Validation of pharmaceutical potency determinations by quantitative nuclear magnetic resonance spectrometry.

PubMed

Webster, Gregory K; Marsden, Ian; Pommerening, Cynthia A; Tyrakowski, Christina M

2010-05-01

With the changing development paradigms in the pharmaceutical industry, laboratories are challenged to release materials for clinical studies with rapid turnaround times. To minimize cost demands, many businesses are looking to develop ways of using early Good Manufacturing Practice (GMP) materials of active pharmaceutical ingredients (API) for Good Laboratory Practice (GLP) toxicology studies. To make this happen, the analytical laboratory releases the material by one of three scenarios: (1) holding the GLP release until full GMP testing is ready, (2) issuing a separate lot number for a portion of the GMP material and releasing the material for GLP use, or (3) releasing the lot of material for GLP using alternate (equivalent) method(s) not specified for GMP release testing. Many companies are finding the third scenario to be advantageous in terms of cost and efficiency through the use of quantitative nuclear magnetic resonance (q-NMR). The use of q-NMR has proved to be a single-point replacement for routine early development testing that previously combined elements of identity testing, chromatographic assay, moisture analysis, residual solvent analysis, and elemental analysis. This study highlights that q-NMR can be validated to meet current regulatory analytical method guidelines for routine pharmaceutical analysis.

Concerns about the safety of obesity agents from a manufacturing perspective.

PubMed

Kanfer, Isadore

2008-07-01

Salt derivatives of active pharmaceutical ingredients (API), such as hydrochloride and mesylate salts, are frequently used during drug product development. Compared with the underivatized API, salt derivatives are often associated with beneficial properties, including improved solubility and better absorption. Although the obesity agent sibutramine was initially approved as the hydrochloride salt, it has also been formulated as a mesylate salt (sibutramine mesylate). In order to qualify as interchangeable, generic products generally must be both pharmaceutically equivalent and bioequivalent to an approved reference product. Because generic versions of hydrochloride salt formulations that have been reformulated as mesylate salts are not pharmaceutically equivalent to the approved reference products, they would not be interchangeable, even if bioequivalent. The safety of APIs and drug products manufactured outside the United States in non-Food and Drug Administration-regulated facilities are of concern, particularly agents that may contain harmful impurities, such as obesity products formulated as mesylate salts.

42 CFR 423.132 - Public disclosure of pharmaceutical prices for equivalent drugs.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., a Part D sponsor must require a pharmacy that dispenses a covered Part D drug to inform an enrollee... that pharmacy, unless the particular covered Part D drug being purchased is the lowest-priced therapeutically equivalent and bioequivalent version of that drug available at that pharmacy. (b) Timing of notice...

42 CFR 423.132 - Public disclosure of pharmaceutical prices for equivalent drugs.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., a Part D sponsor must require a pharmacy that dispenses a covered Part D drug to inform an enrollee... that pharmacy, unless the particular covered Part D drug being purchased is the lowest-priced therapeutically equivalent and bioequivalent version of that drug available at that pharmacy. (b) Timing of notice...

42 CFR 423.132 - Public disclosure of pharmaceutical prices for equivalent drugs.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., a Part D sponsor must require a pharmacy that dispenses a covered Part D drug to inform an enrollee... that pharmacy, unless the particular covered Part D drug being purchased is the lowest-priced therapeutically equivalent and bioequivalent version of that drug available at that pharmacy. (b) Timing of notice...

42 CFR 423.132 - Public disclosure of pharmaceutical prices for equivalent drugs.

Code of Federal Regulations, 2011 CFR

2011-10-01

... sponsor must require a pharmacy that dispenses a covered Part D drug to inform an enrollee of any... Part D drug that is therapeutically equivalent and bioequivalent and available at that pharmacy, unless... bioequivalent version of that drug available at that pharmacy. (b) Timing of notice. Subject to paragraph (d) of...

42 CFR 423.132 - Public disclosure of pharmaceutical prices for equivalent drugs.

Code of Federal Regulations, 2010 CFR

2010-10-01

... sponsor must require a pharmacy that dispenses a covered Part D drug to inform an enrollee of any... Part D drug that is therapeutically equivalent and bioequivalent and available at that pharmacy, unless... bioequivalent version of that drug available at that pharmacy. (b) Timing of notice. Subject to paragraph (d) of...

Trends in prescription drug utilization and spending for the Department of Defense, 2002-2007.

PubMed

Devine, Joshua W; Trice, Shana; Spridgen, Stacia L; Bacon, Thomas A

2009-09-01

Examine trends in U.S. Department of Defense (DoD) outpatient drug spending and utilization between 2002 and 2007. We analyzed pharmacy claims data from the U.S. Military Health System (MHS), using a cross-sectional analysis at the prescription and patient-year level and measuring utilization in 30-day equivalent prescriptions and expenditures in dollars. Pharmaceutical spending more than doubled in DoD, from $3 billion in FY02 to $6.5 billion in FY07. The largest increase occurred in the DoD community pharmacy network, where utilization grew from 6 million 30-day equivalent prescriptions in the first quarter of FY02 to more than 16 million in the last quarter of FY07. The smallest increase in annual spending occurred in FY07 (5.5%), down from a high of 27.5% in FY03. The MHS has experienced rapid growth in pharmaceutical spending since FY02. However, there are signs that growth in pharmaceutical spending may be slowing.

Kinetic Tetrazolium Microtiter Assay

NASA Technical Reports Server (NTRS)

Pierson, Duane L.; Stowe, Raymond; Koenig, David

1993-01-01

Kinetic tetrazolium microtiter assay (KTMA) involves use of tetrazolium salts and Triton X-100 (or equivalent), nontoxic, in vitro color developer solubilizing colored metabolite formazan without injuring or killing metabolizing cells. Provides for continuous measurement of metabolism and makes possible to determine rate of action of antimicrobial agent in real time as well as determines effective inhibitory concentrations. Used to monitor growth after addition of stimulatory compounds. Provides for kinetic determination of efficacy of biocide, greatly increasing reliability and precision of results. Also used to determine relative effectiveness of antimicrobial agent as function of time. Capability of generating results on day of test extremely important in treatment of water and waste, disinfection of hospital rooms, and in pharmaceutical, agricultural, and food-processing industries. Assay also used in many aspects of cell biology.

21 CFR 26.45 - Monitoring continued equivalence.

Code of Federal Regulations, 2010 CFR

2010-04-01

... MUTUAL RECOGNITION OF PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE QUALITY SYSTEM AUDIT REPORTS, AND CERTAIN MEDICAL DEVICE PRODUCT EVALUATION REPORTS: UNITED STATES AND THE EUROPEAN...

Development, optimization and validation of a rapid colorimetric microplate bioassay for neomycin sulfate in pharmaceutical drug products.

PubMed

Francisco, Fabiane Lacerda; Saviano, Alessandro Morais; Pinto, Terezinha de Jesus Andreoli; Lourenço, Felipe Rebello

2014-08-01

Microbiological assays have been used to evaluate antimicrobial activity since the discovery of the first antibiotics. Despite their limitations, microbiological assays are widely employed to determine antibiotic potency of pharmaceutical dosage forms, since they provide a measure of biological activity. The aim of this work is to develop, optimize and validate a rapid colorimetric microplate bioassay for the potency of neomycin in pharmaceutical drug products. Factorial and response surface methodologies were used in the development and optimization of the choice of microorganism, culture medium composition, amount of inoculum, triphenyltetrazolium chloride (TTC) concentration and neomycin concentration. The optimized bioassay method was validated by the assessment of linearity (range 3.0 to 5.0μg/mL, r=0.998 and 0.994 for standard and sample curves, respectively), precision (relative standard deviation (RSD) of 2.8% and 4.0 for repeatability and intermediate precision, respectively), accuracy (mean recovery=100.2%) and robustness. Statistical analysis showed equivalency between agar diffusion microbiological assay and rapid colorimetric microplate bioassay. In addition, microplate bioassay had advantages concerning the sensitivity of response, time of incubation, and amount of culture medium and solutions required. Copyright © 2014 Elsevier B.V. All rights reserved.

Regulatory framework on bioequivalence criteria for locally acting gastrointestinal drugs: the case for oral modified release mesalamine formulations.

PubMed

Sferrazza, Gianluca; Siviero, Paolo D; Nicotera, Giuseppe; Turella, Paola; Serafino, Annalucia; Blandizzi, Corrado; Pierimarchi, Pasquale

2017-09-01

Bioequivalence testing for locally acting gastrointestinal drugs is a challenging issue for both regulatory authorities and pharmaceutical industries. The international regulatory framework has been characterized by the lack of specific bioequivalence tests that has generated a negative impact on the market competition and drug use in clinical practice. Areas covered: This review article provides an overview of the European Union and United States regulatory frameworks on bioequivalence criteria for locally acting gastrointestinal drugs, also discussing the most prominent scientific issues and advances that has been made in this field. A focus on oral modified release mesalamine formulations will be also provided, with practical examples of the regulatory pathways followed by pharmaceutical companies to determine bioequivalence. Expert commentary: The development of a scientific rationale to demonstrate bioequivalence in this field has been complex and often associated with uncertainties related to scientific and regulatory aspects. Only in recent years, thanks to advanced knowledge in this field, the criteria for bioequivalence assessment are undergoing substantial changes. This new scenario will likely result in a significant impact on pharmaceutical companies, promoting more competition through a clearer regulatory approach, conceived for streamlining the demonstration of therapeutic equivalence for locally acting gastrointestinal drugs.

How do the top 12 pharmaceutical companies operate safety pharmacology?

PubMed

Ewart, Lorna; Gallacher, David J; Gintant, Gary; Guillon, Jean-Michel; Leishman, Derek; Levesque, Paul; McMahon, Nick; Mylecraine, Lou; Sanders, Martin; Suter, Willi; Wallis, Rob; Valentin, Jean-Pierre

2012-09-01

How does safety pharmacology operate in large pharmaceutical companies today? By understanding our current position, can we prepare safety pharmacology to successfully navigate the complex process of drug discovery and development? A short anonymous survey was conducted, by invitation, to safety pharmacology representatives of the top 12 pharmaceutical companies, as defined by 2009 revenue figures. A series of multiple choice questions was designed to explore group size, accountabilities, roles and responsibilities of group members, outsourcing policy and publication record. A 92% response rate was obtained. Six out of 11 companies have 10 to 30 full time equivalents in safety pharmacology, who hold similar roles and responsibilities; although the majority of members are not qualified at PhD level or equivalent. Accountabilities were similar across companies and all groups have accountability for core battery in vivo studies and problem solving activities but differences do exist for example with in vitro safety screening and pharmacodynamic/pharmokinetic modeling (PK/PD). The majority of companies outsource less than 25% of studies, with in vitro profiling being the most commonly outsourced activity. Finally, safety pharmacology groups are publishing 1 to 4 articles each year. This short survey has highlighted areas of similarity and differences in the way large pharmaceutical companies operate safety pharmacology. Copyright © 2012 Elsevier Inc. All rights reserved.

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

PubMed

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

2016-01-01

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

21 CFR 314.53 - Submission of patent information.

Code of Federal Regulations, 2014 CFR

2014-04-01

... pharmaceutical equivalence and comparable product stability; and (v) Comparative in vitro dissolution testing on... copy, to the Central Document Room, Center for Drug Evaluation and Research, Food and Drug...

21 CFR 314.53 - Submission of patent information.

Code of Federal Regulations, 2012 CFR

2012-04-01

... pharmaceutical equivalence and comparable product stability; and (v) Comparative in vitro dissolution testing on... copy, to the Central Document Room, Center for Drug Evaluation and Research, Food and Drug...

21 CFR 314.53 - Submission of patent information.

Code of Federal Regulations, 2013 CFR

2013-04-01

... pharmaceutical equivalence and comparable product stability; and (v) Comparative in vitro dissolution testing on... copy, to the Central Document Room, Center for Drug Evaluation and Research, Food and Drug...

21 CFR 314.53 - Submission of patent information.

Code of Federal Regulations, 2010 CFR

2010-04-01

... pharmaceutical equivalence and comparable product stability; and (v) Comparative in vitro dissolution testing on... copy, to the Central Document Room, Center for Drug Evaluation and Research, Food and Drug...

21 CFR 314.53 - Submission of patent information.

Code of Federal Regulations, 2011 CFR

2011-04-01

... pharmaceutical equivalence and comparable product stability; and (v) Comparative in vitro dissolution testing on... copy, to the Central Document Room, Center for Drug Evaluation and Research, Food and Drug...

Investigation of runoff generation in small catchments with dissolved veterinary and human pharmaceuticals

NASA Astrophysics Data System (ADS)

Krein, Andreas; Pailler, Jean-Yannick; Guignard, Cédric; Pfister, Laurent; Hoffmann, Lucien

2010-05-01

This investigation focuses on the analysis of four classes of veterinary and human pharmaceuticals in surface water in Luxembourg. The selected pharmaceuticals include four sulfonamides, two tetracyclines, two analgesics, and three hormones. Solid-phase extraction with liquid chromatography-tandem mass spectrometry resulted in detection limits ranging from 0.3 to 2.0 ng/L, allowing the determination of pharmaceuticals in storm waters. The analysis of pharmaceuticals by liquid chromatography-tandem mass spectrometry is a useful tool to trace their behaviour in the aquatic environment. Application of this method to river concentration and flood events revealed high concentrations of ibuprofen, with highest levels during flood events, while concentrations of estrogens and sulfonamides were comparatively low. So far, the yeast estrogen screen has been applied for some of the samples. The measured steroid values were converted to estrogenic activity by taking into account the relative potency of each chemical compared to the reference, estradiol. This method considers the relative affinity of the steroids for the hormone receptor. The measured estrogenic activity in the surface water is regularly at levels larger than 5 ng/L estradiol equivalents which might be of concern to reproductive success of native fish populations. The concentration and transport of xenobiotics in surface waters depend on hydraulic conditions including rainfall pattern and sewage overflow, on the properties of the substances, including sorption, degradation, and metabolism. The analysis of flood events using the rainfall pattern, the hydrograph, and dissolved pharmaceutical chemographs provides an insight into the temporal structure of flood events. The corresponding anthropogenic sources show a high temporal and spatial variability that is caused by different rainfall patterns and distributions, and the different characteristics (e.g. retention capacities) of the combined sewer systems. We can show that the combined sewer overflows deliver an important part of the dissolved pharmaceuticals into the river network.

Application of Recombinant Factor C Reagent for the Detection of Bacterial Endotoxins in Pharmaceutical Products.

PubMed

Bolden, Jay; Smith, Kelly

2017-01-01

Recombinant Factor C (rFC) is non-animal-derived reagent used to detect bacterial endotoxins in pharmaceutical products. Despite the fact that the reagent was first commercially available nearly 15 years ago, the broad use of rFC in pharmaceutical industry has long been lagging, presumably due to historical single-source supplier concerns and the lack of inclusion in worldwide pharmacopeias. Commercial rFC reagents are now available from multiple manufacturers, thus single sourcing is no longer an issue. We report here the successful validation of several pharmaceutical products by an end-point florescence-based endotoxin method using the rFC reagent. The method is equivalent or superior to the compendia bacterial endotoxins test method. Based on the comparability data and extenuating circumstances, the incorporation of the end point fluorescence technique and rFC reagent in global compendia bacterial endotoxins test chapters is desired and warranted. LAY ABSTRACT: Public health has been protected for over 30 years with the use of a purified blood product of the horseshoe crab, limulus amebocyte lysate. More recently, this blood product can be produced in biotech manufacturing processes, which reduces potential impacts to the horseshoe crab and related species dependent upon the crab, for example, migrating shorebirds. The pharmaceutical industry has been slow to adopt the use of this reagent, Recombinant Factor C (rFC), for various reasons. We evaluated the use of rFC across many pharmaceutical products, and in other feasibility demonstration experiments, and found rFC to be a suitable alternative to the animal-derived limulus amebocyte lysate. Incorporation of rFC and its analytical method into national testing standards would provide an equivalent or better test while continuing to maintain patient safety for those who depend on medicines and while securing pharmaceutical supply chains. In addition, widespread use of this method would benefit existing animal conservation efforts. © PDA, Inc. 2017.

21 CFR 26.10 - Regulatory authorities not listed as currently equivalent.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES GENERAL MUTUAL RECOGNITION OF PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE QUALITY SYSTEM AUDIT REPORTS, AND CERTAIN MEDICAL DEVICE PRODUCT EVALUATION REPORTS: UNITED STATES AND THE...

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

PubMed

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

2014-10-01

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

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

PubMed Central

Nutan, Mohammad T.; Dodla, Uday Krishna Reddy

2014-01-01

Background: The accessibility of prescription drugs produced outside of the United States, most notably sildenafil citrate (innovator product, Viagra®), has been made much easier by the Internet. Of greatest concern to clinicians and policymakers is product quality and patient safety. The US Food and Drug Administration (FDA) has issued warnings to potential buyers that the safety of drugs purchased from the Internet cannot be guaranteed, and may present a health risk to consumers from substandard products. Objective: The objective of this study was to determine whether generic sildenafil citrate tablets from international markets obtained via the Internet are equivalent to the US innovator product regarding major aspects of pharmaceutical quality: potency, accuracy of labeling, and presence and level of impurities. This will help identify aspects of drug quality that may impact public health risks. Methods: A total of 15 sildenafil citrate tablets were obtained for pharmaceutical analysis: 14 generic samples from international Internet pharmacy websites and the US innovator product. According to US Pharmacopeial guidelines, tablet samples were tested using high-performance liquid chromatography for potency of active pharmaceutical ingredient (API) and levels of impurities (impurities A, B, C, and D). Impurity levels were compared with International Conference on Harmonisation (ICH) limits. Results: Among the 15 samples, 4 samples possessed higher impurity B levels than the ICH qualification threshold, 8 samples possessed higher impurity C levels than the ICH qualification threshold, and 4 samples possessed more than 1% impurity quantity of maximum daily dose (MDD). For API, 6 of the samples failed to fall within the 5% assay limit. Conclusions: Quality assurance tests are often used to detect formulation defects of drug products during the manufacturing and/or storage process. Results suggest that manufacturing standards for sildenafil citrate generic drug products compared with the US innovator product are not equivalent with regards to potency and levels of impurities. These findings have implications for safety and effectiveness that should be addressed by clinicians to safeguard consumers who choose to purchase sildenafil citrate and foreign-manufactured drugs, in general, via the Internet. PMID:25360239

Comparison of Pharmaceutical Calculations Learning Outcomes Achieved Within a Traditional Lecture or Flipped Classroom Andragogy.

PubMed

Anderson, H Glenn; Frazier, Lisa; Anderson, Stephanie L; Stanton, Robert; Gillette, Chris; Broedel-Zaugg, Kim; Yingling, Kevin

2017-05-01

Objective. To compare learning outcomes achieved from a pharmaceutical calculations course taught in a traditional lecture (lecture model) and a flipped classroom (flipped model). Methods. Students were randomly assigned to the lecture model and the flipped model. Course instructors, content, assessments, and instructional time for both models were equivalent. Overall group performance and pass rates on a standardized assessment (Pcalc OSCE) were compared at six weeks and at six months post-course completion. Results. Student mean exam scores in the flipped model were higher than those in the lecture model at six weeks and six months later. Significantly more students passed the OSCE the first time in the flipped model at six weeks; however, this effect was not maintained at six months. Conclusion. Within a 6 week course of study, use of a flipped classroom improves student pharmacy calculation skill achievement relative to a traditional lecture andragogy. Further study is needed to determine if the effect is maintained over time.

Comparison of Pharmaceutical Calculations Learning Outcomes Achieved Within a Traditional Lecture or Flipped Classroom Andragogy

PubMed Central

Frazier, Lisa; Anderson, Stephanie L.; Stanton, Robert; Gillette, Chris; Broedel-Zaugg, Kim; Yingling, Kevin

2017-01-01

Objective. To compare learning outcomes achieved from a pharmaceutical calculations course taught in a traditional lecture (lecture model) and a flipped classroom (flipped model). Methods. Students were randomly assigned to the lecture model and the flipped model. Course instructors, content, assessments, and instructional time for both models were equivalent. Overall group performance and pass rates on a standardized assessment (Pcalc OSCE) were compared at six weeks and at six months post-course completion. Results. Student mean exam scores in the flipped model were higher than those in the lecture model at six weeks and six months later. Significantly more students passed the OSCE the first time in the flipped model at six weeks; however, this effect was not maintained at six months. Conclusion. Within a 6 week course of study, use of a flipped classroom improves student pharmacy calculation skill achievement relative to a traditional lecture andragogy. Further study is needed to determine if the effect is maintained over time. PMID:28630511

42 CFR 60.50 - Which schools are eligible to be HEAL schools?

Code of Federal Regulations, 2010 CFR

2010-10-01

... Osteopathic Medicine Doctor of Dentistry or equivalent degree Bachelor or Master of Science in Pharmacy or...) Council on Podiatric Medical Education. (G) American Council on Pharmaceutical Education. (H) Council on...

WHO Expert Committee on Specifications for Pharmaceutical Preparations. Forty-ninth report.

PubMed

2015-01-01

The Expert Committee on Specifications for Pharmaceutical Preparations works towards clear, independent and practical standards and guidelines for the quality assurance of medicines. Standards are developed by the Committee through worldwide consultation and an international consensus-building process. The following new guidelines were adopted and recommended for use. Revised procedure for the development of monographs and other texts for The International Pharmacopoeia; Revised updating mechanism for the section on radiopharmaceuticals in The International Pharmacopoeia; Revision of the supplementary guidelines on good manufacturing practices: validation, Appendix 7: non-sterile process validation; General guidance for inspectors on hold-time studies; 16 technical supplements to Model guidance for the storage and transport of time- and temperature-sensitive pharmaceutical products; Recommendations for quality requirements when plant-derived artemisinin is used as a starting material in the production of antimalarial active pharmaceutical ingredients; Multisource (generic) pharmaceutical products: guidelines on registration requirements to establish interchangeability: revision; Guidance on the selection of comparator pharmaceutical products for equivalence assessment of interchangeable multisource (generic) products: revision; and Good review practices: guidelines for national and regional regulatory authorities.

Pharmaceutical Spending and German Reunification: Parity Comes Quickly to Berlin

PubMed Central

Katz, Eric M.

1994-01-01

As the Berlin Wall fell and the population of the Federal Republic of Germany (FRG, West Germany) swelled by 25 percent with the addition of the former German Democratic Republic (GDR, East Germany), the health care system struggled to keep pace. This article examines drug outlays by the statutory sickness funds during the first 2 years of unified operations. It shows that providing equivalent coverage quickly led to equal rates of pharmaceutical consumption nationwide, while in Berlin the former East outdistanced the West by a considerable margin. PMID:10137795

Does government subsidy for costs of medical and pharmaceutical services result in higher service utilization by older widowed women in Australia?

PubMed

Tooth, Leigh R; Hockey, Richard; Treloar, Susan; McClintock, Christine; Dobson, Annette

2012-06-27

In Australia, Medicare, the national health insurance system which includes the Medical Benefits Scheme (MBS) and Pharmaceutical Benefits Scheme (PBS), provides partial coverage for most medical services and pharmaceuticals. For war widows, the Department of Veterans' Affairs (DVA) covers almost the entire cost of their health care. The objective of this study was to test whether war widows have higher usage of medical services and pharmaceuticals. Data were from 730 women aged 70-84 years (mostly World War II widows) participating in the Australian Longitudinal Study on Women's Health who consented to data linkage to Medicare Australia. The main outcome measures were PBS costs, claims, co-payments and scripts presented, and MBS total costs, claims and gap payments for medical services in 2005. There was no difference between the war widows and similarly aged widows in the Australian population without DVA support on use of medical services. While war widows had more pharmaceutical prescriptions filled they generated equivalent total costs, number of claims and co-payments for pharmaceuticals than widows without DVA support. Older war widows are not using more medical services and pharmaceuticals than other older Australian women despite having financial incentives to do so.

General and mechanistic optimal relationships for tensile strength of doubly convex tablets under diametrical compression.

PubMed

Razavi, Sonia M; Gonzalez, Marcial; Cuitiño, Alberto M

2015-04-30

We propose a general framework for determining optimal relationships for tensile strength of doubly convex tablets under diametrical compression. This approach is based on the observation that tensile strength is directly proportional to the breaking force and inversely proportional to a non-linear function of geometric parameters and materials properties. This generalization reduces to the analytical expression commonly used for flat faced tablets, i.e., Hertz solution, and to the empirical relationship currently used in the pharmaceutical industry for convex-faced tablets, i.e., Pitt's equation. Under proper parametrization, optimal tensile strength relationship can be determined from experimental results by minimizing a figure of merit of choice. This optimization is performed under the first-order approximation that a flat faced tablet and a doubly curved tablet have the same tensile strength if they have the same relative density and are made of the same powder, under equivalent manufacturing conditions. Furthermore, we provide a set of recommendations and best practices for assessing the performance of optimal tensile strength relationships in general. Based on these guidelines, we identify two new models, namely the general and mechanistic models, which are effective and predictive alternatives to the tensile strength relationship currently used in the pharmaceutical industry. Copyright © 2015 Elsevier B.V. All rights reserved.

Relevance of various animal models of human infections to establish therapeutic equivalence of a generic product of piperacillin/tazobactam.

PubMed

Agudelo, Maria; Rodriguez, Carlos A; Zuluaga, Andres F; Vesga, Omar

2015-02-01

After demonstrating with diverse intravenous antibacterials that pharmaceutical equivalence (PE) does not predict therapeutic equivalence, we tested a single generic product of piperacillin/tazobactam (TZP) in terms of PE, pharmacokinetics and in vitro/vivo pharmacodynamics against several pathogens in neutropenic mouse thigh, lung and brain infection models. A generic product was compared head-to-head against the innovator. PE was evaluated by microbiological assay. Single-dose serum pharmacokinetics were determined in infected mice, and the MIC/MBC were determined by broth microdilution. In vivo experiments were done in a blind fashion. Reproducibility was tested on different days using different infecting organisms and animal models. Neutropenic MPF mice were infected in the thighs with Staphylococcus aureus GRP-0057 or Pseudomonas aeruginosa PA01 and in the lungs or brain with Klebsiella pneumoniae ATCC 10031. Treatment started 2h (thigh and brain) or 14 h (lung) after infection and was administered every 3h over 24h (thigh and lung) or 48 h (brain). Both products exhibited the same MIC/MBC against each strain, yielded overlaid curves in the microbiological assay (P>0.21) and were bioequivalent (IC90 83-117% for AUC test/reference ratio). In vivo, the generic product and innovator were again undistinguishable in all models and against the different bacterial pathogens involved. The relevance of these neutropenic murine models of infection was established by demonstrating their accuracy to predict the biological response following simultaneous treatment with a generic product or the innovator of TZP. Therapeutic equivalence of the generic product was proved in every model and against different pathogens. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

21 CFR 26.32 - Scope.

Code of Federal Regulations, 2010 CFR

2010-04-01

... PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE QUALITY SYSTEM AUDIT REPORTS, AND CERTAIN... bodies (CAB's) assessed to be equivalent: (1) Under the U.S. system, surveillance/postmarket and initial/preapproval inspection reports; (2) Under the U.S. system, premarket (510(k)) product evaluation reports; (3...

Computerized Drug Information Services

ERIC Educational Resources Information Center

And Others; Smith, Daniel R.

1972-01-01

To compare computerized services in chemistry, pharmacology, toxicology, and clinical medicine of pharmaceutical interest, equivalent profiles were run on magnetic tape files of CA-Condensates," CBAC," Excerpta Medica," MEDLARS" and Ringdoc." The results are tabulated for overlap of services, relative speed of citing references, and unique…

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

PubMed

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

2016-09-01

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

Toxicological relevance of pharmaceuticals in drinking water.

PubMed

Bruce, Gretchen M; Pleus, Richard C; Snyder, Shane A

2010-07-15

Interest in the public health significance of trace levels of pharmaceuticals in potable water is increasing, particularly with regard to the effects of long-term, low-dose exposures. To assess health risks and establish target concentrations for water treatment, human health risk-based screening levels for 15 pharmaceutically active ingredients and four metabolites were compared to concentrations detected at 19 drinking water treatment plants across the United States. Compounds were selected based on rate of use, likelihood of occurrence, and potential for toxicity. Screening levels were established based on animal toxicity data and adverse effects at therapeutic doses, focusing largely on reproductive and developmental toxicity and carcinogenicity. Calculated drinking water equivalent levels (DWELs) ranged from 0.49 microg/L (risperidone) to 20,000 microg/L (naproxen). None of the 10 detected compounds exceeded their DWEL. Ratios of DWELs to maximum detected concentrations ranged from 110 (phenytoin) to 6,000,000 (sulfamethoxazole). Based on this evaluation, adverse health effects from targeted pharmaceuticals occurring in U.S. drinking water are not expected.

Toward global standards for comparator pharmaceutical products: case studies of amoxicillin, metronidazole, and zidovudine in the Americas.

PubMed

Löbenberg, Raimar; Chacra, Nadia B; Stippler, Erika S; Shah, Vinod P; DeStefano, Anthony J; Hauck, Walter W; Williams, Roger L

2012-09-01

This study compared in vitro dissolution characteristics and other quality measures of different amoxicillin, metronidazole, and zidovudine products purchased in the Americas to a comparator pharmaceutical product (CPP). These three drugs are classified as Biopharmaceutics Classification System Class I drugs with the possibility that dissolution findings might be used to document bioequivalence. All investigated zidovudine products were found to be in vitro equivalent to the CPP. Only 3 of 12 tested amoxicillin products were found to be in vitro equivalent to the CPP. None of the tested metronidazole products were in vitro equivalent to the CPP. These findings suggest but do not confirm bioinequivalence where in vitro comparisons failed, given that an in vivo blood level study might have confirmed bioequivalence. At times, identifying a CPP in one of the selected markets proved difficult. The study demonstrates that products sold across national markets may not be bioequivalent. When coupled with the challenge of identifying a CPP in different countries, the results of this study suggest the value of an international CPP as well as increased use of BCS approaches as means of either documenting bioequivalence or signaling the need for further in vivo studies. Because of increased movement of medicines across national borders, practitioners and patients would benefit from these approaches.

Restrictions of the sale of pharmaceuticals and medical devices such as contact lenses over the internet and the free movement of goods.

PubMed

de Sadeleer, Nicolas

2012-03-01

In the light of new case law development, this article examines whether national restrictions on the online sale of pharmaceuticals and medical devices such as contact lenses are consistent either with EU secondary law, either with Article 34 TFEU that prohibits measures having equivalent effect to quantitative restrictions on imports. In particular, this article focuses on an analysis of two judgments on this important issue delivered by the Court of Justice of the European Union in 2003 and 2010, namely the Deutscher Apothekerverband decision and the Ker-Optika decision.

Validation of artificial skin equivalents as in vitro testing systems

NASA Astrophysics Data System (ADS)

Schmitt, Robert; Marx, Ulrich; Walles, Heike; Schober, Lena

2011-03-01

With the increasing complexity of the chemical composition of pharmaceuticals, cosmetics and everyday substances, the awareness of potential health issues and long term damages for humanoid organs is shifting into focus. Artificial in vitro testing systems play an important role in providing reliable test conditions and replacing precarious animal testing. Especially artificial skin equivalents ASEs are used for a broad spectrum of studies like penetration, irritation and corrosion of substances. One major challenge in tissue engineering is the qualification of each individual ASE as in vitro testing system. Due to biological fluctuations, the stratum corneum hornified layer of some ASEs may not fully develop or other defects might occur. For monitoring these effects we developed an fully automated Optical Coherence Tomography device. Here, we present different methods to characterize and evaluate the quality of the ASEs based on image and data processing of OCT B-scans. By analysing the surface structure, defects, like cuts or tears, are detectable. A further indicator for the quality of the ASE is the morphology of the tissue. This allows to determine if the skin model has reached the final growth state. We found, that OCT is a well suited technology for automatically characterizing artificial skin equivalents and validating the application as testing system.

Scientific and Regulatory Considerations for Generic Complex Drug Products Containing Nanomaterials.

PubMed

Zheng, Nan; Sun, Dajun D; Zou, Peng; Jiang, Wenlei

2017-05-01

In the past few decades, the development of medicine at the nanoscale has been applied to oral and parenteral dosage forms in a wide range of therapeutic areas to enhance drug delivery and reduce toxicity. An obvious response to these benefits is reflected in higher market shares of complex drug products containing nanomaterials than that of conventional formulations containing the same active ingredient. The surging market interest has encouraged the pharmaceutical industry to develop cost-effective generic versions of complex drug products based on nanotechnology when the associated patent and exclusivity on the reference products have expired. Due to their complex nature, nanotechnology-based drugs present unique challenges in determining equivalence standards between generic and innovator products. This manuscript attempts to provide the scientific rationales and regulatory considerations of key equivalence standards (e.g., in vivo studies and in vitro physicochemical characterization) for oral drugs containing nanomaterials, iron-carbohydrate complexes, liposomes, protein-bound drugs, nanotube-forming drugs, and nano emulsions. It also presents active research studies in bridging regulatory and scientific gaps for establishing equivalence of complex products containing nanomaterials. We hope that open communication among industry, academia, and regulatory agencies will accelerate the development and approval processes of generic complex products based on nanotechnology.

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

PubMed

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 on quality and transparency, triggered by, amongst others, current legislation (Hospital Structures Act, anti-corruption legislation). Copyright © 2017. Published by Elsevier GmbH.

21 CFR 26.39 - Equivalence assessment.

Code of Federal Regulations, 2010 CFR

2010-04-01

... RECOGNITION OF PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE QUALITY SYSTEM AUDIT REPORTS... perform any type of quality system or product evaluation covered by this subpart and with regard to any... any type of quality system or product evaluation. (b) The parties shall allow CAB's not listed for...

[Detection of Physiological Activity of Pharmaceuticals in Wastewater and River Water].

PubMed

Ihara, Masaru; Zhang, Han; Hanamoto, Seiya; Tanaka, Hiroaki

2018-01-01

　Pharmaceuticals are widely found in aquatic environments worldwide. Concern about their potential risks to aquatic species has been raised because they are designed to be biologically active. To address this concern, we must know whether biological activity of pharmaceuticals can be detected in waters. Nearly half of all marketed pharmaceuticals act by binding to the G protein-coupled receptor (GPCR). In this study, we measured the physiological activity of GPCR-acting pharmaceuticals in effluent from a wastewater treatment plant (WWTP) and upstream and downstream of its outfall in Japan during 2 years. We used the in vitro transforming growth factor-α (TGFα) shedding assay, which accurately and sensitively detects GPCR activation, to investigate the antagonistic activities of water extracts against receptors for dopamine (D2) and histamine (H1). Activities detected in waters were quantified as antagonist equivalent quantities (EQs). In WWTP effluent extracts, antagonistic activity was detected at several hundred ng/L of sulpiride-EQ (D2) and several μg/L of diphenhydramine (DIP)-EQ (H1). In downstream river water extracts, antagonistic activity against H1 was around several hundred ng/L of DIP-EQ, higher than that upstream owing to the WWTP effluent. This review discusses the research needed to resolve the concern about potential risks of pharmaceuticals in waters to aquatic species.

Accumulation and leaching potential of some pharmaceuticals and potential endocrine disruptors in soils irrigated with wastewater in the Tula Valley, Mexico.

PubMed

Gibson, Richard; Durán-Álvarez, Juan C; Estrada, Karina León; Chávez, Alma; Jiménez Cisneros, Blanca

2010-12-01

The reuse of wastewater for irrigation of agricultural land is a well established practice but introduces many contaminants into the terrestrial environment including pharmaceuticals and personal care products. This study reports the persistence and leaching potential of a group of acidic pharmaceuticals, carbamazepine, and three endocrine disruptors in soils from the Tula Valley in Mexico, one of the largest irrigation districts in the world that uses untreated wastewater. After irrigation of soil columns with fortified wastewater over the equivalent of one crop cycle, between 0% and 7% of the total added amounts of ibuprofen, naproxen, and diclofenac and between 0% and 25% of 4-nonylphenol, triclosan, and bisphenol-A were recovered from the soil profiles. Carbamazepine was more persistent, between 55% and 107% being recovered. Amounts in leachates suggested that movement through the soil was possible for all of the analytes, particularly in profiles of low organic matter and clay content. Analysis of soil samples from the Tula Valley confirmed the general lack of accumulation of the acidic pharmaceuticals (concentrations from below the limit of detection to 0.61 μgkg(-1)) and endocrine disruptors (concentrations from below the limit of detection to 109 μgkg(-1)) despite continual addition through regular irrigation with untreated wastewater; there was little evidence of movement through the soil profiles. In contrast, carbamazepine was present in horizon A of the soil at concentrations equivalent to several years of additions by irrigation (2.6-7.5 μgkg(-1)) and was also present in the deeper horizons. The persistence and mobility of carbamazepine suggested a potential to contaminate groundwater. Copyright © 2010 Elsevier Ltd. All rights reserved.

Comparison of a Lyophilized Drug Product to Other Solid and Liquid Media for the Extraction of Elastomeric Oligomers from a Butyl Rubber Stopper.

PubMed

Zdravkovic, Steven A

2017-01-01

Lyophilization is commonly used to extend the shelf life of pharmaceutical products that are otherwise unstable when stored as a liquid formulation. However, the ability of a lyophilized drug, or other solid medium, to leach or extract substances from a pharmaceutical packaging material is not well characterized. To provide insight into this area of uncertainty, the extraction properties of a lyophilized drug product, the lyophilized drug product reconstituted in water, and several other solid and liquid media of varying polarity were determined using a glass vial with a butyl rubber stopper as a representative pharmaceutical packaging system. The results obtained in this study show that the extracting power of a medium, whether solid or liquid, was primarily a function of polarity. Thus, the amount of each extractable observed for the lyophilized and reconstituted drug product were in trend with the other solid and liquid media, respectively. Nevertheless, it was notable that the lyophilized drug product was able to leach substances from the stopper in quantifiable amounts, whereas the reconstituted drug product contained no detectable leachables. Using a mathematical relationship, it was determined that the extraction power of the lyophilized drug product was equivalent to a 50/50 isopropanol/water solution. LAY ABSTRACT: Freeze drying is commonly used to extend the shelf life of pharmaceutical products that are otherwise unstable when stored as a liquid formulation. However, the propensity for substances to migrate from a pharmaceutical packaging material and into a solid drug formulation is not well characterized. To provide insight into this area of uncertainty, the migration of substances from a glass vial with a butyl rubber stopper and into a lyophilized drug product, the drug product reconstituted with water, as well as several solid and liquid media of varying polarity were assessed. The results obtained in this study show that the extracting power of a medium, whether solid or liquid, was primarily a function of polarity and thus could be related to one another. Furthermore, the results for the freeze-dried and reconstituted drug products were in trend with the other solid and liquid media tested, respectively, and showed that the freeze-dried drug was able to leach substances from the stopper in measureable amounts, whereas the reconstituted drug product contained no substances that had originated from the stopper. © PDA, Inc. 2017.

Identification of phenolic compounds in petals of nasturtium flowers (Tropaeolum majus) by high-performance liquid chromatography coupled to mass spectrometry and determination of oxygen radical absorbance capacity (ORAC).

PubMed

Garzón, G Astrid; Manns, David C; Riedl, Ken; Schwartz, Steven J; Padilla-Zakour, Olga

2015-02-18

The contents and profile of polyphenols were analyzed in edible petals of nasturtium flowers (Tropaeolum majus) of three colors, and their oxygen radical absorbance capacities (ORAC) were compared. Three primary anthocyanins (ACNs) and 15 non-ACN phenolic compounds including hydroxycinammic acids (HCAs) and flavonoids (myricetin, quercetin, and kaempferol derivatives) were detected. Anthocyanin concentration was within 31.9 ± 21.7 and 114.5 ± 2.3 mg cyanidin-3-glucoside (cy-3-glu)/100 g fresh weight (FW) in yellow and red petals, respectively. The concentration of HCAs varied between 33.3 ± 7.1 and 235.6 ± 8.1 mg chlorogenic acid equivalents/100 g FW for red and yellow flowers, respectively. Red flowers had the highest level of flavonoids (315.1 ± 2.4 mg myricetin equivalents/100 g FW) and the highest ORAC radical-scavenging activity. These results show the diversity and abundance of polyphenolic compounds in nasturtium flowers, which could be the basis for applications in functional foods, cosmetics, and pharmaceuticals.

GC-MS quantitative analysis of black market pharmaceutical products containing anabolic androgenic steroids seized by the Brazilian Federal Police.

PubMed

Neves, Diana Brito da Justa; Caldas, Eloisa Dutra

2017-06-01

The use of counterfeit or substandard medicines can have an important health impact, resulting in therapeutic failure, be toxic or even cause death. Anabolic steroids are a frequent target for counterfeiters worldwide, being the second most frequent counterfeited class in Brazil. The aims of this work were to optimize and validate a GC-MS method for the quantitative determination of anabolic steroids in tablet, aqueous suspension and oil solution forms, and to analyze pharmaceutical products sent to Brazilian Federal Police (BFP) for forensic analysis. Sample preparation included extraction with methanol in ultrasonic bath followed by centrifugation. The method was successfully validated and 345 samples of pharmaceutical products were analyzed (328 medicines and 17 dietary supplements). About 42% of the medicines were counterfeits, 28.7% of tablets, 12.0% of suspensions and 65.2% of oil solutions; 11% were considered substandards. Five dietary supplements contained undeclared anabolic steroids, including two containing methandrostenolone at 5.4 and 5.8mg/capsule, equivalent to levels found in medicines. The proposed method is suitable for implementation in routine analysis for identification of counterfeits and substandard products. The analytical results show the need to raise awareness of consumers over the risks from the consumption of anabolic steroids from the clandestine market and for more incisive actions from government agencies aiming at decreasing the availability of these products. Copyright © 2017 Elsevier B.V. All rights reserved.

Current challenges in bioequivalence, quality, and novel assessment technologies for topical products.

PubMed

Yacobi, Avraham; Shah, Vinod P; Bashaw, Edward D; Benfeldt, Eva; Davit, Barbara; Ganes, Derek; Ghosh, Tapash; Kanfer, Isadore; Kasting, Gerald B; Katz, Lindsey; Lionberger, Robert; Lu, Guang Wei; Maibach, Howard I; Pershing, Lynn K; Rackley, Russell J; Raw, Andre; Shukla, Chinmay G; Thakker, Kailas; Wagner, Nathalie; Zovko, Elizabeta; Lane, Majella E

2014-04-01

This paper summarises the proceedings of a recent workshop which brought together pharmaceutical scientists and dermatologists from academia, industry and regulatory agencies to discuss current regulatory issues and industry practices for establishing therapeutic bioequivalence (BE) of dermatologic topical products. The methods currently available for assessment of BE were reviewed as well as alternatives and the advantages and disadvantages of each method were considered. Guidance on quality and performance of topical products was reviewed and a framework to categorise existing and alternative methods for evaluation of BE was discussed. The outcome of the workshop emphasized both a need for greater attention to quality, possibly, via a Quality-By-Design (QBD) approach and a need to develop a "whole toolkit" approach towards the problem of determination of rate and extent in the assessment of topical bioavailability. The discussion on the BE and clinical equivalence of topical products revealed considerable concerns about the variability present in the current methodologies utilized by the industry and regulatory agencies. It was proposed that academicians, researchers, the pharmaceutical industry and regulators work together to evaluate and validate alternative methods that are based on both the underlying science and are adapted to the drug product itself instead of single "universal" method.

Determination of human-use pharmaceuticals in filtered water by direct aqueous injection: high-performance liquid chromatography/tandem mass spectrometry

USGS Publications Warehouse

Furlong, Edward T.; Noriega, Mary C.; Kanagy, Christopher J.; Kanagy, Leslie K.; Coffey, Laura J.; Burkhardt, Mark R.

2014-01-01

This report describes a method for the determination of 110 human-use pharmaceuticals using a 100-microliter aliquot of a filtered water sample directly injected into a high-performance liquid chromatograph coupled to a triple-quadrupole tandem mass spectrometer using an electrospray ionization source operated in the positive ion mode. The pharmaceuticals were separated by using a reversed-phase gradient of formic acid/ammonium formate-modified water and methanol. Multiple reaction monitoring of two fragmentations of the protonated molecular ion of each pharmaceutical to two unique product ions was used to identify each pharmaceutical qualitatively. The primary multiple reaction monitoring precursor-product ion transition was quantified for each pharmaceutical relative to the primary multiple reaction monitoring precursor-product transition of one of 19 isotope-dilution standard pharmaceuticals or the pesticide atrazine, using an exact stable isotope analogue where possible. Each isotope-dilution standard was selected, when possible, for its chemical similarity to the unlabeled pharmaceutical of interest, and added to the sample after filtration but prior to analysis. Method performance for each pharmaceutical was determined for reagent water, groundwater, treated drinking water, surface water, treated wastewater effluent, and wastewater influent sample matrixes that this method will likely be applied to. Each matrix was evaluated in order of increasing complexity to demonstrate (1) the sensitivity of the method in different water matrixes and (2) the effect of sample matrix, particularly matrix enhancement or suppression of the precursor ion signal, on the quantitative determination of pharmaceutical concentrations. Recovery of water samples spiked (fortified) with the suite of pharmaceuticals determined by this method typically was greater than 90 percent in reagent water, groundwater, drinking water, and surface water. Correction for ambient environmental concentrations of pharmaceuticals hampered the determination of absolute recoveries and method sensitivity of some compounds in some water types, particularly for wastewater effluent and influent samples. The method detection limit of each pharmaceutical was determined from analysis of pharmaceuticals fortified at multiple concentrations in reagent water. The calibration range for each compound typically spanned three orders of magnitude of concentration. Absolute sensitivity for some compounds, using isotope-dilution quantitation, ranged from 0.45 to 94.1 nanograms per liter, primarily as a result of the inherent ionization efficiency of each pharmaceutical in the electrospray ionization process. Holding-time studies indicate that acceptable recoveries of pharmaceuticals can be obtained from filtered water samples held at 4 °C for as long as 9 days after sample collection. Freezing samples to provide for storage for longer periods currently (2014) is under evaluation by the National Water Quality Laboratory.

42 CFR 447.514 - Upper limits for multiple source drugs.

Code of Federal Regulations, 2010 CFR

2010-10-01

... State agency plus an amount established by CMS that is equal to 250 percent of the AMP (as computed... will consider the following additional criteria: (1) The AMP of a terminated NDC will not be used to... section, the AMP of the lowest priced therapeutically and pharmaceutically equivalent drug that is not...

Estimating the Fiscal Effects of Public Pharmaceutical Expenditure Reduction in Greece

PubMed Central

Souliotis, Kyriakos; Papageorgiou, Manto; Politi, Anastasia; Frangos, Nikolaos; Tountas, Yiannis

2015-01-01

The purpose of the present study is to estimate the impact of pharmaceutical spending reduction on public revenue, based on data from the national health accounts as well as on reports of Greece’s organizations. The methodology of the analysis is structured in two basic parts. The first part presents the urgency for rapid cutbacks on public pharmaceutical costs due to the financial crisis and provides a conceptual framework for the contribution of the Greek pharmaceutical branch to the country’s economy. In the second part, we perform a quantitative analysis for the estimation of multiplier effects of public pharmaceutical expenditure reduction on main revenue sources, such as taxes and social contributions. We also fit projection models with multipliers as regressands for the evaluation of the efficiency of the particular fiscal measure in the short run. According to the results, nearly half of the gains from the measure’s application is offset by financially equivalent decreases in the government’s revenue, i.e., losses in tax revenues and social security contributions alone, not considering any other direct or indirect costs. The findings of multipliers’ high value and increasing short-term trend imply the measure’s inefficiency henceforward and signal the risk of vicious circles that will provoke the economy’s deprivation of useful resources. PMID:26380249

Estimating the Fiscal Effects of Public Pharmaceutical Expenditure Reduction in Greece.

PubMed

Souliotis, Kyriakos; Papageorgiou, Manto; Politi, Anastasia; Frangos, Nikolaos; Tountas, Yiannis

2015-01-01

The purpose of the present study is to estimate the impact of pharmaceutical spending reduction on public revenue, based on data from the national health accounts as well as on reports of Greece's organizations. The methodology of the analysis is structured in two basic parts. The first part presents the urgency for rapid cutbacks on public pharmaceutical costs due to the financial crisis and provides a conceptual framework for the contribution of the Greek pharmaceutical branch to the country's economy. In the second part, we perform a quantitative analysis for the estimation of multiplier effects of public pharmaceutical expenditure reduction on main revenue sources, such as taxes and social contributions. We also fit projection models with multipliers as regressands for the evaluation of the efficiency of the particular fiscal measure in the short run. According to the results, nearly half of the gains from the measure's application is offset by financially equivalent decreases in the government's revenue, i.e., losses in tax revenues and social security contributions alone, not considering any other direct or indirect costs. The findings of multipliers' high value and increasing short-term trend imply the measure's inefficiency henceforward and signal the risk of vicious circles that will provoke the economy's deprivation of useful resources.

Physicochemical equivalence of generic antihypertensive medicines (EQUIMEDS): protocol for a quality of medicines assessment

PubMed Central

Redfern, Julie; Adedoyin, Rufus Adesoji; Ofori, Sandra; Anchala, Raghupathy; Ajay, Vamadevan S; De Andrade, Luciano; Zelaya, Jose; Kaur, Harparkash; Balabanova, Dina; Sani, Mahmoud U

2016-01-01

Background Prevention and optimal management of hypertension in the general population is paramount to the achievement of the World Heart Federation (WHF) goal of reducing premature cardiovascular disease (CVD) mortality by 25% by the year 2025 and widespread access to good quality antihypertensive medicines is a critical component for achieving the goal. Despite research and evidence relating to other medicines such as antimalarials and antibiotics, there is very little known about the quality of generic antihypertensive medicines in low-income and middle-income countries. The aim of this study was to determine the physicochemical equivalence (percentage of active pharmaceutical ingredient, API) of generic antihypertensive medicines available in the retail market of a developing country. Methods An observational design will be adopted, which includes literature search, landscape assessment, collection and analysis of medicine samples. To determine physicochemical equivalence, a multistage sampling process will be used, including (1) identification of the 2 most commonly prescribed classes of antihypertensive medicines prescribed in Nigeria; (2) identification of a random sample of 10 generics from within each of the 2 most commonly prescribed classes; (3) a geographical representative sampling process to identify a random sample of 24 retail outlets in Nigeria; (4) representative sample purchasing, processing to assess the quality of medicines, storage and transport; and (5) assessment of the physical and chemical equivalence of the collected samples compared to the API in the relevant class. In total, 20 samples from each of 24 pharmacies will be tested (total of 480 samples). Discussion Availability of and access to quality antihypertensive medicines globally is therefore a vital strategy needed to achieve the WHF 25×25 targets. However, there is currently a scarcity of knowledge about the quality of antihypertensive medicines available in developing countries. Such information is important for enforcing and for ensuring the quality of antihypertensive medicines. PMID:28588941

Chemical composition of various Ephedra species

PubMed Central

Ibragic, Saida; Sofić, Emin

2015-01-01

The medicinal significance of Ephedra is based on the sympathomimetic properties of ephedrine (E) alkaloids. Pharmacological effects depend on the phytocomposition of individual Ephedra species. The aim of this study was to measure the total alkaloids content (TAC), total phenolics content (TPC), and total flavonoids content (TFC) and determine their relationship in dry herb of Ephedra major, Ephedra distachya subsp. helvetica, Ephedra monosperma, Ephedra fragilis, Ephedra foeminea, Ephedra alata, Ephedra altissima and Ephedra foliata. Nowadays, medicinal use of Ephedrae herba is limited, but the abuse of its psychostimulants is rising. In this study, TAC, TPC and TFC were determined using spectrophotometric methods. For the first time, ultra-performance liquid chromatography with ultraviolet detection (UPLC-UV) was used for separation and quantification of E-type alkaloids of various Ephedra species. The highest TPC and TFC were found in E. alata (53.3 ± 0.1 mg Gallic acid equivalents/g dry weight, 2.8 mg quercetin equivalents/g dry weight, respectively). The total content of E and pseudoephedrine determined by UPLC-UV varied between 20.8 mg/g dry weight (E. distachya subsp. helvetica) and 34.7 mg/g dry weight (E. monosperma). The variable content and ratio between secondary metabolites determined in different Ephedra species reflects their metabolic activities. Utilization of UPLC-UV unveiled that this technique is sensitive, selective, and useful for separation and quantification of different alkaloids in complex biological matrixes. The limit of detection was 5 ng. Application of UPLC-UV can be recommended in quick analyses of E-type alkaloids in forensic medicine and quality control of pharmaceutical preparations. PMID:26295290

Radiation treatment of pharmaceuticals

NASA Astrophysics Data System (ADS)

Dám, A. M.; Gazsó, L. G.; Kaewpila, S.; Maschek, I.

1996-03-01

Product specific doses were calculated for pharmaceuticals to be radiation treated. Radio-pasteurization dose were determined for some heat sensitive pharmaceutical basic materials (pancreaton, neopancreatin, neopancreatin USP, duodenum extract). Using the new recommendation (ISO standards, Method 1) dose calculations were performed and radiation sterilization doses were determined for aprotinine and heparine Na.

The U.S. draft guidance regarding population and individual bioequivalence approaches: comments by a research-based pharmaceutical company.

PubMed

Hauschke, D; Steinijans, V W

2000-10-30

Generally, the motivation for switching from average bioequivalence to population and/or individual bio-equivalence is well recognized in the light of certain limitations of the concept of average bioequivalence. However, this switch still results in unresolved issues which should be addressed before the regulatory guidance is finalized.

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

PubMed

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

2004-01-01

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

Diclofenac removal in urine using strong-base anion exchange polymer resins.

PubMed

Landry, Kelly A; Boyer, Treavor H

2013-11-01

One of the major sources of pharmaceuticals in the environment is wastewater effluent of which human urine contributes the majority of pharmaceuticals. Urine source separation has the potential to isolate pharmaceuticals at a higher concentration for efficient removal as well as produce a nutrient byproduct. This research investigated the efficacy of using strong-base anion exchange polymer resins to remove the widely detected and abundant pharmaceutical, diclofenac, from synthetic human urine under fresh and ureolyzed conditions. The majority of experiments were conducted using a strong-base, macroporous, polystyrene resin (Purolite A520E). Ion-exchange followed a two-step removal rate with rapid removal in 1 h and equilibrium removal in 24 h. Diclofenac removal was >90% at a resin dose of 8 mL/L in both fresh and ureolyzed urine. Sorption of diclofenac onto A520E resin was concurrent with desorption of an equivalent amount of chloride, which indicates the ion-exchange mechanism is occurring. The presence of competing ions such as phosphate and citrate did not significantly impact diclofenac removal. Comparisons of three polystyrene resins (A520E, Dowex 22, Dowex Marathon 11) as well as one polyacrylic resin (IRA958) were conducted to determine the major interactions between anion exchange resin and diclofenac. The results showed that polystyrene resins provide the highest level of diclofenac removal due to electrostatic interactions between quaternary ammonium functional groups of resin and carboxylic acid of diclofenac and non-electrostatic interactions between resin matrix and benzene rings of diclofenac. Diclofenac was effectively desorbed from A520E resin using a regeneration solution that contained 4.5% (m/m) NaCl in an equal-volume mixture of methanol and water. The greater regeneration efficiency of the NaCl/methanol-water mixture over the aqueous NaCl solution supports the importance of non-electrostatic interactions between resin matrix and benzene rings of diclofenac. Experiments with ketoprofen, in addition to diclofenac, suggest that polystyrene anion exchange resins can be used to selectively remove other acidic pharmaceuticals from urine. Copyright © 2013 Elsevier Ltd. All rights reserved.

Recent advances in capillary electrophoretic migration techniques for pharmaceutical analysis.

PubMed

Deeb, Sami El; Wätzig, Hermann; El-Hady, Deia Abd; Albishri, Hassan M; de Griend, Cari Sänger-van; Scriba, Gerhard K E

2014-01-01

Since the introduction about 30 years ago, CE techniques have gained a significant impact in pharmaceutical analysis. The present review covers recent advances and applications of CE for the analysis of pharmaceuticals. Both small molecules and biomolecules such as proteins are considered. The applications range from the determination of drug-related substances to the analysis of counterions and the determination of physicochemical parameters. Furthermore, general considerations of CE methods in pharmaceutical analysis are described. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The effect of hydraulic retention time in onsite wastewater treatment and removal of pharmaceuticals, hormones and phenolic utility substances.

PubMed

Ejhed, H; Fång, J; Hansen, K; Graae, L; Rahmberg, M; Magnér, J; Dorgeloh, E; Plaza, G

2018-03-15

Micropollutants such as pharmaceuticals, hormones and phenolic utility chemicals in sewage water are considered to be an emerging problem because of increased use and observed adverse effects in the environment. The study provides knowledge on the removal efficiency of micropollutants with a range of physical and chemical properties in three commercially available onsite wastewater treatment facilities (OWTFs), tested on influent wastewater collected from 2500 person equivalents in Bildchen, Germany. A longer hydraulic retention time would in theory be expected to have a positive effect, and this study presents results for three different OWTFs in full-scale comparable tests under natural conditions. A range of 24 different pharmaceuticals, five phenols and three hormones were analyzed. Flow-proportional consecutive sampling was performed in order to determine the removal efficiency. Twenty-eight substances were detected in the effluent wastewater out of 32 substances included. Average effluent concentrations of Simvastatin, Estrone, Estradiol and Ethinylestradiol were above the indicative critical-effect concentration of pharmacological effect on fish in all facilities. Average effluent concentrations of both Diclofenac and Estradiol were higher than the Environmental Quality Standards applied in Sweden (190-240 times and 9-35 times respectively). The removal efficiency of micropollutants was high for substances with high logK ow , which enhance the adsorption and removal with sludge. Low removal was observed for substances with low logK ow and acidic characteristics, and for substances with stabilizing elements of the chemical structure. Facilities that use activated sludge processes removed hormones more efficiently than facilities using trickling filter treatment technique. Moreover, longer hydraulic retention time increased the removal of pharmaceuticals, hormones, turbidity and total nitrogen. Removal of Caffeine, Ibuprofen, Estrone, Naproxen and Estradiol, was strongly correlated to the sludge and particles removal. Thus, the efficiency of the tested OWTFs could be improved by adjusting the technical methods and increasing the hydraulic retention time. Copyright © 2017 Elsevier B.V. All rights reserved.

Standard addition method for the determination of pharmaceutical residues in drinking water by SPE-LC-MS/MS.

PubMed

Cimetiere, Nicolas; Soutrel, Isabelle; Lemasle, Marguerite; Laplanche, Alain; Crocq, André

2013-01-01

The study of the occurrence and fate of pharmaceutical compounds in drinking or waste water processes has become very popular in recent years. Liquid chromatography with tandem mass spectrometry is a powerful analytical tool often used to determine pharmaceutical residues at trace level in water. However, many steps may disrupt the analytical procedure and bias the results. A list of 27 environmentally relevant molecules, including various therapeutic classes and (cardiovascular, veterinary and human antibiotics, neuroleptics, non-steroidal anti-inflammatory drugs, hormones and other miscellaneous pharmaceutical compounds), was selected. In this work, a method was developed using ultra performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) and solid-phase extraction to determine the concentration of the 27 targeted pharmaceutical compounds at the nanogram per litre level. The matrix effect was evaluated from water sampled at different treatment stages. Conventional methods with external calibration and internal standard correction were compared with the standard addition method (SAM). An accurate determination of pharmaceutical compounds in drinking water was obtained by the SAM associated with UPLC-MS/MS. The developed method was used to evaluate the occurrence and fate of pharmaceutical compounds in some drinking water treatment plants in the west of France.

Aspects of research and development contract terms in the bio/pharmaceutical sector.

PubMed

Banerjee, Tannista

2012-01-01

The cost of new drug development is increasing every year. Pharmaceutical companies use R&D joint ventures, mergers, and outsource different stages of pharmaceutical R&D activities for a faster and cost minimizing method of innovation. Pharmaceutical companies outsource R&D activities to independent small biotech or pharmaceutical companies that specialize in different stages of pharmaceutical R&D. This chapter examines the determinants of the payment structure of research contracts between large bio/pharmaceutical companies and specialized research firms. Determinants of R&D contracts are analyzed using detailed R&D contract data between bio/pharmaceutical companies and independent research firms for 10 years. A multinomial logit model is used in order to understand the determinants of three different types of contracts; royalty contracts, fixed payment contracts, and the mixed contracts. Under uncertainty, the likelihood of a royalty contract rises for the early stages of the research and with the patent stock of the research firm. It is more likely to observe both royalty and fixed payment if the pharmaceutical client has past contracts with the same research firm. The results also suggest that if Food and Drug Administration (FDA) is more stringent in any disease area in reviewing the new drug application, then the likelihood of signing pure royalty contract decreases. Understanding the nature of R&D contracts and the effects of FDA's behavior on the pharmaceutical R&D contract is important because these contracts not only affect the cost of new drug invention but also the quality and the rate of invention. VALUE: Results are useful for both the pharmaceutical companies and the economic/business researchers.

[The introduction of generic pharmaceutical products into Galicia].

PubMed

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

1999-11-30

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

Simultaneous determination of 29 pharmaceuticals in fish muscle and plasma by ultrasonic extraction followed by SPE-UHPLC-MS/MS.

