Analytical approaches for the detection of epoxides and hydroperoxides in active pharmaceutical ingredients, drug products and herbals.

Science.gov (United States)

Elder, D P; Snodin, D; Teasdale, A

2010-04-06

This review summarizes the analytical approaches reported in the literature relating to epoxide and hydroperoxide impurities. It is intended that it should provide guidance for analysts faced by the need to control such impurities, particularly where this is due to concerns relating to their potential genotoxicity. An extensive search of the literature relating to this class of impurities revealed a large number of references relating to analysis of epoxides/hydroperoxides associated with herbal remedies. Given the general applicability of the analytical methodology and due to the widespread use of herbal products the authors decided to include herbal medicines in this review. The review also reflects on the very different approaches taken in terms of the assessment/control of genotoxic impurities for such herbal remedies to that required for pharmaceutical products. Copyright 2009 Elsevier B.V. All rights reserved.

Annual banned-substance review: analytical approaches in human sports drug testing.

Science.gov (United States)

Thevis, Mario; Kuuranne, Tiia; Geyer, Hans; Schänzer, Wilhelm

2017-01-01

There has been an immense amount of visibility of doping issues on the international stage over the past 12 months with the complexity of doping controls reiterated on various occasions. Hence, analytical test methods continuously being updated, expanded, and improved to provide specific, sensitive, and comprehensive test results in line with the World Anti-Doping Agency's (WADA) 2016 Prohibited List represent one of several critical cornerstones of doping controls. This enterprise necessitates expediting the (combined) exploitation of newly generated information on novel and/or superior target analytes for sports drug testing assays, drug elimination profiles, alternative test matrices, and recent advances in instrumental developments. This paper is a continuation of the series of annual banned-substance reviews appraising the literature published between October 2015 and September 2016 concerning human sports drug testing in the context of WADA's 2016 Prohibited List. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Sample preparation composite and replicate strategy case studies for assay of solid oral drug products.

Science.gov (United States)

Nickerson, Beverly; Harrington, Brent; Li, Fasheng; Guo, Michele Xuemei

2017-11-30

Drug product assay is one of several tests required for new drug products to ensure the quality of the product at release and throughout the life cycle of the product. Drug product assay testing is typically performed by preparing a composite sample of multiple dosage units to obtain an assay value representative of the batch. In some cases replicate composite samples may be prepared and the reportable assay value is the average value of all the replicates. In previously published work by Harrington et al. (2014) [5], a sample preparation composite and replicate strategy for assay was developed to provide a systematic approach which accounts for variability due to the analytical method and dosage form with a standard error of the potency assay criteria based on compendia and regulatory requirements. In this work, this sample preparation composite and replicate strategy for assay is applied to several case studies to demonstrate the utility of this approach and its application at various stages of pharmaceutical drug product development. Copyright © 2017 Elsevier B.V. All rights reserved.

Analyses of marketplace tacrolimus drug product quality: bioactivity, NMR and LC-MS.

Science.gov (United States)

Sommers, Cynthia D; Pang, Eric S; Ghasriani, Houman; Berendt, Robert T; Vilker, Vincent L; Keire, David A; Boyne, Michael T

2013-11-01

Tacrolimus (FK506) is a potent, narrow therapeutic index, immunosuppressive drug used to avoid organ rejection in patients that have undergone organ transplantation. Recent clinical reports suggested a significant reduction in the tacrolimus concentration/dose ratio in the plasma of liver and kidney recipients when the reference listed drug was substituted with a generic drug. In response to these concerns about switching between tacrolimus from different approved manufacturers during treatment, the FDA initiated purity, potency and quality studies of the innovator and generic tacrolimus products available in the US marketplace. A combination of analytical methods, including mass spectrometry (LC-MS), nuclear magnetic resonance (NMR) and bioactivity assay were developed and validated to assess the quality of tacrolimus. These tests measured the identity, impurities and activity of tacrolimus from active pharmaceutical ingredient (API) sources and with formulated drug product from five different approved manufactures. In addition, some testing was performed on tacrolimus capsules obtained from a non US approved Indian source. The data obtained showed no discernible difference in the impurity profiles and potency between the generic and innovator tacrolimus products. Copyright © 2013. Published by Elsevier B.V.

Drug product selection: legal issues.

Science.gov (United States)

Christensen, T P; Kirking, D M; Ascione, F J; Welage, L S; Gaither, C A

2001-01-01

To review the potential legal liability of the pharmacist in the drug product selection process. Published articles identified through MEDLINE, published law reviews identified through InfoTrac, and appellate court decisions. Search terms used included pharmacist liability, drug product selection, and generic substitution. Additional articles, books, and appellate court decisions were identified from the bibliographies of retrieved articles and citations in appellate court decisions. Pharmacists engaging in drug product selection are civilly liable under three legal theories: negligence, express or implied warranties, and strict product liability. Potential criminal liability includes prosecution for insurance fraud, deceptive business practices, and violation of state drug product selection laws and regulation. Pharmacists increase their liability when engaging in drug product selection, but the increase is small. Still, the law continues to evolve as pharmacists seek expanded roles and responsibilities. When courts give closer examination to pharmacists' expanded role, it is likely that pharmacists' liability will increase.

Prescription Drugs, Over-the-Counter Drugs, Supplements and Herbal Products

Science.gov (United States)

... at risk? Zika virus and pregnancy Folic acid Medicine safety and pregnancy Birth defects prevention Learn how ... the-counter drugs, supplements and herbal products Prescription drugs, over-the-counter drugs, supplements and herbal products ...

Functional evaluation of healthcare products such as cosmetics, drugs, and foods

International Nuclear Information System (INIS)

Hatta, Ichiro

2008-01-01

The present paper surveys analytical methods recently employed in the field of healthcare products such as cosmetics, drugs, and foods by using Spring-8 facility which delivers high-intensity X-ray beams from electron cyclotron accelerator. These X-ray beams can be used to analyze atoms and their chemical state in human tissues such as skin, hair, whisker, teeth, and new developed products. Thus, a variety of products related with medical supplies, health food products, health maintenance, and preventive medicine concern this research group. Here, the results on colloidal states, such as lipid-molecule aggregates and lamellar structure type, generally present in cosmetic products and food substances, are focused and reported, specifically focusing on hair cuticle and honey cell layer of the skin regarding to cosmetic and pharmaceutical products. (S. Ohno)

Photostability and Photostabilization of Drugs and Drug Products

OpenAIRE

Ahmad, Iqbal; Ahmed, Sofia; Anwar, Zubair; Sheraz, Muhammad Ali; Sikorski, Marek

2016-01-01

Photostability studies of drugs and drug products are an integral part of the product development process in the pharmaceutical industry. These studies are carried out to ensure quality, efficacy, and safety of the formulated products during manufacture, storage, and use. This review deals with the concept of photostability and related aspects and the literature available in the field. It highlights the role of the photochemistry in the photostability studies, describes the functional groups ...

Assessing Analytical Similarity of Proposed Amgen Biosimilar ABP 501 to Adalimumab.

Science.gov (United States)

Liu, Jennifer; Eris, Tamer; Li, Cynthia; Cao, Shawn; Kuhns, Scott

2016-08-01

ABP 501 is being developed as a biosimilar to adalimumab. Comprehensive comparative analytical characterization studies have been conducted and completed. The objective of this study was to assess analytical similarity between ABP 501 and two adalimumab reference products (RPs), licensed by the United States Food and Drug Administration (adalimumab [US]) and authorized by the European Union (adalimumab [EU]), using state-of-the-art analytical methods. Comprehensive analytical characterization incorporating orthogonal analytical techniques was used to compare products. Physicochemical property comparisons comprised the primary structure related to amino acid sequence and post-translational modifications including glycans; higher-order structure; primary biological properties mediated by target and receptor binding; product-related substances and impurities; host-cell impurities; general properties of the finished drug product, including strength and formulation; subvisible and submicron particles and aggregates; and forced thermal degradation. ABP 501 had the same amino acid sequence and similar post-translational modification profiles compared with adalimumab RPs. Primary structure, higher-order structure, and biological activities were similar for the three products. Product-related size and charge variants and aggregate and particle levels were also similar. ABP 501 had very low residual host-cell protein and DNA. The finished ABP 501 drug product has the same strength with regard to protein concentration and fill volume as adalimumab RPs. ABP 501 and the RPs had a similar stability profile both in normal storage and thermal stress conditions. Based on the comprehensive analytical similarity assessment, ABP 501 was found to be similar to adalimumab with respect to physicochemical and biological properties.

The Analytical Chemistry of Drug Monitoring in Athletes

Science.gov (United States)

Bowers, Larry D.

2009-07-01

The detection and deterrence of the abuse of performance-enhancing drugs in sport are important to maintaining a level playing field among athletes and to decreasing the risk to athletes’ health. The World Anti-Doping Program consists of six documents, three of which play a role in analytical development: The World Anti-Doping Code, The List of Prohibited Substances and Methods, and The International Standard for Laboratories. Among the classes of prohibited substances, three have given rise to the most recent analytical developments in the field: anabolic agents; peptide and protein hormones; and methods to increase oxygen delivery to the tissues, including recombinant erythropoietin. Methods for anabolic agents, including designer steroids, have been enhanced through the use of liquid chromatography/tandem mass spectrometry and gas chromatography/combustion/isotope-ratio mass spectrometry. Protein and peptide identification and quantification have benefited from advances in liquid chromatography/tandem mass spectrometry. Incorporation of techniques such as flow cytometry and isoelectric focusing have supported the detection of blood doping.

Process analytical technology in continuous manufacturing of a commercial pharmaceutical product.

Science.gov (United States)

Vargas, Jenny M; Nielsen, Sarah; Cárdenas, Vanessa; Gonzalez, Anthony; Aymat, Efrain Y; Almodovar, Elvin; Classe, Gustavo; Colón, Yleana; Sanchez, Eric; Romañach, Rodolfo J

2018-03-01

The implementation of process analytical technology and continuous manufacturing at an FDA approved commercial manufacturing site is described. In this direct compaction process the blends produced were monitored with a Near Infrared (NIR) spectroscopic calibration model developed with partial least squares (PLS) regression. The authors understand that this is the first study where the continuous manufacturing (CM) equipment was used as a gravimetric reference method for the calibration model. A principal component analysis (PCA) model was also developed to identify the powder blend, and determine whether it was similar to the calibration blends. An air diagnostic test was developed to assure that powder was present within the interface when the NIR spectra were obtained. The air diagnostic test as well the PCA and PLS calibration model were integrated into an industrial software platform that collects the real time NIR spectra and applies the calibration models. The PCA test successfully detected an equipment malfunction. Variographic analysis was also performed to estimate the sampling analytical errors that affect the results from the NIR spectroscopic method during commercial production. The system was used to monitor and control a 28 h continuous manufacturing run, where the average drug concentration determined by the NIR method was 101.17% of label claim with a standard deviation of 2.17%, based on 12,633 spectra collected. The average drug concentration for the tablets produced from these blends was 100.86% of label claim with a standard deviation of 0.4%, for 500 tablets analyzed by Fourier Transform Near Infrared (FT-NIR) transmission spectroscopy. The excellent agreement between the mean drug concentration values in the blends and tablets produced provides further evidence of the suitability of the validation strategy that was followed. Copyright © 2018 Elsevier B.V. All rights reserved.

The analytical solution for drug delivery system with nonhomogeneous moving boundary condition

Science.gov (United States)

Saudi, Muhamad Hakimi; Mahali, Shalela Mohd; Harun, Fatimah Noor

2017-08-01

This paper discusses the development and the analytical solution of a mathematical model based on drug release system from a swelling delivery device. The mathematical model is represented by a one-dimensional advection-diffusion equation with nonhomogeneous moving boundary condition. The solution procedures consist of three major steps. Firstly, the application of steady state solution method, which is used to transform the nonhomogeneous moving boundary condition to homogeneous boundary condition. Secondly, the application of the Landau transformation technique that gives a significant impact in removing the advection term in the system of equation and transforming the moving boundary condition to a fixed boundary condition. Thirdly, the used of separation of variables method to find the analytical solution for the resulted initial boundary value problem. The results show that the swelling rate of delivery device and drug release rate is influenced by value of growth factor r.

Development Considerations for Nanocrystal Drug Products.

Science.gov (United States)

Chen, Mei-Ling; John, Mathew; Lee, Sau L; Tyner, Katherine M

2017-05-01

Nanocrystal technology has emerged as a valuable tool for facilitating the delivery of poorly water-soluble active pharmaceutical ingredients (APIs) and enhancing API bioavailability. To date, the US Food and Drug Administration (FDA) has received over 80 applications for drug products containing nanocrystals. These products can be delivered by different routes of administration and are used in a variety of therapeutic areas. To aid in identifying key developmental considerations for these products, a retrospective analysis was performed on the submissions received by the FDA to date. Over 60% of the submissions were for the oral route of administration. Based on the Biopharmaceutics Classification System (BCS), most nanocrystal drugs submitted to the FDA are class II compounds that possess low aqueous solubility and high intestinal permeability. Impact of food on drug bioavailability was reduced for most nanocrystal formulations as compared with their micronized counterparts. For all routes of administration, dose proportionality was observed for some, but not all, nanocrystal products. Particular emphasis in the development of nanocrystal products was placed on the in-process tests and controls at critical manufacturing steps (such as milling process), mitigation and control of process-related impurities, and the stability of APIs or polymorphic form (s) during manufacturing and upon storage. This emphasis resulted in identifying challenges to the development of these products including accurate determination of particle size (distribution) of drug substance and/or nanocrystal colloidal dispersion, identification of polymorphic form (s), and establishment of drug substance/product specifications.

Electronic Animal Drug Product Listing Directory

Data.gov (United States)

U.S. Department of Health & Human Services — The Electronic Animal Drug Product Listing Directory is a directory of all animal drug products that have been listed electronically since June 1, 2009, to comply...

Applicability of bioanalysis of multiple analytes in drug discovery and development: review of select case studies including assay development considerations.

Science.gov (United States)

Srinivas, Nuggehally R

2006-05-01

The development of sound bioanalytical method(s) is of paramount importance during the process of drug discovery and development culminating in a marketing approval. Although the bioanalytical procedure(s) originally developed during the discovery stage may not necessarily be fit to support the drug development scenario, they may be suitably modified and validated, as deemed necessary. Several reviews have appeared over the years describing analytical approaches including various techniques, detection systems, automation tools that are available for an effective separation, enhanced selectivity and sensitivity for quantitation of many analytes. The intention of this review is to cover various key areas where analytical method development becomes necessary during different stages of drug discovery research and development process. The key areas covered in this article with relevant case studies include: (a) simultaneous assay for parent compound and metabolites that are purported to display pharmacological activity; (b) bioanalytical procedures for determination of multiple drugs in combating a disease; (c) analytical measurement of chirality aspects in the pharmacokinetics, metabolism and biotransformation investigations; (d) drug monitoring for therapeutic benefits and/or occupational hazard; (e) analysis of drugs from complex and/or less frequently used matrices; (f) analytical determination during in vitro experiments (metabolism and permeability related) and in situ intestinal perfusion experiments; (g) determination of a major metabolite as a surrogate for the parent molecule; (h) analytical approaches for universal determination of CYP450 probe substrates and metabolites; (i) analytical applicability to prodrug evaluations-simultaneous determination of prodrug, parent and metabolites; (j) quantitative determination of parent compound and/or phase II metabolite(s) via direct or indirect approaches; (k) applicability in analysis of multiple compounds in select

Drug abuse and aggression between intimate partners: a meta-analytic review.

Science.gov (United States)

Moore, Todd M; Stuart, Gregory L; Meehan, Jeffrey C; Rhatigan, Deborah L; Hellmuth, Julianne C; Keen, Stefanie M

2008-02-01

The present investigation employed meta-analytic procedures to quantitatively evaluate the empirical evidence on the relationship between drug abuse and aggression between intimate partners. Data from 96 studies yielding 547 effect sizes indicated that increases in drug use and drug-related problems were significantly associated with increases in aggression between intimate partners (d= .27). Cocaine emerged as the illicit substance with the strongest relationship to psychological, physical, and sexual aggression (ds= .39 to .62). Marijuana was also identified as having a significant association with partner aggression. Results showed comparable effect sizes for men and women, regardless of the sex of the drug user and/or perpetrator of partner aggression, with female reports of aggression having yielded larger effect sizes than male reports. Moderator analyses revealed that relative to other groups, married or cohabiting couples and Black participants evidenced significantly stronger effect sizes. The findings are discussed in relation to possible mechanisms linking drugs to partner aggression, and implications for future research are discussed in terms of focusing on conducting studies that assess the interaction of context and temporal sequencing of drugs and partner aggression.

Nanomaterials in consumer products: a challenging analytical problem

Directory of Open Access Journals (Sweden)

Catia eContado

2015-08-01

Full Text Available Many products used in everyday life are made with the assistance of nanotechnologies. Cosmetic, pharmaceuticals, sunscreen, powdered food are only few examples of end products containing nano-sized particles (NPs, generally added to improve the product quality. To evaluate correctly benefits versus risks of engineered nanomaterials and consequently to legislate in favor of consumer’s protection, it is necessary to know the hazards connected with the exposure levels. This information implies transversal studies and a number of different competences.On analytical point of view the identification, quantification and characterization of NPs in food matrices and in cosmetic or personal care products pose significant challenges, because NPs are usually present at low concentration levels and the matrices, in which they are dispersed, are complexes and often incompatible with analytical instruments that would be required for their detection and characterization.This paper focused on some analytical techniques suitable for the detection, characterization and quantification of NPs in food and cosmetics products, reports their recent application in characterizing specific metal and metal-oxide NPs in these two important industrial and market sectors.The need of a characterization of the NPs as much as possible complete, matching complementary information about different metrics, possible achieved through validate procedures, is what clearly emerges from this research. More work should be done to produce standardized materials and to set-up methodologies to determine number-based size distributions and to get quantitative date about the NPs in such a complex matrices.

Nanomaterials in consumer products: a challenging analytical problem.

Science.gov (United States)

Contado, Catia

2015-01-01

Many products used in everyday life are made with the assistance of nanotechnologies. Cosmetic, pharmaceuticals, sunscreen, powdered food are only few examples of end products containing nano-sized particles (NPs), generally added to improve the product quality. To evaluate correctly benefits vs. risks of engineered nanomaterials and consequently to legislate in favor of consumer's protection, it is necessary to know the hazards connected with the exposure levels. This information implies transversal studies and a number of different competences. On analytical point of view the identification, quantification and characterization of NPs in food matrices and in cosmetic or personal care products pose significant challenges, because NPs are usually present at low concentration levels and the matrices, in which they are dispersed, are complexes and often incompatible with analytical instruments that would be required for their detection and characterization. This paper focused on some analytical techniques suitable for the detection, characterization and quantification of NPs in food and cosmetics products, reports their recent application in characterizing specific metal and metal-oxide NPs in these two important industrial and market sectors. The need of a characterization of the NPs as much as possible complete, matching complementary information about different metrics, possible achieved through validate procedures, is what clearly emerges from this research. More work should be done to produce standardized materials and to set-up methodologies to determine number-based size distributions and to get quantitative date about the NPs in such a complex matrices.

21 CFR 333.350 - Labeling of acne drug products.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of acne drug products. 333.350 Section... Acne Drug Products § 333.350 Labeling of acne drug products. (a) Statement of identity. The labeling of the product contains the established name of the drug, if any, and identifies the product as an “acne...

Investigation of drug products received for analysis in the Swedish STRIDA project on new psychoactive substances.

Science.gov (United States)

Bäckberg, Matilda; Jönsson, Karl-Henrik; Beck, Olof; Helander, Anders

2018-02-01

The web-based open sale of unregulated new psychoactive substances (NPS) has shown a steady increase in recent years. Analysis of drug products sold as NPS is useful to confirm the true chemical contents, for comparison with the substances detected in corresponding body fluids, but also to study drug trends. This work describes the examination of 251 drug products that were randomly submitted for analysis in 173 cases of suspected NPS-related intoxications in the Swedish STRIDA project in 2010-2015. Of the products, 39% were powders/crystals, 32% tablets/capsules, 16% herbal materials, 8% liquids, 1% blotters, and 4% others. The analysis involved tandem mass spectrometry and nuclear magnetic resonance spectroscopy. In 88 products (35%), classic psychoactive substances, prescription pharmaceuticals, dietary supplements, or doping agents were found; however, in none of these cases had an NPS-related intoxication been indicated from product markings or patient self-reports. Another 12 products tested negative for psychoactive substances. The remaining 151 products contained 86 different NPS (30% contained ≥2 substances). In 104 drug products, a specific NPS ingredient was indicated based on labelling (69%) or patient self-report; in 92 cases this was also analytically confirmed to be correct. Overall, the NPS products submitted for analysis in the STRIDA project showed a high degree of consistency between suspected and actual content (88%). The results of related urine and/or blood analysis further demonstrated that the patients commonly (89%) tested positive for the indicated NPS, but also revealed that polysubstance intoxication was common (83%), indicating use of additional drug products. Copyright © 2017 John Wiley & Sons, Ltd.

Comparison of high-resolution ultrasonic resonator technology and Raman spectroscopy as novel process analytical tools for drug quantification in self-emulsifying drug delivery systems.

Science.gov (United States)

Stillhart, Cordula; Kuentz, Martin

2012-02-05

Self-emulsifying drug delivery systems (SEDDS) are complex mixtures in which drug quantification can become a challenging task. Thus, a general need exists for novel analytical methods and a particular interest lies in techniques with the potential for process monitoring. This article compares Raman spectroscopy with high-resolution ultrasonic resonator technology (URT) for drug quantification in SEDDS. The model drugs fenofibrate, indomethacin, and probucol were quantitatively assayed in different self-emulsifying formulations. We measured ultrasound velocity and attenuation in the bulk formulation containing drug at different concentrations. The formulations were also studied by Raman spectroscopy. We used both, an in-line immersion probe for the bulk formulation and a multi-fiber sensor for measuring through hard-gelatin capsules that were filled with SEDDS. Each method was assessed by calculating the relative standard error of prediction (RSEP) as well as the limit of quantification (LOQ) and the mean recovery. Raman spectroscopy led to excellent calibration models for the bulk formulation as well as the capsules. The RSEP depended on the SEDDS type with values of 1.5-3.8%, while LOQ was between 0.04 and 0.35% (w/w) for drug quantification in the bulk. Similarly, the analysis of the capsules led to RSEP of 1.9-6.5% and LOQ of 0.01-0.41% (w/w). On the other hand, ultrasound attenuation resulted in RSEP of 2.3-4.4% and LOQ of 0.1-0.6% (w/w). Moreover, ultrasound velocity provided an interesting analytical response in cases where the drug strongly affected the density or compressibility of the SEDDS. We conclude that ultrasonic resonator technology and Raman spectroscopy constitute suitable methods for drug quantification in SEDDS, which is promising for their use as process analytical technologies. Copyright © 2011 Elsevier B.V. All rights reserved.

21 CFR 211.94 - Drug product containers and closures.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Drug product containers and closures. 211.94 Section 211.94 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... and use that can cause deterioration or contamination of the drug product. (c) Drug product containers...

Drugs from the Oceans: Marine Natural Products as Leads for Drug Discovery.

Science.gov (United States)

Altmann, Karl-Heinz

2017-10-25

The marine environment harbors a vast number of species that are the source of a wide array of structurally diverse bioactive secondary metabolites. At this point in time, roughly 27'000 marine natural products are known, of which eight are (were) at the origin of seven marketed drugs, mostly for the treatment of cancer. The majority of these drugs and also of drug candidates currently undergoing clinical evaluation (excluding antibody-drug conjugates) are unmodified natural products, but synthetic chemistry has played a central role in the discovery and/or development of all but one of the approved marine-derived drugs. More than 1000 new marine natural products have been isolated per year over the last decade, but the pool of new and unique structures is far from exhausted. To fully leverage the potential offered by the structural diversity of marine-produced secondary metabolites for drug discovery will require their broad assessment for different bioactivities and the productive interplay between new fermentation technologies, synthetic organic chemistry, and medicinal chemistry, in order to secure compound supply and enable lead optimization.

Role of modern analytical techniques in the production of uranium metal

International Nuclear Information System (INIS)

Hareendran, K.N.; Roy, S.B.

2009-01-01

Production of nuclear grade uranium metal conforming to its stringent specification with respect to metallic and non metallic impurities necessitates implementation of a comprehensive quality control regime. Founding members of Uranium Metal Plant realised the importance of this aspect of metal production and a quality control laboratory was set up as part of the production plant. In the initial stages of its existence, the laboratory mainly catered to the process control analysis of the plant process samples and Spectroscopy Division and Analytical Division of BARC provided analysis of trace metallic impurities in the intermediates as well as in the product uranium metal. This laboratory also provided invaluable R and D support for the optimization of the process involving both calciothermy and magnesiothermy. Prior to 1985, analytical procedures used were limited to classical methods of analysis with minimal instrumental procedures. The first major analytical instrument, a Flame AAS was installed in 1985 and a beginning to the trace analysis was made. However during the last 15 years the Quality Control Section has modernized the analytical set up by acquiring appropriate instruments. Presently the facility has implemented a complete quality control and quality assurance program required to cover all aspects of uranium metal production viz analysis of raw materials, process samples, waste disposal samples and also determination of all the specification elements in uranium metal. The current analytical practices followed in QCS are presented here

Integrated Application of Quality-by-Design Principles to Drug Product Development: A Case Study of Brivanib Alaninate Film-Coated Tablets.

Science.gov (United States)

Badawy, Sherif I F; Narang, Ajit S; LaMarche, Keirnan R; Subramanian, Ganeshkumar A; Varia, Sailesh A; Lin, Judy; Stevens, Tim; Shah, Pankaj A

2016-01-01

Modern drug product development is expected to follow quality-by-design (QbD) paradigm. At the same time, although there are several issue-specific examples in the literature that demonstrate the application of QbD principles, a holistic demonstration of the application of QbD principles to drug product development and control strategy, is lacking. This article provides an integrated case study on the systematic application of QbD to product development and demonstrates the implementation of QbD concepts in the different aspects of product and process design for brivanib alaninate film-coated tablets. Using a risk-based approach, the strategy for development entailed identification of product critical quality attributes (CQAs), assessment of risks to the CQAs, and performing experiments to understand and mitigate identified risks. Quality risk assessments and design of experiments were performed to understand the quality of the input raw materials required for a robust formulation and the impact of manufacturing process parameters on CQAs. In addition to the material property and process parameter controls, the proposed control strategy includes use of process analytical technology and conventional analytical tests to control in-process material attributes and ensure quality of the final product. Copyright © 2016. Published by Elsevier Inc.

21 CFR 310.509 - Parenteral drug products in plastic containers.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Parenteral drug products in plastic containers... Parenteral drug products in plastic containers. (a) Any parenteral drug product packaged in a plastic... parenteral drug product for intravenous use in humans that is packaged in a plastic immediate container on or...

21 CFR 340.50 - Labeling of stimulant drug products.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of stimulant drug products. 340.50 Section 340.50 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 Labeling § 340.50...

The Methodical Instrumentarium for Analytical Monitoring of Markets for High-Tech Products

Directory of Open Access Journals (Sweden)

Mikaelian Suren G.

2017-10-01

Full Text Available The article is aimed at clarifying the essential characteristics of high-tech products and specifying the features of analytical monitoring of markets for high-tech products. The conceptual approaches to interpretation of the essence of high-tech products as a basic concept in the categorical apparatus for researching the systemic and complex processes of technological development have been clarified. The most efficient instruments for assessing innovation processes in the high-tech sphere have been systematized. The methodical instrumentarium for analytical monitoring of the markets for high-tech products has been clarified. The terminology of a high-tech product has been clarified in order to formulate the methodical instrumentarium for analytical monitoring of market for high-tech products. It has been determined that «high-tech products» are the original basic concept in the categorical apparatus for researching the systemic and complex processes of the high-tech market that needs to be concretized. Conceptual approaches to the essence of high-tech products have been systematized.

Prioritization of Programmer's Productivity Using Analytic Hierarchy ...

African Journals Online (AJOL)

This paper focuses on the application of Analytic Hierarchy Process (AHP) model in the context of prioritizing programmer's productivity in University of Benin, Benin City Nigeria. This is achieved by evaluating the way in which the AHP model can be used to select the best programmer for the purpose of developing software ...

Examining the production costs of antiretroviral drugs.

Science.gov (United States)

Pinheiro, Eloan; Vasan, Ashwin; Kim, Jim Yong; Lee, Evan; Guimier, Jean Marc; Perriens, Joseph

2006-08-22

To present direct manufacturing costs and price calculations of individual antiretroviral drugs, enabling those responsible for their procurement to have a better understanding of the cost structure of their production, and to indicate the prices at which these antiretroviral drugs could be offered in developing country markets. Direct manufacturing costs and factory prices for selected first and second-line antiretroviral drugs were calculated based on cost structure data from a state-owned company in Brazil. Prices for the active pharmaceutical ingredients (API) were taken from a recent survey by the World Health Organization (WHO). The calculated prices for antiretroviral drugs are compared with quoted prices offered by privately-owned, for-profit manufacturers. The API represents the largest component of direct manufacturing costs (55-99%), while other inputs, such as salaries, equipment costs, and scale of production, have a minimal impact. The calculated prices for most of the antiretroviral drugs studied fall within the lower quartile of the range of quoted prices in developing country markets. The exceptions are those drugs, primarily for second-line therapy, for which the API is either under patent, in short supply, or in limited use in developing countries (e.g. abacavir, lopinavir/ritonavir, nelfinavir, saquinavir). The availability of data on the cost of antiretroviral drug production and calculation of factory prices under a sustainable business model provide benchmarks that bulk purchasers of antiretroviral drugs could use to negotiate lower prices. While truly significant price decreases for antiretroviral drugs will depend largely on the future evolution of API prices, the present study demonstrates that for several antiretroviral drugs price reduction is currently possible. Whether or not these reductions materialize will depend on the magnitude of indirect cost and profit added by each supplier over the direct production costs. The ability to

The interpretation of hair analysis for drugs and drug metabolites.

Science.gov (United States)

Cuypers, Eva; Flanagan, Robert J

2018-02-01

Head hair analysis for drugs and drug metabolites has been used widely with the aim of detecting exposure in the weeks or months prior to sample collection. However, inappropriate interpretation of results has likely led to serious miscarriages of justice, especially in child custody cases. The aim of this review is to assess critically what can, and perhaps more importantly, what cannot be claimed as regards the interpretation of hair test results in a given set of circumstances in order to inform future testing. We searched the PubMed database for papers published 2010-2016 using the terms "hair" and "drug" and "decontamination", the terms "hair" and "drug" and "contamination", the terms "hair" and "drug-facilitated crime", the terms "hair" and "ethyl glucuronide", and the terms "hair", "drug testing" and "analysis". Study of the reference lists of the 46 relevant papers identified 25 further relevant citations, giving a total of 71 citations. Hair samples: Drugs, drug metabolites and/or decomposition products may arise not only from deliberate drug administration, but also via deposition from a contaminated atmosphere if drug(s) have been smoked or otherwise vaporized in a confined area, transfer from contaminated surfaces via food/fingers, etc., and transfer from sweat and other secretions after a single large exposure, which could include anesthesia. Excretion in sweat of endogenous analytes such as γ-hydroxybutyric acid is a potential confounder if its use is to be investigated. Cosmetic procedures such as bleaching or heat treatment of hair may remove analytes prior to sample collection. Hair color and texture, the area of the head the sample is taken from, the growth rate of individual hairs, and how the sample has been stored, may also affect the interpretation of results. Toxicological analysis: Immunoassay results alone do not provide reliable evidence on which to base judicial decisions. Gas or liquid chromatography with mass spectrometric detection

Summary report of PQRI Workshop on Nanomaterial in Drug Products: current experience and management of potential risks.

Science.gov (United States)

Bartlett, Jeremy A; Brewster, Marcus; Brown, Paul; Cabral-Lilly, Donna; Cruz, Celia N; David, Raymond; Eickhoff, W Mark; Haubenreisser, Sabine; Jacobs, Abigail; Malinoski, Frank; Morefield, Elaine; Nalubola, Ritu; Prud'homme, Robert K; Sadrieh, Nakissa; Sayes, Christie M; Shahbazian, Hripsime; Subbarao, Nanda; Tamarkin, Lawrence; Tyner, Katherine; Uppoor, Rajendra; Whittaker-Caulk, Margaret; Zamboni, William

2015-01-01

At the Product Quality Research Institute (PQRI) Workshop held last January 14-15, 2014, participants from academia, industry, and governmental agencies involved in the development and regulation of nanomedicines discussed the current state of characterization, formulation development, manufacturing, and nonclinical safety evaluation of nanomaterial-containing drug products for human use. The workshop discussions identified areas where additional understanding of material attributes, absorption, biodistribution, cellular and tissue uptake, and disposition of nanosized particles would continue to inform their safe use in drug products. Analytical techniques and methods used for in vitro characterization and stability testing of formulations containing nanomaterials were discussed, along with their advantages and limitations. Areas where additional regulatory guidance and material characterization standards would help in the development and approval of nanomedicines were explored. Representatives from the US Food and Drug Administration (USFDA), Health Canada, and European Medicines Agency (EMA) presented information about the diversity of nanomaterials in approved and newly developed drug products. USFDA, Health Canada, and EMA regulators discussed the applicability of current regulatory policies in presentations and open discussion. Information contained in several of the recent EMA reflection papers was discussed in detail, along with their scope and intent to enhance scientific understanding about disposition, efficacy, and safety of nanomaterials introduced in vivo and regulatory requirements for testing and market authorization. Opportunities for interaction with regulatory agencies during the lifecycle of nanomedicines were also addressed at the meeting. This is a summary of the workshop presentations and discussions, including considerations for future regulatory guidance on drug products containing nanomaterials.

Liposomal Drug Product Development and Quality: Current US Experience and Perspective.

Science.gov (United States)

Kapoor, Mamta; Lee, Sau L; Tyner, Katherine M

2017-05-01

Research in the area of liposomes has grown substantially in the past few decades. Liposomes are lipid bilayer structures that can incorporate drug substances to modify the drug's pharmacokinetic profile thereby improving drug delivery. The agency has received over 400 liposomal drug product submissions (excluding combination therapies), and there are currently eight approved liposomal drug products on the US market. In order to identify the pain points in development and manufacturing of liposomal drug products, a retrospective analysis was performed from a quality perspective on submissions for new and generic liposomal drug products. General analysis on liposomal drug product submissions was also performed. Results indicated that 96% of the submissions were Investigational New Drug (IND) applications, 3% were New Drug Applications (NDAs), and the remaining 1% was Abbreviated New Drug Applications (ANDAs). Doxorubicin hydrochloride was the most commonly used drug substance incorporated into the liposomes (31%). The majority of the liposomal products were administered via intravenous route (84%) with cancer (various types) being the most common indication (63%). From a quality perspective, major challenges during the development of liposomal drug products included identification and (appropriate) characterization of critical quality attributes of liposomal drug products and suitable control strategies during product development. By focusing on these areas, a faster and more efficient development of liposomal drug products may be achieved. Additionally, in this way, the drug review process for such products can be streamlined.

Optimizing clinical drug product performance

DEFF Research Database (Denmark)

Dickinson, Paul A.; Kesisoglou, Filippos; Flanagan, Talia

2016-01-01

The aim of Biopharmaceutics Risk Assessment Roadmap (BioRAM) and the BioRAM Scoring Grid is to facilitate optimization of clinical performance of drug products. BioRAM strategy relies on therapy-driven drug delivery and follows an integrated systems approach for formulating and addressing critical...... questions and decision-making (J Pharm Sci. 2014,103(11): 3777-97). In BioRAM, risk is defined as not achieving the intended in vivo drug product performance, and success is assessed by time to decision-making and action. Emphasis on time to decision-making and time to action highlights the value of well....... Application of the BioRAM Scoring Grid is illustrated using published literature. Organizational considerations for implementing BioRAM strategy, including the interactions, function, and skillsets of the BioRAM group members, are also reviewed. As a creative and innovative systems approach, we believe...

The production and sales of anti-tuberculosis drugs in China.

Science.gov (United States)

Huang, Yang-Mu; Zhao, Qi-Peng; Ren, Qiao-Meng; Peng, Dan-Lu; Guo, Yan

2016-10-04

Tuberculosis (TB) is a major infectious disease globally. Adequate and proper use of anti-TB drugs is essential for TB control. This study aims to study China's production capacity and sales situation of anti-TB drugs, and to further discuss the potential for China to contribute to global TB control. The production data of anti-TB drugs in China from 2011 to 2013 and the sales data from 2010 to 2014 were extracted from Ministry of Industry and Information Technology database of China and IMS Health database, respectively. The number of drugs was standardized to the molecular level of the key components before calculating. All data were described and analyzed by Microsoft Excel. First-line drugs were the majority in both sales (89.5 %) and production (92.3 %) of anti-TB drugs in China. The production of rifampicin held the majority share in active pharmaceutical ingredients (APIs) and finished products, whilst ethambutol and pyrazinamide were the top two sales in finished products. Fixed-dose combinations only held small percentages in total production and sales weight, though a slight increase was observed. The production and sales of streptomycin showed a tendency of decrease after 2012. The trends and proportion of different anti-TB drugs were similar in production and sales, however, the production weight was much larger than that of sales, especially for rifampicin and isoniazid. First-line drugs were the predominant medicine produced and used in China. While the low production and sales of the second-line TB drugs and FDCs rose concerns for the treatment of multiple drug resistant TB. The redundant production amount, as well as the prompt influence of national policy on drug production and sales, indicated the potential for China to better contribute to global TB control.

Process analytical technology (PAT) tools for the cultivation step in biopharmaceutical production

NARCIS (Netherlands)

Streefland, M.; Martens, D.E.; Beuvery, E.C.; Wijffels, R.H.

2013-01-01

The process analytical technology (PAT) initiative is now 10 years old. This has resulted in the development of many tools and software packages dedicated to PAT application on pharmaceutical processes. However, most applications are restricted to small molecule drugs, mainly for the relatively

Evaluation of the health effects of occupational exposure of analytic laboratory workers processing illicit drug investigation files.

Science.gov (United States)

Bentur, Y; Bentur, L; Rotenberg, M; Tepperberg, M; Leiba, R; Wolf, E Udi

2013-05-01

The Analytic Laboratory of Israel Police processes illicit drug files. In recent years, workers of this laboratory have complained of health problems. Limited information exists on the effect of occupational exposure to illicit drugs; biomonitoring was never done. To assess health effects and systemic absorption of illicit drugs in workers of the Analytic Laboratory occupationally exposed to illicit drugs. A prospective cohort study using health and occupational questionnaires, clinical assessments, and monitoring of urinary excretion of illicit drugs was conducted. The study included three blocks of one week each. At each week workers were assessed at the beginning (baseline), and the assessments were repeated at the end of the three working days. Urine specimens were analyzed for illicit drugs in an independent laboratory. Demographic, clinical, occupational, and laboratory data were subjected to descriptive analysis, and paired Student's t-test, chi-square analysis, and repeated measures model. Twenty-seven workers (age, 39.2 ± 8.3 years; 77.8% females) were included, yielding 122 paired samples. The following parameters were reduced at the end of shift compared with baseline: diastolic blood pressure (71.2 ± 11.2 and 77.2 ± 13.6 mmHg, respectively, p health complaints included headache, fatigue, and dry eyes. No illicit drug was detected in the urine specimens. It is suggested that the health concerns of the laboratory workers were not related to the absorption of illicit drugs; environmental conditions (e.g. inadequate ventilation and respirable dust) can contribute to these concerns.

Microfluidic Diatomite Analytical Devices for Illicit Drug Sensing with ppb-Level Sensitivity.

Science.gov (United States)

Kong, Xianming; Chong, Xinyuan; Squire, Kenny; Wang, Alan X

2018-04-15

The escalating research interests in porous media microfluidics, such as microfluidic paper-based analytical devices, have fostered a new spectrum of biomedical devices for point-of-care (POC) diagnosis and biosensing. In this paper, we report microfluidic diatomite analytical devices (μDADs), which consist of highly porous photonic crystal biosilica channels, as an innovative lab-on-a-chip platform to detect illicit drugs. The μDADs in this work are fabricated by spin-coating and tape-stripping diatomaceous earth on regular glass slides with cross section of 400×30µm 2 . As the most unique feature, our μDADs can simultaneously perform on-chip chromatography to separate small molecules from complex biofluidic samples and acquire the surface-enhanced Raman scattering spectra of the target chemicals with high specificity. Owing to the ultra-small dimension of the diatomite microfluidic channels and the photonic crystal effect from the fossilized diatom frustules, we demonstrate unprecedented sensitivity down to part-per-billion (ppb) level when detecting pyrene (1ppb) from mixed sample with Raman dye and cocaine (10 ppb) from human plasma. This pioneering work proves the exclusive advantage of μDADs as emerging microfluidic devices for chemical and biomedical sensing, especially for POC drug screening.

High-throughput oxidation screen of antibody-drug conjugates by analytical protein A chromatography following IdeS digest.

Science.gov (United States)

Buecheler, Jakob W; Winzer, Matthias; Weber, Christian; Gieseler, Henning

2018-05-01

Oxidation of protein therapeutics is a major chemical degradation pathway which may impact bioactivity, serum half-life and stability. Therefore, oxidation is a relevant parameter which has to be monitored throughout formulation development. Methods such as HIC, RPLC and LC/MS achieve a separation of oxidized and non-oxidized species by differences in hydrophobicity. Antibody-drug conjugates (ADC) although are highly more complex due to the heterogeneity in linker, drug, drug-to-antibody ratio (DAR) and conjugation site. The analytical protein A chromatography can provide a simple and fast alternative to these common methods. A miniature analytical protein A chromatography method in combination with an IdeS digest was developed to analyse ADCs. The IdeS digest efficiency of an IgG1 was monitored using SEC-HPLC and non-reducing SDS-PAGE. An antibody-fluorescent dye conjugate was conjugated at different dye-to-antibody ratios as model construct to mimic an ADC. With IdeS, an almost complete digest of a model IgG1 can be achieved (digested protein amount >98%). This enables subsequent analytical protein A chromatography, which consequently eliminates any interference of payload with the stationary phase. A novel high-throughput method for an interchain cysteine-linked ADC oxidation screens during formulation development was developed. © 2018 Royal Pharmaceutical Society.

Applied metabolomics in drug discovery.

Science.gov (United States)

Cuperlovic-Culf, M; Culf, A S

2016-08-01

The metabolic profile is a direct signature of phenotype and biochemical activity following any perturbation. Metabolites are small molecules present in a biological system including natural products as well as drugs and their metabolism by-products depending on the biological system studied. Metabolomics can provide activity information about possible novel drugs and drug scaffolds, indicate interesting targets for drug development and suggest binding partners of compounds. Furthermore, metabolomics can be used for the discovery of novel natural products and in drug development. Metabolomics can enhance the discovery and testing of new drugs and provide insight into the on- and off-target effects of drugs. This review focuses primarily on the application of metabolomics in the discovery of active drugs from natural products and the analysis of chemical libraries and the computational analysis of metabolic networks. Metabolomics methodology, both experimental and analytical is fast developing. At the same time, databases of compounds are ever growing with the inclusion of more molecular and spectral information. An increasing number of systems are being represented by very detailed metabolic network models. Combining these experimental and computational tools with high throughput drug testing and drug discovery techniques can provide new promising compounds and leads.

21 CFR 333.150 - Labeling of first aid antibiotic drug products.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of first aid antibiotic drug products... First Aid Antibiotic Drug Products § 333.150 Labeling of first aid antibiotic drug products. (a... identifies the product as a “first aid antibiotic.” (b) Indications. The labeling of the product states...

21 CFR 347.50 - Labeling of skin protectant drug products.

Science.gov (United States)

2010-04-01

... omitted. (f) Products containing only cocoa butter, petrolatum, or white petrolatum identified in § 347.10... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of skin protectant drug products. 347.50... (CONTINUED) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Labeling § 347...

Electronic tongue: An analytical gustatory tool

Directory of Open Access Journals (Sweden)

Rewanthwar Swathi Latha

2012-01-01

Full Text Available Taste is an important organoleptic property governing acceptance of products for administration through mouth. But majority of drugs available are bitter in taste. For patient acceptability and compliance, bitter taste drugs are masked by adding several flavoring agents. Thus, taste assessment is one important quality control parameter for evaluating taste-masked formulations. The primary method for the taste measurement of drug substances and formulations is by human panelists. The use of sensory panelists is very difficult and problematic in industry and this is due to the potential toxicity of drugs and subjectivity of taste panelists, problems in recruiting taste panelists, motivation and panel maintenance are significantly difficult when working with unpleasant products. Furthermore, Food and Drug Administration (FDA-unapproved molecules cannot be tested. Therefore, analytical taste-sensing multichannel sensory system called as electronic tongue (e-tongue or artificial tongue which can assess taste have been replacing the sensory panelists. Thus, e-tongue includes benefits like reducing reliance on human panel. The present review focuses on the electrochemical concepts in instrumentation, performance qualification of E-tongue, and applications in various fields.

Drug-device combination products: regulatory landscape and market growth.

Science.gov (United States)

Bayarri, L

2015-08-01

Combination products are therapeutic and diagnostic products that combine drugs, devices and/or biological products, leading to safer and more effective treatments thanks to careful and precise drug targeting, local administration and individualized therapy. These technologies can especially benefit patients suffering from serious diseases and conditions such as cancer, heart disease, multiple sclerosis and diabetes, among others. On the other hand, drug-device combination products have also introduced a new dynamic in medical product development, regulatory approval and corporate interaction. Due to the increasing integration of drugs and devices observed in the latest generation of combination products, regulatory agencies have developed specific competences and regulations over the last decade. Manufacturers are required to fully understand the specific requirements in each country in order to ensure timely and accurate market access of new combination products, and the development of combination products involves a very specific pattern of interactions between manufacturers and regulatory agencies. The increased sophistication of the products brought to market over the last couple of decades has accentuated the need to develop drugs and devices collaboratively using resources from both industries, fostering the need of business partnering and technology licensing. This review will provide a global overview of the market trends, as well as (in the last section) an analysis of the drug-device combination products approved by the FDA during the latest 5 years. Copyright 2015 Prous Science, S.A.U. or its licensors. All rights reserved.

Considerations of critical quality attributes in the analytical comparability assessment of biosimilar products.

Science.gov (United States)

Kwon, Ohseok; Joung, Jeewon; Park, Younjoo; Kim, Chan Wha; Hong, Seung Hwa

2017-07-01

Based on experience in clinical trial approvals and marketing authorizations for biosimilar products in Korea, we suggest principles for the analytical comparability assessment of biosimilar products with respect to regulatory considerations. The composition and manufacturing processes of biosimilar products can differ from those of the reference product depending on the information available for the reference product and the time of product development; however, the analytical characteristics of biosimilar products should be highly similar to those of the reference product. Although manufacturing an identical product in terms of the quality profile is nearly impossible due to the high molecular weight and complex structure of biological products, the developer of the biosimilar product should attempt to establish a quality level as similar to that of the reference product as possible. When comparing the similarity of quality attributes, the criticality of the quality attributes and the characteristics of orthogonal quality attributes need to be considered carefully. Based on the results from the analytical comparability assessment, the comparability results of non-clinical and clinical studies should be evaluated before claiming biosimilarity to the reference product. In this review, we focus on quality attribute evaluation based on our regulatory experience. Copyright © 2017 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

Patient centric drug product design in modern drug delivery as an opportunity to increase safety and effectiveness.

