents in I. herklotsii and I. decorus leaves increased with leaf age. The optimal period for harvesting Indocalamus leaves was from December to next March. Among the three Indocalamus species, I. latifolius had the highest contents of the three active ingredients in leaves, suggesting that I. latifolius had greater potential value in the utilization of its leaf active ingredients than the other two species.

Application of ion chromatography in pharmaceutical and drug analysis.

PubMed

Jenke, Dennis

2011-08-01

Ion chromatography (IC) has developed and matured into an important analytical methodology in a number of diverse applications and industries, including pharmaceuticals. This manuscript provides a review of IC applications for the determinations of active and inactive ingredients, excipients, degradation products, and impurities relevant to pharmaceutical analyses and thus serves as a resource for investigators looking for insights into the use of the IC methodology in this field of application.

[Effects of Betel shisanwei ingredients pill on AC-cAMP-PKA signal transduction pathways in hippocampus and prefrontal cortex of depressive rats].

PubMed

Tong, Hai-Ying; Wu, Jisiguleng; Bai, Liang-Feng; Bao, Wu-Ye; Hu, Rilebagen; Li, Jing; Zhang, Yue

2014-05-01

To observe the effects of Mongolian pharmaceutical Betel shisanwei ingredients pill on AC-cAMP-PKA signal transduction pathways in hippocampus and prefrontal cortex of depressive rats. Sixty male Wistar rats were randomly divided into six groups according to the sugar consumption test (10 rats in each group), normal control group,model group,fluoxetine group (3.3 mg x kg(-1)) and low dose, medium dose and high dose group (0.25, 0.5, 1 g x kg(-1)) of Betel shisanwei ingredients pill. Except the normal control,the other groups were treated with the chronic unpredictable mild stress stimulation combined with lonely raising for 28 days. 10 mL x kg(-1) of drugs were given to each rat once daily,continuously for 28 days. The AC activity of the hippocampus and prefrontal cortex were determined by radiation immunity analysis (RIA), while cAMP and PKA quantity were determinated by Enzyme-linked immunosorbent (ELISA). The AC activity, cAMP and PKA quantity of hippocampus and prefrontal of mouse model of Chronic stress depression decreased significantly than those of control group (P < 0.05 or P < 0.01). However, the AC activity, cAMP and PKA quantity of rat hippocampus and prefrontal cortex in the fluoxetine group and the Mongolian pharmaceutical Betel shisanwei ingredients pill group indecreased significantly than those of model group (P < 0.01 or P < 0.05). Especially for the high dose group of Mongolian pharmaceutical Betel shisanwei ingredients pill. The AC-cAMP-PKA signal transduction pathways in hippocampus and prefrontal cortex of depression model of rats is down-regulated, whereas Mongolian pharmaceutical Betel shisanwei ingredients pill could up-regulated it to resist depression.

Choleretic Activity of Turmeric and its Active Ingredients.

PubMed

Wang, Yonglu; Wang, Liyao; Zhu, Xinyi; Wang, Dong; Li, Xueming

2016-07-01

Turmeric, a rhizome of Curcumin longa L. is widely used as both a spice and an herbal medicine. The traditional use of turmeric in gastroenterology is mainly based on its choleretic activity. The aim of this study is to determine the effects of turmeric on bile flow (BF) and total bile acids (TBAs) excretion in a bile fistula rat model after acute duodenal administration. A significant dose-dependent enhancement in both BF and TBAs was detected after treatment with the turmeric decoctions which suggested the choleretic activity was bile acid-dependent secretion. In order to direct the active group of compounds, aqueous (AE), ethyl acetate (EtOAc), and petroleum ether (PE) extracts were investigated. The EtOAc and PE extracts showing high effects were purified to locate the active ingredients. Three curcuminoids (curcumin, demethoxycurcumin, and bisdemethoxycurcumin) and 2 sesquiterpenes (bisacurone B and ar-turmerone) were isolated. It was found Bisacurone B was the most potent choleretic ingredient followed by ar-turmerone, bisdemethoxycurcumin demethoxycurcumin, and then curcumin. The amounts of the active ingredients were quantitatively analyzed by high-performance liquid chromatography. The EtOAc and PE extracts had high sesquiterpenes and curcuminoids content, while the AE extract had poor content of sesquiterpenes and curcuminoids which affected neither BF nor TBAs. Based on the results of multiple linear regression analysis, the content of BIS and TUR were dominant factors (P < 0.01) of controlling BL and TBAs in EtOAC and PE extracts. © 2016 Institute of Food Technologists®

[The introduction of generic pharmaceutical products into Galicia].

PubMed

Verdejo González, A; López-Lázaro, L; Rodríguez Moreno, C; Piñeiro Lago, B; Pereira Martínez, M L

1999-11-30

To know the evolution of the introduction of generic drugs (GDs) in Galicia. Secondarily, to evaluate its potential impact on pharmaceutical expenditure. Descriptive study of GDs utilization. Cost-minimization analysis. Galician autonomous region, year 1998. Using data from the prescription billing registry of Social Security we have selected the active ingredients corresponding to GDs with prescriptions in Galicia in 1997. We have analyzed the data for their oral single substance preparations by quarters. Consumption in DHDs of allopurinol, atenolol, captopril, naproxen and ranitidine remained stable during 1998. The market share for their GDs in quantitative terms relative to both total consumption of the active ingredients and to their pharmaceutical equivalents, showed an overall growing trend. The maximum observed value was seen for ranitidine at last quarter. Total expenditure (in final customer prices) during 1998 on the selected active substances was higher than 1864 million pesetas. Potential savings afforded by substitution for the lowest price GD prescribed in Galicia would reach 427 million pesetas. GDs market penetration in Galicia during 1998 was limited but increasing. Its utilization may afford estimated savings of 21-28% of the cost for the selected drugs. However, the expenditure on the above drugs was just 2.7% of total pharmaceutical expenditure.

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

21 CFR 333.320 - Permitted combinations of active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Permitted combinations of active ingredients. 333.320 Section 333.320 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Topical Acne Drug Products § 333.320 Permitted combinations of active ingredients. (a) Resorcinol...

21 CFR 333.320 - Permitted combinations of active ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Permitted combinations of active ingredients. 333.320 Section 333.320 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Topical Acne Drug Products § 333.320 Permitted combinations of active ingredients. (a) Resorcinol...

21 CFR 333.320 - Permitted combinations of active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Permitted combinations of active ingredients. 333.320 Section 333.320 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Topical Acne Drug Products § 333.320 Permitted combinations of active ingredients. (a) Resorcinol...

21 CFR 333.320 - Permitted combinations of active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Permitted combinations of active ingredients. 333.320 Section 333.320 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Topical Acne Drug Products § 333.320 Permitted combinations of active ingredients. (a) Resorcinol...

Availability, Pharmaceutics, Security, Pharmacokinetics, and Pharmacological Activities of Patchouli Alcohol.

PubMed

Hu, Guanying; Peng, Cheng; Xie, Xiaofang; Zhang, Sanyin; Cao, Xiaoyu

2017-01-01

Patchouli alcohol (PA), a tricyclic sesquiterpene, is one of the critical bioactive ingredients and is mainly isolated from aerial part of Pogostemon cablin (known as guanghuoxiang in China) belonging to Labiatae. So far, PA has been widely applied in perfume industries. This review was written with the use of reliable information published between 1974 and 2016 from libraries and electronic researches including NCKI, PubMed, Reaxys, ACS, ScienceDirect, Springer, and Wiley-Blackwell, aiming at presenting comprehensive outline of security, pharmacokinetics, and bioactivities of PA and at further providing a potential guide in exploring the PA and its use in various medical fields. We found that PA maybe was a low toxic drug that was acquired numerously through vegetable oil isolation and chemical synthesis and its stability and low water dissolution were improved in pharmaceutics. It also possessed specific pharmacokinetic characteristics, such as two-compartment open model, first-order kinetic elimination, and certain biometabolism and biotransformation process, and was shown to have multiple biological activities, that is, immunomodulatory, anti-inflammatory, antioxidative, antitumor, antimicrobial, insecticidal, antiatherogenic, antiemetic, whitening, and sedative activity. However, the systematic evaluations of preparation, pharmaceutics, toxicology, pharmacokinetics, and bioactivities underlying molecular mechanisms of action also required further investigation prior to practices of PA in clinic.