PubMed

Liu, You-Yu; Hu, Xia-Lin; Bao, Yi-Fan; Yin, Da-Qiang

2018-02-12

A confirmatory method for the simultaneous detection of 29 pharmaceuticals in fish muscle and plasma was developed by using solid-phase extraction combined with ultra high performance liquid chromatography and tandem mass spectrometry. Fish samples were extracted with methanol and enriched using Oasis HLB solid-phase extraction columns in one step. Twenty-nine target pharmaceuticals were quantified by the internal standard method and the calibration curves showed good linearity in a wide range with determination coefficients of greater than 0.913. The detection limits of the pharmaceuticals ranged from 0.01 to 2.00 μg/kg (μg/L). The applicability of the method was checked by precision and recovery experiments. The average recoveries of the 29 pharmaceuticals were between 61 and 111%, and all the relative standard deviations were below 25%. Our reported method has been demonstrated to be sensitive, convenient, rapid and reliable for the simultaneous determination of 29 pharmaceuticals in fish muscle and plasma. Real sample determination showed that 25 and 9 of the 29 compounds were detected in fish muscle and plasma, respectively. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Concentrations of hormones, pharmaceuticals and other micropollutants in groundwater affected by septic systems in New England and New York

USGS Publications Warehouse

Phillips, Patrick J.; Schubert, Christopher E.; Argue, Denise M.; Fisher, Irene J.; Furlong, Edward T.; Foreman, William T.; Gray, James L.; Chalmers, Ann T.

2015-01-01

The highest micropollutant concentrations for the NY network were present in the shoreline wells and reflect groundwater that is most affected by septic system discharges. One of the shoreline wells had personal care/domestic use, pharmaceutical, and plasticizer concentrations ranging from 0.4 to 5.7 μg/L. Estradiol equivalency quotient concentrations were also highest in a shoreline well sample (3.1 ng/L). Most micropollutant concentrations increase with increasing specific conductance and total nitrogen concentrations for shoreline well samples. These findings suggest that septic systems serving institutional settings and densely populated areas in coastal settings may be locally important sources of micropollutants to adjacent aquifer and marine systems.

77 FR 30326 - Importer of Controlled Substances; Notice Of Registration; Mylan Pharmaceuticals, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-22

... Registration; Mylan Pharmaceuticals, Inc. By Notice dated February 23, 2012, and published in the Federal Register on March 1, 2012, 77 FR 12620, Mylan Pharmaceuticals, Inc., 781 Chestnut Ridge Road, Morgantown...), and determined that the registration of Mylan Pharmaceuticals, Inc. to import the basic classes of...

78 FR 33441 - Importer of Controlled Substances; Notice of Registration; Caraco Pharmaceutical Laboratories, LTD

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-04

... Registration; Caraco Pharmaceutical Laboratories, LTD By Notice dated February 8, 2013, and published in the Federal Register on February 21, 2013, 78 FR 12101, Caraco Pharmaceutical Laboratories, Ltd., 270 Prospect... 952(a), and determined that the registration of Caraco Pharmaceutical Laboratories, Ltd., to import...

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

PubMed

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

2018-07-01

Individual treatment processes like biological treatment or ozonation have their limitations for the removal of pharmaceuticals from secondary clarified effluents with high organic matter concentrations (i.e. 17 mg TOC/L). These limitations can be overcome by combining these two processes for a cost-effective pharmaceutical removal. A three-step biological-ozone-biological (BO 3 B) treatment process was therefore designed for the enhanced pharmaceutical removal from wastewater effluent. The first biological step removed 38% of ozone scavenging TOC, thus proportionally reducing the absolute ozone input for the subsequent ozonation. Complementariness between biological and ozone treatment, i.e. targeting different pharmaceuticals, resulted in cost-effective pharmaceutical removal by the overall BO 3 B process. At a low ozone dose of 0.2 g O 3 /g TOC and an HRT of 1.46 h in the biological reactors, the removal of 8 out of 9 pharmaceuticals exceeded 85%, except for metoprolol (60%). Testing various ozone doses and HRTs revealed that pharmaceuticals were ineffectively removed at 0.1 g O3/g TOC and an HRT of 0.3 h. At HRTs of 0.47 and 1.46 h easily and moderately biodegradable pharmaceuticals such as caffeine, gemfibrozil, ibuprofen, naproxen and sulfamethoxazole were over 95% removed by biological treatment. The biorecalcitrant carbamazepine was completely ozonated at a dose of 0.4 g O 3 /g TOC. Ozonation products are likely biodegraded in the last biological reactor as a 17% TOC removal was found. No appreciable acute toxicity towards D. magna, P. subcapitata and V. fischeri was found after exposure to the influents and effluents of the individual BO 3 B reactors. The BO 3 B process is estimated to increase the yearly wastewater treatment tariff per population equivalent in the Netherlands by less than 10%. Overall, the BO 3 B process is a cost-effective treatment process for the removal of pharmaceuticals from secondary clarified effluents. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

78 FR 52802 - Manufacturer of Controlled Substances; Notice of Registration; Morton Grove Pharmaceuticals

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-26

...; Notice of Registration; Morton Grove Pharmaceuticals By Notice dated March 12, 2013, and published in the Federal Register on March 20, 2013, 78 FR 17231, Morton Grove Pharmaceuticals, 6451 Main Street, Morton... 21 U.S.C. 823(a), and determined that the registration of Morton Grove Pharmaceuticals to manufacture...

78 FR 46371 - Importer of Controlled Substances; Notice of Registration; Meda Pharmaceuticals, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-31

... Registration; Meda Pharmaceuticals, Inc. By Notice dated February 8, 2013, and published in the Federal Register on February 21, 2013, 78 FR 12101, Meda Pharmaceuticals, Inc., 705 Eldorado Street, Decatur... 21 U.S.C. 823(a) and 952(a), and determined that the registration of Meda Pharmaceuticals Inc., to...

78 FR 5503 - Manufacturer of Controlled Substances, Notice of Registration; Morton Grove Pharmaceuticals

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-25

..., Notice of Registration; Morton Grove Pharmaceuticals By Notice dated September 25, 2012, and published in the Federal Register on October 2, 2012, 77 FR 60144, Morton Grove Pharmaceuticals, 6451 Main Street... the factors in 21 U.S.C. 823(a), and determined that the registration of Morton Grove Pharmaceuticals...

77 FR 75672 - Manufacturer of Controlled Substances, Notice of Registration, Halo Pharmaceutical, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-21

..., Notice of Registration, Halo Pharmaceutical, Inc. By Notice dated July 30, 2012, and published in the Federal Register on August 7, 2012, 77 FR 47114, Halo Pharmaceutical, Inc., 30 North Jefferson Road... 21 U.S.C. 823(a), and determined that the registration of Halo Pharmaceutical, Inc., to manufacture...

75 FR 33824 - Pharmaceutical Products and Chemical Intermediates, Fourth Review: Advice Concerning the Addition...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-15

... production of pharmaceuticals (pharmaceuticals zero-for-zero initiative) and to conduct periodic reviews to... eliminated duties on additional pharmaceutical items. The USTR indicated that participants in the zero- for-zero initiative are conducting a fourth review to determine if products can be added to the initiative...

Toward an In Vivo Dissolution Methodology: A Comparison of Phosphate and Bicarbonate Buffers

PubMed Central

Sheng, Jennifer J.; McNamara, Daniel P.; Amidon, Gordon L.

2011-01-01

Purpose To evaluate the difference between the pharmaceutical phosphate buffers and the gastrointestinal bicarbonates in dissolution of ketoprofen and indomethacin, to illustrate the dependence of buffer differential on biopharmaceutical properties of BCS II weak acids, and to recommend phosphate buffers equivalent to bicarbonates. Methods The intrinsic dissolution rates of, ketoprofen and indomethacin, were experimentally measured using rotating disk method at 37°C in USP SIF/FaSSIF and various concentrations of bicarbonates. Theoretical models including an improved reaction plane model and a film model were applied to estimate the surrogate phosphate buffers equivalent to the bicarbonates. Results Experimental results show that the intrinsic dissolution rates of ketoprofen and indomethacin, in USP and FaSSIF phosphate buffers are 1.5–3.0 times of that in the 15 mM bicarbonates. Theoretical analysis demonstrates that the buffer differential is largely dependent on the drug pKa and secondly on solubility, and weakly dependent on the drug diffusivity. Further, in accordance with the drug pKa, solubility and diffusivity, simple phosphate surrogate was proposed to match an average bicarbonate value (15 mM) of the upper gastrointestinal region. Specifically, phosphate buffers of 13–15 mM and 3–4 mM were recommended for ketoprofen and indomethacin, respectively. For both ketoprofen and indomethacin, the intrinsic dissolution using the phosphate surrogate buffers closely approximated the 15 mM bicarbonate buffer. Conclusions This work demonstrates the substantial difference between pharmaceutical phosphates and physiological bicarbonates in determining the drug intrinsic dissolution rates of BCS II weak acids, such as ketoprofen and indomethacin. Surrogate phosphates were recommended in order to closely reflect the in vivo dissolution of ketoprofen and indomethacin in gastrointestinal bicarbonates, which has significant implications for defining buffer systems for BCS II weak acids in developing in vitro bioequivalence dissolution methodology. PMID:19183104

A meta-analysis of the association between gender and protective behaviors in response to respiratory epidemics

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

Moran, Kelly Renee; Del Valle, Sara Yermimah

Respiratory infectious disease epidemics and pandemics are recurring events that levy a high cost on individuals and society. The health-protective behavioral response of the public plays an important role in limiting respiratory infectious disease spread. Health-protective behaviors take several forms. Behaviors can be categorized as pharmaceutical (e.g., vaccination uptake, antiviral use) or non-pharmaceutical (e.g., hand washing, face mask use, avoidance of public transport). Due to the limitations of pharmaceutical interventions during respiratory epidemics and pandemics, public health campaigns aimed at limiting disease spread often emphasize both non-pharmaceutical and pharmaceutical behavioral interventions. Understanding the determinants of the public’s behavioral response ismore » crucial for devising public health campaigns, providing information to parametrize mathematical models, and ultimately limiting disease spread. While other reviews have qualitatively analyzed the body of work on demographic determinants of health-protective behavior, this meta-analysis quantitatively combines the results from 85 publications to determine the global relationship between gender and health-protective behavioral response. The results show that women in the general population are about 50% more likely than men to adopt/practice non-pharmaceutical behaviors. Conversely, men in the general population are marginally (about 12%) more likely than women to adopt/practice pharmaceutical behaviors. It is possible that factors other than pharmaceutical/non-pharmaceutical status not included in this analysis act as moderators of this relationship. We find these results suggest an inherent difference in how men and women respond to epidemic and pandemic respiratory infectious diseases. In conclusion, this information can be used to target specific groups when developing non-pharmaceutical public health campaigns and to parameterize epidemic models incorporating demographic information.« less

A meta-analysis of the association between gender and protective behaviors in response to respiratory epidemics

DOE PAGES

Moran, Kelly Renee; Del Valle, Sara Yermimah

2016-10-21

Respiratory infectious disease epidemics and pandemics are recurring events that levy a high cost on individuals and society. The health-protective behavioral response of the public plays an important role in limiting respiratory infectious disease spread. Health-protective behaviors take several forms. Behaviors can be categorized as pharmaceutical (e.g., vaccination uptake, antiviral use) or non-pharmaceutical (e.g., hand washing, face mask use, avoidance of public transport). Due to the limitations of pharmaceutical interventions during respiratory epidemics and pandemics, public health campaigns aimed at limiting disease spread often emphasize both non-pharmaceutical and pharmaceutical behavioral interventions. Understanding the determinants of the public’s behavioral response ismore » crucial for devising public health campaigns, providing information to parametrize mathematical models, and ultimately limiting disease spread. While other reviews have qualitatively analyzed the body of work on demographic determinants of health-protective behavior, this meta-analysis quantitatively combines the results from 85 publications to determine the global relationship between gender and health-protective behavioral response. The results show that women in the general population are about 50% more likely than men to adopt/practice non-pharmaceutical behaviors. Conversely, men in the general population are marginally (about 12%) more likely than women to adopt/practice pharmaceutical behaviors. It is possible that factors other than pharmaceutical/non-pharmaceutical status not included in this analysis act as moderators of this relationship. We find these results suggest an inherent difference in how men and women respond to epidemic and pandemic respiratory infectious diseases. In conclusion, this information can be used to target specific groups when developing non-pharmaceutical public health campaigns and to parameterize epidemic models incorporating demographic information.« less

Mushrooms as possible antioxidant and antimicrobial agents.

PubMed

Kosanić, Marijana; Ranković, Branislav; Dašić, Marko

2012-01-01

The aim of the study is to examine in-vitro antioxidant and antimicrobial activity of the acetonic and methanolic extracts of the mushrooms Boletus aestivalis, Boletus edulis and Leccinum carpini. Antioxidant activity was evaluated by using free radical scavenging activity and reducing power. In addition, total content of phenol and flavonoid in extracts were determined as pyrocatechol equivalent, and as rutin equivalent, respectively. As a result of the study acetonic extracts from Boletus edulis was more powerful antioxidant activity with IC50 value of 4.72 μg/mL which was similar or greater than the standard antioxidants, ascorbic acid (IC50 = 4.22 μg/mL), BHA (IC50 = 6.42 μg/mL) and α-tocopherol (IC50 = 62.43 μg/mL). Moreover, the tested extracts had effective reducing power. A significant relationship between total phenolic and flavonoid contents and their antioxidative activities was significantly observed. The antimicrobial activity of each extract was estimated by determination of the minimum inhibitory concentration by using microdilution plate method against five species of bacteria and five species of fungi. Generally, the tested mushroom extracts had relatively strong antimicrobial activity against the tested microorganisms. The minimum inhibitory concentration for both extracts related to the tested bacteria and fungi were 1.25 - 10 mg/ mL. The present study shows that tested mushroom species demonstrated a strong antioxidant and antimicrobial activity. It suggests that mushroom may be used as good sources of natural antioxidants and for pharmaceutical purposes in treating of various deseases.

The impact of pharmaceutical policy measures: an endogenous structural-break approach.

PubMed

Barros, Pedro Pita; Nunes, Luis C

2010-08-01

Pharmaceutical spending in many countries has seen a steep increase in recent years. Governments have adopted several measures to reduce pharmaceutical expenditure growth, ranging from increased co-payments to price decreases determined administratively. Promotion of generic consumption has also ranked high in political priorities. We adopt a novel time series approach to the detection of which policy measures have a noticeable impact. The number and timing of the structural breaks are endogenously determined. As an illustration, we assess the overall impact of the several policy measures on total pharmaceutical spending, using monthly data from January 1995 to August 2008 for the Portuguese market. Our findings suggest that, in general, policy measures aimed at controlling pharmaceutical expenditure have been unsuccessful. Two breaks that were identified coincide with administratively determined price decreases. Measures aimed at increasing competition in the market had no visible effect on the dynamics of Government spending in pharmaceutical products. In particular, the introduction of reference pricing had only a transitory effect of less than one year, with historical growth resuming quickly. The consequence of this policy ineffectiveness is a transfer of financial burden from the Government to the patients, with no apparent effect on the dynamics of total pharmaceutical spending. Copyright 2010 Elsevier Ltd. All rights reserved.

77 FR 16264 - Manufacturer of Controlled Substances, Notice of Registration; Halo Pharmaceutical Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-20

..., Notice of Registration; Halo Pharmaceutical Inc. By Notice dated December 2, 2011, and published in the Federal Register on December 14, 2011, 76 FR 77850, Halo Pharmaceutical Inc., 30 North Jefferson Road... considered the factors in 21 U.S.C. 823(a) and determined that the registration of Halo Pharmaceutical Inc...

[Evaluation of Gastric Mucosal Injury Model Animals of Rebamipide Formulation--Study of Therapeutic Equivalence].

PubMed

Abe, Noriaki; Funato, Hiroki; Hirata, Ayumu; Nakai, Megumi; Iizuka, Michiro; Shiraishi, Hisashi; Jobu, Kohei; Yagi, Yusuke; Kadota, Aki; Ogi, Kyoko; Yokota, Junko; Miyamura, Mitsuhiko

2016-01-01

The introduction of generic drugs is promoted from the perspective of medical economics. In this context, we need to understand not only the bioequivalence of generic drugs specified in "the Guidelines for Bioequivalence Studies of Generic Products", but also formulation properties to consider their effect on pharmacological therapy. We evaluated the pharmaceutical characteristics of rebamipide formulations, a brand-name drug and two generic drugs, and their clinical functionality by using rat models of gastric mucosal injury induced by non-steroidal anti-inflammatory drugs (NSAIDs). Pharmaceutical evaluation showed significant differences in hardness. The inter-lot variation was small in all rebamipide formulations. In the clinical functionality study, biochemistry test values 7 d after the administration of rebamipide showed no differences among formulations. Higher levels of mucosal fluid secretion and antioxidative enzymes were observed in the groups administered rebamipide than in the control group. The levels of lipid peroxide were lower in the groups administered rebamipide than the control group. Multivariate analysis showed slight divergence between the brand-name and generic drugs. In future, it will be necessary to select generic drugs after careful consideration of bioequivalence, clinical functionality, and therapeutic equivalence by reviewing scientific evidence such as indication and formulation design, not to mention stable provision.

GC-MS characterization of n-hexane soluble fraction from dandelion (Taraxacum officinale Weber ex F.H. Wigg.) aerial parts and its antioxidant and antimicrobial properties.

PubMed

Ivanov, Ivan; Petkova, Nadezhda; Tumbarski, Julian; Dincheva, Ivayla; Badjakov, Ilian; Denev, Panteley; Pavlov, Atanas

2018-01-26

A comparative investigation of n-hexane soluble compounds from aerial parts of dandelion (Taraxacum officinale Weber ex F.H. Wigg.) collected during different vegetative stages was carried out. The GC-MS analysis of the n-hexane (unpolar) fraction showed the presence of 30 biologically active compounds. Phytol [14.7% of total ion current (TIC)], lupeol (14.5% of TIC), taraxasteryl acetate (11.4% of TIC), β-sitosterol (10.3% of TIC), α-amyrin (9.0% of TIC), β-amyrin (8.3% of TIC), and cycloartenol acetate (5.8% of TIC) were identified as the major components in n-hexane fraction. The unpolar fraction exhibited promising antioxidant activity - 46.7 mmol Trolox equivalents/g extract (determined by 1,1-diphenyl-2-picrylhydrazyl method). This fraction demonstrated insignificant antimicrobial activity and can be used in cosmetic and pharmaceutical industries.

ANALYSIS OF TRENDS IN LIFE EXPECTANCIES AND PER CAPITA GROSS DOMESTIC PRODUCT AS WELL AS PHARMACEUTICAL AND NON-PHARMACEUTICAL HEALTHCARE EXPENDITURES.

PubMed

Hermanowski, Tomasz; Bystrov, Victor; Staszewska-Bystrova, Anna; Szafraniec-Buryło, Sylwia I; Rabczenko, Daniel; Kolasa, Katarzyna; Orlewska, Ewa

2015-01-01

Life expectancy is a common measure of population health. Macro-perspective based on aggregated data makes it possible to approximate the impact of different levels of pharmaceutical expenditure on general population health status and is often used in cross-country comparisons. The aim of the study was to determine whether there are long-run relations between life expectancy, total healthcare expenditures, and pharmaceutical expenditures in OECD countries. Common trends in per capita gross domestic products (GDPs) (excluding healthcare expenditures), per capita healthcare expenditures (excluding pharmaceutical expenditures), per capita pharmaceutical expenditures, and life expectancies of women and men aged 60 and 65 were analyzed across OECD countries. Short-term effect of pharmaceutical expenditure onto life expectancy was also estimated by regressing the deviations of life expectancies from their long-term trends onto the deviations of pharmaceutical and non-pharmaceutical health expenditures, as well as GDP from their trends. The dataset was created on the basis of OECD Health Data for 34 countries and the years 1991-2010. Life expectancy variables were used as proxies for the health outcomes, whereas the pharmaceutical and healthcare expenditures represented drug and healthcare consumption, respectively. In general, both expenditures and life expectancies tended to increase in all of the analyzed countries; however, the growth rates differed across the countries. The analysis of common trends indicated the existence of common long-term trends in life expectancies and per capita GDP as well as pharmaceutical and non-pharmaceutical healthcare expenditures. However, there was no evidence that pharmaceutical expenditures provided additional information about the long-term trends in life expectancies beyond that contained in the GDP series. The analysis based on the deviations of variables from their long-term trends allowed concluding that pharmaceutical expenditures significantly influenced life expectancies in the short run. Non-pharmaceutical healthcare expenditures were found to be significant in one out of four models (for life expectancy of women aged 65), while GDPs were found to be insignificant in all four models. The results of the study indicate that there are common long-term trends in life expectancies and per capita GDP as well as pharmaceutical and non-pharmaceutical healthcare expenditures. The available data did not reveal any cause- effect relationship. Other factors, for which the systematic data were not available, may have determined the increase in life expectancy in OECD countries. Significant positive short-term relations between pharmaceutical expenditures and life expectancies in OECD countries were found. The significant short-term effect of pharmaceutical expenditures onto life expectancy means that an increase of pharmaceutical expenditures above long-term trends would lead to a temporary increase in life expectancy above its corresponding long-term trend. However, this effect would not persist as pharmaceutical expenditures and life expectancy would converge to levels determined by the long-term trends.

Pigment identification, antioxidant activity, and nutrient composition of Tinospora cordifolia (willd.) Miers ex Hook. f & Thoms fruit.

PubMed

Khan, Mohammad Imtiyaj; Harsha, P S C Sri; Giridhar, P; Ravishankar, G A

2011-05-01

The stem, leaf, and root of Tinospora cordifolia (willd.) have been highly exploited for medicinal preparations; however, the nutritional and nutraceutical potential of its attractive red berries (fruits) have not so far been studied. Pigments, berberine (107.0 mg/100 g) and lycopene (50.8 mg/100 g), were identified in the deseeded fruit. Total phenol content in the fruit was 3.2 mg gallic acid equivalent/g. The IC(50) of DPPH· (82, and 468 ppm) and OH· (100, and 1,000 ppm) scavenging activity, and the EC(50) of reducing power (2,616, and 1,472 ppm) of hexane and methanol extracts, respectively, were observed. Oxygen radical absorbance capacities of the fruit extracts (150 and 300 ppm) were 1,107 and 2,614 μM trolox equivalent/g, respectively. Nutrient composition including carbohydrate (18.4%), proteins (1.5%), lipids (6%) of which ∼62% was unsaturated fatty acids, vitamins like ascorbic acid (0.24 μg), niacin (0.7 mg), and tocopherols (2.4 mg) in 100 g fruits were determined. Potassium content was 1.2 g/100 g dry tissue of berries. These findings show that components of T. cordifolia fruit could be bioactive and used in food, pharmaceutical, and cosmetics.

Reimbursement of pharmaceuticals: reference pricing versus health technology assessment.

PubMed

Drummond, Michael; Jönsson, Bengt; Rutten, Frans; Stargardt, Tom

2011-06-01

Reference pricing and health technology assessment are policies commonly applied in order to obtain more value for money from pharmaceuticals. This study focussed on decisions about the initial price and reimbursement status of innovative drugs and discussed the consequences for market access and cost. Four countries were studied: Germany, The Netherlands, Sweden and the United Kingdom. These countries have operated one, or both, of the two policies at certain points in time, sometimes in parallel. Drugs in four groups were considered: cholesterol-lowering agents, insulin analogues, biologic drugs for rheumatoid arthritis and "atypical" drugs for schizophrenia. Compared with HTA, reference pricing is a relatively blunt instrument for obtaining value for money from pharmaceuticals. Thus, its role in making reimbursement decisions should be limited to drugs which are therapeutically equivalent. HTA is a superior strategy for obtaining value for money because it addresses not only price but also the appropriate indications for the use of the drug and the relation between additional value and additional costs. However, given the relatively higher costs of conducting HTAs, the most efficient approach might be a combination of both policies.

Determination of low ppm levels of dimethyl sulfate in an aqueous soluble API intermediate using liquid-liquid extraction and GC-MS.

PubMed

Zheng, Jie; Pritts, Wayne A; Zhang, Shuhong; Wittenberger, Steve

2009-12-05

Dimethyl sulfate (DMS) is an alkylating reagent commonly used in organic syntheses and pharmaceutical manufacturing processes. Due to its potential carcinogenicity, the level of DMS in the API process needs to be carefully monitored. However, in-process testing for DMS is challenging because of its reactivity and polarity as well as complex matrix effects. In this short communication, we report a GC-MS method for determination of DMS in an API intermediate that is a methyl sulfate salt. To overcome the complex matrix interference, DMS and an internal standard, d6-DMS, were extracted from the matrix with methyl tert-butyl ether. GC separation was conducted on a DB-624 column (30 m long, 0.32 mm ID, 1.8 microm film thickness). MS detection was performed on a single-quad Agilent MSD equipped with an electron impact source while the MSD signal was acquired in selected ion monitoring mode. This GC/MS method showed a linear response for DMS equivalent from 1.0 to 60 ppm. The practical quantitation limit for DMS was 1.0 ppm and the practical detection limit was 0.3 ppm. The relative standard derivation for analyte response was found as 0.1% for six injections of a working standard equivalent to 18.6 ppm of DMS. The spike recovery was ranged from 102.1 to 108.5% for a sample of API intermediate spiked with 8.0 ppm of DMS. In summary, the GC/MS method showed adequate specificity, linearity, sensitivity, repeatability and accuracy for determination of DMS in the API intermediate. This method has been successfully applied to study the efficiency of removing DMS from the process.

Regulation and competition in the Taiwanese pharmaceutical market under national health insurance.

PubMed

Liu, Ya-Ming; Yang, Yea-Huei Kao; Hsieh, Chee-Ruey

2012-05-01

This article investigates the determinants of the prices of pharmaceuticals and their impact on the demand for prescription drugs in the context of Taiwan's pharmaceutical market where medical providers earn profit directly from prescribing and dispensing drugs. Based on product-level data, we find evidence that the profit-seeking behavior of the medical providers in the prescription drug market transfers the force of competition from the unregulated wholesale market to the regulated retail market and hence market competition still plays an important role in the determination of the regulated price. We also find that the profit-seeking behavior plays a similar role to advertising in that it increases the brand loyalty and hence lowers price elasticity. An important implication of our study is that the institutional features in the pharmaceutical market matter in shaping the nature of pharmaceutical competition and the responsiveness of pharmaceutical consumption with respect to changes in price. Copyright © 2012 Elsevier B.V. All rights reserved.

A cross-sectional study of the availability and pharmacist's knowledge of nano-pharmaceutical drugs in Palestinian hospitals.

PubMed

Assali, Mohyeddin; Shakaa, Ali; Abu-Hejleh, Sabaa; Abu-Omar, Reham; Karajeh, Nareman; Ajory, Nawal; Zyoud, Saed; Sweileh, Waleed

2018-04-05

Nanomedicine is the medical application of nanomaterials that may have an infinite size with the range less than 100 nm. This science has provided solutions to many of the current limitations in the diagnosis and treatment of diseases. Therefore, the pharmacist's knowledge and awareness of nano-pharmaceutical drugs will increase their availability in the market, and will improve the patient's compliance to their drug therapy. This study aimed to determine the availability of nano-pharmaceutical drugs in Palestinian hospitals and evaluate the extent of pharmacist's knowledge about them. A cross-sectional study design questionnaire was used to determine the availability of nano-pharmaceutical drugs based on the database of the ministry of health in the Palestinian hospitals (governmental, private and non- governmental organizations). Moreover, the knowledge of these nano-pharmaceutical drugs among pharmacists working in Palestinian hospitals was assessed based on developed questionnaire from the literature of the pharmaceutical formulations and nano-formulations. The variables were analyzed using Statistical Package for Social Sciences (SPSS 22). Fifty six pharmacists from 27 hospitals in the West bank completed the survey. The results regarding the availability of nano-pharmaceutical drugs indicated only eight available in hospitals with a frequency range 0-39.3%. Moreover, pharmacist's knowledge in the pharmaceutical formulations was better than that in nano-formulations. The availability of nano-pharmaceutical drugs in Palestinian hospitals was not adequate due to the lack of various nano-pharmaceutical drugs. The knowledge among pharmacists regarding nano-pharmaceutical drugs should be improved by providing courses in nanomedicine during the undergraduate pharmacy programs.

Application of six sigma and AHP in analysis of variable lead time calibration process instrumentation

NASA Astrophysics Data System (ADS)

Rimantho, Dino; Rahman, Tomy Abdul; Cahyadi, Bambang; Tina Hernawati, S.

2017-02-01

Calibration of instrumentation equipment in the pharmaceutical industry is an important activity to determine the true value of a measurement. Preliminary studies indicated that occur lead-time calibration resulted in disruption of production and laboratory activities. This study aimed to analyze the causes of lead-time calibration. Several methods used in this study such as, Six Sigma in order to determine the capability process of the calibration instrumentation of equipment. Furthermore, the method of brainstorming, Pareto diagrams, and Fishbone diagrams were used to identify and analyze the problems. Then, the method of Hierarchy Analytical Process (AHP) was used to create a hierarchical structure and prioritize problems. The results showed that the value of DPMO around 40769.23 which was equivalent to the level of sigma in calibration equipment approximately 3,24σ. This indicated the need for improvements in the calibration process. Furthermore, the determination of problem-solving strategies Lead Time Calibration such as, shortens the schedule preventive maintenance, increase the number of instrument Calibrators, and train personnel. Test results on the consistency of the whole matrix of pairwise comparisons and consistency test showed the value of hierarchy the CR below 0.1.

Double-Track Electrochemical Green Approach for Simultaneous Dissolution Profiling of Naproxen Sodium and Diphenhydramine Hydrochloride.

PubMed

Shehata, Mostafa A; Fawaz, Esraa M; El-Rahman, Mohamed K Abd; Abdel-Moety, Ezzat M

2017-11-30

Acquisition of the dissolution profiles of more than single active ingredient in a multi-analyte pharmaceutical formulation is a mandatory manufacturing practice that is dominated by utilization of the off-line separation-based chromatographic methods. This contribution adopts a new "Double-Track" approach with the ultimate goal of advancing the in-line potentiometric sensors to their most effective applicability for simultaneous acquisition of the dissolution profiles of two active ingredients in a binary pharmaceutical formulation. The unique abilities of these sensors for real-time measurements is the key driver for adoption of "green analytical chemistry" (GAC) principles aiming to expand the application of eco-friendly analytical methods With the aim of performing a side-by-side comparison, this work investigates the degree of adherence of ISEs to the 12 principles of GAC in multicomponent dissolution profiling with respect to the HPLC. For the proof of concept, a binary mixture of naproxen sodium (NAPR) and diphenhydramine hydrochloride (DIPH) marketed as Aleve pm ® tablets was selected as a model for which dissolution profiles were attained by two techniques. The first "Double-Track" in-line strategy depends on dipping two highly integrated membrane sensors for continuous monitoring of the dissolution of each active pharmaceutical ingredient (API) by tracing the e.m.f change over the time scale. For the determination of NAPR, sensor I was developed using tridodecyl methyl ammonium chloride as an anion exchanger, while sensor II was developed for the determination of DIPH using potassium tetrakis (4-chlorophenyl) borate as a cation exchanger. The second off-line strategy utilizes a separation-based HPLC method via off-line tracking the increase of peak area by UV detection at 220nm over time using a mobile phase of acetonitrile: water (90:10) pH 3. The advantages of the newly introduced "Double-Track" approach regarding GAC principles are highlighted, and the merits of these benign real-time analyzers (ISEs) that can deliver equivalent analytical results as HPLC while significantly reducing solvent consumption/waste generation are described. Copyright © 2017 Elsevier B.V. All rights reserved.

[The system of information concerning pharmaceuticals and its role in efficient using of medicines: opinion of medical specialists].

PubMed

Rostova, N B; Kudriashova, A I

2016-01-01

The issues of efficient application of pharmaceuticals by national authorities and supranational institutions are considered as important ones. The WHO recommends implementing twelve key propositions enhancing efficient application of pharmaceuticals. The development of independent information system concerning pharmaceuticals. The WHO recognizes that absence of neatly organized information system concerning pharmaceuticals information is usually spreading through different channels by manufacturers of medicines. The WHO determines admissible sources of information concerning pharmaceuticals and also requirements to content of presented information. The article presents results of survey of opinions of medical professionals about information sources concerning pharmaceuticals regulated in the Russian Federation and the WHO and also about actual information system concerning pharmaceuticals in the Russian Federation and its role in efficient application of medicines.

Ethics considerations for medical device R&D.

PubMed

Citron, Paul

2012-01-01

Medical devices have emerged as an important clinical option to treat certain serious diseases for which there are no equivalently effective surgical or pharmaceutical alternatives. Although all clinical activities impose high ethical standards of comportment to protect patients, medical device R&D and product application have a number of relatively unique aspects that distinguish them from other technologies such as pharmaceuticals. These include the following: R&D project selection; regulatory requirements, and their intended and unintended effects; when is a new product design sufficiently safe and effective for routine use in patients; and, physician-industry relationships in the innovation process in the context of real or perceived conflict of interest (COI). Each of these factors has implications for the delivery of care, health care leadership, and patient well-being. Copyright © 2012 Elsevier Inc. All rights reserved.

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

EPA Science Inventory

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

Exact test-based approach for equivalence test with parameter margin.

PubMed

Cassie Dong, Xiaoyu; Bian, Yuanyuan; Tsong, Yi; Wang, Tianhua

2017-01-01

The equivalence test has a wide range of applications in pharmaceutical statistics which we need to test for the similarity between two groups. In recent years, the equivalence test has been used in assessing the analytical similarity between a proposed biosimilar product and a reference product. More specifically, the mean values of the two products for a given quality attribute are compared against an equivalence margin in the form of ±f × σ R , where ± f × σ R is a function of the reference variability. In practice, this margin is unknown and is estimated from the sample as ±f × S R . If we use this estimated margin with the classic t-test statistic on the equivalence test for the means, both Type I and Type II error rates may inflate. To resolve this issue, we develop an exact-based test method and compare this method with other proposed methods, such as the Wald test, the constrained Wald test, and the Generalized Pivotal Quantity (GPQ) in terms of Type I error rate and power. Application of those methods on data analysis is also provided in this paper. This work focuses on the development and discussion of the general statistical methodology and is not limited to the application of analytical similarity.

Development of fast and robust multiresidual LC-MS/MS method for determination of pharmaceuticals in soils.

PubMed

Golovko, Oksana; Koba, Olga; Kodesova, Radka; Fedorova, Ganna; Kumar, Vimal; Grabic, Roman

2016-07-01

The aim of this study was to develop a simple extraction procedure and a multiresidual liquid chromatography-tandem mass spectrometry method for determination of a wide range of pharmaceuticals from various soil types. An extraction procedure for 91 pharmaceuticals from 13 soil types, followed by liquid chromatography-tandem mass spectrometry analysis, was optimized. The extraction efficiencies of three solvent mixtures for ultrasonic extraction were evaluated for 91 pharmaceuticals. The best results were obtained using acetonitrile/water (1/1 v/v with 0.1 % formic acid) followed by acetonitrile/2-propanol/water (3/3/4 v/v/v with 0.1 % formic acid) for extracting 63 pharmaceuticals. The method was validated at three fortification levels (10, 100, and 1000 ng/g) in all types of representative soils; recovery of 44 pharmaceuticals ranged between 55 and 135 % across all tested soils. The method was applied to analyze actual environmental samples of sediments, soils, and sludge, and 24 pharmaceuticals were found above limit of quantification with concentrations ranging between 0.83 ng/g (fexofenadine) and 223 ng/g (citalopram).

Determination of pharmaceutical residues in drinking water in Poland using a new SPE-GC-MS(SIM) method based on Speedisk extraction disks and DIMETRIS derivatization.

PubMed

Caban, Magda; Lis, Ewa; Kumirska, Jolanta; Stepnowski, Piotr

2015-12-15

The presence of pharmaceuticals in drinking water, even at very low concentrations, has raised concerns among stakeholders such as drinking-water regulators, governments, water suppliers and the public, with regard to the potential risks to humans. Despite this, the occurrence and the fate of pharmaceuticals in drinking waters of many countries (e.g. in Poland) remains unknown. There is a lack of sufficiently sensitive and reliable analytical methods for such analyses and a need for more in-depth hydrogeological analysis of the possible sources of drug residues in drinking water. In this paper, a multi-residual method for the simultaneous determination of seventeen human pharmaceuticals in drinking waters has been developed. Large-volume extractions using Speedisk extraction disks, and derivatization prior to GC-MS-SIM analysis using a new silylating agent DIMETRIS were applied. The method detection limits (MDLs) ranged from 0.9 to 5.7ng/L and the absolute recoveries of the target compounds were above 80% for most analytes. The developed method was successfully applied in the analysis of the target compounds in drinking water collected in Gdansk (Poland), and of the 17 pharmaceuticals, 6 compounds were detected at least once. During the investigation, the geomorphology of the site region was taken into account, possible sources of pharmaceuticals in the analysed drinking water samples were investigated, and the presence of the drugs in ground and surface waters, raw and treated drinking waters was determined. Concentrations were also compared with those observed in other countries. As a result, this study has not only developed a new analytical method for determining pharmaceuticals in drinking waters as well as rendering missing information for Poland (a country with one of the highest consumptions of pharmaceuticals in Europe), but it also presents a modelled in-depth hydrogeological analysis of the real sources of drugs in drinking waters. Copyright © 2015 Elsevier B.V. All rights reserved.

Selected analytical challenges in the determination of pharmaceuticals in drinking/marine waters and soil/sediment samples.

PubMed

Białk-Bielińska, Anna; Kumirska, Jolanta; Borecka, Marta; Caban, Magda; Paszkiewicz, Monika; Pazdro, Ksenia; Stepnowski, Piotr

2016-03-20

Recent developments and improvements in advanced instruments and analytical methodologies have made the detection of pharmaceuticals at low concentration levels in different environmental matrices possible. As a result of these advances, over the last 15 years residues of these compounds and their metabolites have been detected in different environmental compartments and pharmaceuticals have now become recognized as so-called 'emerging' contaminants. To date, a lot of papers have been published presenting the development of analytical methodologies for the determination of pharmaceuticals in aqueous and solid environmental samples. Many papers have also been published on the application of the new methodologies, mainly to the assessment of the environmental fate of pharmaceuticals. Although impressive improvements have undoubtedly been made, in order to fully understand the behavior of these chemicals in the environment, there are still numerous methodological challenges to be overcome. The aim of this paper therefore, is to present a review of selected recent improvements and challenges in the determination of pharmaceuticals in environmental samples. Special attention has been paid to the strategies used and the current challenges (also in terms of Green Analytical Chemistry) that exist in the analysis of these chemicals in soils, marine environments and drinking waters. There is a particular focus on the applicability of modern sorbents such as carbon nanotubes (CNTs) in sample preparation techniques, to overcome some of the problems that exist in the analysis of pharmaceuticals in different environmental samples. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed

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

2014-10-01

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

Comparison of accelerated solvent extraction and quick, easy, cheap, effective, rugged and safe method for extraction and determination of pharmaceuticals in vegetables.

PubMed

Chuang, Ya-Hui; Zhang, Yingjie; Zhang, Wei; Boyd, Stephen A; Li, Hui

2015-07-24

Land application of biosolids and irrigation with reclaimed water in agricultural production could result in accumulation of pharmaceuticals in vegetable produce. To better assess the potential human health impact from long-term consumption of pharmaceutical-contaminated vegetables, it is important to accurately quantify the amount of pharmaceuticals accumulated in vegetables. In this study, a quick, easy, cheap, effective, rugged and safe (QuEChERS) method was developed and optimized to extract multiple classes of pharmaceuticals from vegetables, which were subsequently quantified by liquid chromatography coupled to tandem mass spectrometry. For the eleven target pharmaceuticals in celery and lettuce, the extraction recovery of the QuEChERS method ranged from 70.1 to 118.6% with relative standard deviation <20%, and the method detection limit was achieved at the levels of nanograms of pharmaceuticals per gram of vegetables. The results revealed that the performance of the QuEChERS method was comparable to, or better than that of accelerated solvent extraction (ASE) method for extraction of pharmaceuticals from plants. The two optimized extraction methods were applied to quantify the uptake of pharmaceuticals by celery and lettuce growing hydroponically. The results showed that all the eleven target pharmaceuticals could be absorbed by the vegetables from water. Compared to the ASE method, the QuEChERS method offers the advantages of short time and reduced costs of sample preparation, and less amount of organic solvents used. The established QuEChERS method could be used to determine the accumulation of multiple classes of pharmaceutical residues in vegetables and other plants, which is needed to evaluate the quality and safety of agricultural produce consumed by humans. Copyright © 2015 Elsevier B.V. All rights reserved.

Mushrooms as Possible Antioxidant and Antimicrobial Agents

PubMed Central

Kosanić, Marijana; Ranković, Branislav; Dašić, Marko

2012-01-01

The aim of the study is to examine in-vitro antioxidant and antimicrobial activity of the acetonic and methanolic extracts of the mushrooms Boletus aestivalis, Boletus edulis and Leccinum carpini. Antioxidant activity was evaluated by using free radical scavenging activity and reducing power. In addition, total content of phenol and flavonoid in extracts were determined as pyrocatechol equivalent, and as rutin equivalent, respectively. As a result of the study acetonic extracts from Boletus edulis was more powerful antioxidant activity with IC50 value of 4.72 μg/mL which was similar or greater than the standard antioxidants, ascorbic acid (IC50 = 4.22 μg/mL), BHA (IC50 = 6.42 μg/mL) and α-tocopherol (IC50 = 62.43 μg/mL). Moreover, the tested extracts had effective reducing power. A significant relationship between total phenolic and flavonoid contents and their antioxidative activities was significantly observed. The antimicrobial activity of each extract was estimated by determination of the minimum inhibitory concentration by using microdilution plate method against five species of bacteria and five species of fungi. Generally, the tested mushroom extracts had relatively strong antimicrobial activity against the tested microorganisms. The minimum inhibitory concentration for both extracts related to the tested bacteria and fungi were 1.25 - 10 mg/ mL. The present study shows that tested mushroom species demonstrated a strong antioxidant and antimicrobial activity. It suggests that mushroom may be used as good sources of natural antioxidants and for pharmaceutical purposes in treating of various deseases. PMID:24250542

The Pharmaceutical Sector of Kazakhstan's Economy: Trends and Problems

ERIC Educational Resources Information Center

Nurpeisov, Borankul G.; Nabiev, Erboz N.; Mukashev, Temirbay A.; Daribekov, Serik S.; Raimbekov, Bagdat Kh.; Asanova, Maral K.; Bazarbaeva, Leila M.

2016-01-01

This research is devoted to the investigation of the general trends in the development of the pharmaceutical industry in the current conditions of economical socialization. The determination of the economic specificity of the modern operation of the pharmaceutical industry is the purpose of the research. It was found that pharmacy is a profitable…

Characteristics of Tacca leontopetaloides L. Kuntze collected from An Giang in Vietnam

NASA Astrophysics Data System (ADS)

Vu, Quan Thi Hong; Le, Phung Thi Kim; Vo, Huy Pham Hoang; Nguyen, Triet Thanh; Nguyen, Tam Kim Minh

2017-09-01

Tacca leontopetaloides L. Kuntze has been known as a remedy in folk medicine and also a staple food source in many tropical countries. Nonetheless, there are currently few literature and research on the potential pharmaceutical benefits of this herbal plant. In this study, the constituents of leaves, peels and peeled tubers as well as its antioxidant and antimicrobial activities of Tacca cultivated from mountainous regions in Tinh Bien, An Giang Province, Vietnam were investigated. The results indicated that the highest of total phenolic content (TPC) and total flavonoid content (TFC) were presented in leaves of Tacca which were 16.69 mg GAE (gallic acid equivalent)/g dried weight, 57.24 mg QE (quercetin equivalent)/g dried weight, respectively. Besides, the yield of flour recovery process from Tacca tuber estimated from 18%-20%. The chemical compositions of Tacca flour were 0.66 % total of nitrogen, 0.91% lipid, 0.05% ash and 85.7% starch content on dried weight. Furthermore, the extract of peels possessed potential antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Enterococcus faecalis whilst the extract of others did not show any significant inhibition at the same concentration. As a results, with high starch content (nearly 20% in tuber) is a highly promising new starch for food and pharmaceutical excipient industry, while the usefullness of peel in treatment need further investigation.

Abuse-Deterrent Opioid Formulations: Pharmacokinetic and Pharmacodynamic Considerations.

PubMed

Walter, Carmen; Knothe, Claudia; Lötsch, Jörn

2016-07-01

Abuse-deterrent formulations (ADFs) are technologically sophisticated pharmaceutical formulations that impede manipulation and extraction of opioids and/or provoke unpleasant effects when they are taken in excessive quantity. This is implemented by creating physical barriers, inseparably combining the opioid with an opioid antagonist or adding aversive agents to the formulation. These pharmaceutical changes may potentially alter the pharmacokinetics and consequently the pharmacodynamics of the opioid. In this review, comparative evidence on pharmacokinetic differences between abuse-deterrent and classical formulations of the same opioids is summarized; furthermore, pharmacodynamic differences, with a focus on analgesia and abuse-related symptoms, are addressed. Most of the 12 studies comparing opioid pharmacokinetics have judged the physically intact ADF as being bioequivalent to the corresponding classical formulation. Pharmacokinetic differences have, however, been reported with physically manipulated ADFs and have ranged from moderate deviations from bioequivalence to complete changes in the pharmacokinetic profile (e.g. from a sustained-release formulation to a fast-release formulation). Pharmacodynamic effects were assessed in 14 comparative studies, which reported that intact ADFs usually provided clinically equivalent analgesia and clear advantages with respect to their addiction potential. However, withdrawal symptoms could be induced by the ADFs, although rarely and, in particular, when the ADFs had been physically altered. This evidence suggests that opioid ADFs are a working concept resulting in mostly minor pharmacokinetic and pharmacodynamic differences in comparison with classical formulations; however, they may deviate from this equivalence when physically altered.

Measuring Equity in Access to Pharmaceutical Services Using Concentration Curve; Model Development.

PubMed

Davari, Majid; Khorasani, Elahe; Bakhshizade, Zahra; Jafarian Jazi, Marzie; Ghaffari Darab, Mohsen; Maracy, Mohammad Reza

2015-01-01

This paper has two objectives. First, it establishes a model for scoring the access to pharmaceutical services. Second, it develops a model for measuring socioeconomic indicators independent of the time and place of study. These two measures are used for measuring equity in access to pharmaceutical services using concentration curve. We prepared an open-ended questionnaire and distributed it to academic experts to get their ideas to form access indicators and assign score to each indicator based on the pharmaceutical system. An extensive literature review was undertaken for the selection of indicators in order to determine the socioeconomic status (SES) of individuals. Experts' opinions were also considered for scoring these indicators. These indicators were weighted by the Stepwise Adoption of Weights and were used to develop a model for measuring SES independent of the time and place of study. Nine factors were introduced for assessing the access to pharmaceutical services, based on pharmaceutical systems in middle-income countries. Five indicators were selected for determining the SES of individuals. A model for income classification based on poverty line was established. Likewise, a model for scoring home status based on national minimum wage was introduced. In summary, five important findings emerged from this study. These findings may assist researchers in measuring equity in access to pharmaceutical services and also could help them to apply a model for determining SES independent of the time and place of study. These also could provide a good opportunity for researchers to compare the results of various studies in a reasonable way; particularly in middle-income countries.

Use of atypical antipsychotics in nursing homes and pharmaceutical marketing.

PubMed

Pimentel, Camilla B; Donovan, Jennifer L; Field, Terry S; Gurwitz, Jerry H; Harrold, Leslie R; Kanaan, Abir O; Lemay, Celeste A; Mazor, Kathleen M; Tjia, Jennifer; Briesacher, Becky A

2015-02-01

To describe the current extent and type of pharmaceutical marketing in nursing homes (NHs) in one state and to provide preliminary evidence for the potential influence of pharmaceutical marketing on the use of atypical antipsychotics in NHs. Nested mixed-methods, cross-sectional study of NHs in a cluster randomized trial. Forty-one NHs in Connecticut. NH administrators, directors of nursing, and medical directors (n = 93, response rate 75.6%). Quantitative data, including prescription drug dispensing data (September 2009-August 2010) linked with Nursing Home Compare data (April 2011), were used to determine facility-level prevalence of atypical antipsychotic use, facility-level characteristics, NH staffing, and NH quality. Qualitative data, including semistructured interviews and surveys of NH leaders conducted in the first quarter of 2011, were used to determine encounters with pharmaceutical marketing. Leadership at 46.3% of NHs (n = 19) reported pharmaceutical marketing encounters, consisting of educational training, written and Internet-based materials, and sponsored training. No association was detected between level of atypical antipsychotic prescribing and reports of any pharmaceutical marketing by at least one NH leader. NH leaders frequently encounter pharmaceutical marketing through a variety of ways, although the impact on atypical antipsychotic prescribing is unclear. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

Phenolic Compounds and Antioxidant Activity of Phalaenopsis Orchid Hybrids

PubMed Central

Minh, Truong Ngoc; Khang, Do Tan; Tuyen, Phung Thi; Minh, Luong The; Anh, La Hoang; Quan, Nguyen Van; Ha, Pham Thi Thu; Quan, Nguyen Thanh; Toan, Nguyen Phu; Elzaawely, Abdelnaser Abdelghany; Xuan, Tran Dang

2016-01-01

Phalaenopsis spp. is the most commercially and economically important orchid, but their plant parts are often left unused, which has caused environmental problems. To date, reports on phytochemical analyses were most available on endangered and medicinal orchids. The present study was conducted to determine the total phenolics, total flavonoids, and antioxidant activity of ethanol extracts prepared from leaves and roots of six commercial hybrid Phalaenopsis spp. Leaf extracts of “Chian Xen Queen” contained the highest total phenolics with a value of 11.52 ± 0.43 mg gallic acid equivalent per g dry weight and the highest total flavonoids (4.98 ± 0.27 mg rutin equivalent per g dry weight). The antioxidant activity of root extracts evaluated by DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging assay and β-carotene bleaching method was higher than those of the leaf extracts. Eleven phenolic compounds were identified, namely, protocatechuic acid, p-hydroxybenzoic acid, vanillic acid, caffeic acid, syringic acid, vanillin, ferulic acid, sinapic acid, p-coumaric acid, benzoic acid, and ellagic acid. Ferulic, p-coumaric and sinapic acids were concentrated largely in the roots. The results suggested that the root extracts from hybrid Phalaenopsis spp. could be a potential source of natural antioxidants. This study also helps to reduce the amount of this orchid waste in industrial production, as its roots can be exploited for pharmaceutical purposes. PMID:27649250

Differences in the volume of pharmaceutical advertisements between print general medical journals.

PubMed

Gettings, Jennifer; O'Neill, Braden; Chokshi, Dave A; Colbert, James A; Gill, Peter; Lebovic, Gerald; Lexchin, Joel; Persaud, Navindra

2014-01-01

Pharmaceutical advertisements have been argued to provide revenue that medical journals require but they are intended to alter prescribing behaviour and they are known to include low quality information. We determined whether a difference exists in the current level of pharmaceutical advertising in print general medical journals, and we estimated the revenue generated from print pharmaceutical advertising. Six print general medical journals in Canada, the United States, and the United Kingdom were sampled between 2007 and 2012. The number of advertisements and other journal content in selected issues of the Canadian Medical Association Journal (CMAJ), Canadian Family Physician (CFP), Journal of the American Medical Association (JAMA), New England Journal of Medicine (NEJM), British Medical Journal (BMJ), and Lancet were determined. Revenue gained from pharmaceutical advertising was estimated using each journal's 2013 advertising price list. The two Canadian journals sampled (CMAJ, CFP) contained five times more advertisements than the two American journals (JAMA, NEJM), and two British journals (BMJ, Lancet) (p<0.0001). The estimated annual revenue from pharmaceutical advertisements ranged from £0.025 million (for Lancet) to £3.8 million (for JAMA). The cost savings due to revenue from pharmaceutical advertising to each individual subscriber ranged from £0.02 (for Lancet) to £3.56 (for CFP) per issue. The volume of pharmaceutical advertisements differs between general medical journals, with the two Canadian journals sampled containing the most advertisements. International and temporal variations suggest that there is an opportunity for all general medical journals to reduce the number of pharmaceutical advertisements, explore other sources of revenue, and increase transparency regarding sources of revenue.

Therapeutic Equivalence Requires Pharmaceutical, Pharmacokinetic, and Pharmacodynamic Identities: True Bioequivalence of a Generic Product of Intravenous Metronidazole

PubMed Central

Agudelo, M.

2012-01-01

Animal models of infection have been used to demonstrate the therapeutic failure of “bioequivalent” generic products, but their applicability for this purpose requires the accurate identification of those products that are truly bioequivalent. Here, we present data comparing one intravenous generic product of metronidazole with the innovator product in a neutropenic mouse thigh anaerobic infection model. Simultaneous experiments allowed comparisons (generic versus innovator) of potency and the concentration of the active pharmaceutical ingredient (API), analytical chemistry (liquid chromatography/mass spectrometry [LC/MS]), in vitro susceptibility testing, single-dose serum pharmacokinetics (PK) in infected mice, and in vivo pharmacodynamics (PD) against Bacteroides fragilis ATCC 25825 in synergy with Escherichia coli SIG-1 in the neutropenic mouse thigh anaerobic infection model. The Hill dose-response model followed by curve-fitting analysis was used to calculate and compare primary and secondary PD parameters. The generic and the innovator products were identical in terms of the concentration and potency of the API, chromatographic and spectrographic profiles, MIC and minimal bactericidal concentrations (MBC) (2.0 mg/liter), and mouse PK. We found no differences between products in bacteriostatic doses (BD) (15 to 22 mg/kg of body weight per day) or the doses needed to kill 1 log (1LKD) (21 to 29 mg/kg per day) or 2 logs (2LKD) (28 to 54 mg/kg per day) of B. fragilis under dosing schedules of every 12 h (q12h), q8h, or q6h. The area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC ratio) was the best PD index to predict the antibacterial efficacy of metronidazole (adjusted coefficient of determination [AdjR2] = 84.6%), and its magnitude to reach bacteriostasis in vivo (56.6 ± 5.17 h) or to kill the first (90.8 ± 9.78 h) and second (155.5 ± 22.2 h) logs was the same for both products. Animal models of infection allow a thorough demonstration of the therapeutic equivalence of generic antimicrobials. PMID:22330928

Out-of-pocket expenditures for pharmaceuticals: lessons from the Austrian household budget survey.

PubMed

Sanwald, Alice; Theurl, Engelbert

2017-05-01

Paying pharmaceuticals out of pocket is an important source of financing pharmaceutical consumption. Only limited empirical knowledge is available on the determinants of these expenditures. In this article we analyze which characteristics of private households influence out-of-pocket pharmaceutical expenditure (OOPPE) in Austria. We use cross-sectional information on OOPPE and household characteristics provided by the Austrian household budget survey 2009/10. We split pharmaceutical expenditures into the two components prescription fees and over-the-counter (OTC) expenditures. To adjust for the specific characteristics of the data, we compare different econometric approaches: a two-part model, hurdle model, generalized linear model and zero-inflated negative binomial regression model. The finally selected econometric approaches give a quite consistent picture. The probability of expenditures of both types is strongly influenced by the household structure. It increases with age, doctoral visits and the presence of a female householder. The education level and income only increase the probability of OTC pharmaceuticals. The level of OTC expenditures remains widely unexplained while the household structure and age influence the expenditures for prescription fees. Insurance characteristics of private households, either private or public, play a minor role in explaining the expenditure levels in all specifications. This refers to a homogeneous and comprehensive provision of pharmaceuticals in the public part of the Austrian health care system. The article gives useful insights into the determinants of pharmaceutical expenditures of private households and supplements the previous research that focuses on the individual level.

Use of Atypical Antipsychotics in Nursing Homes and Pharmaceutical Marketing

PubMed Central

Pimentel, Camilla B.; Donovan, Jennifer L.; Field, Terry S.; Gurwitz, Jerry H.; Harrold, Leslie R.; Kanaan, Abir O.; Lemay, Celeste A.; Mazor, Kathleen M.; Tjia, Jennifer; Briesacher, Becky A.

2014-01-01

BACKGROUND Many nursing home (NH) residents are prescribed atypical antipsychotics despite US Food and Drug Administration warnings of increased risk of death in older adults with dementia. Aggressive pharmaceutical marketing has been cited as a potential cause, although data are scarce. The objectives of this study were to describe the current extent and type of pharmaceutical marketing in NHs in one state, and to provide preliminary evidence for the potential influence of pharmaceutical marketing on the use of atypical antipsychotics in NHs. DESIGN Nested mixed-methods, cross-sectional study of NHs in a cluster randomized trial. SETTING 41 NHs in Connecticut. PARTICIPANTS NH administrators, directors of nursing and medical directors (n = 93, response rate 75.6%). MEASUREMENTS Quantitative data, including prescription drug dispensing data (September 2009–August 2010) linked with Nursing Home Compare data (April 2011), were used to determine facility-level prevalence of atypical antipsychotic use, facility-level characteristics, NH staffing and NH quality. Qualitative data, including semi-structured interviews and surveys of NH leaders conducted in the first quarter of 2011, were used to determine encounters with pharmaceutical marketing. RESULTS Leadership at 46.3% of NHs (19/41) reported pharmaceutical marketing encounters, consisting of educational training, written/Internet-based materials and/or sponsored training. No association was detected between the level of atypical antipsychotic prescribing and reports of any pharmaceutical marketing by at least one NH leader. CONCLUSION NH leaders frequently encounter pharmaceutical marketing through a variety of ways, although the impact on atypical antipsychotic prescribing is unclear. PMID:25688605

Investigating pharmaceutical marketing in Canada using American prosecutions.

PubMed

Shoucri, Rami; Persaud, Navindra

2014-01-01

Pharmaceutical companies are prohibited from marketing medications for off-label uses in both the United States and Canada. In the United States, there have been several recent multi-billion dollar settlements with pharmaceutical companies based, partly, on off-label promotion. Health Canada has not publicized any investigations into, or prosecutions of, pharmaceutical companies for off-label promotion in Canada even though many of the same medications are marketed here. The prohibition on off-label promotion is largely directed at preventing pharmaceutical companies from circumventing the drug licensing process and attendant safety checks. To determine if sanctions for off-label pharmaceutical promotion in one jurisdiction can be used to regulate marketing in another. We reviewed and compared the laws and regulatory bodies in Canada and the United States to determine if Canadian regulators could use the findings of American regulators. There were no important differences in the laws and regulatory bodies in Canada and the United States related to off-label promotion. Canadian regulators can use the findings of American regulators to investigate off-label promotion in Canada. All countries should consider using sanctions in other jurisdictions to direct the deployment of limited regulatory resources.

On the ethics of withholding and withdrawing medical treatment.

PubMed

Reichlin, Massimo

2014-01-01

A general rationale is presented for withholding and withdrawing medical treatment in end-of-life situations, and an argument is offered for the moral irrelevance of the distinction, both in the context of pharmaceutical treatments, such as chemotherapy in cancer, and in the context of life-sustaining treatments, such as the artificial ventilator in lateral amyotrophic sclerosis. It is argued that this practice is not equivalent to sanctioning voluntary active euthanasia and that it is not likely to favour it.

Latent structure modeling underlying theophylline tablet formulations using a Bayesian network based on a self-organizing map clustering.

PubMed

Yasuda, Akihito; Onuki, Yoshinori; Obata, Yasuko; Takayama, Kozo

2015-01-01

The "quality by design" concept in pharmaceutical formulation development requires the establishment of a science-based rationale and design space. In this article, we integrate thin-plate spline (TPS) interpolation, Kohonen's self-organizing map (SOM) and a Bayesian network (BN) to visualize the latent structure underlying causal factors and pharmaceutical responses. As a model pharmaceutical product, theophylline tablets were prepared using a standard formulation. We measured the tensile strength and disintegration time as response variables and the compressibility, cohesion and dispersibility of the pretableting blend as latent variables. We predicted these variables quantitatively using nonlinear TPS, generated a large amount of data on pretableting blends and tablets and clustered these data into several clusters using a SOM. Our results show that we are able to predict the experimental values of the latent and response variables with a high degree of accuracy and are able to classify the tablet data into several distinct clusters. In addition, to visualize the latent structure between the causal and latent factors and the response variables, we applied a BN method to the SOM clustering results. We found that despite having inserted latent variables between the causal factors and response variables, their relation is equivalent to the results for the SOM clustering, and thus we are able to explain the underlying latent structure. Consequently, this technique provides a better understanding of the relationships between causal factors and pharmaceutical responses in theophylline tablet formulation.

Modeling the motion and orientation of various pharmaceutical tablet shapes in a film coating pan using DEM.

PubMed

Ketterhagen, William R

2011-05-16

Film coating uniformity is an important quality attribute of pharmaceutical tablets. Large variability in coating thickness can limit process efficiency or cause significant variation in the amount or delivery rate of the active pharmaceutical ingredient to the patient. In this work, the discrete element method (DEM) is used to computationally model the motion and orientation of several novel pharmaceutical tablet shapes in a film coating pan in order to predict coating uniformity. The model predictions are first confirmed with experimental data obtained from an equivalent film coating pan using a machine vision system. The model is then applied to predict coating uniformity for various tablet shapes, pan speeds, and pan loadings. The relative effects of these parameters on both inter- and intra-tablet film coating uniformity are assessed. The DEM results show intra-tablet coating uniformity is strongly influenced by tablet shape, and the extent of this can be predicted by a measure of the tablet shape. The tablet shape is shown to have little effect on the mixing of tablets, and thus, the inter-tablet coating uniformity. The pan rotation speed and pan loading are shown to have a small effect on intra-tablet coating uniformity but a more significant impact on inter-tablet uniformity. These results demonstrate the usefulness of modeling in guiding drug product development decisions such as selection of tablet shape and process operating conditions. Copyright © 2011 Elsevier B.V. All rights reserved.