Science.gov (United States)

Stegemann, Sven

2018-06-01

The advances in drug delivery technologies have enabled pharmaceutical scientists to deliver a drug through various administration routes and optimize the drug release and absorption. The wide range of drug delivery systems and dosage forms represent a toolbox of technology for the development of pharmaceutical drug products but might also be a source of medication errors and nonadherence. Patient centric drug product development is being suggested as an important factor to increase therapeutic outcomes. Areas covered: Patients have impaired health and potentially disabilities and they are not medical or pharmaceutical experts but are requested to manage complex therapeutic regimens. As such the application of technology should also serve to reduce complexity, build on patients' intuition and ease of use. Patients form distinct populations based on the targeted disease, disease cluster or age group with specific characteristics or therapeutic contexts. Expert opinion: Establishing a target product and patient profile is essential to guide drug product design development. Including the targeted patient populations in the process is a prerequisite to achieve patient-centric pharmaceutical drug product design. Addressing the needs early on in the product design process, will create more universal design, avoiding the necessity for multiple product presentations to cover the different patient populations.

21 CFR 344.52 - Labeling of ear drying aid drug products.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of ear drying aid drug products. 344.52 Section 344.52 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Labeling of ear drying aid drug products. (a) Statement of identity. The labeling of the product contains...

Pricing for finished products of the enterprise: accounting and analytical aspect

Directory of Open Access Journals (Sweden)

N.L. Pravdyuk

2017-03-01

Full Text Available The pricing policy chosen by the enterprise in respect of goods and finished products of own production, has a decisive influence on the formation of financial results. In modern economic conditions we need to strengthen managerial decisions on the choice and carrying out price policy and a means of solving this problem is accounting. To determine the boundaries and competence of decision-making we analyzed the regulation of these terms and processes, as well as the dynamics of the stocks across sectors of the economy, the consumer price index, producer price index, the price index of realization of industrial products. Widely used data analytical reviews of the national Bank of Ukraine, enterprises' expectations regarding efficiency, the analysis of financial market indicators, etc. Established that the provision of information management pricing of goods shall conform to the requirements of the economy, by deepening complexity of accounting, to ensure the needs of consumers. According to the study substantiates the basics of accounting and analytical aspect of the pricing policy for finished products businesses. In the study of pricing policies in respect of goods in accounting and analytical aspect, we have established the following. The existing normative-legal acts and definitions of researchers on economic and accounting analysis of the concept give a sufficiently wide interpretation, which depends on the orientation and activity of the enterprise. Factors and points of influence on the efficiency of the pricing policy are: information support of process of pricing assessment of pricing factors, establish the objectives of price policy, assessment of customer demand, cost analysis, competition analysis, selecting a pricing method that measures the price adjustment, the evaluation price risk. The economic impact of the market environment is the most significant to the pricing policy of agricultural enterprises, which revealed the analysis

Surveillance of emerging drugs of abuse in Hong Kong: validation of an analytical tool.

Science.gov (United States)

Tang, Magdalene H Y; Ching, C K; Tse, M L; Ng, Carol; Lee, Caroline; Chong, Y K; Wong, Watson; Mak, Tony W L

2015-04-01

To validate a locally developed chromatography-based method to monitor emerging drugs of abuse whilst performing regular drug testing in abusers. Cross-sectional study. Eleven regional hospitals, seven social service units, and a tertiary level clinical toxicology laboratory in Hong Kong. A total of 972 drug abusers and high-risk individuals were recruited from acute, rehabilitation, and high-risk settings between 1 November 2011 and 31 July 2013. A subset of the participants was of South Asian ethnicity. In total, 2000 urine or hair specimens were collected. Proof of concept that surveillance of emerging drugs of abuse can be performed whilst conducting routine drug of abuse testing in patients. The method was successfully applied to 2000 samples with three emerging drugs of abuse detected in five samples: PMMA (paramethoxymethamphetamine), TFMPP [1-(3-trifluoromethylphenyl)piperazine], and methcathinone. The method also detected conventional drugs of abuse, with codeine, methadone, heroin, methamphetamine, and ketamine being the most frequently detected drugs. Other findings included the observation that South Asians had significantly higher rates of using opiates such as heroin, methadone, and codeine; and that ketamine and cocaine had significantly higher detection rates in acute subjects compared with the rehabilitation population. This locally developed analytical method is a valid tool for simultaneous surveillance of emerging drugs of abuse and routine drug monitoring of patients at minimal additional cost and effort. Continued, proactive surveillance and early identification of emerging drugs will facilitate prompt clinical, social, and legislative management.

Analytical calculation of heavy quarkonia production processes in computer

International Nuclear Information System (INIS)

Braguta, V V; Likhoded, A K; Luchinsky, A V; Poslavsky, S V

2014-01-01

This report is devoted to the analytical calculation of heavy quarkonia production processes in modern experiments such as LHC, B-factories and superB-factories in computer. Theoretical description of heavy quarkonia is based on the factorization theorem. This theorem leads to special structure of the production amplitudes which can be used to develop computer algorithm which calculates these amplitudes automatically. This report is devoted to the description of this algorithm. As an example of its application we present the results of the calculation of double charmonia production in bottomonia decays and inclusive the χ cJ mesons production in pp-collisions

21 CFR 1310.11 - Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. 1310.11 Section 1310.11 Food and Drugs DRUG ENFORCEMENT... Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. (a) The...

Approved Drug Products with Therapuetic Equivalence Evaluations (Orange Book)

Data.gov (United States)

U.S. Department of Health & Human Services — The publication Approved Drug Products with Therapeutic Equivalence Evaluations (the List, commonly known as the Orange Book) identifies drug products approved on...

Using Nonexperts for Annotating Pharmacokinetic Drug-Drug Interaction Mentions in Product Labeling: A Feasibility Study.

Science.gov (United States)

Hochheiser, Harry; Ning, Yifan; Hernandez, Andres; Horn, John R; Jacobson, Rebecca; Boyce, Richard D

2016-04-11

Because vital details of potential pharmacokinetic drug-drug interactions are often described in free-text structured product labels, manual curation is a necessary but expensive step in the development of electronic drug-drug interaction information resources. The use of nonexperts to annotate potential drug-drug interaction (PDDI) mentions in drug product label annotation may be a means of lessening the burden of manual curation. Our goal was to explore the practicality of using nonexpert participants to annotate drug-drug interaction descriptions from structured product labels. By presenting annotation tasks to both pharmacy experts and relatively naïve participants, we hoped to demonstrate the feasibility of using nonexpert annotators for drug-drug information annotation. We were also interested in exploring whether and to what extent natural language processing (NLP) preannotation helped improve task completion time, accuracy, and subjective satisfaction. Two experts and 4 nonexperts were asked to annotate 208 structured product label sections under 4 conditions completed sequentially: (1) no NLP assistance, (2) preannotation of drug mentions, (3) preannotation of drug mentions and PDDIs, and (4) a repeat of the no-annotation condition. Results were evaluated within the 2 groups and relative to an existing gold standard. Participants were asked to provide reports on the time required to complete tasks and their perceptions of task difficulty. One of the experts and 3 of the nonexperts completed all tasks. Annotation results from the nonexpert group were relatively strong in every scenario and better than the performance of the NLP pipeline. The expert and 2 of the nonexperts were able to complete most tasks in less than 3 hours. Usability perceptions were generally positive (3.67 for expert, mean of 3.33 for nonexperts). The results suggest that nonexpert annotation might be a feasible option for comprehensive labeling of annotated PDDIs across a broader

A primer of drug safety surveillance: an industry perspective. Part II: Product labeling and product knowledge.

Science.gov (United States)

Allan, M C

1992-01-01

To place the fundamentals of clinical drug safety surveillance in a conceptual framework that will facilitate understanding and application of adverse drug event data to protect the health of the public and support a market for pharmaceutical manufacturers' products. Part II of this series discusses specific issues regarding product labeling, such as developing the labeling, changing the labeling, and the legal as well as commercial ramifications of the contents of the labeling. An adverse event report scenario is further analyzed and suggestions are offered for maintaining the product labeling as an accurate reflection of the drug safety surveillance data. This article also emphasizes the necessity of product knowledge in adverse event database management. Both scientific and proprietary knowledge are required. Acquiring product knowledge is a part of the day-to-day activities of drug safety surveillance. A knowledge of the history of the product may forestall adverse publicity, as shown in the illustration. This review uses primary sources from the federal laws (regulations), commentaries, and summaries. Very complex topics are briefly summarized in the text. Secondary sources, ranging from newspaper articles to judicial summaries, illustrate the interpretation of adverse drug events and opportunities for drug safety surveillance intervention. The reference materials used were articles theoretically or practically applicable in the day-to-day practice of drug safety surveillance. The role of clinical drug safety surveillance in product monitoring and drug development is described. The process of drug safety surveillance is defined by the Food and Drug Administration regulations, product labeling, product knowledge, and database management. Database management is subdivided into the functions of receipt, retention, retrieval, and review of adverse event reports. Emphasis is placed on the dynamic interaction of the components of the process. Suggestions are offered

Characterization of SNARE Cleavage Products Generated by Formulated Botulinum Neurotoxin Type-A Drug Products

Directory of Open Access Journals (Sweden)

Jack Xie

2010-08-01

Full Text Available The study evaluated substrate cleavage product(s generated by three botulinum neurotoxin serotype A (BoNT/A medicinal drug products utilizing a novel and highly specific, light-chain activity, high-performance liquid chromatography (LCA-HPLC method. Samples were reacted with a commercially available BoNT/A fluorescent substrate derived from the SNAP-25 sequence. Reaction products were separated by reversed-phase HPLC. The method detected an atypical cleavage pattern by one of the formulated drug products. IncobotulinumtoxinA produced two cleavage fragments rather than the single fragment typically generated by BoNT/A. Identification confirmed the secondary cleavage at a position corresponding to SNAP-25 Arg198–Ala199 (normal BoNT/A cleavage is Gln197–Arg198. Arg198–Ala199 is also the cleavage site for trypsin and serotype C toxin. Normal cleavage was observed for all other BoNT/A drug product samples, as well as 900-kD and 150-kD bulk toxin BoNT/A. The reason for this unexpected secondary cleavage pattern by one formulated BoNT/A drug product is unknown. Possible explanations include a contaminating protease and/or damage to the 150-kD type-A toxin causing nonspecific substrate recognition and subsequent cleavage uncharacteristic of type-A toxin. The BoNT/A drug products were also analyzed via the LCA-HPLC assay using a commercial BoNT/C fluorescent substrate derived from the syntaxin sequence. Cleavage of the serotype C substrate by incobotulinumtoxinA was also confirmed whilst neither of the other drug products cleaved the syntaxin substrate.

Development of Radiometric and Allied Analytical Methods and Strategies to Strengthen National Residue Control Programmes for Antibiotic and Anthelmintic Veterinary Drug Residues. Final Report of a Coordinated Research Project

International Nuclear Information System (INIS)

2016-08-01

Awareness of food safety is rising among consumers, and many importing countries implement food control regulations to guarantee the quality and safety of imported foods for their consumers. Many developing countries have also taken steps to put in place control systems that encourage responsible use of veterinary medicines to combat possible drug resistance, control drug residues and ensure compliance with international and national standards. However, these countries still require the necessary know-how and skills to protect local consumers and to access international markets. One significant constraint is the capacity of laboratory services to generate surveillance data using reliable and cost effective analytical methods validated to national and international standards. The IAEA coordinated research project (CRP) on the Development of Radiometric and Allied Analytical Methods to Strengthen National Residue Control Programmes for Antibiotic and Anthelmintic Veterinary Drug Residues was initiated in 2009 to conduct work on robust nuclear and related technologies suitable for the screening and confirmatory analysis of residues of veterinary medicines, including antimicrobials and anthelmintics commonly used in animal production, with public health and trade significance. The CRP also explored mechanisms to enhance networking among research institutions involved in research on pharmacologically active veterinary drug residues in food (primarily) and environmental samples. The project was implemented by the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture between 2009 and 2014 and involved eleven research contracts and one technical contract, five research agreements and one institution. The CRP was a continuation of the CRP on the Development of Strategies for the Effective Monitoring of Veterinary Drug Residues in Livestock and Livestock Products in Developing Countries and the key findings are also summarized in this publication.

Success rates for product development strategies in new drug development.

Science.gov (United States)

Dahlin, E; Nelson, G M; Haynes, M; Sargeant, F

2016-04-01

While research has examined the likelihood that drugs progress across phases of clinical trials, no research to date has examined the types of product development strategies that are the most likely to be successful in clinical trials. This research seeks to identify the strategies that are most likely to reach the market-those generated using a novel product development strategy or strategies that combine a company's expertise with both drugs and indications, which we call combined experience strategies. We evaluate the success of product development strategies in the drug development process for a sample of 2562 clinical trials completed by 406 US pharmaceutical companies. To identify product development strategies, we coded each clinical trial according to whether it consisted of an indication or a drug that was new to the firm. Accordingly, a clinical trial that consists of both an indication and a drug that were both new to the firm represents a novel product development strategy; indication experience is a product development strategy that consists of an indication that a firm had tested previously in a clinical trial, but with a drug that was new to the firm; drug experience is a product development strategy that consists of a drug that the firm had prior experience testing in clinical trials, but with an indication that was new to the firm; combined experience consists of both a drug and an indication that the firm had experience testing in clinical trials. Success rates for product development strategies across clinical phases were calculated for the clinical trials in our sample. Combined experience strategies had the highest success rate. More than three and a half percent (0·036) of the trials that combined experience with drugs and indications eventually reached the market. The next most successful strategy is drug experience (0·025) with novel strategies trailing closely (0·024). Indication experience strategies are the least successful (0·008

Analytical characterization of recombinant hCG and comparative studies with reference product.

Science.gov (United States)

Thennati, Rajamannar; Singh, Sanjay Kumar; Nage, Nitin; Patel, Yena; Bose, Sandip Kumar; Burade, Vinod; Ranbhor, Ranjit Sudhakar

2018-01-01

Regulatory agencies recommend a stepwise approach for demonstrating biosimilarity between a proposed biosimilar and reference biological product emphasizing for functional and structural characterization to trace if there is any difference which may impact safety and efficacy. We studied the comparative structural and biological attributes of recombinant human chorionic gonadotropin (rhCG), SB005, with reference product, Ovidrel ® and Ovitrelle ® . Recombiant hCG was approved in 2000 by the US Food and Drug Administration for the induction of final follicular maturation, early luteinization in infertile women as part of assisted reproductive technology program. It is also indicated for the induction of ovulation and pregnancy in ovulatory infertile patients whose cause of infertility is not due to ovarian failure. Primary structure was studied by intact mass analysis, peptide fingerprinting, peptide mass fingerprinting and sequence coverage analysis. Higher order structure was studied by circular dichroism, ultraviolet-visible spectroscopy, fluorescence spectroscopy, and disulfide bridge analysis. Different isoforms of reference product and SB005 were identified using capillary isoelectric focusing and capillary zone electrophoresis. Glycosylation was studied by N-glycan mapping using LC-ESI-MS, point of glycosylation, released glycan analysis using ultra performance liquid chromatography and sialic acid analysis. Product related impurities such as oligomer content analysis and oxidized impurities were studied using size exclusion chromatography and reverse phase high performance liquid chromatography, respectively. Biological activity in term of potency of reference product and SB005 was studied by in vivo analysis. In this study we have compared analytical similarity of recombinant rhCG (SB005) produced at Sun Pharmaceuticals with the reference product with respect to its primary, higher order structure, isoforms, charge variants, glycosylation, sialyation

Semi-analytic calculations for the impact parameter dependence of electromagnetic multi-lepton pair production

International Nuclear Information System (INIS)

Gueclue, M.C.

2000-01-01

We provide a new general semi-analytic derivation of the impact parameter dependence of lowest order electromagnetic lepton-pair production in relativistic heavy-ion collisions. By using this result we have also calculated the related analytic multiple-pair production in the two-photon external-field model. We have compared our results with the equivalent-photon approximation and other calculations

Complex compounds of terbium(III) with some nonsteroidal anti-inflammatory drugs and their analytical applications

International Nuclear Information System (INIS)

Teslyuk, O.I.; Egorova, A.V.; Yagodkin, B.N.; Bel'tyukova, S.V.

2007-01-01

Luminescence properties of the complexes of terbium(III) with nonsteroidal anti-inflammatory drugs (ibuprofen and orthofen) were studied. It was demonstrated that in the presence of organic bases (2,2'-dipyridyl and 1,10-phenanthroline) mixed-ligand complexes are formed and the luminescence intensity of terbium(III) increases by a factor of up to 250. The optimum complexation conditions were determined. It was proposed to use these complexes as analytical forms for the luminescence determination of nonsteroidal anti-inflammatory drugs (ibuprofen and orthofen) in pharmaceutical dosage forms. The detection limits are 2 and 0.05 μg/ml, respectively [ru

Analytical Web Tool for CERES Products

Science.gov (United States)

Mitrescu, C.; Chu, C.; Doelling, D.

2012-12-01

The CERES project provides the community climate quality observed TOA fluxes, consistent cloud properties, and computed profile and surface fluxes. The 11-year long data set proves invaluable for remote sensing and climate modeling communities for annual global mean energy, meridianal heat transport, consistent cloud and fluxes and climate trends studies. Moreover, a broader audience interested in Earth's radiative properties such as green energy, health and environmental companies have showed their interest in CERES derived products. A few years ago, the CERES team start developing a new web-based Ordering Tool tailored for this wide diversity of users. Recognizing the potential that web-2.0 technologies can offer to both Quality Control (QC) and scientific data visualization and manipulation, the CERES team began introducing a series of specialized functions that addresses the above. As such, displaying an attractive, easy to use modern web-based format, the Ordering Tool added the following analytical functions: i) 1-D Histograms to display the distribution of the data field to identify outliers that are useful for QC purposes; ii) an "Anomaly" map that shows the regional differences between the current month and the climatological monthly mean; iii) a 2-D Histogram that can identify either potential problems with the data (i.e. QC function) or provides a global view of trends and/or correlations between various CERES flux, cloud, aerosol, and atmospheric properties. The large volume and diversity of data, together with the on-the-fly execution were the main challenges that had to be tackle with. Depending on the application, the execution was done on either the browser side or the server side with the help of auxiliary files. Additional challenges came from the use of various open source applications, the multitude of CERES products and the seamless transition from previous development. For the future, we plan on expanding the analytical capabilities of the

Lessons from innovation in drug-device combination products.

Science.gov (United States)

Couto, Daniela S; Perez-Breva, Luis; Saraiva, Pedro; Cooney, Charles L

2012-01-01

Drug-device combination products introduced a new dynamic on medical product development, regulatory approval, and corporate interaction that provide valuable lessons for the development of new generations of combination products. This paper examines the case studies of drug-eluting stents and transdermal patches to facilitate a detailed understanding of the challenges and opportunities introduced by combination products when compared to previous generations of traditional medical or drug delivery devices. Our analysis indicates that the largest barrier to introduce a new kind of combination products is the determination of the regulatory center that is to oversee its approval. The first product of a new class of combination products offers a learning opportunity for the regulator and the sponsor. Once that first product is approved, the leading regulatory center is determined, and the uncertainty about the entire class of combination products is drastically reduced. The sponsor pioneering a new class of combination products assumes a central role in reducing this uncertainty by advising the decision on the primary function of the combination product. Our analysis also suggests that this decision influences the nature (pharmaceutical, biotechnology, or medical devices) of the companies that will lead the introduction of these products into the market, and guide the structure of corporate interaction thereon. Copyright © 2011 Elsevier B.V. All rights reserved.

Analytical approaches for the detection of emerging therapeutics and non-approved drugs in human doping controls.

Science.gov (United States)

Thevis, Mario; Schänzer, Wilhelm

2014-12-01

The number and diversity of potentially performance-enhancing substances is continuously growing, fueled by new pharmaceutical developments but also by the inventiveness and, at the same time, unscrupulousness of black-market (designer) drug producers and providers. In terms of sports drug testing, this situation necessitates reactive as well as proactive research and expansion of the analytical armamentarium to ensure timely, adequate, and comprehensive doping controls. This review summarizes literature published over the past 5 years on new drug entities, discontinued therapeutics, and 'tailored' compounds classified as doping agents according to the regulations of the World Anti-Doping Agency, with particular attention to analytical strategies enabling their detection in human blood or urine. Among these compounds, low- and high-molecular mass substances of peptidic (e.g. modified insulin-like growth factor-1, TB-500, hematide/peginesatide, growth hormone releasing peptides, AOD-9604, etc.) and non-peptidic (selective androgen receptor modulators, hypoxia-inducible factor stabilizers, siRNA, S-107 and ARM036/aladorian, etc.) as well as inorganic (cobalt) nature are considered and discussed in terms of specific requirements originating from physicochemical properties, concentration levels, metabolism, and their amenability for chromatographic-mass spectrometric or alternative detection methods. Copyright © 2014 Elsevier B.V. All rights reserved.

Analytical evaluation of fission product sensitivities

International Nuclear Information System (INIS)

Sola, A.

1977-01-01

Evaluating the concentration of a fission product produced in a reactor requires the knowledge of a fairly large number of variables. Sensitivity studies were made to ascertain the important variables. Analytical formulae were developed sufficiently simple to allow numerical computations. Some simplified formulas are also given and they are applied to the following isotopes: 80 Se, 82 Se, 81 Br, 82 Br, 82 Kr, 83 Kr, 84 Kr, 85 Kr, 86 Kr. Their sensitivities to capture cross sections, fission yields, ratios of activation cross sections, half-lives (during and after irradiation), branching ratios, as well as to the neutron flux and to the time are considered

Drug Production in Tertiary Health Institutions – Needs, Constraints ...

African Journals Online (AJOL)

The use of questionnaires was employed in the study covering all pharmacists in the pharmaceutical services department, pharmacy technicians and quality control technologist in the drug production unit of the hospital. It was unanimously agreed by the respondents that local drug production was necessary in tertiary ...

Transporter-mediated natural product-drug interactions for the treatment of cardiovascular diseases.

Science.gov (United States)

Zha, Weibin

2018-04-01

The growing use of natural products in cardiovascular (CV) patients has been greatly raising the concerns about potential natural product-CV drug interactions. Some of these may lead to unexpected cardiovascular adverse effects and it is, therefore, essential to identify or predict potential natural product-CV drug interactions, and to understand the underlying mechanisms. Drug transporters are important determinants for the pharmacokinetics of drugs and alterations of drug transport has been recognized as one of the major causes of natural product-drug interactions. In last two decades, many CV drugs (e.g., angiotensin II receptor blockers, beta-blockers and statins) have been identified to be substrates and inhibitors of the solute carrier (SLC) transporters and the ATP-binding cassette (ABC) transporters, which are two major transporter superfamilies. Meanwhile, in vitro and in vivo studies indicate that a growing number of natural products showed cardioprotective effects (e.g., gingko biloba, danshen and their active ingredients) are also substrates and inhibitors of drug transporters. Thus, to understand transporter-mediated natural product-CV drug interactions is important and some transporter-mediated interactions have already shown to have clinical relevance. In this review, we review the current knowledge on the role of ABC and SLC transporters in CV therapy, as well as transporter modulation by natural products used in CV diseases and their induced natural product-CV drug interactions through alterations of drug transport. We hope our review will aid in a comprehensive summary of transporter-mediated natural product-CV drug interactions and help public and physicians understand these type of interactions. Copyright © 2017. Published by Elsevier B.V.

Production of drug nanosuspensions: effect of drug physical properties on nanosizing efficiency.

Science.gov (United States)

Liu, Tao; Müller, Rainer H; Möschwitzer, Jan P

2018-02-01

Drug nanosuspension is one of the established methods to improve the bioavailability of poorly soluble drugs. Drug physical properties aspect (morphology, solid state, starting size et al) is a critical parameter determining the production efficiency. Some drug modification approaches such as spray-drying were proved to improve the millability of drug powders. However, the mechanism behind those improved performances is unclear. This study is to systematically investigate the influence of those physical properties. Five different APIs (active pharmaceutical ingredients) with different millabilities, i.e. resveratrol, hesperetin, glibenclamide, rutin, and quercetin, were processed by standard high pressure homogenization (HPH), wet bead milling (WBM), and a combinative method of spray-drying and HPH. Smaller starting sizes of certain APIs could accelerate the particle size reduction velocity during both HPH and WBM processes. Spherical particles were observed for almost all spray-dried powders (except spray-dried hesperetin) after spray-drying. The crystallinity of some spray-dried samples such as rutin and glibenclamide became much lower than their corresponding unmodified powders. Almost all spray-dried drug powders after HPH processes could lead to smaller nanocrystal particle size than unmodified APIs. The modified microstructure instead of solid state after spray-drying explained the potential reason for improved nanosizing efficiency. In addition, the contribution of starting size on the production efficiency was also critical according to both HPH and WBM results.

Analytical tools for determination of new oral antidiabetic drugs, glitazones, gliptins, gliflozins and glinides, in bulk materials, pharmaceuticals and biological samples

Directory of Open Access Journals (Sweden)

Gumieniczek Anna

2016-01-01

Full Text Available The review presents analytical methods for determination of new oral drugs for the treatment of type 2 diabetes mellitus (T2DM, focusing on peroxisome proliferator-activated receptor gamma agonists (glitazones, dipeptidyl peptidase 4 inhibitors (gliptins and sodium/glucose co-transporter 2 inhibitors (gliflozins. Drugs derived from prandial glucose regulators, such as glinides, are considered because they are present in some new therapeutic options. The review presents analytical procedures suitable for determination of the drugs in bulk substances, such as pharmaceuticals and biological samples, including HPLC-UV, HPLC/LC-MS, TLC/HPTLC, CE/CE-MS, spectrophotometric (UV/VIS, spectrofluorimetric and electrochemical methods, taken from the literature over the past ten years (2006-2016. Some new procedures for extraction, separation and detection of the drugs, including solid phase extraction with molecularly imprinted polymers (SPE-MIP, liquid phase microextraction using porous hollow fibers (HP-LPME, HILIC chromatography, micellar mobile phases, ion mobility spectrometry (IMS and isotopically labeled internal standards, are discussed.

21 CFR 864.4020 - Analyte specific reagents.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Analyte specific reagents. 864.4020 Section 864.4020 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Specimen Preparation Reagents § 864.4020 Analyte specific...

Toward a generic approach for : Stress testing of drug substances and drug products

NARCIS (Netherlands)

Klick, Silke; Muijselaar, Pim G.; Waterval, Joop; Eichinger, Thomas; Korn, Christian; Gerding, Thijs K.; Debets, Alexander J.; Sänger-Van De Griend, Cari; Van Den Beld, Cas; Somsen, Govert W.; De Jong, Gerhardus J.

The Impurity Profiling Group has developed a generic approach for conducting stress testing on drug substances and drug products. The proposed strategy is evaluated and verified with historical data and new experiments. Results demonstrate that the proposed approach is reasonable and generates

Statistical Approaches to Assess Biosimilarity from Analytical Data.

Science.gov (United States)

Burdick, Richard; Coffey, Todd; Gutka, Hiten; Gratzl, Gyöngyi; Conlon, Hugh D; Huang, Chi-Ting; Boyne, Michael; Kuehne, Henriette

2017-01-01

Protein therapeutics have unique critical quality attributes (CQAs) that define their purity, potency, and safety. The analytical methods used to assess CQAs must be able to distinguish clinically meaningful differences in comparator products, and the most important CQAs should be evaluated with the most statistical rigor. High-risk CQA measurements assess the most important attributes that directly impact the clinical mechanism of action or have known implications for safety, while the moderate- to low-risk characteristics may have a lower direct impact and thereby may have a broader range to establish similarity. Statistical equivalence testing is applied for high-risk CQA measurements to establish the degree of similarity (e.g., highly similar fingerprint, highly similar, or similar) of selected attributes. Notably, some high-risk CQAs (e.g., primary sequence or disulfide bonding) are qualitative (e.g., the same as the originator or not the same) and therefore not amenable to equivalence testing. For biosimilars, an important step is the acquisition of a sufficient number of unique originator drug product lots to measure the variability in the originator drug manufacturing process and provide sufficient statistical power for the analytical data comparisons. Together, these analytical evaluations, along with PK/PD and safety data (immunogenicity), provide the data necessary to determine if the totality of the evidence warrants a designation of biosimilarity and subsequent licensure for marketing in the USA. In this paper, a case study approach is used to provide examples of analytical similarity exercises and the appropriateness of statistical approaches for the example data.

Product design planning with the analytic hierarchy process in inter-organizational networks

NARCIS (Netherlands)

Hummel, J. Marjan; van Rossum, Wouter; Verkerke, Gijsbertus Jacob; Rakhorst, Gerhard

2002-01-01

In the second half of inter–organizational product development, the new product is likely to face significant design changes. Our study focused on the adequacy of the analytic hierarchy process (AHP) to support the collaborative partners to steer and align the accompanying design activities. It

Product design planning with the analytic hierarchy process in inter-organizational networks

NARCIS (Netherlands)

Hummel, J.M.; van Rossum, Wouter; Verkerke, Bart; Rakhorst, G

2002-01-01

In the second half of inter-organizational product developments the new product is likely to face significant design changes. Our study focused on the adequacy of the analytic hierarchy process (AHP) to support the collaborative partners to steer and align the accompanying design activities. It

Recreational drug discovery: natural products as lead structures for the synthesis of smart drugs.

Science.gov (United States)

Appendino, Giovanni; Minassi, Alberto; Taglialatela-Scafati, Orazio

2014-07-01

Covering: up to December 2013. Over the past decade, there has been a growing transition in recreational drugs from natural materials (marijuana, hashish, opium), natural products (morphine, cocaine), or their simple derivatives (heroin), to synthetic agents more potent than their natural prototypes, which are sometimes less harmful in the short term, or that combine properties from different classes of recreational prototypes. These agents have been named smart drugs, and have become popular both for personal consumption and for collective intoxication at rave parties. The reasons for this transition are varied, but are mainly regulatory and commercial. New analogues of known illegal intoxicants are invisible to most forensic detection techniques, while the alleged natural status and the lack of avert acute toxicity make them appealing to a wide range of users. On the other hand, the advent of the internet has made possible the quick dispersal of information among users and the on-line purchase of these agents and/or the precursors for their synthesis. Unlike their natural products chemotypes (ephedrine, mescaline, cathinone, psilocybin, THC), most new drugs of abuse are largely unfamiliar to the organic chemistry community as well as to health care providers. To raise awareness of the growing plague of smart drugs we have surveyed, in a medicinal chemistry fashion, their development from natural products leads, their current methods of production, and the role that clandestine home laboratories and underground chemists have played in the surge of popularity of these drugs.

21 CFR 250.250 - Hexachlorophene, as a component of drug and cosmetic products.

Science.gov (United States)

2010-04-01

... cosmetic products. 250.250 Section 250.250 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Requirements for Drugs and Cosmetics § 250.250 Hexachlorophene, as a component of drug and cosmetic products... cosmetic products has expanded widely in recent years. It is used in such products because of its...

Using the analytic hierarchy process to support teams in defining new product objectives

NARCIS (Netherlands)

Hummel, J.M.; Verkerke, G.J.; van Rossum, W.; Rakhorst, G.; Hummel, J.M.

2001-01-01

Defining new product objectives is a critical problem solving activity to new product success. The analytic hierarchy process appears to be an adequate technique for multi-criteria decision analysis to support the definition of new product objectives. To illustrate this support, we applied this

OPEC production ceilings and quotas: an analytical review

International Nuclear Information System (INIS)

Bakhtiari, A.M.S.

1992-01-01

After the onset of Gulf hostilities in August 1990, oil production, equivalent to some five million barrels per day, dried up. With two major exporters, Iraq and Kuwait, out of contention, other OPEC Members were suddenly free to produce and export at will. For the rest of 1990 and the whole of 1991, the issue of quotas was put on the backburner. Hence, the present analytical paper on past OPEC production quota agreements has been prepared. It is an attempt to correlate individual OPEC quotas with meaningful and tangible variables, using a curve-fitting computer programme. The main endeavour in this project is to find either a theoretical or an empirical basis for the generation of OPEC quotas. (author)

A Review of Analytical Methods for p-Coumaric Acid in Plant-Based Products, Beverages, and Biological Matrices.

Science.gov (United States)

Ferreira, Paula Scanavez; Victorelli, Francesca Damiani; Fonseca-Santos, Bruno; Chorilli, Marlus

2018-05-14

p-Coumaric acid (p-CA), also known as 4-hydroxycinnamic acid, is a phenolic acid, which has been widely studied due to its beneficial effects against several diseases and its wide distribution in the plant kingdom. This phenolic compound can be found in the free form or conjugated with other molecules; therefore, its bioavailability and the pathways via which it is metabolized change according to its chemical structure. p-CA has potential pharmacological effects because it has high free radical scavenging, anti-inflammatory, antineoplastic, and antimicrobial activities, among other biological properties. It is therefore essential to choose the most appropriate and effective analytical method for qualitative and quantitative determination of p-CA in different matrices, such as plasma, urine, plant extracts, and drug delivery systems. The most-reported analytical method for this purpose is high-performance liquid chromatography, which is mostly coupled with some type of detectors, such as UV/Vis detector. However, other analytical techniques are also used to evaluate this compound. This review presents a summary of p-CA in terms of its chemical and pharmacokinetic properties, pharmacological effects, drug delivery systems, and the analytical methods described in the literature that are suitable for its quantification.

77 FR 71803 - Guidance on Food and Drug Administration Oversight of Positron Emission Tomography Drug Products...

Science.gov (United States)

2012-12-04

... PET Drug Products--Questions and Answers.'' This guidance provides questions and answers that address.... 2201, Silver Spring, MD 20993-0002. Send one self-addressed adhesive label to assist that office in... availability of a guidance entitled ``FDA Oversight of PET Drug Products--Questions and Answers.'' In 1997...

Taste clusters of music and drugs: evidence from three analytic levels.

Science.gov (United States)

Vuolo, Mike; Uggen, Christopher; Lageson, Sarah

2014-09-01

This article examines taste clusters of musical preferences and substance use among adolescents and young adults. Three analytic levels are considered: fixed effects analyses of aggregate listening patterns and substance use in US radio markets, logistic regressions of individual genre preferences and drug use from a nationally representative survey of US youth, and arrest and seizure data from a large American concert venue. A consistent picture emerges from all three levels: rock music is positively associated with substance use, with some substance-specific variability across rock sub-genres. Hip hop music is also associated with higher use, while pop and religious music are associated with lower use. These results are robust to fixed effects models that account for changes over time in radio markets, a comprehensive battery of controls in the individual-level survey, and concert data establishing the co-occurrence of substance use and music listening in the same place and time. The results affirm a rich tradition of qualitative and experimental studies, demonstrating how symbolic boundaries are simultaneously drawn around music and drugs. © London School of Economics and Political Science 2014.

21 CFR 336.50 - Labeling of antiemetic drug products.

Science.gov (United States)

2010-04-01

... years of age. “Do not take this product, unless directed by a doctor, if you have a breathing problem... Section 336.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... under 12 years of age. “Do not give this product to children who have a breathing problem such as...

Evaluation of In-Use Stability of Anticoagulant Drug Products: Warfarin Sodium.

Science.gov (United States)

Nguyenpho, Agnes; Ciavarella, Anthony B; Siddiqui, Akhtar; Rahman, Ziyaur; Akhtar, Sohail; Hunt, Robert; Korang-Yeboah, Maxwell; Khan, Mansoor A

2015-12-01

The objective of the study was to evaluate the stability of warfarin products during use by patients or caregivers. For evaluation, three commercial products manufactured by different processes were selected and placed at 30°C/75%RH to simulate in use condition. Samples were withdrawn up to 12 weeks and analyzed for the physicochemical changes. Scanning electron microscopy demonstrated increasing holes and craters in the tablets over the timeframe. Near-infrared chemical imaging and powder X-ray powder diffraction corroborated the change arising from conversion of crystalline to amorphous forms of the drug. Hardness and disintegration time of the tablets were found to increase progressively. With increasing time, moisture contents of the products were found to increase and consequent decrease in isopropyl alcohol content of the product. Dissolution of the tablets in media at pH 4.5 demonstrated discrimination between crystalline and amorphous drug products. Overall, percent drug dissolved in each product at 30 min was found to decrease with increasing exposure time. Dissolution of drug decreased from 54% to 38% and 82% to 54% for the two products while the third product maintained consistently high level of dissolution. These results suggest that the drug product quality attributes can change during use. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Driving under the influence of drugs -- evaluation of analytical data of drugs in oral fluid, serum and urine, and correlation with impairment symptoms.

Science.gov (United States)

Toennes, Stefan W; Kauert, Gerold F; Steinmeyer, Stefan; Moeller, Manfred R

2005-09-10

A study was performed to acquire urine, serum and oral fluid samples in cases of suspected driving under the influence of drugs of abuse. Oral fluid was collected using a novel sampling/testing device (Dräger DrugTest System). The aim of the study was to evaluate oral fluid and urine as a predictor of blood samples positive for drugs and impairment symptoms. Analysis for cannabinoids, amphetamine and its derivatives, opiates and cocaine was performed in urine using the Mahsan Kombi/DOA4-test, in serum using immunoassay and gas chromatography-mass spectrometry (GC-MS) confirmation and in oral fluid by GC-MS. Police and medical officer observations of impairment symptoms were rated and evaluated using a threshold value for the classification of driving inability. Accuracy in correlating drug detection in oral fluid and serum were >90% for all substances and also >90% in urine and serum except for THC (71.0%). Of the cases with oral fluid positive for any drug 97.1% of corresponding serum samples were also positive for at least one drug; of drug-positive urine samples this were only 82.4%. In 119 of 146 cases, impairment symptoms above threshold were observed (81.5%). Of the cases with drugs detected in serum, 19.1% appeared not impaired which were the same with drug-positive oral fluid while more persons with drug-positive urine samples appeared uninfluenced (32.7%). The data demonstrate that oral fluid is superior to urine in correlating with serum analytical data and impairment symptoms of drivers under the influence of drugs of abuse.

Cell culture media impact on drug product solution stability.

Science.gov (United States)

Purdie, Jennifer L; Kowle, Ronald L; Langland, Amie L; Patel, Chetan N; Ouyang, Anli; Olson, Donald J

2016-07-08

To enable subcutaneous administration of monoclonal antibodies, drug product solutions are often needed at high concentrations. A significant risk associated with high drug product concentrations is an increase in aggregate level over the shelf-life dating period. While much work has been done to understand the impact of drug product formulation on aggregation, there is limited understanding of the link between cell culture process conditions and soluble aggregate growth in drug product. During cell culture process development, soluble aggregates are often measured at harvest using cell-free material purified by Protein A chromatography. In the work reported here, cell culture media components were evaluated with respect to their impact on aggregate levels in high concentration solution drug product during accelerated stability studies. Two components, cysteine and ferric ammonium citrate, were found to impact aggregate growth rates in our current media (version 1) leading to the development of new chemically defined media and concentrated feed formulations. The new version of media and associated concentrated feeds (version 2) were evaluated across four cell lines producing recombinant IgG4 monoclonal antibodies and a bispecific antibody. In all four cell lines, the version 2 media reduced aggregate growth over the course of a 12 week accelerated stability study compared with the version 1 media, although the degree to which aggregate growth decreased was cell line dependent. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:998-1008, 2016. © 2016 American Institute of Chemical Engineers.

21 CFR 349.65 - Labeling of ophthalmic emollient drug products.

Science.gov (United States)

2010-04-01

... product contains the established name of the drug(s), if any, and identifies the product as a “lubricant... the eye or to exposure to wind or sun.” (3) “For use as a protectant against further irritation or to...

21 CFR 349.60 - Labeling of ophthalmic demulcent drug products.

Science.gov (United States)

2010-04-01

... product contains the established name of the drug(s), if any, and identifies the product as a “lubricant... exposure to wind or sun.” (3) “For use as a protectant against further irritation or to relieve dryness of...

75 FR 24394 - Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of a New Animal Drug...

Science.gov (United States)

2010-05-05

... [Docket No. FDA-2010-N-0002] Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of a New Animal Drug Application; Buquinolate; Coumaphos AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations by...

Toward greener analytical techniques for the absolute quantification of peptides in pharmaceutical and biological samples.

Science.gov (United States)

Van Eeckhaut, Ann; Mangelings, Debby

2015-09-10

Peptide-based biopharmaceuticals represent one of the fastest growing classes of new drug molecules. New reaction types included in the synthesis strategies to reduce the rapid metabolism of peptides, along with the availability of new formulation and delivery technologies, resulted in an increased marketing of peptide drug products. In this regard, the development of analytical methods for quantification of peptides in pharmaceutical and biological samples is of utmost importance. From the sample preparation step to their analysis by means of chromatographic or electrophoretic methods, many difficulties should be tackled to analyze them. Recent developments in analytical techniques emphasize more and more on the use of green analytical techniques. This review will discuss the progresses in and challenges observed during green analytical method development for the quantification of peptides in pharmaceutical and biological samples. Copyright © 2015 Elsevier B.V. All rights reserved.

Therapeutic drug monitoring of digoxin in cardiac heart failure outpatients: comparisons of two analytical methods

Directory of Open Access Journals (Sweden)

Isabel Cristina Medeiros Barros

2014-01-01

Full Text Available Objective: To compare two analytical techniques used in the determination of plasma digoxin (LC-MS/MS and immunoassay and to verify which one better answer the need of the clinical monitoring routine of patients with cardiac heart failure. Method: The clinical findings in 15 cardiac heart failure (CHF outpatients of the Cardiac Heart Service of the Goias Federal University Clinical Hospital were investigated. Blood samples of the patients were collected and analysed by Immunoassay and by Liquid Chromatography coupled to Mass Spectrometry (LC-MS/MS. Results: The results of the statistic test (Student p = 0,05 showed a significant difference between the analytical methods: immunoassay concentrations were higher than the concentrations determined by LCMS/ MS. The explanation may be because immunoassay method measures digoxin plus other metabolites and endogenous substances, while the LC-MS/MS method measures only the digoxin molecule. None of the patients, showed relevant clinical data suggestive of digitalis intoxication, even several drugs with potential interaction were associated with treatment. Conclusion: It was concluded, therefore, that LC-MS/MS me thod is safer, more selective and specific than immunoassay, being an option for therapeutic drug monitoring of digoxin, since the reference values would be obtain for digoxinemia by LC-MS/MS.

Defining Patient Centric Pharmaceutical Drug Product Design.

Science.gov (United States)

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

2016-09-01

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

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

Science.gov (United States)

2010-04-01

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

Package selection for moisture protection for solid, oral drug products.

Science.gov (United States)

Waterman, Kenneth C; MacDonald, Bruce C

2010-11-01

This review describes how best to select the appropriate packaging options for solid, oral drug products based on both chemical and physical stability, with respect to moisture protection. This process combines an accounting for the initial moisture content of dosage form components, moisture transfer into (out of) packaging based on a moisture vapor transfer rate (MVTR), and equilibration between drug products and desiccants based on their moisture sorption isotherms to provide an estimate of the instantaneous relative humidity (RH) within the packaging. This time-based RH is calculationally combined with a moisture-sensitive Arrhenius equation (determined using the accelerated stability assessment program, ASAP) to predict the drug product's chemical stability over time as a function of storage conditions and packaging options. While physical stability of dosage forms with respect to moisture has been less well documented, a process is recommended based on the threshold RH at which changes (e.g., dosage form dissolution, tablet hardness, drug form) become problematic. The overall process described allows packaging to be determined for a drug product scientifically, with the effect of any changes to storage conditions or packaging to be explicitly accounted for. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association

Product-line extensions and pricing strategies of brand-name drugs facing patent expiration.

Science.gov (United States)

Hong, Song Hee; Shepherd, Marvin D; Scoones, David; Wan, Thomas T H

2005-01-01

This study proposed an alternative to brand loyalty as the explanation for the continued price rigidity of patent-expired brand-name prescription drugs despite the increase in market entry of generic drugs facilitated by the 1984 Drug Price Competition and Patent Term Restoration Act. Study hypotheses were to test (1) whether market entries of new-product extensions are associated with market success of original brand-name drugs before generic drug entry, and (2) whether original brand-name drugs exhibit price rigidity to generic entry only when they are extended. The design is a retrospective follow-up study for the prescription drug brands that lost their patents between 1987 and 1992. The drug brands were limited to nonantibiotic, orally administered drugs containing only 1 active pharmaceutical ingredient. Information on patent expiration, entry of a product extension, and market success were determined from the U.S. Food and Drug Administration.s Orange Book, First DataBank, and American Druggist, respectively. Market success was defined as whether an original drug brand was listed in the top 100 prescriptions most frequently dispensed before facing generic entry. Product-line extension was defined as the appearance of another product that a company introduces within the same market after its existing product. Drug prices were average wholesale prices from the Drug Topics Red Book. The relationship between product-line extension and market success was examined using a logistic regression analysis. The price rigidity to entry was tested using a panel regression analysis. A total of 27 drug brands lost their patents between 1987 and 1992. Drug brands that achieved market success were 16 times more likely to be extended than were those that did not (OR=16, 95% confidence interval, 2.12-120.65). The price rigidity to entry existed in drug brands with extensions (beta=2.65%, P new product-line extension introduced for an original brand helps the original price be

Plant natural products research in tuberculosis drug discovery and ...

African Journals Online (AJOL)

Plant natural products research in tuberculosis drug discovery and development: A situation report ... African Journal of Biotechnology ... tuberculosis (XDR-TB), call for the development of new anti-tuberculosis drugs to combat this disease.

Analytical challenges in drug counterfeiting and falsification-The NMR approach.

Science.gov (United States)

Holzgrabe, Ulrike; Malet-Martino, Myriam

2011-06-25

Counterfeiting of products is a global problem. As long as clothes, clocks, leather wear, etc. are faked there is no danger, but when it comes to drugs, counterfeiting can be life-threatening. In the last years sub-standard active pharmaceutical ingredients (APIs) were found more often even though the use of the quality-ensuring methods of international pharmacopoeias should have detected additional impurities and the low content of the API. Methods orthogonal to the separating methods used in the pharmacopoeias are necessary to find counterfeits. Beside Raman and NIR spectroscopies as well as powder X-ray analysis, NMR spectroscopy being a primary ratio method of measurement is highly suitable to identify and quantify a drug and its related substances as well as to recognize a drug of sub-standard quality. DOSY experiments are suitable to identify the ingredients of formulations and therefore to identify wrong and/or additional ingredients. This review gives an overview of the application of quantitative NMR spectroscopy and DOSY NMR in anticounterfeiting. Copyright © 2010 Elsevier B.V. All rights reserved.

Marine natural products: a new wave of drugs?

Science.gov (United States)

Montaser, Rana; Luesch, Hendrik

2011-01-01

The largely unexplored marine world that presumably harbors the most biodiversity may be the vastest resource to discover novel ‘validated’ structures with novel modes of action that cover biologically relevant chemical space. Several challenges, including the supply problem and target identification, need to be met for successful drug development of these often complex molecules; however, approaches are available to overcome the hurdles. Advances in technologies such as sampling strategies, nanoscale NMR for structure determination, total chemical synthesis, fermentation and biotechnology are all crucial to the success of marine natural products as drug leads. We illustrate the high degree of innovation in the field of marine natural products, which in our view will lead to a new wave of drugs that flow into the market and pharmacies in the future. PMID:21882941

Simulated Leaching (Migration) Study for a Model Container-Closure System Applicable to Parenteral and Ophthalmic Drug Products.