Availability, Pharmaceutics, Security, Pharmacokinetics, and Pharmacological Activities of Patchouli Alcohol

PubMed Central

Hu, Guanying; Xie, Xiaofang; Cao, Xiaoyu

2017-01-01

Patchouli alcohol (PA), a tricyclic sesquiterpene, is one of the critical bioactive ingredients and is mainly isolated from aerial part of Pogostemon cablin (known as guanghuoxiang in China) belonging to Labiatae. So far, PA has been widely applied in perfume industries. This review was written with the use of reliable information published between 1974 and 2016 from libraries and electronic researches including NCKI, PubMed, Reaxys, ACS, ScienceDirect, Springer, and Wiley-Blackwell, aiming at presenting comprehensive outline of security, pharmacokinetics, and bioactivities of PA and at further providing a potential guide in exploring the PA and its use in various medical fields. We found that PA maybe was a low toxic drug that was acquired numerously through vegetable oil isolation and chemical synthesis and its stability and low water dissolution were improved in pharmaceutics. It also possessed specific pharmacokinetic characteristics, such as two-compartment open model, first-order kinetic elimination, and certain biometabolism and biotransformation process, and was shown to have multiple biological activities, that is, immunomodulatory, anti-inflammatory, antioxidative, antitumor, antimicrobial, insecticidal, antiatherogenic, antiemetic, whitening, and sedative activity. However, the systematic evaluations of preparation, pharmaceutics, toxicology, pharmacokinetics, and bioactivities underlying molecular mechanisms of action also required further investigation prior to practices of PA in clinic. PMID:28421121

Chemometrically assisted development and validation of LC-MS/MS method for the analysis of potential genotoxic impurities in meropenem active pharmaceutical ingredient.

PubMed

Grigori, Katerina; Loukas, Yannis L; Malenović, Anđelija; Samara, Vicky; Kalaskani, Anastasia; Dimovasili, Efi; Kalovidouri, Magda; Dotsikas, Yannis

2017-10-25

A sensitive Liquid Chromatography tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantitative analysis of three potential genotoxic impurities (318BP, M9, S5) in meropenem Active Pharmaceutical Ingredient (API). Due to the requirement for LOD values in ppb range, a high concentration of meropenem API (30mg/mL) had to be injected. Therefore, efficient determination of meropenem from its impurities became a critical aim of this study, in order to divert meropenem to waste, via a switching valve. ‎ After the selection of the important factors affecting analytes' elution, a Box-Behnken design was utilized to set the plan of experiments conducted with UV detector. As responses, the separation factor s between the last eluting impurity and meropenem, as well as meropenem retention factor k were used. Grid point search methodology was implemented aiming to obtain the optimal conditions that simultaneously comply to the conflicted criteria. Optimal mobile phase consisted of ACN, methanol and 0.09% HCOOH at a ratio 71/3.5/15.5v/v. All impurities and internal standard omeprazole were eluted before 7.5min and at 8.0min the eluents were directed to waste. The protocol was transferred to LC-MS/MS and validated according to ICH guidelines. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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.

Ionic Liquid-Like Pharmaceutical Ingredients and Applications of Ionic Liquids in Medicinal Chemistry: Development, Status and Prospects.

PubMed

Tang, Jie; Song, Hang; Feng, Xueting; Yohannes, Alula; Yao, Shun

2018-06-05

As a new kind of green media and bioactive compounds with special structure, ionic liquids (ILs) are attracting much attention and applied widely in many fields. However, their roles and potential have not been fully recognized by many researchers of medicinal chemistry. Because of obvious differences from other traditional drugs and reagents, their uses and performance together with advantages and disadvantages need to be explored and reviewed in detail. For systematic and explicit description of the relationship between ILs and medicinal chemistry, all of the contents were elucidated and summarized in a series of independent parts. In each part, it started from the research background or a conceptual framework and then specific examples were introduced to illustrate the theme. Finally, the important conclusions were drawn and its future was outlooked after the discussion about related key problems appearing in each mentioned research. Meanwhile, methodologies such as empirical analysis, comparison and induction were applied in different sections to exposit our subject. The whole review was composed of five parts, and 148 papers were cited in total. Related basic information of ionic liquids was provided on the basis of representative references, including their concepts and important characters. Then 82 papers outlined ionic liquid-like active pharmaceutical ingredients, which unfolded with their major biological activities (antimicrobial activity, antibiofilm activity, antitumor activity, anticholinesterase activity and so on). Applications of ionic liquids in synthesis of drugs and pharmaceutical intermediates were elaborated in 92 papers to illustrate the important roles of ILs and their extraordinary properties in this field. Moreover, new technologies (such as immobilization of IL, microwave reaction, solvent-free synthesis, microreactor, etc) were introduced for further innovation. Finally, 26 papers were included to expound the status about the IL

77 FR 48519 - Registration Applications for Pesticide Products Containing New Active Ingredients

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-14

... Pesticide Products Containing New Active Ingredients AGENCY: Environmental Protection Agency (EPA). ACTION... new active ingredients not included in any currently registered products pursuant to the provisions of... as follows to register pesticide products containing active ingredients not included in any...

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…

Applications of Quantum Cascade Laser Spectroscopy in the Analysis of Pharmaceutical Formulations.

PubMed

Galán-Freyle, Nataly J; Pacheco-Londoño, Leonardo C; Román-Ospino, Andrés D; Hernandez-Rivera, Samuel P

2016-09-01

Quantum cascade laser spectroscopy was used to quantify active pharmaceutical ingredient content in a model formulation. The analyses were conducted in non-contact mode by mid-infrared diffuse reflectance. Measurements were carried out at a distance of 15 cm, covering the spectral range 1000-1600 cm(-1) Calibrations were generated by applying multivariate analysis using partial least squares models. Among the figures of merit of the proposed methodology are the high analytical sensitivity equivalent to 0.05% active pharmaceutical ingredient in the formulation, high repeatability (2.7%), high reproducibility (5.4%), and low limit of detection (1%). The relatively high power of the quantum-cascade-laser-based spectroscopic system resulted in the design of detection and quantification methodologies for pharmaceutical applications with high accuracy and precision that are comparable to those of methodologies based on near-infrared spectroscopy, attenuated total reflection mid-infrared Fourier transform infrared spectroscopy, and Raman spectroscopy. © The Author(s) 2016.

21 CFR 332.15 - Combination with non-antiflatulent active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Combination with non-antiflatulent active... SERVICES (CONTINUED) DRUGS FOR HUMAN USE ANTIFLATULENT PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 332.15 Combination with non-antiflatulent active ingredients. An antiflatulent may contain any...

21 CFR 332.15 - Combination with non-antiflatulent active ingredients.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Combination with non-antiflatulent active... SERVICES (CONTINUED) DRUGS FOR HUMAN USE ANTIFLATULENT PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 332.15 Combination with non-antiflatulent active ingredients. An antiflatulent may contain any...

21 CFR 332.15 - Combination with non-antiflatulent active ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Combination with non-antiflatulent active... SERVICES (CONTINUED) DRUGS FOR HUMAN USE ANTIFLATULENT PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 332.15 Combination with non-antiflatulent active ingredients. An antiflatulent may contain any...

21 CFR 332.15 - Combination with non-antiflatulent active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Combination with non-antiflatulent active... SERVICES (CONTINUED) DRUGS FOR HUMAN USE ANTIFLATULENT PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 332.15 Combination with non-antiflatulent active ingredients. An antiflatulent may contain any...