Fate and mobility of pharmaceuticals in solid matrices.

PubMed

Drillia, Panagiota; Stamatelatou, Katerina; Lyberatos, Gerasimos

2005-08-01

The sorption and mobility of six pharmaceuticals were investigated in two soil types with different organic carbon and clay content, and in bacterial biomass (aerobic and anaerobic). The pharmaceuticals examined were carbamazepine, propranolol, diclofenac sodium, clofibric acid, sulfamethoxazole and ofloxacin. The sorption experiments were performed according to the OECD test Guideline 106. The distribution coefficients determined by this batch equilibrium method varied with the pharmaceutical tested and the solid matrix type. Ofloxacin was particularly strongly adsorbed (except of the case of using anaerobic biomass for the solid matrix) while clofibric acid was found to be weakly adsorbed. The fate of pharmaceuticals in soil was also assessed using lysimeters. Important parameters that were studied were: the pharmaceutical loading rate and the hydraulic loading rate for adsorption and the rate and duration of a "rain" event for desorption. Major differences in the mobility of the six pharmaceuticals were observed and correlated with the adsorption/desorption properties of the compounds.

Effects of pharmaceuticals present in aquatic environment on Phase I metabolism in fish.

PubMed

Burkina, Viktoriia; Zlabek, Vladimir; Zamaratskaia, Galia

2015-09-01

The fate of pharmaceuticals in aquatic environments is an issue of concern. Current evidence indicates that the risks to fish greatly depend on the nature and concentrations of the pharmaceuticals and might be species-specific. Assessment of risks associated with the presence of pharmaceuticals in water is hindered by an incomplete understanding of the metabolism of these pharmaceuticals in aquatic species. In mammals and fish, pharmaceuticals are primarily metabolized by cytochrome P450 enzymes (CYP450). Thus, CYP450 activity is a crucial factor determining the detoxification abilities of organisms. Massive numbers of toxicological studies have investigated the interactions of human pharmaceuticals with detoxification systems in various fish species. In this paper, we review the effects of pharmaceuticals found in aquatic environments on fish hepatic CYP450. Moreover, we discuss the roles of nuclear receptors in cellular regulation and the effects of various groups of chemicals on fish, presented in the recent literature. Copyright © 2015 Elsevier B.V. All rights reserved.

Pollution pathways of pharmaceutical residues in the aquatic environment on the island of Mallorca, Spain.

PubMed

Rodríguez-Navas, Carlos; Björklund, Erland; Bak, Søren A; Hansen, Martin; Krogh, Kristine A; Maya, Fernando; Forteza, Rafael; Cerdà, Víctor

2013-07-01

This work determines the principal environmental pollution pathways of pharmaceuticals on the island of Mallorca (Spain). The evaluation was made on the basis of the quantification of pharmaceutical residues by liquid chromatography-tandem mass spectrometry in several environmental water samples, including wastewater-treatment plant effluents, municipal solid waste landfill leachates, groundwater (GW), and marine water. An overall set of 19 pharmaceuticals has been identified in the environment of the 27 human pharmaceuticals investigated in this study. WWTP effluents are the main source of discharge of the pharmaceuticals into the aquatic environment. The data indicate that reuse of treated domestic wastewater for irrigation (which supplies some 30 % of the total water demand in Mallorca) contributes to the contamination of GW. In addition, leaching from landfills is identified as another, but minor, possible source of introduction of pharmaceuticals to GW aquifers. Finally, WWTP effluents ending in the Mediterranean Sea, primarily highly urbanized coastal areas, cause pharmaceutical residues to occur in marine water bodies.

Pharmaceutical innovation: impact on expenditure and outcomes and subsequent challenges for pharmaceutical policy, with a special reference to Greece.

PubMed

Karampli, E; Souliotis, K; Polyzos, N; Kyriopoulos, J; Chatzaki, E

2014-04-01

Over the recent decades, advances in healthcare technology have led to significant improvements in the quality of healthcare and in population health. At the same time, technological change in healthcare, rising national income and expansion of insurance coverage have been acknowledged as the main determinants of the historical growth in health spending in industrialized countries. The pharmaceutical sector is of particular interest as it constitutes a market characterized by rapid technological change and high expenditure growth rates. The purpose of this article is to provide an overview of research findings on the impact of pharmaceutical innovation on pharmaceutical expenditure growth, total health expenditure and population health outcomes and to bring forward the challenges that arise for pharmaceutical policy in Greece.

A Comparative Review of Waivers Granted in Pediatric Drug Development by FDA and EMA from 2007-2013.

PubMed

Egger, Gunter F; Wharton, Gerold T; Malli, Suzanne; Temeck, Jean; Murphy, M Dianne; Tomasi, Paolo

2016-09-01

The European Union and the United States have different legal frameworks in place for pediatric drug development, which can potentially lead to different pediatric research requirements for the pharmaceutical industry. This manuscript compares pediatric clinical trial waivers granted by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). This is a retrospective review comparing EMA's Paediatric Committee (PDCO) decisions with FDA's Pediatric Review Committee (PeRC) recommendations for all product-specific pediatric full waiver applications submitted to EMA from January 2007 through December 2013. Using baseline data from EMA, we matched product-specific waivers with their FDA equivalents during the study period. For single active substance products, PDCO and PeRC adopted similar opinions in 42 of 49 indications (86%). For fixed-dose combinations, PDCO and PeRC adopted similar opinions in 24 of 31 indications (77%). Despite the different legal frameworks, criteria, and processes of determination, the waiver decisions of the 2 agencies were similar in the majority of cases.

Nutritional and phytochemical composition of Annona cherimola Mill. fruits and by-products: Potential health benefits.

PubMed

Albuquerque, Tânia Gonçalves; Santos, Filipa; Sanches-Silva, Ana; Beatriz Oliveira, M; Bento, Ana Cristina; Costa, Helena S

2016-02-15

Annona cherimola Mill., commonly known as cherimoya, is a tropical fruit well known due to its tasty flavour. In the present study the antioxidant activity of pulp, peel and seeds of four cultivars from A. cherimola Mill. from Madeira Island (Madeira, Funchal, Perry Vidal and Mateus II) was analysed. Moreover, nutritional composition (proximates and vitamins) and bioactive compounds content were determined. The peel of Madeira cultivar showed the highest antioxidant capacity, with an EC50 of 0.97mg/mL, and total flavonoids (44.7 epicatechin equivalents/100g). The most abundant carotenoid was lutein, with values ranging from 129 to 232μg/100g. The highest l-ascorbic acid content (4.41mg/100g) was found in the peel of Perry Vidal cultivar. These results highlight A. cherimola Mill. antioxidant properties, especially in its by-products and encourage their application in cosmetic, pharmaceutical and food processing industries, as added value natural extracts. Copyright © 2014 Elsevier Ltd. All rights reserved.

Uptake from water, biotransformation, and biliary excretion of pharmaceuticals by rainbow trout.

PubMed

Lahti, Marja; Brozinski, Jenny-Maria; Jylhä, Antti; Kronberg, Leif; Oikari, Aimo

2011-06-01

An urgent need exists to assess the exposure of fish to pharmaceuticals. The aim of the present study was to assess the uptake and metabolism of waterborne pharmaceuticals in rainbow trout (Oncorhynchus mykiss). A further objective was to determine the possibility of monitoring exposure to low levels of pharmaceuticals by bile assays. Rainbow trout were exposed for 10 d under flow-through conditions to mixtures of five pharmaceuticals (diclofenac, naproxen, ibuprofen, bisoprolol, and carbamazepine) at high and low concentrations. The low concentration was used to mimic the conditions prevailing in the vicinity of the discharge points of wastewater treatment plants. The uptake and the bioconcentration were determined by blood plasma and bile analyses. The average bioconcentration factor in plasma ranged from below 0.1 for bisoprolol to 4.9 for diclofenac, the values being approximately similar at low and high ambient concentrations. The biotransformation of diclofenac, naproxen, and ibuprofen was considered efficient, because several metabolites could be detected in concentrations clearly exceeding those of the unmetabolized compounds. The glucuronides were the dominant metabolites for all three pharmaceuticals. The total bioconcentration in the bile was two to four orders of magnitude higher than in the plasma. The results of this work show that the exposure of fish to pharmaceuticals in environmentally relevant concentrations may be monitored by blood plasma and bile analyses, the latter allowing detection at markedly lower ambient concentration. Copyright © 2011 SETAC.

Quality assessment of pharmaceutical tablet samples using Fourier transform near infrared spectroscopy and multivariate analysis

NASA Astrophysics Data System (ADS)

Kandpal, Lalit Mohan; Tewari, Jagdish; Gopinathan, Nishanth; Stolee, Jessica; Strong, Rick; Boulas, Pierre; Cho, Byoung-Kwan

2017-09-01

Determination of the content uniformity, assessed by the amount of an active pharmaceutical ingredient (API), and hardness of pharmaceutical materials is important for achieving a high-quality formulation and to ensure the intended therapeutic effects of the end-product. In this work, Fourier transform near infrared (FT-NIR) spectroscopy was used to determine the content uniformity and hardness of a pharmaceutical mini-tablet and standard tablet samples. Tablet samples were scanned using an FT-NIR instrument and tablet spectra were collected at wavelengths of 1000-2500 nm. Furthermore, multivariate analysis was applied to extract the relationship between the FT-NIR spectra and the measured parameters. The results of FT-NIR spectroscopy for API and hardness prediction were as precise as the reference high-performance liquid chromatography and mechanical hardness tests. For the prediction of mini-tablet API content, the highest coefficient of determination for the prediction (R2p) was found to be 0.99 with a standard error of prediction (SEP) of 0.72 mg. Moreover, the standard tablet hardness measurement had a R2p value of 0.91 with an SEP of 0.25 kg. These results suggest that FT-NIR spectroscopy is an alternative and accurate nondestructive measurement tool for the detection of the chemical and physical properties of pharmaceutical samples.

Size exclusion chromatography with evaporative light scattering detection as a method for speciation analysis of polydimethylsiloxanes. III. Identification and determination of dimeticone and simeticone in pharmaceutical formulations.

PubMed

Mojsiewicz-Pieńkowska, Krystyna

2012-01-25

The pharmaceutical industry is one of the more important sectors for the use of polydimethylsiloxanes (PDMS), which belong to the organosilicon polymers. In drugs for internal use, they are used as an active pharmaceutical ingredient (API) called dimeticone or simeticone. Due to their specific chemical nature, PDMS can have different degrees of polymerization, which determine the molecular weight and viscosity. The Pharmacopoeial monographs for dimeticone and simeticone, only give the permitted polymerization and viscosity range. It is, however, essential to know also the degree of polymerization or the specific molecular weight of PDMS that are present in pharmaceutical formulations. In the literature there is information about the impact of particle size, and thus molecular weight, on the toxicity, absorption and migration in living organisms. This study focused on the use of a developed method - the exclusion chromatography with evaporative light scattering detector (SEC-ELSD) - for identification and determination of dimeticone and simeticone in various pharmaceutical formulations. The method had a high degree of specificity and was suitable for speciation analysis of these polymers. So far the developed method has not been used in the control of medicinal products containing dimeticone or simeticone. Copyright © 2011 Elsevier B.V. All rights reserved.

Differences in the Volume of Pharmaceutical Advertisements between Print General Medical Journals

PubMed Central

Gettings, Jennifer; O'Neill, Braden; Chokshi, Dave A.; Colbert, James A.; Gill, Peter; Lebovic, Gerald; Lexchin, Joel; Persaud, Navindra

2014-01-01

Background Pharmaceutical advertisements have been argued to provide revenue that medical journals require but they are intended to alter prescribing behaviour and they are known to include low quality information. We determined whether a difference exists in the current level of pharmaceutical advertising in print general medical journals, and we estimated the revenue generated from print pharmaceutical advertising. Methods Six print general medical journals in Canada, the United States, and the United Kingdom were sampled between 2007 and 2012. The number of advertisements and other journal content in selected issues of the Canadian Medical Association Journal (CMAJ), Canadian Family Physician (CFP), Journal of the American Medical Association (JAMA), New England Journal of Medicine (NEJM), British Medical Journal (BMJ), and Lancet were determined. Revenue gained from pharmaceutical advertising was estimated using each journal's 2013 advertising price list. Findings The two Canadian journals sampled (CMAJ, CFP) contained five times more advertisements than the two American journals (JAMA, NEJM), and two British journals (BMJ, Lancet) (p<0.0001). The estimated annual revenue from pharmaceutical advertisements ranged from £0.025 million (for Lancet) to £3.8 million (for JAMA). The cost savings due to revenue from pharmaceutical advertising to each individual subscriber ranged from £0.02 (for Lancet) to £3.56 (for CFP) per issue. Conclusion The volume of pharmaceutical advertisements differs between general medical journals, with the two Canadian journals sampled containing the most advertisements. International and temporal variations suggest that there is an opportunity for all general medical journals to reduce the number of pharmaceutical advertisements, explore other sources of revenue, and increase transparency regarding sources of revenue. PMID:24416286

Determination of selected pharmaceuticals in tap water and drinking water treatment plant by high-performance liquid chromatography-triple quadrupole mass spectrometer in Beijing, China.

PubMed

Cai, Mei-Quan; Wang, Rong; Feng, Li; Zhang, Li-Qiu

2015-02-01

A simultaneous determination method of 14 multi-class pharmaceuticals using solid-phase extraction (SPE) followed by high-performance liquid chromatography-tandem mass spectrometer (HPLC-MS/MS) was established to measure the occurrence and distribution of these pharmaceuticals in tap water and a drinking water treatment plant (DWTP) in Beijing, China. Target compounds included seven anti-inflammatory drugs, two antibacterial drugs, two lipid regulation drugs, one antiepileptic drug, and one hormone. Limits of detection (LODs) and limits of quantitation (LOQs) ranged from 0.01 to 1.80 ng/L and 0.05 to 3.00 ng/L, respectively. Intraday and inter-day precisions, recoveries of different matrices, and matrix effects were also investigated. Of the 14 pharmaceutical compounds selected, nine were identified in tap water of Beijing downtown with the concentration up to 38.24 ng/L (carbamazepine), and the concentration levels of detected pharmaceuticals in tap water (<5 ng/L for most pharmaceuticals) were lower than previous studies in other countries. In addition, ten and six pharmaceuticals were measured in raw water and finished water at the concentration ranged from 0.10 to 16.23 and 0.13 to 17.17 ng/L, respectively. Five compounds were detected most frequently in DWTP, namely antipyrine, carbamazepine, isopropylantipyrine, aminopyrine, and bezafibrate. Ibuprofen was found to be the highest concentration pharmaceutical during DWTP, up to 53.30 ng/L. DWTP shows a positive effect on the removal of most pharmaceuticals with 81.2-99.5 % removal efficiencies, followed by carbamazepine with 55.4 % removal efficiency, but it has no effect for removing ibuprofen and bezafibrate.

5 CFR 531.407 - Equivalent increase determinations.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Equivalent increase determinations. 531... PAY UNDER THE GENERAL SCHEDULE Within-Grade Increases § 531.407 Equivalent increase determinations. (a) GS employees. For a GS employee, an equivalent increase is considered to occur at the time of any of...

5 CFR 531.407 - Equivalent increase determinations.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Equivalent increase determinations. 531... PAY UNDER THE GENERAL SCHEDULE Within-Grade Increases § 531.407 Equivalent increase determinations. (a) GS employees. For a GS employee, an equivalent increase is considered to occur at the time of any of...

Publication bias in the pulmonary/allergy literature: effect of pharmaceutical company sponsorship.

PubMed

Liss, Howard

2006-07-01

A publication bias exists towards positive results in studies funded by pharmaceutical companies. To determine whether drug studies in the pulmonary/allergy literature also demonstrate a publication bias towards more favorable results when a pharmaceutical company funds the study. We reviewed all original articles published in seven pulmonary and allergy journals between October 2002 and September 2003. Included in the review were studies of inhaled corticosteroids (oral or nasal), long- or short-acting bronchodilators, or leukotriene receptor antagonists. Articles with funding from a pharmaceutical company and/or one or more authors employed by a pharmaceutical company were considered pharmaceutical company-sponsored studies. The remaining studies were considered not sponsored by a pharmaceutical company. Results were compared to ascertain whether positive results were obtained more frequently in the company-sponsored studies. Of the 100 articles included in this review 63 were considered pharmaceutical company-sponsored research. Results favorable for the drugs studies were significantly more common in those funded by a pharmaceutical company (98% vs. 32%). In the pulmonary and allergy literature, as in other fields, there is a publication bias towards positive results in pharmaceutical company-sponsored research.

Growth of near-infrared spectroscopy in pharmaceutical and medical sciences

NASA Astrophysics Data System (ADS)

Ciurczak, Emil W.

2002-06-01

Near-IR Spectroscopy (NIRS) is used extensively in the health services industries: medical research, pharmaceutical production, and bioprocessing. NIRS Is rugged, simple to operate, flexible, and relatively inexpensive. It may be used to monitor the progress biochemical reactions. It is used to control mixing, blending, drying, and coating in pharmaceutical production and is used for imaging and chemical determinations in living patients.

Determination of diosmin in pharmaceutical formulations using Fourier transform infrared spectrophotometry

PubMed Central

Bunaciu, Andrei A.; Udristioiu, Gabriela Elena; Ruţă, Lavinia L.; Fleschin, Şerban; Aboul-Enein, Hassan Y.

2009-01-01

A Fourier transform infrared (FT-IR) spectrometric method was developed for the rapid, direct measurement of diosmin in different pharmaceutical drugs. Conventional KBr-spectra were compared for best determination of active substance in commercial preparations. The Beer–Lambert law and two chemometric approaches, partial least squares (PLS) and principal component regression (PCR+) methods, were tried in data processing. PMID:23960715

Glucocorticoid activity detected by in vivo zebrafish assay and in vitro glucocorticoid receptor bioassay at environmental relevant concentrations.

PubMed

Chen, Qiyu; Jia, Ai; Snyder, Shane A; Gong, Zhiyuan; Lam, Siew Hong

2016-02-01

Glucocorticoids are pharmaceutical contaminants of emerging concern due to their incomplete removal during wastewater treatment, increased presence in aquatic environment and their biological potency. The zebrafish is a popular model for aquatic toxicology and environmental risk assessment. This study aimed to determine if glucocorticoids at environmental concentrations would perturb expression of selected glucocorticoid-responsive genes in zebrafish and to investigate their potentials as an in vivo zebrafish assay in complementing in vitro glucocorticoid receptor bioassay. The relative expression of eleven glucocorticoid-responsive genes in zebrafish larvae and liver of adult male zebrafish exposed to three representative glucocorticoids (dexamethasone, prednisolone and triamcinolone) was determined. The expression of pepck, baiap2 and pxr was up-regulated in zebrafish larvae and the expression of baiap2, pxr and mmp-2 was up-regulated in adult zebrafish exposed to glucocorticoids at concentrations equivalent to total glucocorticoids reported in environmental samples. The responsiveness of the specific genes were sufficiently robust in zebrafish larvae exposed to a complex environmental sample detected with in vitro glucocorticoid activity equivalent to 478 pM dexamethasone (DEX-EQ) and confirmed to contain low concentration (0.2 ng/L or less) of the targeted glucocorticoids, and possibly other glucocorticoid-active compounds. The findings provided in vivo relevance to the in vitro glucocorticoid activity and suggested that the environmental sample can perturb glucocorticoid-responsive genes in its original, or half the diluted, concentration as may be found in the environment. The study demonstrated the important complementary roles of in vivo zebrafish and in vitro bioassays coupled with analytical chemistry in monitoring environmental glucocorticoid contaminants. Copyright © 2015 Elsevier Ltd. All rights reserved.

High-speed liquid chromatographic determination of pilocarpine in pharmaceutical dosage forms.

PubMed

Khalil, S K

1977-11-01

A specific method for the direct determination of pilocarpine in aqueous pharmaceuticals in the presence of decomposition products, methylcellulose, and other ingredients usually present in pharmaceuticals is described. The method involves separation by high-speed liquid chromatography using, in series, octadecylsilane bonded to silica and cyanopropylsilane bonded to silica columns and a tetrahydrofuran-pH 9.2 borate buffer (3:7) eluant. Quantitation is achieved by monitoring the absorbance of the effluent at 254 nm and using a pyridine internal standard and a calibration curve prepared from known concentrations of pilocarpine nitrate. The reproducibility of the retention time and peak area was better than 2.0%.

Determination of preservatives in cosmetics, cleaning agents and pharmaceuticals using fast liquid chromatography.

PubMed

Baranowska, Irena; Wojciechowska, Iwona; Solarz, Natalia; Krutysza, Ewa

2014-01-01

This paper reports the development of a method for simultaneously determining five preservatives in cosmetics, cleaning agents and pharmaceuticals by fast liquid chromatography. Methylisothiazolinone, methylchloroisothiazolinone, benzyl alcohol, sodium benzoate and methylparaben were separated on a Chromolith Fast Gradient reversed-phase 18e column using gradient elution with acetonitrile and a 0.1% aqueous solution of formic acid, with a run time of 3 min. The preparation of solid and liquid samples included ultrasonic extraction with methanol with recoveries ranging from 69 to 119%. The developed method was used to analyze samples of cosmetics (66 samples), cleaning agents (five samples) and pharmaceutical industry products (17 samples).

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

PubMed

Jenke, Dennis

2015-01-01

An accelerating trend in the pharmaceutical industry is the use of plastic components in systems used to produce an active pharmaceutical ingredient or a finished drug product. If the active pharmaceutical ingredient, the finished drug product, or any solution used to generate them (for example, a process stream such as media, buffers, eluents, and the like) is contacted by a plastic component at any time during the production process, substances leached from the component may accumulate in the active pharmaceutical ingredient or finished drug product, affecting its safety and/or efficacy. In this article the author develops and justifies a semi-quantitative risk evaluation matrix that is used to determine the amount and rigor of component testing necessary and appropriate to establish that the component is chemically suitable for its intended use. By considering key properties of the component, the contact medium, the contact conditions, and the active pharmaceutical ingredient's or finished drug product's clinical conditions of use, use of the risk evaluation matrix produces a risk score whose magnitude reflects the accumulated risk that the component will interact with the contact solution to such an extent that component-related extractables will accumulate in the active pharmaceutical ingredient or finished drug product as leachables at levels sufficiently high to adversely affect user safety. The magnitude of the risk score establishes the amount and rigor of the testing that is required to select and qualify the component, and such testing is broadly grouped into three categories: baseline assessment, general testing, and full testing (extractables profiling). Production suites used to generate pharmaceuticals can include plastic components. It is possible that substances in the components could leach into manufacturing solutions and accumulate in the pharmaceutical product. In this article the author develops and justifies a semi-quantitative risk evaluation matrix that can be used to determine the amount and rigor of component testing that may be necessary and appropriate to establish that the component is suitable for its intended use. Use of the risk evaluation matrix allows a user of a component to determine the type and amount of testing that should be performed to establish the patient safety risk associated with using that component in order to manufacture an active pharmaceutical ingredient or a finished drug product. © PDA, Inc. 2015.

Rapid determination of isoamyl nitrite in pharmaceutical preparations by flow injection analysis with on-line UV irradiation and luminol chemiluminescence detection.

PubMed

Kishikawa, Naoya; Kondo, Naoko; Amponsaa-Karikari, Abena; Kodamatani, Hitoshi; Ohyama, Kaname; Nakashima, Kenichiro; Yamazaki, Shigeo; Kuroda, Naotaka

2014-02-01

Isoamyl nitrite is used as a therapeutic reagent for cardiac angina and as an antidote for cyanide poisoning, but it is abused because of its euphoric properties. Therefore, a method to determine isoamyl nitrite is required in many fields, including pharmaceutical and forensic studies. In this study, a simple, rapid and sensitive method for the determination of isoamyl nitrite was developed using a flow injection analysis system equipped with a chemiluminescence detector and on-line photoreactor. This method is based on on-line ultraviolet irradiation of isoamyl nitrite and subsequent luminol chemiluminescence detection without the addition of an oxidant. A linear standard curve was obtained up to 1.0 μM of isoamyl nitrite with a detection limit (blank + 3SD) of 0.03 μM. The method was successfully applied to determine isoamyl nitrite content in pharmaceutical preparations. Copyright © 2013 John Wiley & Sons, Ltd.

High performance liquid chromatographic determination of ambroxol in the presence of different preservatives in pharmaceutical formulations.

PubMed

Koundourellis, J E; Malliou, E T; Broussali, T A

2000-08-15

A high-performance chromatographic method is described for simultaneous determination of ambroxol in the presence of different preservatives in syrups. The method separates ambroxol from methyl- ethyl-, propyl- and butyl paraben and from other multi-component mixtures. The retention behaviour of ambroxol and parabens as a function of both pH and mobile phase composition was investigated. The eluents were monitored with a UV detector at 247 nm. Linear relationships between the amount of pharmaceutical compounds and peak heights were confirmed at the concentrations of 0.74-14.08 microg ml(-1). The high recovery (no extraction of the samples is required) and the low %RSD confirm the suitability of the proposed method for the determination of ambroxol in different pharmaceutical preparations.

On-line monitoring of the crystallization process: relationship between crystal size and electrical impedance spectra

NASA Astrophysics Data System (ADS)

Zhao, Yanlin; Yao, Jun; Wang, Mi

2016-07-01

On-line monitoring of crystal size in the crystallization process is crucial to many pharmaceutical and fine-chemical industrial applications. In this paper, a novel method is proposed for the on-line monitoring of the cooling crystallization process of L-glutamic acid (LGA) using electrical impedance spectroscopy (EIS). The EIS method can be used to monitor the growth of crystal particles relying on the presence of an electrical double layer on the charged particle surface and the polarization of double layer under the excitation of alternating electrical field. The electrical impedance spectra and crystal size were measured on-line simultaneously by an impedance analyzer and focused beam reflectance measurement (FBRM), respectively. The impedance spectra were analyzed using the equivalent circuit model and the equivalent circuit elements in the model can be obtained by fitting the experimental data. Two equivalent circuit elements, including capacitance (C 2) and resistance (R 2) from the dielectric polarization of the LGA solution and crystal particle/solution interface, are in relation with the crystal size. The mathematical relationship between the crystal size and the equivalent circuit elements can be obtained by a non-linear fitting method. The function can be used to predict the change of crystal size during the crystallization process.

28 CFR 36.605 - Procedure following preliminary determination of equivalency.

Code of Federal Regulations, 2010 CFR

2010-07-01

... State Laws or Local Building Codes § 36.605 Procedure following preliminary determination of equivalency... of the preliminary determination of equivalency with respect to the particular code, and invite...

Application of the near-infrared spectroscopy in the pharmaceutical technology.

PubMed

Jamrógiewicz, Marzena

2012-07-01

Near-infrared (NIR) spectroscopy is currently the fastest-growing and the most versatile analytical method not only in the pharmaceutical sciences but also in the industry. This review focuses on recent NIR applications in the pharmaceutical technology. This article covers monitoring, by NIR, of many manufacturing processes, such as granulation, mixing or drying, in order to determine the end-point of these processes. In this paper, apart from basic theoretical information concerning the NIR spectra, there are included determinations of the quality and quantity of pharmaceutical compounds. Some examples of measurements and control of physicochemical parameters of the final medicinal products, such as hardness, porosity, thickness size, compression strength, disintegration time and potential counterfeit are included. Biotechnology and plant drug analysis using NIR is also described. Moreover, some disadvantages of this method are stressed and future perspectives are anticipated. Copyright © 2012 Elsevier B.V. All rights reserved.

Spectrofluorimetric analysis of famotidine in pharmaceutical preparations and biological fluids by derivatization with benzoin

NASA Astrophysics Data System (ADS)

Alamgir, Malik; Khuhawar, Muhammad Yar; Memon, Saima Q.; Hayat, Amir; Zounr, Rizwan Ali

2015-01-01

A sensitive and simple spectrofluorimetric method has been developed for the analysis of famotidine, from pharmaceutical preparations and biological fluids after derivatization with benzoin. The reaction was carried out in alkaline medium with measurement of fluorescence intensity at 446 nm with excitation wavelength at 286 nm. Linear calibration was obtained with 0.5-15 μg/ml with coefficient of determination (r2) 0.997. The factors affecting the fluorescence intensity were optimized. The pharmaceutical additives and amino acid did not interfere in the determination. The mean percentage recovery (n = 4) calculated by standard addition from pharmaceutical preparation was 94.8-98.2% with relative standard deviation (RSD) 1.56-3.34% and recovery from deproteinized spiked serum and urine of healthy volunteers was 98.6-98.9% and 98.0-98.4% with RSD 0.34-0.84% and 0.29-0.87% respectively.

Determination of Gentamicin Sulphate Composition and Related Substances in Pharmaceutical Preparations by LC with Charged Aerosol Detection

PubMed Central

Stypulkowska, Karolina; Fijalek, Zbigniew; Sarna, Katarzyna

2010-01-01

A new, simple and repeatable liquid chromatography method with charged aerosol detection (LC-CAD) for the determination of gentamicin sulphate composition and related substances has been developed. Gentamicin lacks of chromophores, therefore its determination is quite problematic. Using a universal CAD enables to achieve good separation without sample derivatization. Mass spectrometry was employed to confirm the LC-CAD peak profile. The proposed method was validated and applied for the determination of gentamicin sulphate composition and related substances in pharmaceutical preparations. PMID:21212825

What Can We Expect from Value-Based Funding of Medicines? A Retrospective Study.

PubMed

Harris, Anthony; Li, Jing Jing; Yong, Karen

2016-04-01

Deciding on public funding for pharmaceuticals on the basis of value for money is now widespread. We suggest that evidence-based assessment of value has restricted the availability of medicines in Australia in a way that reflects the relative bargaining power of government and the pharmaceutical industry. We propose a simple informal game-theoretic model of bargaining between the funding agency and industry and test its predictions using a logistic multiple regression model of past funding decisions made by the Pharmaceutical Benefits Advisory Committee in Australia. The model estimates the probability of a drug being recommended for subsidy as a function of incremental cost per quality-adjusted life-year (QALY), as well as other drug and market characteristics. Data are major submissions or resubmissions from 1993 to 2009 where there was a claim of superiority and evidence of a difference in quality of life. Independent variables measure the incremental cost per QALY, the cost to the public budget, the strength and quality of the clinical and economic evidence, need as measured by severity of illness and the availability of alternative treatments, whether or not a resubmission, and newspaper reports as a measure of public pressure. We report the odds ratio for each variable and calculate the ratio of the marginal effect of each variable to the marginal effect of the cost per QALY as a measure of the revealed willingness to pay for each of the variables that influence the decision. The results are consistent with a bargaining model where a 10,000 Australian dollar ($A) fall in value (increase in cost per QALY) reduces the average probability of public funding from 37 to 33% (95% CI 34-32). If the condition is life threatening or the drug has no active comparator, then the odds of a positive recommendation are 3.18 (95% CI 1.00-10.11) and 2.14 (95% CI 0.95-4.83) greater, equivalent to a $A33,000 and a $A21,000 increase in value (fall in cost per QALY). If both conditions are met, the odds are increased by 4.41 (95% CI 1.28-15.24) times, equivalent to an increase in value of $A46,000. Funding is more likely as time elapses and price falls, but we did not find clear evidence that public or corporate pressure influences decisions. Evidence from Australia suggests that the determinants of public funding and pricing decisions for medicines reflect the relative bargaining power of government and drug companies. Value for money depends on the quality of evidence, timing, patient need, perceived benefit and opportunity cost; these factors reflect the potential gains from striking a bargain and the risk of loss from not doing so.

Rheological and molecular weight comparisons of approved hyaluronic acid products - preliminary standards for establishing class III medical device equivalence.

PubMed

Braithwaite, Gavin J C; Daley, Michael J; Toledo-Velasquez, David

2016-01-01

Hyaluronic acid of various molecular weights has been in use for the treatment of osteoarthritis knee pain for decades. Worldwide, these products are regulated as either as drugs or devices and in some countries as both. In the US, this class of products is regulated as Class III medical devices, which places specific regulatory requirements on developers of these materials under a Pre-Market Approval process, typically requiring data from prospective randomized controlled clinical studies. In 1984 pharmaceutical manufacturers became able to file an Abbreviated New Drug Application for approval of a generic drug, thus establishing standards for demonstrating equivalence to an existing chemical entity. Recently, the first biosimilar, or 'generic biologic', was approved. Biosimilars are biological products that are approved by the FDA because they are 'highly similar' to a reference product, and have been shown to have no clinically meaningful differences from the reference product. For devices, Class II medical devices have a pathway for declaring equivalence to an existing product by filing a 510 k application for FDA clearance. However, until recently no equivalent regulatory pathway was available to Class III devices. In this paper, we consider the critical mechanical performance parameters for intra-articular hyaluronic products to demonstrate indistinguishable characteristics. Analogous to the aforementioned pathways that allow for a demonstration of equivalence, we examine these parameters for an existing, marketed device and compare molecular weight and rheological properties of multiple batches of a similar product. We propose that this establishes a scientific rationale for establishing Class III medical device equivalence.

Inequalities in out-of-pocket payments for health care services among elderly Germans – results of a population-based cross-sectional study

PubMed Central

2014-01-01

Introduction In order to limit rising publicly-financed health expenditure, out-of-pocket payments for health care services (OOPP) have been raised in many industrialized countries. However, higher health-related OOPP may burden social subgroups unequally. In Germany, inequalities in OOPP have rarely been analyzed. The aim of this study was to examine OOPP of the German elderly population in the different sectors of the health care system. Socio-economic and morbidity-related determinants of inequalities in OOPP were analyzed. Methods This cross-sectional analysis used data of N = 3,124 subjects aged 57 to 84 years from a population-based prospective cohort study (ESTHER study) collected in the Saarland, Germany, from 2008 to 2010. Subjects passed a geriatric assessment, including a questionnaire for health care utilization and OOPP covering a period of three months in the following sectors: inpatient care, outpatient physician and non-physician services, medical supplies, pharmaceuticals, dental prostheses and nursing care. Determinants of OOPP were analyzed by a two-part model. The financial burden of OOPP for certain social subgroups (measured by the OOPP-income-ratio) was investigated by a generalized linear model for the binomial family. Results Mean OOPP during three months amounted to €119, with 34% for medical supplies, 22% for dental prostheses, 21% for pharmaceuticals, 17% for outpatient physician and non-physician services, 5% for inpatient care and 1% for nursing care. The two-part model showed a significant positive association between income (square root equivalence scale) and total OOPP. Increasing morbidity was associated with significantly higher total OOPP, and in particular with higher OOPP for pharmaceuticals. Total OOPP amounted to about 3% of disposable income. The generalized linear model for the binomial family showed a significantly lower financial burden for the wealthiest quintile as compared to the poorest one. Conclusions This is the first study providing evidence of inequalities in OOPP in the German elderly population. Socio-economic and morbidity-related inequalities in OOPP and the resulting financial burden could be identified. The results of this study may contribute to the discussion about the mechanisms causing the observed inequalities and can thus help decision makers to consider them when adapting future regulations on OOPP. PMID:24397544

Determination of propranolol hydrochloride in pharmaceutical preparations using near infrared spectrometry with fiber optic probe and multivariate calibration methods.

PubMed

Marques Junior, Jucelino Medeiros; Muller, Aline Lima Hermes; Foletto, Edson Luiz; da Costa, Adilson Ben; Bizzi, Cezar Augusto; Irineu Muller, Edson

2015-01-01

A method for determination of propranolol hydrochloride in pharmaceutical preparation using near infrared spectrometry with fiber optic probe (FTNIR/PROBE) and combined with chemometric methods was developed. Calibration models were developed using two variable selection models: interval partial least squares (iPLS) and synergy interval partial least squares (siPLS). The treatments based on the mean centered data and multiplicative scatter correction (MSC) were selected for models construction. A root mean square error of prediction (RMSEP) of 8.2 mg g(-1) was achieved using siPLS (s2i20PLS) algorithm with spectra divided into 20 intervals and combination of 2 intervals (8501 to 8801 and 5201 to 5501 cm(-1)). Results obtained by the proposed method were compared with those using the pharmacopoeia reference method and significant difference was not observed. Therefore, proposed method allowed a fast, precise, and accurate determination of propranolol hydrochloride in pharmaceutical preparations. Furthermore, it is possible to carry out on-line analysis of this active principle in pharmaceutical formulations with use of fiber optic probe.

Precise determination of N-acetylcysteine in pharmaceuticals by microchip electrophoresis.

PubMed

Rudašová, Marína; Masár, Marián

2016-01-01

A novel microchip electrophoresis method for the rapid and high-precision determination of N-acetylcysteine, a pharmaceutically active ingredient, in mucolytics has been developed. Isotachophoresis separations were carried out at pH 6.0 on a microchip with conductivity detection. The methods of external calibration and internal standard were used to evaluate the results. The internal standard method effectively eliminated variations in various working parameters, mainly run-to-run fluctuations of an injected volume. The repeatability and accuracy of N-acetylcysteine determination in all mucolytic preparations tested (Solmucol 90 and 200, and ACC Long 600) were more than satisfactory with the relative standard deviation and relative error values <0.7 and <1.9%, respectively. A recovery range of 99-101% of N-acetylcysteine in the analyzed pharmaceuticals predetermines the proposed method for accurate analysis as well. This work, in general, indicates analytical possibilities of microchip isotachophoresis for the quantitative analysis of simplified samples such as pharmaceuticals that contain the analyte(s) at relatively high concentrations. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Application of ion chromatography in pharmaceutical and drug analysis.

PubMed

Jenke, Dennis

2011-08-01

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

Development and optimization of the determination of pharmaceuticals in water samples by SPE and HPLC with diode-array detection.

PubMed

Pavlović, Dragana Mutavdžić; Ašperger, Danijela; Tolić, Dijana; Babić, Sandra

2013-09-01

This paper describes the development, optimization, and validation of a method for the determination of five pharmaceuticals from different therapeutic classes (antibiotics, anthelmintics, glucocorticoides) in water samples. Water samples were prepared using SPE and extracts were analyzed by HPLC with diode-array detection. The efficiency of 11 different SPE cartridges to extract the investigated compounds from water was tested in preliminary experiments. Then, the pH of the water sample, elution solvent, and sorbent mass were optimized. Except for optimization of the SPE procedure, selection of the optimal HPLC column with different stationary phases from different manufacturers has been performed. The developed method was validated using spring water samples spiked with appropriate concentrations of pharmaceuticals. Good linearity was obtained in the range of 2.4-200 μg/L, depending on the pharmaceutical with the correlation coefficients >0.9930 in all cases, except for ciprofloxacin (0.9866). Also, the method has revealed that low LODs (0.7-3.9 μg/L), good precision (intra- and interday) with RSD below 17% and recoveries above 98% for all pharmaceuticals. The method has been successfully applied to the analysis of production wastewater samples from the pharmaceutical industry. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Suspensions as a Valuable Alternative to Extemporaneously Compounded Capsules.

PubMed

Dijkers, Eli; Nanhekhan, Valerie; Thorissen, Astrid; Polonini, Hudson

2017-01-01

The objective of this study was to determine the variation in content of 74 different active pharmaceutical ingredients (APIs) and compare it with what is known in the literature for the content uniformity of extemporaneous prepared capsules. Active pharmaceutical ingredients quantification was performed by high-performance liquid chromatography, via a stability-indicating method. Samples for all active pharmaceutical ingredients were taken throughout a 90-day period and the content was determined. In total, 5,190 different samples were analyzed for 74 different active pharmaceutical ingredients at room (15°C to 25°C) or controlled refrigerated temperature (2°C to 8°C). Each of these datasets was analyzed according to the United States Pharmacopeia Content Uniformity monograph, corrected for the sample number. The mean acceptance values were well within specifications. In addition, all suspensions complied with the criteria defined by the British Pharmacopoeia monograph for Content Uniformity of Liquid Dispersions for both room and controlled refrigerated temperature. In previous studies, it was found that a routine weight variation check is often not sufficient for quality assurance of extemporaneous prepared capsules. Compounded oral liquids show little variation in content for 74 different active pharmaceutical ingredients; therefore, compounded oral liquids are a suitable alternative when compounding individualized medications for patients. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Automated Dissolution for Enteric-Coated Aspirin Tablets: A Case Study for Method Transfer to a RoboDis II.

PubMed

Ibrahim, Sarah A; Martini, Luigi

2014-08-01

Dissolution method transfer is a complicated yet common process in the pharmaceutical industry. With increased pharmaceutical product manufacturing and dissolution acceptance requirements, dissolution testing has become one of the most labor-intensive quality control testing methods. There is an increased trend for automation in dissolution testing, particularly for large pharmaceutical companies to reduce variability and increase personnel efficiency. There is no official guideline for dissolution testing method transfer from a manual, semi-automated, to automated dissolution tester. In this study, a manual multipoint dissolution testing procedure for an enteric-coated aspirin tablet was transferred effectively and reproducibly to a fully automated dissolution testing device, RoboDis II. Enteric-coated aspirin samples were used as a model formulation to assess the feasibility and accuracy of media pH change during continuous automated dissolution testing. Several RoboDis II parameters were evaluated to ensure the integrity and equivalency of dissolution method transfer from a manual dissolution tester. This current study provides a systematic outline for the transfer of the manual dissolution testing protocol to an automated dissolution tester. This study further supports that automated dissolution testers compliant with regulatory requirements and similar to manual dissolution testers facilitate method transfer. © 2014 Society for Laboratory Automation and Screening.

Quality and cost assessment of a recombinant antibody fragment produced from mammalian, yeast and prokaryotic host cells: A case study prior to pharmaceutical development.

PubMed

Lebozec, Kristell; Jandrot-Perrus, Martine; Avenard, Gilles; Favre-Bulle, Olivier; Billiald, Philippe

2018-09-25

Monoclonal antibody fragments (Fab) are a promising class of therapeutic agents. Fabs are aglycosylated proteins and so many expression platforms have been developed including prokaryotic, yeast and mammalian cells. However, these platforms are not equivalent in terms of cell line development and culture time, product quality and possibly cost of production that greatly influence the success of a drug candidate's pharmaceutical development. This study is an assessment of the humanized Fab fragment ACT017 produced from two microorganisms (Escherichia coli and Pichia pastoris) and one mammalian cell host (CHO). Following low scale production and Protein L-affinity purification under generic conditions, physico-chemical and functional quality assessments were carried out prior to economic analysis of industrial scale production using a specialized software (Biosolve, Biopharm Services, UK). Results show higher titer production when using E. coli but associated with high heterogeneity of the protein content recovered in the supernatant. We also observed glycoforms of the Fab produced from P. pastoris, while Fab secreted from CHO was the most homogeneous despite a much longer culture time and slightly higher estimated cost of goods. This study may help inform future pharmaceutical development of this class of therapeutic proteins. Copyright © 2018 Elsevier B.V. All rights reserved.

Pharmaceutical advertising revenue and physician organizations: how much is too much?

PubMed Central

Glassman, P A; Hunter-Hayes, J; Nakamura, T

1999-01-01

OBJECTIVE: To determine if revenue generated from pharmaceutical advertisements in medical journals creates potential financial conflicts of interest for nonprofit physician organizations that own those journals. DESIGN: Convenience sample of six professional medical societies and their respective journals. Calculation of pharmaceutical advertising revenue generated by these journals for their respective professional medical societies. METHODS: Random selection of each journal for one month per quarter in calendar year 1996 and tabulation per edition of the average number of pharmaceutical advertising pages for each journal. OUTCOME MEASURES: Published advertising rates were used to estimate pharmaceutical advertising revenue for calendar year 1996 and compared with each organization's gross revenue and membership dues and assessments, based on Internal Revenue Service documents for the last available fiscal year (1995). RESULTS: Estimated pharmaceutical advertising revenue ranged from $715,000 to $18,630,000. Five organizations raised more than 10% of their gross income (range 2% to 30%) from a single journal's pharmaceutical advertising. Four organizations raised as much or more from pharmaceutical advertising as from members (range 17% to 790%). CONCLUSIONS: Potential financial conflicts of interest arising from pharmaceutical advertisements in medical journals may be substantial. The impact on professional societies' financial independence and behavior is unknown. PMID:10578674

Pharmaceutical advertising revenue and physician organizations: how much is too much?

PubMed

Glassman, P A; Hunter-Hayes, J; Nakamura, T

1999-10-01

To determine if revenue generated from pharmaceutical advertisements in medical journals creates potential financial conflicts of interest for nonprofit physician organizations that own those journals. Convenience sample of six professional medical societies and their respective journals. Calculation of pharmaceutical advertising revenue generated by these journals for their respective professional medical societies. Random selection of each journal for one month per quarter in calendar year 1996 and tabulation per edition of the average number of pharmaceutical advertising pages for each journal. Published advertising rates were used to estimate pharmaceutical advertising revenue for calendar year 1996 and compared with each organization's gross revenue and membership dues and assessments, based on Internal Revenue Service documents for the last available fiscal year (1995). Estimated pharmaceutical advertising revenue ranged from $715,000 to $18,630,000. Five organizations raised more than 10% of their gross income (range 2% to 30%) from a single journal's pharmaceutical advertising. Four organizations raised as much or more from pharmaceutical advertising as from members (range 17% to 790%). Potential financial conflicts of interest arising from pharmaceutical advertisements in medical journals may be substantial. The impact on professional societies' financial independence and behavior is unknown.

Factors affecting the dissipation of pharmaceuticals in freshwater sediments.

PubMed

Al-Khazrajy, Omar S A; Bergström, Ed; Boxall, Alistair B A

2018-03-01

Degradation is one of the key processes governing the impact of pharmaceuticals in the aquatic environment. Most studies on the degradation of pharmaceuticals have focused on soil and sludge, with fewer exploring persistence in aquatic sediments. We investigated the dissipation of 6 pharmaceuticals from different therapeutic classes in a range of sediment types. Dissipation of each pharmaceutical was found to follow first-order exponential decay. Half-lives in the sediments ranged from 9.5 (atenolol) to 78.8 (amitriptyline) d. Under sterile conditions, the persistence of pharmaceuticals was considerably longer. Stepwise multiple linear regression analysis was performed to explore the relationships between half-lives of the pharmaceuticals, sediment physicochemical properties, and sorption coefficients for the compounds. Sediment clay, silt, and organic carbon content and microbial activity were the predominant factors related to the degradation rates of diltiazem, cimetidine, and ranitidine. Regression analysis failed to highlight a key property which may be responsible for observed differences in the degradation of the other pharmaceuticals. The present results suggest that the degradation rate of pharmaceuticals in sediments is determined by different factors and processes and does not exclusively depend on a single sediment parameter. Environ Toxicol Chem 2018;37:829-838. © 2017 SETAC. © 2017 SETAC.

Current Status and Issues in Basic Pharmaceutical Education.

PubMed

Yasuhara, Tomohisa

2017-01-01

Basic research in pharmaceutical sciences has a long and successful history. Researchers in this field have long given prime importance to the knowledge they have gained through their pharmaceutical education. The transition of pharmacy education to a 6-year course term has not only extended its duration but also placed more emphasis on practical clinical education. The School Education Act (in article 87, second paragraph) determines that "the term of the course, whose main purpose is to cultivate practical ability in clinical pharmacy, shall be six years" (excerpt). The 6-year pharmacy education is an exception to the general 4-year university term determined by the School Education Act. Therefore, the purpose of the 6-year course in pharmacy is clearly proscribed. This is true of the basic course in pharmaceutical education as well; hence, the basic course must be oriented toward developing "practical ability in clinical" education, too. The 6-year pharmacy course, starting from practice (Do), has evolved with the development of a syllabus that includes a model core curriculum (Plan). Furthermore, improvement in the course can be seen by the promoted development of faculty (Act). Now, evidence-based education research will be introduced (Check). This is how the Plan-Do-Check-Act cycle in pharmaceutical education is expected to work. Currently, pedagogy research in pharmacy education has just begun, so it is difficult to evaluate at this time whether basic pharmaceutical education does in fact contribute to enhancing the "practical clinical ability" component of pharmaceutical education.

Gaultheria trichophylla (Royle): a source of minerals and biologically active molecules, its antioxidant and anti-lipoxygenase activities.

PubMed

Alam, Fiaz; Saqib, Qazi Najam Us; Ashraf, Mohammad

2017-01-03

Gaultheria trichophylla (Royle) is used as food and for treating many ailments in folk medicine especially against inflammation. The purpose of this in vitro study was to evaluate the ability of extracts of G. trichophylla as anti-oxidant and anti-inflammatory agent and for its mineral contents. Powdered plant material (100 g) was extracted with 100 ml each of methanol, chloroform, and n-hexane using soxhlet extractor. Antioxidant activity of methanol extract was assessed by DPPH radical scavenging and FRAP assays. Determination of enzyme inhibition activity was determined using 5-LOX inhibitory activity. Total phenolic and flavonoids contents were measured by Folin-Chicalteu and colorimeteric methods respectively. Minerals and heavy metals contents were determined using Atomic absorption spectrophotometer. Qualitative HPLC analysis were performed using some standard phenolic compounds. The highest phenolic (17.5 ± 2.5 mg GA equivalent/g) and flavonoids (41.3 ± 0.1 mg QE equivalent/g) concentrations were found in methanol extract, which also showed more scavenging activity of 1, 1-diphenyl-2-picrylhydrazyl and ferrous reducing power with IC 50  = 81.2 ± 0.2 and IC 50  = 11.2 ± 0.1 μg/ml, respectively. The methanol and chloroform extracts showed best inhibition of 5-lipoxygenase enzyme with 90.5 ± 0.7% and 66.9 ± 0.1% at 0.5 mg/ml, respectively. G. trichophylla extract was also evaluated for mineral contents (K, Na, Ca, Mg, Fe, and Cu), and for chemical profiling of heavy metals (Cr, Pb, Cd, Co, Zn, Ni and Hg). Our current findings suggest that this plant is good source of minerals and concentration of all heavy metals were within permissible limits. The results revealed that this ignored plant has great pharmaceutical and nutraceutical potential.

Derivative spectrophotometric method for simultaneous determination of clindamycin phosphate and tretinoin in pharmaceutical dosage forms.

PubMed

Barazandeh Tehrani, Maliheh; Namadchian, Melika; Fadaye Vatan, Sedigheh; Souri, Effat

2013-04-10

A derivative spectrophotometric method was proposed for the simultaneous determination of clindamycin and tretinoin in pharmaceutical dosage forms. The measurement was achieved using the first and second derivative signals of clindamycin at (1D) 251 nm and (2D) 239 nm and tretinoin at (1D) 364 nm and (2D) 387 nm.The proposed method showed excellent linearity at both first and second derivative order in the range of 60-1200 and 1.25-25 μg/ml for clindamycin phosphate and tretinoin respectively. The within-day and between-day precision and accuracy was in acceptable range (CV<3.81%, error<3.20%). Good agreement between the found andadded concentrations indicates successful application of the proposed method for simultaneous determination of clindamycin and tretinoin in synthetic mixtures and pharmaceutical dosage form.

Developing a suitable model for supplier selection based on supply chain risks: an empirical study from Iranian pharmaceutical companies.

PubMed

Mehralian, Gholamhossein; Rajabzadeh Gatari, Ali; Morakabati, Mohadese; Vatanpour, Hossein

2012-01-01

The supply chain represents the critical link between the development of new product and the market in pharmaceutical industry. Over the years, improvements made in supply chain operations have focused largely on ways to reduce cost and gain efficiencies in scale. In addition, powerful regulatory and market forces have provided new incentives for pharmaceutical firms to basically rethink the way they produce and distribute products, and also to re-imagine the role of the supply chain in driving strategic growth, brand differentiation and economic value in the health continuum. The purpose of this paper is to formulate basic factors involved in risk analysis of pharmaceutical industry, and also determine the effective factors involved in suppliers selection and their priorities. This paper is based on the results of literature review, experts' opinion acquisition, statistical analysis and also using MADM models on data gathered from distributed questionnaires. The model consists of the following steps and components: first factors involved in to supply chain risks are determined. Based on them a framework is considered. According the result of statistical analysis and MADM models the risk factors are formulated. The paper determines the main components and influenceial factors involving in the supply chain risks. Results showed that delivery risk can make an important contribution to mitigate the risk of pharmaceutical industry.

Developing a Suitable Model for Supplier Selection Based on Supply Chain Risks: An Empirical Study from Iranian Pharmaceutical Companies

PubMed Central

Mehralian, Gholamhossein; Rajabzadeh Gatari, Ali; Morakabati, Mohadese; Vatanpour, Hossein

2012-01-01

The supply chain represents the critical link between the development of new product and the market in pharmaceutical industry. Over the years, improvements made in supply chain operations have focused largely on ways to reduce cost and gain efficiencies in scale. In addition, powerful regulatory and market forces have provided new incentives for pharmaceutical firms to basically rethink the way they produce and distribute products, and also to re-imagine the role of the supply chain in driving strategic growth, brand differentiation and economic value in the health continuum. The purpose of this paper is to formulate basic factors involved in risk analysis of pharmaceutical industry, and also determine the effective factors involved in suppliers selection and their priorities. This paper is based on the results of literature review, experts’ opinion acquisition, statistical analysis and also using MADM models on data gathered from distributed questionnaires. The model consists of the following steps and components: first factors involved in to supply chain risks are determined. Based on them a framework is considered. According the result of statistical analysis and MADM models the risk factors are formulated. The paper determines the main components and influenceial factors involving in the supply chain risks. Results showed that delivery risk can make an important contribution to mitigate the risk of pharmaceutical industry. PMID:24250442

Gore offers to help drug companies pursue research.

PubMed

1996-03-08

A meeting convened between Vice President Al Gore and executives of leading pharmaceutical companies to determine means of accelerating efforts to develop vaccines, therapeutics, and microbicides for people with HIV. Gore explained that the administration will work with pharmaceutical companies to determine the long-term effectiveness of drugs approved by the Food and Drug Administration (FDA), work with international groups to increase investment in vaccine development, help develop new microbicides for women with HIV, and identify promising areas of AIDS research. According to advocates, the Clinton Administration has made great strides in improving and accelerating the FDA's drug approval process. The next goal of the pharmaceutical research agenda should be to include consumer advocates in the decision-making process.

Pharmaceutical representatives' beliefs and practices about their professional practice: a study in Sudan.

PubMed

Idris, K M; Mustafa, A F; Yousif, M A

2012-08-01

Pharmaceutical representatives are an important promotional tool for pharmaceutical companies. This cross-sectional, exploratory study aimed to determine pharmaceutical representatives' beliefs and practices about their professional practice in Sudan. A random sample of 160 pharmaceutical representatives were interviewed using a pretested questionnaire. The majority were male (84.4%) and had received training in professional sales skills (86.3%) and about the products being promoted (82.5%). Only 65.6% agreed that they provided full and balanced information about products. Not providing balanced information was attributed by 23.1% to doctors' lack of time. However, 28.1% confessed they sometimes felt like hiding unfavourable information, 21.9% were sometimes or always inclined to give untrue information to make sales and 66.9% considered free gifts as ethically acceptable. More attention is needed to dissemination of ethical codes of conduct and training about the ethics of drug promotion for pharmaceutical representatives in Sudan.

Raising the Barriers to Access to Medicines in the Developing World - The Relentless Push for Data Exclusivity.

PubMed

Diependaele, Lisa; Cockbain, Julian; Sterckx, Sigrid

2017-04-01

Since the adoption of the WTO-TRIPS Agreement in 1994, there has been significant controversy over the impact of pharmaceutical patent protection on the access to medicines in the developing world. In addition to the market exclusivity provided by patents, the pharmaceutical industry has also sought to further extend their monopolies by advocating the need for additional 'regulatory' protection for new medicines, known as data exclusivity. Data exclusivity limits the use of clinical trial data that need to be submitted to the regulatory authorities before a new drug can enter the market. For a specified period, generic competitors cannot apply for regulatory approval for equivalent drugs relying on the originator's data. As a consequence, data exclusivity lengthens the monopoly for the original drug, impairing the availability of generic drugs. This article illustrates how the pharmaceutical industry has convinced the US and the EU to impose data exclusivity on their trade partners, many of them developing countries. The key arguments formulated by the pharmaceutical industry in favor of adopting data exclusivity and their underlying ethical assumptions are described in this article, analyzed, and found to be unconvincing. Contrary to industry's arguments, it is unlikely that data exclusivity will promote innovation, especially in developing countries. Moreover, the industry's appeal to a property rights claim over clinical test data and the idea that data exclusivity can prevent the generic competitors from 'free-riding' encounters some important problems: Neither legitimize excluding all others. © 2016 The Authors Developing World Bioethics Published by John Wiley & Sons Ltd.

Development of a new procedure for the determination of captopril in pharmaceutical formulations employing chemiluminescence and a multicommuted flow analysis approach.

PubMed

Lima, Manoel J A; Fernandes, Ridvan N; Tanaka, Auro A; Reis, Boaventura F

2016-02-01

This paper describes a new technique for the determination of captopril in pharmaceutical formulations, implemented by employing multicommuted flow analysis. The analytical procedure was based on the reaction between hypochlorite and captopril. The remaining hypochlorite oxidized luminol that generated electromagnetic radiation detected using a homemade luminometer. To the best of our knowledge, this is the first time that this reaction has been exploited for the determination of captopril in pharmaceutical products, offering a clean analytical procedure with minimal reagent usage. The effectiveness of the proposed procedure was confirmed by analyzing a set of pharmaceutical formulations. Application of the paired t-test showed that there was no significant difference between the data sets at a 95% confidence level. The useful features of the new analytical procedure included a linear response for captopril concentrations in the range 20.0-150.0 µmol/L (r = 0.997), a limit of detection (3σ) of 2.0 µmol/L, a sample throughput of 164 determinations per hour, reagent consumption of 9 µg luminol and 42 µg hypochlorite per determination and generation of 0.63 mL of waste. A relative standard deviation of 1% (n = 6) for a standard solution containing 80 µmol/L captopril was also obtained. Copyright © 2015 John Wiley & Sons, Ltd.

40 CFR 63.55 - Maximum achievable control technology (MACT) determinations for affected sources subject to case...

Code of Federal Regulations, 2010 CFR

2010-07-01

... (MACT) determinations for affected sources subject to case-by-case determination of equivalent emission... sources subject to case-by-case determination of equivalent emission limitations. (a) Requirements for... hazardous air pollutant emissions limitations equivalent to the limitations that would apply if an emission...

Investigating the dissolution profiles of amoxicillin, metronidazole, and zidovudine formulations used in Trinidad and Tobago, West Indies.

PubMed

Stuart, Arlene Villarroel; Zuo, Jieyu; Löbenberg, Raimar

2014-10-01

Trinidad and Tobago is a twin-island Republic in the Caribbean and like many developing countries, it has included generic drugs on the national drug formulary to decrease the financial burden of pharmaceutical medications. However, to ensure that medications received by patients are beneficial, generic drugs need to be interchangeable with the innovator which has demonstrated safety, efficacy, and quality. The objective of the study was to compare the dissolution profiles and weight variations for different formulations of amoxicillin, metronidazole, and zidovudine that are on the national drug formulary and marketed in Trinidad and Tobago. All the products investigated are categorized as class 1 drugs according to the Biopharmaceutics Classification System (BCS) and the dissolution profiles were assessed according to the World Health Organization (WHO) criteria for interchangeability between products. The similarity factor, f 2, was used to determine sameness between the products. No generic formulation was found to be similar to Amoxil® 500-mg capsules. The two generic products for metronidazole 200-mg tablets demonstrated more than 85% drug release within 15 min in all three of the buffers; however, their 400-mg counterparts did not fulfill this requirement. The zidovudine 300-mg tablet complied with the requirements in buffer pH 4.5 and simulated gastric fluid (SGF) but not for simulated intestinal fluid (SIF). Some Class 1 pharmaceutical formulations may possess the same active ingredient and amount of drug but may show significant differences to in vitro equivalence requirements. Nevertheless, the dissolution process is suitable to detect these variations.

Impact of regulatory science on global public health.

PubMed

Patel, Meghal; Miller, Margaret Ann

2012-07-01

Regulatory science plays a vital role in protecting and promoting global public health by providing the scientific basis for ensuring that food and medical products are safe, properly labeled, and effective. Regulatory science research was first developed for the determination of product safety in the early part of the 20th Century, and continues to support innovation of the processes needed for regulatory policy decisions. Historically, public health laws and regulations were enacted following public health tragedies, and often the research tools and techniques required to execute these laws lagged behind the public health needs. Throughout history, similar public health problems relating to food and pharmaceutical products have occurred in countries around the world, and have usually led to the development of equivalent solutions. For example, most countries require a demonstration of pharmaceutical safety and efficacy prior to marketing these products using approaches that are similar to those initiated in the United States. The globalization of food and medical products has created a shift in regulatory compliance such that gaps in food and medical product safety can generate international problems. Improvements in regulatory research can advance the regulatory paradigm toward a more preventative, proactive framework. These improvements will advance at a greater pace with international collaboration by providing additional resources and new perspectives for approaching and anticipating public health problems. The following is a review of how past public health disasters have shaped the current regulatory landscape, and where innovation can facilitate the shift from reactive policies to proactive policies. Copyright © 2012. Published by Elsevier B.V.