Science.gov (United States)

Jenke, Dennis; Egert, Thomas; Hendricker, Alan; Castner, James; Feinberg, Tom; Houston, Christopher; Hunt, Desmond G; Lynch, Michael; Nicholas, Kumudini; Norwood, Daniel L; Paskiet, Diane; Ruberto, Michael; Smith, Edward J; Holcomb, Frank; Markovic, Ingrid

2017-01-01

A simulating leaching (migration) study was performed on a model container-closure system relevant to parenteral and ophthalmic drug products. This container-closure system consisted of a linear low-density polyethylene bottle (primary container), a polypropylene cap and an elastomeric cap liner (closure), an adhesive label (labeling), and a foil overpouch (secondary container). The bottles were filled with simulating solvents (aqueous salt/acid mixture at pH 2.5, aqueous buffer at pH 9.5, and 1/1 v/v isopropanol/water), a label was affixed to the filled and capped bottles, the filled bottles were placed into the foil overpouch, and the filled and pouched units were stored either upright or inverted for up to 6 months at 40 °C. After storage, the leaching solutions were tested for leached substances using multiple complementary analytical techniques to address volatile, semi-volatile, and non-volatile organic and inorganic extractables as potential leachables.The leaching data generated supported several conclusions, including that (1) the extractables (leachables) profile revealed by a simulating leaching study can qualitatively be correlated with compositional information for materials of construction, (2) the chemical nature of both the extracting medium and the individual extractables (leachables) can markedly affect the resulting profile, and (3) while direct contact between a drug product and a system's material of construction may exacerbate the leaching of substances from that material by the drug product, direct contact is not a prerequisite for migration and leaching to occur. LAY ABSTRACT: The migration of container-related extractables from a model pharmaceutical container-closure system and into simulated drug product solutions was studied, focusing on circumstances relevant to parenteral and ophthalmic drug products. The model system was constructed specifically to address the migration of extractables from labels applied to the outside of the

Analytic network process (ANP approach for product mix planning in railway industry

Directory of Open Access Journals (Sweden)

Hadi Pazoki Toroudi

2016-08-01

Full Text Available Given the competitive environment in the global market in recent years, organizations need to plan for increased profitability and optimize their performance. Planning for an appropriate product mix plays essential role for the success of most production units. This paper applies analytical network process (ANP approach for product mix planning for a part supplier in Iran. The proposed method uses four criteria including cost of production, sales figures, supply of raw materials and quality of products. In addition, the study proposes different set of products as alternatives for production planning. The preliminary results have indicated that that the proposed study of this paper could increase productivity, significantly.

Regulatory considerations concerning IND radiopharmaceutical drug products

International Nuclear Information System (INIS)

Nissel, M.

1985-01-01

The Food and Drug Administration is charged by the Food, Drug, and Cosmetic Act, as presently amended, to assure that any drug introduced into interstate commerce is safe and effective for the purposes for which it is labeled. A radiopharmaceutical is, by definition, a new drug unless there is in effect an approved New Drug Application (NDA) for it. Before the data for the NDA are compiled, investigative studies have to be done. Before such studies can be performed in humans, an exemption from the Act is necessary. This exemption, technically the Claimed Exemption for an Investigational New Drug, is termed the IND. Both the scientific and the administrative requirements for an IND are discussed. For radiopharmaceutical drug products (RDP's), the radiation hazards, as well as the pharmacological ones, must be documented. Should the early studies demonstrate a potential for efficacy in a certain condition or disease state, an investigative protocol for an extended clinical trial is presented. The necessary requirements for Institutional Review Board (IRB) approval and consent forms are discussed. For certain research purposes, uniquely for radioactive drugs, an IND is not required for certain specific studies; the requirements for such a research study, conducted under the auspices of an approved radioactive drug research committee, are outlined

Process analytical technology to understand the disintegration behavior of alendronate sodium tablets.

Science.gov (United States)

Xu, Xiaoming; Gupta, Abhay; Sayeed, Vilayat A; Khan, Mansoor A

2013-05-01

Various adverse events including esophagus irritations have been reported with the use of alendronate tablets, likely attributed to the rapid tablet disintegration in the mouth or esophagus. Accordingly, the disintegration of six alendronate tablet drug products was studied using a newly developed testing device equipped with in-line sensors, in addition to the official compendial procedure for measuring the disintegration time. The in-line sensors were used to monitor the particle count and solution pH change to assess the onset and duration of disintegration. A relatively large variation was observed in the disintegration time of the tested drug products using the compendial method. The data collected using the in-line sensors suggested that all tested drug products exhibited almost instantaneous onset of disintegration, under 2 s, and a sharp drop in solution pH. The drop in pH was slower for tablets with slower disintegration. The in-house prepared alendronate test tablets also showed similar trends suggesting rapid solubilization of the drug contributed to the fast tablet disintegration. This research highlights the usefulness of the newly developed in-line analytical method in combination with the compendial method in providing a better understanding of the disintegration and the accompanying drug solubilization processes for fast disintegrating tablet drug products. Copyright © 2013 Wiley Periodicals, Inc.

Pharmaceutical quality of docetaxel generics versus originator drug product: a comparative analysis.

Science.gov (United States)

Vial, Jérôme; Cohen, Mélanie; Sassiat, Patrick; Thiébaut, Didier

2008-07-01

The aim of this study was to evaluate the quality of 31 commercially available generic formulations of docetaxel purchased in 14 countries by comparing their docetaxel content, impurity levels and pH versus those of the proprietary product Taxotere (Tx). Generic formulations were purchased in 14 countries in Asia, Africa, the Middle East and Latin America. Levels of docetaxel and impurities (chromatographic peaks above 0.05%) were obtained for each sample using reverse-phase liquid chromatography with ultraviolet detection. The pH of aqueous solutions of generic docetaxel formulations and Tx was also measured. A global evaluation of quality was conducted on each product using a multicriteria desirability analysis based on standards defined by the International Conference on Harmonisation guidelines and the US Pharmacopeia paclitaxel injection monograph. Most generic formulations contained a lower than expected amount of docetaxel and/or a high level of impurities: 21 generic docetaxel formulations had an average mass of docetaxel that was generic docetaxel formulations had a total impurity content of >3.0%, almost twice the level of impurities in Tx 20 mg. In total, 33 impurities not present in Tx were detected in the generic samples. Desirability analysis demonstrated that none of the generic docetaxel formulations had composition characteristics similar to those of Tx. This study demonstrated that from an analytical point of view, 90% of the generic docetaxel formulations evaluated contained insufficient active drug, high levels of impurities or both. This has the potential to affect both efficacy and safety of the drug.

Physico-chemical Stability of MabThera Drug-product Solution for Subcutaneous Injection under in-use Conditions with Different Administration Materials.

Science.gov (United States)

Mueller, Claudia; Dietel, Elke; Heynen, Severin R; Nalenz, Heiko; Goldbach, Pierre; Mahler, Hanns-Christian; Schmidt, Johannes; Grauschopf, Ulla; Schoenhamnmer, Karin

2015-01-01

MabThera is an essential component of the standard-of-care regimens in the treatment of non-Hodgkin lymphoma and Chronic Lymphatic Leukemia. MabThera for subcutaneous injection is a novel line extension that has been approved by the European Medicines Agency for the treatment of patients with follicular lymphoma and diffuse large B-cell lymphoma. This study aimed to evaluate in-use stability data of MabThera subcutaneous drug-product solution in single-use syringes for subcutaneous administration according to the European Medicines Agency guideline. The drug-product solution was exposed to material contact surfaces of five different administration setups commonly used in subcutaneous drug delivery. MabThera subcutaneous was transferred under aseptic conditions into polypropylene and polycarbonate syringes and stored for 1, 2, and 4 weeks at 2°C to 8°C followed by 24 hours at 30°C. After storage, subcutaneous administration was simulated and MabThera subcutaneous drug-product solution quality attributes were evaluated by using compendial physico-chemical tests, as well as suitable and validated molecule- and formulation-specific analytical methods. MabThera subcutaneous vials were treated and analyzed in parallel. The physico-chemical results of MabThera subcutaneous in the different setups were comparable to the control for all timepoints. No change in drug-product quality after storage and simulated administration was found compared to the control. However, since single-dose products do not contain preservatives, microbial contamination and growth needs to be avoided and product sterility needs to be ensured. The results showed that MabThera subcutaneous remains compatible and stable, from a physico-chemical perspective, for up to 4 weeks at 2°C to 8°C followed by 24 hours at 30°C with the contact materials tested in this study. In order to avoid and minimize microbial growth, MabThera subcutaneous should be used immediately after removal from the original

75 FR 73108 - Guidance for Industry on Abbreviated New Drug Applications: Impurities in Drug Products...

Science.gov (United States)

2010-11-29

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0584... Products.'' This guidance updates recommendations regarding degradation products and updates the draft... information on listing of degradation products, setting acceptance criteria, and qualifying degradation...

Drogas de abuso em águas naturais e residuárias urbanas: ocorrência, determinação e aplicações forenses Drugs of abuse in waters and wastewaters: occurrence, analytical determination and forensic applications

Directory of Open Access Journals (Sweden)

Rafael Silva Feitosa

2013-01-01

Full Text Available Drugs of abuse are commonly used outside medical or legal settings where their production, marketing and consumption are subject to legal summons and/or intervention. Classified as emerging contaminants, these substances have been recently detected in samples of environmental concern, such as waters and wastewaters. This review presents the state-of-the-art on the methodological approaches used in sample preparation, the main techniques applied in analytical determination at trace levels, as well as the use of information related to the drug or its metabolite concentration in sewage samples to empirically estimate the consumption of drugs of abuse in a city or region.

21 CFR 20.2 - Production of records by Food and Drug Administration employees.

Science.gov (United States)

2010-04-01

... upon an officer or employee of the Food and Drug Administration commanding the production of any record... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Production of records by Food and Drug Administration employees. 20.2 Section 20.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND...

Nano-sized crystalline drug production by milling technology.

Science.gov (United States)

Moribe, Kunikazu; Ueda, Keisuke; Limwikrant, Waree; Higashi, Kenjirou; Yamamoto, Keiji

2013-01-01

Nano-formulation of poorly water-soluble drugs has been developed to enhance drug dissolution. In this review, we introduce nano-milling technology described in recently published papers. Factors affecting the size of drug crystals are compared based on the preparation methods and drug and excipient types. A top-down approach using the comminution process is a method conventionally used to prepare crystalline drug nanoparticles. Wet milling using media is well studied and several wet-milled drug formulations are now on the market. Several trials on drug nanosuspension preparation using different apparatuses, materials, and conditions have been reported. Wet milling using a high-pressure homogenizer is another alternative to preparing production-scale drug nanosuspensions. Dry milling is a simple method of preparing a solid-state drug nano-formulation. The effect of size on the dissolution of a drug from nanoparticles is an area of fundamental research, but it is sometimes incorrectly evaluated. Here, we discuss evaluation procedures and the associated problems. Lastly, the importance of quality control, process optimization, and physicochemical characterization are briefly discussed.

Downstream processing and chromatography based analytical methods for production of vaccines, gene therapy vectors, and bacteriophages

Science.gov (United States)

Kramberger, Petra; Urbas, Lidija; Štrancar, Aleš

2015-01-01

Downstream processing of nanoplexes (viruses, virus-like particles, bacteriophages) is characterized by complexity of the starting material, number of purification methods to choose from, regulations that are setting the frame for the final product and analytical methods for upstream and downstream monitoring. This review gives an overview on the nanoplex downstream challenges and chromatography based analytical methods for efficient monitoring of the nanoplex production. PMID:25751122

75 FR 33312 - Indexing Structured Product Labeling for Human Prescription Drug and Biological Products; Request...

Science.gov (United States)

2010-06-11

...] Indexing Structured Product Labeling for Human Prescription Drug and Biological Products; Request for... Biologics Evaluation and Research (CBER) are indexing certain categories of information in product labeling for use as terms to search repositories of approved prescription medical product structured product...

physico-chemical studies on DNA-drugs interaction and their analytical applications

International Nuclear Information System (INIS)

Kandil, S.A

2003-01-01

The present thesis is devoted to study the interaction of some antibacterial agents i.e. fluoroquinolones . these agents include ciprofloxacin, norfloxacin , ofloxacin , pefloxacin and levofloxacin with DNA. voltammetric and spectrophotometric methods were used to carry out this study. Also the interaction of the suggested drugs with DNA at the surface of carbon electrode by cyclic voltammetry and differential pulse techniques is examined. The work comprises three chapters: (1) includes an introduction of voltammetry , differential pulse, drug-DNA interaction and fluoroquinoline- DNA interaction and literature survey on fluoroquinolones.Chapter (II) includes preparation of the solutions and instruments which were used for the measurements using the different techniques.Chapter(III) comprises three parts; (1) deals with the interaction of fluoroquinolones (ciprofloxacin, norfloxacin, ofloxacin, pefloxacin and levofloxacin) with DNA in solution have been investigated by means of voltammetry and spectroscopy . the results show that the values of binding constant of fluoroquinolne drugs with DNA obtained through the changes of the anodic peak current, and their values are, 30900,31000,32300,32000 and 32500 M -1 respectively. or changes of absorption and values are, 36000,30200.38300,36500 and 34400 M -1 receptively.(II) includes voltammetric behavior of fluoroquinolones on DNA-modified carbon paste electrode. (III)includes analytical application for proposed method for the determination of levofloxacin as a typical example for fluoroquinolones. Concentration in the range 5.0x10 -7 ∼ 5.0x10 -6 mol/L , with a detection limit of 1.0x10 -7 mol/L. direct and simple determination of levofloxacin in urine was established with no manipulation of urine sample other than dilution 1:10

Drug-drug interaction and doping, part 1: an in vitro study on the effect of non-prohibited drugs on the phase I metabolic profile of toremifene.

Science.gov (United States)

Mazzarino, Monica; de la Torre, Xavier; Fiacco, Ilaria; Palermo, Amelia; Botrè, Francesco

2014-05-01

The present study was designed to provide preliminary information on the potential impact of metabolic drug-drug interaction on the effectiveness of doping control strategies currently followed by the anti-doping laboratories to detect the intake of banned agents. In vitro assays based on the use of human liver microsomes and recombinant CYP isoforms were designed and performed to characterize the phase I metabolic profile of the prohibited agent toremifene, selected as a prototype drug of the class of selective oestrogen receptor modulators, both in the absence and in the presence of medicaments (fluconazole, ketoconazole, itraconazole, miconazole, cimetidine, ranitidine, fluoxetine, paroxetine, nefazodone) not included in the World Anti-Doping Agency list of prohibited substances and methods and frequently administered to athletes. The results show that the in vitro model developed in this study was adequate to simulate the in vivo metabolism of toremifene, confirming the results obtained in previous studies. Furthermore, our data also show that ketoconazole, itraconazole, miconazole and nefazodone cause a marked modification in the production of the metabolic products (i.e. hydroxylated and carboxylated metabolites) normally selected by the anti-doping laboratories as target analytes to detect toremifene intake; moderate variations were registered in the presence of fluconazole, paroxetine and fluoxetine; while no significant modifications were measured in the presence of ranitidine and cimetidine. This evidence imposes that the potential effect of drug-drug interactions is duly taken into account in anti-doping analysis, also for a broader significance of the analytical results. Copyright © 2014 John Wiley & Sons, Ltd.

Analytical characterization of recombinant hCG and comparative studies with reference product

Directory of Open Access Journals (Sweden)

Thennati R

2018-01-01

Full Text Available Rajamannar Thennati,1 Sanjay Kumar Singh,1 Nitin Nage,1 Yena Patel,1 Sandip Kumar Bose,1 Vinod Burade,2 Ranjit Sudhakar Ranbhor1 1Sun Pharmaceutical Industries Limited, 2Sun Pharmaceutical Advanced Research Center, Vadodara, Gujarat, India Introduction: Regulatory agencies recommend a stepwise approach for demonstrating biosimilarity between a proposed biosimilar and reference biological product emphasizing for functional and structural characterization to trace if there is any difference which may impact safety and efficacy. We studied the comparative structural and biological attributes of recombinant human chorionic gonadotropin (rhCG, SB005, with reference product, Ovidrel® and Ovitrelle®. Recombiant hCG was approved in 2000 by the US Food and Drug Administration for the induction of final follicular maturation, early luteinization in infertile women as part of assisted reproductive technology program. It is also indicated for the induction of ovulation and pregnancy in ovulatory infertile patients whose cause of infertility is not due to ovarian failure. Materials and methods: Primary structure was studied by intact mass analysis, peptide fingerprinting, peptide mass fingerprinting and sequence coverage analysis. Higher order structure was studied by circular dichroism, ultraviolet-visible spectroscopy, fluorescence spectroscopy, and disulfide bridge analysis. Different isoforms of reference product and SB005 were identified using capillary isoelectric focusing and capillary zone electrophoresis. Glycosylation was studied by N-glycan mapping using LC-ESI-MS, point of glycosylation, released glycan analysis using ultra performance liquid chromatography and sialic acid analysis. Product related impurities such as oligomer content analysis and oxidized impurities were studied using size exclusion chromatography and reverse phase high performance liquid chromatography, respectively. Biological activity in term of potency of reference product

An Analytical Model for Multilayer Well Production Evaluation to Overcome Cross-Flow Problem

KAUST Repository

Hakiki, Farizal; Wibowo, Aris T.; Rahmawati, Silvya D.; Yasutra, Amega; Sukarno, Pudjo

2017-01-01

One of the major concerns in a multi-layer system is that interlayer cross-flow may occur if reservoir fluids are produced from commingled layers that have unequal initial pressures. Reservoir would commonly have bigger average reservoir pressure (pore fluid pressure) as it goes deeper. The phenomenon is, however, not followed by the reservoir productivity or injectivity. The existence of reservoir with quite low average-pressure and high injectivity would tend experiencing the cross-flow problem. It is a phenomenon of fluid from bottom layer flowing into upper layer. It would strict upper-layer fluid to flow into wellbore. It is as if there is an injection treatment from bottom layer. The study deploys productivity index an approach parameter taking into account of cross-flow problem instead of injectivity index since it is a production well. The analytical study is to model the reservoir multilayer by addressing to avoid cross-flow problem. The analytical model employed hypothetical and real field data to test it. The scope of this study are: (a) Develop mathematical-based solution to determine the production rate from each layer; (b) Assess different scenarios to optimize production rate, those are: pump setting depth and performance of in-situ choke (ISC) installation. The ISC is acting as an inflow control device (ICD) alike that help to reduce cross-flow occurrence. This study employed macro program to write the code and develop the interface. Fast iterative procedure happens on solving the analytical model. Comparison results recognized that the mathematical-based solution shows a good agreement with the commercial software derived results.

An Analytical Model for Multilayer Well Production Evaluation to Overcome Cross-Flow Problem

KAUST Repository

Hakiki, Farizal

2017-10-17

One of the major concerns in a multi-layer system is that interlayer cross-flow may occur if reservoir fluids are produced from commingled layers that have unequal initial pressures. Reservoir would commonly have bigger average reservoir pressure (pore fluid pressure) as it goes deeper. The phenomenon is, however, not followed by the reservoir productivity or injectivity. The existence of reservoir with quite low average-pressure and high injectivity would tend experiencing the cross-flow problem. It is a phenomenon of fluid from bottom layer flowing into upper layer. It would strict upper-layer fluid to flow into wellbore. It is as if there is an injection treatment from bottom layer. The study deploys productivity index an approach parameter taking into account of cross-flow problem instead of injectivity index since it is a production well. The analytical study is to model the reservoir multilayer by addressing to avoid cross-flow problem. The analytical model employed hypothetical and real field data to test it. The scope of this study are: (a) Develop mathematical-based solution to determine the production rate from each layer; (b) Assess different scenarios to optimize production rate, those are: pump setting depth and performance of in-situ choke (ISC) installation. The ISC is acting as an inflow control device (ICD) alike that help to reduce cross-flow occurrence. This study employed macro program to write the code and develop the interface. Fast iterative procedure happens on solving the analytical model. Comparison results recognized that the mathematical-based solution shows a good agreement with the commercial software derived results.

MASTERS OF ANALYTICAL TRADECRAFT: CERTIFYING THE STANDARDS AND ANALYTIC RIGOR OF INTELLIGENCE PRODUCTS

Science.gov (United States)

2016-04-01

AU/ACSC/2016 AIR COMMAND AND STAFF COLLEGE AIR UNIVERSITY MASTERS OF ANALYTICAL TRADECRAFT: CERTIFYING THE STANDARDS AND ANALYTIC RIGOR OF...establishing unit level certified Masters of Analytic Tradecraft (MAT) analysts to be trained and entrusted to evaluate and rate the standards and...cues) ideally should meet or exceed effective rigor (based on analytical process).4 To accomplish this, decision makers should not be left to their

Analytical model for advective-dispersive transport involving flexible boundary inputs, initial distributions and zero-order productions

Science.gov (United States)

Chen, Jui-Sheng; Li, Loretta Y.; Lai, Keng-Hsin; Liang, Ching-Ping

2017-11-01

A novel solution method is presented which leads to an analytical model for the advective-dispersive transport in a semi-infinite domain involving a wide spectrum of boundary inputs, initial distributions, and zero-order productions. The novel solution method applies the Laplace transform in combination with the generalized integral transform technique (GITT) to obtain the generalized analytical solution. Based on this generalized analytical expression, we derive a comprehensive set of special-case solutions for some time-dependent boundary distributions and zero-order productions, described by the Dirac delta, constant, Heaviside, exponentially-decaying, or periodically sinusoidal functions as well as some position-dependent initial conditions and zero-order productions specified by the Dirac delta, constant, Heaviside, or exponentially-decaying functions. The developed solutions are tested against an analytical solution from the literature. The excellent agreement between the analytical solutions confirms that the new model can serve as an effective tool for investigating transport behaviors under different scenarios. Several examples of applications, are given to explore transport behaviors which are rarely noted in the literature. The results show that the concentration waves resulting from the periodically sinusoidal input are sensitive to dispersion coefficient. The implication of this new finding is that a tracer test with a periodic input may provide additional information when for identifying the dispersion coefficients. Moreover, the solution strategy presented in this study can be extended to derive analytical models for handling more complicated problems of solute transport in multi-dimensional media subjected to sequential decay chain reactions, for which analytical solutions are not currently available.

78 FR 75570 - Guidance for Industry on New Animal Drugs and New Animal Drug Combination Products Administered...

Science.gov (United States)

2013-12-12

... Guidance for Industry (GFI) 209, ``The Judicious Use of Medically Important Antimicrobial Drugs in Food... of certain antimicrobial new animal drug products who are interested in revising conditions of use... Medically Important Antimicrobial Drugs in Food-Producing Animals,'' and to set timelines for stakeholders...

75 FR 65565 - Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of New Animal Drug Applications...

Science.gov (United States)

2010-10-26

... 558 [Docket No. FDA-2010-N-0002] Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of New Animal Drug Applications; Aklomide; Levamisole Hydrochloride; Nitromide and Sulfanitran AGENCY...) is amending the animal drug regulations by removing those portions that reflect approval of eight new...

The Product Quality Research Institute (PQRI) Leachables and Extractables Working Group Initiatives for Parenteral and Ophthalmic Drug Product (PODP).

Science.gov (United States)

Paskiet, Diane; Jenke, Dennis; Ball, Douglas; Houston, Christopher; Norwood, Daniel L; Markovic, Ingrid

2013-01-01

The Product Quality Research Institute (PQRI) is a non-profit consortium of organizations working together to generate and share timely, relevant, and impactful information that advances drug product quality and development. The collaborative activities of PQRI participants have, in the case of orally inhaled and nasal drug products (OINDPs), resulted in comprehensive and widely-accepted recommendations for leachables assessments to help ensure patient safety with respect to this class of packaged drug products. These recommendations, which include scientifically justified safety thresholds for leachables, represent a significant milestone towards establishing standardized approaches for safety qualification of leachables in OINDP. To build on the success of the OINDP effort, PQRI's Parenteral and Ophthalmic Drug Products (PODP) Leachables and Extractables Working Group was formed to extrapolate the OINDP threshold concepts and best practice recommendations to other dosage forms with high concern for interaction with packaging/delivery systems. This article considers the general aspects of leachables and their safety assessment, introduces the PODP Work Plan and initial study Protocol, discusses the laboratory studies being conducted by the PODP Chemistry Team, outlines the strategy being developed by the PODP Toxicology Team for the safety qualification of PODP leachables, and considers the issues associated with application of the safety thresholds, particularly with respect to large-volume parenterals. Lastly, the unique leachables issues associated with biologics are described. The Product Quality Research Institute (PQRI) is a non-profit consortium involving industry organizations, academia, and regulatory agencies that together provide recommendations in support of regulatory guidance to advance drug product quality. The collaborative activities of the PQRI Orally Inhaled and Nasal Drug Products Leachables and Extractables Working Group resulted in a

Drug-enhanced carbon monoxide production from heme by cytochrome P450 reductase

Directory of Open Access Journals (Sweden)

Dragic Vukomanovic

2017-01-01

Full Text Available Carbon monoxide (CO formed endogenously is considered to be cytoprotective, and the vast majority of CO formation is attributed to the degradation of heme by heme oxygenases-1 and -2 (HO-1, HO-2. Previously, we observed that brain microsomes containing HO-2 produced many-fold more CO in the presence of menadione and its congeners; herein we explored these observations further. We determined the effects of various drugs on CO production of rat brain microsomes and recombinant human cytochrome P450 reductase (CPR; CO was measured by gas chromatography with reductive detection. Brain microsomes of Sprague-Dawley rats or recombinant human cytochrome P450 reductase (CPR were incubated with NADPH and various drugs in closed vials in phosphate buffer at pH 7.4 and 37°C. After 15 minutes, the reaction was stopped by cooling in dry ice, and the headspace gas was analyzed for CO production using gas chromatography with reductive (mercuric oxide detection. We observed drug-enhanced CO production in the presence of both microsomes and recombinant CPR alone; the presence of HO was not required. A range of structurally diverse drugs were capable of amplifying this CO formation; these molecules had structures consistent with redox cycling capability. The addition of catalase to a reaction mixture, that contained activating drugs, inhibited the production of CO. Drug-enhanced CO formation can be catalyzed by CPR. The mechanism of CPR activation was not through classical drug-receptor mediation. Redox cycling may be involved in the drug-induced amplification of CO production by CPR through the production of reactive oxygen species.

Raman spectroscopy in pharmaceutical product design

DEFF Research Database (Denmark)

Paudel, Amrit; Raijada, Dhara; Rantanen, Jukka

2015-01-01

Almost 100 years after the discovery of the Raman scattering phenomenon, related analytical techniques have emerged as important tools in biomedical sciences. Raman spectroscopy and microscopy are frontier, non-invasive analytical techniques amenable for diverse biomedical areas, ranging from...... molecular-based drug discovery, design of innovative drug delivery systems and quality control of finished products. This review presents concise accounts of various conventional and emerging Raman instrumentations including associated hyphenated tools of pharmaceutical interest. Moreover, relevant...... application cases of Raman spectroscopy in early and late phase pharmaceutical development, process analysis and micro-structural analysis of drug delivery systems are introduced. Finally, potential areas of future advancement and application of Raman spectroscopic techniques are discussed....

Inactive ingredient Search for Approved Drug Products

Data.gov (United States)

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

Identification of antimycotic drugs transformation products upon UV exposure

Energy Technology Data Exchange (ETDEWEB)

Casado, Jorge; Rodríguez, Isaac, E-mail: isaac.rodriguez@usc.es; Ramil, María; Cela, Rafael

2015-05-30

Highlights: • Evaluation of antimycotic drugs UV stabilities in model supports. • Simultaneous detection of precursor drugs and transformation products. • Transformation products identification from their scan, accurate MS/MS spectra. • Directed search of identified transformation products in sand and soil samples. • Preliminary toxicity estimations. - Abstract: The reactivity of three imidazolic, environmental persistent antimycotic drugs (clotrimazole, CTZ; ketoconazole, KTZ; and miconazole, MCZ) upon exposure to ultraviolet (UV) radiation is discussed. First, precursor compounds were immobilized in a silicone support which was further exposed to UV light at two different wavelengths: 254 and 365 nm. After solvent desorption, degradation kinetics of the precursor pharmaceuticals, identification of the arising transformation products (TPs) and evaluation of their time-course were investigated by liquid chromatography (LC) with quadrupole time-of-flight (QTOF) mass spectrometry (MS) detection. The three antimycotics displayed similar stabilities when exposed to 254 nm light; however, CTZ was significantly more stable than MCZ and KTZ when irradiated with the 365 nm lamp. TPs identified in silicone supports resulted from de-chlorination, cleavage, intra-molecular cyclization and hydroxylation reactions. Many of these species were also detected when exposing other solid matrices, such as sand and agricultural soil, previously spiked with target compounds, to UV light. The 50% estimated lethal concentration, calculated using the 48-h Daphnia magna test, for the two main TPs of CTZ and MCZ, at both wavelengths, were lower than those corresponding to the precursor drugs.

Identification of antimycotic drugs transformation products upon UV exposure

International Nuclear Information System (INIS)

Casado, Jorge; Rodríguez, Isaac; Ramil, María; Cela, Rafael

2015-01-01

Highlights: • Evaluation of antimycotic drugs UV stabilities in model supports. • Simultaneous detection of precursor drugs and transformation products. • Transformation products identification from their scan, accurate MS/MS spectra. • Directed search of identified transformation products in sand and soil samples. • Preliminary toxicity estimations. - Abstract: The reactivity of three imidazolic, environmental persistent antimycotic drugs (clotrimazole, CTZ; ketoconazole, KTZ; and miconazole, MCZ) upon exposure to ultraviolet (UV) radiation is discussed. First, precursor compounds were immobilized in a silicone support which was further exposed to UV light at two different wavelengths: 254 and 365 nm. After solvent desorption, degradation kinetics of the precursor pharmaceuticals, identification of the arising transformation products (TPs) and evaluation of their time-course were investigated by liquid chromatography (LC) with quadrupole time-of-flight (QTOF) mass spectrometry (MS) detection. The three antimycotics displayed similar stabilities when exposed to 254 nm light; however, CTZ was significantly more stable than MCZ and KTZ when irradiated with the 365 nm lamp. TPs identified in silicone supports resulted from de-chlorination, cleavage, intra-molecular cyclization and hydroxylation reactions. Many of these species were also detected when exposing other solid matrices, such as sand and agricultural soil, previously spiked with target compounds, to UV light. The 50% estimated lethal concentration, calculated using the 48-h Daphnia magna test, for the two main TPs of CTZ and MCZ, at both wavelengths, were lower than those corresponding to the precursor drugs

21 CFR 341.72 - Labeling of antihistamine drug products.

Science.gov (United States)

2010-04-01

..., unless directed by a doctor, if you have a breathing problem such as emphysema or chronic bronchitis, or... Section 341.72 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... product if you are taking sedatives or tranquilizers, without first consulting your doctor. Use caution...

Harnessing scientific literature reports for pharmacovigilance. Prototype software analytical tool development and usability testing.

Science.gov (United States)

Sorbello, Alfred; Ripple, Anna; Tonning, Joseph; Munoz, Monica; Hasan, Rashedul; Ly, Thomas; Francis, Henry; Bodenreider, Olivier

2017-03-22

We seek to develop a prototype software analytical tool to augment FDA regulatory reviewers' capacity to harness scientific literature reports in PubMed/MEDLINE for pharmacovigilance and adverse drug event (ADE) safety signal detection. We also aim to gather feedback through usability testing to assess design, performance, and user satisfaction with the tool. A prototype, open source, web-based, software analytical tool generated statistical disproportionality data mining signal scores and dynamic visual analytics for ADE safety signal detection and management. We leveraged Medical Subject Heading (MeSH) indexing terms assigned to published citations in PubMed/MEDLINE to generate candidate drug-adverse event pairs for quantitative data mining. Six FDA regulatory reviewers participated in usability testing by employing the tool as part of their ongoing real-life pharmacovigilance activities to provide subjective feedback on its practical impact, added value, and fitness for use. All usability test participants cited the tool's ease of learning, ease of use, and generation of quantitative ADE safety signals, some of which corresponded to known established adverse drug reactions. Potential concerns included the comparability of the tool's automated literature search relative to a manual 'all fields' PubMed search, missing drugs and adverse event terms, interpretation of signal scores, and integration with existing computer-based analytical tools. Usability testing demonstrated that this novel tool can automate the detection of ADE safety signals from published literature reports. Various mitigation strategies are described to foster improvements in design, productivity, and end user satisfaction.

Developing an Emergency Physician Productivity Index Using Descriptive Health Analytics.

Science.gov (United States)

Khalifa, Mohamed

2015-01-01

Emergency department (ED) crowding became a major barrier to receiving timely emergency care. At King Faisal Specialist Hospital and Research Center, Saudi Arabia, we identified variables and factors affecting crowding and performance to develop indicators to help evaluation and improvement. Measuring efficiency of work and activity of throughput processes; it was important to develop an ED physician productivity index. Data on all ED patients' encounters over the last six months of 2014 were retrieved and descriptive health analytics methods were used. Three variables were identified for their influence on productivity and performance; Number of Treated Patients per Physician, Patient Acuity Level and Treatment Time. The study suggested a formula to calculate the productivity index of each physician through dividing the Number of Treated Patients by Patient Acuity Level squared and Treatment Time to identify physicians with low productivity index and investigate causes and factors.

Metabonomics and drug development.

Science.gov (United States)

Ramana, Pranov; Adams, Erwin; Augustijns, Patrick; Van Schepdael, Ann

2015-01-01

Metabolites as an end product of metabolism possess a wealth of information about altered metabolic control and homeostasis that is dependent on numerous variables including age, sex, and environment. Studying significant changes in the metabolite patterns has been recognized as a tool to understand crucial aspects in drug development like drug efficacy and toxicity. The inclusion of metabonomics into the OMICS study platform brings us closer to define the phenotype and allows us to look at alternatives to improve the diagnosis of diseases. Advancements in the analytical strategies and statistical tools used to study metabonomics allow us to prevent drug failures at early stages of drug development and reduce financial losses during expensive phase II and III clinical trials. This chapter introduces metabonomics along with the instruments used in the study; in addition relevant examples of the usage of metabonomics in the drug development process are discussed along with an emphasis on future directions and the challenges it faces.

Trends in Process Analytical Technology: Present State in Bioprocessing.

Science.gov (United States)

Jenzsch, Marco; Bell, Christian; Buziol, Stefan; Kepert, Felix; Wegele, Harald; Hakemeyer, Christian

2017-08-04

Process analytical technology (PAT), the regulatory initiative for incorporating quality in pharmaceutical manufacturing, is an area of intense research and interest. If PAT is effectively applied to bioprocesses, this can increase process understanding and control, and mitigate the risk from substandard drug products to both manufacturer and patient. To optimize the benefits of PAT, the entire PAT framework must be considered and each elements of PAT must be carefully selected, including sensor and analytical technology, data analysis techniques, control strategies and algorithms, and process optimization routines. This chapter discusses the current state of PAT in the biopharmaceutical industry, including several case studies demonstrating the degree of maturity of various PAT tools. Graphical Abstract Hierarchy of QbD components.

Tuberculosis drug issues: prices, fixed-dose combination products and second-line drugs.

Science.gov (United States)

Laing, R O; McGoldrick, K M

2000-12-01

Access to tuberculosis drugs depends on multiple factors. Selection of a standard list of TB drugs to procure is the first step. This paper reviews the advantages and disadvantages of procuring and using fixed-dose combination (FDC) products for both the intensive and continuation phases of treatment. The major advantages are to prevent the emergence of resistance, to simplify logistic management and to reduce costs. The major disadvantage is the need for the manufacturers to assure the quality of these FDCs by bioavailability testing. The paper reports on the inclusion of second-line TB drugs in the 1999 WHO Essential Drug List (EDL). The need to ensure that these drugs are used within established DOTS-Plus programs is stressed. The price of TB drugs is determined by many factors, including producer prices, local taxes and duties as well as mark-ups and fees. TB drug prices for both the public and private sectors from industrialized and developing countries are reported. Price trends over time are also reported. The key findings of this study are that TB drug prices have generally declined in developing countries while they have increased in developed countries, both for the public and private sectors. Prices vary between countries, with the US paying as much as 95 times the price paid in a specific developing country. The prices of public sector first-line TB drugs vary little between countries, although differences do exist due to the procurement methods used. The price of tuberculin, a diagnostic agent, has increased dramatically in the US, with substantial inter-country variations in price. The paper suggests that further research is necessary to identify the reasons for the price disparities and changes over time, and suggests methods which can be used by National Tuberculosis Programme managers to ensure availability of quality assured TB drugs at low prices.

Numerical and analytical simulation of the production process of ZrO2 hollow particles

Science.gov (United States)

Safaei, Hadi; Emami, Mohsen Davazdah

2017-12-01

In this paper, the production process of hollow particles from the agglomerated particles is addressed analytically and numerically. The important parameters affecting this process, in particular, the initial porosity level of particles and the plasma gun types are investigated. The analytical model adopts a combination of quasi-steady thermal equilibrium and mechanical balance. In the analytical model, the possibility of a solid core existing in agglomerated particles is examined. In this model, a range of particle diameters (50μm ≤ D_{p0} ≤ 160 μ m) and various initial porosities ( 0.2 ≤ p ≤ 0.7) are considered. The numerical model employs the VOF technique for two-phase compressible flows. The production process of hollow particles from the agglomerated particles is simulated, considering an initial diameter of D_{p0} = 60 μm and initial porosity of p = 0.3, p = 0.5, and p = 0.7. Simulation results of the analytical model indicate that the solid core diameter is independent of the initial porosity, whereas the thickness of the particle shell strongly depends on the initial porosity. In both models, a hollow particle may hardly develop at small initial porosity values ( p disintegrates at high initial porosity values ( p > 0.6.

Analytical properties of multiple production amplitudes

Energy Technology Data Exchange (ETDEWEB)

Medvedev, B V; Pavlov, V P; Polivanov, M K; Sukhanov, A D [Gosudarstvennyj Komitet po Ispol' zovaniyu Atomnoj Ehnergii SSSR, Moscow. Inst. Teoreticheskoj i Ehksperimental' noj Fiziki; AN SSSR, Moscow. Matematicheskij Inst.)

1984-05-01

Local analytical properties of amplitudes 2..-->..3 and 2..-->..4 are studied. The amplitudes are shown to be analytical functions of total and partial energies at fixed momentum transfers in the neighbourhood of any physical point on the energy shell 14 (for the 2..-->..3 case) and 242 (for the 2..-->..4 case) boundary values are expressed through the amplitudes of real processes.

Equivalence of complex drug products: advances in and challenges for current regulatory frameworks.

Science.gov (United States)

Hussaarts, Leonie; Mühlebach, Stefan; Shah, Vinod P; McNeil, Scott; Borchard, Gerrit; Flühmann, Beat; Weinstein, Vera; Neervannan, Sesha; Griffiths, Elwyn; Jiang, Wenlei; Wolff-Holz, Elena; Crommelin, Daan J A; de Vlieger, Jon S B

2017-11-01

Biotechnology and nanotechnology provide a growing number of innovator-driven complex drug products and their copy versions. Biologics exemplify one category of complex drugs, but there are also nonbiological complex drug products, including many nanomedicines, such as iron-carbohydrate complexes, drug-carrying liposomes or emulsions, and glatiramoids. In this white paper, which stems from a 1-day conference at the New York Academy of Sciences, we discuss regulatory frameworks in use worldwide (e.g., the U.S. Food and Drug Administration, the European Medicines Agency, the World Health Organization) to approve these complex drug products and their follow-on versions. One of the key questions remains how to assess equivalence of these complex products. We identify a number of points for which consensus was found among the stakeholders who were present: scientists from innovator and generic/follow-on companies, academia, and regulatory bodies from different parts of the world. A number of topics requiring follow-up were identified: (1) assessment of critical attributes to establish equivalence for follow-on versions, (2) the need to publish scientific findings in the public domain to further progress in the field, (3) the necessity to develop worldwide consensus regarding nomenclature and labeling of these complex products, and (4) regulatory actions when substandard complex drug products are identified. © 2017 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals, Inc. on behalf of New York Academy of Sciences.

Combinative Particle Size Reduction Technologies for the Production of Drug Nanocrystals

Directory of Open Access Journals (Sweden)

Jaime Salazar

2014-01-01

Full Text Available Nanosizing is a suitable method to enhance the dissolution rate and therefore the bioavailability of poorly soluble drugs. The success of the particle size reduction processes depends on critical factors such as the employed technology, equipment, and drug physicochemical properties. High pressure homogenization and wet bead milling are standard comminution techniques that have been already employed to successfully formulate poorly soluble drugs and bring them to market. However, these techniques have limitations in their particle size reduction performance, such as long production times and the necessity of employing a micronized drug as the starting material. This review article discusses the development of combinative methods, such as the NANOEDGE, H 96, H 69, H 42, and CT technologies. These processes were developed to improve the particle size reduction effectiveness of the standard techniques. These novel technologies can combine bottom-up and/or top-down techniques in a two-step process. The combinative processes lead in general to improved particle size reduction effectiveness. Faster production of drug nanocrystals and smaller final mean particle sizes are among the main advantages. The combinative particle size reduction technologies are very useful formulation tools, and they will continue acquiring importance for the production of drug nanocrystals.

Analytical monitoring of systems for the production of high-purity, desalinated water

International Nuclear Information System (INIS)

Kunert, I.

1988-01-01

The purity requirements to be met by high-purity water currently push the most sensitive analytical methods to their utmost limits of sensitivity. The required degree of purity of the water at present can only be achieved by application of membrane processes, and pre-purification of the feedwater to a quality corresponding to that of the raw water source. The contribution in hand discusses the analytical monitoring of the raw water treatment plant, the water treatment prior to the treatment by reverse osmosis, monitoring and control of the modules for reverse osmosis, and the monitoring of high-purity water production for the microelectronics industry. (orig./RB) [de

Screening for illicit drugs in pooled human urine and urinated soil samples and studies on the stability of urinary excretion products of cocaine, MDMA, and MDEA in wastewater by hyphenated mass spectrometry techniques.

Science.gov (United States)

Mardal, Marie; Kinyua, Juliet; Ramin, Pedram; Miserez, Bram; Van Nuijs, Alexander L N; Covaci, Adrian; Meyer, Markus R

2017-01-01

Monitoring population drug use through wastewater-based epidemiology (WBE) is a useful method to quantitatively follow trends and estimate total drug consumption in communities. Concentrations of drug biomarkers might be low in wastewater due to dilution; and therefore analysis of pooled urine (PU) is useful to detect consumed drugs and identify targets of illicit drugs use. The aims of the study were (1) to screen PU and urinated soil (US) samples collected at festivals for illicit drug excretion products using hyphenated techniques; (2) to develop and validate a hydrophilic interaction liquid chromatography - mass spectrometry / mass spectrometry (HILIC-MS/MS) method of quantifying urinary targets of identified drugs in wastewater; and (3) to conduct a 24 h stability study, using PU and US to better reflect the chemical environment for targets in wastewater. Cocaine (COC) and ecstasy-like compounds were the most frequently detected illicit drugs; an analytical method was developed to quantify their excretion products. Hydroxymethoxymethamphetamine (HMMA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), HMMA sulfate (HMMA-S), benzoylecgonine (BE), and cocaethylene (CE) had 85-102% of initial concentration after 8 h of incubation, whereas COC and ecgonine methyl ester (EME) had 74 and 67% after 8 h, respectively. HMMA showed a net increase during 24 h of incubation (107% ± 27, n = 8), possibly due to the cleavage of HMMA conjugates, and biotransformation of MDMA. The results suggest HMMA as analytical target for MDMA consumption in WBE, due to its stability in wastewater and its excretion as the main phase I metabolite of MDMA. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

21 CFR 216.24 - Drug products withdrawn or removed from the market for reasons of safety or effectiveness.

Science.gov (United States)

2010-04-01

.... Bromfenac sodium: All drug products containing bromfenac sodium. Butamben: All parenteral drug products...). Dexfenfluramine hydrochloride: All drug products containing dexfenfluramine hydrochloride. Diamthazole... dihydrostreptomycin sulfate. Dipyrone: All drug products containing dipyrone. Encainide hydrochloride: All drug...

Biomarker Analysis of Stored Blood Products: Emphasis on Pre-Analytical Issues

Science.gov (United States)

Delobel, Julien; Rubin, Olivier; Prudent, Michel; Crettaz, David; Tissot, Jean-Daniel; Lion, Niels

2010-01-01

Millions of blood products are transfused every year; many lives are thus directly concerned by transfusion. The three main labile blood products used in transfusion are erythrocyte concentrates, platelet concentrates and fresh frozen plasma. Each of these products has to be stored according to its particular components. However, during storage, modifications or degradation of those components may occur, and are known as storage lesions. Thus, biomarker discovery of in vivo blood aging as well as in vitro labile blood products storage lesions is of high interest for the transfusion medicine community. Pre-analytical issues are of major importance in analyzing the various blood products during storage conditions as well as according to various protocols that are currently used in blood banks for their preparations. This paper will review key elements that have to be taken into account in the context of proteomic-based biomarker discovery applied to blood banking. PMID:21151459

Analytical Chemistry in the Regulatory Science of Medical Devices.

Science.gov (United States)

Wang, Yi; Guan, Allan; Wickramasekara, Samanthi; Phillips, K Scott

2018-06-12

In the United States, regulatory science is the science of developing new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of all Food and Drug Administration-regulated products. Good regulatory science facilitates consumer access to innovative medical devices that are safe and effective throughout the Total Product Life Cycle (TPLC). Because the need to measure things is fundamental to the regulatory science of medical devices, analytical chemistry plays an important role, contributing to medical device technology in two ways: It can be an integral part of an innovative medical device (e.g., diagnostic devices), and it can be used to support medical device development throughout the TPLC. In this review, we focus on analytical chemistry as a tool for the regulatory science of medical devices. We highlight recent progress in companion diagnostics, medical devices on chips for preclinical testing, mass spectrometry for postmarket monitoring, and detection/characterization of bacterial biofilm to prevent infections.

Understanding Customer Product Choices: A Case Study Using the Analytical Hierarchy Process

Science.gov (United States)

Robert L. Smith; Robert J. Bush; Daniel L. Schmoldt

1996-01-01

The Analytical Hierarchy Process (AHP) was used to characterize the bridge material selection decisions of highway officials across the United States. Understanding product choices by utilizing the AHP allowed us to develop strategies for increasing the use of timber in bridge construction. State Department of Transportation engineers, private consulting engineers, and...

AmO₂ Analysis for Analytical Method Testing and Assessment: Analysis Support for AmO₂ Production

Energy Technology Data Exchange (ETDEWEB)

Kuhn, Kevin John [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Bland, Galey Jean [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Fulwyler, James Brent [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Garduno, Katherine [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Keller, Russell C. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Klundt, Dylan James [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Lujan, Elmer J. W [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Mark, Zoe Francoise Elise [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Mathew, Kattathu Joseph [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Ortega, Laura Claire [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Ottenfeld, Chelsea Faith [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Porterfield, Donivan R. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Rearick, Michael Sean [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Rim, Jung Ho [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Schake, Ann Rene [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Schappert, Michael Francis [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Stanley, Floyd E. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Thomas, Mariam R. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Wylie, Ernest Miller II [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Xu, Ning [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Tandon, Lav [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2017-09-08

Americium oxide samples will be measured for various analytes to support AmO₂ production. The key analytes that are currently requested by the Am production customer at LANL include total Am content, Am isotopics, Pu assay, Pu isotopics, and trace element content including ²³⁷Np content. Multiple analytical methods will be utilized depending on the sensitivity, accuracy and precision needs of the Am matrix. Traceability to the National Institute of Standards and Technology (NIST) will be achieved, where applicable, by running NIST traceable quality control materials. This given that there are no suitable AmO₂ reference materials currently available for requested analytes. The primary objective is to demonstrate the suitability of actinide analytical chemistry methods to support AmO₂ production operations.