21 CFR 332.15 - Combination with non-antiflatulent active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Combination with non-antiflatulent active... SERVICES (CONTINUED) DRUGS FOR HUMAN USE ANTIFLATULENT PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 332.15 Combination with non-antiflatulent active ingredients. An antiflatulent may contain any...

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.

X-ray powder diffractometry of intact film coated tablets--an approach to monitor the physical form of the active pharmaceutical ingredient during processing and storage.

PubMed

Yamada, Hiroyuki; Suryanarayanan, Raj

2007-08-01

The antiviral compound, 2-amino-6-(4-methoxyphenylthio)-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl)ester (MCC-478), can exist in several anhydrous polymorphic forms and also as a hemihydrate. The XRD patterns of the tablets, containing each form of the active pharmaceutical ingredient (API), revealed at least one peak unique to each form. A semiquantitative microdiffractometric method was developed to nondestructively characterize the physical form of the API in intact film-coated tablets. This was accomplished even though the weight fraction of the API was <0.2 and that of mannitol, a highly crystalline excipient, was approximately 0.6. The method was used to determine the effect of aqueous film-coating process on the physical form of the API. The final dosage form was also monitored following storage at 40 degrees C/75% RH for 6 months. There was no phase transformation of the API either due to the film-coating process or following accelerated storage. This technique has potential utility not only for process control during manufacture, but also for the quality control of the final product. (c) 2007 Wiley-Liss, Inc. and the American Pharmacists Association.

21 CFR 346.22 - Permitted combinations of anorectal active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Permitted combinations of anorectal active... SERVICES (CONTINUED) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.22 Permitted combinations of anorectal active ingredients. (a) Any two, three, or four...

21 CFR 346.22 - Permitted combinations of anorectal active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Permitted combinations of anorectal active... SERVICES (CONTINUED) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.22 Permitted combinations of anorectal active ingredients. (a) Any two, three, or four...

21 CFR 346.22 - Permitted combinations of anorectal active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Permitted combinations of anorectal active... SERVICES (CONTINUED) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.22 Permitted combinations of anorectal active ingredients. (a) Any two, three, or four...

Development and Justification of a Risk Evaluation Matrix To Guide Chemical Testing Necessary To Select and Qualify Plastic Components Used in Production Systems for Pharmaceutical Products.

PubMed

Jenke, Dennis

2015-01-01

An accelerating trend in the pharmaceutical industry is the use of plastic components in systems used to produce an active pharmaceutical ingredient or a finished drug product. If the active pharmaceutical ingredient, the finished drug product, or any solution used to generate them (for example, a process stream such as media, buffers, eluents, and the like) is contacted by a plastic component at any time during the production process, substances leached from the component may accumulate in the active pharmaceutical ingredient or finished drug product, affecting its safety and/or efficacy. In this article the author develops and justifies a semi-quantitative risk evaluation matrix that is used to determine the amount and rigor of component testing necessary and appropriate to establish that the component is chemically suitable for its intended use. By considering key properties of the component, the contact medium, the contact conditions, and the active pharmaceutical ingredient's or finished drug product's clinical conditions of use, use of the risk evaluation matrix produces a risk score whose magnitude reflects the accumulated risk that the component will interact with the contact solution to such an extent that component-related extractables will accumulate in the active pharmaceutical ingredient or finished drug product as leachables at levels sufficiently high to adversely affect user safety. The magnitude of the risk score establishes the amount and rigor of the testing that is required to select and qualify the component, and such testing is broadly grouped into three categories: baseline assessment, general testing, and full testing (extractables profiling). Production suites used to generate pharmaceuticals can include plastic components. It is possible that substances in the components could leach into manufacturing solutions and accumulate in the pharmaceutical product. In this article the author develops and justifies a semi-quantitative risk

[Injectable hospital preparation of valine labeled with the carbon 13 and nitrogen 15 (5 mg/mL) for a clinical trial on the brain tumor metabolism: Pharmaceutical control of active pharmaceutical ingredient and stability study of the finished product].

PubMed

Tall, M L; Diouf, E; Filali, S; Sauvinet, V; Laleye, D; Dhelens, C; Salmon, D; Gabert, L; Nugue, G; Sandre-Balester, C; Berger, F; Pirot, F; Pivot, C

2015-09-01

The L-Valine labeled (L-[U-(13)C,(15)N] Val) is a stable isotopic tracer administered by parenteral route within the framework of a new clinical research program concerning the brain tumor metabolism. To meet regulatory requirements and have ready to use solution with an expiration date, a pharmaceutical control of active pharmaceutical ingredient followed by stability study of hospital preparation were realised. After the pharmaceutical control of the L-[U-(13)C,(15)N] Val, the hospital preparation was prepared according to the good manufacturing preparation. Prepared bottles were stored at 5°C±3°C and 25°C±2°C for six months. The stability of the preparation was determined by physico-chemical controls (pH, osmolality, sub-visible particles, L-[U-(13)C,(15)N] Val concentration, sodium concentration, isotopic enrichment) and microbiological (bacterial endotoxin and sterility). Concentrations of L-[U-(13)C, (15)N] Val and sodium does not significantly decrease during the stability study. In parallel, no change in pH and osmolality were highlighted. Isotopic enrichment higher than 99.9% reflected the stability of labeling of L-valine molecule. The sub-visible particles, the bacterial endotoxin and sterility were in accordance with the European Pharmacopoeia attesting limpidity, apyrogenicity and sterility of this injectable preparation. The stability of this hospital preparation of L-[U-(13)C, (15)N] Val has been demonstrated for six months at 5°C±3°C and 25°C±2°C, ensuring a parenteral administration as part of the clinical trial. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

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.

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. © 2011 Pharmaceutical Society of Japan

Organic solvents in the pharmaceutical industry.

PubMed

Grodowska, Katarzyna; Parczewski, Andrzej

2010-01-01

Organic solvents are commonly used in the pharmaceutical industry as reaction media, in separation and purification of synthesis products and also for cleaning of equipment. This paper presents some aspects of organic solvents utilization in an active pharmaceutical ingredient and a drug product manufacturing process. As residual solvents are not desirable substances in a final product, different methods for their removal may be used, provided they fulfill safety criteria. After the drying process, analyses need to be performed to check if amounts of solvents used at any step of the production do not exceed acceptable limits (taken from ICH Guideline or from pharmacopoeias). Also new solvents like supercritical fluids or ionic liquids are developed to replace "traditional" organic solvents in the pharmaceutical production processes.

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

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-11

...; 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... products containing active ingredients not included in any currently registered pesticide products...

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 ...

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.

Engineering yeast metabolism for production of terpenoids for use as perfume ingredients, pharmaceuticals and biofuels.

PubMed

Zhang, Yueping; Nielsen, Jens; Liu, Zihe

2017-12-01

Terpenoids represent a large class of natural products with significant commercial applications. These chemicals are currently mainly obtained through extraction from plants and microbes or through chemical synthesis. However, these sources often face challenges of unsustainability and low productivity. In order to address these issues, Escherichia coli and yeast have been metabolic engineered to produce non-native terpenoids. With recent reports of engineering yeast metabolism to produce several terpenoids at high yields, it has become possible to establish commercial yeast production of terpenoids that find applications as perfume ingredients, pharmaceuticals and advanced biofuels. In this review, we describe the strategies to rewire the yeast pathway for terpenoid biosynthesis. Recent advances will be discussed together with challenges and perspectives of yeast as a cell factory to produce different terpenoids. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Internal wall losses of pharmaceutical dusts during closed-face, 37-mm polystyrene cassette sampling.