5-(Chloromethyl)furfural is the New HMF: Functionally Equivalent But More Practical in Terms of its Production From Biomass.

PubMed

Mascal, Mark

2015-10-26

5-(Chloromethyl)furfural (CMF) is a disruptive innovation in the biorefinery. Chemically, it is at least as versatile as the well-known HMF but, unlike HMF, it is accessible in high yield directly from cellulosic biomass due to its lipophilicity and stability under acidic conditions, which facilitate isolation. It has a rich derivative chemistry that includes biofuels, renewable polymers, specialty chemicals, and value-added agrochemical and pharmaceutical products. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biodynamic profiling of three-dimensional tissue growth techniques

NASA Astrophysics Data System (ADS)

Sun, Hao; Merrill, Dan; Turek, John; Nolte, David

2016-03-01

Three-dimensional tissue culture presents a more biologically relevant environment in which to perform drug development than conventional two-dimensional cell culture. However, obtaining high-content information from inside three dimensional tissue has presented an obstacle to rapid adoption of 3D tissue culture for pharmaceutical applications. Biodynamic imaging is a high-content three-dimensional optical imaging technology based on low-coherence interferometry and digital holography that uses intracellular dynamics as high-content image contrast. In this paper, we use biodynamic imaging to compare pharmaceutical responses to Taxol of three-dimensional multicellular spheroids grown by three different growth techniques: rotating bioreactor, hanging-drop and plate-grown spheroids. The three growth techniques have systematic variations among tissue cohesiveness and intracellular activity and consequently display different pharmacodynamics under identical drug dose conditions. The in vitro tissue cultures are also compared to ex vivo living biopsies. These results demonstrate that three-dimensional tissue cultures are not equivalent, and that drug-response studies must take into account the growth method.

Canned bluefin tuna, an in vitro cardioprotective functional food potentially safer than commercial fish oil based pharmaceutical formulations.

PubMed

Tenore, Gian Carlo; Calabrese, Giorgio; Ritieni, Alberto; Campiglia, Pietro; Giannetti, Daniela; Novellino, Ettore

2014-09-01

Commercial canned fish species typical in the Italian market were evaluated for their lipid profile. Bluefin tuna samples showed the highest content in omega-3 fatty acids (n-3 PUFA) among the canned fish samples analyzed. Tests on H9C2 cardiomyocytes revealed that bluefin tuna n-3 PUFA may responsible for a significant cell protection against both physiological and doxorubicin-induced oxidative stress. Analogous tests performed by incubating cardiac cells with n-3 PUFA ethyl esters, of which most of fish oil pharmaceutical formulations (FOPF) are based, showed cytotoxicity at high doses. Our results highlighted that n-3 PUFA contents in a 50 g canned bluefin tuna portion would be almost equivalent to and potentially safer than those of 1 FOPF capsule (1000 mg)/die usually suggested for hyperlipidaemic subjects. Thus, Italian commercial canned bluefin tuna could be indicated as a functional food with potential health benefits for the prevention and care of cardiovascular disorders. Copyright © 2014 Elsevier Ltd. All rights reserved.

Pharmaceutical patent applications in freeze-drying.

PubMed

Ekenlebie, Edmond; Einfalt, Tomaž; Karytinos, Arianna Irò; Ingham, Andrew

2016-09-01

Injectable products are often the formulation of choice for new therapeutics; however, formulation in liquids often enhances degradation through hydrolysis. Thus, freeze-drying (lyophilization) is regularly used in pharmaceutical manufacture to reduce water activity. Here we examine its contribution to 'state of the art' and look at its future potential uses. A comprehensive search of patent databases was conducted to characterize the international patent landscape and trends in the use of freeze-drying. A total of 914 disclosures related to freeze-drying, lyophilization or drying of solid systems in pressures and temperatures equivalent to those of freeze-drying were considered over the period of 1992-2014. Current applications of sublimation technology were contrasted across two periods those with patents due to expire (1992-1993) and those currently filed. The number of freeze-drying technology patents has stabilized after initial activity across the biotechnology sector in 2011 and 2012. Alongside an increasing trend for patent submissions, freeze-drying submissions have slowed since 2002 and is indicative of a level of maturity.

THE ROLE OF MAMMALIAN DATA IN DETERMINING PHARMACEUTICAL RESPONSES IN AQUATIC SPECIES

EPA Science Inventory

Human pharmaceuticals are designed to be biologically active, and are extensively studies for physicalchemical, pharmacological, and toxicological properties. In those studies, efficacy and safety endpoints ED50s, LCSOs, NOAELs, LOAELs, etc.) are linked to plasma exposures (Cmax ...

Pyrocatechol violet in pharmaceutical analysis. Part I. A spectrophotometric method for the determination of some beta-lactam antibiotics in pure and in pharmaceutical dosage forms.

PubMed

Amin, A S

2001-03-01

A fairly sensitive, simple and rapid spectrophotometric method for the determination of some beta-lactam antibiotics, namely ampicillin (Amp), amoxycillin (Amox), 6-aminopenicillanic acid (6APA), cloxacillin (Clox), dicloxacillin (Diclox) and flucloxacillin sodium (Fluclox) in bulk samples and in pharmaceutical dosage forms is described. The proposed method involves the use of pyrocatechol violet as a chromogenic reagent. These drugs produce a reddish brown coloured ion pair with absorption maximum at 604, 641, 645, 604, 649 and 641 nm for Amp, Amox, 6APA, Clox, Diclox and Flucolx, respectively. The colours produced obey Beer's law and are suitable for the quantitative determination of the named compounds. The optimization of different experimental conditions is described. The molar ratio of the ion pairs was established and a proposal for the reaction pathway is given. The procedure described was applied successfully to determine the examined drugs in dosage forms and the results obtained were comparable to those obtained with the official methods.

28 CFR 36.604 - Procedure following preliminary determination of equivalency.

Code of Federal Regulations, 2014 CFR

2014-07-01

... State Laws or Local Building Codes § 36.604 Procedure following preliminary determination of equivalency... of the preliminary determination of equivalency with respect to the particular code, and invite... enforcement of the code, at which interested individuals, including individuals with disabilities, are...

28 CFR 36.604 - Procedure following preliminary determination of equivalency.

Code of Federal Regulations, 2011 CFR

2011-07-01

... State Laws or Local Building Codes § 36.604 Procedure following preliminary determination of equivalency... of the preliminary determination of equivalency with respect to the particular code, and invite... enforcement of the code, at which interested individuals, including individuals with disabilities, are...

28 CFR 36.604 - Procedure following preliminary determination of equivalency.

Code of Federal Regulations, 2012 CFR

2012-07-01

... State Laws or Local Building Codes § 36.604 Procedure following preliminary determination of equivalency... of the preliminary determination of equivalency with respect to the particular code, and invite... enforcement of the code, at which interested individuals, including individuals with disabilities, are...

28 CFR 36.604 - Procedure following preliminary determination of equivalency.

Code of Federal Regulations, 2013 CFR

2013-07-01

... State Laws or Local Building Codes § 36.604 Procedure following preliminary determination of equivalency... of the preliminary determination of equivalency with respect to the particular code, and invite... enforcement of the code, at which interested individuals, including individuals with disabilities, are...

Derivative spectrophotometric method for simultaneous determination of clindamycin phosphate and tretinoin in pharmaceutical dosage forms

PubMed Central

2013-01-01

A derivative spectrophotometric method was proposed for the simultaneous determination of clindamycin and tretinoin in pharmaceutical dosage forms. The measurement was achieved using the first and second derivative signals of clindamycin at (1D) 251 nm and (2D) 239 nm and tretinoin at (1D) 364 nm and (2D) 387 nm. The proposed method showed excellent linearity at both first and second derivative order in the range of 60–1200 and 1.25–25 μg/ml for clindamycin phosphate and tretinoin respectively. The within-day and between-day precision and accuracy was in acceptable range (CV<3.81%, error<3.20%). Good agreement between the found and added concentrations indicates successful application of the proposed method for simultaneous determination of clindamycin and tretinoin in synthetic mixtures and pharmaceutical dosage form. PMID:23575006

Spectrofluorimetric determination of DL-N-methyl-3-phenyl-3-[(α,α,α-trifluoro-p-tolyl)oxy]propylamine in pharmaceuticals and chitosan solution.

PubMed

Rodrigues, Máira Regina

2012-02-01

A spectrofluorimetric method for the determination of D,L-N-methyl-3-phenyl-3-[(α,α,α-trifluoro-p-tolyl)oxy]propylamine, fluoxetine (F), in pharmaceuticals was evaluated in the 50.0-500.0 μg ml⁻¹ range. Linearity, sensibility, quantification and detection limit, and precision values are satisfactory. The method does not need pre-treatment and was successfully applied to the determination in pharmaceuticals and chitosan (Ch) solution. Ch has an ability to carry and absorb fat and may eventually be used together with F in slimming diets, and then interactions of Ch-F may occur. This work seeks to study these interactions by monitoring the photophysics of a drug in the presence of Ch. The results warn about the care that must be taken when both compounds are prescribed together.

Application of attenuated total reflectance Fourier transform infrared spectroscopy for determination of cefixime in oral pharmaceutical formulations.

PubMed

Kandhro, Aftab A; Laghari, Abdul Hafeez; Mahesar, Sarfaraz A; Saleem, Rubina; Nelofar, Aisha; Khan, Salman Tariq; Sherazi, S T H

2013-11-01

A quick and reliable analytical method for the quantitative assessment of cefixime in orally administered pharmaceutical formulations is developed by using diamond cell attenuated total reflectance (ATR) Fourier transform infrared (FT-IR) spectroscopy as an easy procedure for quality control laboratories. The standards for calibration were prepared in aqueous medium ranging from 350 to 6000mg/kg. The calibration model was developed based on partial least square (PLS) using finger print region of FT-IR spectrum in the range from 1485 to 887cm(-1). Excellent coefficient of determination (R(2)) was achieved as high as 0.99976 with root mean square error of 44.8 for calibration. The application of diamond cell (smart accessory) ATR FT-IR proves a reliable determination of cefixime in pharmaceutical formulations to assess the quality of the final product. Copyright © 2013 Elsevier B.V. All rights reserved.

Occurrence of pharmaceuticals in a municipal wastewater treatment plant: mass balance and removal processes.

PubMed

Gao, Pin; Ding, Yunjie; Li, Hui; Xagoraraki, Irene

2012-06-01

Occurrence and removal efficiencies of fifteen pharmaceuticals were investigated in a conventional municipal wastewater treatment plant in Michigan. Concentrations of these pharmaceuticals were determined in both wastewater and sludge phases by a high-performance liquid chromatograph coupled to a tandem mass spectrometer. Detailed mass balance analysis was conducted during the whole treatment process to evaluate the contributing processes for pharmaceutical removal. Among the pharmaceuticals studied, demeclocycline, sulfamerazine, erythromycin and tylosin were not detected in the wastewater treatment plant influent. Other target pharmaceuticals detected in wastewater were also found in the corresponding sludge phase. The removal efficiencies of chlortetracycline, tetracycline, sulfamerazine, acetaminophen and caffeine were >99%, while doxycycline, oxytetracycline, sulfadiazine and lincomycin exhibited relatively lower removal efficiencies (e.g., <50%). For sulfamethoxazole, the removal efficiency was approximately 90%. Carbamazepine manifested a net increase of mass, i.e. 41% more than the input from the influent. Based on the mass balance analysis, biotransformation is believed to be the predominant process responsible for the removal of pharmaceuticals (22% to 99%), whereas contribution of sorption to sludge was relatively insignificant (7%) for the investigated pharmaceuticals. Copyright © 2012 Elsevier Ltd. All rights reserved.

DISTRIBUTION OF ORGANIC WASTEWATER CONTAMINANTS BETWEEN WATER AND SEDIMENT IN SURFACE WATERS OF THE UNITED STATES

EPA Science Inventory

Trace concentrations of pharmaceuticals and other organic wastewater contaminants have been determined in the surface waters of Europe and the United States. A preliminary report of substantially higher concentrations of pharmaceuticals in sediment suggests that bottom sediment ...

THE ROLE OF MAMMALIAN DATA IN DETERMINING PHARMACEUTICAL RESPONSES IN AQUATIC ORGANISMS

EPA Science Inventory

The limitations surrounding application of pharmaceutical data are restricted to extrapolation of the animal and human data across phyla. Experience dictates that mammalian data are most likely to extrapolate predictably to fish and other aquatic vertebrates (e.g. Amphibia), and ...

Anodic Oxidation of Etodolac and its Linear Sweep, Square Wave and Differential Pulse Voltammetric Determination in Pharmaceuticals

PubMed Central

Yilmaz, B.; Kaban, S.; Akcay, B. K.

2015-01-01

In this study, simple, fast and reliable cyclic voltammetry, linear sweep voltammetry, square wave voltammetry and differential pulse voltammetry methods were developed and validated for determination of etodolac in pharmaceutical preparations. The proposed methods were based on electrochemical oxidation of etodolac at platinum electrode in acetonitrile solution containing 0.1 M lithium perchlorate. The well-defined oxidation peak was observed at 1.03 V. The calibration curves were linear for etodolac at the concentration range of 2.5-50 μg/ml for linear sweep, square wave and differential pulse voltammetry methods, respectively. Intra- and inter-day precision values for etodolac were less than 4.69, and accuracy (relative error) was better than 2.00%. The mean recovery of etodolac was 100.6% for pharmaceutical preparations. No interference was found from three tablet excipients at the selected assay conditions. Developed methods in this study are accurate, precise and can be easily applied to Etol, Tadolak and Etodin tablets as pharmaceutical preparation. PMID:26664057

Determination of residual solvents in pharmaceuticals by thermal desorption-GC/MS.

PubMed

Hashimoto, K; Urakami, K; Fujiwara, Y; Terada, S; Watanabe, C

2001-05-01

A novel method for the determination of residual solvents in pharmaceuticals by thermal desorption (TD)-GC/MS has been established. A programmed temperature pyrolyzer (double shot pyrolyzer) is applied for the TD. This method does not require any sample pretreatment and allows very small amounts of the sample. Directly desorbed solvents from intact pharmaceuticals (ca. 1 mg) in the desorption cup (5 mm x 3.8 mm i.d.) were cryofocused at the head of a capillary column prior to a GC/MS analysis. The desorption temperature was set at a point about 20 degrees C higher than the melting point of each sample individually, and held for 3 min. The analytical results using 7 different pharmaceuticals were in agreement with those obtained by direct injection (DI) of the solution, followed by USP XXIII. This proposed TD-GC/MS method was demonstrated to be very useful for the identification and quantification of residual solvents. Furthermore, this method was simple, allowed rapid analysis and gave good repeatability.

Spectrofluorimetric analysis of famotidine in pharmaceutical preparations and biological fluids by derivatization with benzoin.

PubMed

Alamgir, Malik; Khuhawar, Muhammad Yar; Memon, Saima Q; Hayat, Amir; Zounr, Rizwan Ali

2015-01-05

A sensitive and simple spectrofluorimetric method has been developed for the analysis of famotidine, from pharmaceutical preparations and biological fluids after derivatization with benzoin. The reaction was carried out in alkaline medium with measurement of fluorescence intensity at 446 nm with excitation wavelength at 286 nm. Linear calibration was obtained with 0.5-15 μg/ml with coefficient of determination (r(2)) 0.997. The factors affecting the fluorescence intensity were optimized. The pharmaceutical additives and amino acid did not interfere in the determination. The mean percentage recovery (n=4) calculated by standard addition from pharmaceutical preparation was 94.8-98.2% with relative standard deviation (RSD) 1.56-3.34% and recovery from deproteinized spiked serum and urine of healthy volunteers was 98.6-98.9% and 98.0-98.4% with RSD 0.34-0.84% and 0.29-0.87% respectively. Copyright © 2014 Elsevier B.V. All rights reserved.

Determination of pKa values of nonsteroidal antiinflammatory drug-oxicams by RP-HPLC and their analysis in pharmaceutical dosage forms.

PubMed

Demiralay, Ebru Cubuk; Alsancak, Guleren; Ozkan, Sibel A

2009-09-01

In this study, pK(a) values were determined by using the dependence of the capacity factor on the pH of the mobile phase for four ionizable substances, namely, tenoxicam, piroxicam, meloxicam, and naproxen (I.S.). The effect of the mobile phase composition on the ionization constant was studied by measuring the pK(a) at different ACN concentrations, ranging from 30 to 40%. The adequate condition for the chromatographic determination of these compounds in pharmaceutical dosage forms was established based on the different retention behaviors of the species. An octadecylsilica Nucleosil C18 column (150 x 4.6 mm, 5 microm) was used for all the determinations. The chromatographic separation of oxicams was carried out using acetonitrile (ACN)/water at 35% v/v, containing 65 mM phosphoric acid and UV detection at a wavelength of 355 nm. The method developed was successfully applied to the simultaneous determination of these drug compounds in laboratory-prepared mixtures and their commercial pharmaceutical dosage forms. Each analysis requires no longer than 12 min.

Pharmacists' Perceptions of the Economic Value of Compounded Pharmaceuticals: A Comparison of Compounded and Commercial Pharmaceuticals in Select Disease States.

PubMed

Lobb, William B; Wilkin, Noel E; Holmes, Erin R

2015-01-01

Studies have been conducted to assess patient satisfaction with compounded pharmaceuticals and to directly compare compounded pharmaceuticals with their comparable commercial pharmaceuticals. Yet, the economic value of or potential for economic value derived from compounded pharmaceuticals relative to commercial pharmaceuticals is still not known. Therefore, the purpose of this study was to assess and compare compounding and non-compounding pharmacists' perceptions of the economic value of compounded preparations relative to commercial products. In-depth interviews with 10 compounding pharmacists and physicians who prescribe compounded prescription pharmaceutical preparations were conducted to help develop a self-administered questionnaire distributed to 50 compounding and 50 non-compounding pharmacists. Compounding and non-compounding pharmacists' perceptions differed most often in the context of compounded pharmaceuticals for pediatric patients. However, both groups responded with moderate agreement that compounded prescription treatments are more profitable for the pharmacy than commercial prescription treatments in most therapeutic areas. This research sought to understand the perception of pharmacists of areas for potential direct and indirect economic cost savings as a result of compounding. For all items whereby compounding and non-compounding pharmacists' ratings were significantly different, compounding pharmacists more strongly believed that compounding pharmaceuticals offered benefit and vice versa. The differences in ratings that were most common were those that directly compared the economic value of compounding and commercial pharmaceuticals, with compounding pharmacists more strongly agreeing with the potential cost savings associated with compounded pharmaceuticals. Based on these findings, prescription compounds are believed to have a benefit to the health system by those who provide them. Future research should proactively explore the economic benefit of compounded preparations compared to conventionally manufactured products to determine the economic value of compounded pharmaceuticals for patients, pharmacies, physicians, and the healthcare system.

Occurrence and distribution of selected pharmaceuticals and personal care products in aquatic environments: a comparative study of regions in China with different urbanization levels.

PubMed

Chen, Hong; Li, Xiaojuan; Zhu, Saichang

2012-07-01

We analyzed and compared the distributions of 13 target pharmaceuticals in different water samples from the Hangzhou metropolitan area and Linan County, Southeast China. Sampling was conducted in five hospitals, two wastewater treatment plants (WWTPs), and Qiantang River. Samples were concentrated by solid-phase extraction and PPCP concentrations were determined by UPLC-MS/MS. Trimethoprim, erythromycin A dihydrate, norfloxacin, ofloxacin, diclofenac sodium, and atenolol were the most frequently detected pharmaceuticals in hospital effluents. Most of the pharmaceutical concentrations in hospital effluents were higher than those in the WWTP influents. Although both WWTPs adopt the anaerobic-aerobic-anoxic treatment process, the removal rates for pharmaceuticals, such as trimethoprim and diclofenac sodium, were completely different. Meanwhile, erythromycin A dihydrate, ofloxacin, penicillin-G, cephalexin, cefazolin, ibuprofen, and diclofenac sodium were detected in Qiantang River. These results indicate that hospitals are more concentrated sources of pharmaceuticals than WWTPs, and the WWTPs are not the only route of entry of pharmaceuticals into aquatic environments in these two regions.

Factors associated with the diffusion rate of innovations: a pilot study from the perspective of the Brazilian Unified National Health System.

PubMed

Schneiders, Roberto Eduardo; Ronsoni, Ricardo de March; Sarti, Flávia Mori; Nita, Marcelo Eidi; Bastos, Ediane de Assis; Zimmermann, Ivan Ricardo; Ferreira, Fernando Fagundes

2016-10-10

Budget Impact Analyses require a set of essential information on health technology innovation, including expected rates of adoption. There is an absence of studies investigating trends, magnitude of budgetary effects and determinants of diffusion rates for health technology innovations worldwide during the last decades. The present study proposes a pilot assessment on main determinants influencing diffusion rates of pharmaceutical innovations within the Brazilian Unified National Health System (SUS). Data from the Brazilian Health Informatics Department (DATASUS) was gathered to establish the main determinants of diffusion rates of health technology innovations in Brazil, specifically referring to pharmaceutical innovations incorporated in the Brazilian Program for Specialized Pharmaceutical Services (CEAF) at SUS. Information was retrieved on DATASUS relating to patients who had used one of the medicines incorporated into CEAF at least three years prior to the beginning of the study (2015) for treatment of each health condition available. Thus, data from patients adopting 10 different medicines were analyzed in the study. Results from the zero-one inflated beta model showed a higher influence on diffusion rates of pharmaceutical innovations due to: number of pharmaceutical competitors for treatment of the same disease available at CEAF (negative); medicine used in combination with other medication (positive); and innovative medicine within the SUS (positive). Further research on diffusion rates of health technology innovations is required, including wider scope of diseases and medications, potential confusion factors and other variables that may influence rates of adoption in different health systems.

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

PubMed

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

2017-10-25

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

[Comparison of commercial HIV-1 viral load tests by using proficiency test results in China, 2013- 2015].

PubMed

Zhang, L; Jin, C; Jiang, Z; Tang, T; Jiang, Y; Pan, P L

2017-09-10

Objective: To compare the bio-equivalence among commercial HIV-1 viral load tests, including EasyQ HIV-1 v2.0 (EasyQ) from bioMerieux NucliSens of France; VERSANT HIV-1 RNA 3.0 assay (bDNA) from Siemens Healthcare Diagnostics of USA; COBAS AmpliPrep/COBAS TaqMan HIV-1 test (Taqman) from Roche Molecular Diagnosis of USA; Abbott Real Time HIV-1 Kit (M2000) from Abbott Molecular of USA and two domestic HIV-1 viral load test kits (domestic kit) from DaAn Gene Company of Sun Yat-Sen University and Liaoning Bio-Pharmaceutical company of Northeast pharmaceutical group, by using proficiency test results in China from 2013 to 2015. Methods: A total of 2 954 proficiency test results, obtained from 22 positive samples of 6 proficiency tests in 155 laboratories conducted by China CDC were analyzed during 2013-2015. The results from each sample were first logarithmic transformed and then grouped according to the method used, the mean value of logarithmic results was calculated. Subsequently, 22 clusters of mean values were analyzed by Bland-Altman analysis for the consistency, and linear regression analysis for the interdependency. Results: The results indicated that, by taking Taqman as the reference, EasyQ, M2000, bDNA and domestic kit had good consistency (90 % -100 % ) and interdependency. Conclusion: All the viral load tests were bio-equivalent. Moreover, according to the conversion formula derived from domestic proficiency test results, all the viral load results could be converted, which is critical for epidemiological analysis.

Temporal and spatial behavior of pharmaceuticals in Narragansett Bay, Rhode Island, United States

EPA Science Inventory

The behavior of active pharmaceutical ingredients (APIs) in urban estuaries is not well understood. In this study, 15 high volume usage APIs were measured over a one year period throughout Narragansett Bay, RI, USA to determine factors controlling their concentration and distrib...

FATE OF PHARMACEUTICALS: EFFECTS OF CHLORINATION AND ENVIRONMENTAL PERSISTENCE

EPA Science Inventory

The presence of pharmaceuticals in environmental waters has become an area of concern around the world. To maximize the impact of occurrence studies, pre-screening can help determine which compounds are likely to survive waste water treatment, as well as what by-products are for...

DETERMINATION OF THE POTENTIAL FOR ANAEROBIC DEGRADATION OF UNUSED PHARMACEUTICALS IN MUNICIPAL SOLID WASTE LANDFILLS

EPA Science Inventory

For many years the recommended method of disposal for unused household medications was the sewage system. However, research studies have emerged showing that many pharmaceuticals and endocrine disrupting compounds are not fully removed by wastewater treatment systems and enter t...

77 FR 22282 - Milk in the Northeast and Other Marketing Areas; Determination of Equivalent Price Series

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-13

... DEPARTMENT OF AGRICULTURE Agricultural Marketing Service [Doc. No. AMS-DA-10-0089; DA-11-01] Milk in the Northeast and Other Marketing Areas; Determination of Equivalent Price Series AGENCY: Agricultural Marketing Service, USDA. ACTION: Determination of equivalent price series. SUMMARY: It has been...

Comparison between micellar liquid chromatography and capillary zone electrophoresis for the determination of hydrophobic basic drugs in pharmaceutical preparations.

PubMed

Torres-Cartas, S; Martín-Biosca, Y; Sagrado, S; Villanueva-Camañas, R M; Medina-Hernández, M J

2007-01-01

The determination of highly hydrophobic basic compounds by means of conventional reversed-phase liquid chromatographic methods has several drawbacks. Owing to the characteristics of micellar liquid chromatography (MLC) and capillary electrophoresis (CE), these techniques could be advantageous alternatives to reversed-phase chromatographic methods for the determination of these kinds of compounds. The objective of this study was to develop and compare MLC and CE methods for the determination of antipsychotic basic drugs (amitryptiline, haloperidol, perphenazine and thioridazine) in pharmaceutical preparations. The chromatographic determination of the analytes was performed on a Kromasil C(18) analytical column; the mobile phase was 0.04 m cetyltrimethylammonium bromide (CTAB), at pH 3, containing 5% 1-butanol, at a flow rate of 1 mL/min. The CE separation was performed in a fused-silica capillary with a 50 mm tris-(hydroxymethyl)-aminomethane buffer, pH 7, at an applied voltage of 20 kV, using barbital as internal stardard. The proposed methods are suitable for a reliable quantitation of these compounds in the commercial tablets and drops in terms of accuracy and precision and require a very simple pre-treatment of the samples. By comparing the performance characteristics and experimental details of the MLC and CE methods we conclude that CE seems to be slightly better than MLC in the determination of highly hydrophobic compounds in pharmaceuticals in terms of resolution and economy, taking into account that the limits of detection are not a handicap in pharmaceutical samples. Copyright 2006 John Wiley & Sons, Ltd.

Daily dynamics of emerging pollutants in a sewer network (région Centre, France)

NASA Astrophysics Data System (ADS)

Thiebault, Thomas; Réty, Maxime; Jacob, Jérémy; Destandau, Emilie; Fougère, Laetitia; Morio, Cédric

2017-04-01

As any catchment, cities are characterized by important flux of various materials. The specificity of urban socio-ecosystems lies in the nature of these materials that mainly result from human activities or are man-made. An important issue concerns emerging pollutants for which an understanding of their temporal dynamics is crucial to better forecast flux and adapt remediation treatments before waters are released in the environment. This study aims at better understanding the socio-economic drivers of emerging pollutants temporal dynamics by monitoring, on a daily basis during 85 consecutive days, a series of fifty illicit drugs and pharmaceuticals as well as their metabolites in a sewer network that collects wastewater from 90,000 inhabitants and upstream a wastewater plant. Flow-enslaved composite samples were automatically collected over 24h, then filtered, and target compounds were concentrated by solid-phase extraction before quantitation by HPLC-MS. Concentrations were converted into mass loads per population equivalent by several corrections (i) the flow, (ii) the solid/liquid partition and the molar ratio between target residue and parent-compound (iii) the number of population-equivalent on the catchment and (iv) the excretion rate of target residue. The large dataset obtained, combined to a literature survey, allows us discussing several issues. (1) Calculated daily mass loads of pharmaceuticals are in agreement with literature data for comparable cities except for to anti-inflammatory drugs: ketoprofen that shows the highest values and ibuprofen that displays the lowest values. This would attest to local therapeutic preference that remains to be explained. Daily mass loads for illicit drugs are lower than those measured in more populated cities, except for tetrahydrocannabinol that exceeds the highest reported values. (2) Consumption estimates of pharmaceutical based on our approach are very close to theoretical values from the literature. Additionally, ratios of co-consumed antibiotics such as sulfamethoxazole and trimethoprim are constant over the study and afford similar estimates for their consumption. For evident reasons, this comparison between theoretical and calculated consumption could not be achieved for illicit drugs. (3) Distinction can clearly be made on the temporal pattern of consumptions. Some compounds (e.g. acetaminophen, atenolol) do not exhibit clear week/week-end pattern whereas it is clearly expressed for cocaine and ecstasy. For the first time, some week/week-end patterns were also found for some pharmaceuticals such as metoprolol. Lower values noticed during week-end days could result from the mobility of the population in the catchment. Our study reveals that monitoring of pharmaceuticals and illicit drugs in wastewaters can bring significant information on the evolution of consumption practices in urban areas. Additional work in engaged to evaluate temporal trends on shorter (hour, minute) and longer (season, year) timescales. Applying this approach to a larger set of cities could reveal useful for developing decision tools for stakeholders and health agencies.

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

NASA Astrophysics Data System (ADS)

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

2015-08-01

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

Pharmaceutical penetration of new drug and pharmaceutical market structure in Taiwan: hospital-level prescription of thiazolidinediones for diabetes.

PubMed

Tsai, Yi-Wen; Wen, Yu-Wen; Huang, Weng-Foung; Kuo, Ken N; Chen, Pei-Fen; Shih, Hsin-Wei; Lee, Yue-Chune

2010-06-01

This study used Taiwan's National Health Insurance claim database (years 2000-2005) to examine how thiazolidinediones (TZD), a new class of drugs for diabetes, penetrated into Taiwan's hospitals, and its association with the concentration of all diabetes drugs at the hospital level. We collected 72 monthly summaries of diabetes prescriptions from all hospitals in Taiwan. Hospital-level pharmaceutical concentration was measured by penetration of TZD, defined as monthly market share of TZD in each hospital. Concentration of diabetes drugs was measured by Herfindahl-Hirschman indices. We found a negative association (coefficient = -0.3610) between TZD penetration and concentration of diabetes drug but a positive association between penetration of TZD and the volume of prescribed diabetes drugs (coefficient = 0.4088). In conclusion, hospital characteristics and volume of services determined the concentration of pharmaceuticals at the institution level, reflecting the heterogeneous competition between pharmaceutical companies within each hospital. Institution-level pharmaceutical concentration influences the adoption and penetration of new drugs.

Examining the link between price regulation and pharmaceutical R&D investment.

PubMed

Vernon, John A

2005-01-01

This paper examines the link between price regulation and pharmaceutical research and development (R&D) investment. I identify two mechanisms through which price regulation may exert an influence on R&D: an expected-profit effect and a cash-flow effect. Using established models of the determinants of pharmaceutical R&D, I exploit a unique fact to quantify firm exposure to pharmaceutical price regulation: relative to the rest of the world, the U.S. pharmaceutical market is largely unregulated with respect to price. Using this fact within the context of a system of quasi-structural equations, I simulate how a new policy regulating pharmaceutical prices in the U.S. will affect R&D investment. I find that such a policy will lead to a decline in industry R&D by between 23.4 and 32.7%. This prediction, however, is accompanied by several caveats. Moreover, it says nothing about the implications for social welfare; therefore, these issues are also discussed. Copyright 2004 John Wiley & Sons, Ltd.

Voltammetric determination of copper in selected pharmaceutical preparations--validation of the method.

PubMed

Lutka, Anna; Maruszewska, Małgorzata

2011-01-01

It were established and validated the conditions of voltammetric determination of copper in pharmaceutical preparations. The three selected preparations: Zincuprim (A), Wapń, cynk, miedź z wit. C (B), Vigor complete (V) contained different salts and different quantity of copper (II) and increasing number of accompanied ingredients. For the purpose to transfer copper into solution, the samples of powdered tablets of the first and second preparation were undergone extraction and of the third the mineralization procedures. The concentration of copper in solution was determined by differential pulse voltammetry (DP) using comparison with standard technique. In the validation process, the selectivity, accuracy, precision and linearity of DP determination of copper in three preparations were estimated. Copper was determined within the concentration range of 1-9 ppm (1-9 microg/mL): the mean recoveries approached 102% (A), 100% (B), 102% (V); the relative standard deviations of determinations (RSD) were 0.79-1.59% (A), 0.62-0.85% (B) and 1.68-2.28% (V), respectively. The mean recoveries and the RSDs of determination satisfied the requirements for the analyte concentration at the level 1-10 ppm. The statistical verification confirmed that the tested voltammetric method is suitable for determination of copper in pharmaceutical preparation.

High-Resolution Solid-State NMR Spectroscopy: Characterization of Polymorphism in Cimetidine, a Pharmaceutical Compound

ERIC Educational Resources Information Center

Pacilio, Julia E.; Tokarski, John T.; Quiñones, Rosalynn; Iuliucci, Robbie J.

2014-01-01

High-resolution solid-state NMR (SSNMR) spectroscopy has many advantages as a tool to characterize solid-phase material that finds applications in polymer chemistry, nanotechnology, materials science, biomolecular structure determination, and others, including the pharmaceutical industry. The technology associated with achieving high resolution…

The distribution of environmental contaminants and pharmaceuticals among skim milk, milk fat, curd, whey, and milk protein fractions through milk processing

USDA-ARS?s Scientific Manuscript database

Twenty-seven environmental contaminants and pharmaceuticals encompassing a wide range of physicochemical properties were utilized to determine the effects of milk processing on xenobiotic distribution among milk fractions. Target compounds included radiolabeled antibiotics [ciprofloxacin (CIPR), cl...

Pharmaceuticals and organochlorine pesticides in sediments of an urban river in Florida, United States

USDA-ARS?s Scientific Manuscript database

Purpose Sediments from a rural to urban gradient along the Alafia River in Florida, United States were investigated to determine the risk of environmental contamination with legacy (organochlorine pesticides, OCPs) and new contaminants (pharmaceuticals). Materials and methods Bed sediments (0-10 cm)...

Presence of Pharmaceuticals in Groundwater Down Gradient from Wastewater Lagoons Receiving Partially Treated Wastewater

EPA Science Inventory

Wastewater can contain traces of the pharmaceutical compounds that are used within a given household or community. These chemicals can act as markers of the wastewater, and their presence can help determine potential sources of contamination of water resources. For this study, gr...

Presence of pharmaceuticals in benthic fauna living in a small stream affected by effluent from a municipal sewage treatment plant.

PubMed

Grabicova, Katerina; Grabic, Roman; Blaha, Martin; Kumar, Vimal; Cerveny, Daniel; Fedorova, Ganna; Randak, Tomas

2015-04-01

Aquatic organisms can be affected not only via polluted water but also via their food. In the present study, we examined bioaccumulation of seventy pharmaceuticals in two benthic organisms, Hydropsyche sp. and Erpobdella octoculata in a small stream affected by the effluent from a sewage treatment plant (STP) in Prachatice (South Bohemia region, Czech Republic). Furthermore, water samples from similar locations were analyzed for all seventy pharmaceuticals. In water samples from a control locality situated upstream of the STP, ten of the seventy pharmaceuticals were found with average total concentrations of 200 ng L(-1). In water samples collected at STP-affected sites (downstream the STP's effluent), twenty-nine, twenty-seven and twenty-nine pharmaceuticals were determined at average total concentrations of 2000, 2100 and 1700 ng L(-1), respectively. Six of the seventy pharmaceuticals (azithromycin, citalopram, clarithromycin, clotrimazole, sertraline, and verapamil) were found in Hydropsyche. Four pharmaceuticals (clotrimazole, diclofenac, sertraline, and valsartan) were detected in Erpobdella. Using evaluation criterion bioconcentration factor (BCF) is higher than 2000 we can assign azithromycin and sertraline as bioaccumulative pharmaceuticals. Even pharmaceuticals present at low levels in water were found in benthic organisms at relatively high concentrations (up to 85 ng g(-1) w.w. for azithromycin). Consequently, the uptake of pharmaceuticals via the food web could be an important exposure pathway for the wild fish population. Copyright © 2014. Published by Elsevier Ltd.

Cell-Based Veterinary Pharmaceuticals – Basic Legal Parameters Set by the Veterinary Pharmaceutical Law and the Genetic Engineering Law of the European Union

PubMed Central

Faltus, Timo; Brehm, Walter

2016-01-01

Cell-based therapies have been in use in veterinary medicine for years. However, the legal requirement of manufacturing, placing on the market and use of cell-based veterinary pharmaceuticals are not as well developed as the respective requirements of chemical pharmaceuticals. Cell-based veterinary pharmaceuticals are medicinal products in the sense of the pharmaceutical law of the European Union (EU). For that reason, such medicinal products principally require official approval for their manufacture and an official marketing authorization for their placement on the market before being used by the veterinarian. The manufacture, placing on the market, and use of cell-based veterinary pharmaceuticals without manufacturing approval and marketing authorization is permitted only in certain exceptional cases determined by EU and individual Member State law. Violations of this requirement may have consequences for the respective veterinarian under criminal law and under the code of professional conduct in the respective Member State. The regular use of cell-based veterinary pharmaceuticals within the scope of a therapeutic emergency as well as the import of such veterinary pharmaceuticals from non-European countries for use in the EU are currently out of the question in the EU because of a lack of legal bases. Here, we review the general legal requirement of manufacturing, placing on the market, and use of cell-based veterinary pharmaceuticals within the EU and point out different implementations of EU law within the different Member States. PMID:27965965

Pharmaceutical concentrations in screened municipal wastewaters in Victoria, British Columbia: A comparison with prescription rates and predicted concentrations.

PubMed

Saunders, Leslie J; Mazumder, Asit; Lowe, Christopher J

2016-04-01

Pharmaceuticals and personal care products (PPCPs) are emerging chemicals of concern detected in surface waters globally. Recent reviews advocate that PPCP occurrence, fate, and exposure need to be better predicted and characterized. The use of pharmaceutical prescription rates to estimate PPCP concentrations in the environment has been suggested. Concentrations of 7 pharmaceuticals (acetylsalicylic acid, diclofenac, fenoprofen, gemfibrozil, ibuprofen, ketoprofen, and naproxen) were measured in municipal wastewater using gas chromatography/ion trap-tandem mass spectroscopy (GC/IT-MS/MS). Subregional pharmaceutical prescription data were investigated to determine whether they could predict measured effluent concentrations (MECs) in wastewaters. Predicted effluent concentrations (PECs) for 5 of the 7 pharmaceuticals were within 2-fold agreement of the MECs when the fraction of parent pharmaceutical excreted was not considered. When the fraction of parent pharmaceutical excreted was considered, the respective PECs decreased, and most were within an order of magnitude of the MECs. Regression relationships of monthly PECs versus MECs were statistically significant (p < 0.05) but weak (R(2) = 0.18-0.56) for all pharmaceuticals except ketoprofen. This suggests high variability in the data and may be the result of factors influencing MECs such as the analytical methods used, wastewater sampling frequency, and methodology. The PECs were based solely on prescription rates and did not account for inputs of pharmaceuticals that had a significant over-the-counter component or were from other sources (e.g., hospitals). © 2015 SETAC.

Interactions with the pharmaceutical industry: a survey of family medicine residents in Ontario.

PubMed Central

Sergeant, M D; Hodgetts, P G; Godwin, M; Walker, D M; McHenry, P

1996-01-01

OBJECTIVE: To determine the attitudes, knowledge and practices of family medicine residents relating to the pharmaceutical industry and to assess the effectiveness of existing guidelines on appropriate interactions with the pharmaceutical industry. DESIGN: Survey by mailed questionnaire. SETTING: Ontario. PARTICIPANTS: All 262 second-year family medicine residents in Ontario (seven centres); 226 (86.3%) responded. RESULTS: Fifty-two (23.0%) of the residents who responded stated that they had read the CMA policy statement on appropriate interactions between physicians and the pharmaceutical industry. A total of 124 (54.9%) stated that they would attend a private dinner paid for by a pharmaceutical representative; the proportion was not significantly reduced among those who had read the CMA guidelines, which prohibit the acceptance of personal gifts. In all, 186 (82.3%) reported that they would like the opportunity to interact with pharmaceutical representatives in an educational setting, even though several programs now discourage these interactions. Approximately three quarters (172/226 [76.1%]) of the residents indicated that they plan to see pharmaceutical representatives in their future practice. Residents at Centre 2 were significantly more critical of the pharmaceutical industry than those from the other centres. Overall, being aware of, and familiar with, departmental policy or CMA policy on interactions with the pharmaceutical industry did not affect the residents' attitudes or intended future practices. CONCLUSION: The presence of guidelines concerning physicians' interactions with the pharmaceutical industry does not appear to have a significant impact on family medicine residents in Ontario. PMID:8911290

Cell-Based Veterinary Pharmaceuticals - Basic Legal Parameters Set by the Veterinary Pharmaceutical Law and the Genetic Engineering Law of the European Union.

PubMed

Faltus, Timo; Brehm, Walter

2016-01-01

Cell-based therapies have been in use in veterinary medicine for years. However, the legal requirement of manufacturing, placing on the market and use of cell-based veterinary pharmaceuticals are not as well developed as the respective requirements of chemical pharmaceuticals. Cell-based veterinary pharmaceuticals are medicinal products in the sense of the pharmaceutical law of the European Union (EU). For that reason, such medicinal products principally require official approval for their manufacture and an official marketing authorization for their placement on the market before being used by the veterinarian. The manufacture, placing on the market, and use of cell-based veterinary pharmaceuticals without manufacturing approval and marketing authorization is permitted only in certain exceptional cases determined by EU and individual Member State law. Violations of this requirement may have consequences for the respective veterinarian under criminal law and under the code of professional conduct in the respective Member State. The regular use of cell-based veterinary pharmaceuticals within the scope of a therapeutic emergency as well as the import of such veterinary pharmaceuticals from non-European countries for use in the EU are currently out of the question in the EU because of a lack of legal bases. Here, we review the general legal requirement of manufacturing, placing on the market, and use of cell-based veterinary pharmaceuticals within the EU and point out different implementations of EU law within the different Member States.

Nontraditional roles for certified pharmacy technicians in a pharmaceutical company.

PubMed

Fung, Stacey M; Gilmour, Christine; McCracken, David; Shane, Korban; Matsuura, Gary

2006-01-01

To describe nontraditional roles for Certified Pharmacy Technicians (CPhTs) within pharmaceutical industry. Drug information department within a large biotechnology/pharmaceutical organization. The Medical Communications department within Genentech uses a skills-mix staffing model in which employees with varying educational and training backgrounds work as a team on meeting the informational needs of consumers and health professionals who contact the company. One position within the department is that of Medical Communications Associate, responsible primarily for managing product inquiries. Medical Communications Associates have degrees in life sciences or an equivalent combination of education and experience, including a minimum of 2 years of related experience in the health care industry. Currently, four of the seven Medical Communications Associates in the department are CPhTs. Not applicable. Ability to recruit CPhTs for Medical Communications Associate positions, and job satisfaction of those hired into these positions. Critical basic skills needed for the Medical Communications Associate position include strong computer literacy, ability to multitask, and ability to work in an environment with frequent interruptions. Strong oral and written communications skills, customer service skills, ability to deal with stressful situations, product-specific knowledge, ability to work on a daily basis with Medical Communications Pharmacists, and knowledge of medical terminology are also important. The skills set of CPhTs matches these requirements, as evidenced by the experiences of the four staff members who have worked in the department for a total of 17 person-years. This nontraditional role for CPhTs can be rewarding and beneficial to all, affording an unique opportunity within the pharmaceutical industry. The skill set and experience of CPhTs can be used in the nontraditional pharmacy practice setting of drug information.

Development and validation of NIR-chemometric methods for chemical and pharmaceutical characterization of meloxicam tablets.

PubMed

Tomuta, Ioan; Iovanov, Rares; Bodoki, Ede; Vonica, Loredana

2014-04-01

Near-Infrared (NIR) spectroscopy is an important component of a Process Analytical Technology (PAT) toolbox and is a key technology for enabling the rapid analysis of pharmaceutical tablets. The aim of this research work was to develop and validate NIR-chemometric methods not only for the determination of active pharmaceutical ingredients content but also pharmaceutical properties (crushing strength, disintegration time) of meloxicam tablets. The development of the method for active content assay was performed on samples corresponding to 80%, 90%, 100%, 110% and 120% of meloxicam content and the development of the methods for pharmaceutical characterization was performed on samples prepared at seven different compression forces (ranging from 7 to 45 kN) using NIR transmission spectra of intact tablets and PLS as a regression method. The results show that the developed methods have good trueness, precision and accuracy and are appropriate for direct active content assay in tablets (ranging from 12 to 18 mg/tablet) and also for predicting crushing strength and disintegration time of intact meloxicam tablets. The comparative data show that the proposed methods are in good agreement with the reference methods currently used for the characterization of meloxicam tablets (HPLC-UV methods for the assay and European Pharmacopeia methods for determining the crushing strength and disintegration time). The results show the possibility to predict both chemical properties (active content) and physical/pharmaceutical properties (crushing strength and disintegration time) directly, without any sample preparation, from the same NIR transmission spectrum of meloxicam tablets.

Mitigating pharmaceutical waste exposures: policy and program considerations.

PubMed

Amster, Eric D

2016-01-01

Pharmaceutical disposal and the environmental fate of medication metabolites directly impacts the public's health in two significant ways: accidental medication ingestion of pharmaceuticals that were not disposed of properly results in inadvertent toxicity; and environmental health consequences of pharmaceuticals that were inappropriately disposed and which contaminate municipal water supply. In reviewing the effectiveness of medication disposal policy globally, it is crucial to not only determine which policies are effective but also to assess why they are effective. By assessing the root causes for a specific policy's effectiveness it can be determined if those successes could be translated to another country with a different health care system, unique culture and divergent policy ecosystem. Any intervention regarding pharmaceutical disposal would require a multifaceted approach beyond raising awareness and coordinating pharmaceutical disposal on a national level. While consumer participation is important, effective primary prevention would also include research on drug development that is designed to biodegrade in the environment as opposed to medications that persist and accumulate in the natural environment even when properly disposed. Countries that lack a nationalized disposal policy should leverage the resources and infrastructure already in place in the national health care system to implement a unified policy to address medication disposal in the short-term. In tandem, efforts should be made to recruit the biotechnology sector in high-tech and academia to develop new technologies in medication design and water filtration to decrease exposures in the long-term.

Degradation of 40 selected pharmaceuticals by UV/H2O2.

PubMed

Wols, B A; Hofman-Caris, C H M; Harmsen, D J H; Beerendonk, E F

2013-10-01

The occurrence of pharmaceuticals in source waters is increasing. Although UV advanced oxidation is known to be an effective barrier against micropollutants, degradation rates are only available for limited amounts of pharmaceuticals. Therefore, the degradation of a large group of pharmaceuticals has been studied in this research for the UV/H2O2 process under different conditions, including pharmaceuticals of which the degradation by UV/H2O2 was never reported before (e.g., metformin, paroxetine, pindolol, sotalol, venlafaxine, etc.). Monochromatic low pressure (LP) and polychromatic medium pressure (MP) lamps were used for three different water matrices. In order to have well defined hydraulic conditions, all experiments were conducted in a collimated beam apparatus. Degradation rates for the pharmaceuticals were determined. For those compounds used in this research that are also reported in literature, measured degradation results are in good agreement with literature data. Pharmaceutical degradation for only photolysis with LP lamps is small, which is increased by using a MP lamp. Most of the pharmaceuticals are well removed when applying both UV (either LP or MP) and H2O2. However, differences in degradation rates between pharmaceuticals can be large. For example, ketoprofen, prednisolone, pindolol are very well removed by UV/H2O2, whereas metformin, cyclophosphamide, ifosfamide are very little removed by UV/H2O2. Copyright © 2013 Elsevier Ltd. All rights reserved.

Pharmaceuticals in settleable particulate material in urban and non-urban waters.

PubMed

Lahti, Marja; Oikari, Aimo

2011-10-01

Wastewater treatment plants (WWTP) are important sources of settleable particulate material (SPM), heading to sediments with natural suspended solids. To date, there is little information about the fate of pharmaceuticals in sediment systems. In this study, the objective was to determine if pharmaceuticals are detected in SPM at locations near WWTPs or even in rural areas, thus being susceptible for sedimentation. SPM samples were collected from 10 sites in Finland, grouped as reference, rural and wastewater effluent sites. SPM collectors were placed about 35 cm above bottom for about 2 months during summer. After extraction, a set of 17 pharmaceuticals was analyzed. Several pharmaceuticals were detected in SPM accumulated at sites next to WWTPs. The concentration of citalopram was notably high (300-1350 ng g⁻¹ dw). Also bisoprolol and ciprofloxacin were detected at high concentrations (6-325 and 9-390 ng g⁻¹ dw, respectively). In contrast, none of the pharmaceuticals were detected from reference sites and only two were found from a single rural site. There is no previous information about the presence of pharmaceuticals in SPM. The results showed that pharmaceuticals are sorbed to particles in WWTP and nearby, eventually ending up in sediments. These results also indicate that pharmaceuticals are not markedly contaminating sediments of rural areas in Finland. Copyright © 2011 Elsevier Ltd. All rights reserved.

Patients' willingness to pay for pharmaceutical care.

PubMed

Larson, R A

2000-01-01

To determine the level at which patients receive pharmaceutical care services and their willingness to pay for comprehensive pharmaceutical care services. A mail survey was sent to 2,500 adults in the United States. Surveys were mailed to subjects' homes. Subjects were randomly selected from a marketing database that included representation from each of the 50 states of the United States. The survey provided a description of comprehensive pharmaceutical care, and survey items asked about the level of care subjects were receiving and their willingness to pay for these services. Level of various pharmacy services subjects reported receiving, and the dollar amount subjects were willing to pay for comprehensive pharmaceutical care. The majority of the subjects were not receiving pharmaceutical care services. The average amount all respondents were willing to pay for these services was $13 for a one-time consultation and $28 for this plus 1 year of monitoring. Looking only at those respondents willing to pay (56%), the means rise to $23 and $50, respectively. A majority of patients are willing to pay for pharmaceutical care services, even if they are not now receiving this level of care. Direct payment from patients who recognize the therapeutic benefits of pharmaceutical care may be a more viable option than is generally believed, at least until the profession can prove pharmaceutical care's utility and cost-effectiveness to third party payers.

78 FR 18352 - Determination That QUESTRAN (Cholestyramine for Oral Suspension, USP), Equivalent to 4 Grams, and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-26

...] Determination That QUESTRAN (Cholestyramine for Oral Suspension, USP), Equivalent to 4 Grams, and QUESTRAN LIGHT (Cholestyramine for Oral Suspension, USP), Equivalent to 4 Grams, Were Not Withdrawn From Sale for Reasons of...), equivalent to (EQ) 4 grams (g), and QUESTRAN LIGHT (cholestyramine for oral suspension, USP), EQ 4 g, were...

A Comparative Review of Waivers Granted in Pediatric Drug Development by FDA and EMA from 2007-2013

PubMed Central

Egger, Gunter F.; Wharton, Gerold T.; Malli, Suzanne; Temeck, Jean; Murphy, M. Dianne; Tomasi, Paolo

2016-01-01

Background The European Union and the United States have different legal frameworks in place for pediatric drug development, which can potentially lead to different pediatric research requirements for the pharmaceutical industry. This manuscript compares pediatric clinical trial waivers granted by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). Methods This is a retrospective review comparing EMA’s Paediatric Committee (PDCO) decisions with FDA’s Pediatric Review Committee (PeRC) recommendations for all product-specific pediatric full waiver applications submitted to EMA from January 2007 through December 2013. Using baseline data from EMA, we matched product-specific waivers with their FDA equivalents during the study period. Results For single active substance products, PDCO and PeRC adopted similar opinions in 42 of 49 indications (86%). For fixed-dose combinations, PDCO and PeRC adopted similar opinions in 24 of 31 indications (77%). Conclusion Despite the different legal frameworks, criteria, and processes of determination, the waiver decisions of the 2 agencies were similar in the majority of cases. PMID:27274951

Occurrence of veterinary pharmaceuticals in the aquatic environment in Flanders

NASA Astrophysics Data System (ADS)

Servaes, K.; Vanermen, G.; Seuntjens, P.

2009-04-01

There is a growing interest in the occurrence of pharmaceuticals in the aquatic environment. Pharmaceuticals are classified as so-called ‘emerging pollutants'. ‘Emerging pollutants' are not necessarily new chemical compounds. Often these compounds are already present in the environment for a long time. But, their occurrence and especially their impact on the environment has only recently become clear. Consequently, data on their occurrence are rather scarce. In this study, we focus on the occurrence of veterinary pharmaceuticals in surface water in Flanders. We have only considered active substances administered to cattle, pigs and poultry. Based on the literature and information concerning the use in Belgium, a selection of 25 veterinary pharmaceuticals has been made. This selection consists of the most important antibiotics and antiparasitic substances applied in veterinary medicine in Belgium. We develop an analytical methodology based on UPLC-MS/MS for the detection of these veterinary pharmaceuticals in surface water. Therefore, the mass characteristics as well as the optimum LC conditions will be determined. To obtain limits of detection as low as possible, the samples are concentrated prior to analysis using solid phase extraction (SPE). Different SPE cartridges will be tested during the method development. At first, this SPE sample pre-treatment is performed off-line. In a next step, online SPE is optimized for this purpose. The analytical procedure will be subject to an in-house validation study, thereby determining recovery, repeatability (% RSD), limits of detection and limits of quantification. Finally, the developed methodology will be applied for monitoring the occurrence of veterinary pharmaceuticals in surface water and groundwater in Flanders. These water samples will be taken in areas characterized by intensive cattle breeding. Moreover, the samples will be collected during springtime. In this season, farmers apply manure, stored during winter, onto the fields.

Green approach towards the determination of hydroxyzine dihydrochloride in pure and pharmaceutical dosage forms.

PubMed

Mumtaz, Amina; Hussain, Shahid; Yasir, Muhammad

2014-09-01

A simple eco-friendly method has been developed for detection of hydroxyzine dihydrochloride in pure and pharmaceutical dosage forms. Both conventional system and microwave assisted procedures are used for the development of color. The blue coloured complex is measured spectrophotometrically at 750nm. Peak shift in FT-IR spectra also indicated the formation of complex. The reaction obeys Beer's law over the concentration range of 50- 250βg/mL of hydroxyzine dihydrochloride. The precision value (intra-day and inter-day RSD) for the drug is not greater than 0.79% and recoveries were found to be in range of 99.01-99.99%. The designed method is applicable for periodic determination of hydroxyzine dihydrochloride in pure and pharmaceutical dosage forms.

Application of ion chromatography in clinical studies and pharmaceutical industry.

PubMed

Michalski, Rajmund

2014-01-01

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

Orientation to determine quality attributes of flavoring excipients containing volatile molecules.

PubMed

Kiene, Florian E; Pein, Miriam; Thommes, Markus

2015-06-10

Pharmaceutical excipients containing volatile odor-active molecules can be used in pharmaceutical development to increase patients' compliance. However, capturing the molecular composition of these odor-active substances is challenging. Therefore, guidance for the analytical investigation of these excipients should be developed. Using a model flavor, lead molecules were chosen and a gas chromatographic method was validated according to pharmaceutical guidelines. Changes during storage as well as batch homogeneity and conformity were investigated. The knowledge gained could be used to understand molecular differences between batches caused by aging. A suitable attempt to capture the volatile molecular composition of flavoring substance was presented and the found results could be used for the determination and interpretation of quality attributes. Copyright © 2015 Elsevier B.V. All rights reserved.

Pharmaceutical company internet sites as sources of information about antidepressant medications.

PubMed

Graber, Mark A; Weckmann, Michelle

2002-01-01

To determine the informational content of nine pharmaceutical company websites about the antidepressant medication marketed by the company. A structured, explicit review of materials found on pharmaceutical company websites about nine antidepressants for which no generic drug is available was conducted using eight popular search engines. The accessibility of these websites was also determined using these search engines. Of 72 searches (one for each drug using each search engine), 46 yielded the pharmaceutical company website within the top 10 links. When outliers were removed, the company website was found in the top 10 links for 45 of 56 searches. All of the websites contain information of an advertising and emotive nature. Of the nine company websites, three contain anecdotal information; only two mention electroconvulsive therapy and four mention other types of drug therapy; and only one mentions the tradenames of other drugs. None of the websites mention drug costs, only one has efficacy statistics for the company's drug and, although all of the websites mention at least one adverse effect of the company's drug, only one lists percentages for adverse effects. The information about drugs for treating depression on pharmaceutical company websites aimed at consumers is limited and makes it difficult for consumers to compare drugs.

Determination of pharmaceutical compounds in surface- and ground-water samples by solid-phase extraction and high-performance liquid chromatography-electrospray ionization mass spectrometry

USGS Publications Warehouse

Cahill, J.D.; Furlong, E.T.; Burkhardt, M.R.; Kolpin, D.; Anderson, L.G.

2004-01-01

Commonly used prescription and over-the-counter pharmaceuticals are possibly present in surface- and ground-water samples at ambient concentrations less than 1 μg/L. In this report, the performance characteristics of a combined solid-phase extraction isolation and high-performance liquid chromatography–electrospray ionization mass spectrometry (HPLC–ESI-MS) analytical procedure for routine determination of the presence and concentration of human-health pharmaceuticals are described. This method was developed and used in a recent national reconnaissance of pharmaceuticals in USA surface waters. The selection of pharmaceuticals evaluated for this method was based on usage estimates, resulting in a method that contains compounds from diverse chemical classes, which presents challenges and compromises when applied as a single routine analysis. The method performed well for the majority of the 22 pharmaceuticals evaluated, with recoveries greater than 60% for 12 pharmaceuticals. The recoveries of angiotensin-converting enzyme inhibitors, a histamine (H2) receptor antagonist, and antihypoglycemic compound classes were less than 50%, but were retained in the method to provide information describing the potential presence of these compounds in environmental samples and to indicate evidence of possible matrix enhancing effects. Long-term recoveries, evaluated from reagent-water fortifications processed over 2 years, were similar to initial method performance. Method detection limits averaged 0.022 μg/L, sufficient for expected ambient concentrations. Compound-dependent matrix effects on HPLC/ESI-MS analysis, including enhancement and suppression of ionization, were observed as a 20–30% increase in measured concentrations for three compounds and greater than 50% increase for two compounds. Changing internal standard and more frequent ESI source maintenance minimized matrix effects. Application of the method in the national survey demonstrates that several pharmaceuticals are routinely detected at 0.010–0.100 μg/L concentrations.

A comprehensive approach for the determination of extractable and leachable metals in pharmaceutical products by inductively-coupled plasma.

PubMed

Zuccarello, Daniel J; Murphy, Michael P; Meyer, Richard F; Winslow, Paul A

2009-01-01

A comprehensive digestive approach for determining the extractable and leachable metals in pharmaceutical products by inductively-coupled plasma is investigated. This study examines several acid digestion strategies for packaging materials, containers, and formulated products for complete trace metals analysis. Packaging materials, a food product, and a simulated drug product are evaluated for leachable metals by stressing the materials under accelerated stability conditions. Trace metal profiles of 64 elements for these materials are reported.

Microcap pharmaceutical firms: linking drug pipelines to market value.

PubMed

Beach, Robert

2012-01-01

This article examines predictors of the future market value of microcap pharmaceutical companies. This is problematic since the large majority of these firms seldom report positive net income. Their value comes from the potential of a liquidity event such as occurs when a key drug is approved by the FDA. The typical scenario is one in which the company is either acquired by a larger pharmaceutical firm or enters into a joint venture with another pharmaceutical firm. Binary logistic regression is used to determine the impact of the firm's drug treatment pipeline and its investment in research and development on the firm's market cap. Using annual financial data from 2007 through 2010, this study finds that the status of the firm's drug treatment pipeline and its research and development expenses are significant predictors of the firm's future stock value relative to other microcap pharmaceutical firms.

[History of pharmaceutical packaging in modern Japan. II--Package size of pharmaceuticals].

PubMed

Hattori, Akira

2014-01-01

When planning pharmaceutical packaging, the package size for the product is important for determining the basic package concept. Initially, the sales unit for herbal medicines was the weight; however in 1868, around the early part of the Meiji era, Japanese and Western units were being used and the sales unit was confusing. Since the Edo era, the packing size for OTC medicines was adopted using weight, numbers, dosage or treatment period. These were devised in various ways in consideration of convenience for the consumer, but the concept was not simple. In 1887, from the time that the first edition of the Japanese Pharmacopoeia came out, use of the metric system began to spread in Japan. Its use spread gradually for use in the package size of pharmaceutical products. At the time, the number of pharmaceutical units (i.e., tablets), became the sales unit, which is easy to understand by the purchaser.

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

PubMed

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

2010-11-02

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

Spectrophotometric studies of reactions between pseudo-ephedrine with different inorganic and organic reagents and its micro-determination in pure and in pharmaceutical preparations

NASA Astrophysics Data System (ADS)

Zayed, M. A.; El-Rasheedy, El-Gazy A.