Permanent Discontinuance or Interruption in Manufacturing of Certain Drug or Biological Products. Final rule.

Science.gov (United States)

2015-07-08

The Food and Drug Administration (FDA or the Agency) is amending its regulations to implement certain drug shortages provisions of the Federal Food, Drug, and Cosmetic Act (the FD&C Act), as amended by the Food and Drug Administration Safety and Innovation Act (FDASIA). The rule requires all applicants of covered approved drugs or biological products--including certain applicants of blood or blood components for transfusion and all manufacturers of covered drugs marketed without an approved application--to notify FDA electronically of a permanent discontinuance or an interruption in manufacturing of the product that is likely to lead to a meaningful disruption in supply (or a significant disruption in supply for blood or blood components) of the product in the United States.

Advanced Analytics service to enhance workflow control at the ATLAS Production System

CERN Document Server

Titov, Mikhail; The ATLAS collaboration

2018-01-01

Modern workload management systems that are responsible for central data production and processing in High Energy and Nuclear Physics experiments have highly complicated architectures and require a specialized control service for resource and processing components balancing. Such a service represents a comprehensive set of analytical tools, management utilities and monitoring views aimed at providing a deep understanding of internal processes, and is considered as an extension for situational awareness analytic service. Its key points are analysis of task processing, e.g., selection and regulation of key task features that affect its processing the most; modeling of processed data lifecycles for further analysis, e.g., generate guidelines for particular stage of data processing; and forecasting processes with focus on data and tasks states as well as on the management system itself, e.g., to detect the source of any potential malfunction. The prototype of the advanced analytics service will be an essential pa...

Direct analyte-probed nanoextraction coupled to nanospray ionization-mass spectrometry of drug residues from latent fingerprints.

Science.gov (United States)

Clemons, Kristina; Wiley, Rachel; Waverka, Kristin; Fox, James; Dziekonski, Eric; Verbeck, Guido F

2013-07-01

Here, we present a method of extracting drug residues from fingerprints via Direct Analyte-Probed Nanoextraction coupled to nanospray ionization-mass spectrometry (DAPNe-NSI-MS). This instrumental technique provides higher selectivity and lower detection limits over current methods, greatly reducing sample preparation, and does not compromise the integrity of latent fingerprints. This coupled to Raman microscopy is an advantageous supplement for location and identification of trace particles. DAPNe uses a nanomanipulator for extraction and differing microscopies for localization of chemicals of interest. A capillary tip with solvent of choice is placed in a nanopositioner. The surface to be analyzed is placed under a microscope, and a particle of interest is located. Using a pressure injector, the solvent is injected onto the surface where it dissolves the analyte, and then extracted back into the capillary tip. The solution is then directly analyzed via NSI-MS. Analyses of caffeine, cocaine, crystal methamphetamine, and ecstasy have been performed successfully. © 2013 American Academy of Forensic Sciences.

[Raman spectroscopy applied to analytical quality control of injectable drugs: analytical evaluation and comparative economic versus HPLC and UV / visible-FTIR].

Science.gov (United States)

Bourget, P; Amin, A; Vidal, F; Merlette, C; Troude, P; Corriol, O

2013-09-01

In France, central IV admixture of chemotherapy (CT) treatments at the hospital is now required by law. We have previously shown that the shaping of Therapeutic Objects (TOs) could profit from an Analytical Quality Assurance (AQA), closely linked to the batch release, for the three key parameters: identity, purity, and initial concentration of the compound of interest. In the course of recent and diversified works, we showed the technical superiority of non-intrusive Raman Spectroscopy (RS) vs. any other analytical option and, especially for both HPLC and vibrational method using a UV/visible-FTIR coupling. An interconnected qualitative and economic assessment strongly helps to enrich these relevant works. The study compares in operational situation, the performance of three analytical methods used for the AQC of TOs. We used: a) a set of evaluation criteria, b) the depreciation tables of the machinery, c) the cost of disposables, d) the weight of equipment and technical installations, e) the basic accounting unit (unit of work) and its composite costs (Euros), which vary according to the technical options, the weight of both human resources and disposables; finally, different combinations are described. So, the unit of work can take 12 different values between 1 and 5.5 Euros, and we provide various recommendations. A qualitative evaluation grid constantly places the SR technology as superior or equal to the 2 other techniques currently available. Our results demonstrated: a) the major interest of the non-intrusive AQC performed by RS, especially when it is not possible to analyze a TO with existing methods e.g. elastomeric portable pumps, and b) the high potential for this technique to be a strong contributor to the security of the medication circuit, and to fight the iatrogenic effects of drugs especially in the hospital. It also contributes to the protection of all actors in healthcare and of their working environment.

Medicinal importance, pharmacological activities, and analytical aspects of aloin: A concise report

Directory of Open Access Journals (Sweden)

Kanika Patel

2013-01-01

Full Text Available Natural products such as pure phytoconstituents and plant extracts offer limitless opportunities for the new drug development due to its unmatched chemical diversity. Plants play an important role in the medicinal preparations for both preventive and curative purpose. Some of the currently available drugs i.e. aspirin, digitalis, anti-malarial (quinine and anti-cancer (vincristine, vinblastine were derived from the plant sources. Aloin (C21H22O9, a yellow colour compound is a mixture of two diastereoisomers, aloin A and aloin B. Aloin is an anthrone C-glucoside having molecular weight 418, and it is the main phytoconstituents of aloes. Aloin is used for various pharmacological purposes such as laxative agent. It is also used as ingredients of various laxative pharmaceutical preparations. So far, varieties of analytical methods have been developed for the estimation of aloin in aloes product, which are mainly based on HPLC and TLC techniques. In the present review, pharmacological activities and analytical aspects of aloin were highlighted along with some useful tissue culture techniques. This review could be helpful to the researcher for the investigation of new molecule from aloin in the future.

Drug Products in the Medicaid Drug Rebate Program

Data.gov (United States)

U.S. Department of Health & Human Services — Active drugs that have been reported by participating drug manufacturers under the Medicaid Drug Rebate Program. All drugs are identified by National Drug Code...

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

Science.gov (United States)

Lin, Shan-Yang; Wang, Shun-Li

2012-04-01

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

Resonant particle production during inflation: a full analytical study

Energy Technology Data Exchange (ETDEWEB)

Pearce, Lauren; Peloso, Marco [School of Physics and Astronomy, University of Minnesota, 116 Church Street S.E., Minneapolis, MN 55455 (United States); Sorbo, Lorenzo, E-mail: lpearce@physics.umn.edu, E-mail: peloso@physics.umn.edu, E-mail: sorbo@physics.umass.edu [Amherst Center for Fundamental Interactions, Department of Physics, University of Massachusetts, 1126 Lederle Graduate Research Tower (LGRT), Amherst, MA 01003 (United States)

2017-05-01

We revisit the study of the phenomenology associated to a burst of particle production of a field whose mass is controlled by the inflaton field and vanishes at one given instance during inflation. This generates a bump in the correlators of the primordial scalar curvature. We provide a unified formalism to compute various effects that have been obtained in the literature and confirm that the dominant effects are due to the rescattering of the produced particles on the inflaton condensate. We improve over existing results (based on numerical fits) by providing exact analytic expressions for the shape and height of the bump, both in the power spectrum and the equilateral bispectrum. We then study the regime of validity of the perturbative computations of this signature. Finally, we extend these computations to the case of a burst of particle production in a sector coupled only gravitationally to the inflaton.

Principal component analysis as a tool for library design: a case study investigating natural products, brand-name drugs, natural product-like libraries, and drug-like libraries.

Science.gov (United States)

Wenderski, Todd A; Stratton, Christopher F; Bauer, Renato A; Kopp, Felix; Tan, Derek S

2015-01-01

Principal component analysis (PCA) is a useful tool in the design and planning of chemical libraries. PCA can be used to reveal differences in structural and physicochemical parameters between various classes of compounds by displaying them in a convenient graphical format. Herein, we demonstrate the use of PCA to gain insight into structural features that differentiate natural products, synthetic drugs, natural product-like libraries, and drug-like libraries, and show how the results can be used to guide library design.

7 CFR 94.4 - Analytical methods.

Science.gov (United States)

2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Analytical methods. 94.4 Section 94.4 Agriculture... POULTRY AND EGG PRODUCTS Mandatory Analyses of Egg Products § 94.4 Analytical methods. The majority of analytical methods used by the USDA laboratories to perform mandatory analyses for egg products are listed as...

Analytical method used for intermediate products in continuous distillation of furfural

Energy Technology Data Exchange (ETDEWEB)

Wang, Z.L.; Jia, M.; Wang, L.J.; Deng, Y.X.

1981-01-01

During distillation of furfural, analysis of main components in the crude furfural condensate and intermediate products is very important. Since furfural and methylfurfural are homologous and both furfural and acetone contain a carbonyl group, components in the sample must be separated before analysis. An improved analytical method has been studied, the accuracy and precision of which would meet the requirement of industrial standards. The analytical procedure was provided as follows: to determine the furfural content with gravimetric method of barbituric acid; to determine the methanol content with dichromate method after precipitating furfural and acetone, and distilling the liquid for analysis; and to determine the methylfurfural content with bromide-bromate method, which can be used only in the sample containing higher content of methylfurfural. For the sample in low content, the gas-liquid chromatographic method can be used. 7 references.

Analytical review of modern herbal medicines used in musculoskeletal system diseases

Directory of Open Access Journals (Sweden)

Анна Ігорівна Крюкова

2015-10-01

Full Text Available Effective and safe treatment of the musculoskeletal system diseases is one of the main branches of medicine in general and rheumatology in particular. The relevance of this problem is caused mainly by the high incidence in the population, and temporary and permanent work disability status development in patients. The duration of rheumatologic diseases necessitates the optimal regimen selection, providing effective treatment and helping to prevent potential side effects associated with long-term use of remedies.Aim of research. The aim of our research was to perform an analytical review of modern herbal products registered in Ukraine and used for musculoskeletal system treatment. The drug analysis was made according to next parameters: producing country, manufacturer, dosage form, and the origin of remedies (natural or synthetic.Methods. Conventional analytical studies of electronic and paper sources were used for realization of the given problem.Results. As a result of the analytical review of modern herbal remedies registered in Ukraine and used for musculoskeletal system treatment, it was found that 20 trade names of drugs, more than 90% of which are homeopathic, are displayed on the pharmaceutical market. Concerning dosage forms, pills (38,5 %, injection solutions and oral drops (23,1 % and 11,5 %, respectively gain the biggest market share.Conclusion. It was found that imported drugs are widely available (80 % on the analyzed market segment, while local remedies gain rather minor market share (about 20 %.Among medicines of this group presented on Ukrainian market, imported homeopathic remedies gain the biggest share. Phytotheurapeutic drugs gain minor market share and have limited composition of natural active ingredients represented by the extracts of Harpagophytum procumbens, Apium graveolens, Salix alba, and Zingiber officinale

Natural Products as Leads in Schistosome Drug Discovery

Directory of Open Access Journals (Sweden)

Bruno J. Neves

2015-01-01

Full Text Available Schistosomiasis is a neglected parasitic tropical disease that claims around 200,000 human lives every year. Praziquantel (PZQ, the only drug recommended by the World Health Organization for the treatment and control of human schistosomiasis, is now facing the threat of drug resistance, indicating the urgent need for new effective compounds to treat this disease. Therefore, globally, there is renewed interest in natural products (NPs as a starting point for drug discovery and development for schistosomiasis. Recent advances in genomics, proteomics, bioinformatics, and cheminformatics have brought about unprecedented opportunities for the rapid and more cost-effective discovery of new bioactive compounds against neglected tropical diseases. This review highlights the main contributions that NP drug discovery and development have made in the treatment of schistosomiasis and it discusses how integration with virtual screening (VS strategies may contribute to accelerating the development of new schistosomidal leads, especially through the identification of unexplored, biologically active chemical scaffolds and structural optimization of NPs with previously established activity.

Analytical measurements of fission products during a severe nuclear accident

Science.gov (United States)

Doizi, D.; Reymond la Ruinaz, S.; Haykal, I.; Manceron, L.; Perrin, A.; Boudon, V.; Vander Auwera, J.; tchana, F. Kwabia; Faye, M.

2018-01-01

The Fukushima accident emphasized the fact that ways to monitor in real time the evolution of a nuclear reactor during a severe accident remain to be developed. No fission products were monitored during twelve days; only dose rates were measured, which is not sufficient to carry out an online diagnosis of the event. The first measurements were announced with little reliability for low volatile fission products. In order to improve the safety of nuclear plants and minimize the industrial, ecological and health consequences of a severe accident, it is necessary to develop new reliable measurement systems, operating at the earliest and closest to the emission source of fission products. Through the French program ANR « Projet d'Investissement d'Avenir », the aim of the DECA-PF project (diagnosis of core degradation from fission products measurements) is to monitor in real time the release of the major fission products (krypton, xenon, gaseous forms of iodine and ruthenium) outside the nuclear reactor containment. These products are released at different times during a nuclear accident and at different states of the nuclear core degradation. Thus, monitoring these fission products gives information on the situation inside the containment and helps to apply the Severe Accident Management procedures. Analytical techniques have been proposed and evaluated. The results are discussed here.

Analytical measurements of fission products during a severe nuclear accident

Directory of Open Access Journals (Sweden)

Doizi D.

2018-01-01

Full Text Available The Fukushima accident emphasized the fact that ways to monitor in real time the evolution of a nuclear reactor during a severe accident remain to be developed. No fission products were monitored during twelve days; only dose rates were measured, which is not sufficient to carry out an online diagnosis of the event. The first measurements were announced with little reliability for low volatile fission products. In order to improve the safety of nuclear plants and minimize the industrial, ecological and health consequences of a severe accident, it is necessary to develop new reliable measurement systems, operating at the earliest and closest to the emission source of fission products. Through the French program ANR « Projet d’Investissement d’Avenir », the aim of the DECA-PF project (diagnosis of core degradation from fission products measurements is to monitor in real time the release of the major fission products (krypton, xenon, gaseous forms of iodine and ruthenium outside the nuclear reactor containment. These products are released at different times during a nuclear accident and at different states of the nuclear core degradation. Thus, monitoring these fission products gives information on the situation inside the containment and helps to apply the Severe Accident Management procedures. Analytical techniques have been proposed and evaluated. The results are discussed here.

Potential of Continuous Manufacturing for Liposomal Drug Products.

Science.gov (United States)

Worsham, Robert D; Thomas, Vaughan; Farid, Suzanne S

2018-05-21

Over the last several years, continuous manufacturing of pharmaceuticals has evolved from bulk APIs and solid oral dosages into the more complex realm of biologics. The development of continuous downstream processing techniques has allowed biologics manufacturing to realize the benefits (e.g. improved economics, more consistent quality) that come with continuous processing. If relevant processing techniques and principles are selected, the opportunity arises to develop continuous manufacturing designs for additional pharmaceutical products including liposomal drug formulations. Liposome manufacturing has some inherent aspects that make it favorable for a continuous process. Other aspects such as formulation refinement, materials of construction, and aseptic processing need development, but present an achievable challenge. This paper reviews the current state of continuous manufacturing technology applicable to liposomal drug product manufacturing and an assessment of the challenges and potential of this application. This article is protected by copyright. All rights reserved.

77 FR 71006 - Sodium Nitrite Injection and Sodium Thiosulfate Injection Drug Products Labeled for the Treatment...

Science.gov (United States)

2012-11-28

... poisoning and unapproved injectable drug products containing sodium thiosulfate labeled for the treatment of... for the treatment of cyanide poisoning are new drugs that require approved new drug applications (NDAs... Injection and Sodium Thiosulfate Injection drug product, labeled for treatment of acute cyanide poisoning...

Characterization of titanium dioxide nanoparticles in food products: analytical methods to define nanoparticles.

Science.gov (United States)

Peters, Ruud J B; van Bemmel, Greet; Herrera-Rivera, Zahira; Helsper, Hans P F G; Marvin, Hans J P; Weigel, Stefan; Tromp, Peter C; Oomen, Agnes G; Rietveld, Anton G; Bouwmeester, Hans

2014-07-09

Titanium dioxide (TiO2) is a common food additive used to enhance the white color, brightness, and sometimes flavor of a variety of food products. In this study 7 food grade TiO2 materials (E171), 24 food products, and 3 personal care products were investigated for their TiO2 content and the number-based size distribution of TiO2 particles present in these products. Three principally different methods have been used to determine the number-based size distribution of TiO2 particles: electron microscopy, asymmetric flow field-flow fractionation combined with inductively coupled mass spectrometry, and single-particle inductively coupled mass spectrometry. The results show that all E171 materials have similar size distributions with primary particle sizes in the range of 60-300 nm. Depending on the analytical method used, 10-15% of the particles in these materials had sizes below 100 nm. In 24 of the 27 foods and personal care products detectable amounts of titanium were found ranging from 0.02 to 9.0 mg TiO2/g product. The number-based size distributions for TiO2 particles in the food and personal care products showed that 5-10% of the particles in these products had sizes below 100 nm, comparable to that found in the E171 materials. Comparable size distributions were found using the three principally different analytical methods. Although the applied methods are considered state of the art, they showed practical size limits for TiO2 particles in the range of 20-50 nm, which may introduce a significant bias in the size distribution because particles <20 nm are excluded. This shows the inability of current state of the art methods to support the European Union recommendation for the definition of nanomaterials.

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

OpenAIRE

Römer, Meike

2008-01-01

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

Validation of a liquid chromatographic method for the pharmaceutical quality control of products containing elacridar

Directory of Open Access Journals (Sweden)

Emilia Sawicki

2016-08-01

Full Text Available Many anticancer drugs have an impaired bioavailability and poor brain penetration because they are substrates to drug efflux pumps such as P-glycoprotein and Breast Cancer Resistance Protein. Elacridar is a strong inhibitor of these two drug efflux pumps and therefore has great potential to improve oral absorption and brain penetration of many anticancer drugs. Currently, a clinical formulation of elacridar is unavailable and therefore the pharmaceutical development of a drug product is highly warranted. This also necessitates the availability of an analytical method for its quality control. A reverse-phase high-performance liquid chromatographic method with ultraviolet detection was developed for the pharmaceutical quality control of products containing elacridar as the active pharmaceutical ingredient. The analytical method was validated for linearity, accuracy, precision, selectivity, carry-over, stability of stock and reference solutions, stability of the final extract, stability-indicating capability and impurity testing. We found that elacridar is unstable in aqueous solutions that are exposed to light because a hydroxylation product of elacridar is formed. Therefore, sample solutions with elacridar must be protected from light.

FDA's requirements for radiation dosimetry of radiopharmaceutical drug products

International Nuclear Information System (INIS)

Abel, N.M.

1986-01-01

The primary concern of the Office of Drug Research and Review of the Food and Drug Administration in the field of radiation dosimetry is to ensure that radiopharmaceutical drug products are safe when used as investigational drugs (INDs) and are both safe and effective when a new drug application (NDA) is approved. In order to accomplish this, the sponsor of either an IND or applicant in the case of NDA must provide information that clearly describes the radiation dose that a patient will receive from the administration of the drug. The submitted numerical estimates of the radiation dose should be based on an absorbed fraction method of radiation dose calculation, such as the system set forth by the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine or the system set forth by the International Commission on Radiological Protection (ICRP). This presentation will describe in detail the data that a sponsor of an IND needs to submit to satisfy the regulatory requirements. Examples will be given of common mistakes and omissions by sponsors in their presentation of data

Analysis of veterinary drug residue monitoring results for commercial livestock products in Taiwan between 2011 and 2015

Directory of Open Access Journals (Sweden)

Hsin-Chun Lee

2018-04-01

Full Text Available Antibiotics have been widely used in the treatment of livestock diseases. However, the emergence of issues related to drug resistance prompted governments to enact a series of laws regulating the use of antibiotics in livestock. Following control of the problem of drug resistant bacteria, public attention has shifted to the recurring incidence of human health and safety issues caused by residual veterinary drugs in livestock products. To guarantee the safety and hygiene of meat, milk, and eggs from food-producing animals, governments and relevant agencies established laws and regulations for the use of veterinary drugs. It is, therefore, necessary to monitor the content of residual drugs in livestock products at regular intervals to assess whether the regulations have resulted in the effective management of food product safety, and to prevent and manage sudden problems related to this issue. A 2011–2015 livestock product post-marketing monitoring program launched by the Taiwan Food and Drug Administration (TFDA inspected 1487 livestock products. Over the past 5 years, there were 34 samples identified that did not conform to the regulations; these samples included residue drugs such as β-agonists, chloramphenicols, β-lactam antibiotics, sulfa drugs, enrofloxacin, and lincomycin. Inspections of commercial livestock products with the consistent cooperation of agricultural authorities did not detect the drugs that were banned by the government, whereas the detection of other drugs decreased annually with an increase in the post-market monitoring sample size. In the future, the TFDA will continue to monitor the status of residual veterinary drugs in commercial livestock products, adjust the sampling of food products annually according to monitoring results, and closely cooperate with agricultural authorities on source management. Keywords: Agricultural authorities, Livestock products, Post-market monitoring, Veterinary drug residues

Hazardous drug residue on exterior vial surfaces: evaluation of a commercial manufacturing process.

Science.gov (United States)

Power, Luci A; Sessink, Paul J M; Gesy, Kathy; Charbonneau, Flay

2014-04-01

Hazardous drug residue on the exterior surface of drug vials poses a potential risk for exposure of health care workers involved in handling these products. The purpose of this article is to heighten the awareness of this serious issue and to evaluate a commercial manufacturing process for removing and containing hazardous drug (HD) residue on exterior vial surfaces. Additionally, findings from this study are interpreted, incorporated into the current body of evidence, and discussed by experts in this field. This study includes separate evaluations for the presence or absence of surface drug contamination on the vials of 3 HD products: 5-fluorouracil, cisplatin, and methotrexate. The drug products were packaged in vials using a patented prewashing/decontamination method, application of a polyvinylchloride (PVC) base, and use of clear glass vials. An additional step of encasing the vial in a shrink-wrapped sheath was used for 5-fluorouracil and cisplatin. Of all 5-fluorouracil (110 vials), methotrexate (60 vials), and cisplatin (60 vials) tested, only 2 had detectable amounts of surface residue. One 5-fluorouracil vial was found to have approximately 4 mg of 5-fluorouracil on the surface of the vial. The second contaminated vial was cisplatin, which was discovered to have 131 ng of platinum, equal to 200 ng of cisplatin or 0.2 μL of cisplatin solution, on the vial sheath. Using validated extraction and analytic methods, all but 2 of the 230 tested vials were found to be free of surface drug contamination. Pharmacy leaders need to take an active role in promoting the need for clean HD vials. Manufacturers should be required to provide their clients with data derived from externally validated analytic studies, reporting the level of HD contamination on the exterior of their vial products.

7 CFR 94.103 - Analytical methods.

Science.gov (United States)

2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Analytical methods. 94.103 Section 94.103 Agriculture... POULTRY AND EGG PRODUCTS Voluntary Analyses of Egg Products § 94.103 Analytical methods. The analytical methods used by the Science and Technology Division laboratories to perform voluntary analyses for egg...

7 CFR 94.303 - Analytical methods.

Science.gov (United States)

2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Analytical methods. 94.303 Section 94.303 Agriculture... POULTRY AND EGG PRODUCTS Processed Poultry Products § 94.303 Analytical methods. The analytical methods... latest edition of the Official Methods of Analysis of AOAC INTERNATIONAL, Suite 500, 481 North Frederick...

Scaffold architecture and pharmacophoric properties of natural products and trade drugs: application in the design of natural product-based combinatorial libraries.

Science.gov (United States)

Lee, M L; Schneider, G

2001-01-01

Natural products were analyzed to determine whether they contain appealing novel scaffold architectures for potential use in combinatorial chemistry. Ring systems were extracted and clustered on the basis of structural similarity. Several such potential scaffolds for combinatorial chemistry were identified that are not present in current trade drugs. For one of these scaffolds a virtual combinatorial library was generated. Pharmacophoric properties of natural products, trade drugs, and the virtual combinatorial library were assessed using a self-organizing map. Obviously, current trade drugs and natural products have several topological pharmacophore patterns in common. These features can be systematically explored with selected combinatorial libraries based on a combination of natural product-derived and synthetic molecular building blocks.

Optimization of drug-drug interaction alert rules in a pediatric hospital's electronic health record system using a visual analytics dashboard.

Science.gov (United States)

Simpao, Allan F; Ahumada, Luis M; Desai, Bimal R; Bonafide, Christopher P; Gálvez, Jorge A; Rehman, Mohamed A; Jawad, Abbas F; Palma, Krisha L; Shelov, Eric D

2015-03-01

To develop and evaluate an electronic dashboard of hospital-wide electronic health record medication alerts for an alert fatigue reduction quality improvement project. We used visual analytics software to develop the dashboard. We collaborated with the hospital-wide Clinical Decision Support committee to perform three interventions successively deactivating clinically irrelevant drug-drug interaction (DDI) alert rules. We analyzed the impact of the interventions on care providers' and pharmacists' alert and override rates using an interrupted time series framework with piecewise regression. We evaluated 2 391 880 medication alerts between January 31, 2011 and January 26, 2014. For pharmacists, the median alert rate prior to the first DDI deactivation was 58.74 alerts/100 orders (IQR 54.98-60.48) and 25.11 alerts/100 orders (IQR 23.45-26.57) following the three interventions (pdashboard facilitated safe rapid-cycle reductions in alert burden that were temporally associated with lower pharmacist override rates in a subgroup of DDIs not directly affected by the interventions; meanwhile, the pharmacists' frequency of selecting the 'cancel' option increased. We hypothesize that reducing the alert burden enabled pharmacists to devote more attention to clinically relevant alerts. © The Author 2014. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Sample preparation composite and replicate strategy for assay of solid oral drug products.

Science.gov (United States)

Harrington, Brent; Nickerson, Beverly; Guo, Michele Xuemei; Barber, Marc; Giamalva, David; Lee, Carlos; Scrivens, Garry

2014-12-16

In pharmaceutical analysis, the results of drug product assay testing are used to make decisions regarding the quality, efficacy, and stability of the drug product. In order to make sound risk-based decisions concerning drug product potency, an understanding of the uncertainty of the reportable assay value is required. Utilizing the most restrictive criteria in current regulatory documentation, a maximum variability attributed to method repeatability is defined for a drug product potency assay. A sampling strategy that reduces the repeatability component of the assay variability below this predefined maximum is demonstrated. The sampling strategy consists of determining the number of dosage units (k) to be prepared in a composite sample of which there may be a number of equivalent replicate (r) sample preparations. The variability, as measured by the standard error (SE), of a potency assay consists of several sources such as sample preparation and dosage unit variability. A sampling scheme that increases the number of sample preparations (r) and/or number of dosage units (k) per sample preparation will reduce the assay variability and thus decrease the uncertainty around decisions made concerning the potency of the drug product. A maximum allowable repeatability component of the standard error (SE) for the potency assay is derived using material in current regulatory documents. A table of solutions for the number of dosage units per sample preparation (r) and number of replicate sample preparations (k) is presented for any ratio of sample preparation and dosage unit variability.

Cumulative exposure to phthalates from phthalate-containing drug products

DEFF Research Database (Denmark)

Ennis, Zandra Nymand; Broe, Anne; Pottegård, Anton

2018-01-01

European regulatory limit of exposure ranging between 380-1710 mg/year throughout the study period. Lithium-products constituted the majority of dibutyl phthalate exposure. Diethyl phthalate exposure, mainly caused by erythromycin, theophylline and diclofenac products, did not exceed the EMA regulatory...... to quantify annual cumulated phthalate exposure from drug products among users of phthalate-containing oral medications in Denmark throughout the period of 2004-2016. METHODS: We conducted a Danish nationwide cohort study using The Danish National Prescription Registry and an internal database held...

Mass spectrometry-driven drug discovery for development of herbal medicine.

Science.gov (United States)

Zhang, Aihua; Sun, Hui; Wang, Xijun

2018-05-01

Herbal medicine (HM) has made a major contribution to the drug discovery process with regard to identifying products compounds. Currently, more attention has been focused on drug discovery from natural compounds of HM. Despite the rapid advancement of modern analytical techniques, drug discovery is still a difficult and lengthy process. Fortunately, mass spectrometry (MS) can provide us with useful structural information for drug discovery, has been recognized as a sensitive, rapid, and high-throughput technology for advancing drug discovery from HM in the post-genomic era. It is essential to develop an efficient, high-quality, high-throughput screening method integrated with an MS platform for early screening of candidate drug molecules from natural products. We have developed a new chinmedomics strategy reliant on MS that is capable of capturing the candidate molecules, facilitating their identification of novel chemical structures in the early phase; chinmedomics-guided natural product discovery based on MS may provide an effective tool that addresses challenges in early screening of effective constituents of herbs against disease. This critical review covers the use of MS with related techniques and methodologies for natural product discovery, biomarker identification, and determination of mechanisms of action. It also highlights high-throughput chinmedomics screening methods suitable for lead compound discovery illustrated by recent successes. © 2016 Wiley Periodicals, Inc.

Scientific and Regulatory Considerations in Solid Oral Modified Release Drug Product Development.

Science.gov (United States)

Li, Min; Sander, Sanna; Duan, John; Rosencrance, Susan; Miksinski, Sarah Pope; Yu, Lawrence; Seo, Paul; Rege, Bhagwant

2016-11-01

This review presents scientific and regulatory considerations for the development of solid oral modified release (MR) drug products. It includes a rationale for patient-focused development based on Quality-by-Design (QbD) principles. Product and process understanding of MR products includes identification and risk-based evaluation of critical material attributes (CMAs), critical process parameters (CPPs), and their impact on critical quality attributes (CQAs) that affect the clinical performance. The use of various biopharmaceutics tools that link the CQAs to a predictable and reproducible clinical performance for patient benefit is emphasized. Product and process understanding lead to a more comprehensive control strategy that can maintain product quality through the shelf life and the lifecycle of the drug product. The overall goal is to develop MR products that consistently meet the clinical objectives while mitigating the risks to patients by reducing the probability and increasing the detectability of CQA failures.

Analysis of veterinary drug residue monitoring results for commercial livestock products in Taiwan between 2011 and 2015.

Science.gov (United States)

Lee, Hsin-Chun; Chen, Chi-Min; Wei, Jen-Ting; Chiu, Hsiu-Yi

2018-04-01

Antibiotics have been widely used in the treatment of livestock diseases. However, the emergence of issues related to drug resistance prompted governments to enact a series of laws regulating the use of antibiotics in livestock. Following control of the problem of drug resistant bacteria, public attention has shifted to the recurring incidence of human health and safety issues caused by residual veterinary drugs in livestock products. To guarantee the safety and hygiene of meat, milk, and eggs from food-producing animals, governments and relevant agencies established laws and regulations for the use of veterinary drugs. It is, therefore, necessary to monitor the content of residual drugs in livestock products at regular intervals to assess whether the regulations have resulted in the effective management of food product safety, and to prevent and manage sudden problems related to this issue. A 2011-2015 livestock product post-marketing monitoring program launched by the Taiwan Food and Drug Administration (TFDA) inspected 1487 livestock products. Over the past 5 years, there were 34 samples identified that did not conform to the regulations; these samples included residue drugs such as β-agonists, chloramphenicols, β-lactam antibiotics, sulfa drugs, enrofloxacin, and lincomycin. Inspections of commercial livestock products with the consistent cooperation of agricultural authorities did not detect the drugs that were banned by the government, whereas the detection of other drugs decreased annually with an increase in the post-market monitoring sample size. In the future, the TFDA will continue to monitor the status of residual veterinary drugs in commercial livestock products, adjust the sampling of food products annually according to monitoring results, and closely cooperate with agricultural authorities on source management. Copyright © 2017. Published by Elsevier B.V.

7 CFR 93.4 - Analytical methods.

Science.gov (United States)

2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Analytical methods. 93.4 Section 93.4 Agriculture... PROCESSED FRUITS AND VEGETABLES Citrus Juices and Certain Citrus Products § 93.4 Analytical methods. (a) The majority of analytical methods for citrus products are found in the Official Methods of Analysis of AOAC...

Use of drugs and antibiotics in poultry production in Ghana | Turkson ...

African Journals Online (AJOL)

This study was designed to assess the extent of drug and antibiotic use in small and large commercial poultry producers in Ghana, and the extent of the knowledge, perceptions and practice of drug withdrawal period in poultry production. In all, 483 poultry farmers in Greater Accra, Ashanti and Central regions were ...

77 FR 12311 - Guidance for Industry on Size of Beads in Drug Products Labeled for Sprinkle; Availability

Science.gov (United States)

2012-02-29

...] Guidance for Industry on Size of Beads in Drug Products Labeled for Sprinkle; Availability AGENCY: Food and... the availability of a guidance for industry entitled ``Size of Beads in Drug Products Labeled for... Evaluation and Research's (CDER's) current thinking on appropriate size ranges for beads in drug products...

Predictive analytics as an essential mechanism for situational awareness at the ATLAS Production System

CERN Document Server

Titov, Mikhail; The ATLAS collaboration

2017-01-01

The workflow management process should be under the control of the certain service that is able to forecast the processing time dynamically according to the status of the processing environment and workflow itself, and to react immediately on any abnormal behaviour of the execution process. Such situational awareness analytic service would provide the possibility to monitor the execution process, to detect the source of any malfunction, and to optimize the management process. The stated service for the second generation of the ATLAS Production System (ProdSys2, an automated scheduling system) is based on predictive analytics approach to estimate the duration of the data processings (in terms of ProdSys2, it is task and chain of tasks) with later usage in decision making processes. Machine learning ensemble methods are chosen to estimate completion time (i.e., “Time To Complete”, TTC) for every (production) task and chain of tasks, thus “abnormal” task processing times would warn about possible failure...

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

Science.gov (United States)

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

2017-04-01

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

76 FR 60504 - Guidance for Industry on Time and Extent Applications for Nonprescription Drug Products...

Science.gov (United States)

2011-09-29

... monograph need not obtain FDA approval before marketing if their drug product meets the conditions in part... introduce into the United States an OTC drug product that had been marketed solely in a foreign country...

Quantitative high throughput analytics to support polysaccharide production process development.

Science.gov (United States)

Noyes, Aaron; Godavarti, Ranga; Titchener-Hooker, Nigel; Coffman, Jonathan; Mukhopadhyay, Tarit

2014-05-19

The rapid development of purification processes for polysaccharide vaccines is constrained by a lack of analytical tools current technologies for the measurement of polysaccharide recovery and process-related impurity clearance are complex, time-consuming, and generally not amenable to high throughput process development (HTPD). HTPD is envisioned to be central to the improvement of existing polysaccharide manufacturing processes through the identification of critical process parameters that potentially impact the quality attributes of the vaccine and to the development of de novo processes for clinical candidates, across the spectrum of downstream processing. The availability of a fast and automated analytics platform will expand the scope, robustness, and evolution of Design of Experiment (DOE) studies. This paper details recent advances in improving the speed, throughput, and success of in-process analytics at the micro-scale. Two methods, based on modifications of existing procedures, are described for the rapid measurement of polysaccharide titre in microplates without the need for heating steps. A simplification of a commercial endotoxin assay is also described that features a single measurement at room temperature. These assays, along with existing assays for protein and nucleic acids are qualified for deployment in the high throughput screening of polysaccharide feedstreams. Assay accuracy, precision, robustness, interference, and ease of use are assessed and described. In combination, these assays are capable of measuring the product concentration and impurity profile of a microplate of 96 samples in less than one day. This body of work relies on the evaluation of a combination of commercially available and clinically relevant polysaccharides to ensure maximum versatility and reactivity of the final assay suite. Together, these advancements reduce overall process time by up to 30-fold and significantly reduce sample volume over current practices. The

Production and Investigation of Controlled Drug Release Properties of Tamoxifen Loaded Alginate-Gum Arabic Microbeads

Directory of Open Access Journals (Sweden)

Rukiye Yavaşer

2016-08-01

Full Text Available The entrapment of tamoxifen onto alginate-gum arabic beads and the production of controlled drug release was investigated in this study. The polymeric system that would provide the controlled release of tamoxifen was formed using alginate and gum arabic. In the first phase of the study, the optimization of the alginate-gum arabic beads production was conducted; then the study continued with drug entrapment experiments. Tamoxifen entrapment yield was found to be approximately 90% of initial tamoxifen concentration. In vitro drug release experiments were performed in simulated gastric juice and intestinal fluid where the tamoxifen release was 20% and 53% of the initial drug present, respectively. As a result of this study, it is expected that a valuable contribution to the field of controlled drug release system production is realized.

Interdisciplinary researches for potential developments of drugs and natural products

Directory of Open Access Journals (Sweden)

Arunrat Chaveerach

2017-04-01

Full Text Available Developments of drugs or natural products from plants are possibly made, simple to use and lower cost than modern drugs. The development processes can be started with studying local wisdom and literature reviews to choose the plants which have long been used in diverse areas, such as foods, traditional medicine, fragrances and seasonings. Then those data will be associated with scientific researches, namely plant collection and identification, phytochemical screening by gas chromatography-mass spectrometry, pharmacological study/review for their functions, and finally safety and efficiency tests in human. For safety testing, in vitro cell toxicity by cell viability assessment and in vitro testing of DNA breaks by the comet assay in human peripheral blood mononuclear cells can be performed. When active chemicals and functions containing plants were chosen with safety and efficacy for human uses, then, the potential medicinal natural products will be produced. Based on these procedures, the producing cost will be cheaper and the products can be evaluated for their clinical properties. Thus, the best and lowest-priced medicines and natural products can be distributed worldwide.

Interdisciplinary researches for potential developments of drugs and natural products

Institute of Scientific and Technical Information of China (English)

Arunrat Chaveerach; Runglawan Sudmoon; Tawatchai Tanee

2017-01-01

Developments of drugs or natural products from plants are possibly made,simple to use and lower cost than modern drugs.The development processes can be started with studying local wisdom and literature reviews to choose the plants which have long been used in diverse areas,such as foods,traditional medicine,fragrances and seasonings.Then those data will be associated with scientific researches,namely plant collection and identification,phytochemical screening by gas chromatography-mass spectrometry,pharmacological study/review for their functions,and finally safety and efficiency tests in human.For safety testing,in vitro cell toxicity by cell viability assessment and in vitro testing of DNA breaks by the comet assay in human peripheral blood mononuclear cells can be performed.When active chemicals and functions containing plants were chosen with safety and efficacy for human uses,then,the potential medicinal natural products will be produced.Based on these procedures,the producing cost will be cheaper and the products can be evaluated for their clinical properties.Thus,the best and lowest-priced medicines and natural products can be distributed worldwide.

21 CFR 338.50 - Labeling of nighttime sleep-aid drug products.

Science.gov (United States)

2010-04-01

... for more than 2 weeks, consult your doctor. Insomnia may be a symptom of serious underlying medical illness.” (3) “Do not take this product, unless directed by a doctor, if you have a breathing problem such....50 Section 338.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

Structure-based synthesis from natural products to drug prototypes

International Nuclear Information System (INIS)

Hanessian, S.

2009-01-01

X-Ray crystallographic data available from complexes of natural and synthetic molecules with the enzyme thrombin has aided to the design and synthesis of truncated and hybrid molecules exhibiting excellent inhibition in vitro. The vital importance of natural products for the well-being of man has been known lor millennia. Their therapeutic benefits to alleviate pain or cure diseases continue to rank natural products among the primary sources of potential drugs. Great advances have been made in the methods of isolation, identification, and structure elucidation of some of the most complex natural products in recent years. The advent of molecular biology and genetic mapping has also aided in our understanding of the intriguing biosynthetic pathways leading to various classes of therapeutically relevant antibiotic, anticancer, and related natural products. Elegant and practical methodology has been developed leading to the total synthesis of virtually every class of medicinally important natural product. In some cases, natural products or their chemically modified congeners have been manufactured by total synthesis on an industrial level which is a testament to the ingenuity of process chemists. In spite of their potent activities HI enzymatic ox receptor-mediated assays, not all natural products are amenable to being developed as marketable drags. In many instances unfavorable pharmacological effects cannot be overcome without drastic structural and functional modifications, which may also result in altered efficacy. Structure modification through truncation, functional group variations, isosteric replacements, and skeletal rigidifications aided by molecular modeling, X ray crystallography of protein targets, or NMR data are valid objectives in the context of small molecule drug discovery starting with bioactive natural products. A large proportion of these pertain to chemotherapeutic agents against cancer

21 CFR 350.50 - Labeling of antiperspirant drug products.

Science.gov (United States)

2010-04-01

...: ‘dampness,’ ‘perspiration,’ ‘sweat,’ ‘sweating,’ or ‘wetness’] due to stress”. (3) For products that... this chapter for definition of bullet. (ii) The warning required by § 369.21 of this chapter for drugs...

Fission product release from nuclear fuel II. Validation of ASTEC/ELSA on analytical and large scale experiments

International Nuclear Information System (INIS)

Brillant, G.; Marchetto, C.; Plumecocq, W.

2013-01-01

Highlights: • A wide range of experiments is presented for the ASTEC/ELSA code validation. • Analytical tests such as AECL, ORNL and VERCORS are considered. • A large-scale experiment, PHEBUS FPT1, is considered. • The good agreement with measurements shows the efficiency of the ASTEC modelling. • Improvements concern the FP release modelling from MOX and high burn-up UO 2 fuels. - Abstract: This article is the second of two articles dedicated to the mechanisms of fission product release from a degraded core. The models of fission product release from nuclear fuel in the ASTEC code have been described in detail in the first part of this work (Brillant et al., this issue). In this contribution, the validation of ELSA, the module of ASTEC that deals with fission product and structural material release from a degraded core, is presented. A large range of experimental tests, with various temperature and conditions for the fuel surrounding atmosphere (oxidising and reducing), is thus simulated with the ASTEC code. The validation database includes several analytical experiments with both bare fuel (e.g. MCE1 experiments) and cladded fuel (e.g. HCE3, VERCORS). Furthermore, the PHEBUS large-scale experiments are used for the validation of ASTEC. The rather satisfactory comparison between ELSA calculations and experimental measurements demonstrates the efficiency of the analytical models to describe fission product release in severe accident conditions

Differences in rates of switchbacks after switching from branded to authorized generic and branded to generic drug products: cohort study

Science.gov (United States)

Sarpatwari, Ameet; Dejene, Sara; Khan, Nazleen F; Lii, Joyce; Rogers, James R; Dutcher, Sarah K; Raofi, Saeid; Bohn, Justin; Connolly, John; Fischer, Michael A; Kesselheim, Aaron S; Gagne, Joshua J

2018-01-01

Abstract Objectives To compare rates of switchbacks to branded drug products for patients switched from branded to authorized generic drug products, which have the same active ingredients, appearance, and excipients as the branded product, with patients switched from branded to generic drug products, which have the same active ingredients as the branded product but may differ in appearance and excipients. Design Observational cohort study. Setting Private (a large commercial health plan) and public (Medicaid) insurance programs in the US. Participants Beneficiaries of a large US commercial health insurer between 2004 and 2013 (primary cohort) and Medicaid beneficiaries between 2000 and 2010 (replication cohort). Main outcome measures Patients taking branded products for one of the study drugs (alendronate tablets, amlodipine tablets, amlodipine-benazepril capsules, calcitonin salmon nasal spray, escitalopram tablets, glipizide extended release tablets, quinapril tablets, and sertraline tablets) were identified when they switched to an authorized generic or a generic drug product after the date of market entry of generic drug products. These patients were followed for switchbacks to the branded drug product in the year after their switch to an authorized generic or a generic drug product. Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals after adjusting for demographics, including age, sex, and calendar year. Inverse variance meta-analysis was used to pool adjusted hazard ratios across all drug products. Results A total of 94 909 patients switched from branded to authorized generic drug products and 116 017 patients switched from branded to generic drug products and contributed to the switchback analysis. Unadjusted incidence rates of switchback varied across drug products, ranging from a low of 3.8 per 100 person years (for alendronate tablets) to a high of 17.8 per 100 person years (for amlodipine

Medicinal importance, pharmacological activities, and analytical aspects of hispidulin: A concise report

Directory of Open Access Journals (Sweden)

Kanika Patel

2017-07-01

Full Text Available Herbal medicines have been played an important role in the human civilization since very ancient time as a food, cloth, medicine and other aspects. Some of the important drugs in the modern medicine were derived from the natural sources such as aspirin, digitalis, quinine, vincristine, vinblastine etc. Hispidulin (4′, 5, 7-trihydroxy-6-methoxyflavone is a flavones derivative found in plant such as Grindelia argentina, Arrabidaea chica, Saussurea involucrate, Crossostephium chinense, Artemisia and Salvia species. Hispidulin have antioxidant, antifungal, anti-inflammatory, antimutagenic, and antineoplastic properties. So far, various analytical methods have been investigated and developed for detection of hispidulin in the plant materials. Productions of hispidulin through different tissue culture techniques have been also investigated. Present review summarized medicinal uses, pharmacological activities and analytical aspects of hispidulin. From the above mentioned aspects, we can conclude that, this review will be helpful to the researcher in the field of natural product for the development of novel molecule for the treatment of different disorders.

Statin Drugs Markedly Inhibit Testosterone Production by Rat Leydig Cells In Vitro: Implications for Men

Science.gov (United States)

Statin drugs lower blood cholesterol by inhibiting hepatic 3-hydroxy-3-methylglutaryl-Coenzyme-A reductase. During drug development it was shown that statins inhibit production of cholesterol in the testis. We evaluated testosterone production in vitro, using highly purified rat ...

[Adverse muscle effects of a podofyllotoxin-containing cytotoxic drug product with simvastatin].

Science.gov (United States)

Kaipiainen-Seppänen, Oili; Savolainen, Elina; Elfving, Pia; Kononoff, Aulikki

2009-01-01

With the ageing population, drug interactions pose an increasing challenge to health professionals. We describe four patients, for whom concurrent administration of a podofyllotoxin-containing cytotoxic drug product and simvastatin caused severe adverse effects on muscles, including muscle pain, soreness or fatigue or weakness, and in some patients also disintegration of muscle tissue, i.e. rhabdomyolysis. The metabolism of both drugs proceeds via the common CYP3A4 enzyme pathway.