PubMed

Puskar, M A; Harkins, J M; Moomey, J D; Hecker, L H

1991-07-01

A current practice for the determination of personal exposures to dusts involves the aspiration of known quantities of air through membrane filters held in 37-mm plastic cassettes. Samples are collected with the cassettes in the closed-face configuration. A major negative bias error has been identified with this sampling procedure for low-level pharmaceutical dusts. For the pharmaceuticals studied, on average, 62% of the active dust collected in each sample was found on the inside surface of the cassette top. Only 22% of the total active ingredient of the dust was found on the filters. The remaining 16% was found on the inside of the cassette bottoms; electrostatic attraction appears to be the reason that pharmaceutical dusts adhere to the inside surface of the cassette. Adherence to the inside surfaces of the polystyrene cassette occurs without regard to the type of material used to seal the two-piece cassette together. The use of shrink wrap versus plastic tape versus using no sealing material had no effect on where or how much of the active ingredient was found on the inside cassette surfaces. Because very little active ingredient was identified in backup cassettes, it is hypothesized that the active ingredient found on the inside of the bottom portion of the cassettes (past the filter and support pad) got there by falling off the filter during filter removal from the cassette prior to analysis. To eliminate both of these errors, an internal cassette extraction procedure was developed that (1) negates the error caused by static charging and (2) eliminates the need for opening the cassettes prior to analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

21 CFR 331.20 - Determination of percent contribution of active ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Determination of percent contribution of active... Procedures § 331.20 Determination of percent contribution of active ingredients. To determine the percent contribution of an antacid active ingredient, place an accurately weighed amount of the antacid active...

21 CFR 331.20 - Determination of percent contribution of active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Determination of percent contribution of active... Procedures § 331.20 Determination of percent contribution of active ingredients. To determine the percent contribution of an antacid active ingredient, place an accurately weighed amount of the antacid active...

21 CFR 331.20 - Determination of percent contribution of active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Determination of percent contribution of active... Procedures § 331.20 Determination of percent contribution of active ingredients. To determine the percent contribution of an antacid active ingredient, place an accurately weighed amount of the antacid active...

21 CFR 331.20 - Determination of percent contribution of active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Determination of percent contribution of active... Procedures § 331.20 Determination of percent contribution of active ingredients. To determine the percent contribution of an antacid active ingredient, place an accurately weighed amount of the antacid active...

Assessment of the anaerobic degradation of six active pharmaceutical ingredients.

PubMed

Musson, Stephen E; Campo, Pablo; Tolaymat, Thabet; Suidan, Makram; Townsend, Timothy G

2010-04-01

Research examined the anaerobic degradation of 17 alpha-ethynylestradiol, acetaminophen, acetylsalicylic acid, ibuprofen, metoprolol tartrate, and progesterone by methanogenic bacteria. Using direct sample analysis and respirometric testing, anaerobic degradation was examined with (a) each compound as the sole organic carbon source and (b) each compound at a lower concentration (250 microg/L) and cellulose serving as the primary organic carbon source. The change in pharmaceutical concentration was determined following 7, 28, 56, and 112 days of anaerobic incubation at 37 degrees C. Only acetylsalicylic acid demonstrated significant degradation; the remaining compounds showed a mixture of degradation and abiotic removal mechanisms. Experimental results were compared with BIOWIN, an anaerobic degradation prediction model of the US Environmental Protection Agency. The BIOWIN model predicted anaerobic biodegradability of the compounds in the order: acetylsalicylic acid > metoprolol tartrate > ibuprofen > acetaminophen > 17 alpha-ethinylestradiol >progesterone. This corresponded well with the experimental findings which found degradability in the order: acetylsalicylic acid > metoprolol tartrate > acetaminophen > ibuprofen. (c) 2010 Elsevier B.V. All rights reserved.

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 by their bodies, and excreted through urine or feces. However, it has been estimated that somewhere between 30 and 90% of administered active ingredients pass through the human and anima...

Pesticide Active Ingredients

Science.gov Websites

; Environment Human Health Animal Health Safe Use Practices Food Safety Environment Air Water Soil Wildlife Ingredients Low-Risk Pesticides Organic Pesticide Ingredients Pesticide Incidents Human Exposure Pet Exposure :00PM Pacific Time, Mon-Fri A B C D E F G H I J K L M N O P Q R S T U V W X Y Z A-Z Index Health &

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

PubMed

Casanova, Francisca; Santos, Lúcia

2016-02-01

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

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...

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. The...

Anthocyanidins and anthocyanins: colored pigments as food, pharmaceutical ingredients, and the potential health benefits.

PubMed

Khoo, Hock Eng; Azlan, Azrina; Tang, Sou Teng; Lim, See Meng

2017-01-01

Anthocyanins are colored water-soluble pigments belonging to the phenolic group. The pigments are in glycosylated forms. Anthocyanins responsible for the colors, red, purple, and blue, are in fruits and vegetables. Berries, currants, grapes, and some tropical fruits have high anthocyanins content. Red to purplish blue-colored leafy vegetables, grains, roots, and tubers are the edible vegetables that contain a high level of anthocyanins. Among the anthocyanin pigments, cyanidin-3-glucoside is the major anthocyanin found in most of the plants. The colored anthocyanin pigments have been traditionally used as a natural food colorant. The color and stability of these pigments are influenced by pH, light, temperature, and structure. In acidic condition, anthocyanins appear as red but turn blue when the pH increases. Chromatography has been largely applied in extraction, separation, and quantification of anthocyanins. Besides the use of anthocyanidins and anthocyanins as natural dyes, these colored pigments are potential pharmaceutical ingredients that give various beneficial health effects. Scientific studies, such as cell culture studies, animal models, and human clinical trials, show that anthocyanidins and anthocyanins possess antioxidative and antimicrobial activities, improve visual and neurological health, and protect against various non-communicable diseases. These studies confer the health effects of anthocyanidins and anthocyanins, which are due to their potent antioxidant properties. Different mechanisms and pathways are involved in the protective effects, including free-radical scavenging pathway, cyclooxygenase pathway, mitogen-activated protein kinase pathway, and inflammatory cytokines signaling. Therefore, this review focuses on the role of anthocyanidins and anthocyanins as natural food colorants and their nutraceutical properties for health. Abbreviations : CVD: Cardiovascular disease VEGF: Vascular endothelial growth factor.

Anthocyanidins and anthocyanins: colored pigments as food, pharmaceutical ingredients, and the potential health benefits

PubMed Central

Khoo, Hock Eng; Azlan, Azrina; Tang, Sou Teng; Lim, See Meng

2017-01-01

ABSTRACT Anthocyanins are colored water-soluble pigments belonging to the phenolic group. The pigments are in glycosylated forms. Anthocyanins responsible for the colors, red, purple, and blue, are in fruits and vegetables. Berries, currants, grapes, and some tropical fruits have high anthocyanins content. Red to purplish blue-colored leafy vegetables, grains, roots, and tubers are the edible vegetables that contain a high level of anthocyanins. Among the anthocyanin pigments, cyanidin-3-glucoside is the major anthocyanin found in most of the plants. The colored anthocyanin pigments have been traditionally used as a natural food colorant. The color and stability of these pigments are influenced by pH, light, temperature, and structure. In acidic condition, anthocyanins appear as red but turn blue when the pH increases. Chromatography has been largely applied in extraction, separation, and quantification of anthocyanins. Besides the use of anthocyanidins and anthocyanins as natural dyes, these colored pigments are potential pharmaceutical ingredients that give various beneficial health effects. Scientific studies, such as cell culture studies, animal models, and human clinical trials, show that anthocyanidins and anthocyanins possess antioxidative and antimicrobial activities, improve visual and neurological health, and protect against various non-communicable diseases. These studies confer the health effects of anthocyanidins and anthocyanins, which are due to their potent antioxidant properties. Different mechanisms and pathways are involved in the protective effects, including free-radical scavenging pathway, cyclooxygenase pathway, mitogen-activated protein kinase pathway, and inflammatory cytokines signaling. Therefore, this review focuses on the role of anthocyanidins and anthocyanins as natural food colorants and their nutraceutical properties for health. Abbreviations: CVD: Cardiovascular disease VEGF: Vascular endothelial growth factor PMID:28970777

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

PubMed

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.

Prioritization of pharmaceuticals based on risks to aquatic environments in Kazakhstan.