2012-03-01

Two simple, sensitive, cheep and reliable spectrophotometric methods are suggested for micro-determination of pseudoephedrine in its pure form and in pharmaceutical preparation (Sinofree Tablets). The first one depends on the drug reaction with inorganic sensitive reagent like molybdate anion in aqueous media via formation of ion-pair mechanism. The second one depends on the drug reaction with π-acceptor reagent like DDQ in non-aqueous media via formation of charge transfer complex. These reactions were studied under various conditions and the optimum parameters were selected. Under proper conditions the suggested procedures were successfully applied for micro-determination of pseudoephedrine in pure and in Sinofree Tablets without interference from excepients. The values of SD, RSD, recovery %, LOD, LOQ and Sandell sensitivity refer to the high accuracy and precession of the applied procedures. The results obtained were compared with the data obtained by an official method, referring to confidence and agreement with DDQ procedure results; but it referred to the more accuracy of the molybdate data. Therefore, the suggested procedures are now successfully being applied in routine analysis of this drug in its pharmaceutical formulation (Sinofree) in Saudi Arabian Pharmaceutical Company (SPIMACO) in Boridah El-Qaseem, Saudi Arabia instead of imported kits had been previously used.

Determinants of Chronic Respiratory Symptoms among Pharmaceutical Factory Workers

PubMed Central

Enquselassie, Fikre; Tefera, Yifokire; Gizaw, Muluken; Wakuma, Samson; Woldemariam, Messay

2018-01-01

Background Chronic respiratory symptoms including chronic cough, chronic phlegm, wheezing, shortness of breath, and chest pain are manifestations of respiratory problems which are mainly evolved as a result of occupational exposures. This study aims to assess determinants of chronic respiratory symptoms among pharmaceutical factory workers. Methods A case control study was carried out among 453 pharmaceutical factory workers with 151 cases and 302 controls. Data was collected using pretested and structured questionnaire. The data was analyzed using descriptive statistics and bivariate and multivariate analysis. Result Previous history of chronic respiratory diseases (AOR = 3.36, 95% CI = 1.85–6.12), family history of chronic respiratory diseases (AOR = 2.55, 95% CI = 1.51–4.32), previous dusty working environment (AOR = 2.26, 95% CI = 1.07–4.78), ever smoking (AOR = 3.66, 95% CI = 1.05–12.72), and service years (AOR = 1.86, 95% CI = 1.16–2.99) showed statistically significant association with chronic respiratory symptoms. Conclusion Previous history of respiratory diseases, family history of chronic respiratory diseases, previous dusty working environment, smoking, and service years were determinants of chronic respiratory symptoms. Public health endeavors to prevent the burden of chronic respiratory symptoms among pharmaceutical factory workers should target the reduction of adverse workplace exposures and discouragement of smoking. PMID:29666655

Physicochemical Characterization of Iron Carbohydrate Colloid Drug Products.

PubMed

Zou, Peng; Tyner, Katherine; Raw, Andre; Lee, Sau

2017-09-01

Iron carbohydrate colloid drug products are intravenously administered to patients with chronic kidney disease for the treatment of iron deficiency anemia. Physicochemical characterization of iron colloids is critical to establish pharmaceutical equivalence between an innovator iron colloid product and generic version. The purpose of this review is to summarize literature-reported techniques for physicochemical characterization of iron carbohydrate colloid drug products. The mechanisms, reported testing results, and common technical pitfalls for individual characterization test are discussed. A better understanding of the physicochemical characterization techniques will facilitate generic iron carbohydrate colloid product development, accelerate products to market, and ensure iron carbohydrate colloid product quality.

Kinetic Spectrophotometric Determination of Biotin in Pharmaceutical Preparations

PubMed Central

Walash, M. I.; Rizk, M.; Sheribah, Z. A.; Salim, M. M.

2008-01-01

A simple accurate kinetic spectrophotometric method was developed for the determination of biotin in pure form and pharmaceutical preparations. The proposed method is based on a catalytic acceleration of biotin on the reaction between sodium azide and tri-iodide in an aqueous solution. Concentration range of 4-16 μg/mL for biotin was determined by measuring the decrease in the absorbance of tri-iodide at 348 nm by a fixed time method. The decrease in absorbance after 14 min from the initiation of the reaction was markedly correlated to the concentration with correlation coefficient of 0.9999. The detection limit (LOD) of biotin was 0.18 μg/mL while quantitation limit (LOQ) was 0.54 μg/mL. The percentage recovery of the spiked samples was 100.08 ± 0.761. The proposed procedure was successfully applied for the determination of biotin in its pharmaceutical preparations with mean recoveries of 101.17 ± 2.05 and 97.87 ± 1.50 for biotin ampoules and capsules, respectively. The results obtained were in good agreement with those obtained using official method. PMID:23675096

Development and validation of simple spectrophotometric and chemometric methods for simultaneous determination of empagliflozin and metformin: Applied to recently approved pharmaceutical formulation

NASA Astrophysics Data System (ADS)

Ayoub, Bassam M.

2016-11-01

New univariate spectrophotometric method and multivariate chemometric approach were developed and compared for simultaneous determination of empagliflozin and metformin manipulating their zero order absorption spectra with application on their pharmaceutical preparation. Sample enrichment technique was used to increase concentration of empagliflozin after extraction from tablets to allow its simultaneous determination with metformin without prior separation. Validation parameters according to ICH guidelines were satisfactory over the concentration range of 2-12 μg mL- 1 for both drugs using simultaneous equation with LOD values equal to 0.20 μg mL- 1 and 0.19 μg mL- 1, LOQ values equal to 0.59 μg mL- 1 and 0.58 μg mL- 1 for empagliflozin and metformin, respectively. While the optimum results for the chemometric approach using partial least squares method (PLS-2) were obtained using concentration range of 2-10 μg mL- 1. The optimized validated methods are suitable for quality control laboratories enable fast and economic determination of the recently approved pharmaceutical combination Synjardy® tablets.

Using the Rasch Model to Determine Equivalence of Forms In the Trilingual Lollipop Readiness Test

ERIC Educational Resources Information Center

Lang, W. Steve; Chew, Alex L.; Crownover, Carol; Wilkerson, Judy R.

2007-01-01

Determining the cross-cultural equivalence of multilingual tests is a challenge that is more complex than simple horizontal equating of test forms. This study examines the functioning of a trilingual test of preschool readiness to determine the equivalence. Different forms of the test have previously been examined using classical statistical…

Method Description, Quality Assurance, Environmental Data, and other Information for Analysis of Pharmaceuticals in Wastewater-Treatment-Plant Effluents, Streamwater, and Reservoirs, 2004-2009

USGS Publications Warehouse

Phillips, Patrick J.; Smith, Steven G.; Kolpin, Dana W.; Zaugg, Steven D.; Buxton, Herbert T.; Furlong, Edward T.

2010-01-01

Abstract Wastewater-treatment-plant (WWTP) effluents are a demonstrated source of pharmaceuticals to the environment. During 2004-09, a study was conducted to identify pharmaceutical compounds in effluents from WWTPs (including two that receive substantial discharges from pharmaceutical formulation facilities), streamwater, and reservoirs. The methods used to determine and quantify concentrations of seven pharmaceuticals are described. In addition, the report includes information on pharmaceuticals formulated or potentially formulated at the two pharmaceutical formulation facilities that provide substantial discharge to two of the WWTPs, and potential limitations to these data are discussed. The analytical methods used to provide data on the seven pharmaceuticals (including opioids, muscle relaxants, and other pharmaceuticals) in filtered water samples also are described. Data are provided on method performance, including spike data, method detection limit results, and an estimation of precision. Quality-assurance data for sample collection and handling are included. Quantitative data are presented for the seven pharmaceuticals in water samples collected at WWTP discharge points, from streams, and at reservoirs. Occurrence data also are provided for 19 pharmaceuticals that were qualitatively identified. Flow data at selected WWTP and streams are presented. Between 2004-09, 35-38 effluent samples were collected from each of three WWTPs in New York and analyzed for seven pharmaceuticals. Two WWTPs (NY2 and NY3) receive substantial inflows (greater than 20 percent of plant flow) from pharmaceutical formulation facilities (PFF) and one (NY1) receives no PFF flow. Samples of effluents from 23 WWTPs across the United States were analyzed once for these pharmaceuticals as part of a national survey. Maximum pharmaceutical effluent concentrations for the national survey and NY1 effluent samples were generally less than 1 ug/L. Four pharmaceuticals (methadone, oxycodone, butalbital and metaxalone) in samples of NY3 effluent had median concentrations ranging from 3.4 to greater than 400 ug/L. Maximum concentrations of oxycodone (1,700 ug/L) and metaxalone (3,800 ug/L) in samples from NY3 effluent exceeded 1,000 ug/L. Three pharmaceuticals (butalbital, carisoprodol, and oxycodone) in samples of NY2 effluent had median concentrations ranging from 2 to 11 ug/L. These findings suggest that current 2 manufacturing practices at these PFFs can result in pharmaceutical concentrations from 10 to 1,000 times higher than those typically found in WWTP effluents.

Method Development and Application to Determine Potential Plant Uptake of Antibiotics and Other Drugs in Irrigated Crop Production Systems

EPA Science Inventory

Recent studies have shown the detection of pharmaceuticals in surface waters across the United States. The objective of this study was to develop methods, and apply them, to evaluate the potential for food chain transfer when pharmaceutical containing wastewaters are used for cr...

Pharmacy Law and Pharmacy Administration in the New Zealand B.Pharm Curriculum.

ERIC Educational Resources Information Center

Coville, Peter F.

1993-01-01

The role of pharmacy law and management in New Zealand's system of undergraduate pharmacy education is discussed. The areas of pharmaceutical sciences and pharmaceutical practice are seen as distinct but complementary and intersecting. The challenge is for educators to determine how to fit them into an already crowded curriculum. (MSE)

Determination of Bosentan in Pharmaceutical Preparations by Linear Sweep, Square Wave and Differential Pulse Voltammetry Methods

PubMed Central

Atila, Alptug; Yilmaz, Bilal

2015-01-01

In this study, simple, fast and reliable cyclic voltammetry (CV), linear sweep voltammetry (LSV), square wave voltammetry (SWV) and differential pulse voltammetry (DPV) methods were developed and validated for determination of bosentan in pharmaceutical preparations. The proposed methods were based on electrochemical oxidation of bosentan at platinum electrode in acetonitrile solution containing 0.1 M TBACIO4. The well-defined oxidation peak was observed at 1.21 V. The calibration curves were linear for bosentan at the concentration range of 5-40 µg/mL for LSV and 5-35 µg/mL for SWV and DPV methods, respectively. Intra- and inter-day precision values for bosentan were less than 4.92, and accuracy (relative error) was better than 6.29%. The mean recovery of bosentan was 100.7% for pharmaceutical preparations. No interference was found from two tablet excipients at the selected assay conditions. Developed methods in this study are accurate, precise and can be easily applied to Tracleer and Diamond tablets as pharmaceutical preparation. PMID:25901151

Comparative artificial neural network and partial least squares models for analysis of Metronidazole, Diloxanide, Spiramycin and Cliquinol in pharmaceutical preparations.

PubMed

Elkhoudary, Mahmoud M; Abdel Salam, Randa A; Hadad, Ghada M

2014-09-15

Metronidazole (MNZ) is a widely used antibacterial and amoebicide drug. Therefore, it is important to develop a rapid and specific analytical method for the determination of MNZ in mixture with Spiramycin (SPY), Diloxanide (DIX) and Cliquinol (CLQ) in pharmaceutical preparations. This work describes simple, sensitive and reliable six multivariate calibration methods, namely linear and nonlinear artificial neural networks preceded by genetic algorithm (GA-ANN) and principle component analysis (PCA-ANN) as well as partial least squares (PLS) either alone or preceded by genetic algorithm (GA-PLS) for UV spectrophotometric determination of MNZ, SPY, DIX and CLQ in pharmaceutical preparations with no interference of pharmaceutical additives. The results manifest the problem of nonlinearity and how models like ANN can handle it. Analytical performance of these methods was statistically validated with respect to linearity, accuracy, precision and specificity. The developed methods indicate the ability of the previously mentioned multivariate calibration models to handle and solve UV spectra of the four components' mixtures using easy and widely used UV spectrophotometer. Copyright © 2014 Elsevier B.V. All rights reserved.

Spectrofluorimetric determination of tobramycin in human serum and pharmaceutical preparations by derivatization with fluorescamine.

PubMed

Tekkeli, Serife Evrim Kepekci; Önal, Armağan; Sağırlı, A Olcay

2014-02-01

A simple, sensitive and selective spectrofluorimetric method has been developed for the determination of tobramycin (TOB) in human serum and pharmaceutical preparations. The method is based on the reaction between the primary amino group of TOB and fluorescamine in borate buffer, pH 8.5, to give a highly fluorescent derivative which is measured at 469 nm after excitation at 388 nm. The fluorescence intensity was directly proportional to the concentration over the range 300-1500 ng/mL, with a limit of detection of 65 ng/mL and limit of quantitation of 215 ng/mL. All variables were investigated to optimize the reaction conditions. The method was validated according to International Conference on Harmonization guidelines in terms of specificity, linearity, limit of detection, limit of quantification, accuracy, precision and robustness. Good recoveries were obtained ranging from 97.4 to 100.64%, indicating that no interference was observed from concomitants usually present in pharmaceutical dosage forms. The method was successfully, applied for the analysis of the drug substance in its pharmaceutical preparations and spiked serum samples. Copyright © 2013 John Wiley & Sons, Ltd.

Comparative artificial neural network and partial least squares models for analysis of Metronidazole, Diloxanide, Spiramycin and Cliquinol in pharmaceutical preparations

NASA Astrophysics Data System (ADS)

Elkhoudary, Mahmoud M.; Abdel Salam, Randa A.; Hadad, Ghada M.

2014-09-01

Metronidazole (MNZ) is a widely used antibacterial and amoebicide drug. Therefore, it is important to develop a rapid and specific analytical method for the determination of MNZ in mixture with Spiramycin (SPY), Diloxanide (DIX) and Cliquinol (CLQ) in pharmaceutical preparations. This work describes simple, sensitive and reliable six multivariate calibration methods, namely linear and nonlinear artificial neural networks preceded by genetic algorithm (GA-ANN) and principle component analysis (PCA-ANN) as well as partial least squares (PLS) either alone or preceded by genetic algorithm (GA-PLS) for UV spectrophotometric determination of MNZ, SPY, DIX and CLQ in pharmaceutical preparations with no interference of pharmaceutical additives. The results manifest the problem of nonlinearity and how models like ANN can handle it. Analytical performance of these methods was statistically validated with respect to linearity, accuracy, precision and specificity. The developed methods indicate the ability of the previously mentioned multivariate calibration models to handle and solve UV spectra of the four components’ mixtures using easy and widely used UV spectrophotometer.

Determination of bosentan in pharmaceutical preparations by linear sweep, square wave and differential pulse voltammetry methods.

PubMed

Atila, Alptug; Yilmaz, Bilal

2015-01-01

In this study, simple, fast and reliable cyclic voltammetry (CV), linear sweep voltammetry (LSV), square wave voltammetry (SWV) and differential pulse voltammetry (DPV) methods were developed and validated for determination of bosentan in pharmaceutical preparations. The proposed methods were based on electrochemical oxidation of bosentan at platinum electrode in acetonitrile solution containing 0.1 M TBACIO4. The well-defined oxidation peak was observed at 1.21 V. The calibration curves were linear for bosentan at the concentration range of 5-40 µg/mL for LSV and 5-35 µg/mL for SWV and DPV methods, respectively. Intra- and inter-day precision values for bosentan were less than 4.92, and accuracy (relative error) was better than 6.29%. The mean recovery of bosentan was 100.7% for pharmaceutical preparations. No interference was found from two tablet excipients at the selected assay conditions. Developed methods in this study are accurate, precise and can be easily applied to Tracleer and Diamond tablets as pharmaceutical preparation.

Validated spectrofluorimetric method for the determination of tamsulosin in spiked human urine, pure and pharmaceutical preparations.

PubMed

Karasakal, A; Ulu, S T

2014-05-01

A novel, sensitive and selective spectrofluorimetric method was developed for the determination of tamsulosin in spiked human urine and pharmaceutical preparations. The proposed method is based on the reaction of tamsulosin with 1-dimethylaminonaphthalene-5-sulfonyl chloride in carbonate buffer pH 10.5 to yield a highly fluorescent derivative. The described method was validated and the analytical parameters of linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, precision, recovery and robustness were evaluated. The proposed method showed a linear dependence of the fluorescence intensity on drug concentration over the range 1.22 × 10(-7) to 7.35 × 10(-6)  M. LOD and LOQ were calculated as 1.07 × 10(-7) and 3.23 × 10(-7)  M, respectively. The proposed method was successfully applied for the determination of tamsulosin in pharmaceutical preparations and the obtained results were in good agreement with those obtained using the reference method. Copyright © 2013 John Wiley & Sons, Ltd.

Application of liquid-liquid microextraction for the effective separation and simultaneous determination of 11 pharmaceuticals in wastewater samples using HPLC-MS/MS.

PubMed

Diuzheva, Alina; Balogh, József; Jekő, József; Cziáky, Zoltán

2018-05-17

A dispersive liquid-liquid microextraction method for the simultaneous determination of 11 pharmaceuticals has been developed. The method is based on a microextraction procedure applied to wastewater samples from different regions of Hungary followed by high performance liquid chromatography with mass spectrometry. The effect of the nature of the extractant, dispersive solvent, different additives and extraction time were examined on the extraction efficiently of the dispersive liquid-liquid microextraction method. Under optimal conditions, the linearity for determining the pharmaceuticals was in the range of 1-500 ng mL -1 , with the correlation coefficients ranging from 0.9922 to 0.9995. The limits of detection and limits of quantification were in the range 0.31-6.65 and 0.93-22.18 ng mL -1 , respectively. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Simultaneous spectrophotometric determination of indacaterol and glycopyrronium in a newly approved pharmaceutical formulation using different signal processing techniques of ratio spectra

NASA Astrophysics Data System (ADS)

Abdel Ghany, Maha F.; Hussein, Lobna A.; Magdy, Nancy; Yamani, Hend Z.

2016-03-01

Three spectrophotometric methods have been developed and validated for determination of indacaterol (IND) and glycopyrronium (GLY) in their binary mixtures and novel pharmaceutical dosage form. The proposed methods are considered to be the first methods to determine the investigated drugs simultaneously. The developed methods are based on different signal processing techniques of ratio spectra namely; Numerical Differentiation (ND), Savitsky-Golay (SG) and Fourier Transform (FT). The developed methods showed linearity over concentration range 1-30 and 10-35 (μg/mL) for IND and GLY, respectively. The accuracy calculated as percentage recoveries were in the range of 99.00%-100.49% with low value of RSD% (< 1.5%) demonstrating an excellent accuracy of the proposed methods. The developed methods were proved to be specific, sensitive and precise for quality control of the investigated drugs in their pharmaceutical dosage form without the need for any separation process.

Comparative Validation of the Determination of Sofosbuvir in Pharmaceuticals by Several Inexpensive Ecofriendly Chromatographic, Electrophoretic, and Spectrophotometric Methods.

PubMed

El-Yazbi, Amira F

2017-07-01

Sofosbuvir (SOFO) was approved by the U.S. Food and Drug Administration in 2013 for the treatment of hepatitis C virus infection with enhanced antiviral potency compared with earlier analogs. Notwithstanding, all current editions of the pharmacopeias still do not present any analytical methods for the quantification of SOFO. Thus, rapid, simple, and ecofriendly methods for the routine analysis of commercial formulations of SOFO are desirable. In this study, five accurate methods for the determination of SOFO in pharmaceutical tablets were developed and validated. These methods include HPLC, capillary zone electrophoresis, HPTLC, and UV spectrophotometric and derivative spectrometry methods. The proposed methods proved to be rapid, simple, sensitive, selective, and accurate analytical procedures that were suitable for the reliable determination of SOFO in pharmaceutical tablets. An analysis of variance test with P-value > 0.05 confirmed that there were no significant differences between the proposed assays. Thus, any of these methods can be used for the routine analysis of SOFO in commercial tablets.

Electrochemistry of raloxifene on glassy carbon electrode and its determination in pharmaceutical formulations and human plasma.

PubMed

Bagheri, Akbar; Hosseini, Hadi

2012-12-01

The electrochemical behavior of raloxifene (RLX) on the surface of a glassy carbon electrode (GCE) has been studied by cyclic voltammetry (CV). The CV studies were performed in various supporting electrolytes, wide range of potential scan rates, and pHs. The results showed an adsorption-controlled and quasi-reversible process for the electrochemical reaction of RLX, and a probable redox mechanism was suggested. Under the optimum conditions, differential pulse voltammetry (DPV) was applied for quantitative determination of the RLX in pharmaceutical formulations. The DPV measurements showed that the anodic peak current of the RLX was linear to its concentration in the range of 0.2-50.0μM with a detection limit of 0.0750μM, relative standard deviation (RSD %) below 3.0%, and a good sensitivity. The proposed method was successfully applied for determination of the RLX in pharmaceutical and human plasma samples with a good selectivity and suitable recovery. Copyright © 2012 Elsevier B.V. All rights reserved.

Spectrophotometric determination of dopaminergic drugs used for Parkinson's disease, cabergoline and ropinirole, in pharmaceutical preparations.

PubMed

Onal, Armağan; Cağlar, Sena

2007-04-01

Simple and reproducible spectrophotometric methods have been developed for determination of dopaminergic drugs used for Parkinson's disease, cabergoline (CAB) and ropinirole hydrochloride (ROP), in pharmaceutical preparations. The methods are based on the reactions between the studied drug substances and ion-pair agents [methyl orange (MO), bromocresol green (BCG) and bromophenol blue (BPB)] producing yellow colored ion-pair complexes in acidic buffers, after extracting in dichloromethane, which are spectrophotometrically determined at the appropriate wavelength of ion-pair complexes. Beer's law was obeyed within the concentration range from 1.0 to 35 microg ml(-1). The developed methods were applied successfully for the determination of these drugs in tablets.

Trend analysis of the pharmaceutical market in Iran; 1997–2010; policy implications for developing countries

PubMed Central

2013-01-01

Background So far, no detailed study of the Iranian pharmaceutical market has been conducted, and only a few studies have analyzed medicine consumption and expenditure in Iran. Pharmaceutical market trend analysis remains one of the most useful instruments to evaluate the pharmaceutical systems efficiency. An increase in imports of medicines, and a simultaneous decrease in domestic production prompted us to investigate the pharmaceutical expenditure structure. On the other hand, analyzing statistics provides a suitable method to assess the outcomes of national pharmaceutical policies and regulations. Methods This is a descriptive and cross-sectional study which investigates the Iranian pharmaceutical market over a 13-year period (1997–2010). This study used the Iranian pharmaceutical statistical datasheet published by the Iranian Ministry of Health. Systematic searches of the relevant Persian and English research literature were made. In addition, official government documents were analyzed as sources of both data and detailed statements of policy. Results Analysis of the Iranian pharmaceutical market in the 13-year period shows that medicine consumption sales value growth has been 28.38% annually. Determination of domestic production and import reveals that 9.3% and 42.3% annual growth, respectively, have been experienced. Conclusions The Iranian pharmaceutical market has undergone great growth in comparison with developing countries and the pharmerging group, and the market is expanding quickly while a major share goes to biotechnology drugs, which implies the need to commercialization activities in novel fields like pharmaceutical biotechnology. This market expansion has been in favor of imported medicine in sales terms, caused by the reinforcement of suspicious policies of policy makers that necessitates fundamental rearrangements. PMID:23805853

Structure Determination of Glycogen Synthase Kinase-3 from Leishmania major and Comparative Inhibitor Structure-Activity Relationships with Trypanosoma brucei GSK-3

PubMed Central

Ojo, Kayode K.; Arakaki, Tracy L.; Napuli, Alberto J.; Inampudi, Krishna K.; Keyloun, Katelyn R.; Zhang, Li; Hol, Wim G.J.; Verlinde, Christophe L.M.J.; Merritt, Ethan A.; Van Voorhis, Wesley C.

2011-01-01

Glycogen synthase kinase-3 (GSK-3) is a drug target under intense investigation in pharmaceutical companies and constitutes an attractive piggyback target for eukaryotic pathogens. Two different GSKs are found in trypanosomatids, one about 150 residues shorter than the other. GSK-3 short (GeneDB: Tb927.10.13780) has previously been validated genetically as a drug target in Trypanosoma brucei by RNAi induced growth retardation; and chemically by correlation between enzyme and in vitro growth inhibition. Here, we report investigation of the equivalent GSK-3 short enzymes of L. major (LmjF18.0270) and L. infantum (LinJ18_V3.0270, identical in amino acid sequences to LdonGSK-3 short) and a crystal structure of LmajGSK-3 short at 2 Å resolution. The inhibitor structure-activity relationships (SARs) of L. major and L. infantum are virtually identical, suggesting that inhibitors could be useful for both cutaneous and visceral leishmaniasis. Leishmania spp. GSK-3 short has different inhibitor SARs than TbruGSK-3 short, which can be explained mostly by two variant residues in the ATP-binding pocket. Indeed, mutating these residues in the ATP-binding site of LmajGSK-3 short to the TbruGSK-3 short equivalents results in a mutant LmajGSK-3 short enzyme with SAR more similar to that of TbruGSK-3 short. The differences between human GSK-3β (HsGSK-3β) and LmajGSK-3 short SAR suggest that compounds which selectively inhibit LmajGSK-3 short may be found. PMID:21195115

Comparison of three officinal species of Callicarpa based on a biochemome profiling strategy with UHPLC-IT-MS and chemometrics analysis.

PubMed

Chen, Meng-Lu; Chang, Wen-Qi; Zhou, Jian-Liang; Yin, Ying-Hao; Xia, Wen-Rui; Liu, Jian-Qun; Liu, Li-Fang; Xin, Gui-Zhong

2017-10-25

Traditional Chinese medicine (TCM) materials with closely related species are frequently fungible in clinical use. Therefore, holistic comparison of the composition in bioactive compounds is essential to evaluate whether they are equivalent in efficacy. Taking three officinal species of Callicarpa as a case, we proposed and validated a standardized strategy for the discrimination of closely related TCM materials, which focused on the extraction, profiling and multivariate statistical analysis of their biochemome. Firstly, serial liquid-liquid extractions were utilized to prepare different batches of Callicarpa biochemome, and the preparation yields were utilized for the normalization of sampling quantity prior to UHPLC-IT-MS analysis. Secondly, 34 compounds, including 19 phenylethanoid glycosides, 10 flavonoids and 5 terpenoids, were identified based on an untargeted UHPLC-IT-MS method. Thirdly, method validation of linearity, precision and stability showed that the UHPLC-IT-MS system was qualified (R 2 >0.995, RSD<15%) for subsequent biochemome profiling. After PCA and PLS-DA analysis, 30 marker compounds were screened and demonstrated to be of good predictability using genetic algorithm optimized support vector machines. Finally, a heatmap visualization was employed for clarifying the distribution of marker compounds, which could be helpful to determine whether the three Callicarpa species are, in fact, equivalent substitutes. This study provides a standardized biochemome profiling strategy for systemic comparison analysis of closely related TCM materials, which shows promising perspectives in tracking the supply chain of pharmaceutical suppliers. Copyright © 2017 Elsevier B.V. All rights reserved.

40 CFR 63.325 - Determination of equivalent emission control technology.

Code of Federal Regulations, 2010 CFR

2010-07-01

... control technology. 63.325 Section 63.325 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Determination of equivalent emission control technology. (a) Any person requesting that the use of certain... equivalent emission reductions: (1) Diagrams, as appropriate, illustrating the emission control technology...

Spectrofluorimetric determination of fluoroquinolones in pharmaceutical preparations.

PubMed

Ulu, Sevgi Tatar

2009-02-01

Simple, rapid and highly sensitive spectrofluorimetric method is presented for the determination of four fluoroquinolone (FQ) drugs, ciprofloxacin, enoxacin, norfloxacin and moxifloxacin in pharmaceutical preparations. Proposed method is based on the derivatization of FQ with 4-chloro-7-nitrobenzofurazan (NBD-Cl) in borate buffer of pH 9.0 to yield a yellow product. The optimum experimental conditions have been studied carefully. Beer's law is obeyed over the concentration range of 23.5-500 ng mL(-1) for ciprofloxacin, 28.5-700 ng mL(-1) for enoxacin, 29.5-800 ng mL(-1) for norfloxacin and 33.5-1000 ng mL(-1) for moxifloxacin using NBD-Cl reagent, respectively. The detection limits were found to be 7.0 ng mL(-1) for ciprofloxacin, 8.5 ng mL(-1) for enoxacin, 9.2 ng mL(-1) for norfloxacin and 9.98 ng mL(-1) for moxifloxacin, respectively. Intra-day and inter-day relative standard deviation and relative mean error values at three different concentrations were determined. The low relative standard deviation values indicate good precision and high recovery values indicate accuracy of the proposed methods. The method is highly sensitive and specific. The results obtained are in good agreement with those obtained by the official and reference method. The results presented in this report show that the applied spectrofluorimetric method is acceptable for the determination of the four FQ in the pharmaceutical preparations. Common excipients used as additives in pharmaceutical preparations do not interfere with the proposed method.

Licensing of Generic Medicines: Are There Any Challenges Left? A Pharmaceutical Regulatory Perspective.

PubMed

Borg, John Joseph; Tomasi, Paolo; Pani, Luca; Aislaitner, George; Pirozynski, Michal; Leufkens, Hubert; Melchiorri, Daniela

2014-01-01

When an innovative product (innovator) is not covered anymore by intellectual property rights, cheaper equivalent medicinal products (generic products) may be marketed and used in clinical practice. The regulation of generic products is well-established, and is primarily based on standard rules for quality, therapeutic equivalence requirements (the latter in most instances proven through a bioequivalence study), and safety data for the innovator. The extensive experience from bringing generic products to the market over the last decades allows the conclusion that they are well-accepted and provide a useful alternative option for cost-effective pharmacotherapy. While supporting this conclusion, there are a number of issues to be considered during the assessment of a generic product application. Six scenarios are described in total, from an efficacy and a safety perspective, where potential concerns with the current regulatory standards could arise in the approval of generic products. We also propose solutions to these scenarios in order to foster debate on these issues.

Lipases as biocatalysts for the synthesis of structured lipids.

PubMed

Jala, Ram Chandra Reddy; Hu, Peng; Yang, Tiankui; Jiang, Yuanrong; Zheng, Yan; Xu, Xuebing

2012-01-01

Structured lipids (SL) are broadly referred to as modified or synthetic oils and fats or lipids with functional or pharmaceutical applications. Some structured lipids, such as triglycerides that contain both long-chain (mainly essential) fatty acids and medium- or short-chain fatty acids and also artificial products that mimic the structure of natural materials, namely human milk fat substitutes and cocoa butter equivalents, have been discussed. Further, other modified or synthetic lipids, such as structured phospholipids and synthetic phenolic lipids are also included in this chapter. For all the products described in this chapter, enzymatic production in industry has been already conducted in one way or another. Cocoa butter equivalents, healthy oil containing medium-chain fatty acids, phosphatidyl serine, and phenol lipids from enzyme technology have been reported for commercial operation. As the demand for better quality functional lipids is increasing, the production of structured lipids becomes an interesting area. Thus, in this chapter we have discussed latest developments as well as present industrial situation of all commercially important structured lipids.

Evaluation of a Novel Approach for Reducing Emissions of Pharmaceuticals to the Environment

NASA Astrophysics Data System (ADS)

Bean, Thomas G.; Bergstrom, Ed; Thomas-Oates, Jane; Wolff, Amy; Bartl, Peter; Eaton, Bob; Boxall, Alistair B. A.

2016-10-01

Increased interest over the levels of pharmaceuticals detected in the environment has led to the need for new approaches to manage their emissions. Inappropriate disposal of unused and waste medicines and release from manufacturing plants are believed to be important pathways for pharmaceuticals entering the environment. In situ treatment technologies, which can be used on-site in pharmacies, hospitals, clinics, and at manufacturing plants, might provide a solution. In this study we explored the use of Pyropure, a microscale combined pyrolysis and gasification in situ treatment system for destroying pharmaceutical wastes. This involved selecting 17 pharmaceuticals, including 14 of the most thermally stable compounds currently in use and three of high environmental concern to determine the technology's success in waste destruction. Treatment simulation studies were done on three different waste types and liquid, solid, and gaseous emissions from the process were analyzed for parent pharmaceutical and known active transformation products. Gaseous emissions were also analyzed for NOx, particulates, dioxins, furans, and metals. Results suggest that Pyropure is an effective treatment process for pharmaceutical wastes: over 99 % of each study pharmaceutical was destroyed by the system without known active transformation products being formed during the treatment process. Emissions of the other gaseous air pollutants were within acceptable levels. Future uptake of the system, or similar in situ treatment approaches, by clinics, pharmacists, and manufacturers could help to reduce the levels of pharmaceuticals in the environment and reduce the economic and environmental costs of current waste management practices.

Contamination levels of human pharmaceutical compounds in French surface and drinking water.

PubMed

Mompelat, S; Thomas, O; Le Bot, B

2011-10-01

The occurrence of 20 human pharmaceutical compounds and metabolites from 10 representative therapeutic classes was analysed from resource and drinking water in two catchment basins located in north-west France. 98 samples were analysed from 63 stations (surface water and drinking water produced from surface water). Of the 20 human pharmaceutical compounds selected, 16 were quantified in both the surface water and drinking water, with 22% of the values above the limit of quantification for surface water and 14% for drinking water). Psychostimulants, non-steroidal anti-inflammatory drugs, iodinated contrast media and anxiolytic drugs were the main therapeutic classes of human pharmaceutical compounds detected in the surface water and drinking water. The results for surface water were close to results from previous studies in spite of differences in prescription rates of human pharmaceutical compounds in different countries. The removal rate of human pharmaceutical compounds at 11 water treatment units was also determined. Only caffeine proved to be resistant to drinking water treatment processes (with a minimum rate of 5%). Other human pharmaceutical compounds seemed to be removed more efficiently (average elimination rate of over 50%) by adsorption onto activated carbon and oxidation/disinfection with ozone or chlorine (not taking account of the disinfection by-products). These results add to the increasing evidence of the occurrence of human pharmaceutical compounds in drinking water that may represent a threat to human beings exposed to a cocktail of human pharmaceutical compounds and related metabolites and by-products in drinking water.

The ethics of the medical-pharmaceutical relationship.

PubMed

Vashi, Neelam A; Latkowski, Jo-Ann M

2012-01-01

Physician interaction with the pharmaceutical industry raises many ethical concerns. This relationship is complex, owing to a pluralism of beliefs held by physicians, patients, and third parties. As a result, determining whether physicians fulfill their responsibilities to both the professional and public communities is an arduous endeavor. In an effort to clarify the situation and provide transparency to this complex relationship, medical and pharmaceutical organizations have enacted their own respective codes and guidelines. Even with adherence to these guidelines, questions remain regarding the codependent relationship that interweaves the pharmaceutical industry with the medical community. Owing to the ever-changing landscape enmeshing product development, scientific advancement, corporate realities and patient care, the proper choice for physicians is rarely obvious; however, to operate to the highest standards, those in the medical community must be candid about relations with the pharmaceutical industry and transparent in their financial interests. Further undertakings should focus not on the eradication of physician-pharmaceutical interaction, but instead on the education of physicians about industry marketing strategies and the delineation of boundaries of these interactions to benefit not the individual physician, but our patients. Copyright © 2012. Published by Elsevier Inc.

Optimized and validated flow-injection spectrophotometric analysis of topiramate, piracetam and levetiracetam in pharmaceutical formulations.

PubMed

Hadad, Ghada M; Abdel-Salam, Randa A; Emara, Samy

2011-12-01

Application of a sensitive and rapid flow injection analysis (FIA) method for determination of topiramate, piracetam, and levetiracetam in pharmaceutical formulations has been investigated. The method is based on the reaction with ortho-phtalaldehyde and 2-mercaptoethanol in a basic buffer and measurement of absorbance at 295 nm under flow conditions. Variables affecting the determination such as sample injection volume, pH, ionic strength, reagent concentrations, flow rate of reagent and other FIA parameters were optimized to produce the most sensitive and reproducible results using a quarter-fraction factorial design, for five factors at two levels. Also, the method has been optimized and fully validated in terms of linearity and range, limit of detection and quantitation, precision, selectivity and accuracy. The method was successfully applied to the analysis of pharmaceutical preparations.

On macroeconomic characteristics of pharmaceutical generics and the potential for manufacturing and consumption under fuzzy conditions.

PubMed

Gascón, Fernando; de la Fuente, David; Puente, Javier; Lozano, Jesús

2007-11-01

The aim of this paper is to develop a methodology that is useful for analyzing, from a macroeconomic perspective, the aggregate demand and the aggregate supply features of the market of pharmaceutical generics. In order to determine the potential consumption and the potential production of pharmaceutical generics in different countries, two fuzzy decision support systems are proposed. Two fuzzy decision support systems, both based on the Mamdani model, were applied in this paper. These systems, generated by Matlab Toolbox 'Fuzzy' (v. 2.0), are able to determine the potential of a country for the manufacturing or the consumption of pharmaceutical generics. The systems make use of three macroeconomic input variables. In an empirical application of our proposed methodology, the potential towards consumption and manufacturing in Holland, Sweden, Italy and Spain has been estimated from national indicators. Cross-country comparisons are made and graphical surfaces are analyzed in order to interpret the results. The main contribution of this work is the development of a methodology that is useful for analyzing aggregate demand and aggregate supply characteristics of pharmaceutical generics. The methodology is valid for carrying out a systematic analysis of the potential generics have at a macrolevel in different countries. The main advantages of the use of fuzzy decision support systems in the context of pharmaceutical generics are the flexibility in the construction of the system, the speed in interpreting the results offered by the inference and surface maps and the ease with which a sensitivity analysis of the potential behavior of a given country may be performed.

Studies on gum of Moringa oleifera for its emulsifying properties.

PubMed

Panda, Dibya Sundar

2014-04-01

Emulsion has been a form of presenting water insoluble substances for a long period of time. Now a day, it has been a way of presenting various intravenous additives and diagnostic agents in X-ray examinations. Various substances can be used as emulsifying agent, which can be operationally defined as a stabilizer of the droplets formed of the internal phase. Gum from Moringa oleifera was evaluated for its emulsifying properties. Castor oil emulsions 30 percent (o/w), containing 2 to 4% Moringa oleifera gum was prepared. Emulsions containing equivalent concentration of acacia were also prepared for comparison. All the emulsions prepared were stored at room temperature and studied for stability at various time intervals for 8 weeks. The prepared emulsions were evaluated for creaming rate, globule size and rate of coalescence. 23 factorial design was chosen to investigate the effects of centrifugation, pH, temperature changes and electrolytes on the creaming rate and globule size. The results of the investigations show that the gum of Moringa oleifera possesses better emulsifying properties as compared to gum acacia. Gum of Moringa oleifera could be used in pharmaceutical and non-pharmaceutical preparation.

Effect of the economic recession on pharmaceutical policy and medicine sales in eight European countries.

PubMed

Leopold, Christine; Mantel-Teeuwisse, Aukje K; Vogler, Sabine; Valkova, Silvia; de Joncheere, Kees; Leufkens, Hubert G M; Wagner, Anita K; Ross-Degnan, Dennis; Laing, Richard

2014-09-01

To identify pharmaceutical policy changes during the economic recession in eight European countries and to determine whether policy measures resulted in lower sales of, and less expenditure on, pharmaceuticals. Information on pharmaceutical policy changes between 2008 and 2011 in eight European countries was obtained from publications and pharmaceutical policy databases. Data on the volume and value of the quarterly sales of products between 2006 and 2011 in the 10 highest-selling therapeutic classes in each country were obtained from a pharmaceutical market research database. We compared these indicators in economically stable countries; Austria, Estonia and Finland, to those in economically less stable countries, Greece, Ireland, Portugal, Slovakia and Spain. Economically stable countries implemented two to seven policy changes each, whereas less stable countries implemented 10 to 22 each. Of the 88 policy changes identified, 33 occurred in 2010 and 40 in 2011. They involved changing out-of-pocket payments for patients in 16 cases, price mark-up schemes in 13 and price cuts in 11. Sales volumes increased moderately in all countries except Greece and Portugal, which experienced slight declines after 2009. Sales values decreased in both groups of countries, but fell more in less stable countries. Less economically stable countries implemented more pharmaceutical policy changes during the recession than economically stable countries. Unexpectedly, pharmaceutical sales volumes increased in almost all countries, whereas sales values declined, especially in less stable countries.

Analysis of 70 Environmental Protection Agency priority pharmaceuticals in water by EPA Method 1694.

PubMed

Ferrer, Imma; Zweigenbaum, Jerry A; Thurman, E Michael

2010-09-03

The U.S. Environmental Protection Agency (EPA) Method 1694 for the determination of pharmaceuticals in water recently brought a new challenge for treatment utilities, where pharmaceuticals have been reported in the drinking water of 41-million Americans. This proposed methodology, designed to address this important issue, consists of solid-phase extraction (SPE) followed by liquid chromatography-mass spectrometry (LC/MS-MS) using triple quadrupole. Under the guidelines of Method 1694, a multi-residue method was developed, validated, and applied to wastewater, surface water and drinking water samples for the analysis of 70 pharmaceuticals. Four distinct chromatographic gradients and LC conditions were used according to the polarity and extraction of the different pharmaceuticals. Positive and negative ion electrospray were used with two MRM transitions (a quantifier and a qualifier ion for each compound), which adds extra confirmation not included in the original Method 1694. Finally, we verify, for the first time, EPA Method 1694 on water samples collected in several locations in Colorado, where positive identifications for several pharmaceuticals were found. This study is a valuable indicator of the potential of LC/MS-MS for routine quantitative multi-residue analysis of pharmaceuticals in drinking water and wastewater samples and will make monitoring studies much easier to develop for water utilities across the US, who are currently seeking guidance on analytical methods for pharmaceuticals in their water supplies. 2010 Elsevier B.V. All rights reserved.

Purity Analysis of the Pharmaceuticals Naproxen and Propranolol: A Guided-Inquiry Laboratory Experiment in the Analytical Chemistry Laboratory

ERIC Educational Resources Information Center

Fakayode, Sayo O.

2015-01-01

Counterfeiting and adulteration of prescription drugs, herbal products, and food supplements are a global challenge, causing serious economic loss to drug marketers and health implications for humans. Accordingly, accurate determination of the purity of pharmaceuticals is critical for the quality assurance of prescription drugs. Herein, the first…

Analytical protocol for the sensitive determination of mannitol, sorbitol and glucose containing powders in pharmaceutical workplaces by ion chromatography using a pulsed amperometric detector.

PubMed

Butler, Owen; Forder, James; Saunders, John

2015-03-15

Workers in the pharmaceutical industry can potentially be exposed to airborne dusts and powders that can contain potent active pharmaceutical ingredients (API). Occupational hygienists and health and safety professionals need to assess and ultimately minimise such inhalation and dermal exposure risks. Containment of dusts at source is the first line of defence but the performance of such technologies needs to be verified, for which purpose the good practice guide: assessing the particulate containment performance of pharmaceutical equipment, produced by the International Society for Pharmaceutical Engineering (ISPE), is a widely used reference document. This guide recommends the use of surrogate powders that can be used to challenge the performance of such containment systems. Materials such as lactose and mannitol are recommended as their physical properties (adhesion, compactability, dustiness, flow characteristics and particle sizes) mimic those of API-containing materials typically handled. Furthermore they are safe materials to use, are available in high purity and can be procured at a reasonable cost. The aim of this work was to develop and validate a sensitive ion-chromatography based analytical procedure for the determination of surrogate powders collected on filter samples so as to meet analytical requirements set out in this ISPE guide. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

Evaluation of pharmaceuticals removal by sewage sludge-derived adsorbents with rapid small-scale column tests

NASA Astrophysics Data System (ADS)

Zhang, P.; Ding, R.; Wallace, R.; Bandosz, T.

2015-12-01

New composite adsorbents were developed by pyrolyzing sewage sludge and fish waste (75:25 or 90:10 dry mass ratio) at 650 oC and 950 oC. Batch adsorption experiments demonstrated that the composite adsorbents were able to adsorb a wide range of organic contaminants (volatile organic compounds, pharmaceuticals and endocrine disrupting compounds (EDCs), and nitrosamine disinfection byproducts) with high capacities. Here we further examine the performance of the adsorbents for the simultaneous removal of 8 pharmaceuticals and EDCs with rapid small-scale column tests (RSSCT). Results show that the order of breakthrough in RSSCT is in general consistent with the affinity determined via batch tests. As expected, the maximum amount of adsorption for each compound obtained from RSSCT is identical to or less than that obtained from batch tests (with only one exception), due to adsorption kinetics. However, despite the very different input concentration (1 mg/L vs. 100 mg/L) and contact time (2 min empty bed contact time vs. 16 hour equilibrium time) used in RSSCT and batch tests, the maximum amount of pharmaceuticals and EDCs adsorbed under RSSCT is still about one half of that under equilibrium batch tests, validating the approach of using batch tests with much higher input concentrations to determine adsorption capacities. Results of a pilot-scale column test in a drinking water treatment plant for pharmaceuticals removal will also be presented.

Temporal and spatial behavior of pharmaceuticals in Narragansett Bay, Rhode Island, United States.

PubMed

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

2017-07-01

The behavior and fate of pharmaceutical ingredients in coastal marine ecosystems are not well understood. To address this, the spatial and temporal distribution of 15 high-volume pharmaceuticals were measured over a 1-yr period in Narragansett Bay (RI, USA) to elucidate factors and processes regulating their concentration and distribution. Dissolved concentrations ranged from below detection to 313 ng/L, with 4 pharmaceuticals present at all sites and sampling periods. Eight pharmaceuticals were present in suspended particulate material, ranging in concentration from below detection to 44 ng/g. Partitioning coefficients were determined for some pharmaceuticals, with their range and variability remaining relatively constant throughout the study. Normalization to organic carbon content provided no benefit, indicating other factors played a greater role in regulating partitioning behavior. Within the upper bay, the continuous influx of wastewater treatment plant effluents resulted in sustained, elevated levels of pharmaceuticals. A pharmaceutical concentration gradient was apparent from this zone to the mouth of the bay. For most of the pharmaceuticals, there was a strong relationship with salinity, indicating conservative behavior within the estuary. Short flushing times in Narragansett Bay coupled with pharmaceuticals' presence overwhelmingly in the dissolved phase indicate that most pharmaceuticals will be diluted and transported out of the estuary, with only trace amounts of several compounds sequestered in sediments. The present study identifies factors controlling the temporal and spatial dynamics of dissolved and particulate pharmaceuticals; their partitioning behavior provides an increased understanding of their fate, including bioavailability in an urban estuary. Environ Toxicol Chem 2017;36:1846-1855. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Quantitative Analysis of Drugs with Highly Different Concentrations of Pharmaceutical Components Using Spectral Subtraction Techniques

NASA Astrophysics Data System (ADS)

Ayoub, B. M.

2017-11-01

Two simple spectrophotometric methods were developed for determination of empagliflozin and metformin by manipulating their ratio spectra with application on a recently approved pharmaceutical combination, Synjardy® tablets. A spiking technique was used to increase the concentration of empagliflozin after extraction from the tablets to allow its simultaneous determination with metformin. Validation parameters according to ICH guidelines were acceptable over the concentration range of 2-12 μg/mL for both drugs using constant multiplication and spectrum subtraction methods. The optimized methods are suitable for QC labs.

Determination of benzylpenicillin in pharmaceuticals by capillary zone electrophoresis

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

Hoyt, A.M. Jr.; Sepaniak, M.J.

A rapid and direct method is described for the determination of benzylpenicillin (penicillin G) in pharmaceutical preparations. The method involves very little sample preparation and total analysis time for duplicate results is less 30 minutes per sample. The method takes advantage of the speed and separating power of capillary zone electrophoresis (CZE). Detection of penicillin is by absorption at 228 nm. An internal standard is employed to reduce sample injection error. The method was applied successfully to both tablets and injectable preparations. 14 refs., 5 figs., 3 tabs.

R&D investments for neglected diseases can be sensitive to the economic goal of pharmaceutical companies.

PubMed

Dimitri, Nicola

2012-08-01

A fundamental problem with neglected diseases is how to induce pharmaceutical companies to invest resources for developing effective treatments. A recent debate focused on the role of economic incentives represented by monetary transfers to the firms. In this article I focus on the economic goals of pharmaceutical companies, as determinants for R&D effort. In particular, within a stylized framework, the work compares expected profit and expected productivity maximization, arguing that the former in general induces higher R&D investments than the latter. Therefore, as it is currently the case, when pharmaceutical firms focus on productivity, appropriate economic incentives might be needed for them to invest in R&D for neglected diseases. Copyright © 2012 Elsevier Ltd. All rights reserved.

The pitfalls of deducing ethics from behavioral economics: why the Association of American Medical Colleges is wrong about pharmaceutical detailing.

PubMed

Huddle, Thomas S

2010-01-01

The Association of American Medical Colleges (AAMC) is urging academic medical centers to ban pharmaceutical detailing. This policy followed from a consideration of behavioral and neuroeconomics research. I argue that this research did not warrant the conclusions drawn from it. Pharmaceutical detailing carries risks of cognitive error for physicians, as do other forms of information exchange. Physicians may overcome such risks; those determined to do so may ethically engage in pharmaceutical detailing. Whether or not they should do so is a prudential judgment about which reasonable people may disagree. The AAMC's ethical condemnation of detailing is unwarranted and will subvert efforts to maintain a realm of physician discretion in clinical work that is increasingly threatened in our present practice environment.

20 CFR 404.1526 - Medical equivalence.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false Medical equivalence. 404.1526 Section 404... INSURANCE (1950- ) Determining Disability and Blindness Medical Considerations § 404.1526 Medical equivalence. (a) What is medical equivalence? Your impairment(s) is medically equivalent to a listed...

20 CFR 404.1526 - Medical equivalence.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false Medical equivalence. 404.1526 Section 404... INSURANCE (1950- ) Determining Disability and Blindness Medical Considerations § 404.1526 Medical equivalence. (a) What is medical equivalence? Your impairment(s) is medically equivalent to a listed...

20 CFR 404.1526 - Medical equivalence.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false Medical equivalence. 404.1526 Section 404... INSURANCE (1950- ) Determining Disability and Blindness Medical Considerations § 404.1526 Medical equivalence. (a) What is medical equivalence? Your impairment(s) is medically equivalent to a listed...

20 CFR 404.1526 - Medical equivalence.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Medical equivalence. 404.1526 Section 404... INSURANCE (1950- ) Determining Disability and Blindness Medical Considerations § 404.1526 Medical equivalence. (a) What is medical equivalence? Your impairment(s) is medically equivalent to a listed...

20 CFR 404.1526 - Medical equivalence.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Medical equivalence. 404.1526 Section 404... INSURANCE (1950- ) Determining Disability and Blindness Medical Considerations § 404.1526 Medical equivalence. (a) What is medical equivalence? Your impairment(s) is medically equivalent to a listed...

Pharmaceuticals in Australia: priorities in a teaching hospital.

PubMed

Kearney, B J

1993-01-01

In spite of rigorous government programs for control of the pricing and dissemination of pharmaceutical products in Australia, the list of new drugs continues to grow and prices to increase. To regain control over drug usage at Royal Adelaide Hospital, the Hospital Drug Committee developed a rating method that judged drugs on the basis of their cost-benefit to patients. The ratio of a total quality score to a total cost score becomes the determinant of additions to the hospital formulary. The background for the Australian approach to pharmaceuticals and the new evaluation technique at the teaching hospital are described in this report.

Impacts of compound properties and sediment characteristics on the sorption behaviour of pharmaceuticals in aquatic systems.

PubMed

Al-Khazrajy, Omar S A; Boxall, Alistair B A

2016-11-05

Sorption is a key factor in determining the persistence, attenuation and bioavailability of sediment-associated contaminants. However, our understanding of the sorption behaviour of pharmaceuticals in sediments is poor. In this study, we investigated the sorption behaviour of a diverse set of pharmaceuticals in a range sediment types. Sorption affinity of pharmaceuticals for all sediments was found to increase in the order mefenamic acid

Spectrophotometric studies of reactions between pseudo-ephedrine with different inorganic and organic reagents and its micro-determination in pure and in pharmaceutical preparations.

PubMed

Zayed, M A; El-Rasheedy, El-Gazy A

2012-03-01

Two simple, sensitive, cheep and reliable spectrophotometric methods are suggested for micro-determination of pseudoephedrine in its pure form and in pharmaceutical preparation (Sinofree Tablets). The first one depends on the drug reaction with inorganic sensitive reagent like molybdate anion in aqueous media via formation of ion-pair mechanism. The second one depends on the drug reaction with π-acceptor reagent like DDQ in non-aqueous media via formation of charge transfer complex. These reactions were studied under various conditions and the optimum parameters were selected. Under proper conditions the suggested procedures were successfully applied for micro-determination of pseudoephedrine in pure and in Sinofree Tablets without interference from excepients. The values of SD, RSD, recovery %, LOD, LOQ and Sandell sensitivity refer to the high accuracy and precession of the applied procedures. The results obtained were compared with the data obtained by an official method, referring to confidence and agreement with DDQ procedure results; but it referred to the more accuracy of the molybdate data. Therefore, the suggested procedures are now successfully being applied in routine analysis of this drug in its pharmaceutical formulation (Sinofree) in Saudi Arabian Pharmaceutical Company (SPIMACO) in Boridah El-Qaseem, Saudi Arabia instead of imported kits had been previously used. Copyright © 2011 Elsevier B.V. All rights reserved.

Characteristics and determinants of adult patients with acute poisoning attending the accident and emergency department of a teaching hospital in Qatar.

PubMed

Khudair, I F; Jassim, Z; Hanssens, Y; Alsaad, W A

2013-09-01

Data about etiologic and demographic characteristics of acute poisoning in adults in Qatar are lacking. This prospective observational study was undertaken to analyze characteristics and possible determinants of acute poisoning in adults in Qatar. During 2010, 18,073 patients attended the emergency department of Hamad General Hospital, a teaching hospital in Qatar. Out of them, 599 (3.3%) patients were diagnosed as "poisoning case" with either chemical or pharmaceutical substances. The prevalence rate of poisoning incidence was 35.3/100,000 population. Seven patients died, corresponding with a case-fatality rate of 0.39/1000. The majority were male (65%) and the mean age was 34 years. The poisons involved were mainly chemicals (61.6%) and pharmaceuticals (38.4%). Female, mainly single, suffered more intentional poisoning compared to male. Of the patients aged 60 years and above (7.2%), the majority (95.3%) suffered unintentional poisoning with pharmaceuticals; 56% with warfarin, 12% with digoxin and 7% with insulin. Multivariate analysis shows that female gender, single status, younger than 35 years of age, being poisoned by pharmaceutical products, and the need for hospitalization are significant determinants for acute intentional poisoning after adjusting all other possible covariates. The findings of this study can be used to establish awareness and prophylactic campaigns in Qatar.

Characterization of drug authenticity using thin-layer chromatography imaging with a mobile phone.

PubMed

Yu, Hojeong; Le, Huy M; Kaale, Eliangiringa; Long, Kenneth D; Layloff, Thomas; Lumetta, Steven S; Cunningham, Brian T

2016-06-05

Thin-layer chromatography (TLC) has a myriad of separation applications in chemistry, biology, and pharmacology due to its simplicity and low cost. While benchtop laboratory sample application and detection systems for TLC provide accurate quantitation of TLC spot positions and densities, there are many applications where inexpensive and portable instruments would greatly expand the applicability of the technology. In this work, we demonstrate identity verification and concentration determination of pharmaceutical compounds via TLC using a custom 3D-printed cradle that interfaces with an ordinary mobile phone. The cradle holds the mobile phone's internal, rear-facing camera in a fixed position relative to a UV lamp and a TLC plate that includes a phosphor in the stationary phase. Analysis of photographs thus reveals the locations and intensities of principal spots of UV--absorbing drugs. Automated image analysis software determines the center location and density of dark spots, which, using integrated calibration spots of known drug compounds and concentrations, can be used to determine if a drug has been diluted or substituted. Two independent image processing approaches have been developed that may be selected based upon the processing capabilities of the smartphone. Each approach is able to discern 5% drug concentration differences. Using single-component solutions of nevirapine, amodiaquine, and paracetamol that have been manually applied, the mobile phone-based detection instrument provides measurements that are equivalent to those obtained with a commercially available lab-based desktop TLC densitometer. Copyright © 2016 Elsevier B.V. All rights reserved.

The power of r - pharmaceutical sales decomposition in Cyprus public healthcare sector and determinants of drug expenditure evolution: any lessons learned?

PubMed

Petrou, Panagiotis

2014-04-01

The pharmaceutical sector has been established as the primary cost driver in health. The scope of this paper is to explore the drivers of pharmaceutical expenditure in Cyprus by decomposing sales and assessing impact of prices, volumes and substitution effect. We used a statistical approach to decompose the growth of public pharmaceutical expenditure during 2005-2011 into three elements: 1) substitution effect; 2) price effect; and 3) increase of consumption. We further decomposed consumption into: 1) prescription/visits; 2) visits/beneficiaries; and 3) beneficiaries. Pharmaceutical expenditure grew by 31.4 % and volume of medicines dispensed increased by 55%. Prices declined by 11% and product-mix residual was -5.5%, indicating that Cyprus experienced a switch to cheaper medicines (generics) without compromising access of patients to innovative medicines. This was enhanced by guidelines, monitoring of prescribing behavior, generic substitution and efficient tendering. The increasing number of products per prescriptions should be monitored with caution.

[Research advances in secondary development of Chinese patent medicines based on quality by design concept].

PubMed

Gong, Xing-Chu; Chen, Teng; Qu, Hai-Bin

2017-03-01

Quality by design (QbD) concept is an advanced pharmaceutical quality control concept. The application of QbD concept in the research and development of pharmaceutical processes of traditional Chinese medicines (TCM) mainly contains five parts, including the definition of critical processes and their evaluation criteria, the determination of critical process parameters and critical material attributes, the establishment of quantitative models, the development of design space, as well as the application and continuous improvement of control strategy. In this work, recent research advances in QbD concept implementation methods in the secondary development of Chinese patent medicines were reviewed, and five promising fields of the implementation of QbD concept were pointed out, including the research and development of TCM new drugs and Chinese medicine granules for formulation, modeling of pharmaceutical processes, development of control strategy based on industrial big data, strengthening the research of process amplification rules, and the development of new pharmaceutical equipment.. Copyright© by the Chinese Pharmaceutical Association.

A Simple and Direct LC-MS Method for Determination of Genotoxic Impurity Hydroxylamine in Pharmaceutical compounds.

PubMed

Kumar, Thangarathinam; Ramya, Mohandass; Srinivasan, Viswanathan; Xavier, N

2017-08-01

Hydroxylamine is a known genotoxic impurity compound that needs to be controlled down to ppm level in pharmaceutical processes. It is difficult to detect using conventional analytical techniques due to its physio-chemical properties like lack of chromophore, low molecular weight, absence of carbon atom and high polarity. In addition to that, analysis of the pharmaceutical samples encounters considerable obstruction from matrix components that greatly overshadow the response of hydroxylamine. This study describes a simple, sensitive and direct Liquid Chromatographic-Mass Spectrometric method (LC-MS) for detection of hydroxylamine in pharmaceutical compounds. The LC-MS method was detected up to 0.008 ppm of hydroxylamine with S/N > 3.0 and quantified up to 0.025 ppm of hydroxylamine with S/N ratio >10.0. This validated method can be applied as a generic method to detect the hydroxylamine for pharmaceutical process control and drug substance release. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Mergers and innovation in the pharmaceutical industry.

PubMed

Comanor, William S; Scherer, F M

2013-01-01

Conflicting trends confound the pharmaceutical industry. The productivity of pharmaceutical innovation has declined in recent years. At the same time, the cohort of large companies who are the leading engines of pharmaceutical R&D has become increasingly concentrated. The concurrent presence of these trends is not sufficient to determine causation. In response to lagging innovation prospects, some companies have sought refuge in mergers and acquisitions to disguise their dwindling prospects or gain R&D synergies. On the other hand, the increased concentration brought on by recent mergers may have contributed to the declining rate of innovation. In this paper, we consider the second of these causal relationships: the likely impact of the recent merger wave among the largest pharmaceutical companies on the rate of innovation. In other words, have recent mergers, which may have been taken in response to lagging innovation, represented a self-defeating strategy that only made industry outcomes worse? Copyright © 2012 Elsevier B.V. All rights reserved.

Determination of estradiol valerate in pharmaceutical preparations and human serum by flow injection chemiluminescence.

PubMed

Liu, Wenwen; Xie, Liangxiao; Liu, Hongshuang; Xu, Shichao; Hu, Bingcheng; Cao, Wei

2013-01-01

A novel method for the detection of trace estradiol valerate (EV) in pharmaceutical preparations and human serum was developed by inhibition of luminol chemiluminescence (CL) by estradiol valerate on the zinc deuteroporphyrin (ZnDP)-enhanced luminol-K3 Fe(CN)6 chemiluminescence system. Under optimized experimental conditions, CL intensity and concentration of estradiol valerate had a good linear relationship in the ranges of 8.0 × 10(-8) to 1.0 × 10(-5) g/mL. Detection limit (3σ) was estimated to be 3.5 × 10(-8) g/mL. The proposed method was applied successfully for the determination of estradiol valerate in pharmaceutical preparations and human serum and recoveries were 97.0-105.0% and 95.5-106.0%, respectively. The possible mechanism of the CL system is discussed. Copyright © 2012 John Wiley & Sons, Ltd.