Development of special medical foods and botanical drugs using HemoHIM for cancer patients during radiation therapy

International Nuclear Information System (INIS)

Jo, Sung Kee; Jung, U Hee; Park, Hae Ran

2010-02-01

In vivo evaluation on the reductive effects of HemoHIM on the side-effects of radiation and anticancer drug treatment. - Evaluation on the promoting effects of HemoHIM on the tumor growth inhibitory activities of radiation and anticancer drug(cisplatin) in tumor-bearing mice. - Evaluation of the reductive effects of HemoHIM on the immune suppressive side-effects of radiation and anticancer drug(cisplatin) in tumor-bearing mice. - Evaluation of reductive effects of HemoHIM on the self-renewal tissue(intestine) damage of radiation and anticancer drug(5-FU) in mice. · Assessment of toxicological safety of HemoHIM (GLP) and establishment of analytical methods for active/index components of HemoHIM - Assurance of toxicological safety in single-dose and 3 month repeat-dose toxicity test in rats - Establishment of analytical methods for active/index compounds and content analysis result in various production lots. · Production of Special Medical Food pilot products for cancer patients and development of dosage forms for the natural new drugs. - Establishment of optimal formulations including HemoHIM for the Special Medical Food - Production of Special Medical Food pilot products for clinical test, analysis of nutrients, and official declaration of food production - Establishment of production process of HemoHIM for natural drug and production of pilot products for toxicity tests - Development of drug dosage forms of HemoHIM (tablet, granule, capsule) · Clinical evaluation of HemoHIM on reduction of side-effects of radiation and chemotherapy in cancer patients - Subjects: breast cancer patients who completed surgical operation and chemotherapy, HemoHIM administration during and after the radiation therapy (HemoHIM group: 15, placebo group 13) - Administration period: 3 months from few days before RT commencement - Results - Improvement of immunological biomarkers (immune cell subpopulations, cytokine production) - Reduction of and enhanced recovery from radiation skin

Development of special medical foods and botanical drugs using HemoHIM for cancer patients during radiation therapy

Energy Technology Data Exchange (ETDEWEB)

Jo, Sung Kee; Jung, U Hee; Park, Hae Ran

2010-02-15

In vivo evaluation on the reductive effects of HemoHIM on the side-effects of radiation and anticancer drug treatment. - Evaluation on the promoting effects of HemoHIM on the tumor growth inhibitory activities of radiation and anticancer drug(cisplatin) in tumor-bearing mice. - Evaluation of the reductive effects of HemoHIM on the immune suppressive side-effects of radiation and anticancer drug(cisplatin) in tumor-bearing mice. - Evaluation of reductive effects of HemoHIM on the self-renewal tissue(intestine) damage of radiation and anticancer drug(5-FU) in mice. {center_dot} Assessment of toxicological safety of HemoHIM (GLP) and establishment of analytical methods for active/index components of HemoHIM - Assurance of toxicological safety in single-dose and 3 month repeat-dose toxicity test in rats - Establishment of analytical methods for active/index compounds and content analysis result in various production lots. {center_dot} Production of Special Medical Food pilot products for cancer patients and development of dosage forms for the natural new drugs. - Establishment of optimal formulations including HemoHIM for the Special Medical Food - Production of Special Medical Food pilot products for clinical test, analysis of nutrients, and official declaration of food production - Establishment of production process of HemoHIM for natural drug and production of pilot products for toxicity tests - Development of drug dosage forms of HemoHIM (tablet, granule, capsule) {center_dot} Clinical evaluation of HemoHIM on reduction of side-effects of radiation and chemotherapy in cancer patients - Subjects: breast cancer patients who completed surgical operation and chemotherapy, HemoHIM administration during and after the radiation therapy (HemoHIM group: 15, placebo group 13) - Administration period: 3 months from few days before RT commencement - Results - Improvement of immunological biomarkers (immune cell subpopulations, cytokine production) - Reduction of and enhanced

The Role of Natural Products in Drug Discovery and Development against Neglected Tropical Diseases

Directory of Open Access Journals (Sweden)

Peter Mubanga Cheuka

2016-12-01

Full Text Available Endemic in 149 tropical and subtropical countries, neglected tropical diseases (NTDs affect more than 1 billion people annually, including 875 million children in developing economies. These diseases are also responsible for over 500,000 deaths per year and are characterized by long-term disability and severe pain. The impact of the combined NTDs closely rivals that of malaria and tuberculosis. Current treatment options are associated with various limitations including widespread drug resistance, severe adverse effects, lengthy treatment duration, unfavorable toxicity profiles, and complicated drug administration procedures. Natural products have been a valuable source of drug regimens that form the cornerstone of modern pharmaceutical care. In this review, we highlight the potential that remains untapped in natural products as drug leads for NTDs. We cover natural products from plant, marine, and microbial sources including natural-product-inspired semi-synthetic derivatives which have been evaluated against the various causative agents of NTDs. Our coverage is limited to four major NTDs which include human African trypanosomiasis (sleeping sickness, leishmaniasis, schistosomiasis and lymphatic filariasis.

Production of drug-loaded polymeric nanoparticles by electrospraying technology.

Science.gov (United States)

Sosnik, Alejandro

2014-09-01

The pharmaceutical industry struggles with high attrition. The outbreak of pharmaceutical micro/nanotechnology has been fundamental to overcome several (bio)pharmaceutic drawbacks of drugs such as poor aqueous solubility, physicochemical instability, short half life, inappropriate biodistribution and toxicity. The spatiotemporal release of drugs directly in the site of action and the restriction of the systemic exposure by means of nanotechnology has notoriously improved drug safety ratios. At the same time, the development of production methods that are cost-effective, scalable and reproducible under industrial settings becomes crucial to ensure the clinical translation of any development. The electrospraying process, also known as electrohydrodynamic atomization (EHDA), is a single-stage technique of liquid atomization by means of electrical forces that enables the generation of micro/nanoparticles with especially narrow size distribution. EHDA is based on the ability of an electric field to deform the interface of a liquid drop and break it into smaller mono-disperse droplets. The main advantageous features over conventional methods are the possibility to produce particles without the use of surfactants, at ambient temperature and pressure and with maximum encapsulation efficiency due to the absence of an external medium that allows the migration and/or dissolution of water-soluble cargos. In addition, the mild conditions are optimal for the encapsulation of thermo-sensitive cargos. The present article overviews the applications of this technology for the production of nano-drug delivery systems and discusses its key role to support the transfer of a broad spectrum of nanomedicines to the market.

76 FR 3144 - Draft Guidance for Industry on Size of Beads in Drug Products Labeled for Sprinkle; Availability

Science.gov (United States)

2011-01-19

...] Draft Guidance for Industry on Size of Beads in Drug Products Labeled for Sprinkle; Availability AGENCY... announcing the availability of a draft guidance for industry entitled ``Size of Beads in Drug Products... Evaluation and Research's (CDER's) current thinking on appropriate size ranges for beads in drug products...

Extractables characterization for five materials of construction representative of packaging systems used for parenteral and ophthalmic drug products.

Science.gov (United States)

Jenke, Dennis; Castner, James; Egert, Thomas; Feinberg, Tom; Hendricker, Alan; Houston, Christopher; Hunt, Desmond G; Lynch, Michael; Shaw, Arthur; Nicholas, Kumudini; Norwood, Daniel L; Paskiet, Diane; Ruberto, Michael; Smith, Edward J; Holcomb, Frank

2013-01-01

Polymeric and elastomeric materials are commonly encountered in medical devices and packaging systems used to manufacture, store, deliver, and/or administer drug products. Characterizing extractables from such materials is a necessary step in establishing their suitability for use in these applications. In this study, five individual materials representative of polymers and elastomers commonly used in packaging systems and devices were extracted under conditions and with solvents that are relevant to parenteral and ophthalmic drug products (PODPs). Extraction methods included elevated temperature sealed vessel extraction, sonication, refluxing, and Soxhlet extraction. Extraction solvents included a low-pH (pH = 2.5) salt mixture, a high-pH (pH = 9.5) phosphate buffer, a 1/1 isopropanol/water mixture, isopropanol, and hexane. The resulting extracts were chemically characterized via spectroscopic and chromatographic means to establish the metal/trace element and organic extractables profiles. Additionally, the test articles themselves were tested for volatile organic substances. The results of this testing established the extractables profiles of the test articles, which are reported herein. Trends in the extractables, and their estimated concentrations, as a function of the extraction and testing methodologies are considered in the context of the use of the test article in medical applications and with respect to establishing best demonstrated practices for extractables profiling of materials used in PODP-related packaging systems and devices. Plastic and rubber materials are commonly encountered in medical devices and packaging/delivery systems for drug products. Characterizing the extractables from these materials is an important part of determining that they are suitable for use. In this study, five materials representative of plastics and rubbers used in packaging and medical devices were extracted by several means, and the extracts were analytically

Net analyte signal based statistical quality control

NARCIS (Netherlands)

Skibsted, E.T.S.; Boelens, H.F.M.; Westerhuis, J.A.; Smilde, A.K.; Broad, N.W.; Rees, D.R.; Witte, D.T.

2005-01-01

Net analyte signal statistical quality control (NAS-SQC) is a new methodology to perform multivariate product quality monitoring based on the net analyte signal approach. The main advantage of NAS-SQC is that the systematic variation in the product due to the analyte (or property) of interest is

Cytotoxic Drugs Departments as a precondition for high-quality product

Directory of Open Access Journals (Sweden)

Katarzyna Głuszek

2014-06-01

Full Text Available Cancer control is a tremendous challenge not only for the ill patient and physicians, but also for the whole health care system. For the first time, during the European Conference of Oncology Pharmacists, the highest standards of pharmaceutical care were proposed for cancer patients. Undoubtedly, the lifestyle and prophylaxis which would enable the detection of cancer at an early stage exert an effect on the development of the disease. Cytostatics show toxic, mutagenic, oncogenic and immunosuppressive effects; therefore, their preparation should be handled by the Central Cytotoxic Drugs Department, because the majority of the drugs prepared belong to Register A. Drugs are manufactured in accordance with GMP principles. All-Polish Standards adopted by the Polish Pharmaceutical Association delineate the direction to be developed by every hospital with respect to its own procedures and instructions. The Master of Pharmacy is responsible for the preparation of cytotoxic drugs. At one bench should work an operator and an assistant. The recommended working time should not exceed 2 h without break, and 5 h daily. The person who collects cytotoxic drugs from the Central Department should use a legible sign and a stamp including the hour and date of collection. While manufacturing cytostatics for patients in daily doses it is recommended to use concentrates in the form of solutions rather than lyophilised powders, which results in the shortening of the stage of production of the drug and reduces the possibility of forming aerosols; in the case of closed infusion systems (containers for infusion liquids which are used for the production of daily doses, the cabinet should be equipped in two tight docks for dispensing. Needleless connection of the LUER-LOCK type – a recommendation of the ISOPP – guarantees a tight connection with the drug transfer port even in the case of an increase in pressure during the manufacture of drugs. To a certain extent

A new roadmap for biopharmaceutical drug product development: Integrating development, validation, and quality by design.

Science.gov (United States)

Martin-Moe, Sheryl; Lim, Fredric J; Wong, Rita L; Sreedhara, Alavattam; Sundaram, Jagannathan; Sane, Samir U

2011-08-01

Quality by design (QbD) is a science- and risk-based approach to drug product development. Although pharmaceutical companies have historically used many of the same principles during development, this knowledge was not always formally captured or proactively submitted to regulators. In recent years, the US Food and Drug Administration has also recognized the need for more controls in the drug manufacturing processes, especially for biological therapeutics, and it has recently launched an initiative for Pharmaceutical Quality for the 21st Century to modernize pharmaceutical manufacturing and improve product quality. In the biopharmaceutical world, the QbD efforts have been mainly focused on active pharmaceutical ingredient processes with little emphasis on drug product development. We present a systematic approach to biopharmaceutical drug product development using a monoclonal antibody as an example. The approach presented herein leverages scientific understanding of products and processes, risk assessments, and rational experimental design to deliver processes that are consistent with QbD philosophy without excessive incremental effort. Data generated using these approaches will not only strengthen data packages to support specifications and manufacturing ranges but hopefully simplify implementation of postapproval changes. We anticipate that this approach will positively impact cost for companies, regulatory agencies, and patients, alike. Copyright © 2011 Wiley-Liss, Inc.

Thermodynamic and analytical studies of drugs binary systems of paracetamol mixed with pseudoephedrine.HCl, dextropropoxyphene.HCl and tramadol.HCl

International Nuclear Information System (INIS)

Boumrah, Yacine; Bouzahia, Imane; Bouanani, Sabrina; Khimeche, Kamel; Dahmani, Abdallah

2016-01-01

Highlights: • Solid–liquid equilibria of binary drug mixtures were investigated by DSC. • The study revealed a simple eutectic behavior of the investigated drug binary systems. • DSC results have been exploited for quantification purpose. • DSC quantification results were in good agreement with those obtained by HPTLC. - Abstract: In this paper, we report a DSC investigation of solid–liquid equilibria in three binary mixtures of paracetamol, namely with pseudoephedrine, dextropropoxyphene and tramadol, resulting in a temperature-composition phase diagrams with eutectic equilibrium. Eutectic mole fractions, temperatures and enthalpies were determined and reported for each system. The study reports also a direct exploitation of the DSC results for the quantification purpose, which were in good agreement with those obtained by a standard analytical method namely high performance thin layer chromatography (HPTLC), used in this work for comparison purpose.

Thermodynamic and analytical studies of drugs binary systems of paracetamol mixed with pseudoephedrine.HCl, dextropropoxyphene.HCl and tramadol.HCl

Energy Technology Data Exchange (ETDEWEB)

Boumrah, Yacine [Laboratoire de thermodynamique et modélisation moléculaire, Faculté de chimie, USTHB, BP 32 El-Alia, 16111, Bab-Ezzouar, Alger (Algeria); Institut National de Criminalistique et de Criminologie (INCC-GN), Bouchaoui, Alger (Algeria); Bouzahia, Imane; Bouanani, Sabrina [Institut National de Criminalistique et de Criminologie (INCC-GN), Bouchaoui, Alger (Algeria); Khimeche, Kamel [Ecole Militaire Polytechnique EMP, BP 17 Bordj-El-Bahri, Alger (Algeria); Dahmani, Abdallah, E-mail: adahmani@yahoo.fr [Laboratoire de thermodynamique et modélisation moléculaire, Faculté de chimie, USTHB, BP 32 El-Alia, 16111, Bab-Ezzouar, Alger (Algeria)

2016-06-20

Highlights: • Solid–liquid equilibria of binary drug mixtures were investigated by DSC. • The study revealed a simple eutectic behavior of the investigated drug binary systems. • DSC results have been exploited for quantification purpose. • DSC quantification results were in good agreement with those obtained by HPTLC. - Abstract: In this paper, we report a DSC investigation of solid–liquid equilibria in three binary mixtures of paracetamol, namely with pseudoephedrine, dextropropoxyphene and tramadol, resulting in a temperature-composition phase diagrams with eutectic equilibrium. Eutectic mole fractions, temperatures and enthalpies were determined and reported for each system. The study reports also a direct exploitation of the DSC results for the quantification purpose, which were in good agreement with those obtained by a standard analytical method namely high performance thin layer chromatography (HPTLC), used in this work for comparison purpose.

Prioritizing the barriers to achieve sustainable consumption and production trends in supply chains using fuzzy Analytical Hierarchy Process

DEFF Research Database (Denmark)

Mangla, Sachin Kumar; Govindan, Kannan; Luthra, Sunil

2017-01-01

Currently, production systems and consumption patterns are based on conventional courses of action and utilize methods and technologies that are generally not sustainable. As a result, Sustainable Consumption and Production (SCP) is becoming an important means by which business organizations...... and production trends in a supply chain context. In this work, firstly, 30 barriers related to implementing SCP trends in supply chain are recognized. These barriers are derived from a literature survey and from field and industrial experts' inputs. Secondly, an operational model is suggested using the fuzzy...... Analytical Hierarchy Process to prioritize the identified barriers with the goal of improving overall performance. The fuzzy Analytical Hierarchy Process helps determine the priority of concerns of the identified barriers under fuzzy surroundings. Inputs in this work are based upon an ancillary auto...

A dataset of 200 structured product labels annotated for adverse drug reactions.

Science.gov (United States)

Demner-Fushman, Dina; Shooshan, Sonya E; Rodriguez, Laritza; Aronson, Alan R; Lang, Francois; Rogers, Willie; Roberts, Kirk; Tonning, Joseph

2018-01-30

Adverse drug reactions (ADRs), unintended and sometimes dangerous effects that a drug may have, are one of the leading causes of morbidity and mortality during medical care. To date, there is no structured machine-readable authoritative source of known ADRs. The United States Food and Drug Administration (FDA) partnered with the National Library of Medicine to create a pilot dataset containing standardised information about known adverse reactions for 200 FDA-approved drugs. The Structured Product Labels (SPLs), the documents FDA uses to exchange information about drugs and other products, were manually annotated for adverse reactions at the mention level to facilitate development and evaluation of text mining tools for extraction of ADRs from all SPLs. The ADRs were then normalised to the Unified Medical Language System (UMLS) and to the Medical Dictionary for Regulatory Activities (MedDRA). We present the curation process and the structure of the publicly available database SPL-ADR-200db containing 5,098 distinct ADRs. The database is available at https://bionlp.nlm.nih.gov/tac2017adversereactions/; the code for preparing and validating the data is available at https://github.com/lhncbc/fda-ars.

Analytical and functional similarity of Amgen biosimilar ABP 215 to bevacizumab.

Science.gov (United States)

Seo, Neungseon; Polozova, Alla; Zhang, Mingxuan; Yates, Zachary; Cao, Shawn; Li, Huimin; Kuhns, Scott; Maher, Gwendolyn; McBride, Helen J; Liu, Jennifer

ABP 215 is a biosimilar product to bevacizumab. Bevacizumab acts by binding to vascular endothelial growth factor A, inhibiting endothelial cell proliferation and new blood vessel formation, thereby leading to tumor vasculature normalization. The ABP 215 analytical similarity assessment was designed to assess the structural and functional similarity of ABP 215 and bevacizumab sourced from both the United States (US) and the European Union (EU). Similarity assessment was also made between the US- and EU-sourced bevacizumab to assess the similarity between the two products. The physicochemical properties and structural similarity of ABP 215 and bevacizumab were characterized using sensitive state-of-the-art analytical techniques capable of detecting small differences in product attributes. ABP 215 has the same amino acid sequence and exhibits similar post-translational modification profiles compared to bevacizumab. The functional similarity assessment employed orthogonal assays designed to interrogate all expected biological activities, including those known to affect the mechanisms of action for ABP 215 and bevacizumab. More than 20 batches of bevacizumab (US) and bevacizumab (EU), and 13 batches of ABP 215 representing unique drug substance lots were assessed for similarity. The large dataset allows meaningful comparisons and garners confidence in the overall conclusion for the analytical similarity assessment of ABP 215 to both US- and EU-sourced bevacizumab. The structural and purity attributes, and biological properties of ABP 215 are demonstrated to be highly similar to those of bevacizumab.

Photostability studies on the furosemide-triamterene drug association.

Science.gov (United States)

Fiori, J; Ballardini, R; Andrisano, V; Cavrini, V

2003-09-01

The photostability of the diuretic drugs triamterene and furosemide, individually and combined, was evaluated. Spectrophotometric, spectrofluorimetric and chromatographic (HPLC) methods were applied to monitor the drug photodegradation. Furosemide was confirmed to be highly photolable in both pH 7.4 solution and methanol. Differently triamterene proved to be highly fluorescent (emission quantum yield: 0.9 in methanol and 0.8 in pH 7.4 solution), but essentially photostable (photochemical reaction quantum yield: congruent with 5 x 10(-4)) under exposure at 365 and 313 nm radiations. When the combined drugs in pH 7.4 solutions were exposed to 365 nm radiations a significant photoprotective effect of triamterene on furosemide was observed. The photoreactivity of the drugs was exploited to develop an HPLC method involving a post-column on-line photochemical derivatization useful to confirm the analyte identity in a commercial dosage form (tablets). The commercial product, containing the combined drugs, proved to be photostable also after long (65 h) light exposure.

Recent advances in analytical determination of cisplatin and its hydrolysis products

International Nuclear Information System (INIS)

Ramos Rodriguez, Yalexmiy; Hernandez Castro, Carlos

2009-01-01

Cisplatin (cis-diaminedichloroplatinum [II] is a coordination compound, used in the treatment of several solid tumors. Cisplatin and its hydrolysis products exhibit a great pharmacological effect but are very toxic and probably carcinogenic. The present review summarizes the most important advances in the last years in the techniques employed for the detection and quantification of cisplatin and its hydrolysis products and in the different matrixes studied. The new emerging techniques and their modifications recently developed, fundamentally the combined use of detection and separation techniques for the analysis of platinum species and their impact on the speed, sensitivity and specificity of the analytical determination, with regard to the techniques used in the last century are discussed. High-Performance Liquid Chromatography and Capillary Electrophoresis, coupled with detection methods such as Mass Spectrometry, Inductively Coupled Plasma-Mass Spectrometry, Atomic Absorption Spectrometry and more recently, High-Field Asymmetric Waveform Ion Mobility Spectrometry are the methods more employed. The analysis of cisplatin and its hydrolysis products in new and more complex matrixes is also presented

21 CFR 358.750 - Labeling of drug products for the control of dandruff, seborrheic dermatitis, or psoriasis.

Science.gov (United States)

2010-04-01

... dandruff, seborrheic dermatitis, or psoriasis. 358.750 Section 358.750 Food and Drugs FOOD AND DRUG... Dermatitis, and Psoriasis § 358.750 Labeling of drug products for the control of dandruff, seborrheic dermatitis, or psoriasis. (a) Statement of identity. The labeling of the product contains the established...

21 CFR 310.548 - Drug products containing colloidal silver ingredients or silver salts offered over-the-counter...

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Drug products containing colloidal silver... Drug products containing colloidal silver ingredients or silver salts offered over-the-counter (OTC) for the treatment and/or prevention of disease. (a) Colloidal silver ingredients and silver salts have...

Accelerated approval of oncology products: the food and drug administration experience.

Science.gov (United States)

Johnson, John R; Ning, Yang-Min; Farrell, Ann; Justice, Robert; Keegan, Patricia; Pazdur, Richard

2011-04-20

We reviewed the regulatory history of the accelerated approval process and the US Food and Drug Administration (FDA) experience with accelerated approval of oncology products from its initiation in December 11, 1992, to July 1, 2010. The accelerated approval regulations allowed accelerated approval of products to treat serious or life-threatening diseases based on surrogate endpoints that are reasonably likely to predict clinical benefit. Failure to complete postapproval trials to confirm clinical benefit with due diligence could result in removal of the accelerated approval indication from the market. From December 11, 1992, to July 1, 2010, the FDA granted accelerated approval to 35 oncology products for 47 new indications. Clinical benefit was confirmed in postapproval trials for 26 of the 47 new indications, resulting in conversion to regular approval. The median time between accelerated approval and regular approval of oncology products was 3.9 years (range = 0.8-12.6 years) and the mean time was 4.7 years, representing a substantial time savings in terms of earlier availability of drugs to cancer patients. Three new indications did not show clinical benefit when confirmatory postapproval trials were completed and were subsequently removed from the market or had restricted distribution plans implemented. Confirmatory trials were not completed for 14 new indications. The five longest intervals from receipt of accelerated approval to July 1, 2010, without completion of trials to confirm clinical benefit were 10.5, 6.4, 5.5, 5.5, and 4.7 years. The five longest intervals between accelerated approval and successful conversion to regular approval were 12.6, 9.7, 8.1, 7.5, and 7.4 years. Trials to confirm clinical benefit should be part of the drug development plan and should be in progress at the time of an application seeking accelerated approval to prevent an ineffective drug from remaining on the market for an unacceptable time.

A three-dimensional semi-analytical solution for predicting drug release through the orifice of a spherical device.

Science.gov (United States)

Simon, Laurent; Ospina, Juan

2016-07-25

Three-dimensional solute transport was investigated for a spherical device with a release hole. The governing equation was derived using the Fick's second law. A mixed Neumann-Dirichlet condition was imposed at the boundary to represent diffusion through a small region on the surface of the device. The cumulative percentage of drug released was calculated in the Laplace domain and represented by the first term of an infinite series of Legendre and modified Bessel functions of the first kind. Application of the Zakian algorithm yielded the time-domain closed-form expression. The first-order solution closely matched a numerical solution generated by Mathematica(®). The proposed method allowed computation of the characteristic time. A larger surface pore resulted in a smaller effective time constant. The agreement between the numerical solution and the semi-analytical method improved noticeably as the size of the orifice increased. It took four time constants for the device to release approximately ninety-eight of its drug content. Copyright © 2016 Elsevier B.V. All rights reserved.

Global (and Local) Analyticity for Second Order Operators Constructed from Rigid Vector Fields on Products of Tori

OpenAIRE

Tartakoff, David S.

1994-01-01

We prove global analytic hypoellipticity on a product of tori for partial differential operators which are constructed as rigid (variable coefficient) quadratic polynomials in real vector fields satisfying the H\\"ormander condition and where $P$ satisfies a `maximal' estimate. We also prove an analyticity result that is local in some variables and global in others for operators whose prototype is $$ P= \\left({\\partial \\over {\\partial x_1}}\\right)^2 + \\left({\\partial \\over {\\partial x_2}}\\righ...

Analytic mappings: a new approach in particle production by accelerated observers

International Nuclear Information System (INIS)

Sanchez, N.

1982-01-01

This is a summary of the authors recent results about physical consequences of analytic mappings in the space-time. Classically, the mapping defines an accelerated frame. At the quantum level it gives rise to particle production. Statistically, the real singularities of the mapping have associated temperatures. This concerns a new approach in Q.F.T. as formulated in accelerated frames. It has been considered as a first step in the understanding of the deep connection that could exist between the structure (geometry and topology) of the space-time and thermodynamics, mainly motivated by the works of Hawking since 1975. (Auth.)

21 CFR 310.528 - Drug products containing active ingredients offered over-the-counter (OTC) for use as an...

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Drug products containing active ingredients offered over-the-counter (OTC) for use as an aphrodisiac. 310.528 Section 310.528 Food and Drugs FOOD AND... drug product. Anise, cantharides, don qual, estrogens, fennel, ginseng, golden seal, gotu kola, Korean...

Analytical aspects of the remediation of soil by wet oxidation - Characterisation of tar contaminants and their degradation products

DEFF Research Database (Denmark)

Thomsen, A.B.; Nielsen, T.; Plöger, A.

1999-01-01

Wet oxidation of tar compounds gives rise to a wide range of products. Due to the incorporation of oxygen, these products become increasingly more water soluble and the analytical strategy has to take into account the different physical/chemicalproperties of the compounds. An interplay between ga...

Progressive anticonvulsant hypersensitivity syndrome associated with change of drug product

DEFF Research Database (Denmark)

Sabroe, T.P.; Sabers, A.

2008-01-01

This report describes the laboratory and physical manifestations of lamotrigine-like toxicity in a young man with refractory epilepsy receiving lamotrigine presenting as anticonvulsant hypersensitivity syndrome (AHS) associated with an abrupt change of drug product Udgivelsesdato: 2008/6...

21 CFR 212.70 - What controls and acceptance criteria must I have for my finished PET drug products?

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 4 2010-04-01 2010-04-01 false What controls and acceptance criteria must I have... POSITRON EMISSION TOMOGRAPHY DRUGS (Eff. 12-12-2011) Finished Drug Product Controls and Acceptance § 212.70 What controls and acceptance criteria must I have for my finished PET drug products? (a) Specifications...

Analytical method development and validation of spectrofluorimetric and spectrophotometric determination of some antimicrobial drugs in their pharmaceuticals

Science.gov (United States)

Ibrahim, F.; Wahba, M. E. K.; Magdy, G.

2018-01-01

In this study, three novel, sensitive, simple and validated spectrophotometric and spectrofluorimetric methods have been proposed for estimation of some important antimicrobial drugs. The first two methods have been proposed for estimation of two important third-generation cephalosporin antibiotics namely, cefixime and cefdinir. Both methods were based on condensation of the primary amino group of the studied drugs with acetyl acetone and formaldehyde in acidic medium. The resulting products were measured by spectrophotometric (Method I) and spectrofluorimetric (Method II) tools. Regarding method I, the absorbance was measured at 315 nm and 403 nm with linearity ranges of 5.0-140.0 and 10.0-100.0 μg/mL for cefixime and cefdinir, respectively. Meanwhile in method II, the produced fluorophore was measured at λem 488 nm or 491 nm after excitation at λex 410 nm with linearity ranges of 0.20-10.0 and 0.20-36.0 μg/mL for cefixime and cefdinir, respectively. On the other hand, method III was devoted to estimate nifuroxazide spectrofluorimetrically depending on formation of highly fluorescent product upon reduction of the studied drug with Zinc powder in acidic medium. Measurement of the fluorescent product was carried out at λem 335 nm following excitation at λex 255 nm with linearity range of 0.05 to 1.6 μg/mL. The developed methods were subjected to detailed validation procedure, moreover they were used for the estimation of the concerned drugs in their pharmaceuticals. It was found that there is a good agreement between the obtained results and those obtained by the reported methods.

Worldwide withdrawal of medicinal products because of adverse drug reactions: a systematic review and analysis.

Science.gov (United States)

Onakpoya, Igho J; Heneghan, Carl J; Aronson, Jeffrey K

2016-07-01

We have systematically identified medicinal products withdrawn worldwide because of adverse drug reactions, assessed the level of evidence used for making the withdrawal decisions, and explored the patterns of withdrawals over time. We searched PubMed, the WHO database of withdrawn products, and selected texts. We included products that were withdrawn after launch from 1950 onwards, excluding non-human and over-the-counter medicines. We assessed the levels of evidence on which withdrawals were based using the Oxford Center for Evidence Based Medicine Levels of Evidence. Of 353 medicinal products withdrawn from any country, only 40 were withdrawn worldwide. Anecdotal reports were cited as evidence for withdrawal in 30 (75%) and deaths occurred in 27 (68%). Hepatic, cardiac, and nervous system toxicity accounted for over 60% of withdrawals. In 28 cases, the first withdrawal was initiated by the manufacturer. The median interval between the first report of an adverse drug reaction that led to withdrawal and the first withdrawal was 1 year (range 0-43 years). Worldwide withdrawals occurred within 1 year after the first withdrawal in any country. In conclusion, the time it takes for drugs to be withdrawn worldwide after reports of adverse drug reactions has shortened over time. However, there are inconsistencies in current withdrawal procedures when adverse drug reactions are suspected. A uniform method for establishing worldwide withdrawal of approved medicinal products when adverse drug reactions are suspected should be developed, to facilitate global withdrawals. Rapid synthesis of the evidence on harms should be a priority when serious adverse reactions are suspected.

Hybrid combinations containing natural products and antimicrobial drugs that interfere with bacterial and fungal biofilms.

Science.gov (United States)

Zacchino, Susana A; Butassi, Estefanía; Cordisco, Estefanía; Svetaz, Laura A

2017-12-15

Biofilms contribute to the pathogenesis of many chronic and difficult-to eradicate infections whose treatment is complicated due to the intrinsic resistance to conventional antibiotics. As a consequence, there is an urgent need for strategies that can be used for the prevention and treatment of biofilm-associated infections. The combination therapy comprising an antimicrobial drug with a low molecular weight (MW) natural product and an antimicrobial drug (antifungal or antibacterial) appeared as a good alternative to eradicate biofilms. The aims of this review were to perform a literature search on the different natural products that have showed the ability of potentiating the antibiofilm capacity of antimicrobial drugs, to analyze which are the antimicrobial drugs most used in combination, and to have a look on the microbial species most used to prepare biofilms. Seventeen papers, nine on combinations against antifungal biofilms and eight against antibacterial biofilms were collected. Within the text, the following topics have been developed: breaf history of the discovery of biofilms; stages in the development of a biofilm; the most used methodologies to assess antibiofilm-activity; the natural products with capacity of eradicating biofilms when acting alone; the combinations of low MW natural products with antibiotics or antifungal drugs as a strategy for eradicating microbial biofilms and a list of the low MW natural products that potentiate the inhibition capacity of antifungal and antibacterial drugs against biofilms. Regarding combinations against antifungal biofilms, eight over the nine collected works were carried out with in vitro studies while only one was performed with in vivo assays by using Caenorhabditis elegans nematode. All studies use biofilms of the Candida genus. A 67% of the potentiators were monoterpenes and sesquiterpenes and six over the nine works used FCZ as the antifungal drug. The activity of AmpB and Caspo was enhanced in one and two

A comparison of average wages with age-specific wages for assessing indirect productivity losses: analytic simplicity versus analytic precision.

Science.gov (United States)

Connolly, Mark P; Tashjian, Cole; Kotsopoulos, Nikolaos; Bhatt, Aomesh; Postma, Maarten J

2017-07-01

Numerous approaches are used to estimate indirect productivity losses using various wage estimates applied to poor health in working aged adults. Considering the different wage estimation approaches observed in the published literature, we sought to assess variation in productivity loss estimates when using average wages compared with age-specific wages. Published estimates for average and age-specific wages for combined male/female wages were obtained from the UK Office of National Statistics. A polynomial interpolation was used to convert 5-year age-banded wage data into annual age-specific wages estimates. To compare indirect cost estimates, average wages and age-specific wages were used to project productivity losses at various stages of life based on the human capital approach. Discount rates of 0, 3, and 6 % were applied to projected age-specific and average wage losses. Using average wages was found to overestimate lifetime wages in conditions afflicting those aged 1-27 and 57-67, while underestimating lifetime wages in those aged 27-57. The difference was most significant for children where average wage overestimated wages by 15 % and for 40-year-olds where it underestimated wages by 14 %. Large differences in projecting productivity losses exist when using the average wage applied over a lifetime. Specifically, use of average wages overestimates productivity losses between 8 and 15 % for childhood illnesses. Furthermore, during prime working years, use of average wages will underestimate productivity losses by 14 %. We suggest that to achieve more precise estimates of productivity losses, age-specific wages should become the standard analytic approach.

21 CFR 212.110 - How must I maintain records of my production of PET drugs?

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 4 2010-04-01 2010-04-01 false How must I maintain records of my production of PET drugs? 212.110 Section 212.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... those not stored at the inspected establishment, must be legible, stored to prevent deterioration or...

Practical guidelines for the characterization and quality control of pure drug nanoparticles and nano-cocrystals in the pharmaceutical industry.

Science.gov (United States)

Peltonen, Leena

2018-06-16

The number of poorly soluble drug candidates is increasing, and this is also seen in the research interest towards drug nanoparticles and (nano-)cocrystals; improved solubility is the most important application of these nanosystems. In order to confirm the functionality of these nanoparticles throughout their lifecycle, repeatability of the formulation processes, functional performance of the formed systems in pre-determined way and system stability, a thorough physicochemical understanding with the aid of necessary analytical techniques is needed. Even very minor deviations in for example particle size or size deviation in nanoscale can alter the product bioavailability, and the effect is even more dramatic with the smallest particle size fractions. Also, small particle size sets special requirements for the analytical techniques. In this review most important physicochemical properties of drug nanocrystals and nano-cocrystals are presented, suitable analytical techniques, their pros and cons, are described with the extra input on practical point of view. Copyright © 2018. Published by Elsevier B.V.

Determination and ranking cleaner production criteria by using analytic hierarchy process (Case study: Latif paper products company

Directory of Open Access Journals (Sweden)

Yaghob Asadizadeh

2018-02-01

Full Text Available Cleaner production process is an environmentally friendly approach that attempts to reduce waste and energy consumption then reduce environmental pollutions of industrial processes to provide the possibility of sustainable production in industrial units. To achieve this goal and alignment with cleaner production strategies, paper industries should consider reducing wastes of production processes and irregular consumption of energy as a priority in their programs. In this research Analytic Hierarchy Process has been applied and a three level hierarchy model was structured to facilitate the cleaner production process in Latif paper products firm. Using a literature review and field study, the proposed model provided a framework for cleaner production implementation in the firm. Results showed priorities of the main criteria of cleaner production are process change, product modification, implementation of preventive maintenance system, resititution and man force capitals respectively. Process change criterion allocated 40 percent of the total weighing value and has the highest priority in implementation of cleaner production strategy. Existence of industrial automation and its technology level which is a sub criterion of process change has the highest priority among 31 sub criteria. Also some of higher priority sub criteria such as use of higher quality inclusion and implementation of calibration system are related to process change. Therefore, to achieve cleaner production goals and implementation of its strategic objectives it is necessary to pay more attention to this criterion. Inconsistency ratio of the research is 0.06 which indicates the results are compatible. The results of this research can be used to accelerate the implementation of cleaner production process in Iran’s pulp and paper industry.

"Product on Stopper" in a Lyophilized Drug Product: Cosmetic Defect or a Product Quality Concern?

Science.gov (United States)

Mehta, Shyam B; Roy, Shouvik; Yang, Han-Chang Cathy

2018-06-01

During manufacturing of a lyophilized drug product, operator errors in product handling during loading of product filled vials onto the lyophilizer can lead to a seemingly cosmetic defect which can impact certain critical quality attributes of finished product. In this study, filling of a formulated monoclonal antibody in vials was performed using a peristaltic pump filling unit, and subsequently, the product was lyophilized. After lyophilization, upon visual inspection, around 40% of vials had cosmetic defect with residual product around stopper of the vial and were categorized as "product on stopper" vials, whereas remaining 60% vials with no cosmetic defect were called "acceptable vials." Both groups of vials from 1 single batch were tested for critical quality attributes including protein concentration (ultraviolet absorbance at 280), residual moisture (Karl Fischer), sterility (membrane filtration), and container closure integrity (CCI) (blue dye ingress). Analysis of protein quality attributes such as aggregation, protein concentration, residual moisture showed no significant difference between vials with "product on stopper" and "acceptable vials." However, CCI of the "product on stopper" vials was compromised due to the presence of product around stopper of the vial. The results from this case study demonstrate the following 2 important findings: (1) that a seemingly cosmetic defect may impact product quality, compromising the integrity of the product and (2) that CCI test method can be used as an orthogonal method to sterility testing to evaluate sterility assurance of the product. The corrective action proposed to mitigate this defect is use of a larger sized vial that can potentially minimize this defect that arises because of product handling errors. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Nature is the best source of anticancer drugs: Indexing natural products for their anticancer bioactivity.

Science.gov (United States)

Rayan, Anwar; Raiyn, Jamal; Falah, Mizied

2017-01-01

Cancer is considered one of the primary diseases that cause morbidity and mortality in millions of people worldwide and due to its prevalence, there is undoubtedly an unmet need to discover novel anticancer drugs. However, the traditional process of drug discovery and development is lengthy and expensive, so the application of in silico techniques and optimization algorithms in drug discovery projects can provide a solution, saving time and costs. A set of 617 approved anticancer drugs, constituting the active domain, and a set of 2,892 natural products, constituting the inactive domain, were employed to build predictive models and to index natural products for their anticancer bioactivity. Using the iterative stochastic elimination optimization technique, we obtained a highly discriminative and robust model, with an area under the curve of 0.95. Twelve natural products that scored highly as potential anticancer drug candidates are disclosed. Searching the scientific literature revealed that few of those molecules (Neoechinulin, Colchicine, and Piperolactam) have already been experimentally screened for their anticancer activity and found active. The other phytochemicals await evaluation for their anticancerous activity in wet lab.

78 FR 32667 - Draft Guidance for Industry on Rheumatoid Arthritis: Developing Drug Products for Treatment...

Science.gov (United States)

2013-05-31

... products. This guidance revises the guidance for industry entitled ``Clinical Development Programs for... Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave... (HFM-40), Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville...

21 CFR 212.80 - What are the requirements associated with labeling and packaging PET drug products?

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 4 2010-04-01 2010-04-01 false What are the requirements associated with labeling and packaging PET drug products? 212.80 Section 212.80 Food and Drugs FOOD AND DRUG ADMINISTRATION... POSITRON EMISSION TOMOGRAPHY DRUGS (Eff. 12-12-2011) Packaging and Labeling § 212.80 What are the...

Juvenile Animal Testing: Assessing Need and Use in the Drug Product Label.

Science.gov (United States)

Baldrick, Paul

2018-01-01

Juvenile animal testing has become an established part of drug development to support safe clinical use in the human pediatric population and for eventual drug product label use. A review of European Paediatric Investigation Plan decisions showed that from 2007 to mid-2017, 229 drugs had juvenile animal work requested, almost exclusively incorporating general toxicology study designs, in rat (57.5%), dog (8%), mouse (4.5%), monkey (4%), pig (2%), sheep (1%), rabbit (1%), hamster (0.5%), and species not specified (21.5%). A range of therapeutic areas were found, but the most common areas were infectious diseases (15%), endocrinology (13.5%), oncology (13%), neurology (11%), and cardiovascular diseases (10%). Examination of major clinical indications within these therapeutic areas showed some level of consistency in the species of choice for testing and the pediatric age that required support. Examination of juvenile animal study findings presented in product labels raises questions around how useful the data are to allow prescribing the drug to a child. It is hopeful that the new ICH S11 guideline "Nonclinical Safety Testing in Support of Development of Pediatric Medicines" currently in preparation will aid drug developers in clarifying the need for juvenile animal studies as well as in promoting a move away from toxicology studies with a conventional design. This would permit more focused testing to examine identified areas of toxicity or safety concerns and clarify the presentation/interpretation of juvenile animal study findings for proper risk assessment by a drug prescriber.

Using an innovative combination of quality-by-design and green analytical chemistry approaches for the development of a stability indicating UHPLC method in pharmaceutical products.

Science.gov (United States)

Boussès, Christine; Ferey, Ludivine; Vedrines, Elodie; Gaudin, Karen

2015-11-10

An innovative combination of green chemistry and quality by design (QbD) approach is presented through the development of an UHPLC method for the analysis of the main degradation products of dextromethorphan hydrobromide. QbD strategy was integrated to the field of green analytical chemistry to improve method understanding while assuring quality and minimizing environmental impacts, and analyst exposure. This analytical method was thoroughly evaluated by applying risk assessment and multivariate analysis tools. After a scouting phase aimed at selecting a suitable stationary phase and an organic solvent in accordance with green chemistry principles, quality risk assessment tools were applied to determine the critical process parameters (CPPs). The effects of the CPPs on critical quality attributes (CQAs), i.e., resolutions, efficiencies, and solvent consumption were further evaluated by means of a screening design. A response surface methodology was then carried out to model CQAs as function of the selected CPPs and the optimal separation conditions were determined through a desirability analysis. Resulting contour plots enabled to establish the design space (DS) (method operable design region) where all CQAs fulfilled the requirements. An experimental validation of the DS proved that quality within the DS was guaranteed; therefore no more robustness study was required before the validation. Finally, this UHPLC method was validated using the concept of total error and was used to analyze a pharmaceutical drug product. Copyright © 2015 Elsevier B.V. All rights reserved.

78 FR 65904 - Permanent Discontinuance or Interruption in Manufacturing of Certain Drug or Biological Products

Science.gov (United States)

2013-11-04

... Manufacturing of Certain Drug or Biological Products AGENCY: Food and Drug Administration, HHS. ACTION: Proposed.... The Fabrazyme shortage resulted from contamination at the manufacturing [[Page 65910

Scientific workflows as productivity tools for drug discovery.

Science.gov (United States)

Shon, John; Ohkawa, Hitomi; Hammer, Juergen

2008-05-01

Large pharmaceutical companies annually invest tens to hundreds of millions of US dollars in research informatics to support their early drug discovery processes. Traditionally, most of these investments are designed to increase the efficiency of drug discovery. The introduction of do-it-yourself scientific workflow platforms has enabled research informatics organizations to shift their efforts toward scientific innovation, ultimately resulting in a possible increase in return on their investments. Unlike the handling of most scientific data and application integration approaches, researchers apply scientific workflows to in silico experimentation and exploration, leading to scientific discoveries that lie beyond automation and integration. This review highlights some key requirements for scientific workflow environments in the pharmaceutical industry that are necessary for increasing research productivity. Examples of the application of scientific workflows in research and a summary of recent platform advances are also provided.

Technical Reviews on Pattern Recognition in Process Analytical Technology

International Nuclear Information System (INIS)

Kim, Jong Yun; Choi, Yong Suk; Ji, Sun Kyung; Park, Yong Joon; Song, Kyu Seok; Jung, Sung Hee

2008-12-01

Pattern recognition is one of the first and the most widely adopted chemometric tools among many active research area in chemometrics such as design of experiment(DoE), pattern recognition, multivariate calibration, signal processing. Pattern recognition has been used to identify the origin of a wine and the time of year that the vine was grown by using chromatography, cause of fire by using GC/MS chromatography, detection of explosives and land mines, cargo and luggage inspection in seaports and airports by using a prompt gamma-ray activation analysis, and source apportionment of environmental pollutant by using a stable isotope ratio mass spectrometry. Recently, pattern recognition has been taken into account as a major chemometric tool in the so-called 'process analytical technology (PAT)', which is a newly-developed concept in the area of process analytics proposed by US Food and Drug Administration (US FDA). For instance, identification of raw material by using a pattern recognition analysis plays an important role for the effective quality control of the production process. Recently, pattern recognition technique has been used to identify the spatial distribution and uniformity of the active ingredients present in the product such as tablet by transforming the chemical data into the visual information

Development of a validated liquid chromatographic method for quantification of sorafenib tosylate in the presence of stress-induced degradation products and in biological matrix employing analytical quality by design approach.

Science.gov (United States)

Sharma, Teenu; Khurana, Rajneet Kaur; Jain, Atul; Katare, O P; Singh, Bhupinder

2018-05-01

The current research work envisages an analytical quality by design-enabled development of a simple, rapid, sensitive, specific, robust and cost-effective stability-indicating reversed-phase high-performance liquid chromatographic method for determining stress-induced forced-degradation products of sorafenib tosylate (SFN). An Ishikawa fishbone diagram was constructed to embark upon analytical target profile and critical analytical attributes, i.e. peak area, theoretical plates, retention time and peak tailing. Factor screening using Taguchi orthogonal arrays and quality risk assessment studies carried out using failure mode effect analysis aided the selection of critical method parameters, i.e. mobile phase ratio and flow rate potentially affecting the chosen critical analytical attributes. Systematic optimization using response surface methodology of the chosen critical method parameters was carried out employing a two-factor-three-level-13-run, face-centered cubic design. A method operable design region was earmarked providing optimum method performance using numerical and graphical optimization. The optimum method employed a mobile phase composition consisting of acetonitrile and water (containing orthophosphoric acid, pH 4.1) at 65:35 v/v at a flow rate of 0.8 mL/min with UV detection at 265 nm using a C 18 column. Response surface methodology validation studies confirmed good efficiency and sensitivity of the developed method for analysis of SFN in mobile phase as well as in human plasma matrix. The forced degradation studies were conducted under different recommended stress conditions as per ICH Q1A (R2). Mass spectroscopy studies showed that SFN degrades in strongly acidic, alkaline and oxidative hydrolytic conditions at elevated temperature, while the drug was per se found to be photostable. Oxidative hydrolysis using 30% H 2 O 2 showed maximum degradation with products at retention times of 3.35, 3.65, 4.20 and 5.67 min. The absence of any

Twelfth ISAS national symposium on analytical techniques for safety and sufficiency of natural resources/products: technical papers

International Nuclear Information System (INIS)

Padmanabhan, P.K.; Page, A.G.

1997-02-01

This volume contains the proceedings of the ISAS (Indian Society of Analytical Scientists) national symposium. The main thrust of the symposium was on new fuel cycle technologies relevant to thorium utilisation programmes. The technologies for different separation processes, techniques for measurements of various process parameters and highly sensitive analytical methods for the determination of the chemical constituents were among the other topics covered. Quality upgradation, standardisation of methods and validation of measurements which are integral parts of product evaluation were also discussed. Papers relevant to INIS are indexed separately

Batch-to-batch quality consistency evaluation of botanical drug products using multivariate statistical analysis of the chromatographic fingerprint.

Science.gov (United States)

Xiong, Haoshu; Yu, Lawrence X; Qu, Haibin

2013-06-01

Botanical drug products have batch-to-batch quality variability due to botanical raw materials and the current manufacturing process. The rational evaluation and control of product quality consistency are essential to ensure the efficacy and safety. Chromatographic fingerprinting is an important and widely used tool to characterize the chemical composition of botanical drug products. Multivariate statistical analysis has showed its efficacy and applicability in the quality evaluation of many kinds of industrial products. In this paper, the combined use of multivariate statistical analysis and chromatographic fingerprinting is presented here to evaluate batch-to-batch quality consistency of botanical drug products. A typical botanical drug product in China, Shenmai injection, was selected as the example to demonstrate the feasibility of this approach. The high-performance liquid chromatographic fingerprint data of historical batches were collected from a traditional Chinese medicine manufacturing factory. Characteristic peaks were weighted by their variability among production batches. A principal component analysis model was established after outliers were modified or removed. Multivariate (Hotelling T(2) and DModX) control charts were finally successfully applied to evaluate the quality consistency. The results suggest useful applications for a combination of multivariate statistical analysis with chromatographic fingerprinting in batch-to-batch quality consistency evaluation for the manufacture of botanical drug products.