PubMed

Aubakirova, Bakhyt; Beisenova, Raikhan; Boxall, Alistair Ba

2017-09-01

Over the last 20 years, there has been increasing interest in the occurrence, fate, effects, and risk of pharmaceuticals in the natural environment. However, we still have only limited or no data on ecotoxicological risks of many of the active pharmaceutical ingredients (APIs) currently in use. This is partly due to the fact that the environmental assessment of an API is an expensive, time-consuming, and complicated process. Prioritization methodologies, which aim to identify APIs of most concern in a particular situation, could therefore be invaluable in focusing experimental work on APIs that really matter. The majority of approaches for prioritizing APIs require annual pharmaceutical usage data. These methods cannot therefore be applied to countries, such as Kazakhstan, that have very limited data on API usage. The present paper therefore offers an approach for prioritizing APIs in surface waters in information-poor regions such as Kazakhstan. Initially data were collected on the number of products and active ingredients for different therapeutic classes in use in Kazakhstan and on the typical doses. These data were then used alongside simple exposure modeling approaches to estimate exposure indices for active ingredients (about 240 APIs) in surface waters in the country. Ecotoxicological effects data were obtained from the literature or predicted. Risk quotients were then calculated for each pharmaceutical based on the exposure and the substances were ranked in order of risk quotient. Highest exposure indices were obtained for benzylpenicillin, metronidazole, sulbactam, ceftriaxone, and sulfamethoxazole. The highest risk was estimated for amoxicillin, clarithromycin, azithromycin, ketoconazole, and benzylpenicillin. In the future, the approach could be employed in other regions where usage information is limited. Integr Environ Assess Manag 2017;13:832-839. © 2017 SETAC. © 2017 SETAC.

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

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Labeling of permitted combinations of active... Labeling § 347.60 Labeling of permitted combinations of active ingredients. The statement of identity.... (1) Combinations of skin protectant and external analgesic active ingredients in § 347.20(b). In...

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

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Labeling of permitted combinations of active... Labeling § 347.60 Labeling of permitted combinations of active ingredients. The statement of identity.... (1) Combinations of skin protectant and external analgesic active ingredients in § 347.20(b). In...

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

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Labeling of permitted combinations of active... Labeling § 347.60 Labeling of permitted combinations of active ingredients. The statement of identity.... (1) Combinations of skin protectant and external analgesic active ingredients in § 347.20(b). In...

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...

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... HUMAN USE Deodorant Drug Products for Internal Use § 357.810 Active ingredients for deodorant drug products for internal use. The active ingredient of the product consists of either of the following when...

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... HUMAN USE Deodorant Drug Products for Internal Use § 357.810 Active ingredients for deodorant drug products for internal use. The active ingredient of the product consists of either of the following when...

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... HUMAN USE Deodorant Drug Products for Internal Use § 357.810 Active ingredients for deodorant drug products for internal use. The active ingredient of the product consists of either of the following when...

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... HUMAN USE Deodorant Drug Products for Internal Use § 357.810 Active ingredients for deodorant drug products for internal use. The active ingredient of the product consists of either of the following when...

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... HUMAN USE Deodorant Drug Products for Internal Use § 357.810 Active ingredients for deodorant drug products for internal use. The active ingredient of the product consists of either of the following when...

Sorption of active pharmaceutical ingredients in untreated wastewater effluent and effect of dilution in freshwater: Implications for an "impact zone" environmental risk assessment approach.

PubMed

Bagnis, Simone; Fitzsimons, Mark; Snape, Jason; Tappin, Alan; Comber, Sean

2018-05-15

Evidence of ecotoxicological effects of active pharmaceuticals ingredients (APIs) has increased research into their environmental fate. In low and low-middle income countries (LLMICs) the main source of APIs to surface waters is from discharge of untreated wastewater. Consequently, concentrations of APIs can be relatively high in the "impact zone" downstream of a discharge point. Little is known about the fate of APIs in these impact zones. In this laboratory scale investigation, the effect of successive dilution of synthetic untreated wastewater (dilution factor 1 to 10) on the distribution of APIs was studied. The sorption was consistent with the chemical properties of each compound: charge, lipophilicity, and structure. Dilution increased desorption of the basic and neutral APIs (up to 27.7%) and correlated with their lipophilicity (R 2 >0.980); the positive charge was of secondary importance. Anions did not significantly desorb (<10% loss). Increased concentrations of dissolved organic matter at dilutions of 8 and 10 times that of untreated wastewater coincided with lower dissolved API concentrations. The data showed a clear trend in the desorption process of APIs that may lead to higher exposure risk than anticipated. Therefore, it is suggested that these aspects should be accounted for in the development of dedicated environmental risk assessment approach for APIs in riverine impact zones of LLMICs countries. Copyright © 2017 Elsevier B.V. All rights reserved.

78 FR 10167 - Pesticide Products; Registration Applications for a New Active Ingredient

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-13

...; Registration Applications for a New Active Ingredient AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY: EPA has received applications to register pesticide products containing an active... applications to register pesticide products containing an active ingredient not included in any currently...

21 CFR 352.60 - Labeling of permitted combinations of active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Labeling of permitted combinations of active ingredients. 352.60 Section 352.60 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... INDEFINITELY] Labeling § 352.60 Labeling of permitted combinations of active ingredients. Statements of...

21 CFR 349.79 - Labeling of permitted combinations of active ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Labeling of permitted combinations of active ingredients. 349.79 Section 349.79 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... § 349.79 Labeling of permitted combinations of active ingredients. Statements of identity, indications...

21 CFR 352.60 - Labeling of permitted combinations of active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Labeling of permitted combinations of active ingredients. 352.60 Section 352.60 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... INDEFINITELY] Labeling § 352.60 Labeling of permitted combinations of active ingredients. Statements of...

21 CFR 349.79 - Labeling of permitted combinations of active ingredients.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of permitted combinations of active ingredients. 349.79 Section 349.79 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... § 349.79 Labeling of permitted combinations of active ingredients. Statements of identity, indications...

21 CFR 349.79 - Labeling of permitted combinations of active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Labeling of permitted combinations of active ingredients. 349.79 Section 349.79 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... § 349.79 Labeling of permitted combinations of active ingredients. Statements of identity, indications...

21 CFR 352.60 - Labeling of permitted combinations of active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Labeling of permitted combinations of active ingredients. 352.60 Section 352.60 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... INDEFINITELY] Labeling § 352.60 Labeling of permitted combinations of active ingredients. Statements of...

21 CFR 349.79 - Labeling of permitted combinations of active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Labeling of permitted combinations of active ingredients. 349.79 Section 349.79 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... § 349.79 Labeling of permitted combinations of active ingredients. Statements of identity, indications...

21 CFR 349.79 - Labeling of permitted combinations of active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Labeling of permitted combinations of active ingredients. 349.79 Section 349.79 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... § 349.79 Labeling of permitted combinations of active ingredients. Statements of identity, indications...

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.

Pharmaceutical Cocrystals: New Solid Phase Modification Approaches for the Formulation of APIs

PubMed Central

Karagianni, Anna; Kachrimanis, Kyriakos

2018-01-01

Cocrystals can be used as an alternative approach based on crystal engineering to enhance specific physicochemical and biopharmaceutical properties of active pharmaceutical ingredients (APIs) when the approaches to salt or polymorph formation do not meet the expected targets. In this article, an overview of pharmaceutical cocrystals will be presented, with an emphasis on the intermolecular interactions in cocrystals and the methods for their preparation. Furthermore, cocrystals of direct pharmaceutical interest, along with their in vitro properties and available in vivo data and characterization techniques are discussed, highlighting the potential of cocrystals as an attractive route for drug development. PMID:29370068

Pharmaceutical Cocrystals: New Solid Phase Modification Approaches for the Formulation of APIs.