A highly selective and sensitive Tb3+-acetylacetone photo probe for the assessment of acetazolamide in pharmaceutical and serum samples

NASA Astrophysics Data System (ADS)

Youssef, A. O.

2018-04-01

A novel, simple, sensitive and selective spectrofluorimetric method was developed for the determination of Acetazolamide in pharmaceutical tablets and serum samples using photo probe Tb3+-ACAC. The Acetazolamide can remarkably quench the luminescence intensity of Tb3+-ACAC complex in DMSO at pH 6.8 and λex = 350 nm. The quenching of luminescence intensity of Tb3+-ACAC complex especially the electrical band at λem = 545 nm is used for the assessment of Acetazolamide in the pharmaceutical tablet and serum samples. The dynamic range found for the determination of Acetazolamide concentration is 4.49 × 10-9-1.28 × 10-7 mol L-1, and the limit of detection (LOD) and limit of quantification (LOQ) are (4.0 × 10-9 and 1.21 × 10-8) mol L-1, respectively.

Simultaneous determination of Fluticasone propionate and Azelastine hydrochloride in the presence of pharmaceutical dosage form additives

NASA Astrophysics Data System (ADS)

Merey, Hanan A.; El-Mosallamy, Sally S.; Hassan, Nagiba Y.; El-Zeany, Badr A.

2016-05-01

Fluticasone propionate (FLU) and Azelastine hydrochloride (AZE) are co-formulated with phenylethyl alcohol (PEA) and Benzalkonium chloride (BENZ) (as preservatives) in pharmaceutical dosage form for treatment of seasonal allergies. Different spectrophotometric methods were used for the simultaneous determination of cited drugs in the dosage form. Direct spectrophotometric method was used for determining of AZE, while Derivative of double divisor of ratio spectra (DD-RS), Ratio subtraction coupled with ratio difference method (RS-RD) and Mean centering of the ratio spectra (MCR) are used for the determination of FLU. The linearity of the proposed methods was investigated in the range of 5.00-40.00 and 5.00-80.00 μg/mL for FLU and AZE, respectively. The specificity of the developed methods was investigated by analyzing laboratory prepared mixtures containing different ratios of cited drugs in addition to PEA and their pharmaceutical dosage form. The validity of the proposed methods was assessed using the standard addition technique. The obtained results were statistically compared with those obtained by official or the reported method for FLU or AZE, respectively showing no significant difference with respect to accuracy and precision at p = 0.05.

Investigation into the use of microwave sensors to monitor particulate manufacturing processes

NASA Astrophysics Data System (ADS)

Austin, John Samuel, III

Knowledge of a material's properties in-line during manufacture is of critical importance to many industries, including the pharmaceutical industry, and can be used for either process or quality control. Different microwave sensor configurations were tested to determine both the moisture content and the bulk density in pharmaceutical powders during processing on-line. Although these parameters can significantly affect a material's flowability, compressibility, and cohesivity, in the presence of blends, the picture is incomplete. Due to the ease with which particulate blends tend to segregate, blend uniformity and chemical composition are two critical parameters in nearly all solids manufacturing industries. The prevailing wisdom has been that microwave sensors are not capable of or sensitive enough to measure the relative concentrations of components in a blend. Consequently, it is common to turn to near infrared sensing to determine material composition on-line. In this study, a novel microwave sensor was designed and utilized to determine, separately, the concentrations of different components in a blend of pharmaceutical powders. This custom microwave sensor was shown to have comparable accuracy to the state-of-the-art for both chemical composition and moisture content determination.

Simultaneous Spectrophotometric Determination of Elbasvir and Grazoprevir in a Pharmaceutical Preparation.

PubMed

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

2018-03-01

Three UV spectrophotometric methods have been developed for the simultaneous determination of two new Food and Drug Administration-approved drugs, elbasvir (EBV) and grazoprevir (GRV), in their combined pharmaceutical dosage form. These methods include dual wavelength (DW), classic least-squares (CLS), and principal component regression (PCR). To achieve the DW method, two wavelengths were chosen for each drug in a way to ensure the difference in absorbance was zero from one drug to the other. GRV revealed equal absorbance at 351 and 315 nm, for which the distinctions in absorbance were measured for the determination of EBV. In the same way, distinctions in absorbance at 375 and 334.5 nm were measured for the determination of GRV. Alternatively, the CLS and PCR models were applied to the spectra analysis because the synchronous inclusion of many unreal wavelengths rather than using a single wavelength greatly increased the precision and predictive ability of the methods. The proposed methods were successfully applied to the assay of these drugs in their pharmaceutical formulation. The obtained results were statistically compared with manufacturing methods. The results conclude that there was no significant difference between the proposed methods and the manufacturing method with respect to accuracy and precision.

Prevalence and Determinants of Physician Participation in Conducting Pharmaceutical-sponsored Clinical Trials and Lectures

PubMed Central

Ashar, Bimal H; Miller, Redonda G; Getz, Kelly J; Powe, Nell R

2004-01-01

BACKGROUND The relationship between physicians and the pharmaceutical industry is controversial because of the potential for conflicts of interest. However, little empirical evidence exists on the extent of physician participation in activities sponsored by pharmaceutical companies. OBJECTIVES To determine the prevalence of participation of internal medicine physicians in clinical trials and lectures sponsored by pharmaceutical companies and to describe factors that are associated with such participation. DESIGN, SETTING, AND PARTICIPANTS We conducted a cross-sectional regional survey of 1,000 Maryland internal medicine physicians between February 2000 and January 2001 in order to measure the prevalence of physician participation in pharmaceutical-sponsored clinical trials and lectures. We also collected economic and demographic information to examine potential associations between physician characteristics and engagement in such activities. RESULTS Of 835 eligible physicians 444 (53%) responded, of whom 37% reported engaging in pharmaceutical-sponsored clinical trials and/or lectures to supplement their incomes. In our multivariable analysis, subspecialists versus generalist physicians (odds ratio [OR], 1.85; 95% confidence interval [CI], 1.14 to 2.99), physicians in private group-single specialty and academic practice versus physicians in solo practice (OR, 2.30; 95% CI, 1.19 to 4.44 and OR, 2.56; 95% CI, 1.17 to 5.61, respectively), and physicians with higher versus lower annual incomes (OR, 1.22; 95% CI, 1.04 to 1.44) had a greater odds of participation in these activities. Additionally, physicians dissatisfied with their income had a 140% greater odds of participation (OR, 2.36; 95% CI, 1.45 to 3.83) than those who were satisfied with their income. CONCLUSIONS A substantial number of internists engage in pharmaceutical industry-sponsored clinical trials and/or lectures in an effort to supplement their incomes. Physician dissatisfaction with income appears to partially explain such participation. PMID:15566444

Simple transmission Raman measurements using a single multivariate model for analysis of pharmaceutical samples contained in capsules of different colors.

PubMed

Lee, Yeojin; Kim, Jaejin; Lee, Sanguk; Woo, Young-Ah; Chung, Hoeil

2012-01-30

Direct transmission Raman measurements for analysis of pharmaceuticals in capsules are advantageous since they can be used to determine active pharmaceutical ingredient (API) concentrations in a non-destructive manner and with much less fluorescence background interference from the capsules themselves compared to conventional back-scattering measurements. If a single calibration model such as developed from spectra simply collected in glass vials could be used to determine API concentrations of samples contained in capsules of different colors rather than constructing individual models for each capsule color, the utility of transmission measurements would be further enhanced. To evaluate the feasibility, transmission Raman spectra of binary mixtures of ambroxol and lactose were collected in a glass vial and a partial least squares (PLS) model for the determination of ambroxol concentration was developed. Then, the model was directly applied to determine ambroxol concentrations of samples contained in capsules of 4 different colors (blue, green, white and yellow). Although the prediction performance was slightly degraded when the samples were placed in blue or green capsules, due to the presence of weak fluorescence, accurate determination of ambroxol was generally achieved in all cases. The prediction accuracy was also investigated when the thickness of the capsule was varied. Copyright © 2011 Elsevier B.V. All rights reserved.

APPLICATION OF U.S. EPA METHODS TO THE ANALYSIS OF PHARMACEUTICALS AND PERSONAL CARE PRODUCTS IN THE ENVIRONMENT: DETERMINATION OF CLOFIBRIC ACID IN SEWAGE EFFLUENT BY GC-MS

EPA Science Inventory

An emerging area of research concerns pharmaceuticals and personal care products in the
environment and their possible impact on biota and ecosystems. The long term effects of
constant perfusion of PPCPs into the aquatic environment are presently unknown. Some
compoun...

Quantitative determinations of levofloxacin and rifampicin in pharmaceutical and urine samples using nuclear magnetic resonance spectroscopy

NASA Astrophysics Data System (ADS)

Salem, A. A.; Mossa, H. A.; Barsoum, B. N.

2005-11-01

Rapid, specific and simple methods for determining levofloxacin and rifampicin antibiotic drugs in pharmaceutical and human urine samples were developed. The methods are based on 1H NMR spectroscopy using maleic acid as an internal standard and DMSO-d6 as NMR solvent. Integration of NMR signals at 8.9 and 8.2 ppm were, respectively, used for calculating the concentration of levofloxacin and rifampicin drugs per unit dose. Maleic acid signal at 6.2 ppm was used as the reference signal. Recoveries of (97.0-99.4) ± 0.5 and (98.3-99.7) ± 1.08% were obtained for pure levofloxacin and rifampicin, respectively. Corresponding recoveries of 98.5-100.3 and 96.8-100.0 were, respectively, obtained in pharmaceutical capsules and urine samples. Relative standard deviations (R.S.D.) values ≤2.7 were obtained for analyzed drugs in pure, pharmaceutical and urine samples. Statistical Student's t-test gave t-values ≤2.87 indicating insignificant difference between the real and the experimental values at the 95% confidence level. F-test revealed insignificant difference in precisions between the developed NMR methods and each of fluorimetric and HPLC methods for analyzing levofloxacin and rifampicin.

Uptake, biotransformation and elimination of selected pharmaceuticals in a freshwater invertebrate measured using liquid chromatography tandem mass spectrometry.

PubMed

Miller, Thomas H; Bury, Nicolas R; Owen, Stewart F; Barron, Leon P

2017-09-01

Methods were developed to assess uptake and elimination kinetics in Gammarus pulex of nine pharmaceuticals (sulfamethazine, carbamazepine, diazepam, temazepam, trimethoprim, warfarin, metoprolol, nifedipine and propranolol) using targeted LC-MS/MS to determine bioconcentration factors (BCFs) using a 96 h toxicokinetic exposure and depuration period. The derived BCFs for these pharmaceuticals did not trigger any regulatory thresholds and ranged from 0 to 73 L kg -1 (sulfamethazine showed no bioconcentration). Metabolism of chemicals can affect accurate BCF determination through parameterisation of the kinetic models. The added selectivity of LC-MS/MS allowed us to develop confirmatory methods to monitor the biotransformation of propranolol, carbamazepine and diazepam in G. pulex. Varying concentrations of the biotransformed products; 4-hydroxypropranolol sulphate, carbamazepine-10,11-epoxide, nordiazepam, oxazepam and temazepam were measured following exposure of the precursor compounds. For diazepam, the biotransformation product nordiazepam was present at higher concentrations than the parent compound at 94 ng g -1 dw. Overall, the results indicate that pharmaceutical accumulation is low in these freshwater amphipods, which can potentially be explained by the rapid biotransformation and excretion. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Effects of a mandatory guideline that prohibit hospital doctors from accepting any form of benefits in any form from the pharmaceutical industry].

PubMed

Gundermann, C; Meier-Hellmann, A; Bauer, M; Hartmann, M

2010-05-01

Several hospitals have issued their own guidelines that regulate the conduct of staff members toward the pharmaceutical industry. The effect of theses guidelines on the attitude of the doctors toward the pharmaceutical industry in Germany has so far been unknown. This study investigated whether hospital doctors with guidelines and those without guidelines differ in their attitude toward the pharmaceutical industry. A retrospective analysis was undertaken to determine the influence of hospital guidelines on the attitude of doctors toward the pharmaceutical industry. In May 2008 all doctors in intensive care of a hospital with and one without guidelines were asked anonymously by a questionnaire about their dealings with the pharmaceutical industry. The response rate was 64.9 % (37/57) and 55.1 % (59/107) respectively. The cooperation rate in both groups was 100 %. In the hospital with guidelines every doctor was on average carrying 0.56 +/- 0.64 pharmaceutical advertising gifts with a company logo, while the average in the institution without guidelines was 1.2 +/- 0.61 advertising gifts (p = 0.026). Whereas 49 % of doctors with guidelines considered the acceptance of advertising gifts as not questionable, 81 % without guidelines did (p = 0.001; RRR = 0.65; 95 % CI = 0.48-0.91). Furthermore, 70 % of doctors in the institution with guidelines compared with 92 % of those doctors in the hospital without guidelines believed that the advertising practices of the pharmaceutical industry had no influence on their prescribing behaviour (p = 0.010; RRR = 3.6; 95 % CI = 1.36-9.52). Both groups of doctors are convinced that other doctors are more influenced by the pharmaceutical industry than they are themselves (51 % with and 37 % without guidelines, p = 0.207). 70 % and 90 %, respectively of all participants considered hospital guidelines setting standards of conduct toward the pharmaceutical industry and those not sponsored by industry to have a positive effect. Every other doctor additionally stated the advice by the pharmaceutical industry was not helpful for his work. Hospital guidelines on relations with the pharmaceutical industry appear to further a critical attitude by physicians regarding the pharmaceutical industry. Georg Thieme Verlag KG Stuttgart. New York.

Mechanical Equivalent of Heat--Software for a Thermistor

ERIC Educational Resources Information Center

Boleman, Michael

2008-01-01

The Mechanical Equivalent of Heat Apparatus from PASCO scientific provides the means for doing a simple experiment to determine the mechanical equivalent of heat, "J." A necessary step of this experiment is to determine the temperature of an aluminum cylinder. By measuring the resistance of a thermistor embedded in the cylinder, one is able to…

Role of Cost on Failure to Access Prescribed Pharmaceuticals: The Case of Statins.

PubMed

McRae, Ian; van Gool, Kees; Hall, Jane; Yen, Laurann

2017-10-01

In Australia, as in many other Western countries, patient surveys suggest the costs of medicines lead to deferring or avoiding filling of prescriptions. The Australian Pharmaceutical Benefits Scheme provides approved prescription medicines at subsidised prices with relatively low patient co-payments. The Pharmaceutical Benefits Scheme defines patient co-payment levels per script depending on whether patients are "concessional" (holding prescribed pension or other government concession cards) or "general", and whether they have reached a safety net defined by total out-of-pocket costs for Pharmaceutical Benefits Scheme-approved medicines. The purpose of this study was to explore the impact of costs on adherence to statins in this relatively low-cost environment. Using data from a large-scale survey of older Australians in the state of New South Wales linked to administrative data from the national medical and pharmaceutical insurance schemes, we explore the relationships between adherence to medication regimes for statins and out-of-pocket costs of prescribed pharmaceuticals, income, other health costs, and a wide set of demographic and socio-economic control variables using both descriptive analysis and logistic regressions. Within the general non-safety net group, which has the highest co-payment, those with lowest income have the lowest adherence, suggesting that the general safety threshold may be set at a level that forms a major barrier to statin adherence. This is reinforced by over 75% of those who were not adherent before reaching the safety net threshold becoming adherent after reaching the safety net with its lower co-payments. The main financial determinant of adherence is the concessional/general and safety net category of the patient, which means the main determinant is the level of co-payment.

Influence of microplastics on the toxicity of the pharmaceuticals procainamide and doxycycline on the marine microalgae Tetraselmis chuii.

PubMed

Prata, Joana C; Lavorante, Beatriz R B O; B S M Montenegro, Maria da Conceição; Guilhermino, Lúcia

2018-04-01

Microplastics and pharmaceuticals are considered ubiquitous and emergent pollutants of high concern but the knowledge on their effects on primary producers is still limited, especially those caused by mixtures. Thus, the goal of the present study was to investigate if the presence of microplastics (1-5 μm diameter) influences the toxicity of the pharmaceuticals procainamide and doxycycline to the marine microalga Tetraselmis chuii. Bioassays (96 h) to investigate the toxicity of those substances individually and in mixtures (i.e. microplastics-procainamide mixtures and microplastics-doxycycline mixtures) were carried out. Effect criteria were the average specific growth rate (growth rate) and chlorophyll a concentration (chlorophyll). EC 10 , EC 20 and EC 50 were determined. Microplastics alone had no significant effects on growth rate up to 41.5 mg/l, whereas chlorophyll was significantly reduced at 0.9 and 2.1 mg/l of microplastics, but not at higher concentrations. The 96 h EC 50 (growth rate and chlorophyll, respectively) determined for the other bioassays were: 104 and 143 mg/l for procainamide alone; 125 and 31 mg/l for procainamide in the presence of microplastics; 22 and 14 mg/l for doxycycline alone; 11 and 7 mg/l for doxycycline in the presence of microplastics. Significant differences (p < 0.001) between the toxicity curves of each pharmaceutical alone and in mixture with microplastics were found for procainamide (chlorophyll), and doxycycline (both parameters). Thus, both pharmaceuticals were toxic to T. chuii in the low ppm range, and microplastics-pharmaceutical mixtures were more toxic than the pharmaceuticals alone. Very high decreases of doxycycline concentrations in test media were found, indicating degradation of the antibiotic. Thus, although the biological results are expressed in relation to doxycycline concentration, the effects were likely caused by a mixture of the parental compound and its degradation products. The concentrations of microplastics and pharmaceuticals tested (low ppm range) are higher than those expected to be found in waters of the most part of marine ecosystems (ppt or ppb ranges). However, considering the widespread contamination by microplastics and pharmaceuticals, the concentrations already found in waters, sediments and/or organism of heavily polluted areas, the long-term exposure (over generations) of wild populations to such substances in polluted ecosystems and the possibilities of bioaccumulation and toxicological interactions, these findings are of concern and further research on microplastics-pharmaceuticals toxicological interactions is needed. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

The synthesis of benzimidazoles and quinoxalines from aromatic diamines and alcohols by iridium-catalyzed acceptorless dehydrogenative alkylation.

PubMed

Hille, Toni; Irrgang, Torsten; Kempe, Rhett

2014-05-05

Benzimidazoles and quinoxalines are important N-heteroaromatics with many applications in pharmaceutical and chemical industry. Here, the synthesis of both classes of compounds starting from aromatic diamines and alcohols (benzimidazoles) or diols (quinoxalines) is reported. The reactions proceed through acceptorless dehydrogenative condensation steps. Water and two equivalents of hydrogen are liberated in the course of the reactions. An Ir complex stabilized by the tridentate P^N^P ligand N(2) ,N(6) -bis(di-isopropylphosphino)pyridine-2,6-diamine revealed the highest catalytic activity for both reactions. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Advanced asymmetric synthesis of (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid by alkylation/cyclization of newly designed axially chiral Ni(II) complex of glycine Schiff base.

PubMed

Kawashima, Aki; Shu, Shuangjie; Takeda, Ryosuke; Kawamura, Akie; Sato, Tatsunori; Moriwaki, Hiroki; Wang, Jiang; Izawa, Kunisuke; Aceña, José Luis; Soloshonok, Vadim A; Liu, Hong

2016-04-01

Asymmetric synthesis of (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid (vinyl-ACCA) is in extremely high demand due to the pharmaceutical importance of this tailor-made, sterically constrained α-amino acid. Here we report the development of an advanced procedure for preparation of the target amino acid via two-step SN2 and SN2' alkylation of novel axially chiral nucleophilic glycine equivalent. Excellent yields and diastereoselectivity coupled with reliable and easy scalability render this method of immediate use for practical synthesis of (1R,2S)-vinyl-ACCA.

Effect of the economic recession on pharmaceutical policy and medicine sales in eight European countries

PubMed Central

Mantel-Teeuwisse, Aukje K; Vogler, Sabine; Valkova, Silvia; de Joncheere, Kees; Leufkens, Hubert GM; Wagner, Anita K; Ross-Degnan, Dennis; Laing, Richard

2014-01-01

Abstract Objective To identify pharmaceutical policy changes during the economic recession in eight European countries and to determine whether policy measures resulted in lower sales of, and less expenditure on, pharmaceuticals. Methods Information on pharmaceutical policy changes between 2008 and 2011 in eight European countries was obtained from publications and pharmaceutical policy databases. Data on the volume and value of the quarterly sales of products between 2006 and 2011 in the 10 highest-selling therapeutic classes in each country were obtained from a pharmaceutical market research database. We compared these indicators in economically stable countries; Austria, Estonia and Finland, to those in economically less stable countries, Greece, Ireland, Portugal, Slovakia and Spain. Findings Economically stable countries implemented two to seven policy changes each, whereas less stable countries implemented 10 to 22 each. Of the 88 policy changes identified, 33 occurred in 2010 and 40 in 2011. They involved changing out-of-pocket payments for patients in 16 cases, price mark-up schemes in 13 and price cuts in 11. Sales volumes increased moderately in all countries except Greece and Portugal, which experienced slight declines after 2009. Sales values decreased in both groups of countries, but fell more in less stable countries. Conclusion Less economically stable countries implemented more pharmaceutical policy changes during the recession than economically stable countries. Unexpectedly, pharmaceutical sales volumes increased in almost all countries, whereas sales values declined, especially in less stable countries. PMID:25378754

Optics-based compressibility parameter for pharmaceutical tablets obtained with the aid of the terahertz refractive index.

PubMed

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

2017-06-15

The objective of this study is to propose a novel optical compressibility parameter for porous pharmaceutical tablets. This parameter is defined with the aid of the effective refractive index of a tablet that is obtained from non-destructive and contactless terahertz (THz) time-delay transmission measurement. The optical compressibility parameter of two training sets of pharmaceutical tablets with a priori known porosity and mass fraction of a drug was investigated. Both pharmaceutical sets were compressed with one of the most commonly used excipients, namely microcrystalline cellulose (MCC) and drug Indomethacin. The optical compressibility clearly correlates with the skeletal bulk modulus determined by mercury porosimetry and the recently proposed terahertz lumped structural parameter calculated from terahertz measurements. This lumped structural parameter can be used to analyse the pattern of arrangement of excipient and drug particles in porous pharmaceutical tablets. Therefore, we propose that the optical compressibility can serve as a quality parameter of a pharmaceutical tablet corresponding with the skeletal bulk modulus of the porous tablet, which is related to structural arrangement of the powder particles in the tablet. Copyright © 2017 Elsevier B.V. All rights reserved.

Occurrence and in-stream attenuation of wastewater-derived pharmaceuticals in Iberian rivers.

PubMed

Acuña, Vicenç; von Schiller, Daniel; García-Galán, Maria Jesús; Rodríguez-Mozaz, Sara; Corominas, Lluís; Petrovic, Mira; Poch, Manel; Barceló, Damià; Sabater, Sergi

2015-01-15

A multitude of pharmaceuticals enter surface waters via discharges of wastewater treatment plants (WWTPs), and many raise environmental and health concerns. Chemical fate models predict their concentrations using estimates of mass loading, dilution and in-stream attenuation. However, current comprehension of the attenuation rates remains a limiting factor for predictive models. We assessed in-stream attenuation of 75 pharmaceuticals in 4 river segments, aiming to characterize in-stream attenuation variability among different pharmaceutical compounds, as well as among river segments differing in environmental conditions. Our study revealed that in-stream attenuation was highly variable among pharmaceuticals and river segments and that none of the considered pharmaceutical physicochemical and molecular properties proved to be relevant in determining the mean attenuation rates. Instead, the octanol-water partition coefficient (Kow) influenced the variability of rates among river segments, likely due to its effect on sorption to sediments and suspended particles, and therefore influencing the balance between the different attenuation mechanisms (biotransformation, photolysis, sorption, and volatilization). The magnitude of the measured attenuation rates urges scientists to consider them as important as dilution when aiming to predict concentrations in freshwater ecosystems. Copyright © 2014 Elsevier B.V. All rights reserved.

Investigation of pharmaceuticals in Missouri natural and drinking water using high performance liquid chromatography-tandem mass spectrometry.

PubMed

Wang, Chuan; Shi, Honglan; Adams, Craig D; Gamagedara, Sanjeewa; Stayton, Isaac; Timmons, Terry; Ma, Yinfa

2011-02-01

A comprehensive method has been developed and validated in two different water matrices for the analysis of 16 pharmaceutical compounds using solid phase extraction (SPE) of water samples, followed by liquid chromatography coupled with tandem mass spectrometry. These 16 compounds include antibiotics, hormones, analgesics, stimulants, antiepileptics, and X-ray contrast media. Method detection limits (MDLs) that were determined in both reagent water and municipal tap water ranged from 0.1 to 9.9 ng/L. Recoveries for most of the compounds were comparable to those obtained using U.S. EPA methods. Treated and untreated water samples were collected from 31 different water treatment facilities across Missouri, in both winter and summer seasons, and analyzed to assess the 16 pharmaceutical compounds. The results showed that the highest pharmaceutical concentrations in untreated water were caffeine, ibuprofen, and acetaminophen, at concentrations of 224, 77.2, and 70 ng/L, respectively. Concentrations of pharmaceuticals were generally higher during the winter months, as compared to those in the summer due, presumably, to smaller water quantities in the winter, even though pharmaceutical loadings into the receiving waters were similar for both seasons. © 2010 Elsevier Ltd. All rights reserved.

Development and Validation of Spectrofluorimetric Method for Determination of Biotin in Bulk and Pharmaceutical Preparations via its Oxidation with Cerium (IV)

PubMed Central

Walash, M. I.; Rizk, M.; Sheribah, Z. A.; Salim, M. M.

2010-01-01

A simple and sensitive spectrofluorimetric method was developed for the determination of biotin in pure form and in pharmaceutical preparations. The proposed method is based on the oxidation of the drug with cerium (IV) ammonium sulfate in acidic medium. The fluorescence of the produced Cerium (III) was measured at 365 nm after excitation at 255 nm. The different experimental parameters affecting the development and stability of the reaction were carefully studied and optimized. The method is applicable over the concentration range of 30-120 ng/mL with correlation coefficient of 0.9998. The detection limit (LOD) of biotin was 2.41 ng/mL while quantitation limit (LOQ) was 7.29 ng/mL. The proposed procedure was successfully applied for the determination of biotin in pharmaceutical preparations with mean recoveries of 99.55 ± 0.83 and 101.67 ± 1.53 for biotin ampoules and capsules, respectively. The results obtained were in good agreement with those obtained using the official method. PMID:23675202

Sensitive spectrofluorimetric determination of tizanidine in pharmaceutical preparations, human plasma and urine through derivatization with dansyl chloride.

PubMed

Ulu, Sevgi Tatar

2012-01-01

A sensitive spectrofluorimetric method was developed for the determination of tizanidine in human plasma, urine and pharmaceutical preparations. The method is based on reaction of tizanidine with 1-dimethylaminonaphthalene-5-sulphonyl chloride (dansyl chloride) in an alkaline medium to form a highly fluorescent derivative that was measured at 511 nm after excitation at 383 nm. The different experimental parameters affecting the fluorescence intensity of tizanidine was carefully studied and optimized. The fluorescence-concentration plots were rectilinear over the ranges 50-500 and 20-300 ng/mL for plasma and urine, respectively, detection limits of 1.81 and 0.54 ng/mL and quantification limits of 5.43 and 1.62 ng/mL for plasma and urine, respectively. The method presents good performance in terms of linearity, detection and quantification limits, precision, accuracy and specificity. The proposed method was successfully applied for the determination of tizanidine in pharmaceutical preparations. The results obtained were compared with a reference method, using t- and F-tests. Copyright © 2011 John Wiley & Sons, Ltd.

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

PubMed Central

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

2011-01-01

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

Development of a Simple RP-HPLC-UV Method for Determination of Azithromycin in Bulk and Pharmaceutical Dosage forms as an Alternative to the USP Method

PubMed Central

Ghari, Tayebeh; Kobarfard, Farzad; Mortazavi, Seyed Alireza

2013-01-01

The present study was designed to develop a simple, validated liquid chromatographic method for the analysis of azithromycin in bulk and pharmaceutical dosage forms using ultraviolet detector. The best stationary phase was determined as C18 column, 5 μm, 250 mm × 4.6 mm. Mobile phase was optimized to obtain a fast and selective separation of the drug. Flow rate was 1.5 mL/min, Wavelength was set at 210 nm and the volume of each injection was 500 μL. An isocratic methanol/buffer mobile phase at the ratio of 90:10 v/v gave the best separation and resolution. The proposed method was accurate, precise, sensitive, and linear over a wide range of concentration of azithromycin. The developed method has the advantage of using UV detector compared to the USP method in which electrochemical detector has been used. The validated method was successfully applied to the determination of azithromycin in bulk and pharmaceutical dosage forms. PMID:24250672

Comparative Validation of the Determination of Sofosbuvir in Pharmaceuticals by Several Inexpensive Ecofriendly Chromatographic, Electrophoretic, and Spectrophotometric Methods.

PubMed

El-Yazbi, Amira F

2017-01-20

Sofosbuvir (SOFO) was approved by the U.S. Food and Drug Administration in 2013 for the treatment of hepatitis C virusinfection with enhanced antiviral potency compared with earlier analogs. Notwithstanding, all current editions of the pharmacopeias still do not present any analytical methods for the quantification of SOFO. Thus, rapid, simple, and ecofriendly methods for the routine analysis of commercial formulations of SOFO are desirable. In this study, five accurate methods for the determination of SOFO in pharmaceutical tablets were developed and validated. These methods include HPLC, capillary zone electrophoresis, HPTLC, and UV spectrophotometric and derivative spectrometry methods. The proposed methods proved to be rapid, simple, sensitive, selective, and accurate analytical procedures that were suitable for the reliable determination of SOFO in pharmaceutical tablets. An analysis of variance test with <em>P</em>-value &#x003E; 0.05 confirmed that there were no significant differences between the proposed assays. Thus, any of these methods can be used for the routine analysis of SOFO in commercial tablets.

Derivative spectrophotometry for the determination of faropenem in the presence of degradation products: an application for kinetic studies.

PubMed

Cielecka-Piontek, Judyta

2013-07-01

A simple and selective derivative spectrophotometric method was developed for the quantitative determination of faropenem in pure form and in pharmaceutical dosage. The method is based on the zero-crossing effect of first-derivative spectrophotometry (λ = 324 nm), which eliminates the overlapping effect caused by the excipients present in the pharmaceutical preparation, as well as degradation products, formed during hydrolysis, oxidation, photolysis, and thermolysis. The method was linear in the concentration range 2.5-300 μg/mL (r = 0.9989) at λ = 341 nm; the limits of detection and quantitation were 0.16 and 0.46 μg/mL, respectively. The method had good precision (relative standard deviation from 0.68 to 2.13%). Recovery of faropenem ranged from 97.9 to 101.3%. The first-order rate constants of the degradation of faropenem in pure form and in pharmaceutical dosage were determined by using first-derivative spectrophotometry. A statistical comparison of the validation results and the observed rate constants for faropenem degradation with these obtained with the high-performance liquid chromatography method demonstrated that both were compatible.

Environmental risk analysis and prioritization of pharmaceuticals in a developing world context.

PubMed

Mansour, Fatima; Al-Hindi, Mahmoud; Saad, Walid; Salam, Darine

2016-07-01

The impact of residual pharmaceuticals on the aquatic environment has gained widespread attention over the past years. Various studies have established the occurrence of pharmaceutical compounds in different water bodies throughout the world. In view of the absence of occurrence data in a number of developing world countries, and given the limited availability of analytical resources in these countries, it is prudent to devise methodologies to prioritize pharmaceuticals for environmental monitoring purposes that are site specific. In this work, several prioritization approaches are used to rank the 88 most commonly consumed pharmaceuticals in Lebanon. A simultaneous multi-criteria decision analysis method utilizing the exposure, persistence, bioaccumulation, and toxicity (EPBT) approach is applied to a smaller subset of the original list (69 pharmaceuticals). Several base cases are investigated and sensitivity analysis is applied to one of these base case runs. The similarities and differences in the overall ranking of individual, and classes of, pharmaceuticals for the base cases and the sensitivity runs are elucidated. An environmental risk assessment (ERA), where predicted environmental concentrations (PEC) and risk quotients (RQ) are determined at different dilution factors, is performed as an alternative method of prioritization for a total of 84 pharmaceuticals. The ERA results indicate that metformin and amoxicillin have the highest PECs while 17β-estradiol, naftidrofuryl and dimenhydrinate have the highest RQs. The two approaches, EPBT prioritization and ERA, are compared and a priority list consisting of 26 pharmaceuticals of various classes is developed. Nervous system and alimentary tract and metabolism pharmaceuticals (9/26 and 5/26 respectively) constitute more than half of the numbers on the priority list with the balance consisting of anti-infective (4/26), musculo-skeletal (3/26), genito-urinary (2/26), respiratory (2/26) and cardiovascular (1/26) pharmaceuticals. This list will serve as a basis for the selection of candidate compounds to focus on for future monitoring campaigns. Copyright © 2016 Elsevier B.V. All rights reserved.

"But doctors do it...": nurses' views of gifts and information from the pharmaceutical industry.

PubMed

Jutel, Annemarie; Menkes, David B

2009-06-01

Most nurses, like their physician counterparts, lack education regarding pharmaceutical marketing strategies, and little is known of their beliefs and practices regarding this industry. Nurses are increasingly targeted by pharmaceutical companies as they become more involved in prescription and as policies restrict pharmaceutical companies' contact with physicians. To assess nurses' beliefs and reported practices concerning pharmaceutical marketing and sponsorship strategies. We conducted parallel Web- and paper-based surveys of a sample of senior registered nurses employed by government-funded health boards in 2 regions of New Zealand to explore their contact with the pharmaceutical industry as well as their beliefs and practices regarding information, gifts, and sponsorship provided by pharmaceutical companies. Returns were tested using Fisher's exact test to determine consistency in response between regions. Results for key outcome variables, including attitude toward the value of industry-derived information, were analyzed by region and in aggregate. Most nurses had contact with pharmaceutical sales representatives (69/106), accepted gifts from representatives (79/105), and believed information from the pharmaceutical industry probably improved their practice (71/106). Half believed that they would be able to detect misleading information if it were present, and 35% believed that accepting gifts and sponsorship was ethically acceptable. We found positive associations between the belief that information from the industry improved practice and reported acceptance of conference funding (OR 3.63; 95% CI 1.41 to 11.55), free food (OR 3.24; 95% CI 2.03 to 7.55), or gifts (OR 3.52; 95% CI 1.38 to 8.95). Nurses generally acknowledge the presence of pharmaceutical marketing in the hospital and the ethical challenges it presents; nonetheless, they also generally accept marketing gifts and may underestimate both the ethical challenges and their own susceptibility to persuasion. Given the increasing role that nurses may play in pharmaceutical marketing strategy, the profession should consider its position vis-à-vis the industry.

A Robust Static Headspace GC-FID Method to Detect and Quantify Formaldehyde Impurity in Pharmaceutical Excipients

PubMed Central

Al-Khayat, Mohammad Ammar; Karabet, Francois; Al-Mardini, Mohammad Amer

2018-01-01

Formaldehyde is a highly reactive impurity that can be found in many pharmaceutical excipients. Trace levels of this impurity may affect drug product stability, safety, efficacy, and performance. A static headspace gas chromatographic method was developed and validated to determine formaldehyde in pharmaceutical excipients after an effective derivatization procedure using acidified ethanol. Diethoxymethane, the derivative of formaldehyde, was then directly analyzed by GC-FID. Despite the simplicity of the developed method, however, it is characterized by its specificity, accuracy, and precision. The limits of detection and quantification of formaldehyde in the samples were of 2.44 and 8.12 µg/g, respectively. This method is characterized by using simple and economic GC-FID technique instead of MS detection, and it is successfully used to analyze formaldehyde in commonly used pharmaceutical excipients. PMID:29686930

[Correlation of bacteria in the contaminated drug and the environmental microbes in the clean room for pharmaceutical microbial test investigated by FTIR].

PubMed

Pei, Lin; Hu, Chang-qin; Ma, Shi-hong; Dai, Hui; Hang, Tai-jun

2007-11-01

The FTIR method was used to investigate the correlation of bacteria in the contaminated drug and the environmental microbes in the clean room for pharmaceutical microbial test. The similarity of bacteria in the contaminated drug and environmental microbes was compared by critical hit value method and cluster analysis method. This constructed the FTIR spectra library of clean room environmental microbe, and determined the criterion to promptly judge if the bacteria isolated from pharmaceuticals were contaminated by environment or not, hence the exactness of "one-off report" of sterile test result can be guaranteed, and can be used for the dynamic monitoring of environmental bacteria of clean room. The method is proven to be simple, accurate and rapid, and can be easily spread to the pharmaceutical microbial control.

Microscale chemistry-based design of eco-friendly, reagent-saving and efficient pharmaceutical analysis: a miniaturized Volhard's titration for the assay of sodium chloride.

PubMed

Rojanarata, Theerasak; Sumran, Krissadecha; Nateetaweewat, Paksupang; Winotapun, Weerapath; Sukpisit, Sirarat; Opanasopit, Praneet; Ngawhirunpat, Tanasait

2011-09-15

This work demonstrates the extended application of microscale chemistry which has been used in the educational discipline to the real analytical purposes. Using Volhard's titration for the determination of sodium chloride as a paradigm, the reaction was downscaled to less than 2 mL conducted in commercially available microcentrifuge tubes and using micropipettes for the measurement and transfer of reagents. The equivalence point was determined spectrophotometrically on the microplates which quickened the multi-sample measurements. After the validation and evaluation with bulk and dosage forms, the downsized method showed good accuracy comparable to the British Pharmacopeial macroscale method and gave satisfactory precision (intra-day, inter-day, inter-analyst and inter-equipment) with the relative standard deviation of less than 0.5%. Interestingly, the amount of nitric acid, silver nitrate, ferric alum and ammonium thiocyanate consumed in the miniaturized titration was reduced by the factors of 25, 50, 50 and 215 times, respectively. The use of environmentally dangerous dibutyl phthalate was absolutely eliminated in the proposed method. Furthermore, the release of solid waste silver chloride was drastically reduced by about 25 folds. Therefore, microscale chemistry is an attractive, facile and powerful green strategy for the development of eco-friendly, safe, and cost-effective analytical methods suitable for a sustainable environment. Copyright © 2011 Elsevier B.V. All rights reserved.

Antioxidant activity profiling by spectrophotometric methods of aqueous methanolic extracts of Helichrysum stoechas subsp. rupestre and Phagnalon saxatile subsp. saxatile.

PubMed

Haddouchi, Farah; Chaouche, Tarik Mohammed; Ksouri, Riadh; Medini, Faten; Sekkal, Fatima Zohra; Benmansour, Abdelhafid

2014-06-01

The aqueous methanolic extracts of two plants from Algeria, Helichrysum stoechas subsp. rupestre and Phagnalon saxatile subsp. saxatile, were investigated for their antioxidant activity. Total phenolics, flavonoids, and tannins were determined by spectrophotometric techniques. In vitro antioxidant and radical scavenging profiling was determined by spectrophotometric methods, through: Total antioxidant capacity, and radical scavenging effects by the DPPH and ABTS methods, reducing and chelating power, and blanching inhibition of the β-carotene. All of the extracts showed interesting antioxidant and radical scavenging activity. The highest contents in phenolics, tannins, and the highest total antioxidant capacity as gallic acid equivalents of 97.5 ± 0.33 mg GAE/g DW was obtained for the flowers of H. stoechas subsp. rupestre extract in the phosphomolybdenum assay. An extract of the leafy stems of P. saxatile subsp. saxatile revealed the highest content of flavonoids, and the highest antioxidant activity by the radical scavenging and β-carotene assays when compared with standards. The best activity was by the scavenging radical DPPH with an IC50 value of 5.65 ± 0.10 μg·mL(-1). The studied medicinal plants could provide scientific evidence for some traditional uses in the treatment of diseases related to the production of reactive oxygen species (ROS) and oxidative stress. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

A validated spectrofluorimetric method for the determination of citalopram in bulk and pharmaceutical preparations based on the measurement of the silver nanoparticles-enhanced fluorescence of citalopram/terbium complexes.

PubMed

Khan, Muhammad Naeem; Shah, Jasmin; Jan, Muhammad Rasul; Lee, Sang Hak

2013-01-01

A simple, sensitive, and accurate spectrofluorimetric method was developed for the determination of citalopram in bulk and pharmaceutical preparations. The method is based on the enhancement of the weak fluorescence signal (FL) of the Tb (III)-citalopram system in the presence of silver nanoparticles. Fluorescence intensities were measured at 555 nm after excitation at 281 nm. Prepared silver nanoparticles (AgNPs) were characterized by UV-Visible spectra and transmission electron microscopy (TEM). Various factors affecting the formation of citalopram-Tb (III)-AgNPs complexes were studied and optimized. The fluorescence intensity versus concentration plot was linear over the range 0.02-14 μg mL(-1), with an excellent correlation coefficient of 0.9978. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 7.15 × 10(-6) μg mL(-1) and 2.38 × 10(-5) μg mL(-1) respectively. The proposed method was found to have good reproducibility with a relative standard deviation of 3.66% (n = 6). The interference effects of common excipients found in pharmaceutical preparations were studied. The developed method was validated statistically by performing recoveries studies and successfully applied for the assay of citalopram in bulk powder and pharmaceutical preparations. Percent recoveries were found to range from 98.98% to 100.97% for bulk powder and from 96.57% to 101.77% for pharmaceutical preparations.

Persistence and partitioning of eight selected pharmaceuticals in the aquatic environment: laboratory photolysis, biodegradation, and sorption experiments.

PubMed

Yamamoto, Hiroshi; Nakamura, Yudai; Moriguchi, Shigemi; Nakamura, Yuki; Honda, Yuta; Tamura, Ikumi; Hirata, Yoshiko; Hayashi, Akihide; Sekizawa, Jun

2009-02-01

We selected eight pharmaceuticals with relatively high potential ecological risk and high consumption-namely, acetaminophen, atenolol, carbamazepine, ibuprofen, ifenprodil, indomethacin, mefenamic acid, and propranolol-and conducted laboratory experiments to examine the persistence and partitioning of these compounds in the aquatic environment. In the results of batch sunlight photolysis experiments, three out of eight pharmaceuticals-propranolol, indomethacin, and ifenprodil-were relatively easily photodegraded (i.e., half-life<24h), whereas the other five pharmaceuticals were relatively stable against sunlight. The results of batch biodegradation experiments using river water suggested relatively slow biodegradation (i.e., half-life>24h) for all eight pharmaceuticals, but the rate constant was dependent on sampling site and time. Batch sorption experiments were also conducted to determine the sorption coefficients to river sediments and a model soil sample. The determined coefficients (K(d) values) were much higher for three amines (atenolol, ifenprodil, and propranolol) than for neutral compounds or carboxylic acids; the K(d) values of the amines were comparable to those of a four-ring polycyclic aromatic hydrocarbon (PAH) pyrene. The coefficients were also higher for sediment/soil with higher organic content, and the organic carbon-based sorption coefficient (logK(oc)) showed a poor linear correlation with the octanol-water distribution coefficient (logD(ow)) at neutral pH. These results suggest other sorption mechanisms-such as electrochemical affinity, in addition to hydrophobic interaction-play an important role in sorption to sediment/soil at neutral pH.

Quantitative determination of radio-opacity: equivalence of digital and film X-ray systems.

PubMed

Nomoto, R; Mishima, A; Kobayashi, K; McCabe, J F; Darvell, B W; Watts, D C; Momoi, Y; Hirano, S

2008-01-01

To evaluate the equivalence of a digital X-ray system (DenOptix) to conventional X-ray film in terms of the measured radio-opacity of known filled-resin materials and the suitability of attenuation coefficient for radio-opacity determination. Discs of five thicknesses (0.5-2.5mm) and step-wedges of each of three composite materials of nominal aluminum-equivalence of 50%, 200% and 450% were used. X-ray images of a set of discs (or step-wedge), an aluminum step-wedge, and a lead block were taken at 65 kV and 10 mA at a focus-film distance of 400 mm for 0.15s and 1.6s using an X-ray film or imaging plate. Radio-opacity was determined as equivalent aluminum thickness and attenuation coefficient. The logarithm of the individual optical density or gray scale value, corrected for background, was plotted against thickness, and the attenuation coefficient determined from the slope. The method of ISO 4049 was used for equivalent aluminum thickness. The equivalent aluminum thickness method is not suitable for materials of low radio-opacity, while the attenuation coefficient method could be used for all without difficulty. The digital system gave attenuation coefficients of greater precision than did film, but the use of automatic gain control (AGC) distorted the outcome unusably. Attenuation coefficient is a more precise and generally applicable approach to the determination of radio-opacity. The digital system was equivalent to film but with less noise. The use of AGC is inappropriate for such determinations.

Occurrence and fate of select psychoactive pharmaceuticals and antihypertensives in two wastewater treatment plants in New York State, USA.

PubMed

Subedi, Bikram; Kannan, Kurunthachalam

2015-05-01

The fates of psychoactive pharmaceuticals, including two antischizophrenics, six sedative-hypnotic-anxiolytics, four antidepressants, four antihypertensives, and their select metabolites, were determined in two wastewater treatment plants (WWTPs) in the Albany area of New York. All target psychoactive pharmaceuticals and their metabolites were found at a mean concentration that ranged from 0.98 (quetiapine) to 1220 ng/L (atenolol) in wastewater and from 0.26 (lorazepam) to 1490 ng/g dry weight (sertraline) in sludge. In this study, the fraction of psychoactive pharmaceuticals that was sorbed to suspended particulate matter (SPM) was calculated for the first time. Over 50% of the total mass of aripiprazole, norquetiapine, norsertraline, citalopram, desmethyl citalopram, propranolol, verapamil, and norverapamil was found sorbed to SPM in the influent. The mass loadings, i.e., influx, of target psychoactive pharmaceuticals in WWTPs ranged from 0.91 (diazepam) to 347 mg/d/1000 inhabitants (atenolol), whereas the environmental emissions ranged from 0.01 (dehydro-aripiprazole) to 316 mg/d/1000 inhabitants (atenolol). The highest calculated removal efficiencies were found for antischizophrenics (quetiapine=88%; aripiprazole=71%). However, the removal of some psychoactive pharmaceuticals through adsorption onto sludge was minimal (<1% of the initial mass load), which suggests that bio-degradation and/or chemical-transformation are the dominant mechanisms of removal of these pharmaceuticals in WWTPs. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

Lewen, Nancy

2011-06-25

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

A novel approach for inventory problem in the pharmaceutical supply chain.

PubMed

Candan, Gökçe; Yazgan, Harun Reşit

2016-02-24

In pharmaceutical enterprises, keeping up with global market conditions is possible with properly selected supply chain management policies. Generally; demand-driven classical supply chain model is used in the pharmaceutical industry. In this study, a new mathematical model is developed to solve an inventory problem in the pharmaceutical supply chain. Unlike the studies in literature, the "shelf life and product transition times" constraints are considered, simultaneously, first time in the pharmaceutical production inventory problem. The problem is formulated as a mixed-integer linear programming (MILP) model with a hybrid time representation. The objective is to maximize total net profit. Effectiveness of the proposed model is illustrated considering a classical and a vendor managed inventory (VMI) supply chain on an experimental study. To show the effectiveness of the model, an experimental study is performed; which contains 2 different supply chain policy (Classical and VMI), 24 and 30 months planning horizon, 10 and 15 different cephalosporin products. Finally the mathematical model is compared to another model in literature and the results show that proposed model is superior. This study suggest a novel approach for solving pharmaceutical inventory problem. The developed model is maximizing total net profit while determining optimal production plan under shelf life and product transition constraints in the pharmaceutical industry. And we believe that the proposed model is much more closed to real life unlike the other studies in literature.

Illicit Internet availability of drugs subject to recall and patient safety consequences.

PubMed

Mackey, Tim K; Aung, Phyo; Liang, Bryan A

2015-12-01

Permanently recalled drugs are a public health concern if they remain accessible in violation of applicable regulation. Illicit online pharmacies act as an alternative form of access and have been associated with the sale to patients of counterfeit/falsified/fraudulent/substandard drugs. We wished to determine if permanently recalled and significantly restricted drugs were illegally marketed for sale online. The study was conducted in two phases with two objectives. The first phase attempted to identify drugs subject to permanent recall in certain major pharmaceutical markets as well as those listed as recalled or significantly restricted by the United Nations. We also examined the market authorization status of identified drugs in China and India. The second phase used structured searches on the Internet to determine if identified drugs were marketed for sale online. The World Wide Web. After identification of permanently recalled and restricted drugs we conducted Internet searches for illegal "no prescription" marketing events. We assessed the form of marketing, whether a site offered direct-to-patient sale, use of social media marketing, and the site's compliance status with external monitoring bodies. Number of recalled drugs marketed as available for purchase on the Internet. We identified 16 class I equivalent permanently recalled or restricted drugs, 56.3 % (n = 9) of which maintained market authorization in either China or India. Half (n = 8) were marketed for sale online without a prescription direct-to-patient. Use of social media marketing was mixed, with only 18.8 % (n = 3) of recalled drugs having a presence on Facebook, though 50.0 % (n = 8) had content on Twitter. We also found the majority (68.8 %, n = 11) were available and marketed for sale by vendors on the wholesale/business-to-business website alibaba.com primarily as active pharmaceutical ingredient. Despite efforts in several countries to restrict access to these drugs or permanently remove them from the market, our study indicates that various sources actively market recalled drugs for sale online. Drug regulators, public health agencies, and law enforcement officials should act with urgency to appropriately restrict and regulate these sales to protect global patients and consumers.

Aerodynamic particle size analysis of aerosols from pressurized metered-dose inhalers: comparison of Andersen 8-stage cascade impactor, next generation pharmaceutical impactor, and model 3321 Aerodynamic Particle Sizer aerosol spectrometer.

PubMed

Mitchell, Jolyon P; Nagel, Mark W; Wiersema, Kimberly J; Doyle, Cathy C

2003-10-22

The purpose of this research was to compare three different methods for the aerodynamic assessment of (1) chloroflurocarbon (CFC)--fluticasone propionate (Flovent), (2) CFC-sodium cromoglycate (Intal), and (3) hydrofluoroalkane (HFA)--beclomethasone dipropionate (Qvar) delivered by pressurized metered dose inhaler. Particle size distributions were compared determining mass median aerodynamic diameter (MMAD), geometric standard deviation (GSD), and fine particle fraction <4.7 microm aerodynamic diameter (FPF(<4.7 microm)). Next Generation Pharmaceutical Impactor (NGI)-size distributions for Flovent comprised finer particles than determined by Andersen 8-stage impactor (ACI) (MMAD = 2.0 +/- 0.05 micro m [NGI]; 2.8 +/- 0.07 microm [ACI]); however, FPF(<4.7 microm) by both impactors was in the narrow range 88% to 93%. Size distribution agreement for Intal was better (MMAD = 4.3 +/- 0.19 microm (NGI), 4.2 +/- 0.13 microm (ACI), with FPF(<4.7 microm) ranging from 52% to 60%. The Aerodynamic Particle Sizer (APS) undersized aerosols produced with either formulation (MMAD = 1.8 +/- 0.07 micro m and 3.2 +/- 0.02 micro m for Flovent and Intal, respectively), but values of FPF(<4.7 microm)from the single-stage impactor (SSI) located at the inlet to the APS (82.9% +/- 2.1% [Flovent], 46.4% +/- 2.4% [Intal]) were fairly close to corresponding data from the multi-stage impactors. APS-measured size distributions for Qvar (MMAD = 1.0 +/- 0.03 micro m; FPF(<4.7 micro m)= 96.4% +/- 2.5%), were in fair agreement with both NGI (MMAD = 0.9 +/- 0.03 micro m; FPF(<4.7 microm)= 96.7% +/- 0.7%), and ACI (MMAD = 1.2 +/- 0.02 microm, FPF(<4.7 microm)= 98% +/- 0.5%), but FPF(<4.7 microm) from the SSI (67.1% +/- 4.1%) was lower than expected, based on equivalent data obtained by the other techniques. Particle bounce, incomplete evaporation of volatile constituents and the presence of surfactant particles are factors that may be responsible for discrepancies between the techniques.

N-glycosylation of plant recombinant pharmaceuticals.

PubMed

Bardor, Muriel; Cabrera, Gleysin; Stadlmann, Johannes; Lerouge, Patrice; Cremata, José A; Gomord, Véronique; Fitchette, Anne-Catherine

2009-01-01

N-glycosylation is a maturation event necessary for the correct function, efficiency, and stability of a high number of biopharmaceuticals. This chapter presented here proposes various methods to determine whether, how, and where a plant pharmaceutical is N-glycosylated. These methods rely on blot detection with glycan-specific probes, specific deglycosylation of glycoproteins followed by mass spectrometry, N-glycan profile analysis, and glycopeptide identification by LC-MS.

Teva Pharmaceuticals v. Sandoz: availability of generic glatiramer acetate and the impact to patent litigation claim construction.

PubMed

Fogel, Louis E; Ray, Chad J

2015-01-01

In the upcoming case of Teva Pharmaceuticals v. Sandoz, the U.S. Supreme Court will address how much deference the appellate court should afford to a trial court's claim construction ruling. The effect of this decision will be far-reaching, as how claims are construed can determine whether a patent is infringed or not infringed, valid or invalid.

The availability of references and the sponsorship of original research cited in pharmaceutical advertisements

PubMed Central

Cooper, Richelle J.; Schriger, David L.

2005-01-01

Background The primary goal of pharmaceutical advertisements is to convince physicians to prescribe the manufacturer's product. We sought to determine what materials are cited in support of claims in pharmaceutical ads and medical research articles, and whether health care professionals seeking to verify the claims could obtain these references. Methods We reviewed 438 unique ads from the 1999 issues of 10 American medical journals, and a random sample of 400 references in medical research articles selected from the same journals. We classified references as journal article, data on file, meeting abstract or presentation, book or monograph, marketing report, prescribing information, government document or Internet site. We attempted to confirm or obtain each reference through library and Internet searches or by direct request from the manufacturer. The main outcome we sought to determine was the availability of the reference to a clinician. We also ascertained the source of funding for original research cited in the ads and the research articles. Results In the 438 ads with medical claims, 126 contained no references and 312 contained 721 unique references. Of these ad references, 55% (396/721) cited journal articles and 19% (135/721) cited data on file. In contrast, in the sample of research article references, 88% (351/400) cited journal articles and 8% (33/400) cited books. Overall, 84% of the citations from the ads were available: 98% of journal articles, 86% of books, 71% of meeting abstracts or presentations and 20% of data-on-file references. In all, 99% of the sample of research article references were available. We determined that 58% of the original research cited in the pharmaceutical ads was sponsored by or had an author affiliated with the product's manufacturer, as compared with 8% of the articles cited in the research articles. Interpretation Many pharmaceutical ads contain no references for medical claims. Although references to journal articles were usually obtainable, other published sources were not as easily acquired. The majority of unpublished data-on-file references were not available, and the majority of original research cited to substantiate claims in the pharmaceutical ads was funded by or had authors affiliated with the product's manufacturer. PMID:15710940

The availability of references and the sponsorship of original research cited in pharmaceutical advertisements.

PubMed

Cooper, Richelle J; Schriger, David L

2005-02-15

The primary goal of pharmaceutical advertisements is to convince physicians to prescribe the manufacturer's product. We sought to determine what materials are cited in support of claims in pharmaceutical ads and medical research articles, and whether health care professionals seeking to verify the claims could obtain these references. We reviewed 438 unique ads from the 1999 issues of 10 American medical journals, and a random sample of 400 references in medical research articles selected from the same journals. We classified references as journal article, data on file, meeting abstract or presentation, book or monograph, marketing report, prescribing information, government document or Internet site. We attempted to confirm or obtain each reference through library and Internet searches or by direct request from the manufacturer. The main outcome we sought to determine was the availability of the reference to a clinician. We also ascertained the source of funding for original research cited in the ads and the research articles. In the 438 ads with medical claims, 126 contained no references and 312 contained 721 unique references. Of these ad references, 55% (396/721) cited journal articles and 19% (135/721) cited data on file. In contrast, in the sample of research article references, 88% (351/400) cited journal articles and 8% (33/400) cited books. Overall, 84% of the citations from the ads were available: 98% of journal articles, 86% of books, 71% of meeting abstracts or presentations and 20% of data-on-file references. In all, 99% of the sample of research article references were available. We determined that 58% of the original research cited in the pharmaceutical ads was sponsored by or had an author affiliated with the product's manufacturer, as compared with 8% of the articles cited in the research articles. Many pharmaceutical ads contain no references for medical claims. Although references to journal articles were usually obtainable, other published sources were not as easily acquired. The majority of unpublished data-on-file references were not available, and the majority of original research cited to substantiate claims in the pharmaceutical ads was funded by or had authors affiliated with the product's manufacturer.

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

PubMed

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

2016-11-01

In many coastal watersheds and ecosystems, rivers discharging to estuaries receive waters from domestic wastewater-treatment plants resulting in the release and distribution of pharmaceuticals to the marine environment. In the present study, 15 active pharmaceutical ingredients were measured regularly over 1 yr in the dissolved and particulate phases as they entered Narragansett Bay from the Pawtuxet River in Cranston (Rhode Island, USA). Of the active pharmaceutical ingredients measured, 14 were consistently present in the dissolved phase, with concentrations ranging from below detection to >310 ng/L, whereas 8 were present in the particulate phase (0.2-18 ng/g). Partition coefficients (K d s and K OC s) were determined, and organic carbon normalization reduced variability associated with K d s for the active pharmaceutical ingredients evaluated. Flux estimates based on river flow were calculated for both dissolved and particulate-phase active pharmaceutical ingredients, with particulate fluxes being low (1-12 g/yr) and dissolved fluxes of active pharmaceutical ingredients being 155 g/yr to 11 600 g/yr. Results indicate that the pharmaceuticals measured in the present study reside primarily in the dissolved phase and thus are likely bioavailable on entering the estuarine waters of Narragansett Bay. This long-term temporal study provides important information on seasonal and annual dynamics of pharmaceuticals in an urban estuarine watershed. Environ Toxicol Chem 2016;35:2665-2673. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US Government work and, as such, is in the public domain in the United States of America. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US Government work and, as such, is in the public domain in the United States of America.

Unlicensed pharmaceutical preparations for clinical patient care: Ensuring safety.

PubMed

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

2018-01-01

Most medicinal products dispensed to patients have marketing authorization (MA) to ensure high quality of the product, safety, and efficacy. However, in daily practice, to treat patients adequately, there is a medical need for drugs that do not hold MA. To meet this medical need, medicinal products are used in clinical care without MA (unlicensed), such as products prepared by (local) pharmacies: the pharmaceutical preparations. Three types of pharmaceutical preparations are distinguished: (i) reconstitution in excess of summary of product characteristics; (ii) adaptation of a licensed medicinal product (outside its official labeling); (iii) medicinal products from an active pharmaceutical ingredient. Although unlicensed, patients may expect the same quality for these unlicensed pharmaceutical preparations as for the licensed medicinal products. To assure this quality, a proper risk-benefit assessment and proper documentation in (centralized) patient registries and linking to a national pharmacovigilance database should be in place. Based on a risk assessment matrix, requirements for quality assurance can be determined, which has impact on the level of documentation of a pharmaceutical preparation. In this paper, the approach for good documentation including quality assurance and benefit-risk assessment will be discussed and possibilities for patient registries are described to make these crucial preparations available for regular patient care. KEY POINTS Ensuring pharmaceutical quality and performing a proper benefit-risk assessment will guarantee safe use of pharmaceutical preparations. Good documentation of (ultra-)orphan treatments can be collected in centralized patient registries and should be combined with existing information in (inter)national databases and self-reflection of patients. Linking patient registries to a centralized database for adverse drug events is highly recommended as it increases safety control of the (ultra) orphan pharmaceutical preparations. Copyright © 2017 John Wiley & Sons, Ltd.

Effect of educational interventions and medical school policies on medical students' attitudes toward pharmaceutical marketing practices: a multi-institutional study.

PubMed

Kao, Audiey C; Braddock, Clarence; Clay, Maria; Elliott, Donna; Epstein, Scott K; Filstead, William; Hotze, Tim; May, Win; Reenan, Jennifer

2011-11-01

To determine the effect of educational interventions on medical students' attitudes toward pharmaceutical industry marketing practices and whether restrictive medical school policies governing medicine-industry interactions are associated with student support for banning such interactions. Prospective cohort study involving the graduating classes of 2009 (intervention, n=474) and 2010 (control, n=459) at four U.S. medical schools. Intervention students experienced a former pharmaceutical representative's presentation, faculty debate, and a Web-based course. Both groups completed baseline and follow-up attitude surveys about pharmaceutical marketing. A total of 482 students (51.6%) completed both surveys. In regression analyses, intervention students were more likely than control students to think that physicians are strongly or moderately influenced by pharmaceutical marketing (OR, 2.29; 95% CI, 1.46-3.59) and believed they would be more likely to prescribe a company's drug if they accepted that company's gifts and food (OR, 1.68; 95% CI, 1.12-2.52). Intervention students were more likely to support banning interactions between pharmaceutical representatives and students (OR, 4.82; 95% CI, 3.02-7.68) and with physicians (OR, 6.88; 95% CI, 4.04-11.70). Students from schools with more restrictive policies were more likely to support banning interactions between pharmaceutical representatives and students (OR, 1.99; 95% CI, 1.26-3.16) and with physicians (OR, 3.44; 95% CI, 2.05-5.79). Education about pharmaceutical marketing practices and more restrictive policies governing medicine-industry interactions seem to increase medical students' skepticism about the appropriateness of such marketing practices and disapproval of pharmaceutical representatives in the learning environment.