Drug Product Life-Cycle Management as Anticompetitive Behavior: The Case of Memantine.

Science.gov (United States)

Capati, Vincent C; Kesselheim, Aaron S

2016-04-01

A "product hop" involves the substitution of a new formulation of a prescription drug by a pharmaceutical manufacturer for an old version to forestall generic competition. In 2015, for example, Forest Laboratories, the brand-name drug manufacturer of memantine, an Alzheimer's disease treatment, introduced an extended-release version and tried to restrict patient access to the previous version. Product hops can lead to useful incremental innovation but can also have major public health implications by disrupting patients on stable treatment regimens and increasing costs for patients and payers. This commentary reviews alleged anticompetitive product hopping in the case of memantine, which involved proposed conduct that would have left Alzheimer's disease patients with no effective choice but to transition to memantine XR. Policy solutions that can limit anticompetitive product hops include raising the bar for obtaining patents on new drug product formulations and changing automatic generic substitution laws. No outside funding supported this research. To support his work at PORTAL in the summer of 2015, Capati was the recipient of the University of New Hampshire School of Law Rudman Center Public Service Fellowship. Kesselheim's research was supported by Greenwall Faculty Scholars program, the Laura and John Arnold Foundation, and the Harvard Program in Therapeutic Science. In 2013, Kesselheim served as an expert on behalf of a class of individual plaintiffs against Warner Chilcott regarding potential antitrust violations Kesselheim was responsible for concept and design of this commentary. Capati took the lead in data collection and analysis, along with Kesselheim. Capati wrote the manuscript, which was revised by primarily by Kesselheim, along with Capati.

Consolidating drug data on a global scale using Linked Data.

Science.gov (United States)

Jovanovik, Milos; Trajanov, Dimitar

2017-01-21

supporting tools in transforming drug product data from various, independent and distributed sources, into a comprehensive Linked Drug Data dataset. The presented user-centric and analytical usage scenarios over the dataset show the advantages of having a de-siloed, consolidated and comprehensive dataspace of drug data available via the existing infrastructure of the Web.

Analytical Expressions Pertaining to the Concentration of Substrates and Product in Phenol-Polyphenol Oxidase System Immobilized in Laponite Hydrogels: A Reciprocal Competitive Inhibition Process

Directory of Open Access Journals (Sweden)

K. Indira

2012-01-01

Full Text Available Theoretical analysis corresponding to the diffusion and kinetics of substrate and product in an amperometric biosensor is developed and reported in this paper. The nonlinear coupled system of diffusion equations was analytically solved by Homotopy perturbation method. Herein, we report the approximate analytical expressions pertaining to substrate concentration, product concentration, and current response for all possible values of diffusion and kinetic parameters. The numerical solution of this problem is also reported using Scilab/Matlab program. Also, we found excellent agreement between the analytical results and numerical results upon comparison.

21 CFR 328.50 - Principal display panel of all OTC drug products intended for oral ingestion that contain alcohol.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Principal display panel of all OTC drug products intended for oral ingestion that contain alcohol. 328.50 Section 328.50 Food and Drugs FOOD AND DRUG... PRODUCTS INTENDED FOR ORAL INGESTION THAT CONTAIN ALCOHOL Labeling § 328.50 Principal display panel of all...

Quality Performance of Drugs Analyzed in the Drug Analysis and ...

African Journals Online (AJOL)

ICT TEAM

performance of drug samples analyzed therein. Previous reports have ... wholesalers, non-governmental organizations, hospitals, analytical ..... a dispute concerning discharge of waste water ... Healthcare Industry in Kenya, December. 2008.

Nature is the best source of anticancer drugs: Indexing natural products for their anticancer bioactivity.

Directory of Open Access Journals (Sweden)

Anwar Rayan

Full Text Available Cancer is considered one of the primary diseases that cause morbidity and mortality in millions of people worldwide and due to its prevalence, there is undoubtedly an unmet need to discover novel anticancer drugs. However, the traditional process of drug discovery and development is lengthy and expensive, so the application of in silico techniques and optimization algorithms in drug discovery projects can provide a solution, saving time and costs. A set of 617 approved anticancer drugs, constituting the active domain, and a set of 2,892 natural products, constituting the inactive domain, were employed to build predictive models and to index natural products for their anticancer bioactivity. Using the iterative stochastic elimination optimization technique, we obtained a highly discriminative and robust model, with an area under the curve of 0.95. Twelve natural products that scored highly as potential anticancer drug candidates are disclosed. Searching the scientific literature revealed that few of those molecules (Neoechinulin, Colchicine, and Piperolactam have already been experimentally screened for their anticancer activity and found active. The other phytochemicals await evaluation for their anticancerous activity in wet lab.

An asymptotic analytical solution to the problem of two moving boundaries with fractional diffusion in one-dimensional drug release devices

International Nuclear Information System (INIS)

Yin Chen; Xu Mingyu

2009-01-01

We set up a one-dimensional mathematical model with a Caputo fractional operator of a drug released from a polymeric matrix that can be dissolved into a solvent. A two moving boundaries problem in fractional anomalous diffusion (in time) with order α element of (0, 1] under the assumption that the dissolving boundary can be dissolved slowly is presented in this paper. The two-parameter regular perturbation technique and Fourier and Laplace transform methods are used. A dimensionless asymptotic analytical solution is given in terms of the Wright function

78 FR 72840 - Drug Products That Present Demonstrable Difficulties for Compounding Under Sections 503A and 503B...

Science.gov (United States)

2013-12-04

... reasonably demonstrate an adverse effect on the safety or effectiveness of that drug product'' (section 503A... because it included restrictions on the advertising or promotion of the compounding of any particular drug... effect on the safety or effectiveness of that drug product. In addition, the DQSA adds a new section 503B...

On-site management of investigational products and drug delivery systems in conformity with Good Clinical Practices (GCPs).

Science.gov (United States)

Méthot, Julie; Brisson, Diane; Gaudet, Daniel

2012-04-01

Investigators and research teams participating in clinical trials have to deal with complex investigational products, study designs, and research environments. The emergence of new drug delivery systems and investigational products combining more than one drug and the development of biodrugs such as monoclonal antibodies, peptides, siRNA, and gene therapy to treat orphan or common diseases constitute a new challenge for investigators and clinical sites. We describe the requirements and challenges of drug management in conformity with Good Clinical Practices (GCPs) for investigators and sites participating in clinical trials. Review At all sites participating in clinical trials, standard operating procedures (SOPs) covering the critical path of drug and drug delivery systems management are required. All steps should be auditable, including reception, validation, storage, access, preparation, distribution, techniques of administration, use, return, and destruction of research products. Biodrugs require traceability and specific SOPs on the management of potential immune reactions. Investigational products must be stored under standard auditable conditions. The traceability of storage conditions (including temperature) requires these conditions to be monitored on a continuous basis. A dedicated space with restricted access limited to authorized qualified personnel facilitates the monitoring. The development of standardized, auditable settings and the application of dedicated, site-specific SOPs for the management of investigational products and drug delivery systems contribute to guarantee the compliance to GCP requirements.

Analysis of pharmaceutical market of nootropic drugs in Ukraine

Directory of Open Access Journals (Sweden)

Олена Валеріївна Савельєва

2015-11-01

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

Analytical Techniques in the Pharmaceutical Sciences

DEFF Research Database (Denmark)

Leurs, Ulrike; Mistarz, Ulrik Hvid; Rand, Kasper Dyrberg

2016-01-01

Mass spectrometry (MS) offers the capability to identify, characterize and quantify a target molecule in a complex sample matrix and has developed into a premier analytical tool in drug development science. Through specific MS-based workflows including customized sample preparation, coupling...

Patient Drug Safety Reporting: Diabetes Patients' Perceptions of Drug Safety and How to Improve Reporting of Adverse Events and Product Complaints.

Science.gov (United States)

Patel, Puja; Spears, David; Eriksen, Betina Østergaard; Lollike, Karsten; Sacco, Michael

2018-03-01

Global health care manufacturer Novo Nordisk commissioned research regarding awareness of drug safety department activities and potential to increase patient feedback. Objectives were to examine patients' knowledge of pharmaceutical manufacturers' responsibilities and efforts regarding drug safety, their perceptions and experiences related to these efforts, and how these factors influence their thoughts and behaviors. Data were collected before and after respondents read a description of a drug safety department and its practices. We conducted quantitative survey research across 608 health care consumers receiving treatment for diabetes in the United States, Germany, United Kingdom, and Italy. This research validated initial, exploratory qualitative research (across 40 comparable consumers from the same countries) which served to guide design of the larger study. Before reading a drug safety department description, 55% of respondents were unaware these departments collect safety information on products and patients. After reading the description, 34% reported the department does more than they expected to ensure drug safety, and 56% reported "more confidence" in the industry as a whole. Further, 66% reported themselves more likely to report an adverse event or product complaint, and 60% reported that they were more likely to contact a drug safety department with questions. The most preferred communication methods were websites/online forums (39%), email (27%), and telephone (25%). Learning about drug safety departments elevates consumers' confidence in manufacturers' safety efforts and establishes potential for patients to engage in increased self-monitoring and reporting. Study results reveal potentially actionable insights for the industry across patient and physician programs and communications.

Perspectives on bioanalytical mass spectrometry and automation in drug discovery.

Science.gov (United States)

Janiszewski, John S; Liston, Theodore E; Cole, Mark J

2008-11-01

The use of high speed synthesis technologies has resulted in a steady increase in the number of new chemical entities active in the drug discovery research stream. Large organizations can have thousands of chemical entities in various stages of testing and evaluation across numerous projects on a weekly basis. Qualitative and quantitative measurements made using LC/MS are integrated throughout this process from early stage lead generation through candidate nomination. Nearly all analytical processes and procedures in modern research organizations are automated to some degree. This includes both hardware and software automation. In this review we discuss bioanalytical mass spectrometry and automation as components of the analytical chemistry infrastructure in pharma. Analytical chemists are presented as members of distinct groups with similar skillsets that build automated systems, manage test compounds, assays and reagents, and deliver data to project teams. The ADME-screening process in drug discovery is used as a model to highlight the relationships between analytical tasks in drug discovery. Emerging software and process automation tools are described that can potentially address gaps and link analytical chemistry related tasks. The role of analytical chemists and groups in modern 'industrialized' drug discovery is also discussed.

21 CFR 201.26 - Exceptions or alternatives to labeling requirements for human drug products held by the Strategic...

Science.gov (United States)

2010-04-01

... requirements for human drug products held by the Strategic National Stockpile. 201.26 Section 201.26 Food and... drug products held by the Strategic National Stockpile. (a) The appropriate FDA Center Director may... safety, effectiveness, or availability of such product that is or will be included in the Strategic...

Prudent Use of Veterinary Drugs: Impact on Safe Animal Products ...

African Journals Online (AJOL)

Like any other therapeutic compounds, veterinary drugs are used to alleviate diseases in animals as either therapeutic or prophylactic compounds for specific disease entities. They can also be used as production aids in food producing animals to increase market sale of these animals whereby the producers save on the ...

7 CFR 98.4 - Analytical methods.

Science.gov (United States)

2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Analytical methods. 98.4 Section 98.4 Agriculture....4 Analytical methods. (a) The majority of analytical methods used by the USDA laboratories to perform analyses of meat, meat food products and MRE's are listed as follows: (1) Official Methods of...

75 FR 75482 - Draft Guidance for Industry on Residual Solvents in Animal Drug Products; Questions and Answers...

Science.gov (United States)

2010-12-03

...] Draft Guidance for Industry on Residual Solvents in Animal Drug Products; Questions and Answers... Solvents in Animal Drug Products; Questions and Answers.'' The draft questions and answers (Q&A) guidance addresses the United States Pharmacopeia (USP) General Chapter Residual Solvents that applies to both human...

Magnetic nanoparticles for bio-analytical applications

Science.gov (United States)

Yedlapalli, Sri Lakshmi

Magnetic nanoparticles are widely being used in various fields of medicine, biology and separations. This dissertation focuses on the synthesis and use of magnetic nanoparticles for targeted drug delivery and analytical separations. The goals of this research include synthesis of biocompatible surface modified monodisperse superparamagnetic iron oxide nanoparticles (SPIONs) by novel techniques for targeted drug delivery and use of SPIONs as analytical sensing tools. Surface modification of SPIONs was performed with two different co-polymers: tri block co-polymer Pluronics and octylamine modified polyacrylic acid. Samples of SPIONs were subsequently modified with 4 different commercially available, FDA approved tri-block copolymers (Pluronics), covering a wide range of molecular weights (5.75-14.6 kDa). A novel, technically simpler and faster phase transfer approach was developed to surface modify the SPIONs with Pluronics for drug delivery and other biomedical applications. The hydrodynamic diameter and aggregation properties of the Pluronic modified SPIONs were studied by dynamic light scattering (DLS). The coverage of SPIONs with Pluronics was supported with IR Spectroscopy and characterized by Thermo gravimetric Analysis (TGA). The drug entrapment capacity of SPIONs was studied by UV-VIS spectroscopy using a hydrophobic carbocyanine dye, which serves as a model for hydrophobic drugs. These studies resulted in a comparison of physical properties and their implications for drug loading capacities of the four types of Pluronic coated SPIONs for drug delivery assessment. These drug delivery systems could be used for passive drug targeting. However, Pluronics lack the functional group necessary for bioconjugation and hence cannot achieve active targeting. SPIONs were functionalized with octylamine modified polyacrylic acid-based copolymer, providing water solubility and facile biomolecular conjugation. Epirubicin was loaded onto SPIONs and the drug entrapment was

Measurement of HDO Products Using GC-TCD: Towards Obtaining Reliable Analytical Data

Directory of Open Access Journals (Sweden)

Zuas Oman

2018-03-01

Full Text Available This paper reported the method development and validation of a gas chromatography with thermal conductivity detector (GC-TCD method for the measurement of the gaseous products of hydrodeoxygenation (HDO. The method validation parameters include selectivity, precision (repeatability and reproducibility, accuracy, linearity, limit of detection (LoD, limit of quantitation (LoQ, and robustness. The results showed that the developed method was able to separate the target components (H2, CO2, CH4 and CO from their mixtures without any special sample treatment. The validated method was selective, precise, accurate, and robust. Application of the developed and validated GC-TCD method to the measurement of by-product components of HDO of bio-oil revealed a good performance with relative standard deviation (RSD less than 1.0% for all target components, implying that the process of method development and validation provides a trustworthy way of obtaining reliable analytical data.

Studies in youth, drug and alcohol consumption at the Centre for Alcohol and Drug Research

DEFF Research Database (Denmark)

Kolind, Torsten; Demant, Jakob Johan; Hunt, Geoffrey

2013-01-01

or providing genuine contribution to the sociological analysis and understanding of youth cultures. From the mid-00 s and forward however, a range of analytical tools were developed at Centre for Alcohol and Drug Research (CRF) in order to understand the relationship between youth, drug and alcohol use......Background: During the 90 s and especially in the beginning of the 00 s research in youth, drug and alcohol consumption increased markedly in Denmark. Much of this research was applied and placed in a dilemma between reproducing existing social problem characterizations of youthful behaviors...... and to move beyond the applied perspective into a more social science analytical approach. Aim: The article investigates the relationship developments between drug and alcohol research and youth research in Denmark in general, with a special focus on research conducted at CRF. Specifically, we will focus...

Applying green analytical chemistry for rapid analysis of drugs: Adding health to pharmaceutical industry

Directory of Open Access Journals (Sweden)

Nazrul Haq

2017-02-01

Full Text Available Green RP-HPLC method for a rapid analysis of olmesartan medoxomil (OLM in bulk drugs, self-microemulsifying drug delivery system (SMEDDS and marketed tablets was developed and validated in the present investigation. The chromatographic identification was achieved on Lichrosphere 250 × 4.0 mm RP C8 column having a 5 μm packing as a stationary phase using a combination of green solvents ethyl acetate:ethanol (50:50% v/v as a mobile phase, at a flow rate of 1.0 mL/min with UV detection at 250 nm. The proposed method was validated for linearity, selectivity, accuracy, precision, reproducibility, robustness, sensitivity and specificity. The utility of the proposed method was verified by an assay of OLM in SMEDDS and commercial tablets. The proposed method was found to be selective, precise, reproducible, accurate, robust, sensitive and specific. The amount of OLM in SMEDDS and commercial tablets was found to be 101.25% and 98.67% respectively. The proposed method successfully resolved OLM peak in the presence of its degradation products which indicated stability-indicating property of the proposed method. These results indicated that the proposed method can be successfully employed for a routine analysis of OLM in bulk drugs and commercial formulations.

Biopharming, bananas and bureaucracy: the banana vaccine as a case study for products that straddle the definitional food/drug divide.

Science.gov (United States)

Birdsall, Margaux

2011-01-01

This paper examines the definition of the terms "food" and "drug" as used in the Food, Drug and Cosmetic Act through the lens of biopharmed products. The paper uses the so-called "banana vaccine" as a case study to highlight the problems that occur when attempting to regulate a product that could be safely used as a food or as a drug. Specifically, the examination of this model illustrates the problems in the current definitional scheme. The paper considers how a product that straddles the definitional line between food and drug could be regulated and proposes a reformation to how the definitions are applied to products to better suit new technology in food and drugs.

Recent developments in analytical toxicology : for better or for worse

NARCIS (Netherlands)

de Zeeuw, RA

1998-01-01

When considering the state of the art in toxicology from an analytical perspective, the key developments relate to three major areas. (1) Forensic horizon: Today forensic analysis has broadened its scope dramatically, to include workplace toxicology, drug abuse testing, drugs and driving, doping,

Can Brazil play a more important role in global tuberculosis drug production? An assessment of current capacity and challenges.

Science.gov (United States)

Gemal, Andre; Keravec, Joel; Menezes, Alexandre; Trajman, Anete

2013-03-27

Despite the existence of effective treatment, tuberculosis is still a global public health issue. The World Health Organization recommends a six-month four-drug regimen in fixed-dose combination formulation to treat drug sensitive tuberculosis, and long course regimens with several second-line drugs to treat multi-drug resistant tuberculosis. To achieve the projected tuberculosis elimination goal by 2050, it will be essential to ensure a non-interrupted supply of quality-assured tuberculosis drugs. However, quality and affordable tuberculosis drug supply is still a significant challenge for National Tuberculosis Programs. Quality drug production requires a combination of complex steps. The first challenge is to guarantee the quality of tuberculosis active pharmaceutical ingredients, then ensure an adequate manufacturing process, according to international standards, to guarantee final product's safety, efficacy and quality. Good practices for storage, transport, distribution and quality control procedures must follow. In contrast to other high-burden countries, Brazil produces tuberculosis drugs through a strong network of public sector drug manufacturers regulated by a World Health Organization-certified national sanitary authority. The installed capacity for production surpasses the 71,000 needed treatments in the country. However, in order to be prepared to act as a global supplier, important bottlenecks are to be overcome. This article presents an in-depth analysis of the current status of production of tuberculosis drugs in Brazil and the bottlenecks and opportunities for the country to sustain national demand and play a role as a potential global supplier. Raw material and drug production, quality control, international certification and pre-qualification, political commitment and regulatory aspects are discussed, as well recommendations for tackling these bottlenecks. This discussion becomes more important as new drugs and regimens to treat tuberculosis are

21 CFR 310.530 - Topically applied hormone-containing drug products for over-the-counter (OTC) human use.

Science.gov (United States)

2010-04-01

... labeling or in the ingredient statement is an implied drug claim. The claim implied by the use of this term... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Topically applied hormone-containing drug products for over-the-counter (OTC) human use. 310.530 Section 310.530 Food and Drugs FOOD AND DRUG...

76 FR 36307 - Guidance for Industry on Topical Acne Drug Products for Over-the-Counter Human Use-Revision of...

Science.gov (United States)

2011-06-22

.... FDA-2011-D-0404] Guidance for Industry on Topical Acne Drug Products for Over-the- Counter Human Use... entities entitled ``Topical Acne Drug Products for Over-the-Counter Human Use--Revision of Labeling and... recognized as safe and effective (GRASE) active ingredient in over-the-counter (OTC) topical acne drug...

A comprehensive review of assay methods to determine drugs in breast milk and the safety of breastfeeding when taking drugs.

Science.gov (United States)

Fríguls, Bibiana; Joya, Xavier; García-Algar, Oscar; Pallás, C R; Vall, Oriol; Pichini, Simona

2010-06-01

Most of the licit and illicit drugs consumed by the breastfeeding woman pass into the milk and can modify the production, volume and composition of the milk, as well as hypothetically have short- and long-term harmful effects on the infant. There is much confusion in the scientific community regarding this issue: should a woman breastfeed her baby while continuing to use prescription drugs and/or drugs of abuse? There are many case reports of clinically significant toxicity in breast-fed infants from some substances used by mothers (such as irritability, vomiting, sedation, respiratory depression, shock), but there are too few data on studies conducted in breastfeeding women and their infants to make a realistic risk assessment. The objective measurement of a drug and/or metabolites in maternal milk is the first step when investigating the amount of drug excreted in milk and subsequently calculating the daily dose administered to the breast-fed infant. The present review reports the analytical methods developed to detect different drugs in the breast milk, listing the principal characteristics and validation parameters, advantages and disadvantages. Furthermore, the mechanisms of drug transfer into breast milk are discussed, the correlation between the concentration of the drug in breast milk and potential adverse outcomes on the infant are described for each drug, and suggested harm minimization strategies and approved breastfeeding recommendations are indicated.

The analysis of a trace amount of elements in crude drugs

International Nuclear Information System (INIS)

Wakayama, I.; Akagawa, J.; Yase, Y.; Yoshida, S.; Sasajima, Kazuhisa

2001-01-01

The concentrations and the pharmacological actions of iron and zinc in nearly 30 kinds of crude drugs of Chinese medicine are studied using the neutron activation analysis, quantitatively. The quantitative analytical results are also compared with the semi-quantitative analytical results of iron and zinc obtained by particle induced X-ray emission spectroscopy. The crude drugs with higher iron concentration were almost drugs for the mentality. The crude drugs with highest zinc concentration were also the drugs for the mentality. (H. Katsuta)

Strategies of bringing drug product marketing applications to meet current regulatory standards.

Science.gov (United States)

Wu, Yan; Freed, Anita; Lavrich, David; Raghavachari, Ramesh; Huynh-Ba, Kim; Shah, Ketan; Alasandro, Mark

2015-08-01

In the past decade, many guidance documents have been issued through collaboration of global organizations and regulatory authorities. Most of these are applicable to new products, but there is a risk that currently marketed products will not meet the new compliance standards during audits and inspections while companies continue to make changes through the product life cycle for continuous improvement or market demands. This discussion presents different strategies to bringing drug product marketing applications to meet current and emerging standards. It also discusses stability and method designs to meet process validation and global development efforts.

Application of Absorption Modeling in Rational Design of Drug Product Under Quality-by-Design Paradigm.

Science.gov (United States)

Kesisoglou, Filippos; Mitra, Amitava

2015-09-01

Physiologically based absorption models can be an important tool in understanding product performance and hence implementation of Quality by Design (QbD) in drug product development. In this report, we show several case studies to demonstrate the potential application of absorption modeling in rational design of drug product under the QbD paradigm. The examples include application of absorption modeling—(1) prior to first-in-human studies to guide development of a formulation with minimal sensitivity to higher gastric pH and hence reduced interaction when co-administered with PPIs and/or H2RAs, (2) design of a controlled release formulation with optimal release rate to meet trough plasma concentrations and enable QD dosing, (3) understanding the impact of API particle size distribution on tablet bioavailability and guide formulation design in late-stage development, (4) assess impact of API phase change on product performance to guide specification setting, and (5) investigate the effect of dissolution rate changes on formulation bioperformance and enable appropriate specification setting. These case studies are meant to highlight the utility of physiologically based absorption modeling in gaining a thorough understanding of the product performance and the critical factors impacting performance to drive design of a robust drug product that would deliver the optimal benefit to the patients.

Simultaneous Determination of Antipsychotic Drugs and Their Active Metabolites by LC-MS-MS and its Application to Therapeutic Drug Monitoring.

Science.gov (United States)

Miroshnichenko, Igor I; Baymeeva, Natalia V

2018-04-07

A quantitative method was developed to support therapeutic drug monitoring of eight antipsychotic drugs: chlorpromazine, haloperidol, zuclopenthixol, clozapine, risperidone, quetiapine, aripiprazole or olanzapine and some active metabolites (dehydroaripiprazole, N-desmethylclozapine and 9-hydroxyrisperidone) in human serum. Separation of the compounds was achieved using a Zorbax SB-C18 (150 mm × 4.6 mm, 5 μm) column and mass-spectrometric detection in multiple reaction monitoring mode. Human blood samples were collected in vacutainer tubes and the analytes were extracted with methyl-tert-butyl ether. The lower limits of quantitation were equal 0.5-1 ng/mL for all analytes. The method was applied with success to serum samples from schizophrenic patients undergoing polypharmacy with two or more different antipsychotic drugs. Precision data, accuracy results were satisfactory, and no interference from other psychotropic drugs was found. Hence, the method is suitable for the TDM of the analytes in psychotic patients' serum.

Application of Combination High-Throughput Phenotypic Screening and Target Identification Methods for the Discovery of Natural Product-Based Combination Drugs.

Science.gov (United States)

Isgut, Monica; Rao, Mukkavilli; Yang, Chunhua; Subrahmanyam, Vangala; Rida, Padmashree C G; Aneja, Ritu

2018-03-01

Modern drug discovery efforts have had mediocre success rates with increasing developmental costs, and this has encouraged pharmaceutical scientists to seek innovative approaches. Recently with the rise of the fields of systems biology and metabolomics, network pharmacology (NP) has begun to emerge as a new paradigm in drug discovery, with a focus on multiple targets and drug combinations for treating disease. Studies on the benefits of drug combinations lay the groundwork for a renewed focus on natural products in drug discovery. Natural products consist of a multitude of constituents that can act on a variety of targets in the body to induce pharmacodynamic responses that may together culminate in an additive or synergistic therapeutic effect. Although natural products cannot be patented, they can be used as starting points in the discovery of potent combination therapeutics. The optimal mix of bioactive ingredients in natural products can be determined via phenotypic screening. The targets and molecular mechanisms of action of these active ingredients can then be determined using chemical proteomics, and by implementing a reverse pharmacokinetics approach. This review article provides evidence supporting the potential benefits of natural product-based combination drugs, and summarizes drug discovery methods that can be applied to this class of drugs. © 2017 Wiley Periodicals, Inc.

Pitfalls in TDM of antibiotic drugs : Analytical and modelling issues

NARCIS (Netherlands)

Neef, C.; Touw, D. J.; Harteveld, A. R.; Eerland, J. J.; Uges, D. R. A.

2006-01-01

The quality assurance program of the Dutch KKGT [Association for Quality Assessment in therapeutic drug monitoring (TDM) and Clinical Toxicology] has been running for more than 25 years. One of these programs concerns TDM of the antibiotic drugs gentamicin, tobramycin, amikacin, and vancomycin. We

Analytical method for the identification and assay of 12 phthalates in cosmetic products: application of the ISO 12787 international standard "Cosmetics-Analytical methods-Validation criteria for analytical results using chromatographic techniques".

Science.gov (United States)

Gimeno, Pascal; Maggio, Annie-Françoise; Bousquet, Claudine; Quoirez, Audrey; Civade, Corinne; Bonnet, Pierre-Antoine

2012-08-31

Esters of phthalic acid, more commonly named phthalates, may be present in cosmetic products as ingredients or contaminants. Their presence as contaminant can be due to the manufacturing process, to raw materials used or to the migration of phthalates from packaging when plastic (polyvinyl chloride--PVC) is used. 8 phthalates (DBP, DEHP, BBP, DMEP, DnPP, DiPP, DPP, and DiBP), classified H360 or H361, are forbidden in cosmetics according to the European regulation on cosmetics 1223/2009. A GC/MS method was developed for the assay of 12 phthalates in cosmetics, including the 8 phthalates regulated. Analyses are carried out on a GC/MS system with electron impact ionization mode (EI). The separation of phthalates is obtained on a cross-linked 5%-phenyl/95%-dimethylpolysiloxane capillary column 30 m × 0.25 mm (i.d.) × 0.25 mm film thickness using a temperature gradient. Phthalate quantification is performed by external calibration using an internal standard. Validation elements obtained on standard solutions, highlight a satisfactory system conformity (resolution>1.5), a common quantification limit at 0.25 ng injected, an acceptable linearity between 0.5 μg mL⁻¹ and 5.0 μg mL⁻¹ as well as a precision and an accuracy in agreement with in-house specifications. Cosmetic samples ready for analytical injection are analyzed after a dilution in ethanol whereas more complex cosmetic matrices, like milks and creams, are assayed after a liquid/liquid extraction using ter-butyl methyl ether (TBME). Depending on the type of cosmetics analyzed, the common limits of quantification for the 12 phthalates were set at 0.5 or 2.5 μg g⁻¹. All samples were assayed using the analytical approach described in the ISO 12787 international standard "Cosmetics-Analytical methods-Validation criteria for analytical results using chromatographic techniques". This analytical protocol is particularly adapted when it is not possible to make reconstituted sample matrices. Copyright © 2012

Nature is the best source of anti-inflammatory drugs: indexing natural products for their anti-inflammatory bioactivity.

Science.gov (United States)

Aswad, Miran; Rayan, Mahmoud; Abu-Lafi, Saleh; Falah, Mizied; Raiyn, Jamal; Abdallah, Ziyad; Rayan, Anwar

2018-01-01

The aim was to index natural products for less expensive preventive or curative anti-inflammatory therapeutic drugs. A set of 441 anti-inflammatory drugs representing the active domain and 2892 natural products representing the inactive domain was used to construct a predictive model for bioactivity-indexing purposes. The model for indexing the natural products for potential anti-inflammatory activity was constructed using the iterative stochastic elimination algorithm (ISE). ISE is capable of differentiating between active and inactive anti-inflammatory molecules. By applying the prediction model to a mix set of (active/inactive) substances, we managed to capture 38% of the anti-inflammatory drugs in the top 1% of the screened set of chemicals, yielding enrichment factor of 38. Ten natural products that scored highly as potential anti-inflammatory drug candidates are disclosed. Searching the PubMed revealed that only three molecules (Moupinamide, Capsaicin, and Hypaphorine) out of the ten were tested and reported as anti-inflammatory. The other seven phytochemicals await evaluation for their anti-inflammatory activity in wet lab. The proposed anti-inflammatory model can be utilized for the virtual screening of large chemical databases and for indexing natural products for potential anti-inflammatory activity.

Patient-Reported Outcomes Labeling for Products Approved by the Office of Hematology and Oncology Products of the US Food and Drug Administration (2010-2014).

Science.gov (United States)

Gnanasakthy, Ari; DeMuro, Carla; Clark, Marci; Haydysch, Emily; Ma, Esprit; Bonthapally, Vijayveer

2016-06-01

To review the use of patient-reported outcome (PRO) data in medical product labeling granted by the US Food and Drug Administration (FDA) for new molecular entities and biologic license applications by the FDA Office of Hematology and Oncology Products (OHOP) between January 2010 and December 2014, to elucidate challenges faced by OHOP for approving PRO labeling, and to understand challenges faced by drug manufacturers to include PRO end points in oncology clinical trials. FDA Drug Approval Reports by Month were reviewed to obtain the number of new molecular entities and biologic license applications approved from 2010 to 2014. Drugs approved by the FDA OHOP during this period were selected for further review, focusing on brand and generic name; approval date; applicant; indication; PRO labeling describing treatment benefit, measures, end point status, and significant results; FDA reviewer feedback on PRO end points; and study design of registration trials. First in class, priority review, fast track, orphan drug, or accelerated approval status was retrieved for selected oncology drugs from 2011 to 2014. Descriptive analyses were performed by using Microsoft Excel 2010. Of 160 drugs approved by the FDA (2010-2014), 40 were approved by OHOP. Three (7.5%) of the 40 received PRO-related labeling (abiraterone acetate, ruxolitinib phosphate, and crizotinib). Compared with nononcology drugs (2011-2014), oncology drugs were more likely to be orphan and first in class. The majority of oncology drug reviews by FDA were fast track, priority, or accelerated. Although symptoms and functional decrements are common among patients with cancer, PRO labeling is rare in the United States, likely because of logistical hurdles and oncology study design. Recent developments within the FDA OHOP to capture PROs in oncology studies for the purpose of product labeling are encouraging. © 2016 by American Society of Clinical Oncology.

Process analytical technology (PAT) for biopharmaceuticals

DEFF Research Database (Denmark)

Glassey, Jarka; Gernaey, Krist; Clemens, Christoph

2011-01-01

Process analytical technology (PAT), the regulatory initiative for building in quality to pharmaceutical manufacturing, has a great potential for improving biopharmaceutical production. The recommended analytical tools for building in quality, multivariate data analysis, mechanistic modeling, novel...

Drug-Drug and Herb-Drug Interaction-A Comment | Esimone ...

African Journals Online (AJOL)

Clinically relevant drug-drug interactions may be pharmacodynamic or pharmacokinetic. And herbal medicinal products are becoming increasingly popular. Drug interactions can be in vivo or in vitro. Pharmacodynamic outcomes take such forms as Additive, Synergistic, Antagonistic or Indifferent. The paper reviews and ...

Comprehension of complex biological processes by analytical methods: how far can we go using mass spectrometry?

International Nuclear Information System (INIS)

Gerner, C.

2013-01-01

Comprehensive understanding of complex biological processes is the basis for many biomedical issues of great relevance for modern society including risk assessment, drug development, quality control of industrial products and many more. Screening methods provide means for investigating biological samples without research hypothesis. However, the first boom of analytical screening efforts has passed and we again need to ask whether and how to apply screening methods. Mass spectrometry is a modern tool with unrivalled analytical capacities. This applies to all relevant characteristics of analytical methods such as specificity, sensitivity, accuracy, multiplicity and diversity of applications. Indeed, mass spectrometry qualifies to deal with complexity. Chronic inflammation is a common feature of almost all relevant diseases challenging our modern society; these diseases are apparently highly diverse and include arteriosclerosis, cancer, back pain, neurodegenerative diseases, depression and other. The complexity of mechanisms regulating chronic inflammation is the reason for the practical challenge to deal with it. The presentation shall give an overview of capabilities and limitations of the application of this analytical tool to solve critical questions with great relevance for our society. (author)

Ethnic hair care products may increase false positives in hair drug testing.

Science.gov (United States)

Kidwell, David A; Smith, Frederick P; Shepherd, Arica R

2015-12-01

The question of why different races appear more susceptible to hair contamination by external drugs remains controversial. This research studied susceptibility of head hair to external cocaine and methamphetamine when hair products have been applied. Three different chemical classes of ethnic hair products were applied to Caucasian, Asian, and African hair. Some products increased the methamphetamine and cocaine concentrations in all hair types. A unique finding of this research is that certain ethnic hair products can replace moisture as a diffusion medium, thereby increasing the susceptibility to contamination over 100-fold compared to petroleum-based products. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The Integration of Production-Distribution on Newspapers Supply Chain for Cost Minimization using Analytic Models: Case Study

Science.gov (United States)

Febriana Aqidawati, Era; Sutopo, Wahyudi; Hisjam, Muh.

2018-03-01

Newspapers are products with special characteristics which are perishable, have a shorter range of time between the production and distribution, zero inventory, and decreasing sales value along with increasing in time. Generally, the problem of production and distribution in the paper supply chain is the integration of production planning and distribution to minimize the total cost. The approach used in this article to solve the problem is using an analytical model. In this article, several parameters and constraints have been considered in the calculation of the total cost of the integration of production and distribution of newspapers during the determined time horizon. This model can be used by production and marketing managers as decision support in determining the optimal quantity of production and distribution in order to obtain minimum cost so that company's competitiveness level can be increased.

Screening for illicit drugs in pooled human urine and urinated soil samples and studies on the stability of urinary excretion products of cocaine, MDMA, and MDEA in wastewater by hyphenated mass spectrometry techniques

DEFF Research Database (Denmark)

Mardal, Marie; Kinyua, Juliet; Ramin, Pedram

2017-01-01

were the most frequently detected illicit drugs; an analytical method was developed to quantify their excretion products. Hydroxymethoxymethamphetamine (HMMA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), HMMA sulfate (HMMA-S), benzoylecgonine (BE), and cocaethylene...... (CE) had 85–102% of initial concentration after 8 h of incubation, whereas COC and ecgonine methyl ester (EME) had 74 and 67% after 8 h, respectively. HMMA showed a net increase during 24 h of incubation (107% ± 27, n = 8), possibly due to the cleavage of HMMA conjugates, and biotransformation of MDMA....... The results suggest HMMA as analytical target for MDMA consumption in WBE, due to its stability in wastewater and its excretion as the main phase I metabolite of MDMA. Copyright © 2016 John Wiley & Sons, Ltd....

A critical assessment of antipsychotic drug monitoring.

Science.gov (United States)

Waraska, J; Nagle, J D

1987-06-01

Analytic problems associated with monitoring antipsychotic drug levels have largely been resolved. Despite the establishment of target values for some drugs, the clinical utility of such levels remains to be determined.

Residues of carcinogenic animal drugs in food: difficulties in evaluation of human safety.

Science.gov (United States)

Somogyi, A

1979-01-01

The indisputable need to intensify animal production in order to provide an adequate food supply for the world population involves the use of substances that are highly potent pharmacologically and toxicologically. The history of regulatory action with regard to such additives is similar to that for other substances: first, no regulation; next, an over-reaction; and now decisions based on judicious evaluation of scientific facts. One factor that differentiates the chemicals used in animal production from other food additives is that both the parent compounds and their metabolites appear in edible products, posing problems both for the analytical detection and safety evaluation of such residues. It would be unrealistic to propose 'zero' tolerances for these additives, even if they are carcinogenic. The benefits gained from drugs that cure and prevent infections and parasitic diseases in food-producing animals, and the fact that analytical methods can now detect very small quantities make the presence of low levels of these substances in food unobjectionable.

Vaccination of chickens against coccidiosis ameliorates drug resistance in commercial poultry production

Directory of Open Access Journals (Sweden)

H. David Chapman

2014-12-01

Full Text Available Drug resistance is a problem wherever livestock are raised under intensive conditions and drugs are used to combat parasitic infections. This is particularly true for the anticoccidial agents used for the prevention of coccidiosis caused by protozoa of the apicomplexan genus Eimeria in poultry. Resistance has been documented for all the dozen or so drugs approved for use in chickens and varying levels of resistance is present for those currently employed. A possible solution may be the introduction of drug-sensitive parasites into the houses where poultry are raised so that they may replace such drug-resistant organisms. This can be achieved by utilizing live vaccines that contain strains of Eimeria that were isolated before most anticoccidial compounds were introduced. Such strains are inherently drug-sensitive. Practical proposals to achieve this objective involve the alternation of vaccination with medication (known as rotation programs in successive flocks reared in the same poultry house. A proposal for a yearly broiler production cycle involving chemotherapy and vaccination is presented. There are few, if any, examples in veterinary parasitology where it has proved possible to restore sensitivity to drugs used to control a widespread parasite. Further research is necessary to ascertain whether this can result in sustainable and long-term control of Eimeria infections in poultry.

Vaccination of chickens against coccidiosis ameliorates drug resistance in commercial poultry production

Science.gov (United States)

Chapman, H. David; Jeffers, Thomas K.

2014-01-01

Drug resistance is a problem wherever livestock are raised under intensive conditions and drugs are used to combat parasitic infections. This is particularly true for the anticoccidial agents used for the prevention of coccidiosis caused by protozoa of the apicomplexan genus Eimeria in poultry. Resistance has been documented for all the dozen or so drugs approved for use in chickens and varying levels of resistance is present for those currently employed. A possible solution may be the introduction of drug-sensitive parasites into the houses where poultry are raised so that they may replace such drug-resistant organisms. This can be achieved by utilizing live vaccines that contain strains of Eimeria that were isolated before most anticoccidial compounds were introduced. Such strains are inherently drug-sensitive. Practical proposals to achieve this objective involve the alternation of vaccination with medication (known as rotation programs) in successive flocks reared in the same poultry house. A proposal for a yearly broiler production cycle involving chemotherapy and vaccination is presented. There are few, if any, examples in veterinary parasitology where it has proved possible to restore sensitivity to drugs used to control a widespread parasite. Further research is necessary to ascertain whether this can result in sustainable and long-term control of Eimeria infections in poultry. PMID:25516830

21 CFR 211.132 - Tamper-evident packaging requirements for over-the-counter (OTC) human drug products.

Science.gov (United States)

2010-04-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR...; (ii) Is prominently placed on the package; and (iii) Is so placed that it will be unaffected if the... product or, if the petition seeks an exemption for a drug class, the name of the drug class, and a list of...

Regulatory Notes on Impact of Excipients on Drug Products and the Maillard Reaction.

Science.gov (United States)

Chowdhury, Dipak K; Sarker, Haripada; Schwartz, Paul

2018-02-01

In general, it is an important criterion that excipients remain inert throughout the shelf life of the formulated pharmaceutical product. However, depending on the functionality in chemical structure of active drug and excipients, they may undergo interaction. The well-known Maillard reaction occurs between a primary amine with lactose at high temperature to produce brown pigments. The reactivity of Maillard reaction may vary depending on the concentration as well as other conditions. Commercially, there are products where the active pharmaceutical ingredient is a primary amine and contains less than 75% lactose along with inactive excipients. This product does not show Maillard reaction during its shelf life of around 2 years at ambient conditions. However, when the same type of product contains more than 95 % lactose as an excipient, then there is a possibility of interactions though it is not visible in the initial year. Therefore, this regulatory note discusses involvement of different factors of a known drug-excipient interactions with case studies and provides an overview on how the concentration of lactose in the pharmaceutical product is important in addition to temperature and moisture in Maillard reaction.

Analytical strategies for residue analysis of veterinary drugs and growth-promoting agents in food-producing animals - A review

NARCIS (Netherlands)

Stolker, A.A.M.; Brinkman, U.A.T.

2005-01-01

After a brief introduction into the field of veterinary drugs and growth-promoting agents, the most important EU regulations and directives for the inspection of food-producing animals and animal products regarding the residue control of these substances are presented and discussed. Main attention

Bringing smart pills to market: FDA regulation of ingestible drug/device combination products.

Science.gov (United States)

Avery, Matthew; Liu, Dan

2011-01-01

Imagine a pill that, after you swallow it, can track its position in your body. Or imagine a pill that can transmit a message to a doctor to tell him that you have taken your bitter medicine. Pills like this already exist. These so-called smart pills are an emerging type of medical therapy. However, this nascent technology has yet to reach the market and developers of these novel therapies face significant regulatory challenges. This article predicts how the Food and Drug Administration will regulate smart pills and shows how the current regulatory regime is inadequate. The article then proposes modifying the current regulatory regime to encourage development of smart pills and other innovative combination products by: (1) regulating combination products based on their "novel mode of action" rather than their "primary mode of action," (2) creating a marketing approval pathway specifically for combination products, and (3) eliminating regulations that require sponsors to get marketing approval from multiple centers within FDA and providing regulatory guidance specifically for ingestible drug/device combination products.

Adulteration of proprietary Chinese medicines and health products with undeclared drugs: experience of a tertiary toxicology laboratory in Hong Kong.

Science.gov (United States)

Ching, Chor Kwan; Chen, Sammy Pak Lam; Lee, Hencher Han Chih; Lam, Ying Hoo; Ng, Sau Wah; Chen, Mo Lung; Tang, Magdalene Huen Yin; Chan, Suzanne Suk San; Ng, Candy Wai Yan; Cheung, Jana Wing Lan; Chan, Tina Yee Ching; Lau, Nike Kwai Cheung; Chong, Yeow Kuan; Mak, Tony Wing Lai

2018-01-01

Proprietary Chinese medicines (pCMs) and health products, generally believed to be natural and safe, are gaining popularity worldwide. However, the safety of pCMs and health products has been severely compromised by the practice of adulteration. The current study aimed to examine the problem of adulteration of pCMs and health products in Hong Kong. The present study was conducted in a tertiary referral clinical toxicology laboratory in Hong Kong. All cases involving the use of pCMs or health products, which were subsequently confirmed to contain undeclared adulterants, from 2005 to 2015 were reviewed retrospectively. A total of 404 cases involving the use of 487 adulterated pCMs or health products with a total of 1234 adulterants were identified. The adulterants consisted of approved drugs, banned drugs, drug analogues and animal thyroid tissue. The six most common categories of adulterants detected were nonsteroidal anti-inflammatory drugs (17.7%), anorectics (15.3%), corticosteroids (13.8%), diuretics and laxatives (11.4%), oral antidiabetic agents (10.0%) and erectile dysfunction drugs (6.0%). Sibutramine was the most common adulterant (n = 155). The reported sources of these illicit products included over-the-counter drug stores, the internet and Chinese medicine practitioners. A significant proportion of patients (65.1%) had adverse effects attributable to these illicit products, including 14 severe and two fatal cases. Psychosis, iatrogenic Cushing syndrome and hypoglycaemia were the three most frequently encountered adverse effects. Adulteration of pCMs and health products with undeclared drugs poses severe health hazards. Public education and effective regulatory measures are essential to address the problem. © 2017 The British Pharmacological Society.

Challenges in Modern Anti-Doping Analytical Science.

Science.gov (United States)

Ayotte, Christiane; Miller, John; Thevis, Mario

2017-01-01

The challenges facing modern anti-doping analytical science are increasingly complex given the expansion of target drug substances, as the pharmaceutical industry introduces more novel therapeutic compounds and the internet offers designer drugs to improve performance. The technical challenges are manifold, including, for example, the need for advanced instrumentation for greater speed of analyses and increased sensitivity, specific techniques capable of distinguishing between endogenous and exogenous metabolites, or biological assays for the detection of peptide hormones or their markers, all of which require an important investment from the laboratories and recruitment of highly specialized scientific personnel. The consequences of introducing sophisticated and complex analytical procedures may result in the future in a change in the strategy applied by the Word Anti-Doping Agency in relation to the introduction and performance of new techniques by the network of accredited anti-doping laboratories. © 2017 S. Karger AG, Basel.

Batch-to-Batch Quality Consistency Evaluation of Botanical Drug Products Using Multivariate Statistical Analysis of the Chromatographic Fingerprint

OpenAIRE

Xiong, Haoshu; Yu, Lawrence X.; Qu, Haibin

2013-01-01

Botanical drug products have batch-to-batch quality variability due to botanical raw materials and the current manufacturing process. The rational evaluation and control of product quality consistency are essential to ensure the efficacy and safety. Chromatographic fingerprinting is an important and widely used tool to characterize the chemical composition of botanical drug products. Multivariate statistical analysis has showed its efficacy and applicability in the quality evaluation of many ...

21 CFR 211.110 - Sampling and testing of in-process materials and drug products.

Science.gov (United States)

2010-04-01

... PHARMACEUTICALS Production and Process Controls § 211.110 Sampling and testing of in-process materials and drug... capsule weight variation; (2) Disintegration time; (3) Adequacy of mixing to assure uniformity and... production process, e.g., at commencement or completion of significant phases or after storage for long...