PubMed

Karagianni, Anna; Malamatari, Maria; Kachrimanis, Kyriakos

2018-01-25

Cocrystals can be used as an alternative approach based on crystal engineering to enhance specific physicochemical and biopharmaceutical properties of active pharmaceutical ingredients (APIs) when the approaches to salt or polymorph formation do not meet the expected targets. In this article, an overview of pharmaceutical cocrystals will be presented, with an emphasis on the intermolecular interactions in cocrystals and the methods for their preparation. Furthermore, cocrystals of direct pharmaceutical interest, along with their in vitro properties and available in vivo data and characterization techniques are discussed, highlighting the potential of cocrystals as an attractive route for drug development.

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...

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

PubMed

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

2016-05-01

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. 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. 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. Carrying out and validating a GC method for standardization of the formulated tablet, and having

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

PubMed

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

2016-05-01

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. 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. 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 (IC 50 >100 µg/ml) was calculated for the methanol extract of tablets. Carrying out and validating a GC method for standardization of the formulated tablet, and having

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...

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

...; Receipt of an Application for a New Active Ingredient AGENCY: Environmental Protection Agency (EPA... active ingredient not included in any previously registered pesticide product. Pursuant to the Federal... Application EPA has received an application to register a pesticide product containing an active ingredient...

An update on pharmaceutical film coating for drug delivery.

PubMed

Felton, Linda A; Porter, Stuart C

2013-04-01

Pharmaceutical coating processes have generally been transformed from what was essentially an art form in the mid-twentieth century to a much more technology-driven process. This review article provides a basic overview of current film coating processes, including a discussion on polymer selection, coating formulation additives and processing equipment. Substrate considerations for pharmaceutical coating processes are also presented. While polymeric coating operations are commonplace in the pharmaceutical industry, film coating processes are still not fully understood, which presents serious challenges with current regulatory requirements. Novel analytical technologies and various modeling techniques that are being used to better understand film coating processes are discussed. This review article also examines the challenges of implementing process analytical technologies in coating operations, active pharmaceutical ingredients in polymer film coatings, the use of high-solids coating systems and continuous coating and other novel coating application methods.

21 CFR 346.52 - Labeling of permitted combinations of anorectal active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Labeling of permitted combinations of anorectal active ingredients. 346.52 Section 346.52 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... HUMAN USE Labeling § 346.52 Labeling of permitted combinations of anorectal active ingredients...

21 CFR 346.52 - Labeling of permitted combinations of anorectal active ingredients.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of permitted combinations of anorectal active ingredients. 346.52 Section 346.52 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... HUMAN USE Labeling § 346.52 Labeling of permitted combinations of anorectal active ingredients...

21 CFR 346.52 - Labeling of permitted combinations of anorectal active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Labeling of permitted combinations of anorectal active ingredients. 346.52 Section 346.52 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... HUMAN USE Labeling § 346.52 Labeling of permitted combinations of anorectal active ingredients...

21 CFR 346.52 - Labeling of permitted combinations of anorectal active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Labeling of permitted combinations of anorectal active ingredients. 346.52 Section 346.52 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... HUMAN USE Labeling § 346.52 Labeling of permitted combinations of anorectal active ingredients...

21 CFR 346.52 - Labeling of permitted combinations of anorectal active ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Labeling of permitted combinations of anorectal active ingredients. 346.52 Section 346.52 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... HUMAN USE Labeling § 346.52 Labeling of permitted combinations of anorectal active ingredients...

Health effects of Vaccinium myrtillus L.: evaluation of efficacy and technological strategies for preservation of active ingredients.

PubMed

Smeriglio, Antonella; Monteleone, Domenico; Trombetta, Domenico

2014-01-01

Bilberries are a rich dietary source of various phytonutrients, including anthocyanins which contribute greatly to their antioxidant capacity and have demonstrated a broad spectrum of biomedical functions. These include protection against cardiovascular disorders, age-induced oxidative stress, inflammatory responses and several degenerative diseases. Berry anthocyanins also improve neuronal and cognitive brain functions, ocular health as well as protecting genomic DNA integrity. In recent years, sales of many dietary supplements/pharmaceutical products containing anthocyanins in various dosages and formulations have been made by advertising their wide range of beneficial effects. However, there is a heightened risk of distributing deteriorated formulations to consumers due to lax regulations, in particular those applicable to phytochemical characterization and extract standardization, and in terms of quality regarding the stability of anthocyanins. Anthocyanin pigments readily degrade during industrial processing and this can have a dramatic impact on color quality and may also affect nutritional/pharmaceutical properties. This review aims to summarize the main health effects of bilberry extract used in several food supplements/pharmaceutical formulations focusing on some important aspects of anthocyanin degradation during processing and storage. It will also describe the main technological strategies which can give active ingredients greater stability, solubility and dispersibility in order to enhance formulation quality which is of great interest to the consumer and industry due to its direct and indirect impact on consumer health.

Inkjet printing for pharmaceutics - A review of research and manufacturing.

PubMed

Daly, Ronan; Harrington, Tomás S; Martin, Graham D; Hutchings, Ian M

2015-10-30

Global regulatory, manufacturing and consumer trends are driving a need for change in current pharmaceutical sector business models, with a specific focus on the inherently expensive research costs, high-risk capital-intensive scale-up and the traditional centralised batch manufacturing paradigm. New technologies, such as inkjet printing, are being explored to radically transform pharmaceutical production processing and the end-to-end supply chain. This review provides a brief summary of inkjet printing technologies and their current applications in manufacturing before examining the business context driving the exploration of inkjet printing in the pharmaceutical sector. We then examine the trends reported in the literature for pharmaceutical printing, followed by the scientific considerations and challenges facing the adoption of this technology. We demonstrate that research activities are highly diverse, targeting a broad range of pharmaceutical types and printing systems. To mitigate this complexity we show that by categorising findings in terms of targeted business models and Active Pharmaceutical Ingredient (API) chemistry we have a more coherent approach to comparing research findings and can drive efficient translation of a chosen drug to inkjet manufacturing. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

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

2016-08-26

Drug binding to human serum albumin (HSA) has been characterized by a spin-labeling and continuous-wave (CW) EPR spectroscopic approach. Specifically, the contribution of functional groups (FGs) in a compound on its albumin-binding capabilities is quantitatively described. Molecules from different drug classes are labeled with EPR-active nitroxide radicals (spin-labeled pharmaceuticals (SLPs)) and in a screening approach CW-EPR spectroscopy is used to investigate HSA binding under physiological conditions and at varying ratios of SLP to protein. Spectral simulations of the CW-EPR spectra allow extraction of association constants (KA ) and the maximum number (n) of binding sites per protein. By comparison of data from 23 SLPs, the mechanisms of drug-protein association and the impact of chemical modifications at individual positions on drug uptake can be rationalized. Furthermore, new drug modifications with predictable protein binding tendency may be envisaged. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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 OVER-THE...

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 OVER-THE...

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 OVER-THE...

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 OVER-THE...

Pharmaceutical cocrystals, salts and polymorphs: Advanced characterization techniques.

PubMed

Pindelska, Edyta; Sokal, Agnieszka; Kolodziejski, Waclaw

2017-08-01

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

High-performance thin layer chromatography to assess pharmaceutical product quality.

PubMed

Kaale, Eliangiringa; Manyanga, Vicky; Makori, Narsis; Jenkins, David; Michael Hope, Samuel; Layloff, Thomas

2014-06-01

To assess the sustainability, robustness and economic advantages of high-performance thin layer chromatography (HPTLC) for quality control of pharmaceutical products. We compared three laboratories where three lots of cotrimoxazole tablets were assessed using different techniques for quantifying the active ingredient. The average assay relative standard deviation for the three lots was 1.2 with a range of 0.65-2.0. High-performance thin layer chromatography assessments are yielding valid results suitable for assessing product quality. The local pharmaceutical manufacturer had evolved the capacity to produce very high quality products. © 2014 John Wiley & Sons Ltd.