Sucrose diffusion in aqueous solution

PubMed Central

Murray, Benjamin J.

2016-01-01

The diffusion of sugar in aqueous solution is important both in nature and in technological applications, yet measurements of diffusion coefficients at low water content are scarce. We report directly measured sucrose diffusion coefficients in aqueous solution. Our technique utilises a Raman isotope tracer method to monitor the diffusion of non-deuterated and deuterated sucrose across a boundary between the two aqueous solutions. At a water activity of 0.4 (equivalent to 90 wt% sucrose) at room temperature, the diffusion coefficient of sucrose was determined to be approximately four orders of magnitude smaller than that of water in the same material. Using literature viscosity data, we show that, although inappropriate for the prediction of water diffusion, the Stokes–Einstein equation works well for predicting sucrose diffusion under the conditions studied. As well as providing information of importance to the fundamental understanding of diffusion in binary solutions, these data have technological, pharmaceutical and medical implications, for example in cryopreservation. Moreover, in the atmosphere, slow organic diffusion may have important implications for aerosol growth, chemistry and evaporation, where processes may be limited by the inability of a molecule to diffuse between the bulk and the surface of a particle. PMID:27364512

Antioxidant properties and inhibitory effects of Satureja khozestanica essential oil on LDL oxidation induced-CuSO4 in vitro

PubMed Central

Bagheri, Shahrokh; Ahmadvand, Hassan; Khosrowbeygi, Ali; Ghazanfari, Farshid; Jafari, Narges; Nazem, Habibolah; Hosseini, Reza Haji

2013-01-01

Objective To assess various antioxidative activities of Satureja khozestanica essential oil (SKE) and its effect on oxidation of low density lipoprotein (LDL) induced by CuSO4 in vitro by monitoring the formation of conjugated dienes and malondialdehyde (MDA). Methods The formation of conjugated dienes, lag time and MDA were measured. Inhibition of this Cu-induced oxidation was studied in the presence of several concentrations of SKE. Also total antioxidant activity and free radical scavenging of SKE were determinated. Results It was demonstrated that SKE was able to inhibit LDL oxidation and decrease the resistance of LDL against oxidation. The inhibitory effects of SKE on LDL oxidation were dose-dependent at concentrations ranging from 50 to 200 µg/mL. Total antioxidant capacity of SKE was (3.20±0.40) nmol of ascorbic acid equivalents/g SKE. The SKE showed remarkable scavenging activity on 2, 2-diphenyl-picrylhydrazyl, IC50 (5.30±0.11) ng/mL. Conclusions This study shows that SKE is a source of potent antioxidants and prevents the oxidation of LDL in vitro and it may be suitable for use in food and pharmaceutical applications. PMID:23570012

Amine dehydrogenases: efficient biocatalysts for the reductive amination of carbonyl compounds.

PubMed

Knaus, Tanja; Böhmer, Wesley; Mutti, Francesco G

2017-01-21

Amines constitute the major targets for the production of a plethora of chemical compounds that have applications in the pharmaceutical, agrochemical and bulk chemical industries. However, the asymmetric synthesis of α-chiral amines with elevated catalytic efficiency and atom economy is still a very challenging synthetic problem. Here, we investigated the biocatalytic reductive amination of carbonyl compounds employing a rising class of enzymes for amine synthesis: amine dehydrogenases (AmDHs). The three AmDHs from this study - operating in tandem with a formate dehydrogenase from Candida boidinii (Cb-FDH) for the recycling of the nicotinamide coenzyme - performed the efficient amination of a range of diverse aromatic and aliphatic ketones and aldehydes with up to quantitative conversion and elevated turnover numbers (TONs). Moreover, the reductive amination of prochiral ketones proceeded with perfect stereoselectivity, always affording the ( R )-configured amines with more than 99% enantiomeric excess. The most suitable amine dehydrogenase, the optimised catalyst loading and the required reaction time were determined for each substrate. The biocatalytic reductive amination with this dual-enzyme system (AmDH-Cb-FDH) possesses elevated atom efficiency as it utilizes the ammonium formate buffer as the source of both nitrogen and reducing equivalents. Inorganic carbonate is the sole by-product.

Subcritical Water Technology for Extraction of Phenolic Compounds from Chlorella sp. Microalgae and Assessment on Its Antioxidant Activity.

PubMed

Zakaria, Siti Maisurah; Kamal, Siti Mazlina Mustapa; Harun, Mohd Razif; Omar, Rozita; Siajam, Shamsul Izhar

2017-07-03

Chlorella sp . microalgae is a potential source of antioxidants and natural bioactive compounds used in the food and pharmaceutical industries. In this study, a subcritical water (SW) technology was applied to determine the phenolic content and antioxidant activity of Chlorella sp . This study focused on maximizing the recovery of Chlorella sp. phenolic content and antioxidant activity measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay as a function of extraction temperature (100-250 °C), time (5-20 min) and microalgae concentration (5-20 wt. %) using response surface methodology. The optimal operating conditions for the extraction process were found to be 5 min at 163 °C with 20 wt. % microalgae concentration, which resulted in products with 58.73 mg gallic acid equivalent (GAE)/g phenolic content and 68.5% inhibition of the DPPH radical. Under optimized conditions, the experimental values were in close agreement with values predicted by the model. The phenolic content was highly correlated (R² = 0.935) with the antioxidant capacity. Results indicated that extraction by SW technology was effective and that Chlorella sp . could be a useful source of natural antioxidants.

Generic substitution of antihypertensive drugs: does it affect adherence?

PubMed

Van Wijk, Boris L G; Klungel, Olaf H; Heerdink, Eibert R; de Boer, Anthonius

2006-01-01

Generic substitution is an important opportunity to reduce the costs of pharmaceutical care. However, pharmacists and physicians often find that patients and brand-name manufacturers have doubt about the equivalence of the substituted drug. This may be reflected by decreased adherence to therapy. To assess the association between generic substitution and nonadherence to antihypertensive drugs. We conducted a matched cohort study between January 1, 1999, and December 31, 2002. Data were obtained from PHARMO, a record linkage system containing drug-dispensing records from community pharmacies and linked hospital discharge records of approximately 950,000 people in The Netherlands. Residents of 30 medium-sized cities who initiated antihypertensive drug therapy were potential subjects. Refill adherence with antihypertensive drugs after substitution was determined; those with refill adherence below 80% were considered nonadherent. Four hundred sixty-three patients with a substitution in therapy and 565 controls, matched on age, gender, therapy start date, duration of use, and generic product code, were identified. Of the patients who switched from brand-name to generic formulations ("substituted"), 13.6% were nonadherent, and of the non-substituted patients (those who did not switch to generic), 18.7% were nonadherent (OR 0.68; 95% CI 0.48 to 0.96). The association was absent in males. None of the patients discontinued the medication. No differences in hospitalizations for cardiovascular disease in the 6 months after the substitution were observed. Generic substitution of antihypertensive drugs does not lead to lower adherence or more discontinuation and cardiovascular disease-related hospitalizations compared with brand-name therapy. When a less-expensive antihypertensive generic equivalent becomes available, generic substitution should be considered to achieve economic benefits.

Switch-backs associated with generic drugs approved using product-specific determinations of therapeutic equivalence.

PubMed

Gagne, Joshua J; Polinski, Jennifer M; Jiang, Wenlei; Dutcher, Sarah K; Xie, Jing; Lii, Joyce; Fulchino, Lisa A; Kesselheim, Aaron S

2016-08-01

US Food and Drug Administration approval for generic drugs relies on demonstrating pharmaceutical equivalence and bioequivalence; however, some drug products have unique attributes that necessitate product-specific approval pathways. We evaluated rates of patients' switching back to brand-name versions from generic versions of four drugs approved via such approaches. We used data from Optum LifeSciences Research Database to identify patients using a brand-name version of a study drug (acarbose tablets, salmon calcitonin nasal spray, enoxaparin sodium injection, and venlafaxine extended release tablets) or a control drug. We followed patients to identify switching to generic versions and then followed those who switched to identify whether they switched back to brand-name versions. We calculated switch and switch-back rates and used Kaplan-Meier and log-rank tests to compare rates between study and control drugs. Our cohort included 201 959 eligible patients. Brand-to-generic switch rates ranged from 66 to 106 switches per 100 person-years for study drugs and 80 to 110 for control drugs. Rates of switch-back to brand-name versions ranged from 5 to 37 among study drugs and 3 to 53 among control drugs. Switch-back rates were higher for venlafaxine vs. sertraline (p < 0.01) and calcitonin vs. alendronate (p = 0.01). Switch-back rates were lower for venlafaxine vs. paroxetine (p < 0.01) and acarbose vs. nateglinide (p < 0.01). Rates were similar for acarbose vs. glimepiride (p = 0.97) and for enoxaparin vs. fondiparinux (p = 0.11). As compared to control drugs, patients were not more likely to systematically switch back from generic to brand-name versions of the four study drugs. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Encapsulation of Beetroot Pomace Extract: RSM Optimization, Storage and Gastrointestinal Stability.

PubMed

Tumbas Šaponjac, Vesna; Čanadanović-Brunet, Jasna; Ćetković, Gordana; Jakišić, Mirjana; Djilas, Sonja; Vulić, Jelena; Stajčić, Slađana

2016-04-30

One of the great problems in food production are surplus by-products, usually utilized for feeding animals and for preparation of dietary fibre or biofuel. These products represent potential sources of bioactive antioxidants and colour-giving compounds which could be used in the pharmaceutical industry and as food additives. In the present study beetroot pomace extract was encapsulated in soy protein by a freeze drying method. Process parameters (core: wall ratio, extract concentration and mixing time) were optimized using response surface methodology (RSM) in order to obtain the optimum encapsulate (OE) with the highest polyphenol encapsulation efficiency (EE) and radical scavenging activity on DPPH radicals (SA). Using the calculated optimum conditions, the EE (86.14%) and SA (1668.37 μmol Trolox equivalents/100 g) of OE did not differ significantly (p < 0.05) from the predicted ones. The contents of total polyphenols (326.51 mg GAE/100 g), flavonoids (10.23 mg RE/100 g), and betalains (60.52 mg betanin/100 g and 61.33 mg vulgaxanthin-I/100 g), individual content of phenolic compounds and betalains by HPLC, and the ability to reduce Fe(3+) ions, i.e., reducing power (394.95 μmol Trolox equivalents/100 g) of OE were determined as well. During three months of storage at room temperature, polyphenol retention was much higher (76.67%) than for betalain pigments, betacyanins (17.77%) and betaxanthins (17.72%). In vitro digestion and release of phenolics from OE showed higher release rate in simulated intestinal fluid than in gastric fluid. These results suggest encapsulation as a contemporary method for valorisation of sensitive bioactive compounds from food industry by-products.

Utilization of α-amylase enzyme from Bacillus stearothermophilus RSAII1B for maltodextrin production from sago starch

NASA Astrophysics Data System (ADS)

Arfah, R. A.; Ahmad, A.; Dali, S.; Djide, M. N.; Mahdalia; Arif, A. R.

2018-03-01

The dried sago flour derived from Palopo contains 28.80% amylose and 91.23% total carbohydrate. Based on the data, sago starch has the potential to become an alternative raw material for themaltodextrin production. Maltodextrin is one of the starch derivative products produced by hydrolysis process using the α-amylase enzyme with amaximum DE (dextrose equivalent) value of 20. The use of maltodextrin for food and pharmaceutical industries is increasing because of maltodextrin is widely used as thickener filler, surfactant and sugar substitute in milk powder. The aims of this study are to optimize the addition of enzyme concentration and hydrolysis time of α -amylase enzyme to obtain high quality ofmaltodextrin This study also aimed to characterization the obtained maltodextrin. The first step was isolation and purification α-amylase from the isolate of Bacillus stearothermophilus RSAII1B, followed by determination of the α-amylase concentration (0.05%, 0.07% and 0.09%) in 2.0% starch substrate, and the hydrolysis time ofα-amilase (60, 90, 120, 240 minutes). Maltodextrin characters observed were dextrose equivalent (DE), reducing sugar, moisture content, pH changes, color, solubility, viscosity, and total plate count (TPC). The results showed that the value of DE was 12.31, reducing sugar was 11.4%; water content was 10.92%; pH was 4.85; The color of maltodextrin powder was white bone color; solubility was 153.2 g/L; Viscositywas 210-240 cps, TPCwas 380 cfu/g. Maltodextrins produced from sago starch using the α-amylase enzyme from B.stearothermophillus RSAIIm met the quality requirements of SNI 7599: 2010.

Concentrations of hormones, pharmaceuticals and other micropollutants in groundwater affected by septic systems in New England and New York.

PubMed

Phillips, P J; Schubert, C; Argue, D; Fisher, I; Furlong, E T; Foreman, W; Gray, J; Chalmers, A

2015-04-15

Septic-system discharges can be an important source of micropollutants (including pharmaceuticals and endocrine active compounds) to adjacent groundwater and surface water systems. Groundwater samples were collected from well networks tapping glacial till in New England (NE) and sandy surficial aquifer New York (NY) during one sampling round in 2011. The NE network assesses the effect of a single large septic system that receives discharge from an extended health care facility for the elderly. The NY network assesses the effect of many small septic systems used seasonally on a densely populated portion of Fire Island. The data collected from these two networks indicate that hydrogeologic and demographic factors affect micropollutant concentrations in these systems. The highest micropollutant concentrations from the NE network were present in samples collected from below the leach beds and in a well downgradient of the leach beds. Total concentrations for personal care/domestic use compounds, pharmaceutical compounds and plasticizer compounds generally ranged from 1 to over 20 μg/L in the NE network samples. High tris(2-butoxyethyl phosphate) plasticizer concentrations in wells beneath and downgradient of the leach beds (>20 μg/L) may reflect the presence of this compound in cleaning agents at the extended health-care facility. The highest micropollutant concentrations for the NY network were present in the shoreline wells and reflect groundwater that is most affected by septic system discharges. One of the shoreline wells had personal care/domestic use, pharmaceutical, and plasticizer concentrations ranging from 0.4 to 5.7 μg/L. Estradiol equivalency quotient concentrations were also highest in a shoreline well sample (3.1 ng/L). Most micropollutant concentrations increase with increasing specific conductance and total nitrogen concentrations for shoreline well samples. These findings suggest that septic systems serving institutional settings and densely populated areas in coastal settings may be locally important sources of micropollutants to adjacent aquifer and marine systems. Published by Elsevier B.V.

CrossWater - Modelling micropollutant loads from different sources in the Rhine basin

NASA Astrophysics Data System (ADS)

Moser, Andreas; Bader, Hans-Peter; Fenicia, Fabrizio; Scheidegger, Ruth; Stamm, Christian

2015-04-01

The contamination of fresh surface waters with micropollutants originating from various sources is a growing environmental issue. The challenges for an effective political regulation are numerous, particularly for international water basins. One prerequisite for effective management is the knowledge of water quality across different parts of a basin. In this study within the Rhine basin, the spatial patterns of micropollutant loads and concentrations from different use classes are investigated with a mass flow analysis and compared to the established territorial jurisdictions on micropollutants and water quality. The source area of micropollutants depends on the specific use of a compound. The focus of this study is on i) herbicides from agricultural landuse, ii) biocides from material protection on buildings and iii) human pharmaceuticals from households. The total mass of micropollutants available for release to the stream network is estimated based on statistical application and consumption data. Based on GIS data of agricultural landuse, vector data of buildings, wastewater treatment plant (WWTP) locations, respectively, the available mass of micropollutants is spatially distributed to the catchment areas. The actual release of micropollutants to the stream network is calculated with empirical loss rates related to river discharge for agricultural herbicides and to precipitation for biocides. For the pharmaceuticals the release is coupled to the metabolism rates and elimination rates in WWTP. For a first approximation national sales are downscaled to the catchment level to specify the available mass for selected model compounds (agricultural herbicides: Isoproturon, biocides: Carbendazim, human pharmaceuticals: Carbamazepine and Diclofenac). The available mass of herbicides and biocides is multiplied with empirical loss rates independent from discharge or precipitation to calculate the loads. The release of the pharmaceuticals was calculated by multiplying average consumption numbers with the person equivalent of the WWTP and the elimination rates. The comparison of pollutant loads to 7-day composite samples of all compounds at 15 locations along the Rhine yield plausible results.

Method for detecting water equivalent of snow using secondary cosmic gamma radiation

DOEpatents

Condreva, K.J.

1997-01-14

Water equivalent of accumulated snow determination by measurement of secondary background cosmic radiation attenuation by the snowpack. By measuring the attenuation of 3-10 MeV secondary gamma radiation it is possible to determine the water equivalent of snowpack. The apparatus is designed to operate remotely to determine the water equivalent of snow in areas which are difficult or hazardous to access during winter, accumulate the data as a function of time and transmit, by means of an associated telemetry system, the accumulated data back to a central data collection point for analysis. The electronic circuitry is designed so that a battery pack can be used to supply power. 4 figs.

Method for detecting water equivalent of snow using secondary cosmic gamma radiation

DOEpatents

Condreva, Kenneth J.

1997-01-01

Water equivalent of accumulated snow determination by measurement of secondary background cosmic radiation attenuation by the snowpack. By measuring the attentuation of 3-10 MeV secondary gamma radiation it is possible to determine the water equivalent of snowpack. The apparatus is designed to operate remotely to determine the water equivalent of snow in areas which are difficult or hazardous to access during winter, accumulate the data as a function of time and transmit, by means of an associated telemetry system, the accumulated data back to a central data collection point for analysis. The electronic circuitry is designed so that a battery pack can be used to supply power.

Consumer choice between common generic and brand medicines in a country with a small generic market.

PubMed

Fraeyman, Jessica; Peeters, Lies; Van Hal, Guido; Beutels, Philippe; De Meyer, Guido R Y; De Loof, Hans

2015-04-01

Generic medicines offer an opportunity for governments to contain pharmaceutical expenditures, since generics are generally 10%-80% lower in price than brand medicines. Belgium has a small generic market that takes up 15% of the total pharmaceutical market in packages sold. To determine the knowledge of consumers about the different available packages of a common over-the-counter medicine (acetaminophen) with regard to price advantage, quality, and effectiveness in a country with a small generic market. We conducted an online survey in the general Flemish population using a questionnaire with 25 statements. The questionnaire also contained 2 informative interventions. First, we showed the price per package and per tablet that the patient would pay in the pharmacy. Second, we provided the respondent with general information about generic medication (equivalence, effectiveness, price, and recognition). Before and after the interventions, we probed for preferences and knowledge about the different packages. Multivariate logistic models were used to examine the independent effects of consumer characteristics on responses to the survey statements. We obtained a sample of 1,636 respondents. The general attitude towards generic medication was positive-only 5% would rather not use a generic. Nevertheless, only 17% of the respondents were able to recognize a generic medicine. Older consumers (aged 60 years and above) were more often confused about the different packages (OR = 2.59, 95% CI = 1.76-3.80, P ≤ 0.001). Consumers without a higher education degree tended to be more doubtful about the difference in effectiveness and quality between the different brands (OR = 0.59, 95% CI = 0.44-0.79, P ≤ 0.001). Consumer recognition of the name of the active substance of acetaminophen was poor. When different brands were displayed, possible price advantage seemed to be an important motive to switch to a cheaper brand. Consumers generally found medicines to be too expensive; however, consumers with medical or paramedical training had a different opinion. Two main recommendations can be made to increase the knowledge and enhance the trust in cheaper equivalent medicines. First, highlighting the name of the active substance on the label of medicine packages can reduce confusion and avoid health risks, especially among older consumers. Second, new investments or reallocation of budgets should be considered in order to provide consumers with authoritative information on the bioequivalence and price differences between the different available brands. This would be a cost-effective and potentially cost-saving investment for health care payers.

Informational content of official pharmaceutical industry web sites about treatments for erectile dysfunction.

PubMed

Waack, Katherine E; Ernst, Michael E; Graber, Mark A

2004-12-01

In the last 5 years, several treatments have become available for erectile dysfunction (ED). During this same period, consumer use of the Internet for health information has increased rapidly. In traditional direct-to-consumer advertisements, viewers are often referred to a pharmaceutical company Web site for further information. To evaluate the accessibility and informational content of 5 pharmaceutical company Web sites about ED treatments. Using 10 popular search engines and 1 specialized search engine, the accessibility of the official pharmaceutical company-sponsored Web site was determined by searching under brand and generic names. One company also manufactures an ED device; this site was also included. A structured, explicit review of information found on these sites was conducted. Of 110 searches (1 for each treatment, including corresponding generic drug name, using each search engine), 68 yielded the official pharmaceutical company Web site within the first 10 links. Removal of outliers (for both brand and generic name searches) resulted in 68 of 77 searches producing the pharmaceutical company Web site for the brand-name drug in the top 10 links. Although all pharmaceutical company Web sites contained general information on adverse effects and contraindications to use, only 2 sites gave actual percentages. Three sites provided references for their materials or discussed other treatment or drug options, while 4 of the sites contained profound advertising or emotive content. None mentioned cost of the therapy. The information contained on pharmaceutical company Web sites for ED treatments is superficial and aimed primarily at consumers. It is largely promotional and provides only limited information needed to effectively compare treatment options.

Analysis of pharmaceutical preparations containing antihistamine drugs by micellar liquid chromatography.

PubMed

Martínez-Algaba, C; Bermúdez-Saldaña, J M; Villanueva-Camañas, R M; Sagrado, S; Medina-Hernández, M J

2006-02-13

Rapid chromatographic procedures for analytical quality control of pharmaceutical preparations containing antihistamine drugs, alone or together with other kind of compounds are proposed. The method uses C18 stationary phases and micellar mobile phases of cetyltrimethylammonium bromide (CTAB) with either 1-propanol or 1-butanol as organic modifier. The proposed procedures allow the determination of the antihistamines: brompheniramine, chlorcyclizine, chlorpheniramine, diphenhydramine, doxylamine, flunarizine, hydroxyzine, promethazine, terfenadine, tripelennamine and triprolidine, in addition to caffeine, dextromethorphan, guaifenesin, paracetamol and pyridoxine in different pharmaceutical presentations (tablets, capsules, suppositories, syrups and ointments). The methods require minimum handling sample and are rapid (between 3 and 12 min at 1 mLmin(-1) flow rate) and reproducible (R.S.D. values<5%). Limits of detection are lower than 1 microgmL(-1) and the recoveries of the analytes in the pharmaceutical preparations are in the range 100+/-10%.

Occurrence of pharmaceuticals and cocaine in a Brazilian coastal zone.

PubMed

Pereira, Camilo D Seabra; Maranho, Luciane A; Cortez, Fernando S; Pusceddu, Fabio H; Santos, Aldo R; Ribeiro, Daniel A; Cesar, Augusto; Guimarães, Luciana L

2016-04-01

The present study determined environmental concentrations of pharmaceuticals, cocaine, and the main human metabolite of cocaine in seawater sampled from a subtropical coastal zone (Santos, Brazil). The Santos Bay is located in a metropolitan region and receives over 7367m(3) of wastewater per day. Five sample points under strong influence of the submarine sewage outfall were chosen. Through quantitative analysis by LC-MS/MS, 33 compounds were investigated. Seven pharmaceuticals (atenolol, acetaminophen, caffeine, losartan, valsartan, diclofenac, and ibuprofen), an illicit drug (cocaine), and its main human metabolite (benzoylecgonine) were detected at least once in seawater sampled from Santos Bay at concentrations that ranged from ng·L(-1) to μg·L(-1). In light of the possibility of bioaccumulation and harmful effects, the high concentrations of pharmaceuticals and cocaine found in this marine subtropical ecosystem are of environmental concern. Copyright © 2016 Elsevier B.V. All rights reserved.

Validation of an HPLC method for the quantification of ambroxol hydrochloride and benzoic acid in a syrup as pharmaceutical form stress test for stability evaluation.

PubMed

Heinänen, M; Barbas, C

2001-03-01

A method is described for ambroxol, trans-4-(2-amino-3,5-dibromobenzylamino) cyclohexanol hydrochloride, and benzoic acid separation by HPLC with UV detection at 247 nm in a syrup as pharmaceutical presentation. Optimal conditions were: Column Symmetry Shield RPC8, 5 microm 250 x 4.6 mm, and methanol/(H(3)PO(4) 8.5 mM/triethylamine pH=2.8) 40:60 v/v. Validation was performed using standards and the pharmaceutical preparation which contains the compounds described above. Results from both standards and samples show suitable validation parameters. The pharmaceutical grade substances were tested by factors that could influence the chemical stability. These reaction mixtures were analysed to evaluate the capability of the method to separate degradation products. Degradation products did not interfere with the determination of the substances tested by the assay.

Pharmaceutical Wastewater Effluent—Source of Contaminants of Emerging Concern: Phytotoxicity of Metronidazole to Soybean (Glycine max)

PubMed Central

Yakubu, Okhumode H.

2017-01-01

Industrial discharge of active pharmaceutical ingredients (APIs) into the environment in some middle- and low-income countries is not sufficiently regulated. The phytotoxicity of metronidazole (FLAGYL)—one of the most commonly used over the counter (OTC) antibiotics, to soybean (Glycine max) is investigated. Relative growth rate (RGR) expressed in gram per gram per day (gg−1d−1) was applied to plants destructively harvested at maturity (42 d), to determine the toxicological impact. Differences between mean RGR of the three groups were performed at 0.05 significance level. Multiple comparisons suggest that there was a statistical significant difference among mean RGR for all treatment groups. Metronidazole is toxic to soybean plants (Glycine max) based on dose-response criterion. There is a need to enforce treatment of pharmaceutical wastewater effluent by Pharmaceutical Manufacturing Companies (PMCs) before discharge into the environment. PMID:29051442

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

PubMed

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

2016-04-01

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

A validated silver-nanoparticle-enhanced chemiluminescence method for the determination of citalopram in pharmaceutical preparations and human plasma.

PubMed

Khan, Muhammad Naeem; Jan, Muhammad Rasul; Shah, Jasmin; Lee, Sang Hak

2014-05-01

A simple and sensitive chemiluminescence (CL) method was developed for the determination of citalopram in pharmaceutical preparations and human plasma. The method is based on the enhancement of the weak CL signal of the luminol-H2 O2 system. It was found that the CL signal arising from the reaction between alkaline luminol and H2 O2 was greatly increased by the addition of silver nanoparticles in the presence of citalopram. Prepared silver nanoparticles (AgNPs) were characterized by UV-visible spectroscopy and transmission electron microscopy (TEM). Various experimental parameters affecting CL intensity were studied and optimized for the determination of citalopram. Under optimized experimental conditions, CL intensity was found to be proportional to the concentration of citalopram in the range 40-2500 ng/mL, with a correlation coefficient of 0.9997. The limit of detection (LOD) and limit of quantification (LOQ) of the devised method were 3.78 and 12.62 ng/mL, respectively. Furthermore, the developed method was found to have excellent reproducibility with a relative standard deviation (RSD) of 3.65% (n = 7). Potential interference by common excipients was also studied. The method was validated statistically using recovery studies and was successfully applied to the determination of citalopram in the pure form, in pharmaceutical preparations and in spiked human plasma samples. Percentage recoveries were found to range from 97.71 to 101.99% for the pure form, from 97.84 to 102.78% for pharmaceutical preparations and from 95.65 to 100.35% for spiked human plasma. Copyright © 2013 John Wiley & Sons, Ltd.

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

NASA Astrophysics Data System (ADS)

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

2015-03-01

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

Contrast Experiment on Advanced Treatment of Pharmaceutical and Paper-making Wastewater through Cinder Fenton-like Process

NASA Astrophysics Data System (ADS)

Xiaofeng, Jia; Xiaoyu, Chen; Wenning, Mai

2018-06-01

The Fenton-like process of catalyzing H2O2 with Fe2+ and cinder is adopted to subject pharmaceutical and paper-making wastewater to advanced treatment. The influence of each factor is determined using orthogonal experiment and single factor test. The optimal combination of influencing factors is 0.3mmol · L-1 of FeSO4 · 7H2O, [H2O2]:[Fe2+]=8:1 and 10g · L-1 of pyrites cinder. The reaction time in pharmaceutical wastewater and paper-making wastewater is 30min and 60min respectively, testifying to the fact that the reaction in pharmaceutical wastewater is faster than that in paper-making wastewater and the lower utilization rate of cinder in pharmaceutical wastewater. Under the optimal reaction condition, the COD removal rate of these two kinds of wastewater can reach as high as 65% and 72%. Characterized by simple operation and requiring less reagent dosage, this method does not have to regulate the pH of flooding water and allows the repeated usage of cinder.

The Future of the Pharmaceutical Sciences and Graduate Education: Recommendations from the AACP Graduate Education Special Interest Group

PubMed Central

Gobburu, Jogarao; O’Barr, Stephen; Shah, Kumar; Huber, Jason; Weiner, Daniel

2013-01-01

Despite pharma's recent sea change in approach to drug discovery and development, U.S. pharmaceutical sciences graduate programs are currently maintaining traditional methods for master's and doctoral student education. The literature on graduate education in the biomedical sciences has long been advocating educating students to hone soft skills like communication and teamwork, in addition to maintaining excellent basic skills in research. However, recommendations to date have not taken into account the future trends in the pharmaceutical industry. The AACP Graduate Education Special Interest Group has completed a literature survey of the trends in the pharmaceutical industry and graduate education in order to determine whether our graduate programs are strategically positioned to prepare our graduates for successful careers in the next few decades. We recommend that our pharmaceutical sciences graduate programs take a proactive leadership role in meeting the needs of our future graduates and employers. Our graduate programs should bring to education the innovation and collaboration that our industry also requires to be successful and relevant in this century. PMID:23716757

The future of the pharmaceutical sciences and graduate education: recommendations from the AACP Graduate Education Special Interest Group.

PubMed

Wu-Pong, Susanna; Gobburu, Jogarao; O'Barr, Stephen; Shah, Kumar; Huber, Jason; Weiner, Daniel

2013-05-13

Despite pharma's recent sea change in approach to drug discovery and development, U.S. pharmaceutical sciences graduate programs are currently maintaining traditional methods for master's and doctoral student education. The literature on graduate education in the biomedical sciences has long been advocating educating students to hone soft skills like communication and teamwork, in addition to maintaining excellent basic skills in research. However, recommendations to date have not taken into account the future trends in the pharmaceutical industry. The AACP Graduate Education Special Interest Group has completed a literature survey of the trends in the pharmaceutical industry and graduate education in order to determine whether our graduate programs are strategically positioned to prepare our graduates for successful careers in the next few decades. We recommend that our pharmaceutical sciences graduate programs take a proactive leadership role in meeting the needs of our future graduates and employers. Our graduate programs should bring to education the innovation and collaboration that our industry also requires to be successful and relevant in this century.

Including carrier-mediated transport in oral uptake prediction of nutrients and pharmaceuticals in humans.

PubMed

O'Connor, Isabel A; Veltman, Karin; Huijbregts, Mark A J; Ragas, Ad M J; Russel, Frans G M; Hendriks, A Jan

2014-11-01

Most toxicokinetic models consider passive diffusion as the only mechanism when modeling the oral uptake of chemicals. However, the overall uptake of nutrients and xenobiotics, such as pharmaceuticals and environmental pollutants, can be increased by influx transport proteins. We incorporated carrier-mediated transport into a one-compartment toxicokinetic model originally developed for passive diffusion only. The predictions were compared with measured oral uptake efficiencies of nutrients and pharmaceuticals, i.e. the fraction of the chemical reaching systemic circulation. Including carrier-mediated uptake improved model predictions for hydrophilic nutrients (RMSE=10% vs. 56%, Coefficient of Efficiency CoE=0.5 vs. -9.6) and for pharmaceuticals (RMSE=21% vs. 28% and CoE=-0.4 vs. -1.1). However, the negative CoE for pharmaceuticals indicates that further improvements are needed. Most important in this respect is a more accurate estimation of vMAX and KM as well as the determination of the amount of expressed and functional transport proteins both in vivo and in vitro. Copyright © 2014 Elsevier B.V. All rights reserved.

Chemiluminescence determination of terbutaline sulfate in bovine urine and pharmaceutical preparations based on enhancement of the 2-phenyl-4, 5-di (2-furyl) imidazole-potassium ferricyanide system.

PubMed

Han, Lu; Zhang, Yumin; Kang, Jing; Tang, Jieli; Zhang, Yihua

2012-01-25

In this paper, a novel chemiluminescence (CL) system, 2-phenyl-4, 5-di (2-furyl) imidazole (PDFI)-potassium ferricyanide, for the determination of terbutaline sulfate was described. The method was based on enhancement of CL emission of PDFI-potassium ferricyanide system in the presence of terbutaline sulfate. Under the optimum conditions, the enhanced chemiluminescence intensity is linearly related to the concentration of terbutaline sulfate. The proposed method has been successfully applied to the determination of terbutaline sulfate in bovine urine and pharmaceutical preparations with satisfactory results. Furthermore, the possible mechanism of chemiluminescence reaction was also discussed briefly. Copyright © 2011 Elsevier B.V. All rights reserved.

Rainforest Pharmacopeia in Madagascar Provides High Value for Current Local and Prospective Global Uses

PubMed Central

Golden, Christopher D.; Rasolofoniaina, B. J. Rodolph; Anjaranirina, E. J. Gasta; Nicolas, Lilien; Ravaoliny, Laurent; Kremen, Claire

2012-01-01

Botanical diversity provides value to humans through carbon sequestration, air and water purification, and the provisioning of wild foods and ethnomedicines. Here we calculate the value of botanical ethnomedicines in a rainforest region of Madagascar, the Makira Protected Area, using a substitution method that combines replacement costs and choice modeling. The Makira watershed may comprise approximately 0.8% of global botanical diversity and possesses enormous value both in its ability to provision botanical ethnomedicines to local people and as a source of potentially novel pharmaceutical drugs for society as a whole. Approximately 241 locally-recognized species are used as ethnomedicines, including 113 agricultural or weed species. We equated each ethnomedicinal treatment to the monetary value of a comparable pharmaceutical treatment adjusted by personal preferences in perceived efficacy (rather than from known or assumed medicinal equivalency). The benefit value of these botanical ethnomedicines per individual is $5.40–7.90 per year when using the value of highly subsidized Malagasy pharmaceuticals and $100.60–287.40 when using the value of American pharmaceuticals. Using local pharmaceuticals as substitutes, the value per household is $30.24–44.30 per year, equivalent to 43–63% of median annual household income, demonstrating their local importance. Using the value of American pharmaceuticals, the amount is equivalent to 22–63% of the median annual health care expenditures for American adults under 45 in 2006. The potential for developing novel biomedicines from the Makira watershed’s unique flora ranges in untapped benefit value from $0.3–5.7 billion for American pharmaceutical companies, non-inclusive of the importance of providing novel medicines and improved healthcare to society. This study provides evidence of the tremendous current local and prospective global value of botanical ethnomedicines and furthers arguments for the conservation of tropical forests for sustainable use. Botanique de la diversité apporte de la valeur à l’homme par la séquestration du carbone, de l’air et de purification de l’eau, et le provisionnement des aliments sauvages et ethnomedicines. Ici, nous calculons la valeur de ethnomedicines botaniques dans une région de forêt de Madagascar, la zone protégée de Makira, en utilisant une méthode de substitution qui combine les coûts de remplacement et la modélisation des choix. Le bassin versant de Makira peut comprendre environ 0,8% de la diversité botanique mondiale et possède une valeur énorme à la fois dans sa capacité à fournir ethnomedicines botaniques à la population locale et en tant que source de nouveaux médicaments potentiellement pharmaceutiques pour la société dans son ensemble. Environ 241 espèces localement reconnus sont utilisés comme ethnomedicines, y compris 113 espèces d’agricoles ou de mauvaises herbes. Nous assimilé chaque traitement ethnomédicales à la valeur monétaire d’un traitement comparable pharmaceutique ajusté en fonction des préférences personnelles en matière d’efficacité perçue (plutôt que de l’équivalence médicament connu ou supposé). La valeur de l’avantage de ces ethnomedicines botaniques par individu est de $5,40 à 7.90 par année lors de l’utilisation de la valeur des produits pharmaceutiques malgaches fortement subventionnés et de $100,60 à 287,40 lors de l’utilisation de la valeur des produits pharmaceutiques américains. Utilisation de produits pharmaceutiques locales comme des substituts, la valeur par ménage est de $30.24 à 44.30 par an, équivalent à 43–63% du revenu médian des ménages annuelle, ce qui démontre leur importance locale. Utilisation de la valeur des produits pharmaceutiques américaines, le montant est équivalent à 22–63% de la médiane des dépenses annuelles de soins de santé pour les adultes américains de moins de 45 en 2006. Le potentiel de développement de nouveaux biomédicaments des fourneaux dans le bassin versant de la flore Makira unqiue de la valeur des avantages inexploité de $0,3 à 5,7 milliards pour les sociétés pharmaceutiques américaines, non compris l’importance de fournir de nouveaux médicaments et de soins de santé amélioré à la société. Cette étude fournit une preuve de l’énorme valeur actuelle globale locale et prospective de ethnomedicines botaniques et des arguments fait avancer pour la conservation des forêts tropicales pour l’utilisation durable. PMID:22848447

Concentration and risk of pharmaceuticals in freshwater systems are related to the population density and the livestock units in Iberian Rivers.

PubMed

Osorio, Victoria; Larrañaga, Aitor; Aceña, Jaume; Pérez, Sandra; Barceló, Damià

2016-01-01

Considerable amounts of pharmaceuticals are used in human and veterinary medicine, which are not efficiently removed during wastewater and slurries treatment and subsequently entering continuously into freshwater systems. The intrinsic biological activity of these non-regulated pollutants turns their presence in the aquatic environment into an ecological matter of concern. We present the first quantitative study relating the presence of pharmaceuticals and their predicted ecotoxicological effects with human population and livestock units. Four representative Iberian River basins (Spain) were studied: Llobregat, Ebro, Júcar and Guadalquivir. The levels of pharmaceuticals were determined in surface water and sediment samples collected from 77 locations along their stream networks. Predicted total toxic units to algae, Daphnia and fish were estimated for pharmaceuticals detected in surface waters. The use of chemometrics enabled the study of pharmaceuticals for: their spatial distribution along the rivers in two consecutive years; their potential ecotoxicological risk to aquatic organisms; and the relationships among their occurrence and predicted ecotoxicity with human population and animal farming pressure. The Llobregat and the Ebro River basins were characterized as the most polluted and at highest ecotoxicological risk, followed by Júcar and Guadalquivir. No significant acute risks of pharmaceuticals to aquatic organisms were observed. However potential chronic ecotoxicological effects on algae could be expected at two hot spots of pharmaceuticals pollution identified in the Llobregat and Ebro basins. Analgesics/antiinflammatories, antibiotics and diuretics were the most relevant therapeutic groups across the four river basins. Among them, hydrochlorothiazide and gemfibrozil, as well as azithromycin and ibuprofen were widely spread and concentrated pharmaceuticals in surface waters and sediments, respectively. Regarding their predicted ecotoxicity, sertraline, gemfibrozil and loratidine were identified as the more concerning compounds. Significantly positive relationships were found among levels of pharmaceuticals and toxic units and population density and livestock units in both surface water and sediment matrices. Copyright © 2015. Published by Elsevier B.V.

Enhanced electrocatalytic oxidation of isoniazid at electrochemically modified rhodium electrode for biological and pharmaceutical analysis.

PubMed

Cheemalapati, Srikanth; Chen, Shen-Ming; Ali, M Ajmal; Al-Hemaid, Fahad M A

2014-09-01

A simple and sensitive electrochemical method has been proposed for the determination of isoniazid (INZ). For the first time, rhodium (Rh) modified glassy carbon electrode (GCE) has been employed for the determination of INZ by linear sweep voltammetry technique (LSV). Compared with the unmodified electrode, the proposed Rh modified electrode provides strong electrocatalytic activity toward INZ with significant enhancement in the anodic peak current. Scanning electron microscopy (SEM) and field emission scanning electron microscopy (FESEM) results reveal the morphology of Rh particles. With the advantages of wide linearity (70-1300μM), good sensitivity (0.139μAμM(-1)cm(-2)) and low detection limit (13μM), this proposed sensor holds great potential for the determination of INZ in real samples. The practicality of the proposed electrode for the detection of INZ in human urine and blood plasma samples has been successfully demonstrated using LSV technique. Through the determination of INZ in commercially available pharmaceutical tablets, the practical applicability of the proposed method has been validated. The recovery results are found to be in good agreement with the labeled amounts of INZ in tablets, thus showing its great potential for use in clinical and pharmaceutical analysis. Copyright © 2014 Elsevier B.V. All rights reserved.

Anodic voltammetric behavior and determination of rosiglitazone in pharmaceutical dosage forms and biological fluids on solid electrode.

PubMed

Dogan-Topal, Burcu; Tuncel, Secil; Ozkan, Sibel A

2010-09-01

The anodic voltammetric behavior and electroanalytical determination of rosiglitazone was studied using cyclic, linear sweep, differential pulse and square wave voltammetric techniques on glassy carbon electrode. The oxidation of rosiglitazone was irreversible and exhibited diffusion controlled process depending on pH. Different parameters were tested to optimize the conditions for the determination of the oxidation mechanism of rosiglitazone. The dependence of current intensities and potentials on pH, concentration, scan rate, nature of the buffer was also investigated. According to the linear relationship between the peak current and the concentration, differential pulse and square wave voltammetric methods for rosiglitazone assay in pharmaceutical dosage forms and biological fluids were developed. A linear response was obtained within the range of 1x10-6M - 6x10-5M in 0.1 M H2SO4 and acetate buffer at pH 5.70 for both voltammetric methods in human serum samples. The practical analytical value of the method is demonstrated by quantitative determination of rosiglitazon in pharmaceutical formulation and human serum, without the need for separation or complex sample preparation, since there was no interference from the excipients and endogenous substances. The methods were fully validated and successfully applied to the high throughput determination of the drug in tablets and human serum with good recoveries.

Determination of Dynamic Recrystallization Process by Equivalent Strain

NASA Astrophysics Data System (ADS)

Qin, Xiaomei; Deng, Wei

Based on Tpнoвckiй's displacement field, equivalent strain expression was derived. And according to the dynamic recrystallization (DRX) critical strain, DRX process was determined by equivalent strain. It was found that equivalent strain distribution in deformed specimen is inhomogeneous, and it increases with increasing true strain. Under a certain true strain, equivalent strains at the center, demisemi radius or on tangential plane just below the surface of the specimen are higher than the true strain. Thus, micrographs at those positions can not exactly reflect the true microstructures under the certain true strain. With increasing strain rate, the initial and finish time of DRX decrease. The frozen microstructures of 20Mn23AlV steel with the experimental condition validate the feasibility of predicting DRX process by equivalent strain.

A renaissance in marine pharmacology: from preclinical curiosity to clinical reality.

PubMed

Glaser, Keith B; Mayer, Alejandro M S

2009-09-01

Marine pharmacology, the pharmacology of marine natural products, has been for some time more associated with marine natural products chemistry rather than mainstay pharmacology. However, in recent years a renaissance has occurred in this area of research, and has seen the US Food & Drug Administration (FDA) approval in 2004 of Prialt (ziconotide, omega-conotoxin MVIIA) the synthetic equivalent of a conopeptide found in marine snails, used for the management of severe chronic pain. Furthermore Yondelis) (trabectedin, ET-743) an antitumor agent scovered in a marine colonial tunicate, and now produced synthetically, receiving Orphan Drug designation from the European Commission (EC) and FDA for soft tissue sarcomas and ovarian cancer and its registration in 2007 in the EU for the treatment of soft tissue sarcoma. The approval/marketing of so few marine natural products has come after many years of research primarily by the academic community and the sporadic involvement of major pharmaceutical companies. This commentary, through the opinions provided by several leaders in the marine natural products field, will examine the potential reasons and perceptions from both the academic and pharmaceutical communities regarding the development of marine natural products as viable therapeutic entities.

[Sponsoring of medical conferences, workshops and symposia by pharmaceutical companies. Physicians must be wary of this!].

PubMed

Warntjen, M

2009-12-01

The longstanding conventional forms of cooperation between medical organizations and physicians on the one hand and the pharmaceutical industry and manufacturers of medical products on the other hand nowadays hold the risk of coming into conflict with the public prosecutor. Typical circumstances which are taken up by the investigating authorities are financial supports of medical conferences, workshops and symposia. To understand the problem under criminal law it is important to become acquainted with the protective aim of the statutory offences of the acceptance of benefits according to section sign 331 of the Penal Code (Strafgesetzbuch, StGB) and of corruption according to section sign 332 of the Penal Code. The "trust of the general public in the objectivity of governmental decisions" must be protected and the "evil appearance of the corruptibility of official acts" must be counteracted. A basic differentiation is made between physicians with and without office-bearing functions. By paying attention to the recommendations and basic principles of cooperation between the medical profession and the healthcare industry presented in this article (transparency principle, equivalence principle, documentation principle and separation principle) the emergence of any suspicious factors can be effectively avoided.

“One pill, once daily”: what clinicians need to know about Atripla™

PubMed Central

Clay, Patrick G; Taylor, Tracey AH; Glaros, Alan G; McRae, MaryPeace; Williams, Charlott; McCandless, Don; Oelklaus, Maurice

2008-01-01

As the number of persons chronically prescribed antiretrovirals has grown and the realization that antiretrovirals are required to be continued for life, pharmaceutical manufacturers have developed new classes of agents, improved the pharmacokinetics of marketed products through dosing reformulations, and in an effort to maximize success with respect to adherence, compiled into a single dosing unit all necessary elements for an antiretroviral regimen. Atripla™ represents the first ever fixed-dose combination antiretroviral available. This article reviews currently available data on this agent, the impact of resistance on clinical use and implementation, as well as extensive descriptions of the pharmacokinetics, adverse effects and drug-interactions warranting consideration. Whether beginning in a naïve patient or switching from other regimens for tolerability issues, Atripla™ represents a viable option. Its demonstrated advantages with respect to lipid and hematologic parameters and equivalent incidence of renal toxicity are tempered by the findings of bone mineral density decreases, however. Combining multiple mechanisms of action in a single dosing unit appears to improve efficacy, increase the likelihood for adherence and maintain viral suppression compared to administering these agents independently. It is suggested other pharmaceutical companies assess the potential to replicate this for the remaining antiretrovirals. PMID:18728842

Determinants of FDI Localization in China: A County-Level Analysis for the Pharmaceutical Industry

PubMed Central

Li, Su; Angelino, Antonio; Yin, Haitao

2017-01-01

Foreign direct investments (FDIs) have been widely recognized as a crucial feature of the Chinese industrial development process. Over the past decades, China has been attracting huge amounts of inward FDIs as a consequence of both spontaneous market dynamics and place-based preferential policies at the sub-national level. However, the Chinese market exhibits large dissimilarities in terms of FDI localization across territories that are worth investigating at a more disaggregated level. In this regards, our study explores the determinants of attraction of inward FDIs in China, at the county level. It focuses on the pharmaceutical industry and attempts to assess whether factors related to location advantages, agglomeration dynamics, information cost effects and environmental regulation costs affect foreign firms’ localization choices as well as invested amounts in that location. By means of discrete choice models, our paper confirms the findings of the prevalent literature about the positive effects of location advantages on pharmaceutical FDI attraction. Different from our expectations, a higher proportion of foreign enterprises do not stimulate significant effects on FDI localization, while preferential policies and sectoral agglomeration are positively correlated with the localization of pharmaceutical foreign firms. Finally, our results suggest that investing firms tend to avoid areas with strict environment regulation. PMID:28867815

Determinants of FDI Localization in China: A County-Level Analysis for the Pharmaceutical Industry.

PubMed

Li, Su; Angelino, Antonio; Yin, Haitao; Spigarelli, Francesca

2017-08-30

Foreign direct investments (FDIs) have been widely recognized as a crucial feature of the Chinese industrial development process. Over the past decades, China has been attracting huge amounts of inward FDIs as a consequence of both spontaneous market dynamics and place-based preferential policies at the sub-national level. However, the Chinese market exhibits large dissimilarities in terms of FDI localization across territories that are worth investigating at a more disaggregated level. In this regards, our study explores the determinants of attraction of inward FDIs in China, at the county level. It focuses on the pharmaceutical industry and attempts to assess whether factors related to location advantages, agglomeration dynamics, information cost effects and environmental regulation costs affect foreign firms' localization choices as well as invested amounts in that location. By means of discrete choice models, our paper confirms the findings of the prevalent literature about the positive effects of location advantages on pharmaceutical FDI attraction. Different from our expectations, a higher proportion of foreign enterprises do not stimulate significant effects on FDI localization, while preferential policies and sectoral agglomeration are positively correlated with the localization of pharmaceutical foreign firms. Finally, our results suggest that investing firms tend to avoid areas with strict environment regulation.

Determination of pharmaceuticals in groundwater collected in five cemeteries' areas (Portugal).

PubMed

Paíga, P; Delerue-Matos, C

2016-11-01

There are growing public attention and concern about the possibility of ecosystem and human health effects from pharmaceuticals in environment. Several types of environmental samples were target of studies by the scientific community, namely drinking water, groundwater, surface water (river, ocean), treated water (influent and effluent), soils, and sediments near to Wastewater Treatment Plants or near to others potential sources of contaminations. Normally, studies in the cemeteries areas are for historical and architectural research and questions of the potential risk for adverse impact of cemeteries in environment have never received enough attention. However, this risk may exist when cemeteries are placed in areas that are vulnerable to contamination. The objective of the present work was the determination of pharmaceuticals (nonsteroidal anti-inflammatory/analgesics, antibiotics and psychiatric drugs) in groundwater samples collected inside of the cemeteries areas. Acetaminophen, salicylic acid, ibuprofen, ketoprofen, nimesulide, carbamazepine, fluoxetine, and sertraline were the pharmaceuticals achieved in the analysed samples. None of the studied antibiotics were detected. The highest concentration was obtained for salicylic acid (in the range of 33.7 to 71.0ng/L) and carbamazepine (between 20.0 and 22.3ng/L), respectively. By the cluster analysis similarity between carbamazepine and fluoxetine was achieved. Copyright © 2016. Published by Elsevier B.V.

Evaluation of physicochemical properties as supporting information on quality control of raw materials and veterinary pharmaceutical formulations.

PubMed

Anacleto, Sara da Silva; Borges, Marcella Matos Cordeiro; de Oliveira, Hanna Leijoto; Vicente, Andressa Reis; de Figueiredo, Eduardo Costa; de Oliveira, Marcone Augusto Leal; Borges, Bárbara Juliana Pinheiro; de Oliveira, Marcelo Antonio; Borges, Warley de Souza; Borges, Keyller Bastos

2018-06-01

This study aimed to show that the physicochemical proprieties obtained by Fourier transform infrared spectroscopy (FTIR), thermogravimetry (TG), and scanning electronic microscopy (SEM) can be useful tools for evaluating the quality of active pharmaceutical ingredients (APIs) and pharmaceutical products. In addition, a simple, sensitive, and efficient method employing HPLC-DAD was developed for simultaneous determination of lidocaine (LID), ciprofloxacin (CFX) and enrofloxacin (EFX) in raw materials and in veterinary pharmaceutical formulations. Compounds were separated using a Gemini C 18 (250 mm × 4.6 mm, 5 µm) Phenomenex ® column, at a temperature of 25 °C, with a mobile phase containing 10 mM of phosphoric acid (pH 3.29): acetonitrile (85.7:14.3, v/v) and a flow rate of 1.5 mL/min. Physicochemical characterization by TG, FTIR, and SEM of raw materials of LID, CFX, and EFX provided information useful for the evaluation, differentiation, and qualification of raw materials. Finally, the HPLC method was proved to be useful for evaluation of raw material and finished products, besides satisfying the need for an analytical method that allows simultaneous determination of EFX, CFX, and LID, which can also be extended to other matrices and applications.

Development and validation of an LC-UV method for the quantification and purity determination of the novel anticancer agent C1311 and its pharmaceutical dosage form.

PubMed

den Brok, Monique W J; Nuijen, Bastiaan; Hillebrand, Michel J X; Grieshaber, Charles K; Harvey, Michael D; Beijnen, Jos H

2005-09-01

C1311 (5-[[2-(diethylamino)ethyl]amino]-8-hydroxyimidazo [4,5,1-de]-acridin-6-one-dihydrochloride trihydrate) is the lead compound from the group of imidazoacridinones, a novel group of rationally designed anticancer agents. The pharmaceutical development of C1311 necessitated the availability of an assay for the quantification and purity determination of C1311 active pharmaceutical ingredient (API) and its pharmaceutical dosage form. A reversed-phase liquid chromatographic method (RP-LC) with ultraviolet (UV) detection was developed, consisting of separation on a C18 column with phosphate buffer (60 mM; pH 3 with 1 M citric acid)-acetonitrile-triethylamine (83:17:0.05, v/v/v) as the mobile phase and UV-detection at 280 nm. The method was found to be linear over a concentration range of 2.50-100 microg/mL, precise and accurate. Accelerated stress testing showed degradation products, which were well separated from the parent compound, confirming its stability-indicating capacity. Moreover, the use of LC-MS and on-line photo diode array detection enabled us to propose structures for four degradation products. Two of these products were also found as impurities in the API and more abundantly in an impure lot of API.

Bioaccumulation and trophic dilution of human pharmaceuticals across trophic positions of an effluent-dependent wadeable stream

PubMed Central

Du, Bowen; Haddad, Samuel P.; Luek, Andreas; Scott, W. Casan; Saari, Gavin N.; Kristofco, Lauren A.; Connors, Kristin A.; Rash, Christopher; Rasmussen, Joseph B.; Chambliss, C. Kevin; Brooks, Bryan W.

2014-01-01

Though pharmaceuticals are increasingly observed in a variety of organisms from coastal and inland aquatic systems, trophic transfer of pharmaceuticals in aquatic food webs have not been reported. In this study, bioaccumulation of select pharmaceuticals was investigated in a lower order effluent-dependent stream in central Texas, USA, using isotope dilution liquid chromatography–tandem mass spectrometry (MS). A fish plasma model, initially developed from laboratory studies, was tested to examine observed versus predicted internal dose of select pharmaceuticals. Pharmaceuticals accumulated to higher concentrations in invertebrates relative to fish; elevated concentrations of the antidepressant sertraline and its primary metabolite desmethylsertraline were observed in the Asian clam, Corbicula fluminea, and two unionid mussel species. Trophic positions were determined from stable isotopes (δ15N and δ13C) collected by isotope ratio-MS; a Bayesian mixing model was then used to estimate diet contributions towards top fish predators. Because diphenhydramine and carbamazepine were the only target compounds detected in all species examined, trophic magnification factors (TMFs) were derived to evaluate potential trophic transfer of both compounds. TMFs for diphenhydramine (0.38) and carbamazepine (1.17) indicated neither compound experienced trophic magnification, which suggests that inhalational and not dietary exposure represented the primary route of uptake by fish in this effluent-dependent stream. PMID:25313153

Determination of a broad spectrum of pharmaceuticals and endocrine disruptors in biofilm from a waste water treatment plant-impacted river.

PubMed

Huerta, B; Rodriguez-Mozaz, S; Nannou, C; Nakis, L; Ruhí, A; Acuña, V; Sabater, S; Barcelo, D

2016-01-01

Wastewater treatment plants (WWTPs) are one of the main sources of pharmaceuticals and endocrine disrupting compounds in freshwater ecosystems, and several studies have reported bioaccumulation of these compounds in different organisms in those ecosystems. River biofilms are exceptional indicators of pollution, but very few studies have focused on the accumulation of these emerging contaminants. The objectives of this study were first to develop an efficient analytical methodology for the simultaneous analysis of 44 pharmaceuticals and 13 endocrine disrupting compounds in biofilm, and second, to assess persistence, distribution, and bioaccumulation of these contaminants in natural biofilms inhabiting a WWTP-impacted river. The method is based on pressurized liquid extraction, purification by solid-phase extraction, and analysis by ultra performance liquid chromatography coupled to a mass spectrometer (UPLC-MS/MS) in tandem. Recoveries for pharmaceuticals were 31-137%, and for endocrine disruptors 32-93%. Method detection limits for endocrine disruptors were in the range of 0.2-2.4 ng g(-1), and for pharmaceuticals, 0.07-6.7 ng g(-1). A total of five endocrine disruptors and seven pharmaceuticals were detected in field samples at concentrations up to 100 ng g(-1). Copyright © 2015. Published by Elsevier B.V.

Enhanced degradation of persistent pharmaceuticals found in wastewater treatment effluents using TiO2 nanobelt photocatalysts

NASA Astrophysics Data System (ADS)

Liang, Robert; Hu, Anming; Li, Wenjuan; Zhou, Y. Norman

2013-10-01

Pharmaceuticals in wastewater effluents are a current and emerging global problem and the development of cost-effective methods to facilitate their removal is needed to mitigate this issue. Advanced oxidation processes (AOPs), in particular UV/TiO2, have potential for wastewater treatment. In this study, TiO2 anatase phase nanobelts (30-100 nm in width and 10 μm in length) have been synthesized using a high temperature hydrothermal method as a means to photocatalyze the oxidation of pharmaceutical contaminants. We have investigated a model dye (malachite green), three pharmaceuticals and personal care products—naproxen, carbamazepine, and theophylline—that are difficult to oxidize without AOP processes. TiO2 nanobelts were exposed to 365 nm UV illumination and the measured photocatalytic degradation rates and adsorption parameters of pharmaceuticals were explored using kinetic models. Furthermore we have determined the degree of pharmaceutical degradation as a function of solution pH, illumination time, temperature, and concentration of contaminant. In addition, the roles of active oxygen species—hydroxyl radial (OH·), positive holes (h+), and hydrogen peroxide (H2O2)—involved were also investigated in the degradation process. These studies offer additional applications of hierarchical TiO2 nanobelt membranes, including those harnessing sunlight for water treatment.

How to select equivalent and complimentary reversed phase liquid chromatography columns from column characterization databases.

PubMed

Borges, Endler M

2014-01-07

Three RP-LC column characterization protocols [Tanaka et al. (1989), Snyder et al. (PQRI, 2002), and NIST SRM 870 (2000)] were evaluated using both Euclidian distance and Principal Components Analysis to evaluate effectiveness at identifying equivalent columns. These databases utilize specific chromatographic properties such as hydrophobicity, hydrogen bonding, shape/steric selectivity, and ion exchange capacity of stationary phases. The chromatographic parameters of each test were shown to be uncorrelated. Despite this, the three protocols were equally successful in identifying similar and/or dissimilar stationary phases. The veracity of the results has been supported by some real life pharmaceutical separations. The use of Principal Component Analysis to identify similar/dissimilar phases appears to have some limitations in terms of loss of information. In contrast, the use of Euclidian distances is a much more convenient and reliable approach. The use of auto scaled data is favoured over the use of weighted factors as the former data transformation is less affected by the addition or removal of columns from the database. The use of these free databases and their corresponding software tools shown to be valid for identifying similar columns with equivalent chromatographic selectivity and retention as a "backup column". In addition, dissimilar columns with complimentary chromatographic selectivity can be identified for method development screening strategies. Copyright © 2013 Elsevier B.V. All rights reserved.

Strategic focus on 3R principles reveals major reductions in the use of animals in pharmaceutical toxicity testing.

PubMed

Törnqvist, Elin; Annas, Anita; Granath, Britta; Jalkesten, Elisabeth; Cotgreave, Ian; Öberg, Mattias

2014-01-01

The principles of the 3Rs, Replacement, Reduction and Refinement, are being increasingly incorporated into legislations, guidelines and practice of animal experiments in order to safeguard animal welfare. In the present study we have studied the systematic application of 3R principles to toxicological research in the pharmaceutical industry, with particular focus on achieving reductions in animal numbers used in regulatory and investigatory in vivo studies. The work also details major factors influencing these reductions including the conception of ideas, cross-departmental working and acceptance into the work process. Data from 36 reduction projects were collected retrospectively from work between 2006 and 2010. Substantial reduction in animal use was achieved by different strategies, including improved study design, method development and project coordination. Major animal savings were shown in both regulatory and investigative safety studies. If a similar (i.e. 53%) reduction had been achieved simultaneously within the twelve largest pharmaceutical companies, the equivalent reduction world-wide would be about 150,000 rats annually. The results point at the importance of a strong 3R culture, with scientific engagement, collaboration and a responsive management being vital components. A strong commitment in leadership for the 3R is recommended to be translated into cross-department and inter-profession involvement in projects for innovation, validation and implementation. Synergies between all the three Rs are observed and conclude that in silico-, in vitro- and in vivo-methods all hold the potential for applying the reduction R and should be consequently coordinated at a strategic level.