The Use of Herbal Drugs in Organic Animal Production: The Case of Ethnoveterinary Medicine in Central Anatolia Region

Directory of Open Access Journals (Sweden)

Çağrı Çağlar Sinmez

2017-12-01

Full Text Available Organic animal production is a natural breeding system in which animal health is protected by giving priority to alternative medicines and treatment as needed by applying appropriate management and feeding methods based on the physiological requirements of animals. Increasing numbers of strains resistant to antibiotics and antiparasitic drugs used in animal breeding have brought about the search for alternative herbal remedies that lead to drug residues in animal products and lead to important health problems in people consuming these products. In this study, it was aimed to evaluate the therapeutic and protective effects of herbal drugs used in organic animal production in ethnoveterinary medicine in the Central Anatolia Region. The material of the study collected as written and declared facts as well as visual data were obtained from animal breeders in the Central Anatolia Region. The results indicated that 30 herbal drugs were used for the treatment of internal diseases, surgical diseases, obstetric and gynecological problems and parasitic diseases in cattle, sheep, horse, poultry, bee, and dog species. Based on the evaluation of the facts that the use of all kinds of synthetic drugs, especially antibiotics, is prohibited or restricted in organic livestock, it can be said that natural herbal drugs instead of artificial substances will provide positive contributions in the protection and treatment of herd health.

DEVELOPMENT AND REGISTRATION OF CHIRAL DRUGS

NARCIS (Netherlands)

WITTE, DT; ENSING, K; FRANKE, JP; DEZEEUW, RA

1993-01-01

In this review we describe the impact of chirality on drug development and registration in the United States, Japan and the European Community. Enantiomers may have differences in their pharmacological profiles, and, therefore, chiral drugs ask for special analytical and pharmacological attention

An Overview of Analytical Determination of Diltiazem, Cimetidine, Ranitidine, and Famotidine by UV Spectrophotometry and HPLC Technique

Directory of Open Access Journals (Sweden)

Nighat Shafi

2013-01-01

Full Text Available This review article recapitulates the analytical methods for the quantitative determinations of diltiazem and three H2 receptor antagonists (cimetidine, ranitidine, and famotidine by one of the spectroscopic technique (UV spectrophotometery and separation technique such as high-performance liquid chromatography (HPLC. The clinical and pharmaceutical analysis of these drugs requires effective analytical procedures for quality control, pharmaceutical dosage formulations, and biological fluids. An extensive survey of the literature published in various analytical and pharmaceutical chemistry-related journals has been compiled in its review. A synopsis of reported spectrophotometric and high-performance liquid chromatographic methods for individual drug is integrated. This appraisal illustrates that majority of the HPLC methods reviewed are based on the quantitative analysis of drugs in biological fluids, and they are appropriate for therapeutic drug monitoring purpose.

Drug screening in clinical or forensic toxicology: are there differences?

Science.gov (United States)

Gerostamoulos, Dimitri; Beyer, Jochen

2010-09-01

Legal and medical practitioners need to remember that, with respect to drug analysis, there are two distinct disciplines in analytical toxicology concerned with human biological matrices, namely clinical and forensic toxicology. Both fields use similar analytical techniques designed to detect and quantify drugs, chemicals and poisons in fluids or tissues. In clinical toxicology, analytical results help to specify the appropriate treatment of a poisoned or intoxicated patient. In forensic toxicology, the results often play a vital role in determining the possible impairment or behavioural changes in an individual, or the contribution of drugs or poisons to death in a medico-legal investigation. This column provides an overview of the similarities and differences inherent in clinical and forensic toxicology.

A Review on the Design Structure Matrix as an Analytical Tool for Product Development Management

OpenAIRE

Mokudai, Takefumi

2006-01-01

This article reviews fundamental concepts and analytical techniques of design structure matrix (DSM) as well as recent development of DSM studies. The DSM is a matrix representation of relationships between components of a complex system, such as products, development organizations and processes. Depending on targets of analysis, there are four basic types of DSM: Component-based DSM, Team-based DSM, Task-based DSM, and Parameter-based DSM. There are two streams of recent DSM studies: 1) ...

Advances in downstream processing of biologics - Spectroscopy: An emerging process analytical technology.

Science.gov (United States)

Rüdt, Matthias; Briskot, Till; Hubbuch, Jürgen

2017-03-24

Process analytical technologies (PAT) for the manufacturing of biologics have drawn increased interest in the last decade. Besides being encouraged by the Food and Drug Administration's (FDA's) PAT initiative, PAT promises to improve process understanding, reduce overall production costs and help to implement continuous manufacturing. This article focuses on spectroscopic tools for PAT in downstream processing (DSP). Recent advances and future perspectives will be reviewed. In order to exploit the full potential of gathered data, chemometric tools are widely used for the evaluation of complex spectroscopic information. Thus, an introduction into the field will be given. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

A review on development of analytical methods to determine monitorable drugs in serum and urine by micellar liquid chromatography using direct injection.

Science.gov (United States)

Esteve-Romero, Josep; Albiol-Chiva, Jaume; Peris-Vicente, Juan

2016-07-05

Therapeutic drug monitoring is a common practice in clinical studies. It requires the quantification of drugs in biological fluids. Micellar liquid chromatography (MLC), a well-established branch of Reverse Phase-High Performance Liquid Chromatography (RP-HPLC), has been proven by many researchers as a useful tool for the analysis of these matrices. This review presents several analytical methods, taken from the literature, devoted to the determination of several monitorable drugs in serum and urine by micellar liquid chromatography. The studied groups are: anticonvulsants, antiarrhythmics, tricyclic antidepressants, selective serotonin reuptake inhibitors, analgesics and bronchodilators. We detail the optimization strategy of the sample preparation and the main chromatographic conditions, such as the type of column, mobile phase composition (surfactant, organic solvent and pH), and detection. The finally selected experimental parameters, the validation, and some applications have also been described. In addition, their performances and advantages have been discussed. The main ones were the possibility of direct injection, and the efficient chromatographic elution, in spite of the complexity of the biological fluids. For each substance, the measured concentrations were accurate and precise at their respective therapeutic range. It was found that the MLC-procedures are fast, simple, inexpensive, ecofriendly, safe, selective, enough sensitive and reliable. Therefore, they represent an excellent alternative for the determination of drugs in serum and urine for monitoring purposes. Copyright © 2016 Elsevier B.V. All rights reserved.

The impact of the Orphan Drug Act on drug discovery.

Science.gov (United States)

Haffner, Marlene E; Maher, Paul D

2006-11-01

For nearly a quarter of a century the FDA Office of Orphan Products Development has administered the US Orphan Drug Act, which assists in bringing a wide variety of drug and biological (drug) products to treat rare diseases to market. Enthusiasm for rare disease product development has been sustained, seen throughout a wide spectrum of product types and disease conditions, and has resulted in clinically meaningful medical advances. Development of programmes for rare disease treatment worldwide, coupled with the development of drugs for diseases affecting developing countries, attests to the strength of this legislation. The marketing of almost 300 products in the US for rare diseases also testifies to the depth and intensity of scientific endeavour in this area.

New trends in the analytical determination of emerging contaminants and their transformation products in environmental waters.

Science.gov (United States)

Agüera, Ana; Martínez Bueno, María Jesús; Fernández-Alba, Amadeo R

2013-06-01

Since the so-called emerging contaminants were established as a new group of pollutants of environmental concern, a great effort has been devoted to the knowledge of their distribution, fate and effects in the environment. After more than 20 years of work, a significant improvement in knowledge about these contaminants has been achieved, but there is still a large gap of information on the growing number of new potential contaminants that are appearing and especially of their unpredictable transformation products. Although the environmental problem arising from emerging contaminants must be addressed from an interdisciplinary point of view, it is obvious that analytical chemistry plays an important role as the first step of the study, as it allows establishing the presence of chemicals in the environment, estimate their concentration levels, identify sources and determine their degradation pathways. These tasks involve serious difficulties requiring different analytical solutions adjusted to purpose. Thus, the complexity of the matrices requires highly selective analytical methods; the large number and variety of compounds potentially present in the samples demands the application of wide scope methods; the low concentrations at which these contaminants are present in the samples require a high detection sensitivity, and high demands on the confirmation and high structural information are needed for the characterisation of unknowns. New developments on analytical instrumentation have been applied to solve these difficulties. Furthermore and not less important has been the development of new specific software packages intended for data acquisition and, in particular, for post-run analysis. Thus, the use of sophisticated software tools has allowed successful screening analysis, determining several hundreds of analytes, and assisted in the structural elucidation of unknown compounds in a timely manner.

Thermodynamics of Highly Supersaturated Aqueous Solutions of Poorly Water-Soluble Drugs-Impact of a Second Drug on the Solution Phase Behavior and Implications for Combination Products.

Science.gov (United States)

Trasi, Niraj S; Taylor, Lynne S

2015-08-01

There is increasing interest in formulating combination products that contain two or more drugs. Furthermore, it is also common for different drug products to be taken simultaneously. This raises the possibility of interactions between different drugs that may impact formulation performance. For poorly water-soluble compounds, the supersaturation behavior may be a critical factor in determining the extent of oral absorption. The goal of the current study was to evaluate the maximum achievable supersaturation for several poorly water-soluble compounds alone, and in combination. Model compounds included ritonavir, lopinavir, paclitaxel, felodipine, and diclofenac. The "amorphous solubility" for the pure drugs was determined using different techniques and the change in this solubility was then measured in the presence of differing amounts of a second drug. The results showed that "amorphous solubility" of each component in aqueous solution is substantially decreased by the second component, as long as the two drugs are miscible in the amorphous state. A simple thermodynamic model could be used to predict the changes in solubility as a function of composition. This information is of great value when developing co-amorphous or other supersaturating formulations and should contribute to a broader understanding of drug-drug physicochemical interactions in in vitro assays as well as in the gastrointestinal tract. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

An analytical hierarchy process and fuzzy inference system tsukamoto for production planning: a review and conceptual research

Directory of Open Access Journals (Sweden)

Abdul Talib Bon

2015-03-01

Full Text Available Production planning is an area that is very important on the corporate strategy-level decision-making, especially in the manufacturing companies. The problems that often arise in the production planning are the factors that affect the decline of production and uncertainty that often complicate the decision-making in the production process. These factors are derived from the company’s internal and external factors. The purpose of this study is to introduce the Analytical Hierarchy Process as an effective method that can help to determine the priority of the production factors, so as to facilitate and accelerate decision-making. Other than the AHP methods, this paper will introduce the Tsukamoto Fuzzy Inference System as a method that can help to determine how much product to be manufactured by the company using the variables in the form of fuzzy numbers. These methods hopefully can assist in a better decision making process in the production process and manufacturing generally.

21 CFR 212.90 - What actions must I take to control the distribution of PET drug products?

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 4 2010-04-01 2010-04-01 false What actions must I take to control the... POSITRON EMISSION TOMOGRAPHY DRUGS (Eff. 12-12-2011) Distribution § 212.90 What actions must I take to control the distribution of PET drug products? (a) Written distribution procedures. You must establish...

Pharmaceutical product development: A quality by design approach

Science.gov (United States)

Pramod, Kannissery; Tahir, M. Abu; Charoo, Naseem A.; Ansari, Shahid H.; Ali, Javed

2016-01-01

The application of quality by design (QbD) in pharmaceutical product development is now a thrust area for the regulatory authorities and the pharmaceutical industry. International Conference on Harmonization and United States Food and Drug Administration (USFDA) emphasized the principles and applications of QbD in pharmaceutical development in their guidance for the industry. QbD attributes are addressed in question-based review, developed by USFDA for chemistry, manufacturing, and controls section of abbreviated new drug applications. QbD principles, when implemented, lead to a successful product development, subsequent prompt regulatory approval, reduce exhaustive validation burden, and significantly reduce post-approval changes. The key elements of QbD viz., target product quality profile, critical quality attributes, risk assessments, design space, control strategy, product lifecycle management, and continual improvement are discussed to understand the performance of dosage forms within design space. Design of experiments, risk assessment tools, and process analytical technology are also discussed for their role in QbD. This review underlines the importance of QbD in inculcating science-based approach in pharmaceutical product development. PMID:27606256

Pharmaceutical product development: A quality by design approach.

Science.gov (United States)

Pramod, Kannissery; Tahir, M Abu; Charoo, Naseem A; Ansari, Shahid H; Ali, Javed

2016-01-01

The application of quality by design (QbD) in pharmaceutical product development is now a thrust area for the regulatory authorities and the pharmaceutical industry. International Conference on Harmonization and United States Food and Drug Administration (USFDA) emphasized the principles and applications of QbD in pharmaceutical development in their guidance for the industry. QbD attributes are addressed in question-based review, developed by USFDA for chemistry, manufacturing, and controls section of abbreviated new drug applications. QbD principles, when implemented, lead to a successful product development, subsequent prompt regulatory approval, reduce exhaustive validation burden, and significantly reduce post-approval changes. The key elements of QbD viz., target product quality profile, critical quality attributes, risk assessments, design space, control strategy, product lifecycle management, and continual improvement are discussed to understand the performance of dosage forms within design space. Design of experiments, risk assessment tools, and process analytical technology are also discussed for their role in QbD. This review underlines the importance of QbD in inculcating science-based approach in pharmaceutical product development.

Global Simulation of Bioenergy Crop Productivity: Analytical Framework and Case Study for Switchgrass

Energy Technology Data Exchange (ETDEWEB)

Kang, Shujiang [ORNL; Kline, Keith L [ORNL; Nair, S. Surendran [University of Tennessee, Knoxville (UTK); Nichols, Dr Jeff A [ORNL; Post, Wilfred M [ORNL; Brandt, Craig C [ORNL; Wullschleger, Stan D [ORNL; Wei, Yaxing [ORNL; Singh, Nagendra [ORNL

2013-01-01

A global energy crop productivity model that provides geospatially explicit quantitative details on biomass potential and factors affecting sustainability would be useful, but does not exist now. This study describes a modeling platform capable of meeting many challenges associated with global-scale agro-ecosystem modeling. We designed an analytical framework for bioenergy crops consisting of six major components: (i) standardized natural resources datasets, (ii) global field-trial data and crop management practices, (iii) simulation units and management scenarios, (iv) model calibration and validation, (v) high-performance computing (HPC) simulation, and (vi) simulation output processing and analysis. The HPC-Environmental Policy Integrated Climate (HPC-EPIC) model simulated a perennial bioenergy crop, switchgrass (Panicum virgatum L.), estimating feedstock production potentials and effects across the globe. This modeling platform can assess soil C sequestration, net greenhouse gas (GHG) emissions, nonpoint source pollution (e.g., nutrient and pesticide loss), and energy exchange with the atmosphere. It can be expanded to include additional bioenergy crops (e.g., miscanthus, energy cane, and agave) and food crops under different management scenarios. The platform and switchgrass field-trial dataset are available to support global analysis of biomass feedstock production potential and corresponding metrics of sustainability.

Analytical parametrization and shape classification of anomalous HH production in the EFT approach

CERN Document Server

Carvalho, Alexandra; Manzano, Pablo de Castro; Dorigo, Tommaso; Goertz, Florian; Gouzevich, Maxime; Tosi, Mia

2016-01-01

In this document we study the effect of anomalous Higgs boson couplings on non-resonant pair production of Higgs bosons ($HH$) at the LHC. We explore the space of the five parameters $\\kappa_{\\lambda}$, $\\kappa_{t}$, $c_2$, $c_g$, and $c_{2g}$ in terms of the corresponding kinematics of the final state, and describe a partition of the space into a limited number of regions featuring similar phenomenology in the kinematics of $HH$ final state. We call clusters the sets of points belonging to the same region; to each cluster corresponds a representative point which we call a benchmark. We discuss a possible technique to estimate the sensitivity of an experimental search to the kinematical differences between the phenomenology of the benchmark points and the rest of the parameter space contained in the corresponding cluster. We also provide an analytical parametrization of the cross-section modifications that the variation of anomalous couplings produces with respect to standard model $HH$ production along with ...

Determination of different recreational drugs in sweat by headspace solid-phase microextraction gas chromatography mass spectrometry (HS-SPME GC/MS): Application to drugged drivers.

Science.gov (United States)

Gentili, Stefano; Mortali, Claudia; Mastrobattista, Luisa; Berretta, Paolo; Zaami, Simona

2016-09-10

A procedure based on headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography/mass spectrometry (GC/MS) has been developed for the determination of most commonly used drugs of abuse in sweat of drivers stopped during roadside controls. DrugWipe 5A sweat screening device was used to collect sweat by a specific pad rubbed gently over forehead skin surface. The procedure involved an acid hydrolysis, a HS-SPME extraction for drugs of abuse but Δ(9)-tetrahydrocannabinol, which was directly extracted in alkaline medium HS-SPME conditions, a GC separation of analytes by a capillary column and MS detection by electron impact ionisation. The method was linear from the limit of quantification (LOQ) to 50ng drug per pad (r(2)≥0.99), with an intra- and inter-assay precision and accuracy always less than 15% and an analytical recovery between 95.1% and 102.8%, depending on the considered analyte. Using the validated method, sweat from 60 apparently intoxicated drivers were found positive to one or more drugs of abuse, showing sweat patches testing as a viable economic and simple alternative to conventional (blood and/or urine) and non conventional (oral fluid) testing of drugs of abuse in drugged drivers. Copyright © 2016 Elsevier B.V. All rights reserved.

Microvesicle formulations used in topical drugs and cosmetics affect product efficiency, performance and allergenicity

DEFF Research Database (Denmark)

Madsen, Jakob Torp; Ejner Andersen, Klaus

2010-01-01

transdermal delivery more efficient for a number of drugs. Vesicular systems may also allow a more precise drug delivery to the site of action (ie, the hair follicles) and thereby minimize the applied drug concentration, reducing potential side effects. On the other hand, this may increase the risk of other......Attempts to improve the formulations of topical products are continuing processes (ie, to increase cosmetic performance, enhance effects, and protect ingredients from degradation). The development of micro- and nanovesicular systems has led to the marketing of topical drugs and cosmetics that use...... these technologies. Several articles have reported improved clinical efficacy by the encapsulation of pharmaceuticals in vesicular systems, and the numbers of publications and patents are rising. Some vesicular systems may deliver the drug deeper in the skin as compared to conventional vehicles, or even make...

Degradation of the tricyclic antipsychotic drug chlorpromazine under environmental conditions, identification of its main aquatic biotic and abiotic transformation products by LC-MSn and their effects on environmental bacteria.

Science.gov (United States)

Trautwein, Christoph; Kümmerer, Klaus

2012-03-15

The search for environmental transformation products of organic pollutants (like drugs) is a difficult task and usually only few compounds are detected. This might be due to effective degradation but could also be a result of analytical deficits dealing with complex matrices. Especially transformation products of very low concentrations in sludge were difficult to identify so far. Additionally, the use of standard separation techniques might lead to the loss of isomeric compounds, which possess identical spectroscopic and spectrometric properties. To date no complete study investigating the environmental fate of any tricyclic antipsychotic drug has been reported. Therefore, this study investigated the popular neuroleptic drug chlorpromazine and its potential transformation by all main environmental pathways: aerobic and anaerobic biodegradation as well as abiotic photolytic degradation by sunlight. Analysis of test samples by high performance liquid chromatography coupled to multiple stage mass-spectrometry (HPLC-MS(n)) allowed the detection of numerous compounds. Further, the use of a special software allowed distinguishing between transformation products of small intensities and background "noise" caused by sludge or matrix. Three aerobic tests of different bacterial density (the Closed Bottle test, OECD 301D; the Manometric Respiratory test, OECD 301F; the modified Zahn-Wellens test, 302B; one anaerobic test (a modified anaerobic degradation test according to ISO 11734) as well as a photodegradation test were performed in the present study. According to the individual test guidelines, chlorpromazine had to be classified as not biodegradable in all of the biodegradation tests. However, a special chromatographic column and gradient along with mass spectrometric fragmentation experiments of higher order uncovered the presence of a total of 61 abiotic and biotic transformation products which where formed during the course of the tests. The structures of three

78 FR 48172 - Minimizing Risk for Children's Toy Laser Products; Draft Guidance for Industry and Food and Drug...

Science.gov (United States)

2013-08-07

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-1092] Minimizing Risk for Children's Toy Laser Products; Draft Guidance for Industry and Food and Drug Administration Staff; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food...

Antineoplastic Drugs

Science.gov (United States)

Sadée, Wolfgang; El Sayed, Yousry Mahmoud

The limited scope of therapeutic drug-level monitoring in cancer chemotherapy results from the often complex biochemical mechanisms that contribute to antineoplastic activity and obscure the relationships among drug serum levels and therapeutic benefits. Moreover, new agents for cancer chemotherapy are being introduced at a more rapid rate than for the treatment of other diseases, although the successful application of therapeutic drug-level monitoring may require several years of intensive study of the significance of serum drug levels. However, drug level monitoring can be of considerable value during phase I clinical trials of new antineoplastic agents in order to assess drug metabolism, bioavailability, and intersubject variability; these are important parameters in the interpretation of clinical studies, but have no immediate benefit to the patient. High performance liquid chromatography (HPLC) probably represents the most versatile and easily adaptable analytical technique for drug metabolite screening (1). HPLC may therefore now be the method of choice during phase I clinical trials of antineoplastic drugs. For example, within a single week we developed an HPLC assay—using a C18 reverse-phase column, UV detection, and direct serum injection after protein precipitation—for the new radiosensitizer, misonidazole (2).

Development of analytical methods relating to aerosol and fission product release from hot and boiling sodium pools

International Nuclear Information System (INIS)

Mainka, E.

1978-11-01

Analytical methods are described for (a) sodium; (b) the following anions of sodium aerosols: OH - , CO 2 - and HCO 3 - ; (c) fission products Cs and Sr. For sodium, the ion selective electrode was used. The anions were determined by a titration method using phenolphthalein and methyl orange as indicators. Atomic absorption spectroscopy was used for Cs and Sr. (U.K.)

The effects of four different drugs administered through catheters on slime production in coagulase negative Staphylococci

Directory of Open Access Journals (Sweden)

J. Sedef Göçmen

2012-12-01

Full Text Available Objectives: Higher rate of slime production has been found in pathogen bacteria strains. Accordingly, the factors thatcontribute to higher slime production rate increase the infection risk, while the factors that reduce the slime productionrate will reduce the infection risk. The effect of some drugs that are administered through catheters in intensive careunits on slime production with coagulase negative Staphylococci was investigated.Materials and methods: In this study, the effect of four different preparations containing Glyceryl trinitrate (Perlinganit®, Dexmedetomidine (Precedex®, Esmolol (Brevibloc®, and Propofol (Propofol® on slime production of 24Staphylococcus epidermidis strains isolated from blood cultures of patients, and reference strain were investigated. Slimeproduction was determined using ‘the quantitative microdilution plaque test’ described by Christensen.Results: Under controlled medium, eight strains formed slimes, and in the media containing esmolol, glyceryl trinitrate,dexmedetomidine, and propofol slimes were positive for five, 21, 15, and 18 strains, respectively. The rate of slime productionin glyceryl trinitrate, dexmedetomidine, and propofol containing media were higher than that of the controls.Conclusions: In the light of the results of this study, it is concluded that the drugs and/or additives increase the rate ofslime production. The effects of the preparations administered through catheters on slime production should be investigated,and these effects should be kept in mind during their use. J Microbiol Infect Dis 2012; 2(4: 150-154Key words: Slime Production, Coagulase Negative Staphyloccoci, Parenteral drugs

Nanostructured materials for selective recognition and targeted drug delivery

International Nuclear Information System (INIS)

Kotrotsiou, O; Kotti, K; Dini, E; Kammona, O; Kiparissides, C

2005-01-01

Selective recognition requires the introduction of a molecular memory into a polymer matrix in order to make it capable of rebinding an analyte with a very high specificity. In addition, targeted drug delivery requires drug-loaded vesicles which preferentially localize to the sites of injury and avoid uptake into uninvolved tissues. The rapid evolution of nanotechnology is aiming to fulfill the goal of selective recognition and optimal drug delivery through the development of molecularly imprinted polymeric (MIP) nanoparticles, tailor-made for a diverse range of analytes (e.g., pharmaceuticals, pesticides, amino acids, etc.) and of nanostructured targeted drug carriers (e.g., liposomes and micelles) with increased circulation lifetimes. In the present study, PLGA microparticles containing multilamellar vesicles (MLVs), and MIP nanoparticles were synthesized to be employed as drug carriers and synthetic receptors respectively

Assessing the drug-likeness of lamellarins, a marine-derived natural product class with diverse oncological activities.

Science.gov (United States)

Chittchang, Montakarn; Gleeson, M Paul; Ploypradith, Poonsakdi; Ruchirawat, Somsak

2010-06-01

Natural products currently represent an underutilized source of leads for the pharmaceutical industry, especially when one considers that almost 50% of all drugs were either derived from such sources or are very closely related. Lamellarins are a class of natural products with diverse biological activities and have entered into preclinical development for the treatment of multidrug-resistant tumors. Although these compounds demonstrated good cell penetration, as observed by their low microM activity in whole cell models, they have not been extensively profiled from a physicochemical point of view, and this is the goal of this study. For this study, we have determined the experimental logP values of a set of 25 lamellarins, given it is the single most important parameter in determining multiple ADMET parameters. We also discuss the relationship between this natural product class, natural product derivatives in development and on the market, oral marketed drugs, as well as drug molecules in development, using a range of physicochemical parameters in conjunction with principal components analysis (PCA). The impact of this systematic analysis on our ongoing medicinal chemistry strategy is also discussed. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

Comparative analytics of infusion pump data across multiple hospital systems.

Science.gov (United States)

Catlin, Ann Christine; Malloy, William X; Arthur, Karen J; Gaston, Cindy; Young, James; Fernando, Sudheera; Fernando, Ruchith

2015-02-15

A Web-based analytics system for conducting inhouse evaluations and cross-facility comparisons of alert data generated by smart infusion pumps is described. The Infusion Pump Informatics (IPI) project, a collaborative effort led by research scientists at Purdue University, was launched in 2009 to provide advanced analytics and tools for workflow analyses to assist hospitals in determining the significance of smart-pump alerts and reducing nuisance alerts. The IPI system allows facility-specific analyses of alert patterns and trends, as well as cross-facility comparisons of alert data uploaded by more than 55 participating institutions using different types of smart pumps. Tools accessible through the IPI portal include (1) charts displaying aggregated or breakout data on the top drugs associated with alerts, numbers of alerts per device or care area, and override-to-alert ratios, (2) investigative reports that can be used to characterize and analyze pump-programming errors in a variety of ways (e.g., by drug, by infusion type, by time of day), and (3) "drill-down" workflow analytics enabling users to evaluate alert patterns—both internally and in relation to patterns at other hospitals—in a quick and efficient stepwise fashion. The formation of the IPI analytics system to support a community of hospitals has been successful in providing sophisticated tools for member facilities to review, investigate, and efficiently analyze smart-pump alert data, not only within a member facility but also across other member facilities, to further enhance smart pump drug library design. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Production of candidate natural matrix reference materials for micro-analytical techniques

International Nuclear Information System (INIS)

Zeisler, R.; Fajgelj, A.; Zeiller, E.

2002-01-01

Homogeneity is considered to be the most vital prerequisite for a certified reference material (CRM); more stringent requirements exist for the analysis of small subsamples. Many of the natural matrix CRMs are prepared from bulk samples by grinding and milling them to a certain particle size, which is expected to provide a more homogenous material; however recommended sample sizes for biological and environmental reference materials are found to be more than 100 mg. Since the milling of materials is costly and has some drawbacks, natural materials that already occur as small particles such as air particulate matter, certain sediments, and cellular biological materials may form the basis of the required reference materials. The nature of these materials, i.e. naturally occurring particles, may provide ideal model reference material. We describe here the production of the materials and preliminary tests, the evaluation for the micro-analytical techniques

Chiral drug analysis using mass spectrometric detection relevant to research and practice in clinical and forensic toxicology.

Science.gov (United States)

Schwaninger, Andrea E; Meyer, Markus R; Maurer, Hans H

2012-12-21

This paper reviews analytical approaches published in 2002-2012 for chiral drug analysis and their relevance in research and practice in the field of clinical and forensic toxicology. Separation systems such as gas chromatography, high performance liquid chromatography, capillary electromigration, and supercritical fluid chromatography, all coupled to mass spectrometry, are discussed. Typical applications are reviewed for relevant chiral analytes such as amphetamines and amphetamine-derived designer drugs, methadone, tramadol, psychotropic and other CNS acting drugs, anticoagulants, cardiovascular drugs, and some other drugs. Usefulness of chiral drug analysis in the interpretation of analytical results in clinical and forensic toxicology is discussed as well. Copyright © 2012 Elsevier B.V. All rights reserved.

Recombinant drugs-on-a-chip: The usage of capillary electrophoresis and trends in miniaturized systems – A review

Energy Technology Data Exchange (ETDEWEB)

Morbioli, Giorgio Gianini; Mazzu-Nascimento, Thiago; Aquino, Adriano [Instituto de Química de São Carlos, Universidade de São Paulo, Av. Trabalhador São-carlense, 400, 13566-590 São Carlos, SP (Brazil); Instituto Nacional de Ciência e Tecnologia de Bioanalítica, Campinas, SP (Brazil); Cervantes, Cesar [Instituto de Química de São Carlos, Universidade de São Paulo, Av. Trabalhador São-carlense, 400, 13566-590 São Carlos, SP (Brazil); Carrilho, Emanuel, E-mail: emanuel@iqsc.usp.br [Instituto de Química de São Carlos, Universidade de São Paulo, Av. Trabalhador São-carlense, 400, 13566-590 São Carlos, SP (Brazil); Instituto Nacional de Ciência e Tecnologia de Bioanalítica, Campinas, SP (Brazil)

2016-09-07

We present here a critical review covering conventional analytical tools of recombinant drug analysis and discuss their evolution towards miniaturized systems foreseeing a possible unique recombinant drug-on-a-chip device. Recombinant protein drugs and/or pro-drug analysis require sensitive and reproducible analytical techniques for quality control to ensure safety and efficacy of drugs according to regulatory agencies. The versatility of miniaturized systems combined with their low-cost could become a major trend in recombinant drugs and bioprocess analysis. Miniaturized systems are capable of performing conventional analytical and proteomic tasks, allowing for interfaces with other powerful techniques, such as mass spectrometry. Microdevices can be applied during the different stages of recombinant drug processing, such as gene isolation, DNA amplification, cell culture, protein expression, protein separation, and analysis. In addition, organs-on-chips have appeared as a viable alternative to testing biodrug pharmacokinetics and pharmacodynamics, demonstrating the capabilities of the miniaturized systems. The integration of individual established microfluidic operations and analytical tools in a single device is a challenge to be overcome to achieve a unique recombinant drug-on-a-chip device. - Highlights: • Principal analytical tools for analysis of recombinant drugs are presented. • A critical comparison among different substrates for fabrication of miniaturized systems is made. • Applications of miniaturized systems to produce recombinant drugs are shown. • Future trends of miniaturized systems capable of integrating analytical and proteomic tools in a single device are envisioned.

Recombinant drugs-on-a-chip: The usage of capillary electrophoresis and trends in miniaturized systems – A review

International Nuclear Information System (INIS)

Morbioli, Giorgio Gianini; Mazzu-Nascimento, Thiago; Aquino, Adriano; Cervantes, Cesar; Carrilho, Emanuel

2016-01-01

We present here a critical review covering conventional analytical tools of recombinant drug analysis and discuss their evolution towards miniaturized systems foreseeing a possible unique recombinant drug-on-a-chip device. Recombinant protein drugs and/or pro-drug analysis require sensitive and reproducible analytical techniques for quality control to ensure safety and efficacy of drugs according to regulatory agencies. The versatility of miniaturized systems combined with their low-cost could become a major trend in recombinant drugs and bioprocess analysis. Miniaturized systems are capable of performing conventional analytical and proteomic tasks, allowing for interfaces with other powerful techniques, such as mass spectrometry. Microdevices can be applied during the different stages of recombinant drug processing, such as gene isolation, DNA amplification, cell culture, protein expression, protein separation, and analysis. In addition, organs-on-chips have appeared as a viable alternative to testing biodrug pharmacokinetics and pharmacodynamics, demonstrating the capabilities of the miniaturized systems. The integration of individual established microfluidic operations and analytical tools in a single device is a challenge to be overcome to achieve a unique recombinant drug-on-a-chip device. - Highlights: • Principal analytical tools for analysis of recombinant drugs are presented. • A critical comparison among different substrates for fabrication of miniaturized systems is made. • Applications of miniaturized systems to produce recombinant drugs are shown. • Future trends of miniaturized systems capable of integrating analytical and proteomic tools in a single device are envisioned.

Integration of in vitro biorelevant dissolution and in silico PBPK model of carvedilol to predict bioequivalence of oral drug products.

Science.gov (United States)

Ibarra, Manuel; Valiante, Cristian; Sopeña, Patricia; Schiavo, Alejandra; Lorier, Marianela; Vázquez, Marta; Fagiolino, Pietro

2018-06-15

Bioequivalence implementation in developing countries where a high proportion of similar drug products are being marketed has found several obstacles, impeding regulatory agencies to move forward with this policy. Biopharmaceutical quality of these products, several of which are massively prescribed, remains unknown. In this context, an in vitro-in silico-in vivo approach is proposed as a mean to screen product performance and target specific formulations for bioequivalence assessment. By coupling in vitro biorelevant dissolution testing in USP-4 Apparatus (flow-through cell) with physiologically-based pharmacokinetic (PBPK) modeling in PK-Sim® software (Bayer, Germany), the performance of seven similar products of carvedilol tablets containing 25 mg available in the Uruguayan market were compared with the brand-name drug Dilatrend®. In silico simulations for Dilatrend® were compared with published results of bioequivalence studies performed in fasting conditions allowing model development through a learning and confirming process. Single-dose pharmacokinetic profiles were then simulated for the brand-name drug and two similar drug products selected according to in vitro observations, in a virtual Caucasian population of 1000 subjects (50% male, aged between 18 and 50 years with standard body-weights). Population bioequivalence ratios were estimated revealing that in vitro differences in drug release would have a major impact in carvedilol maximum plasma concentration, leading to a non-bioequivalence outcome. Predictions support the need to perform in vivo bioequivalence for these products of extensive use. Application of the in vitro-in silico-in vivo approach stands as an interesting alternative to tackle and reduce drug product variability in biopharmaceutical quality. Copyright © 2018 Elsevier B.V. All rights reserved.

75 FR 48352 - Determination That MOTRIN (Ibuprofen) Tablets and Four Other Drug Products Were Not Withdrawn...

Science.gov (United States)

2010-08-10

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0391] Determination That MOTRIN (Ibuprofen) Tablets and Four Other Drug Products Were Not Withdrawn From Sale for... Applicant NDA 17-463 MOTRIN (ibuprofen) Tablets, 300 milligrams (mg), McNeil Consumer Healthcare, 7050 Camp...

A novel in situ hydrophobic ion paring (HIP) formulation strategy for clinical product selection of a nanoparticle drug delivery system.

Science.gov (United States)

Song, Young Ho; Shin, Eyoung; Wang, Hong; Nolan, Jim; Low, Susan; Parsons, Donald; Zale, Stephen; Ashton, Susan; Ashford, Marianne; Ali, Mir; Thrasher, Daniel; Boylan, Nicholas; Troiano, Greg

2016-05-10

The present studies were aimed at formulating AZD2811-loaded polylactic acid-polyethylene glycol (PLA-PEG) nanoparticles with adjustable release rates without altering the chemical structures of the polymer or active pharmaceutical ingredient (API). This was accomplished through the use of a hydrophobic ion pairing approach. A series of AZD2811-containing nanoparticles with a variety of hydrophobic counterions including oleic acid, 1-hydroxy-2-naphthoic acid, cholic acid, deoxycholic acid, dioctylsulfosuccinic acid, and pamoic acid is described. The hydrophobicity of AZD2811 was increased through formation of ion pairs with these hydrophobic counterions, producing nanoparticles with exceptionally high drug loading-up to five fold higher encapsulation efficiency and drug loading compared to nanoparticles made without hydrophobic ion pairs. Furthermore, the rate at which the drug was released from the nanoparticles could be controlled by employing counterions with various hydrophobicities and structures, resulting in release half-lives ranging from about 2 to 120h using the same polymer, nanoparticle size, and nanoemulsion process. Process recipe variables affecting drug load and release rate were identified, including pH and molarity of quench buffer. Ion pair formation between AZD2811 and pamoic acid as a model counterion was investigated using solubility enhancement as well as nuclear magnetic resonance spectroscopy to demonstrate solution-state interactions. Further evidence for an ion pairing mechanism of controlled release was provided through the measurement of API and counterion release profiles using high-performance liquid chromatography, which had stoichiometric relationships. Finally, Raman spectra of an AZD2811-pamoate salt compared well with those of the formulated nanoparticles, while single components (AZD2811, pamoic acid) alone did not. A library of AZD2811 batches was created for analytical and preclinical characterization. Dramatically improved

Analysis and analytical techniques

Energy Technology Data Exchange (ETDEWEB)

Batuecas Rodriguez, T [Department of Chemistry and Isotopes, Junta de Energia Nuclear, Madrid (Spain)

1967-01-01

The technology associated with the use of organic coolants in nuclear reactors depends to a large extent on the determination and control of their physical and chemical properties, and particularly on the viability, speed, sensitivity, precision and accuracy (depending on the intended usage) of the methods employed in detection and analytical determination. This has led to the study and development of numerous techniques, some specially designed for the extreme conditions involved in working with the types of product in question and others adapted from existing techniques. In the specific case of polyphenyl and hydropolyphenyl mixtures, which have been the principal subjects of study to date and offer greatest promise, the analytical problems are broadly as follows: Composition of initial product or virgin coolant composition of macro components and amounts of organic and inorganic impurities; Coolant during and after operation. Determination of gases and organic compounds produced by pyrolysis and radiolysis (degradation and polymerization products); Control of systems for purifying and regenerating the coolant after use. Dissolved pressurization gases; Detection of intermediate products during decomposition; these are generally very unstable (free radicals); Degree of fouling and film formation. Tests to determine potential formation of films; Corrosion of structural elements and canning materials; Health and safety. Toxicity, inflammability and impurities that can be activated. Although some of the above problems are closely interrelated and entail similar techniques, they vary as to degree of difficulty. Another question is the difficulty of distinguishing clearly between techniques for determining physical and physico-chemical properties, on one hand, and analytical techniques on the other. Any classification is therefore somewhat arbitrary (for example, in the case of dosimetry and techniques for determining mean molecular weights or electrical conductivity

Recent advances in immunosensor for narcotic drug detection

Science.gov (United States)

Gandhi, Sonu; Suman, Pankaj; Kumar, Ashok; Sharma, Prince; Capalash, Neena; Suri, C. Raman

2015-01-01

Introduction: Immunosensor for illicit drugs have gained immense interest and have found several applications for drug abuse monitoring. This technology has offered a low cost detection of narcotics; thereby, providing a confirmatory platform to compliment the existing analytical methods. Methods: In this minireview, we define the basic concept of transducer for immunosensor development that utilizes antibodies and low molecular mass hapten (opiate) molecules. Results: This article emphasizes on recent advances in immunoanalytical techniques for monitoring of opiate drugs. Our results demonstrate that high quality antibodies can be used for immunosensor development against target analyte with greater sensitivity, specificity and precision than other available analytical methods. Conclusion: In this review we highlight the fundamentals of different transducer technologies and its applications for immunosensor development currently being developed in our laboratory using rapid screening via immunochromatographic kit, label free optical detection via enzyme, fluorescence, gold nanoparticles and carbon nanotubes based immunosensing for sensitive and specific monitoring of opiates. PMID:26929925

Perspective: Dendrimer drugs for infection and inflammation.

Science.gov (United States)

Shaunak, Sunil

2015-12-18

Biologists are dissecting complex biological pathways at breath taking speed. It is opening up new opportunities for the therapeutic evaluation of novel dendrimer drugs. This review focuses on studies of small dendrimers decorated with sulfate, phosphonate, N-acetyl-cysteine, glucosamine and mannose in animal model studies of infection and inflammation. It highlights those animal model studies which have demonstrated the most promising dendrimer drug constructs as potential new medicines. The issues relating to their analytical chemistry that are slowing the progress of dendrimer drugs into the clinic are highlighted. It should be possible to solve these with additional analytical expertise because it is small dendrimers with only 16-32 peripheral groups that make for the best infection and inflammation related medicines. Public-private partnerships are now needed to progress these dendrimer drugs into proof-of-concept clinical trials. Copyright © 2015 Elsevier Inc. All rights reserved.

Case Study : Visual Analytics in Software Product Assessments

NARCIS (Netherlands)

Telea, Alexandru; Voinea, Lucian; Lanza, M; Storey, M; Muller, H

2009-01-01

We present how a combination of static source code analysis, repository analysis, and visualization techniques has been used to effectively get and communicate insight in the development and project management problems of a large industrial code base. This study is an example of how visual analytics

Analytic Expression of Geometric Discord in Arbitrary Mixture of any Two Bi-qubit Product Pure States

International Nuclear Information System (INIS)

Xie Chuan-Mei; Xing Hang; Zhang Zhan-Jun; Liu Yi-Min

2015-01-01

Quantum correlations in a family of states comprising any mixture of a pair of arbitrary bi-qubit product pure states are studied by employing geometric discord [Phys. Rev. Lett. 105 (2010) 190502] as the quantifier. First, the inherent symmetry in the family of states about local unitary transformations is revealed. Then, the analytic expression of geometric discords in the states is worked out. Some concrete discussions and analyses on the captured geometric discords are made so that their distinct features are exposed. It is found that, the more averagely the two bi-qubit product states are mixed, the bigger geometric discord the mixed state owns. Moreover, the monotonic relationships of geometric discord with different parameters are revealed. (paper)

Particle shedding from peristaltic pump tubing in biopharmaceutical drug product manufacturing.

Science.gov (United States)

Saller, Verena; Matilainen, Julia; Grauschopf, Ulla; Bechtold-Peters, Karoline; Mahler, Hanns-Christian; Friess, Wolfgang

2015-04-01

In a typical manufacturing setup for biopharmaceutical drug products, the fill and dosing pump is placed after the final sterile filtration unit in order to ensure adequate dispensing accuracy and avoid backpressure peaks. Given the sensitivity of protein molecules, peristaltic pumps are often preferred over piston pumps. However, particles may be shed from the silicone tubing employed. In this study, particle shedding and a potential turbidity increase during peristaltic pumping of water and buffer were investigated using three types of commercially available silicone tubing. In the recirculates, mainly particles of around 200 nm next to a very small fraction of particles in the lower micrometer range were found. Using 3D laser scanning microscopy, surface roughness of the inner tubing surface was found to be a determining factor for particle shedding from silicone tubing. As the propensity toward particle shedding varied between tubing types and also cannot be concluded from manufacturer's specifications, individual testing with the presented methods is recommended during tubing qualification. Choosing low abrasive tubing can help to further minimize the very low particle counts to be expected in pharmaceutical drug products. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Harnessing the potential of natural products in drug discovery from a cheminformatics vantage point.

Science.gov (United States)

Rodrigues, Tiago

2017-11-15

Natural products (NPs) present a privileged source of inspiration for chemical probe and drug design. Despite the biological pre-validation of the underlying molecular architectures and their relevance in drug discovery, the poor accessibility to NPs, complexity of the synthetic routes and scarce knowledge of their macromolecular counterparts in phenotypic screens still hinder their broader exploration. Cheminformatics algorithms now provide a powerful means of circumventing the abovementioned challenges and unlocking the full potential of NPs in a drug discovery context. Herein, I discuss recent advances in the computer-assisted design of NP mimics and how artificial intelligence may accelerate future NP-inspired molecular medicine.

Analytical detection and biological assay of antileukemic drug using gold nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Selvaraj, V. [Department of Chemical Engineering, Alagappa College of Technology, Anna University, Chennai 600025 (India)]. E-mail: rajselva_77@yahoo.co.in; Alagar, M. [Department of Chemical Engineering, Alagappa College of Technology, Anna University, Chennai 600025 (India)]. E-mail: mkalagar@yahoo.com; Hamerton, I. [Chemistry Division, School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey GU2 7XH (United Kingdom)

2006-11-12

Gold nanoparticles are reported and evaluated as probes for the detection of anticancer drug 6-mercaptopurine (6-MP). The nature of binding between 6-MP and the gold nanoparticles via complexation is investigated using ultraviolet-visible spectrum, cyclic voltammetry, transmission electron microscopy, fluorescence and Fourier transform infrared (FT-IR) spectroscopy. The bound antileukemic drug is fluorescent and the quenching property of gold nanoparticles could be exploited for biological investigations. The 6-MP-colloidal gold complex is observed to have appreciable antibacterial and antifungal activity against Micrococcus luteus, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Aspergillus fumigatus, and Aspergillus niger. The experimental studies suggest that gold nanoparticles have the potential to be used as effective carriers for anticancer drugs.

Comparison of Clobetasol Propionate Generics Using Simplified in Vitro Bioequivalence Method for Topical Drug Products.

Science.gov (United States)

Soares, Kelen Carine Costa; de Souza, Weidson Carlos; de Souza Texeira, Leonardo; da Cunha-Filho, Marcilio Sergio Soares; Gelfuso, Guilherme Martins; Gratieri, Tais

2017-11-20

The aim of this paper is to propose a simple in vitro skin penetration experiment in which the drug is extracted from the whole skin piece as a test valid for formulation screening and optimization during development process, equivalence assessment during quality control or post-approval after changes to the product. Twelve clobetasol propionate (CP) formulations (six creams and six ointments) from the local market were used as a model to challenge the proposed methodology in comparison to in vitro skin penetration following tape-stripping for drug extraction. To support the results, physicochemical tests for pH, viscosity, density and assay, as well as in vitro release were performed. Both protocols, extracting the drug from the skin using the tape-stripping technique or extracting from the full skin were capable of differentiating CP formulations. Only one formulation did not present statistical difference from the reference drug product in penetration tests and only other two oitments presented equivalent release to the reference. The proposed protocol is straightforward and reproducible. Results suggest the bioinequavalence of tested CP formulations reinforcing the necessity of such evaluations. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Essential Drugs Production in Brazil, Russia, India, China and South Africa (BRICS: Opportunities and Challenges

Directory of Open Access Journals (Sweden)

Zoheir Ezziane

2014-12-01

Full Text Available The objective of this work is to elucidate various essential drugs in the Brazil, Russia, India, China and South Africa (BRICS countries. It discusses the opportunities and challenges of the existing biotech infrastructure and the production of drugs and vaccines in member states of the BRICS. This research is based on a systematic literature review between the years 2000 and 2014 of documents retrieved from the databases Embase, PubMed/Medline, Global Health, and Google Scholar, and the websites of relevant international organizations, research institutions and philanthropic organizations. Findings vary from one member state to another. These include useful comparison between the BRICS countries in terms of pharmaceuticals expenditure versus total health expenditure, local manufacturing of drugs/vaccines using technology and know-how transferred from developed countries, and biotech entrepreneurial collaborations under the umbrella of the BRICS region. This study concludes by providing recommendations to support more of inter collaborations among the BRICS countries as well as between BRICS and many developing countries to shrink drug production costs. In addition, this collaboration would also culminate in reaching out to poor countries that are not able to provide their communities and patients with cost-effective essential medicines.

Essential drugs production in Brazil, Russia, India, China and South Africa (BRICS): opportunities and challenges.