Sources of Chemical Toxics and Their Precursors in Pharmaceutical Industry

DTIC Science & Technology

2001-09-01

includes a lot of independent units specialized in synthesis of active substances, their processing as pharmaceutical forms, control of intermediate and...materials (ingredients), synthesis intermediates, intermediate forms (solutions, powders), analytical reactives, drugs itself, residues etc. Secondary...specialist scenario The simplest idea is to orient the attack against chemical synthesis facilities friom where a lot of volatile solvents could be spread

Prioritizing human pharmaceuticals for ecological risks in the freshwater environment of Korea.

PubMed

Ji, Kyunghee; Han, Eun Jeong; Back, Sunhyoung; Park, Jeongim; Ryu, Jisung; Choi, Kyungho

2016-04-01

Pharmaceutical residues are potential threats to aquatic ecosystems. Because more than 3000 active pharmaceutical ingredients (APIs) are in use, identifying high-priority pharmaceuticals is important for developing appropriate management options. Priority pharmaceuticals may vary by geographical region, because their occurrence levels can be influenced by demographic, societal, and regional characteristics. In the present study, the authors prioritized human pharmaceuticals of potential ecological risk in the Korean water environment, based on amount of use, biological activity, and regional hydrologic characteristics. For this purpose, the authors estimated the amounts of annual production of 695 human APIs in Korea. Then derived predicted environmental concentrations, using 2 approaches, to develop an initial candidate list of target pharmaceuticals. Major antineoplastic drugs and hormones were added in the initial candidate list regardless of their production amount because of their high biological activity potential. The predicted no effect concentrations were derived for those pharmaceuticals based on ecotoxicity information available in the literature or by model prediction. Priority lists of human pharmaceuticals were developed based on ecological risks and availability of relevant information. Those priority APIs identified include acetaminophen, clarithromycin, ciprofloxacin, ofloxacin, metformin, and norethisterone. Many of these pharmaceuticals have been neither adequately monitored nor assessed for risks in Korea. Further efforts are needed to improve these lists and to develop management decisions for these compounds in Korean water. © 2015 SETAC.

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

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

PubMed

Snyder, Herman E

2012-07-01

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

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

Code of Federal Regulations, 2013 CFR

2013-04-01

... 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.... (1) Combinations of control of dandruff and external analgesic active ingredients in § 358.720(b...

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

Code of Federal Regulations, 2014 CFR

2014-04-01

... 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.... (1) Combinations of control of dandruff and external analgesic active ingredients in § 358.720(b...

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

Code of Federal Regulations, 2012 CFR

2012-04-01

... 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.... (1) Combinations of control of dandruff and external analgesic active ingredients in § 358.720(b...

Fixed-dose combination and single active ingredient drugs: a comparative cost analysis.

PubMed

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

2016-01-01

Fixed-dose combination (FDC) drugs are formulations of two or more active ingredients. To assess the pricing structure and price difference of all US FDA-approved FDCs and single drugs included in the combination. Data were collected from the FDA Orange Book and Drugs@FDA. Average Wholesale Price (AWP) unit price data were derived from The Red Book. The FDA approved 117 FDC. The average AWP difference percentage between the FDC and the sum of the single drugs in the FDC is 84.9 ± 26.2%, and varied by therapeutic class (p < 0.001). The FDC AWP averaged 83.3 ± 23.4% of the single drug AWP sum when there are no generics, and 95.1 ± 42.3% (p < 0.01) when there are two generic single active ingredients in the FDC. The price difference between FDC and single active ingredients in the combination is correlated with the therapeutic class, the year of FDC approval, and the number of single ingredients in the combination that have generics.

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.

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…

Comprehensive analysis of pharmaceutical products using simultaneous mixed-mode (ion-exchange/reversed-phase) and hydrophilic interaction liquid chromatography.

PubMed

Kazarian, Artaches A; Nesterenko, Pavel N; Soisungnoen, Phimpha; Burakham, Rodjana; Srijaranai, Supalax; Paull, Brett

2014-08-01

Liquid chromatographic assays were developed using a mixed-mode column coupled in sequence with a hydrophilic interaction liquid chromatography column to allow the simultaneous comprehensive analysis of inorganic/organic anions and cations, active pharmaceutical ingredients, and excipients (carbohydrates). The approach utilized dual sample injection and valve-mediated column switching and was based upon a single high-performance liquid chromatography gradient pump. The separation consisted of three distinct sequential separation mechanisms, namely, (i) ion-exchange, (ii) mixed-mode interactions under an applied dual gradient (reversed-phase/ion-exchange), and (iii) hydrophilic interaction chromatography. Upon first injection, the Scherzo SS C18 column (Imtakt) provided resolution of inorganic anions and cations under isocratic conditions, followed by a dual organic/salt gradient to elute active pharmaceutical ingredients and their respective organic counterions and potential degradants. At the top of the mixed-mode gradient (high acetonitrile content), the mobile phase flow was switched to a preconditioned hydrophilic interaction liquid chromatography column, and the standard/sample was reinjected for the separation of hydrophilic carbohydrates, some of which are commonly known excipients in drug formulations. The approach afforded reproducible separation and resolution of up to 23 chemically diverse solutes in a single run. The method was applied to investigate the composition of commercial cough syrups (Robitussin®), allowing resolution and determination of inorganic ions, active pharmaceutical ingredients, excipients, and numerous well-resolved unknown peaks. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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 identified...

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 identified...

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 identified...

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 identified...

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

Code of Federal Regulations, 2010 CFR

2010-04-01

... 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 identified...

77 FR 36997 - Foreign-Trade Zone 61-San Juan, PR; Notification of Proposed Production Activity; Pfizer...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-20

...; Notification of Proposed Production Activity; Pfizer Pharmaceuticals LLC (Subzone 61A); (Ibuprofen...). Pfizer is now requesting to produce ibuprofen pharmaceutical products in bulk mixture or dosage form... to the ibuprofen pharmaceutical products (duty-free) for foreign-status ibuprofen active ingredient...

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

...; Notification of Proposed Production Activity; Albany Molecular Research, Inc., Subzone 121A, (Pharmaceutical... pharmaceutical chemicals and intermediates under FTZ procedures at the former Sanofi Winthrop L.P. plant located...). AMRI is now requesting to produce an active pharmaceutical ingredient, dexpramipexole dihydrochloride...

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

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

PubMed

Jamal, Salma; Scaria, Vinod

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

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

An empirical analysis of primary and secondary pharmaceutical patents in Chile.

PubMed

Abud, María José; Hall, Bronwyn; Helmers, Christian

2015-01-01

We analyze the patent filing strategies of foreign pharmaceutical companies in Chile distinguishing between "primary" (active ingredient) and "secondary" patents (patents on modified compounds, formulations, dosages, particular medical uses, etc.). There is prior evidence that secondary patents are used by pharmaceutical originator companies in the U.S. and Europe to extend patent protection on drugs in length and breadth. Using a novel dataset that comprises all drugs registered in Chile between 1991 and 2010 as well as the corresponding patents and trademarks, we find evidence that foreign originator companies pursue similar strategies in Chile. We find a primary to secondary patents ratio of 1:4 at the drug-level, which is comparable to the available evidence for Europe; most secondary patents are filed over several years following the original primary patent and after the protected active ingredient has obtained market approval in Chile. This points toward effective patent term extensions through secondary patents. Secondary patents dominate "older" therapeutic classes like anti-ulcer and anti-depressants. In contrast, newer areas like anti-virals and anti-neoplastics (anti-cancer) have a much larger share of primary patents.