Science.gov (United States)

Ezziane, Zoheir

2014-12-01

The objective of this work is to elucidate various essential drugs in the Brazil, Russia, India, China and South Africa (BRICS) countries. It discusses the opportunities and challenges of the existing biotech infrastructure and the production of drugs and vaccines in member states of the BRICS. This research is based on a systematic literature review between the years 2000 and 2014 of documents retrieved from the databases Embase, PubMed/Medline, Global Health, and Google Scholar, and the websites of relevant international organizations, research institutions and philanthropic organizations. Findings vary from one member state to another. These include useful comparison between the BRICS countries in terms of pharmaceuticals expenditure versus total health expenditure, local manufacturing of drugs/vaccines using technology and know-how transferred from developed countries, and biotech entrepreneurial collaborations under the umbrella of the BRICS region. This study concludes by providing recommendations to support more of inter collaborations among the BRICS countries as well as between BRICS and many developing countries to shrink drug production costs. In addition, this collaboration would also culminate in reaching out to poor countries that are not able to provide their communities and patients with cost-effective essential medicines.

Implications of the Food, Drug, and Cosmetic Act on the quality assurance of radiopharmaceuticals used in the United States

International Nuclear Information System (INIS)

Kishore, R.; Sheinin, E.B.

1990-01-01

The drug sections of the Federal Food, Drug, and Cosmetic Act (Title 21 U.S.C.) are intended to assure the consumer that drugs are safe and effective for their intended use. The Act requires that new drugs be approved by the FDA before they go on the market. The regulations for the new drug review process, are contained in the Code of Federal Regulations (CFR) Title 21, sections 312 for Investigational New Drugs (INDs), 314 for New Drug Applications (NDAs). Section 361 deals with radioactive drugs for certain research (RDR) uses. The regulations require that sufficient information be provided on the acceptable limits and the analytical methods used for the assurance of the identity, strength, quality, purity and the stability of the new drug as well as the raw materials used in the preparation of the new drug. The impact of the Act on the control of radiopharmaceutical products will be discussed

Medicaid Drug Rebate Program Data

Data.gov (United States)

U.S. Department of Health & Human Services — Product Data for Drugs in the Medicaid Drug Rebate Program. The rebate drug product data file contains the active drugs that have been reported by participating drug...

Permitting product liability litigation for FDA-approved drugs and devices promotes patient safety.

Science.gov (United States)

Kesselheim, A S

2010-06-01

In 2008 and 2009, the Supreme Court reviewed the question of whether patients injured by dangerous prescription drugs or medical devices can bring tort lawsuits against pharmaceutical and device manufacturers. The Court ruled that claims against device manufacturers were preempted while claims against pharmaceutical manufacturers were not. The threat of product liability lawsuits promotes patient safety by encouraging manufacturers to take greater responsibility in providing clear warnings about known adverse effects of their products.

Effect of radioimmunoassay procedures on therapeutic drug monitoring

International Nuclear Information System (INIS)

Kampa, I.S.

1985-01-01

Methods for the measurement of therapeutic drugs have covered every aspect of analysis from extraction to derivatization. In general, published methods were modified to shorten drug extractions and overall analysis time. The use of different standards, as well as the frequent omission of internal standards, often produced large and clinically unacceptable analytical variations. As a result, physicians would adjust drug dosages according to the physiological response to a standard dose. The introduction of radioimmunoassay techniques for the quantitation of therapeutic drugs have made a significant impact on the clinical chemistry laboratory. The similarities of the various assay methods and the technologists' familiarity with the assay protocols have produced clinically relevant results. Clinical laboratories are now able to frequently analyze a large number of samples with acceptable accuracy and precision. The esoteric test once performed infrequently is today a routine analytical assay often performed STAT. Therapeutic drug monitoring has become a major activity in many clinical laboratories

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

Science.gov (United States)

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

2016-01-01

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

Dominance of pre-analytical over analytical variation for measurement of methadone and its main metabolite in postmortem femoral blood

DEFF Research Database (Denmark)

Linnet, Kristian; Johansen, Sys Stybe; Buchard, Anders

2008-01-01

cases comprising mainly drug addicts. A chiral LC-MS/MS method was used for measurement of the R- and S-enantiomers of methadone and its main metabolite 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium (EDDP). The analytical CV% was determined to be in the range 3-4% for methadone enantiomers and 4...

[Drugs and light].

Science.gov (United States)

Tønnesen, H H

1997-06-30

The number of drugs that are found to be photochemically unstable or able to induce phototoxic side-effects is steadily increasing. It can be difficult, however, to obtain relevant information on the photoreactivity of drugs or drug products from the commonly used handbooks. This is because of lack of standard methods of evaluation or a requirement for official specifications for a given product. The author points to the main problems connected with interactions between drugs and light in vitro and in vivo. The most obvious result of exposure to light is reduced potency of the drug because of photodecomposition. Adverse effects due to the formation of photodegradation products during storage and use have also been reported. The drug substance can further cause light-induced side-effects after administration to the patient, e.g. phototoxicity and photoallergy. More data on photoreactivity are needed in order to minimize the side-effects of frequently used drugs. The article includes a list of potential photosensitizing drug substances on the Norwegian market.

An overview of analytical activities of control laboratory in NFC

International Nuclear Information System (INIS)

Balaji Rao, Y.; Subba Rao, Y.; Saibaba, N.

2015-01-01

As per the mandate of Department of Atomic Energy (DAE), Nuclear Fuel Complex (NFC) was established in 1971 for manufacturing Fuel Sub-assemblies for both PHWRs and BWRs operating in India on industrial scale. Control Laboratory (C.Lab) was envisaged as a centralized analytical facility to achieve the objectives of NFC on the similar lines of its predecessor, Analytical Chemistry Division at BARC. With highest ever production of 1200 MT of PHWR Fuel and 16 lakhs PHWR Fuel Tubes achieved during production year of 2014-15 and with increase in demand further for fuel requirements, NFC has got demanding situation in next year and accordingly, C. Lab has also geared up to meet the challenging demands of all the production plant. The average annual analytical load comes around 5 Lakhs estimations and to manage such a massive analytical load a proper synergy between good chemistry, process conditions and analytical methods is a necessity and laboratory is able to meet this important requirement consistently

Hair analysis for the detection of drug use-is there potential for evasion?

Science.gov (United States)

Marrinan, Shanna; Roman-Urrestarazu, Andres; Naughton, Declan; Levari, Emerlinda; Collins, John; Chilcott, Robert; Bersani, Giuseppe; Corazza, Ornella

2017-05-01

Hair analysis for illicit substances is widely used to detect chronic drug consumption or abstention from drugs. Testees are increasingly seeking ways to avoid detection by using a variety of untested adulterant products (e.g., shampoos, cleansers) widely sold online. This study aims to investigate adulteration of hair samples and to assess effectiveness of such methods. The literature on hair test evasion was searched for on PubMed or MEDLINE, Psycinfo, and Google Scholar. Given the sparse nature of peer-reviewed data on this subject, results were integrated with a qualitative assessment of online sources, including user-orientated information or commercial websites, drug fora and "chat rooms". Over four million web sources were identified in a Google search by using "beat hair drug test" and the first 86 were monitored on regular basis and considered for further analysis. Attempts to influence hair test results are widespread. Various "shampoos," and "cleansers" among other products, were found for sale, which claim to remove analytes. Often advertised with aggressive marketing strategies, which include discounts, testimonials, and unsupported claims of efficacy. However, these products may pose serious health hazards and are also potentially toxic. In addition, many anecdotal reports suggest that Novel Psychoactive Substances are also consumed as an evasion technique, as these are not easily detectable via standard drug test. Recent changes on Novel Psychoactive Substances legislations such as New Psychoactive Bill in the UK might further challenge the testing process. Further research is needed by way of chemical analysis and trial of the adulterant products sold online and their effects as well as the development of more sophisticated hair testing techniques. Copyright © 2017 John Wiley & Sons, Ltd.

Analytical chemistry equipment for radioactive products; Installation de chimie analytique pour produits radioactifs

Energy Technology Data Exchange (ETDEWEB)

Douis, M; Guillon, A; Laurent, H; Sauvagnac, R [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1959-07-01

The report deals with a shielded enclosure, hermetic, for analytical examination and handling of radioactive products. Remote handling for the following is provided: pipette absorption - weighing - centrifuging - desiccation - volumetric - pH measurement - potentiometric - colorimetric - polarographic. The above list is not restrictive: the enclosure is designed for the rapid installation of other equipment. Powerfully ventilated and screened to 400 m-curies long life fission product levels by 5 cm of lead, the enclosure is fully safe to the stated level. (author) [French] La presente communication decrit une enceinte etanche et blindee permettant un travail et un controle analytique sur des produits radioactifs. Les techniques suivantes sont adaptees pour une manipulation a distance: pipettage, pesees, centrifugation, dessiccation, volumetrie, mesure de pH, potentiometrie, colorimetrie, polarographie. Cette liste n'est pas limitative. La conception de l'installation permet la mise en place rapide d'autres appareils. Protegee par 5 cm de plomb et fortement ventilee, elle donne toute securite de manipulation jusqu'a un niveau d'activite 400 mcuries en produits de fission a vie longue. (auteur)

Determination of Anthracycline Drug Residual in Cleaning Validation Swabs of Stainless-Steel Equipment after Production of Cytostatic Injections Using HPLC Analytical Method

Directory of Open Access Journals (Sweden)

Zuzana Slivová

2015-01-01

Full Text Available Standard cleaning procedures of production line equipment were verified after manufacture of cytostatic injections containing Anthracycline derivate substance. Residual content of Anthracycline drug substance on stainless-steel equipment surface was determined using swab sampling with a specific HPLC-DAD analysis. The acceptance limit was decided as 200.0 μg/100 cm2. Recovery from the stainless-steel surface was 90.1%. Linearity of the method was observed in the concentration range of 0.155–194 μg/mL when estimated using Zorbax TMS (5 μm, 0.25 m × 4.6 mm ID column at 1.3 mL/min flow rate and 254 nm (DAD 190–600 nm. The mobile phase consisted of lauryl hydrogen sulphate solution (3.7 g/L : methanol : acetonitrile (54 : 16 : 30, v/v/v with pH adjusted to 2.5 using phosphoric acid (85%. The LOD and LOQ for Anthracycline derivate were found to be 0.047 and 0.155 μg/mL, respectively. The method validation confirmed the method provides acceptable degree of selectivity, linearity, accuracy, and precision for the intended purposes.

Analytical Strategies for the Determination of Norepinephrine Reuptake Inhibitors in Pharmaceutical Formulations and Biological Fluids.

Science.gov (United States)

Saka, Cafer

2016-01-01

Norepinephrine reuptake inhibitors (NRIs) are a class of antidepressant drugs that act as reuptake inhibitors for the neurotransmitters norepinephrine and epinephrine. The present review provides an account of analytical methods published in recent years for the determination of NRI drugs. NRIs are atomoxetine, reboxetine, viloxazine and maprotiline. NRIs with less activity at other sites are mazindol, bupropion, tapentadol, and teniloxazine. This review focuses on the analytical methods including chromatographic, spectrophotometric, electroanalytical, and electrophoresis techniques for NRI analysis from pharmaceutical formulations and biological samples. Among all of the published methods, liquid chromatography with UV-vis or MS-MS detection is the most popular technique. The most the common sample preparation techniques in the analytical methods for NRIs include liquid-liquid extraction and solid-phase extraction. Besides the analytical methods for single components, some of the simultaneous determinations are also included in this review.

"Thunderstruck": Plasma-Polymer-Coated Porous Silicon Microparticles As a Controlled Drug Delivery System.

Science.gov (United States)

McInnes, Steven J P; Michl, Thomas D; Delalat, Bahman; Al-Bataineh, Sameer A; Coad, Bryan R; Vasilev, Krasimir; Griesser, Hans J; Voelcker, Nicolas H

2016-02-01

Controlling the release kinetics from a drug carrier is crucial to maintain a drug's therapeutic window. We report the use of biodegradable porous silicon microparticles (pSi MPs) loaded with the anticancer drug camphothecin, followed by a plasma polymer overcoating using a loudspeaker plasma reactor. Homogenous "Teflon-like" coatings were achieved by tumbling the particles by playing AC/DC's song "Thunderstruck". The overcoating resulted in a markedly slower release of the cytotoxic drug, and this effect correlated positively with the plasma polymer coating times, ranging from 2-fold up to more than 100-fold. Ultimately, upon characterizing and verifying pSi MP production, loading, and coating with analytical methods such as time-of-flight secondary ion mass spectrometry, scanning electron microscopy, thermal gravimetry, water contact angle measurements, and fluorescence microscopy, human neuroblastoma cells were challenged with pSi MPs in an in vitro assay, revealing a significant time delay in cell death onset.

75 FR 4973 - Registration Requirements for Importers and Manufacturers of Prescription Drug Products...

Science.gov (United States)

2010-02-01

... diverted to the clandestine manufacture of a controlled substance. Most of the ephedrine, pseudoephedrine... for-profit. Other: Not-for-profit, government agencies. Abstract: The Domestic Chemical Diversion... may be diverted in the United States for the production of illicit drugs must register with DEA...

Natural products, an important resource for discovery of multitarget drugs and functional food for regulation of hepatic glucose metabolism.

Science.gov (United States)

Li, Jian; Yu, Haiyang; Wang, Sijian; Wang, Wei; Chen, Qian; Ma, Yanmin; Zhang, Yi; Wang, Tao

2018-01-01

Imbalanced hepatic glucose homeostasis is one of the critical pathologic events in the development of metabolic syndromes (MSs). Therefore, regulation of imbalanced hepatic glucose homeostasis is important in drug development for MS treatment. In this review, we discuss the major targets that regulate hepatic glucose homeostasis in human physiologic and pathophysiologic processes, involving hepatic glucose uptake, glycolysis and glycogen synthesis, and summarize their changes in MSs. Recent literature suggests the necessity of multitarget drugs in the management of MS disorder for regulation of imbalanced glucose homeostasis in both experimental models and MS patients. Here, we highlight the potential bioactive compounds from natural products with medicinal or health care values, and focus on polypharmacologic and multitarget natural products with effects on various signaling pathways in hepatic glucose metabolism. This review shows the advantage and feasibility of discovering multicompound-multitarget drugs from natural products, and providing a new perspective of ways on drug and functional food development for MSs.

Scientific Perspectives on Extending the Provision for Waivers of In vivo Bioavailability and Bioequivalence Studies for Drug Products Containing High Solubility-Low Permeability Drugs (BCS-Class 3)

OpenAIRE

Stavchansky, Salomon

2008-01-01

Recently, there has been increased interest in extending the provision for waivers of in vivo bioavailability and bioequivalence (BA–BE) studies that appeared in the guidance published by the Food and Drug Administration (FDA) (1) to pharmaceutical products containing Class 3 drugs (High solubility–Low Permeability). The extension of the Biopharmaceutics Classification System (BCS) to Class 3 drugs is meritorious because of its impact on public health policy considerations. The rate limiting ...

Application of multi attribute failure mode analysis of milk production using analytical hierarchy process method

Science.gov (United States)

Rucitra, A. L.

2018-03-01

Pusat Koperasi Induk Susu (PKIS) Sekar Tanjung, East Java is one of the modern dairy industries producing Ultra High Temperature (UHT) milk. A problem that often occurs in the production process in PKIS Sekar Tanjung is a mismatch between the production process and the predetermined standard. The purpose of applying Analytical Hierarchy Process (AHP) was to identify the most potential cause of failure in the milk production process. Multi Attribute Failure Mode Analysis (MAFMA) method was used to eliminate or reduce the possibility of failure when viewed from the failure causes. This method integrates the severity, occurrence, detection, and expected cost criteria obtained from depth interview with the head of the production department as an expert. The AHP approach was used to formulate the priority ranking of the cause of failure in the milk production process. At level 1, the severity has the highest weight of 0.41 or 41% compared to other criteria. While at level 2, identifying failure in the UHT milk production process, the most potential cause was the average mixing temperature of more than 70 °C which was higher than the standard temperature (≤70 ° C). This failure cause has a contributes weight of 0.47 or 47% of all criteria Therefore, this study suggested the company to control the mixing temperature to minimise or eliminate the failure in this process.

Documentation of pediatric drug safety in manufacturers' product monographs: a cross-sectional evaluation of the canadian compendium of pharmaceuticals and specialities.

Science.gov (United States)

Uppal, Navjeet K; Dupuis, Lee L; Parshuram, Christopher S

2008-01-01

To describe the provision of pediatric drug safety information in a national formulary of manufacturers' drug product monographs. We performed a cross-sectional evaluation of comprehensive product monographs contained in the 2005 Canadian Compendium of Pharmaceuticals and Specialities (CPS). We abstracted data describing indications for prescription, statements about pediatric safety, available preparations, and provision of dosing guidelines. For each monograph we classified pediatric safety data as either present, present but limited or absent. We then described the pediatric safety data in CPS monographs for drugs listed in the published formulary of the Hospital for Sick Children, Toronto, Ontario, Canada. A total of 2232 product monographs were screened; 684 were excluded and 1548 (66%) were further analyzed. 1462 (94%) had indications that did not exclude children. Pediatric safety information was present in 592 (38%), present but limited in 148 (10%), and absent in 808 (52%) drug monographs. Safety statements were absent in 224 (14%) drug monographs that provided both dosing guidelines and formulations suitable for administration to children, and in 214 (52%) of 411 drugs in the pediatric hospital formulary. We evaluated a widely available national source of pediatric prescribing information. Safety data for children was not mentioned in more than half of the product monographs. Moreover, the provision of safety data was discordant with indications for prescription, the availability of pediatric formulations, and dosing guidelines within the monographs, and with inclusion in a pediatric hospital formulary. Our study suggests that the presentation of pediatric safety data in drug product monographs can be improved to better inform prescribing and to optimize pharmacotherapy in children.

Development of an analytical methodology for the determination of the antiparasitic drug toltrazuril and its two metabolites in surface water, soil and animal manure

DEFF Research Database (Denmark)

Olsen, Jesper; Björklund, Erland; Krogh, Kristine A

2012-01-01

This paper presents the development, optimization and validation of a LC-MS/MS methodology to determine the antiparasitic veterinary drug toltrazuril and its two main metabolites, toltrazuril sulfoxide and toltrazuril sulfone, in environmental surface water, soil and animal manure. Using solid...... phase extraction and selective pressurized liquid extraction with integrated clean-up, the analytical method allows for the determination of these compounds down to 0.06-0.13 ng L(-1) in water, 0.01-0.03 ng g(-1)dw in soil and 0.22-0.51 ng g(-1) dw in manure. The deuterated analog of toltrazuril...... was used as internal standard, and ensured method accuracy in the range 96-123% for water and 77-110% for soil samples. The developed method can also be applied to simultaneously determine steroid hormones in the solid samples. The antiparasitic drug and its metabolites were found in manure and soil up...

Modifying release characteristics from 3D printed drug-eluting products

DEFF Research Database (Denmark)

Boetker, Johan; Water, Jorrit; Aho, Johanna

2016-01-01

Abstract This work describes an approach to modify the release of active compound from a 3D printed model drug product geometry intended for flexible dosing and precision medication. The production of novel polylactic acid and hydroxypropyl methylcellulose based feed materials containing...... nitrofurantoin for 3D printing purposes is demonstrated. Nitrofurantoin, Metolose® and polylactic acid were successfully co-extruded with up to 40% Metolose® content, and subsequently 3D printed into model disk geometries (ø10 mm, h = 2 mm). Thermal analysis with differential scanning calorimetry and solid phase...... identification with Raman spectroscopy showed that nitrofurantoin remained in its original solid form during both hot-melt extrusion and subsequent 3D printing. Rheological measurements of the different compositions showed that the flow properties were sensitive to the amount of undissolved particles present...

Quality by design case study: an integrated multivariate approach to drug product and process development.

Science.gov (United States)

Huang, Jun; Kaul, Goldi; Cai, Chunsheng; Chatlapalli, Ramarao; Hernandez-Abad, Pedro; Ghosh, Krishnendu; Nagi, Arwinder

2009-12-01

To facilitate an in-depth process understanding, and offer opportunities for developing control strategies to ensure product quality, a combination of experimental design, optimization and multivariate techniques was integrated into the process development of a drug product. A process DOE was used to evaluate effects of the design factors on manufacturability and final product CQAs, and establish design space to ensure desired CQAs. Two types of analyses were performed to extract maximal information, DOE effect & response surface analysis and multivariate analysis (PCA and PLS). The DOE effect analysis was used to evaluate the interactions and effects of three design factors (water amount, wet massing time and lubrication time), on response variables (blend flow, compressibility and tablet dissolution). The design space was established by the combined use of DOE, optimization and multivariate analysis to ensure desired CQAs. Multivariate analysis of all variables from the DOE batches was conducted to study relationships between the variables and to evaluate the impact of material attributes/process parameters on manufacturability and final product CQAs. The integrated multivariate approach exemplifies application of QbD principles and tools to drug product and process development.

Analytical system availability techniques

NARCIS (Netherlands)

Brouwers, J.J.H.; Verbeek, P.H.J.; Thomson, W.R.

1987-01-01

Analytical techniques are presented to assess the probability distributions and related statistical parameters of loss of production from equipment networks subject to random failures and repairs. The techniques are based on a theoretical model for system availability, which was further developed

Relationship among reaction rate, release rate and efficiency of nanomachine-based targeted drug delivery.

Science.gov (United States)

Zhao, Qingying; Li, Min; Luo, Jun

2017-12-04

In nanomachine applications towards targeted drug delivery, drug molecules released by nanomachines propagate and chemically react with tumor cells in aqueous environment. If the nanomachines release drug molecules faster than the tumor cells react, it will result in loss and waste of drug molecules. It is a potential issue associated with the relationship among reaction rate, release rate and efficiency. This paper aims to investigate the relationship among reaction rate, release rate and efficiency based on two drug reception models. We expect to pave a way for designing a control method of drug release. We adopted two analytical methods that one is drug reception process based on collision with tumors and another is based on Michaelis Menten enzymatic kinetics. To evaluate the analytical formulations, we used the well-known simulation framework N3Sim to establish simulations. The analytical results of the relationship among reaction rate, release rate and efficiency is obtained, which match well with the numerical simulation results in a 3-D environment. Based upon two drug reception models, the results of this paper would be beneficial for designing a control method of nanomahine-based drug release.

Review on research of suppression male fertility and male contraceptive drug development by natural products.

Science.gov (United States)

Bajaj, Vijay Kumar; Gupta, Radhey S

2013-08-01

Male contraceptive development in the present scenario is most viable aspect of research due to uncontrolled population growth in the world. In this respect investigators are busy to find out a safe male contraceptive drug. Researchers have started their finding for a suitable drug from natural sources because these are safe and easily acceptable for common man, most of natural sources are plants and their products. In this review 137 plants and their effects on reproduction and reproductive physiology are summarized. Some of them have intense effect on male reproductive system and do not produce any side effects. Reproductive toxicological studies are also important aspects of these kinds of researches, so it is important that drugs are safe and widely acceptable. An ideal male contraceptive can influence semen, testes, hormone level, accessory reproductive organs and general physiology of animals and produced some alterations. Many plants in this review are showing antifertility as well as antispermatogenic effects, so these may be used for further study for contraceptives development but it is important to find out the mechanism of reaction and further laboratory and clinical research on some plants are needed for final male contraceptive drug development. In conclusion this review will help for finding suitable plant products for male contraceptive clinical and laboratory studies.

Relationships among neurocognition, symptoms and functioning in patients with schizophrenia: a path-analytic approach for associations at baseline and following 24 weeks of antipsychotic drug therapy

Directory of Open Access Journals (Sweden)

Keefe Richard SE

2009-07-01

Full Text Available Abstract Background Neurocognitive impairment and psychiatric symptoms have been associated with deficits in psychosocial and occupational functioning in patients with schizophrenia. This post-hoc analysis evaluates the relationships among cognition, psychopathology, and psychosocial functioning in patients with schizophrenia at baseline and following sustained treatment with antipsychotic drugs. Methods Data were obtained from a clinical trial assessing the cognitive effects of selected antipsychotic drugs in patients with schizophrenia. Patients were randomly assigned to 24 weeks of treatment with olanzapine (n = 159, risperidone (n = 158, or haloperidol (n = 97. Psychosocial functioning was assessed with the Heinrichs-Carpenter Quality of Life Scale [QLS], cognition with a standard battery of neurocognitive tests; and psychiatric symptoms with the Positive and Negative Syndrome Scale [PANSS]. A path-analytic approach was used to evaluate the effects of changes in cognitive functioning on subdomains of quality of life, and to determine whether such effects were direct or mediated via changes in psychiatric symptoms. Results At baseline, processing speed affected functioning mainly indirectly via negative symptoms. Positive symptoms also affected functioning at baseline although independent of cognition. At 24 weeks, changes in processing speed affected changes in functioning both directly and indirectly via PANSS negative subscale scores. Positive symptoms no longer contributed to the path-analytic models. Although a consistent relationship was observed between processing speed and the 3 functional domains, variation existed as to whether the paths were direct and/or indirect. Working memory and verbal memory did not significantly contribute to any of the path-analytic models studied. Conclusion Processing speed demonstrated direct and indirect effects via negative symptoms on three domains of functioning as measured by the QLS at baseline and

Sampling and mass spectrometry approaches for the detection of drugs and foreign contaminants in breath for homeland security applications

Energy Technology Data Exchange (ETDEWEB)

Martin, Audrey Noreen [Michigan State Univ., East Lansing, MI (United States)

2009-01-01

Homeland security relies heavily on analytical chemistry to identify suspicious materials and persons. Traditionally this role has focused on attribution, determining the type and origin of an explosive, for example. But as technology advances, analytical chemistry can and will play an important role in the prevention and preemption of terrorist attacks. More sensitive and selective detection techniques can allow suspicious materials and persons to be identified even before a final destructive product is made. The work presented herein focuses on the use of commercial and novel detection techniques for application to the prevention of terrorist activities. Although drugs are not commonly thought of when discussing terrorism, narcoterrorism has become a significant threat in the 21st century. The role of the drug trade in the funding of terrorist groups is prevalent; thus, reducing the trafficking of illegal drugs can play a role in the prevention of terrorism by cutting off much needed funding. To do so, sensitive, specific, and robust analytical equipment is needed to quickly identify a suspected drug sample no matter what matrix it is in. Single Particle Aerosol Mass Spectrometry (SPAMS) is a novel technique that has previously been applied to biological and chemical detection. The current work applies SPAMS to drug analysis, identifying the active ingredients in single component, multi-component, and multi-tablet drug samples in a relatively non-destructive manner. In order to do so, a sampling apparatus was created to allow particle generation from drug tablets with on-line introduction to the SPAMS instrument. Rules trees were developed to automate the identification of drug samples on a single particle basis. A novel analytical scheme was also developed to identify suspect individuals based on chemical signatures in human breath. Human breath was sampled using an RTube{trademark} and the trace volatile organic compounds (VOCs) were preconcentrated using solid

Dandruff, seborrheic dermatitis, and psoriasis drug products containing coal tar and menthol for over-the-counter human use; amendment to the monograph. Final rule

Energy Technology Data Exchange (ETDEWEB)

NONE

2006-03-15

The Food and Drug Administration (FDA) is issuing a final rule amending the final monograph (FM) for over-the-counter (OTC) dandruff, seborrheic dermatitis, and psoriasis drug products to include the combination of 1.8 percent coal tar solution and 1.5 percent menthol in a shampoo drug product to control dandruff. FDA did not receive any comments or data in response to its previously proposed rule to include this combination. This final rule is part of FDA's ongoing review of OTC drug products.

Determination of residual acetone and acetone related impurities in drug product intermediates prepared as Spray Dried Dispersions (SDD) using gas chromatography with headspace autosampling (GCHS).

Science.gov (United States)

Quirk, Emma; Doggett, Adrian; Bretnall, Alison

2014-08-05

Spray Dried Dispersions (SDD) are uniform mixtures of a specific ratio of amorphous active pharmaceutical ingredient (API) and polymer prepared via a spray drying process. Volatile solvents are employed during spray drying to facilitate the formation of the SDD material. Following manufacture, analytical methodology is required to determine residual levels of the spray drying solvent and its associated impurities. Due to the high level of polymer in the SDD samples, direct liquid injection with Gas Chromatography (GC) is not a viable option for analysis. This work describes the development and validation of an analytical approach to determine residual levels of acetone and acetone related impurities, mesityl oxide (MO) and diacetone alcohol (DAA), in drug product intermediates prepared as SDDs using GC with headspace (HS) autosampling. The method development for these analytes presented a number of analytical challenges which had to be overcome before the levels of the volatiles of interest could be accurately quantified. GCHS could be used after two critical factors were implemented; (1) calculation and application of conversion factors to 'correct' for the reactions occurring between acetone, MO and DAA during generation of the headspace volume for analysis, and the addition of an equivalent amount of polymer into all reference solutions used for quantitation to ensure comparability between the headspace volumes generated for both samples and external standards. This work describes the method development and optimisation of the standard preparation, the headspace autosampler operating parameters and the chromatographic conditions, together with a summary of the validation of the methodology. The approach has been demonstrated to be robust and suitable to accurately determine levels of acetone, MO and DAA in SDD materials over the linear concentration range 0.008-0.4μL/mL, with minimum quantitation limits of 20ppm for acetone and MO, and 80ppm for DAA. Copyright

Distributed data networks: a blueprint for Big Data sharing and healthcare analytics.

Science.gov (United States)

Popovic, Jennifer R

2017-01-01

This paper defines the attributes of distributed data networks and outlines the data and analytic infrastructure needed to build and maintain a successful network. We use examples from one successful implementation of a large-scale, multisite, healthcare-related distributed data network, the U.S. Food and Drug Administration-sponsored Sentinel Initiative. Analytic infrastructure-development concepts are discussed from the perspective of promoting six pillars of analytic infrastructure: consistency, reusability, flexibility, scalability, transparency, and reproducibility. This paper also introduces one use case for machine learning algorithm development to fully utilize and advance the portfolio of population health analytics, particularly those using multisite administrative data sources. © 2016 New York Academy of Sciences.

An analytical approach to managing complex process problems

Energy Technology Data Exchange (ETDEWEB)

Ramstad, Kari; Andersen, Espen; Rohde, Hans Christian; Tydal, Trine

2006-03-15

The oil companies are continuously investing time and money to ensure optimum regularity on their production facilities. High regularity increases profitability, reduces workload on the offshore organisation and most important; - reduces discharge to air and sea. There are a number of mechanisms and tools available in order to achieve high regularity. Most of these are related to maintenance, system integrity, well operations and process conditions. However, for all of these tools, they will only be effective if quick and proper analysis of fluids and deposits are carried out. In fact, analytical backup is a powerful tool used to maintain optimised oil production, and should as such be given high priority. The present Operator (Hydro Oil and Energy) and the Chemical Supplier (MI Production Chemicals) have developed a cooperation to ensure that analytical backup is provided efficiently to the offshore installations. The Operator's Research and Development (R and D) departments and the Chemical Supplier have complementary specialties in both personnel and equipment, and this is utilized to give the best possible service when required from production technologists or operations. In order for the Operator's Research departments, Health, Safety and Environment (HSE) departments and Operations to approve analytical work performed by the Chemical Supplier, a number of analytical tests are carried out following procedures agreed by both companies. In the present paper, three field case examples of analytical cooperation for managing process problems will be presented. 1) Deposition in a Complex Platform Processing System. 2) Contaminated Production Chemicals. 3) Improved Monitoring of Scale Inhibitor, Suspended Solids and Ions. In each case the Research Centre, Operations and the Chemical Supplier have worked closely together to achieve fast solutions and Best Practice. (author) (tk)

Scaling in situ cosmogenic nuclide production rates using analytical approximations to atmospheric cosmic-ray fluxes

Science.gov (United States)

Lifton, Nathaniel; Sato, Tatsuhiko; Dunai, Tibor J.

2014-01-01

Several models have been proposed for scaling in situ cosmogenic nuclide production rates from the relatively few sites where they have been measured to other sites of interest. Two main types of models are recognized: (1) those based on data from nuclear disintegrations in photographic emulsions combined with various neutron detectors, and (2) those based largely on neutron monitor data. However, stubborn discrepancies between these model types have led to frequent confusion when calculating surface exposure ages from production rates derived from the models. To help resolve these discrepancies and identify the sources of potential biases in each model, we have developed a new scaling model based on analytical approximations to modeled fluxes of the main atmospheric cosmic-ray particles responsible for in situ cosmogenic nuclide production. Both the analytical formulations and the Monte Carlo model fluxes on which they are based agree well with measured atmospheric fluxes of neutrons, protons, and muons, indicating they can serve as a robust estimate of the atmospheric cosmic-ray flux based on first principles. We are also using updated records for quantifying temporal and spatial variability in geomagnetic and solar modulation effects on the fluxes. A key advantage of this new model (herein termed LSD) over previous Monte Carlo models of cosmogenic nuclide production is that it allows for faster estimation of scaling factors based on time-varying geomagnetic and solar inputs. Comparing scaling predictions derived from the LSD model with those of previously published models suggest potential sources of bias in the latter can be largely attributed to two factors: different energy responses of the secondary neutron detectors used in developing the models, and different geomagnetic parameterizations. Given that the LSD model generates flux spectra for each cosmic-ray particle of interest, it is also relatively straightforward to generate nuclide-specific scaling

Analysis of veterinary drug residue monitoring results for commercial livestock products in Taiwan between 2011 and 2015

OpenAIRE

Hsin-Chun Lee; Chi-Min Chen; Jen-Ting Wei; Hsiu-Yi Chiu

2018-01-01

Antibiotics have been widely used in the treatment of livestock diseases. However, the emergence of issues related to drug resistance prompted governments to enact a series of laws regulating the use of antibiotics in livestock. Following control of the problem of drug resistant bacteria, public attention has shifted to the recurring incidence of human health and safety issues caused by residual veterinary drugs in livestock products. To guarantee the safety and hygiene of meat, milk, and egg...

Identifying and Prioritizing the Effective Parameters on Lack of Timeliness of Operations of Sugarcane Production using Analytical Hierarchy Process (AHP

Directory of Open Access Journals (Sweden)

N Monjezi

2017-10-01

Full Text Available Introduction Planning and scheduling of farming mechanized operations is very important. If the operation is not performed on time, yield will be reduced. Also for sugarcane, any delay in crop planting and harvesting operations reduces the yield. The most useful priority setting method for agricultural projects is the analytic hierarchy process (AHP. So, this article presents an introductry application manner of the Analytical Hierarchy Process (AHP as a mostly common method of setting agricultural projects priorities. Analytic Hierarchy process (AHP is a decision making algorithm developed by Dr. Saatyin 1980. It has many applications as documented in Decision Support System literature. Currently, this technique is widely used in complicated management decision makings which AHP was preferred from other established methodologies as it does not demand prior knowledge of the utility function; it is based on a hierarchy of criteria and attributes reflecting the understanding of the problem, and finally, because it allows relative and absolute comparisons, thus making this method a very robust tool. The purpose of this research is to identify and prioritize the effective parameters on lack of timeliness of operations of sugarcane production using AHP in Khuzestan province of Iran. Materials and Methods The effective parameters effecting on lack of timeliness of operations have been defined based on expert’s opinions. A questionnaire and personal interviews have formed the basis of this research. The study was applied to a panel of qualified informants made up of fourteen experts. Those interviewed were distributed in Sugarcane Development and By-products Company in 2013-2014. Then, by using the Analytical hierarchy process, a questionnaire was designed for defining the weight and importance of parameters affecting on lack of timeliness of operations. For this method of evaluation, three main criteria considered were yield criteria, cost criteria

The Use of Analytic Network Process for Risk Assessment in Production of Renewable Energy from Agriculture Biomass in Latvia

Directory of Open Access Journals (Sweden)

Sandija Rivza

2013-02-01

Full Text Available Risk assessment is an important factor for successful and sustainable entrepreneurship of bioenergy production that has become one of the priorities in energy sector of Latvia. Promotion of the use of renewable energy is included as one of the strategic goals for European Union (EU and Latvia. As this field of energy production in Latvia is rather new and scantily explored there are many risk factors arising in different stages of production, starting with planning and building of a bioreactor and ending with production and further use and distribution of energy. The present research focuses on risk assessment in renewable energy production form biomass as this kind of energy is seen as a perspective source for renewable energy under the conditions of Latvia. A risk assessment module for renewable energy production made by using the Analytic Network Process (ANP software is described in the paper.

Proceedings of the Indian Analytical Science Congress: analytical science for innovations in green energy, technology and industry - souvenir

International Nuclear Information System (INIS)

2013-01-01

The theme of IASC - 2013 is 'Analytical Science for innovations in Green Energy, Technology and Industry'. This theme was chosen to emphasize the unprecedented opportunities for analytical science and technology in the field of green energy, technology and industry, while at the same time recognizing the special challenges faced by analytical science in this field. The objective of the conference is to advance research, development and innovation in analytical sciences for the benefit of its application in the areas of green science and technology. The growing role of analytical science in green energy, technology and industry are significant. The next few years will witness more momentous achievements of analytical science as well as its application in green energy, technology and industry contributing towards the benefit of mankind in terms of healthy, productive, long and comfortable life. Papers relevant to INIS are indexed separately

Drug diffusion across skin with diffusivity spatially modulated

Science.gov (United States)

Montoya Arroyave, Isabel

2014-05-01

A diffusion and delivery model of a drug across the skin with diffusivity spatially modulated is formulated and solved analytically using computer algebra. The model is developed using one-dimensional diffusion equation with a diffusivity which is a function of position in the skin; with an initial condition which is describing that the drug is initially contained inside a therapeutic patch; with a boundary condition according to which the change in concentration in the patch is minimal, such that assumption of zero flux at the patch-skin interface is valid; and with other boundary condition according to which the microcirculation in the capillaries just below the dermis carries the drug molecules away from the site at a very fast rate, maintaining the inner concentration at 0. The model is solved analytically by the method of the Laplace transform, with Bromwich integral and residue theorem. The concentration profile of the drug in the skin is expressed as an infinite series of Bessel functions. The corresponding total amount of delivered drug is expressed as an infinite series of decreasing exponentials. Also, the corresponding effective time for the therapeutic patch is determined. All computations were performed using computer algebra software, specifically Maple. The analytical results obtained are important for understanding and improving currentapplications of therapeutic patches. For future research it is interesting to consider more general models of spatial modulation of the diffusivity and the possible application of other computer algebra software such as Mathematica and Maxima.

ASM Inaugural Lecture 2010: Single crystal X-ray structural determination: A powerful technique for natural products research and drug discovery

International Nuclear Information System (INIS)

Fun Hoong Kun; Chantrapromma, S.; Boonnak, N.; Lee, V.S.

2010-01-01

Drug discovery from natural products resources have been extensively studied worldwide because natural products with their great structural diversity have traditionally provided most of the drugs in use. They offer major opportunities for finding novel low molecular weight leading-structures that are active against a wide range of assay targets. The most important step in the discovery process is the identification of compounds with interesting biological activity. Single crystal X-ray structure determination is a powerful technique for natural products research and drug discovery. The detailed three-dimensional structures that emerge can be co-related to the activities to these structures. In this article the following is presented: (i) co-crystal and disorder structures; (ii) determination of absolute configuration and (iii) the ability to distinguish between whether a natural product compound is a natural product or a natural product artifact. All these three properties are unique to the technique of single crystal X-ray structure determination. Case (iii) was demonstrated with a compound containing a chromene ring, namely macluraxanthone (which was isolated from Cratoxylum formosum subsp. pruniflorum, a Thai medicinal plant). (author)

Characterization of Analytical Reference Glass-1 (ARG-1)

International Nuclear Information System (INIS)

Smith, G.L.

1993-12-01

High-level radioactive waste may be immobilized in borosilicate glass at the West Valley Demonstration Project, West Valley, New York, the Defense Waste Processing Facility (DWPF), Aiken, South Carolina, and the Hanford Waste Vitrification Project (HWVP), Richland, Washington. The vitrified waste form will be stored in stainless steel canisters before its eventual transfer to a geologic repository for long-term disposal. Waste Acceptance Product Specifications (WAPS) (DOE 1993), Section 1.1.2 requires that the waste form producers must report the measured chemical composition of the vitrified waste in their production records before disposal. Chemical analysis of glass waste forms is receiving increased attention due to qualification requirements of vitrified waste forms. The Pacific Northwest Laboratory (PNL) has been supporting the glass producers' analytical laboratories by a continuing program of multilaboratory analytical testing using interlaboratory ''round robin'' methods. At the PNL Materials Characterization Center Analytical Round Robin 4 workshop ''Analysis of Nuclear Waste Glass and Related Materials,'' January 16--17, 1990, Pleasanton, California, the meeting attendees decided that simulated nuclear waste analytical reference glasses were needed for use as analytical standards. Use of common standard analytical reference materials would allow the glass producers' analytical laboratories to calibrate procedures and instrumentation, to control laboratory performance and conduct self-appraisals, and to help qualify their various waste forms

Manual of Standard Operating Procedures for Veterinary Drug Residue Analysis

International Nuclear Information System (INIS)

2016-01-01

Laboratories are crucial to national veterinary drug residue monitoring programmes. However, one of the main challenges laboratories encounter is obtaining access to relevant methods of analysis. Thus, in addition to training, providing technical advice and transferring technology, the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture has resolved to develop clear and practical manuals to support Member State laboratories. The Coordinated Research Project (CRP) on Development of Radiometric and Allied Analytical Methods to Strengthen Residue Control Programs for Antibiotic and Anthelmintic Veterinary Drug Residues has developed a number of analytical methods as standard operating procedures (SOPs), which are now compiled here. This publication contains SOPs on chromatographic and spectrometric techniques, as well as radioimmunoassay and associated screening techniques, for various anthelmintic and antimicrobial veterinary drug residue analysis. Some analytical method validation protocols are also included. The publication is primarily aimed at food and environmental safety laboratories involved in testing veterinary drug residues, including under organized national residue monitoring programmes. It is expected to enhance laboratory capacity building and competence through the use of radiometric and complementary tools and techniques. The publication is also relevant for applied research on residues of veterinary drugs in food and environmental samples

On-chip microreactor system for the production of nano-emulsion loaded liposomes: towards targeted delivery of lipophilic drugs

NARCIS (Netherlands)

Langelaan, M.L.P.; Emmelkamp, J.; Segers, M.J.A.; Lenting, H.B.M.

2011-01-01

An on-chip microreactor system for the production of novel nano-biodevices is presented. This nano-biodevice consists of a nano-emulsion loaded with lipophilic drugs, entrapped in liposomes. These nano-biodevices can be equipped with targeting molecules for higher drug efficiency. The microreactor

Characterization of dilation analytic integral kernels

Energy Technology Data Exchange (ETDEWEB)

Vici, A D [Rome Univ. (Italy). Ist. di Matematica

1979-11-01

The author characterises integral operators belonging to B(L/sup 2/(R/sup 3/)) which are dilatation analytic in the Cartesian product of two sectors Ssub(a) contains C as analytic functions from Ssub(a) X Ssub(a) into B(L/sup 2/(..cap omega..)), the space of bounded operators on square integrable functions on the unit sphere ..cap omega.., which satisfy certain norm estimates uniformly on every subsector.

Evaluation of Container Closure System Integrity for Frozen Storage Drug Products.

Science.gov (United States)

Nieto, Alejandra; Roehl, Holger; Brown, Helen; Nikoloff, Jonas; Adler, Michael; Mahler, Hanns-Christian

2016-01-01

Sometimes, drug product for parenteral administration is stored in a frozen state (e.g., -20 °C or -80 °C), particularly during early stages of development of some biotech molecules in order to provide sufficient stability. Shipment of frozen product could potentially be performed in the frozen state, yet possibly at different temperatures, for example, using dry ice (-80 °C). Container closure systems of drug products usually consist of a glass vial, rubber stopper, and an aluminum crimped cap. In the frozen state, the glass transition temperature (Tg) of commonly used rubber stoppers is between -55 and -65 °C. Below their Tg, rubber stoppers are known to lose their elastic properties and become brittle, and thus potentially fail to maintain container closure integrity in the frozen state. Leaks during frozen temperature storage and transportation are likely to be transient, yet, can possibly risk container closure integrity and lead to microbial contamination. After thawing, the rubber stopper is supposed to re-seal the container closure system. Given the transient nature of the possible impact on container closure integrity in the frozen state, typical container closure integrity testing methods (used at room temperature conditions) are unable to evaluate and thus confirm container closure integrity in the frozen state. Here we present the development of a novel method (thermal physical container closure integrity) for direct assessment of container closure integrity by a physical method (physical container closure integrity) at frozen conditions, using a modified He leakage test. In this study, different container closure systems were evaluated with regard to physical container closure integrity in the frozen state to assess the suitability of vial/stopper combinations and were compared to a gas headspace method. In summary, the thermal physical container closure integrity He leakage method was more sensitive in detecting physical container closure

Analytical approaches for the characterization of nickel proteome.

Science.gov (United States)

Jiménez-Lamana, Javier; Szpunar, Joanna

2017-08-16

The use of nickel in modern industry and in consumer products implies some health problems for the human being. Nickel allergy and nickel carcinogenicity are well-known health effects related to human exposure to nickel, either during production of nickel-containing products or by direct contact with the final item. In this context, the study of nickel toxicity and nickel carcinogenicity involves the understanding of their molecular mechanisms and hence the characterization of the nickel-binding proteins in different biological samples. During the last 50 years, a broad range of analytical techniques, covering from the first chromatographic columns to the last generation mass spectrometers, have been used in order to fully characterize the nickel proteome. The aim of this review is to present a critical view of the different analytical approaches that have been applied for the purification, isolation, detection and identification of nickel-binding proteins. The different analytical techniques used are discussed from a critical point of view, highlighting advantages and limitations.

Fieldable, real-time enzyme immunoassay kits for drugs on surfaces

Science.gov (United States)

Chiappini, Michele W.; Wendel, Gregory J.; Duquette, Peter H.; Hamilton, Martha J.; Chudzik, Stephen J.; Chappa, Ralph A.

1994-03-01

Immunoassays (e.g., RIA, EIA) have been demonstrated to be useful for rapid, convenient detection and semiquantitative analysis of drugs. Thermedics Detection, Inc. manufactures a rapid, sensitive, self-contained, disposable, EIA device, developed by Bio-Metric Systems, Inc., designed to allow untrained personnel to perform in field situations. This format has been developed for drugs in biological fluids and on surfaces. The analyte in the test sample competes with an enzyme-analyte conjugate for a limited number of immobilized antibody sites. The AccuPRESS Test format can detect analytes at 10 ppb in biological fluids, water, and soil, and on surfaces, such as suitcases, vehicles, tables and hands, with positive results indicated by clearly visible color development within 5 minutes. This format is designed to have all dry components and to have an ambient shelf life of greater than one year. The format is available for cocaine and opiate derivatives, including heroin, and is readily adaptable for use with numerous other drugs, explosives, and environmental pollutants.

Modeling Drug-Carrier Interaction in the Drug Release from Nanocarriers

Directory of Open Access Journals (Sweden)

Like Zeng

2011-01-01

Full Text Available Numerous nanocarriers of various compositions and geometries have been developed for the delivery and release of therapeutic and imaging agents. Due to the high specific surface areas of nanocarriers, different mechanisms such as ion pairing and hydrophobic interaction need to be explored for achieving sustained release. Recently, we developed a three-parameter model that considers reversible drug-carrier interaction and first-order drug release from liposomes. A closed-form analytical solution was obtained. Here, we further explore the ability of the model to capture the release of bioactive molecules such as drugs and growth factors from various nanocarriers. A parameter study demonstrates that the model is capable of resembling major categories of drug release kinetics. We further fit the model to 60 sets of experimental data from various drug release systems, including nanoparticles, hollow particles, fibers, and hollow fibers. Additionally, bootstrapping is used to evaluate the accuracy of parameter determination and validate the model in selected cases. The simplicity and universality of the model and the clear physical meanings of each model parameter render the model useful for the design and development of new drug delivery systems.