An Empirical Analysis of Primary and Secondary Pharmaceutical Patents in Chile

PubMed Central

Abud, María José; Hall, Bronwyn; Helmers, Christian

2015-01-01

We analyze the patent filing strategies of foreign pharmaceutical companies in Chile distinguishing between “primary” (active ingredient) and “secondary” patents (patents on modified compounds, formulations, dosages, particular medical uses, etc.). There is prior evidence that secondary patents are used by pharmaceutical originator companies in the U.S. and Europe to extend patent protection on drugs in length and breadth. Using a novel dataset that comprises all drugs registered in Chile between 1991 and 2010 as well as the corresponding patents and trademarks, we find evidence that foreign originator companies pursue similar strategies in Chile. We find a primary to secondary patents ratio of 1:4 at the drug-level, which is comparable to the available evidence for Europe; most secondary patents are filed over several years following the original primary patent and after the protected active ingredient has obtained market approval in Chile. This points toward effective patent term extensions through secondary patents. Secondary patents dominate “older” therapeutic classes like anti-ulcer and anti-depressants. In contrast, newer areas like anti-virals and anti-neoplastics (anti-cancer) have a much larger share of primary patents. PMID:25915050

Specific Chemical (Active Ingredient) Information

Science.gov Websites

; Environment Human Health Animal Health Safe Use Practices Food Safety Environment Air Water Soil Wildlife Ingredients Low-Risk Pesticides Organic Pesticide Ingredients Pesticide Incidents Human Exposure Pet Exposure :00PM Pacific Time, Mon-Fri A B C D E F G H I J K L M N O P Q R S T U V W X Y Z A-Z Index Health &

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.

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...

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 FOR...

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...

The use of atomic spectroscopy in the pharmaceutical industry for the determination of trace elements in pharmaceuticals.

PubMed

Lewen, Nancy

2011-06-25

The subject of the analysis of various elements, including metals and metalloids, in the pharmaceutical industry has seen increasing importance in the last 10-15 years, as modern analytical instrumentation has afforded analysts with the opportunity to provide element-specific, accurate and meaningful information related to pharmaceutical products. Armed with toxicological data, compendial and regulatory agencies have revisited traditional approaches to the testing of pharmaceuticals for metals and metalloids, and analysts have begun to employ the techniques of atomic spectroscopy, such as flame- and graphite furnace atomic absorption spectroscopy (FAAS, Flame AA or FAA and GFAAS), inductively coupled plasma-atomic emission spectroscopy (ICP-AES) and inductively coupled plasma-mass spectrometry (ICP-MS), to meet their analytical needs. Newer techniques, such as laser-induced breakdown spectroscopy (LIBS) and Laser Ablation ICP-MS (LAICP-MS) are also beginning to see wider applications in the analysis of elements in the pharmaceutical industry.This article will provide a perspective regarding the various applications of atomic spectroscopy in the analysis of metals and metalloids in drug products, active pharmaceutical ingredients (API's), raw materials and intermediates. The application of atomic spectroscopy in the analysis of metals and metalloids in clinical samples, nutraceutical, metabolism and pharmacokinetic samples will not be addressed in this work. Copyright © 2010 Elsevier B.V. All rights reserved.

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...

Practices of pharmaceutical waste generation and discarding in households across Portugal.

PubMed

Dias-Ferreira, Celia; Valente, Susana; Vaz, João

2016-10-01

This work is the first nationwide study in Portugal on pharmaceutical waste generated at households, exploring people's attitudes and risk perception. The waste audit was carried out from September to November 2014, targeting pharmaceutical products kept by a sample of families (n = 244). This campaign was an assignment of VALORMED, the non-profit association that manages waste and packaging from expired and unused pharmaceutical products collected by the pharmacies. On average, each household kept at home 1097 g of pharmaceutical products, of which 20% were in use, 72% were not in use, and 8% were mostly expired products ready to discard. Face-to-face interviews with householders showed that 69% of the respondents claimed returning pharmaceutical waste to the local pharmacy. However, this figure is overrated, probably owing to a possible 'good answer' effect. The barriers identified to proper disposal were mainly established routines and lack of close disposal points. This study also provides an insight into the Portuguese awareness and daily practices concerning pharmaceutical waste, which is the cornerstone of any future strategy to reduce the release of active pharmaceutical ingredients into ecosystems. © The Author(s) 2016.

Theory-Based Active Ingredients of Effective Treatments for Substance Use Disorders

PubMed Central

Moos, Rudolf H.

2007-01-01

This paper describes four related theories that specify common social processes that protect individuals from developing substance use disorders and may underlie effective psychosocial treatments for these disorders: social control theory, behavioral economics and behavioral choice theory, social learning theory, and stress and coping theory. It then provides an overview of the rationale and evidence for four effective psychosocial treatments for substance use disorders: motivational interviewing and motivational enhancement therapy, 12-step facilitation treatment, cognitive-behavioral treatment and behavioral family counseling, and contingency management and community reinforcement approaches. The presumed active ingredients of these treatments are described in terms of how they exemplify the social processes highlighted by the four theories. The identified common components of effective treatment include support, goal direction, and structure; an emphasis on rewards that compete with substance use, a focus on abstinence-oriented norms and models, and attempts to develop self-efficacy and coping skills. Several issues that need to be addressed to enhance our understanding of the active ingredients involved in effective treatment are discussed, including how to develop measures of these ingredients, how well the ingredients predict outcomes and influence conceptually comparable aspects of clients’ life contexts, and how much their influence varies depending upon clients’ demographic and personal characteristics. PMID:17129682

Theory-based active ingredients of effective treatments for substance use disorders.

PubMed

Moos, Rudolf H

2007-05-11

This paper describes four related theories that specify common social processes that protect individuals from developing substance use disorders and may underlie effective psychosocial treatments for these disorders: social control theory, behavioral economics and behavioral choice theory, social learning theory, and stress and coping theory. It then provides an overview of the rationale and evidence for four effective psychosocial treatments for substance use disorders: motivational interviewing and motivational enhancement therapy, 12-step facilitation treatment, cognitive-behavioral treatment and behavioral family counseling, and contingency management and community reinforcement approaches. The presumed active ingredients of these treatments are described in terms of how they exemplify the social processes highlighted by the four theories. The identified common components of effective treatment include support, goal direction, and structure; an emphasis on rewards that compete with substance use, a focus on abstinence-oriented norms and models, and attempts to develop self-efficacy and coping skills. Several issues that need to be addressed to enhance our understanding of the active ingredients involved in effective treatment are discussed, including how to develop measures of these ingredients, how well the ingredients predict outcomes and influence conceptually comparable aspects of clients' life contexts, and how much their influence varies depending upon clients' demographic and personal characteristics.

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

PubMed

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, NFKB, 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.

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

EPA Science Inventory

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

Analysis of potential genotoxic impurities in rabeprazole active pharmaceutical ingredient via Liquid Chromatography-tandem Mass Spectrometry, following quality-by-design principles for method development.

PubMed

Iliou, Katerina; Malenović, Anđelija; Loukas, Yannis L; Dotsikas, Yannis

2018-02-05

A novel Liquid Chromatography-tandem mass spectrometry (LC-MS/MS) method is presented for the quantitative determination of two potential genotoxic impurities (PGIs) in rabeprazole active pharmaceutical ingredient (API). In order to overcome the analytical challenges in the trace analysis of PGIs, a development procedure supported by Quality-by-Design (QbD) principles was evaluated. The efficient separation between rabeprazole and the two PGIs in the shortest analysis time was set as the defined analytical target profile (ATP) and to this purpose utilization of a switching valve allowed the flow to be sent to waste when rabeprazole was eluted. The selected critical quality attributes (CQAs) were the separation criterion s between the critical peak pair and the capacity factor k of the last eluted compound. The effect of the following critical process parameters (CPPs) on the CQAs was studied: %ACN content, the pH and the concentration of the buffer salt in the mobile phase, as well as the stationary phase of the analytical column. D-Optimal design was implemented to set the plan of experiments with UV detector. In order to define the design space, Monte Carlo simulations with 5000 iterations were performed. Acceptance criteria were met for C 8 column (50×4mm, 5μm) , and the region having probability π≥95% to achieve satisfactory values of all defined CQAs was computed. The working point was selected with the mobile phase consisting ‎of ACN, ammonium formate 11mM at a ratio 31/69v/v with pH=6,8 for the water phase. The LC protocol was transferred to LC-MS/MS and validated according to ICH guidelines. Copyright © 2017 Elsevier B.V. All rights reserved.