Standardized laboratory tests with 21 species of temperate and tropical sepsid flies confirm their suitability as bioassays of pharmaceutical residues (ivermectin) in cattle dung.

PubMed

Blanckenhorn, Wolf U; Puniamoorthy, Nalini; Schäfer, Martin A; Scheffczyk, Adam; Römbke, Jörg

2013-03-01

Veterinary pharmaceuticals excreted in the dung of treated livestock can have strong non-target effects on the dung organism community. We report results of ecotoxicological tests with ivermectin for 21 species of temperate (Europe, North America) and tropical (Asia, Central America) black scavenger flies (Diptera: Sepsidae), using standardized methods developed previously for the yellow dung fly and the face fly. Our study documents great variation in ivermectin sensitivity of more than two orders of magnitude among species and even populations within species: estimated lethal effect concentrations LC(50) (at which 50% of the flies died) ranged from 0.05 to 18.55 μg/kg dung fresh weight (equivalent to 0.33-132.22 μg/kg dung dry weight). We also show that controlled laboratory tests can--within reasonable limits-be extended to the field or to laboratory settings without climate control, as obtained LC(50) were roughly similar. In addition to lethal effects, our study revealed relevant sub-lethal effects at lower ivermectin concentrations in terms of prolonged development, smaller body size and reduced juvenile growth rate. Finally, oviposition choice experiments showed that females generally do not discriminate against dung containing ivermectin residues. We conclude that sepsid flies are well suited test organisms for pharmaceutical residues in the dung of livestock due to their ease and speed of rearing and handling, particularly in the tropics, where high-tech laboratory equipment is often not available. Copyright © 2012 Elsevier Inc. All rights reserved.

Strategic Focus on 3R Principles Reveals Major Reductions in the Use of Animals in Pharmaceutical Toxicity Testing

PubMed Central

Törnqvist, Elin; Annas, Anita; Granath, Britta; Jalkesten, Elisabeth; Cotgreave, Ian; Öberg, Mattias

2014-01-01

The principles of the 3Rs, Replacement, Reduction and Refinement, are being increasingly incorporated into legislations, guidelines and practice of animal experiments in order to safeguard animal welfare. In the present study we have studied the systematic application of 3R principles to toxicological research in the pharmaceutical industry, with particular focus on achieving reductions in animal numbers used in regulatory and investigatory in vivo studies. The work also details major factors influencing these reductions including the conception of ideas, cross-departmental working and acceptance into the work process. Data from 36 reduction projects were collected retrospectively from work between 2006 and 2010. Substantial reduction in animal use was achieved by different strategies, including improved study design, method development and project coordination. Major animal savings were shown in both regulatory and investigative safety studies. If a similar (i.e. 53%) reduction had been achieved simultaneously within the twelve largest pharmaceutical companies, the equivalent reduction world-wide would be about 150,000 rats annually. The results point at the importance of a strong 3R culture, with scientific engagement, collaboration and a responsive management being vital components. A strong commitment in leadership for the 3R is recommended to be translated into cross-department and inter-profession involvement in projects for innovation, validation and implementation. Synergies between all the three Rs are observed and conclude that in silico-, in vitro- and in vivo-methods all hold the potential for applying the reduction R and should be consequently coordinated at a strategic level. PMID:25054864

Neprilysin inhibition: a brief review of past pharmacological strategies for heart failure treatment and future directions

PubMed Central

Howell, Erik H.; Cameron, Scott J.

2016-01-01

Heart failure (HF) is a manifestation of aberrant vascular responses and remains a public health concern with a worldwide prevalence of around 23 million and a 5-year mortality numerically equivalent to many cancers. Over the last two decades, mortality from HF reached a plateau with current pharmaceutical agents and mechanical cardiac support. In the last several years, various “novel” pharmaceutical agents have been tested in clinical trials and ultimately met with disappointment, showing only incremental benefit in the treatment of HF. Designing a HF drug with enhanced efficacy over existing agents seemed like a Sisyphean task. Yet again, pharmaceutical chemists have demonstrated their prowess in lateral thinking by developing a vasoactive agent which is a co-crystallized compound of valsartan and sacubitril in a one-to-one molar ratio; the former molecule belongs to a family of agents that are the current standard of care for HF and the latter molecule is a novel agent which inhibits neprilysin — a neutral endopeptidase found in human plasma which alters neurohumoral responses. In July of 2015, a drug which is a combination of valsartan and sacubitril was formally licensed by the United States Food and Drug Administration for the treatment of HF. This review describes the evolution of HF medications focusing on rational drug design with the first HF medication, the beta adrenergic receptor antagonist. We then discuss the biochemical and physiological properties of sacubitril/valsartan which likely lead to its dramatic ability to ameliorate HF mortality. PMID:27665860

A Survey of Introductory Statistics Courses at University Faculties of Pharmaceutical Sciences in Japan.

PubMed

Matsumura, Mina; Nakayama, Takuto; Sozu, Takashi

2016-01-01

A survey of introductory statistics courses at Japanese medical schools was published as a report in 2014. To obtain a complete understanding of the way in which statistics is taught at the university level in Japan, it is important to extend this survey to related fields, including pharmacy, dentistry, and nursing. The current study investigates the introductory statistics courses offered by faculties of pharmaceutical sciences (six-year programs) at Japanese universities, comparing the features of these courses with those studied in the survey of medical schools. We collected relevant data from the online syllabi of statistics courses published on the websites of 71 universities. The survey items included basic course information (for example, the course names, the targeted student grades, the number of credits, and course classification), textbooks, handouts, the doctoral subject and employment status of each lecturer, and course contents. The period surveyed was July-September 2015. We found that these 71 universities offered a total of 128 statistics courses. There were 67 course names, the most common of which was "biostatistics (iryou toukeigaku)." About half of the courses were designed for first- or second-year students. Students earned fewer than two credits. There were 62 different types of textbooks. The lecturers held doctoral degrees in 18 different subjects, the most common being a doctorate in pharmacy or science. Some course content differed, reflecting the lecturers' academic specialties. The content of introductory statistics courses taught in pharmaceutical science programs also differed slightly from the equivalent content taught in medical schools.

Liquid chromatography quadrupole time-of-flight mass spectrometry determination of six pharmaceuticals in vegetal biota. Uptake study in Lavandula dentata.

PubMed

Barreales-Suárez, Sofía; Callejón-Mochón, Manuel; Azoulay, Stéphane; Bello-López, Miguel Ángel; Fernández-Torres, Rut

2018-05-01

A procedure based on microwave assisted extraction for the determination of 6 pharmaceuticals in samples of Lavandula dentata, Salicornia ramosissima and Juncus sp. by liquid chromatography-quadrupole time of flight mass spectrometry (LC-QTOF/MS) was optimized and validated. Best results were obtained using microwave assisted extraction of 1.0g of homogeneous lyophilized samples and 5mL of a mixture ACN:H 2 O (1:1 v/v) as extracting solvent. Analytical recoveries ranged from 60 to 107% with relative standard deviation (RSD) lower than 15%. Limits of quantitation (LOQ) for the 6 pharmaceuticals flumequine (FLM), carbamazepine (CBZ), ciprofloxacin (CPR), enrofloxacin (ENR), diclofenac (DCL), and ibuprofen (IBU) were in the range 20.8-125ngg -1 . The method was satisfactory applied for an uptake study in Lavandula dentata samples finding quantifying concentrations of FLM and CBZ in roots, leaf and stem. Copyright © 2017 Elsevier B.V. All rights reserved.

In-line monitoring of granule moisture in fluidized-bed dryers using microwave resonance technology.

PubMed

Buschmüller, Caroline; Wiedey, Wolfgang; Döscher, Claas; Dressler, Jochen; Breitkreutz, Jörg

2008-05-01

This is the first report on in-line moisture measurement of pharmaceutical products by microwave resonance technology. In order to meet the FDA's PAT approach, a microwave resonance sensor appropriate for pharmaceutical use was developed and implemented into two different fluidized-bed dryers. The novel sensor enables a continuous moisture measurement independent from the product density. Hence, for the first time precise real time determination of the moisture in pharmaceutical granules becomes possible. The qualification of the newly developed sensor was performed by drying placebo granules under experimental conditions and the validation using drug loaded granules under real process conditions. The results of the investigations show good correlations between water content of the granules determined by the microwave resonance sensor and both reference methods, loss on drying by infrared light exposure and Karl Fischer titration. Furthermore, a considerable time saving in the drying process was achieved through monitoring the residual water content continuously by microwave resonance technology instead of the formerly used discontinuous methods.

Comparative analysis of Lacistema pubescens and dexamethasone on topical treatment of skin inflammation in a chronic disease model and side effects.

PubMed

da Silva, Josiane M; Conegundes, Jéssica L M; Pinto, Nícolas C C; Mendes, Renata F; Castañon, Maria Christina M N; Scio, Elita

2018-04-01

This study aimed to evaluate the chronic topical anti-inflammatory activity of the pharmaceutical formulation ProHLP containing the hexane fraction of Lacistema pubescens (HLP). It was also investigated the possible cutaneous and systemic adverse effects of HLP and ProHLP in mice when compared to dexamethasone. The chronic topical anti-inflammatory activity was determined by croton oil multiple application-induced mouse ear oedema model. Histopathological analyses of ear tissue samples sensitized with croton oil were performed. Cutaneous atrophy induced by HLP and topical glucocorticoid treatments and excision skin wounds model to evidenced possible adverse reactions were also determined. ProHLP significantly reduced the mice ear oedema and considerably accelerated the wound-healing process. Also, HLP did not lead cutaneous atrophy and preserved the clinical aspect of the thymus, adrenal and spleen, unlike dexamethasone. The results suggested that ProHLP is an efficient and safer pharmaceutical formulation to treat chronic inflammatory diseases. © 2018 Royal Pharmaceutical Society.

[Evaluation of the pharmaceutical stability of polaprezinc/sodium alginate gargle solution containing lidocaine].

PubMed

Myotoku, Michiaki; Matsuyama, Tatsuto; Umetani, Ryosuke; Nakamura, Sayaka; Oka, Takashi; Kitade, Naoko; Urashima, Yoko; Hirotani, Yoshihiko

2015-02-01

A gargle solution(L-P/AG)for the treatment of painful stomatitis was prepared by adding lidocaine to a polaprezinc/sodium alginate gargle solution(P/AG), and its pharmaceutical stability was evaluated. L-P/AG was stored at 5, 25, and 40°C. The strengths of polaprezinc and lidocaine were determined. The viscosity and pH of L-P/AG were also determined, and its appearance was evaluated. When stored at 5 or 25°C in a dark place, L-P/AG showed neither reduction in the strength of either drug nor did it show a change in the viscosity, pH, or appearance. When stored exposed to light at 40°C, L-P/AG showed reductions in the strength of both drugs, as well as in viscosity and pH; furthermore, a change in appearance was noted. L-P/AG prepared for the treatment of painful stomatitis remains pharmaceutically stable for 28 days when stored at 25°C in a dark place.

Determination of ibuprofen and flurbiprofen in pharmaceuticals by capillary zone electrophoresis.

PubMed

Hamoudová, Rafifa; Pospísilová, Marie

2006-06-16

Capillary zone electrophoresis with spectrophotometric detection was used for the determination of ibuprofen (IB) and flurbiprofen (FL) in pharmaceuticals. The separation was carried out in a fused silica capillary (60 cm x 100 microm i.d. effective length 45 cm) at 30 kV with UV detection at 232 nm. The optimized background electrolyte was 20mM N-(2-acetamido)-2-aminoethanesulfonic acid (ACES) with 20mM imidazole and 10mM alpha-cyclodextrin of pH 7.3. 2-Naphthoxyacetic acid was used as internal standard. A single analysis took less than 5 min. Rectilinear calibration ranges were 2-500 mg l(-1) for IB and 1-60 mg l(-1) for FL. The relative standard deviations (R.S.D.) values (n=6) were 1.53% for IB and 1.29% for FL (for 200 mg l(-1) IB and 10 mg l(-1) FL). This validated method has been successfully applied for the routine analysis of 10 commercially available pharmaceutical preparations (syrup, tablets, cream and gel).

Development and validation of a fast static headspace GC method for determination of residual solvents in permethrin.

PubMed

Tian, Jingzhi; Rustum, Abu

2016-09-05

A fast static headspace gas chromatography (HS-GC) method was developed to separate all residual solvents present in commercial active pharmaceutical ingredient (API) batches of permethrin. A total of six residual solvents namely 2-methylpentane, 3-methylpentane, methylcyclopentane, n-hexane, cyclohexane and toluene were found in typical commercial batches of permethrin; and three of them are not in the list of ICH solvents. All six residual solvents were baseline separated in five minutes by the new method presented in this paper. The method was successfully validated as per International Conference on Harmonisation (ICH) guidelines. Evaluation of this method was conducted to separate 26 commonly used solvents in the manufacturing of various APIs, key intermediates of APIs and pharmaceutical excipients. The results of the evaluation demonstrated that this method can also be used as a general method to determine residual solvents in various APIs, intermediates and excipients that are used in pharmaceutical products. Copyright © 2016 Elsevier B.V. All rights reserved.

Clinical Equivalence of Generic and Brand-Name Drugs Used in Cardiovascular Disease

PubMed Central

Kesselheim, Aaron S.; Misono, Alexander S.; Lee, Joy L.; Stedman, Margaret R.; Brookhart, M. Alan; Choudhry, Niteesh K.; Shrank, William H.

2009-01-01

Context Use of generic drugs, which are bioequivalent to brand-name drugs, can help contain prescription drug spending. However, there is concern among patients and physicians that brand-name drugs may be clinically superior to generic drugs. Objectives To summarize clinical evidence comparing generic and brand-name drugs used in cardiovascular disease and to assess the perspectives of editorialists on this issue. Data Sources Systematic searches of peer-reviewed publications in MEDLINE, EMBASE, and International Pharmaceutical Abstracts from January 1984 to August 2008. Study Selection Studies compared generic and brand-name cardiovascular drugs using clinical efficacy and safety end points. We separately identified editorials addressing generic substitution. Data Extraction We extracted variables related to the study design, setting, participants, clinical end points, and funding. Methodological quality of the trials was assessed by Jadad and Newcastle-Ottawa scores, and a meta-analysis was performed to determine an aggregate effect size. For editorials, we categorized authors’ positions on generic substitution as negative, positive, or neutral. Results We identified 47 articles covering 9 subclasses of cardiovascular medications, of which 38 (81%) were randomized controlled trials (RCTs). Clinical equivalence was noted in 7 of 7 RCTs (100%) of β-blockers, 10 of 11 RCTs (91%) of diuretics, 5 of 7 RCTs (71%) of calcium channel blockers, 3 of 3 RCTs (100%) of antiplatelet agents, 2 of 2 RCTs (100%) of statins, 1 of 1 RCT (100%) of angiotensin-converting enzyme inhibitors, and 1 of 1 RCT (100%) of α-blockers. Among narrow therapeutic index drugs, clinical equivalence was reported in 1 of 1 RCT (100%) of class 1 antiarrhythmic agents and 5 of 5 RCTs (100%) of warfarin. Aggregate effect size (n = 837) was −0.03 (95% confidence interval, −0.15 to 0.08), indicating no evidence of superiority of brand-name to generic drugs. Among 43 editorials, 23 (53%) expressed a negative view of generic drug substitution. Conclusions Whereas evidence does not support the notion that brand-name drugs used in cardiovascular disease are superior to generic drugs, a substantial number of editorials counsel against the interchangeability of generic drugs. PMID:19050195

Inequalities in medicine use in Central Eastern Europe: an empirical investigation of socioeconomic determinants in eight countries.

PubMed

Vogler, Sabine; Österle, August; Mayer, Susanne

2015-11-05

Equitable access to essential medicines is a major challenge for policy-makers world-wide, including Central and Eastern European countries. Member States of the European Union situated in Central and Eastern Europe have publicly funded pharmaceutical reimbursement systems that should promote accessibility and affordability of, at least essential medicines. However, there is no knowledge whether socioeconomic inequalities exist in these countries. Against this backdrop, this study analyses whether socioeconomic determinants influence the use of prescribed and non-prescribed medicines in eight Central and Eastern European countries (Bulgaria, Czech Republic, Hungary, Latvia, Poland, Romania, Slovenia, Slovakia). Further, the study discusses observed (in)equalities in medicine use in the context of the pharmaceutical policy framework and the implementation in these countries. The study is based on cross-sectional data from the first wave of the European Health Interview Survey (2007-2009). Multivariate logistic regression analyses were carried out to determine the association between socioeconomic status (measured by employment status, education, income; controlled for age, gender, health status) and medicine use (prescribed and non-prescribed medicines). This was supplemented by a pharmaceutical policy analysis based on indicators in four policy dimensions (sustainable funding, affordability, availability and accessibility, and rational selection and use of medicines). Overall, the analysis showed a gradient favouring individuals from higher socioeconomic groups in the consumption of non-prescribed medicines in the eight surveyed countries, and for prescribed medicines in three countries (Latvia, Poland, Romania). The pharmaceutical systems in the eight countries were, to varying degrees, characterized by a lack of (public) funding, thus resulting in high and growing shares of private financing (including co-payments for prescribed medicines), inefficiencies in the selection of medicines into reimbursement and limitations in medicines availability. Pharmaceutical policies aiming at reducing inequalities in medicine use require not only a consideration of the role of co-payments and other private expenditure but also adequate investment in medicines and transparent and clear processes regarding the inclusion of medicines into reimbursement.

Impact of cross-reference pricing on pharmaceutical prices: manufacturers' pricing strategies and price regulation.

PubMed

Stargardt, Tom; Schreyögg, Jonas

2006-01-01

Several EU countries are determining reimbursement prices of pharmaceuticals by cross-referencing prices of foreign countries. Our objective is to quantify the theoretical cross-border spill-over effects of cross-reference pricing schemes on pharmaceutical prices in the former EU-15 countries. An analytical model was developed estimating the impact of pharmaceutical price changes in Germany on pharmaceutical prices in other countries in the former EU-15 using cross-reference pricing. We differentiated between the direct impact (from referencing to Germany directly) and the indirect impact (from referencing to other countries that conduct their own cross-reference pricing schemes). The relationship between the direct and indirect impact of a price change depends mainly on the method applied to set reimbursement prices. When applying cross-reference pricing, the reimbursement price is either determined by the lowest of foreign prices (e.g. Portugal), the average of foreign prices (e.g. Ireland) or a weighted average of foreign prices (e.g. Italy). If the respective drug is marketed in all referenced countries and prices are regularly updated, a price reduction of 1.00 euro in Germany will reduce maximum reimbursement prices in the former EU-15 countries from 0.15 euros in Austria to 0.36 euros in Italy. On one side, the cross-border spill-over effects of price reductions are undoubtedly welcomed by decision makers and may be favourable to the healthcare system in general. On the other side, these cross-border spill-over effects also provide strong incentives for strategic product launches, launch delays and lobbying activities, and can affect the effectiveness of regulation. To avoid the negative effects of cross-reference pricing, a weighted index of prices from as many countries as possible should be used to determine reimbursement prices in order to reduce the direct and indirect impact of individual countries.

Importance of MS selectivity and chromatographic separation in LC-MS/MS-based methods when investigating pharmaceutical metabolites in water. Dipyrone as a case of study.

PubMed

Ibáñez, M; Gracia-Lor, E; Sancho, J V; Hernández, F

2012-08-01

Pharmaceuticals are emerging contaminants of increasing concern because of their presence in the aquatic environment and potential to reach drinking-water sources. After human and/or veterinary consumption, pharmaceuticals can be excreted in unchanged form, as the parent compound, and/or as free or conjugated metabolites. Determination of most pharmaceuticals and metabolites in the environment is commonly made by liquid chromatography (LC) coupled to mass spectrometry (MS). LC coupled to tandem MS is the technique of choice nowadays in this field. The acquisition of two selected reaction monitoring (SRM) transitions together with the retention time is the most widely accepted criterion for a safe quantification and confirmation assay. However, scarce attention is normally paid to the selectivity of the selected transitions as well as to the chromatographic separation. In this work, the importance of full spectrum acquisition high-resolution MS data using a hybrid quadrupole time-of-flight analyser and/or a suitable chromatographic separation (to reduce the possibility of co-eluting interferences) is highlighted when investigating pharmaceutical metabolites that share common fragment ions. For this purpose, the analytical challenge associated to the determination of metabolites of the widely used analgesic dipyrone (also known as metamizol) in urban wastewater is discussed. Examples are given on the possibilities of reporting false positives of dypirone metabolites by LC-MS/MS under SRM mode due to a wrong assignment of identity of the compounds detected. Copyright © 2012 John Wiley & Sons, Ltd.

A mathematical model of avian influenza with half-saturated incidence.

PubMed

Chong, Nyuk Sian; Tchuenche, Jean Michel; Smith, Robert J

2014-03-01

The widespread impact of avian influenza viruses not only poses risks to birds, but also to humans. The viruses spread from birds to humans and from human to human In addition, mutation in the primary strain will increase the infectiousness of avian influenza. We developed a mathematical model of avian influenza for both bird and human populations. The effect of half-saturated incidence on transmission dynamics of the disease is investigated. The half-saturation constants determine the levels at which birds and humans contract avian influenza. To prevent the spread of avian influenza, the associated half-saturation constants must be increased, especially the half-saturation constant H m for humans with mutant strain. The quantity H m plays an essential role in determining the basic reproduction number of this model. Furthermore, by decreasing the rate β m at which human-to-human mutant influenza is contracted, an outbreak can be controlled more effectively. To combat the outbreak, we propose both pharmaceutical (vaccination) and non-pharmaceutical (personal protection and isolation) control methods to reduce the transmission of avian influenza. Vaccination and personal protection will decrease β m, while isolation will increase H m. Numerical simulations demonstrate that all proposed control strategies will lead to disease eradication; however, if we only employ vaccination, it will require slightly longer to eradicate the disease than only applying non-pharmaceutical or a combination of pharmaceutical and non-pharmaceutical control methods. In conclusion, it is important to adopt a combination of control methods to fight an avian influenza outbreak.

Validation of Milliflex® Quantum for Bioburden Testing of Pharmaceutical Products.

PubMed

Gordon, Oliver; Goverde, Marcel; Staerk, Alexandra; Roesti, David

2017-01-01

This article reports the validation strategy used to demonstrate that the Milliflex ® Quantum yielded non-inferior results to the traditional bioburden method. It was validated according to USP <1223>, European Pharmacopoeia 5.1.6, and Parenteral Drug Association Technical Report No. 33 and comprised the validation parameters robustness, ruggedness, repeatability, specificity, limit of detection and quantification, accuracy, precision, linearity, range, and equivalence in routine operation. For the validation, a combination of pharmacopeial ATCC strains as well as a broad selection of in-house isolates were used. In-house isolates were used in stressed state. Results were statistically evaluated regarding the pharmacopeial acceptance criterion of ≥70% recovery compared to the traditional method. Post-hoc test power calculations verified the appropriateness of the used sample size to detect such a difference. Furthermore, equivalence tests verified non-inferiority of the rapid method as compared to the traditional method. In conclusion, the rapid bioburden on basis of the Milliflex ® Quantum was successfully validated as alternative method to the traditional bioburden test. LAY ABSTRACT: Pharmaceutical drug products must fulfill specified quality criteria regarding their microbial content in order to ensure patient safety. Drugs that are delivered into the body via injection, infusion, or implantation must be sterile (i.e., devoid of living microorganisms). Bioburden testing measures the levels of microbes present in the bulk solution of a drug before sterilization, and thus it provides important information for manufacturing a safe product. In general, bioburden testing has to be performed using the methods described in the pharmacopoeias (membrane filtration or plate count). These methods are well established and validated regarding their effectiveness; however, the incubation time required to visually identify microbial colonies is long. Thus, alternative methods that detect microbial contamination faster will improve control over the manufacturing process and speed up product release. Before alternative methods may be used, they must undergo a side-by-side comparison with pharmacopeial methods. In this comparison, referred to as validation, it must be shown in a statistically verified manner that the effectiveness of the alternative method is at least equivalent to that of the pharmacopeial methods. Here we describe the successful validation of an alternative bioburden testing method based on fluorescent staining of growing microorganisms applying the Milliflex ® Quantum system by MilliporeSigma. © PDA, Inc. 2017.

Determination of human pharmaceuticals in pre- and post-sewage treatment

NASA Astrophysics Data System (ADS)

Tahrim, Nurfaizah Abu; Abdullah, Md. Pauzi; Aziz, Yang Farina Abdul

2013-11-01

In this present work, an analytical method based on solid phase extraction (SPE) followed by liquid chromatography-time-of-flight mass spectrometry (LC-TOF-MS) in positive electrospray ionisation mode was successfully applied to real samples for the determination of human pharmaceuticals in pre- and post-sewage treatment samples. The ten target compounds selected in this study include acetaminophen, theophylline, caffeine, metoprolol, sulfamethoxazole, carbamazepine, prednisolone, ketoprofen, norgestrel and simvastatin. Acetaminophen, theophylline and caffeine were present at all five raw sewage samples. In addition, this work provides the first report on the investigation and detection of theophylline in sewage treatment plant (STP) samples in Malaysia.

Spectrophotometric determination of ketoprofen and its application in pharmaceutical analysis.

PubMed

Kormosh, Zholt; Hunka, Iryna; Basel, Yaroslav

2009-01-01

A new simple rapid and sensitive spectrophotometric method has been developed for the determination of ketoprofen in pharmaceutical preparations. The method is based on the reaction of ketoprofen with an analytical reagent--Astra Phloxin FF--at pH 8.0-10.8 and followed by the extraction of formed ion associate in toluene with spectrophotometric detection (it has an absorption maximum at 563 nm, epsilon = 7.6 x 10(4) L x mol(-1) x cm(-1)). The calibration plot was linear from 0.8-16.0 microg x mL(-1) of ketoprofen, and the detection limit was 0.037 microg x mL(-1).

A RP-LC method with evaporative light scattering detection for the assay of simethicone in pharmaceutical formulations.

PubMed

Moore, Douglas E; Liu, Tina X; Miao, William G; Edwards, Alison; Elliss, Russell

2002-09-05

A reversed-phase liquid chromatographic method has been developed and validated for the determination of the polydimethylsiloxane (PDMS) component of Simethicone, which is used as an anti-foaming agent in pharmaceutical formulations. The method involves acidification to neutralise antacid components of the formulation, then a single extraction of the PDMS with dichloromethane. This is followed by separation with a reversed-phase column using an acetonitrile-chloroform solvent gradient, and quantification by an evaporative light scattering detector. An assay precision of 3% was achieved in intraday and interday determinations. No interference was found from the aluminium and magnesium hydroxide components of antacid formulations.

Investigating sources of pharmaceutical pollution: Survey of over-the-counter and prescription medication purchasing, use, and disposal practices among university students.

PubMed

Vatovec, Christine; Van Wagoner, Emily; Evans, Corey

2017-08-01

Pharmaceutical pollution in surface waters poses a range of risks to public health and aquatic ecosystems. Consumers contribute to pharmaceutical pollution via use and disposal of medications, though data on such behaviors is limited. This paper investigates the purchasing, use, and disposal practices among a population that has been researched only minimally to date, yet will determine pharmaceutical pollution for decades to come: young adults represented by a university student population. We employed an online, 21-question survey to examine behaviors related to pharmaceuticals among students at the University of Vermont (n = 358). Results indicate that the majority of respondents had purchased medications in the previous 12 months (94%), and had leftover drugs (61%). Contrary to previous studies of older populations, only a small proportion of students had disposed of drugs (18%); municipal trash was the primary route of drug disposal (25%), and very few students disposed drugs via flushing (1%). Less than a quarter of students were aware of drug take-back programs (24%), and only 4% had ever used take-back services. These findings indicate that the university student population may be storing a large volume of unused drugs that will require future disposal. Increasing awareness of, access to, and participation in pro-environment pharmaceutical behaviors, such as purchasing over-the-counter medication in smaller quantities and utilizing drug take-back programs, could minimize future pharmaceutical pollution from this population. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pharmaceutical Occurrence in Groundwater and Surface Waters in Forests Land-Applied with Municipal Wastewater

PubMed Central

McEachran, Andrew D.; Shea, Damian; Bodnar, Wanda; Nichols, Elizabeth Guthrie

2016-01-01

The occurrence and fate of pharmaceutical and personal care products in the environment are of increasing public importance because of their ubiquitous nature and documented effects on wildlife, ecosystems, and potentially humans. One potential, yet undefined, source of entry of pharmaceuticals into the environment is via the land application of municipal wastewater onto permitted lands. The objective of the present study is to determine the extent to which pharmaceuticals are mitigated by or exported from managed tree plantations irrigated with municipal wastewater. A specific focus of the present study is the presence of pharmaceutical compounds in groundwater and surface water discharge. The study site is a municipality that land-applies secondary treated wastewater onto 930 hectares of a 2000-hectare managed hardwood and pine plantation. A suite of 33 pharmaceuticals and steroid hormones was targeted in the analysis, which consisted of monthly grab sampling of groundwater, surface water, and wastewater, followed by concentration and cleanup via solid phase extraction and separation, detection, and quantification via liquid chromatography coupled with tandem mass spectrometry. More than one-half of all compounds detected in irrigated wastewater were not present in groundwater and subsequent surface water. However, antibiotics, nonsteroidal anti-inflammatory drugs, caffeine, and other prescription and over-the-counter drugs remained in groundwater and were transported into surface water at concentrations up to 10 ng/L. These results provide important documentation for pharmaceutical fate and transport in forest systems irrigated with municipal wastewater, a previously undocumented source of environmental entry. PMID:26297815

[The pharmaceutical market in Mexico: size, value, and concentration].

PubMed

Torres Guerra, Sandra; Gutiérrez, Juan Pablo

2009-07-01

To describe the pharmaceutical drug market in Mexico in terms of its size, structure, business' market power, and consumer negotiating power. A descriptive study based on data from the 2004 Economics Census and the reports of IMS Health, Inc. (Norwalk, Connecticut, United States of America). Sales amounts and volumes of Mexico's pharmaceutical companies from 2002-2005 were obtained and the Herfindahl-Hirschman Index (HHI) and its inverse were calculated as indicators of the market's degree of concentration; also, price elasticity was determined by a product index. The total value of the products manufactured by the pharmaceutical sector was 115 billion in 2006 Mexican pesos, of which 99% pertained to companies categorized as large. This amount constituted 1.2% of the national gross domestic product that year (20.0% of the health sector's portion, estimated to be 6.0%) and 3.9% of the total value of manufactured goods. The HHI of Mexico's pharmaceutical market during the study period was about 0.04, albeit with a steady decline, and its inverse decreased from 23 to 26. The price elasticity of pharmaceutical products was minimal (0.007, 0.003, and -0.002). This study constitutes a preliminary description of Mexico's pharmaceutical market, one of the country's most dynamic economic sectors. It confirmed that the market is a rigid oligopoly, and thus supports enactment of firmer regulatory tools to reduce the power of the manufacturers in favor of that of the consumers.

Silver nanoparticles enhanced flow injection chemiluminescence determination of gatifloxacin in pharmaceutical formulation and spiked urine sample.

PubMed

Wabaidur, Saikh mohammad; Alam, Seikh Mafiz; Alothman, Zeid A; Mohsin, Kazi

2015-06-05

Silver nanoparticles have been utilized for the enhanced chemiluminogenic estimation of fluoroquinolone antibiotic gatifloxacin. It has been found that the weak chemiluminescence intensity produced from the reaction between calcein and KMnO4 can further be strengthened by the addition of silver nanoparticles in the presence of gatifloxacin. This phenomenon has been exploited to the quantitative determination of gatifloxacin. Under the optimum experimental conditions, the calibration curves are linear over the range of 8.9×10(-9)-4.0×10(-6) M, while the limits of detections were found to be 2.6×10(-9) M with correlation coefficient value (r(2)) 0.9999. The relative standard deviation calculated from six replicate measurements (1.0×10(-4) M gatifloxacin) was 1.70%. The method was applied to pharmaceutical preparations and the results obtained were in reasonable agreement with the amount labeled on the formulations. The proposed method was also used for the determination of gatifloxacin in spiked urine samples with satisfactory results. No interference effects from some common excipients used in pharmaceutical preparations have been found. Copyright © 2015 Elsevier B.V. All rights reserved.

Video approach to chemiluminescence detection using a low-cost complementary metal oxide semiconductor (CMOS)-based camera: determination of paracetamol in pharmaceutical formulations.

PubMed

Lahuerta-Zamora, Luis; Mellado-Romero, Ana M

2017-06-01

A new system for continuous flow chemiluminescence detection, based on the use of a simple and low-priced lens-free digital camera (with complementary metal oxide semiconductor technology) as a detector, is proposed for the quantitative determination of paracetamol in commercial pharmaceutical formulations. Through the camera software, AVI video files of the chemiluminescence emission are captured and then, using friendly ImageJ public domain software (from National Institutes for Health), properly processed in order to extract the analytical information. The calibration graph was found to be linear over the range 0.01-0.10 mg L -1 and over the range 1.0-100.0 mg L -1 of paracetamol, the limit of detection being 10 μg L -1 . No significative interferences were found. Paracetamol was determined in three different pharmaceutical formulations: Termalgin®, Efferalgan® and Gelocatil®. The obtained results compared well with those declared on the formulation label and with those obtained through the official analytical method of British Pharmacopoeia. Graphical abstract Abbreviated scheme of the new chemiluminescence detection system proposed in this paper.

Simultaneous determination of ezetimibe and simvastatin in pharmaceutical preparations by MEKC.

PubMed

Yardimci, Ceren; Ozaltin, Nuran

2010-02-01

A micellar electrokinetic capillary chromatography method was developed and validated for the simultaneous determination of ezetimibe and simvastatin in pharmaceutical preparations. The influence of buffer concentration, buffer pH, sodium dodecyl sulphate (SDS) concentration, organic modifier, capillary temperature, applied voltage, and injection time was investigated, and the method validation studies were performed. The optimum separation for these analytes was achieved in less than 10 min at 30 degrees C with a fused-silica capillary column (56 cm x 50 microm i.d.) and a 25mM borate buffer at pH 9.0 containing 25mM SDS and 10% (v/v) acetonitrile. The samples were injected hydrodynamically for 3 s at 50 mbar, and the applied voltage was +30.0 kV. Detection wavelength was set at 238 nm. Diflunisal was used as internal standard. The method was suitably validated with respect to stability, specificity, linearity, limits of detection and quantification, accuracy, precision, and robustness. The limits of detection and quantification were 1.0 and 2.0 microg/mL for both ezetimibe and simvastatin, respectively. The method developed was successfully applied to the simultaneous determination of ezetimibe and simvastatin in pharmaceutical preparations.

Variance Assistance Document: Land Disposal Restrictions Treatability Variances and Determinations of Equivalent Treatment

EPA Pesticide Factsheets

This document provides assistance to those seeking to submit a variance request for LDR treatability variances and determinations of equivalent treatment regarding the hazardous waste land disposal restrictions program.

PACCE: Perl Algorithm to Compute Continuum and Equivalent Widths

NASA Astrophysics Data System (ADS)

Riffel, Rogério; Borges Vale, Tibério

2011-05-01

PACCE (Perl Algorithm to Compute continuum and Equivalent Widths) computes continuum and equivalent widths. PACCE is able to determine mean continuum and continuum at line center values, which are helpful in stellar population studies, and is also able to compute the uncertainties in the equivalent widths using photon statistics.

The importance of being first: evidence from Canadian generic pharmaceuticals.

PubMed

Hollis, Aidan

2002-12-01

This paper uses pooled cross-section data on Canadian ethical drug sales to examine the effect of entry timing on sales of generic drugs. The data is for all drugs for which the first generic competitor entered during the years 1994-1997. It is found that the first generic entrant has a lasting competitive advantage: being first into the market appears to lead to an increase of around 30% in market share (among generics) over a period of at least 4 years. This finding has considerable implications for the current policy of allowing brandname drug companies to issue pseudo-generic equivalents as a preemptive strike against true generic competitors. Copyright 2002 John Wiley & Sons, Ltd.

76 FR 51992 - Determination That PENTETATE ZINC TRISODIUM (Zinc Trisodium Diethylenetriaminepentaacetate...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-19

... Intravenous or Inhalation Administration, Equivalent to 1 Gram Base/5 Milliliters (Equivalent to 200... for intravenous or inhalation administration, equivalent to (EQ) 1 gram (g) base/5 milliliters (mL...

Quantitative aspects of microchip isotachophoresis for high precision determination of main components in pharmaceuticals.

PubMed

Hradski, Jasna; Chorváthová, Mária Drusková; Bodor, Róbert; Sabo, Martin; Matejčík, Štefan; Masár, Marián

2016-12-01

Although microchip electrophoresis (MCE) is intended to provide reliable quantitative data, so far there is only limited attention paid to these important aspects. This study gives a general overview of key aspects to be followed to reach high-precise determination using isotachophoresis (ITP) on the microchip with conductivity detection. From the application point of view, the procedure for the determination of acetate, a main component in the pharmaceutical preparation buserelin acetate, was developed. Our results document that run-to-run fluctuations in the sample injection volume limit the reproducibility of quantitation based on the external calibration. The use of a suitable internal standard (succinate in this study) improved the repeatability of the precision of acetate determination from six to eight times. The robustness of the procedure was studied in terms of impact of fluctuations in various experimental parameters (driving current, concentration of the leading ions, pH of the leading electrolyte and buffer impurities) on the precision of the ITP determination. The use of computer simulation programs provided means to assess the ITP experiments using well-defined theoretical models. A long-term validity of the calibration curves on two microchips and two MCE equipments was verified. This favors ITP over other microchip electrophoresis techniques, when chip-to-chip or equipment-to-equipment transfer of the analytical method is required. The recovery values in the range of 98-101 % indicate very accurate determination of acetate in buserelin acetate, which is used in the treatment of hormone-dependent tumors. This study showed that microchip ITP is suitable for reliable determination of main components in pharmaceutical preparations.

Determination of Human-Health Pharmaceuticals in Filtered Water by Chemically Modified Styrene-Divinylbenzene Resin-Based Solid-Phase Extraction and High-Performance Liquid Chromatography/Mass Spectrometry

USGS Publications Warehouse

Furlong, Edward T.; Werner, Stephen L.; Anderson, Bruce D.; Cahill, Jeffery D.

2008-01-01

In 1999, the Methods Research and Development Program of the U.S. Geological Survey National Water Quality Laboratory began the process of developing a method designed to identify and quantify human-health pharmaceuticals in four filtered water-sample types: reagent water, ground water, surface water minimally affected by human contributions, and surface water that contains a substantial fraction of treated wastewater. Compounds derived from human pharmaceutical and personal-care product use, which enter the environment through wastewater discharge, are a newly emerging area of concern; this method was intended to fulfill the need for a highly sensitive and highly selective means to identify and quantify 14 commonly used human pharmaceuticals in filtered-water samples. The concentrations of 12 pharmaceuticals are reported without qualification; the concentrations of two pharmaceuticals are reported as estimates because long-term reagent-spike sample recoveries fall below acceptance criteria for reporting concentrations without qualification. The method uses a chemically modified styrene-divinylbenzene resin-based solid-phase extraction (SPE) cartridge for analyte isolation and concentration. For analyte detection and quantitation, an instrumental method was developed that used a high-performance liquid chromatography/mass spectrometry (HPLC/MS) system to separate the pharmaceuticals of interest from each other and coextracted material. Immediately following separation, the pharmaceuticals are ionized by electrospray ionization operated in the positive mode, and the positive ions produced are detected, identified, and quantified using a quadrupole mass spectrometer. In this method, 1-liter water samples are first filtered, either in the field or in the laboratory, using a 0.7-micrometer (um) nominal pore size glass-fiber filter to remove suspended solids. The filtered samples then are passed through cleaned and conditioned SPE cartridges at a rate of about 15 milliliters per minute. Excess water is eliminated from the cartridge sorbent bed by passing air through the cartridges, and the analytes retained on the SPE bed are eluted from the cartridge sequentially, first with methanol, followed by acidified methanol, and combined in collection tubes. This sample extract then is reduced from about 10 milliliters (mL) to about 0.1 mL (or 100 microliters) under a stream of purified nitrogen gas with the collection tubes in a heated (40 degrees C) water bath. The reduced extracts then are fortified with an internal standard solution (when using internal standard quantitation), brought to a final volume of 1 mL with an aqueous ammonium formate buffer solution, and filtered through a 0.2-um Teflon syringe filter as they are transferred into vials for instrumental analysis. Instrumental analysis by the HPLC/MS procedure permits determination of individual pharmaceutical concentrations from 0.005 to 1.0 microgram per liter, based on the lowest and the highest calibration standards routinely used. The reporting levels for this method are compound dependent, and have been experimentally determined based on the precision of quantitation of compounds from eight fortified organic-free water samples in single-operator experiments. The method detection limits and interim reporting levels for the compounds determined by this method were calculated from recoveries of the pharmaceuticals from reagent-water samples amended at 0.05 microgram per liter, and ranged between 0.0069 and 0.0142 microgram per liter, and 0.015 and 0.10 microgram per liter, respectively. Concentrations for 12 compounds are reported without qualification, and for two compounds are reported as qualified estimates. After initial development, the method was applied to more than 1,800 surface-, ground-, and wastewater samples from 2002 to 2005 and documented in a number of published studies. This research application of the method provided the opportunity to collect a l

Simultaneous determination of caffeine, paracetamol, and ibuprofen in pharmaceutical formulations by high-performance liquid chromatography with UV detection and by capillary electrophoresis with conductivity detection.

PubMed

Cunha, Rafael R; Chaves, Sandro C; Ribeiro, Michelle M A C; Torres, Lívia M F C; Muñoz, Rodrigo A A; Dos Santos, Wallans T P; Richter, Eduardo M

2015-05-01

Paracetamol, caffeine and ibuprofen are found in over-the-counter pharmaceutical formulations. In this work, we propose two new methods for simultaneous determination of paracetamol, caffeine and ibuprofen in pharmaceutical formulations. One method is based on high-performance liquid chromatography with diode-array detection and the other on capillary electrophoresis with capacitively coupled contactless conductivity detection. The separation by high-performance liquid chromatography with diode-array detection was achieved on a C18 column (250×4.6 mm(2), 5 μm) with a gradient mobile phase comprising 20-100% acetonitrile in 40 mmol L(-1) phosphate buffer pH 7.0. The separation by capillary electrophoresis with capacitively coupled contactless conductivity detection was achieved on a fused-silica capillary (40 cm length, 50 μm i.d.) using 10 mmol L(-1) 3,4-dimethoxycinnamate and 10 mmol L(-1) β-alanine with pH adjustment to 10.4 with lithium hydroxide as background electrolyte. The determination of all three pharmaceuticals was carried out in 9.6 min by liquid chromatography and in 2.2 min by capillary electrophoresis. Detection limits for caffeine, paracetamol and ibuprofen were 4.4, 0.7, and 3.4 μmol L(-1) by liquid chromatography and 39, 32, and 49 μmol L(-1) by capillary electrophoresis, respectively. Recovery values for spiked samples were between 92-107% for both proposed methods. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

R&D Implementation in a Department of Laboratory Medicine and Pathology: A Systematic Review Based on Pharmaceutical Companies

PubMed Central

Feulefack, Joseph; Sergi, Consolato

2015-01-01

A systematic literature review on pharmaceutical companies may be a tool for guiding some procedures of R&D implementation in a department of Laboratory Medicine and Pathology. The use of pharmaceutical companies for this specific analysis arises from less variability of standards than healthcare facilities. In this qualitative and quantitative analysis, we focused on three useful areas of implementation, including R&D productivity, commercialization strategies, and expenditures determinants of pharmaceutical companies. Studies and reports of online databases from 1965 to 2014 were reviewed according to specific search terms. Initially, 218 articles and reports were found and examined, but only 91 were considered appropriate and used for further analysis. We identified some suggested implementation strategies relevant for marketing to enhance companies’ own R&D strategies; such as reliability of companies on “sourcing-in” R&D facilities and “think-tank” events. Regardless of the study and of the country, cash flow and profitability always positively influenced R&D expenditure, while sales and firm size did not. We consider that handling R&D determinants should require caution. It seems critical that implementation of R&D systems is directly related with productivity, if it reflects dual embodiment of efficiency and effectiveness. Scrutinizing the determinants of R&D expenditures emphasizes significant factors that are worth to highlight when planning an R&D investment strategy. Although there is no receipt fitting every situation, we think that health care plan makers may find relevant data in this systematic review in creating an initial implementation framework. PMID:25946935

Determination of phenols and pharmaceuticals in municipal wastewaters from Polish treatment plants by ultrasound-assisted emulsification-microextraction followed by GC-MS.

PubMed

Kotowska, Urszula; Kapelewska, Justyna; Sturgulewska, Joanna

2014-01-01

A method combining ultrasound-assisted emulsification-microextraction (USAEME) with gas chromatography-mass spectrometry (GC-MS) was developed for simultaneous determination of four acidic pharmaceuticals, ibuprofen, naproxen, ketoprofen, and diclofenac, as well as four phenols, 4-octylphenol, 4-n-nonylphenol, bisphenol A, and triclosan in municipal wastewaters. Conditions of extraction and simultaneous derivatization were optimized with respect to such aspects as type and volume of extraction solvent, volume of derivatization reagent, kind and amount of buffering salt, location of the test tube in the ultrasonic bath, and extraction time. The average correlation coefficient of the calibration curves was 0.9946. The LOD/(LOQ) values in influent and effluent wastewater were in the range of 0.002-0.121/(0.005-0.403) μg L(-1) and 0.002-0.828/(0.006-2.758) μg L(-1), respectively. Quantitative recoveries (≥94%) and satisfactory precision (average RSD 8.2%) were obtained. The optimized USAEME/GC-MS method was applied for determination of the considered pharmaceuticals and phenols in influents and treated effluents from nine Polish municipal wastewater treatment plants. The average concentration of acidic pharmaceuticals in influent and effluent wastewater were in the range of 0.06-551.96 μg L(-1) and 0.01-22.61 μg L(-1), respectively, while for phenols were in the range of 0.03-102.54 μg L(-1) and 0.02-10.84 μg L(-1), respectively. The removal efficiencies of the target compounds during purification process were between 84 and 99%.

A validated high performance thin layer chromatography method for determination of yohimbine hydrochloride in pharmaceutical preparations

PubMed Central

Badr, Jihan M.

2013-01-01

Background: Yohimbine is an indole alkaloid used as a promising therapy for erectile dysfunction. A number of methods were reported for the analysis of yohimbine in the bark or in pharmaceutical preparations. Materials and Method: In the present work, a simple and sensitive high performance thin layer chromatographic method is developed for determination of yohimbine (occurring as yohimbine hydrochloride) in pharmaceutical preparations and validated according to International Conference of Harmonization (ICH) guidelines. The method employed thin layer chromatography aluminum sheets precoated with silica gel as the stationary phase and the mobile phase consisted of chloroform:methanol:ammonia (97:3:0.2), which gave compact bands of yohimbine hydrochloride. Results: Linear regression data for the calibration curves of standard yohimbine hydrochloride showed a good linear relationship over a concentration range of 80–1000 ng/spot with respect to the area and correlation coefficient (R2) was 0.9965. The method was evaluated regarding accuracy, precision, selectivity, and robustness. Limits of detection and quantitation were recorded as 5 and 40 ng/spot, respectively. The proposed method efficiently separated yohimbine hydrochloride from other components even in complex mixture containing powdered plants. The amount of yohimbine hydrochloride ranged from 2.3 to 5.2 mg/tablet or capsule in preparations containing the pure alkaloid, while it varied from zero (0) to 1.5–1.8 mg/capsule in dietary supplements containing powdered yohimbe bark. Conclusion: We concluded that this method employing high performance thin layer chromatography (HPTLC) in quantitative determination of yohimbine hydrochloride in pharmaceutical preparations is efficient, simple, accurate, and validated. PMID:23661986

A validated high performance thin layer chromatography method for determination of yohimbine hydrochloride in pharmaceutical preparations.

PubMed

Badr, Jihan M

2013-01-01

Yohimbine is an indole alkaloid used as a promising therapy for erectile dysfunction. A number of methods were reported for the analysis of yohimbine in the bark or in pharmaceutical preparations. In the present work, a simple and sensitive high performance thin layer chromatographic method is developed for determination of yohimbine (occurring as yohimbine hydrochloride) in pharmaceutical preparations and validated according to International Conference of Harmonization (ICH) guidelines. The method employed thin layer chromatography aluminum sheets precoated with silica gel as the stationary phase and the mobile phase consisted of chloroform:methanol:ammonia (97:3:0.2), which gave compact bands of yohimbine hydrochloride. Linear regression data for the calibration curves of standard yohimbine hydrochloride showed a good linear relationship over a concentration range of 80-1000 ng/spot with respect to the area and correlation coefficient (R(2)) was 0.9965. The method was evaluated regarding accuracy, precision, selectivity, and robustness. Limits of detection and quantitation were recorded as 5 and 40 ng/spot, respectively. The proposed method efficiently separated yohimbine hydrochloride from other components even in complex mixture containing powdered plants. The amount of yohimbine hydrochloride ranged from 2.3 to 5.2 mg/tablet or capsule in preparations containing the pure alkaloid, while it varied from zero (0) to 1.5-1.8 mg/capsule in dietary supplements containing powdered yohimbe bark. We concluded that this method employing high performance thin layer chromatography (HPTLC) in quantitative determination of yohimbine hydrochloride in pharmaceutical preparations is efficient, simple, accurate, and validated.

R&D implementation in a department of laboratory medicine and pathology: a systematic review based on pharmaceutical companies.

PubMed

Feulefack, Joseph; Sergi, Consolato

2015-01-01

A systematic literature review on pharmaceutical companies may be a tool for guiding some procedures of R&D implementation in a department of Laboratory Medicine and Pathology. The use of pharmaceutical companies for this specific analysis arises from less variability of standards than healthcare facilities. In this qualitative and quantitative analysis, we focused on three useful areas of implementation, including R&D productivity, commercialization strategies, and expenditures determinants of pharmaceutical companies. Studies and reports of online databases from 1965 to 2014 were reviewed according to specific search terms. Initially, 218 articles and reports were found and examined, but only 91 were considered appropriate and used for further analysis.  We identified some suggested implementation strategies relevant for marketing to enhance companies' own R&D strategies; such as reliability of companies on "sourcing-in" R&D facilities and "think-tank" events. Regardless of the study and of the country, cash flow and profitability always positively influenced R&D expenditure, while sales and firm size did not. We consider that handling R&D determinants should require caution. It seems critical that implementation of R&D systems is directly related with productivity, if it reflects dual embodiment of efficiency and effectiveness. Scrutinizing the determinants of R&D expenditures emphasizes significant factors that are worth to highlight when planning an R&D investment strategy. Although there is no receipt fitting every situation, we think that health care plan makers may find relevant data in this systematic review in creating an initial implementation framework.

Method validation and determinations of levofloxacin, metronidazole and sulfamethoxazole in an aqueous pharmaceutical, urine and blood plasma samples using quantitative nuclear magnetic resonance spectrometry.

PubMed

Salem, Alaa A; Mossa, Hussein A

2012-01-15

Selective, rapid and accurate quantitative proton nuclear magnetic resonance (qHNMR) method for the determination of levofloxacin, metronidazole benzoate and sulfamethoxazole in aqueous solutions was developed and validated. The method was successfully applied to the determinations of the drugs and their admixtures in pharmaceutical, urine and plasma samples. Maleic acid and sodium malate were used as internal standards. Effect of temperature on spectral measurements was evaluated. Linear dynamic ranges of 0.50-68.00, 0.13-11.30 and 0.24-21.00 mg per 0.60 mL solution were obtained for levofloxacin, metronidazole benzoate and sulfamethoxazole, respectively. Average recovery % in the range of 96.00-104.20 ± (0.17-2.91) was obtained for drugs in pure, pharmaceutical, plasma and urine samples. Inter and intra-day analyses gave average recoveries % in the ranges 96.10-98.40 ± (1.68-2.81) and 96.00-104.20 ± (0.17-2.91), respectively. Instrumental detection limits ≤0.03 mg per 0.6 mL were obtained for the three drugs. Developed method has demonstrated high performance characteristics for analyzing investigated drugs and their admixtures. Student t-test at 95% confidence level revealed insignificant bias between the real and measured contents of investigated drugs in pure, pharmaceutical, urine and plasma samples and its admixtures. Application of the statistical F-test revealed insignificant differences in precisions between the developed method and arbitrary selected reference methods. Copyright © 2011 Elsevier B.V. All rights reserved.

The possibility of obtaining marketing authorization of orphan pharmaceutical compounding preparations: 3,4-DAP for Lambert-Eaton Myasthenic Syndrome.

PubMed

de Wilde, Sofieke; de Jong, Maria G H; Lipka, Alexander F; Guchelaar, Henk-Jan; Schimmel, Kirsten J M

2018-03-01

Pharmaceutical compounding preparations, produced by (hospital) pharmacies, usually do not have marketing authorization. As a consequence, some of these pharmaceutical compounding preparations can be picked-up by a pharmaceutical company to obtain marketing authorization, often leading to price increases. An example is the 3,4-diaminopyridine slow release (3,4-DAP SR) tablets for Lambert-Eaton Myasthenic Syndrome (LEMS). In 2009 marketing authorization was given for the commercial immediate release phosphate salt of the drug, including a fifty-fold price increase compared to the pharmaceutical compounding preparation. Obtaining marketing authorization for 3,4-DAP SR by academia might have been a solution to prevent this price increase. To determine whether the available data of a pharmaceutical compounding preparation with long-term experience in regular care are adequate to obtain marketing authorization, 3,4-DAP SR is used as a case study. A retrospective qualitative case-study was performed. Initially, document analysis was executed by collecting the required data for marketing authorization in general and whether data of Firdapse® and 3,4-DAP SR met these requirements. Secondly, the (non-) available data of the two formulations were compared with each other to determine the differences in availability. At the time of approval, almost all data were available for both Firdapse® and 3,4-DAP SR. Conversely, much of the data used for the approval of Firdapse® originated from the 3,4-DAP immediate release (3,4-DAP IR) formulation. Only two bioequivalence studies and one pharmacology safety study was performed with Firdapse® before marketing authorization application. In conclusion, at time Firdapse® obtained approval, the data available did not differ substantially from 3,4-DAP SR, indicating that approval with 3,4-DAP SR would have been possible. We make a plea for approval of orphan medicinal products developed and manufactured by academic institutions as to keep utilization of these products affordable. Copyright © 2017 Elsevier B.V. All rights reserved.

76 FR 51991 - Determination That PENTETATE CALCIUM TRISODIUM (Trisodium Calcium Diethylenetriaminepentaacetate...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-19

... Intravenous or Inhalation Administration, Equivalent to 1 Gram Base/5 Milliliters (Equivalent to 200...)) solution for intravenous or inhalation administration, equivalent to (EQ) 1 gram (g) base/5 milliliters (mL...

Measurement of the ambient gamma dose equivalent and kerma from the small 252Cf source at 1 meter and the small 60Co source at 2 meters

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

Carl, W. F.

NASA Langley Research Center requested a measurement and determination of the ambient gamma dose equivalent rate and kerma at 100 cm from the 252Cf source and determination of the ambient gamma dose equivalent rate and kerma at 200 cm from the 60Co source for the Radiation Budget Instrument Experiment (Rad-X). An Exradin A6 ion chamber with Shonka air-equivalent plastic walls in combination with a Supermax electrometer were used to measure the exposure rate and free-in-air kerma rate of the two sources at the requested distances. The measured gamma exposure, kerma, and dose equivalent rates are tabulated.

76 FR 11752 - Australia's Meat Safety Enhancement Program; Notice of Affirmation of Equivalence Decision

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-03

... equivalent to the FSIS domestic meat inspection system. MSEP has been renamed the Australian Export Meat Inspection System (AEMIS), but the system itself will remain the same as that determined to be equivalent by... implementing documentation must be equivalent to those of the United States. Specifically, the national meat...

40 CFR 1065.665 - THCE and NMHCE determination.

Code of Federal Regulations, 2011 CFR

2011-07-01

... = The C1-equivalent sum of the concentration of carbon mass contributions of non-oxygenated hydrocarbons, alcohols, and aldehydes. x NOTHC = The C1-equivalent sum of the concentration of nonoxygenated THC. x OHC i... this into a C1-equivalent molar concentration. Add these C1-equivalent molar concentrations to the...

40 CFR 1065.665 - THCE and NMHCE determination.

Code of Federal Regulations, 2013 CFR

2013-07-01

... = The C1-equivalent sum of the concentration of carbon mass contributions of non-oxygenated hydrocarbons, alcohols, and aldehydes. x NOTHC = The C1-equivalent sum of the concentration of nonoxygenated THC. x OHC i... this into a C1-equivalent molar concentration. Add these C1-equivalent molar concentrations to the...

40 CFR 1065.665 - THCE and NMHCE determination.

Code of Federal Regulations, 2012 CFR

2012-07-01

... = The C1-equivalent sum of the concentration of carbon mass contributions of non-oxygenated hydrocarbons, alcohols, and aldehydes. x NOTHC = The C1-equivalent sum of the concentration of nonoxygenated THC. x OHC i... this into a C1-equivalent molar concentration. Add these C1-equivalent molar concentrations to the...

40 CFR 1065.665 - THCE and NMHCE determination.

Code of Federal Regulations, 2010 CFR

2010-07-01

... = The C1-equivalent sum of the concentration of carbon mass contributions of non-oxygenated hydrocarbons, alcohols, and aldehydes. x NOTHC = The C1-equivalent sum of the concentration of nonoxygenated THC. x OHC i... this into a C1-equivalent molar concentration. Add these C1-equivalent molar concentrations to the...

Simultaneous spectrophotometric determination of paracetamol and salicylamide in human serum and pharmaceutical formulations by a differential kinetic method.

PubMed

Zarei, Ali Reza; Afkhami, Abbas; Sarlak, Nahid

2005-01-01

A rapid, simple, and sensitive differential kinetic method is presented for the determinations of acetaminophen (also known as paracetamol) and salicylamide. The method is based on their oxidation reaction by Fe3+ ion in the presence of 1, 10-phenanthroline as indicator. The reactions can be monitored spectrophotometrically by measuring the increase in the absorbance of the solution at 510 nm. Two times were selected one in which only paracetamol is oxidized by Fe3+ ion and the other in which both drugs are oxidized by Fe3+ ion. The data were evaluated by the proportional equations method. The method allowed the simultaneous determination of paracetamol and salicylamide at concentrations between 0.5-20 and 1-40 microg/mL with relative standard deviations of 3.47 and 2.58%, respectively. The method was applied to the simultaneous determination of paracetamol and salicylamide in human serum and pharmaceutical formulations.

Extractive-spectrophotometric determination of disopyramide and irbesartan in their pharmaceutical formulation

NASA Astrophysics Data System (ADS)

Abdellatef, Hisham E.

2007-04-01

Picric acid, bromocresol green, bromothymol blue, cobalt thiocyanate and molybdenum(V) thiocyanate have been tested as spectrophotometric reagents for the determination of disopyramide and irbesartan. Reaction conditions have been optimized to obtain coloured comoplexes of higher sensitivity and longer stability. The absorbance of ion-pair complexes formed were found to increases linearity with increases in concentrations of disopyramide and irbesartan which were corroborated by correction coefficient values. The developed methods have been successfully applied for the determination of disopyramide and irbesartan in bulk drugs and pharmaceutical formulations. The common excipients and additives did not interfere in their determination. The results obtained by the proposed methods have been statistically compared by means of student t-test and by the variance ratio F-test. The validity was assessed by applying the standard addition technique. The results were compared statistically with the official or reference methods showing a good agreement with high precision and accuracy.

Analysis of fish bile with HPLC — fluorescence to determine environmental exposure to benzo(a)pyrene

USGS Publications Warehouse

Johnston, Eric P.; Baumann, Paul C.

1989-01-01

Brown bullhead from the Black River, Ohio, have a high incidence of liver neoplasia which is associated with elevated concentrations of polynuclear aromatic hydrocarbons (PAHs) in the sediment. We evaluated the use of biliary concentrations of benzo(a)pyrene [B(a)P] equivalents as a means for determining PAH exposure. Bile was collected from 16 brown bullheads and 8 common carp taken from each of two Lake Erie tributaries in Ohio, the industrialized Black River and the non-industrialized Old Woman Creek. Hatchery bullhead (n = 8) were used to determine base levels of PAHs. A high performance liquid chromatography (HPLC) — fluorescence technique was used to determine the concentration of B(a)P equivalents in the bile samples. The area of all peaks fluorescing at 380/430 nm was summed to give a single value for B(a)P equivalents in each sample. Concentrations of B(a)P equivalents generally reflected concentrations of PAH in sediment where fish were collected. Bile taken from Black River carp contained the highest concentration of B(a)P equivalents and was significantly different from all other groups. The value obtained for Black River bullhead was also high and was found to be significantly different from hatchery bullhead. B(a)P equivalents varied between carp and bullhead from the same habitat possibly because of differing food habits or metabolic pathways. However, our results indicate that relative levels of B(a)P equivalents in the bile of fish correspond well to B(a)P levels in sediment and may offer a means of determining environmental exposure of fish to the parent compound.

Local unitary equivalence of quantum states and simultaneous orthogonal equivalence

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

Jing, Naihuan, E-mail: jing@ncsu.edu; Yang, Min; Zhao, Hui, E-mail: zhaohui@bjut.edu.cn

2016-06-15

The correspondence between local unitary equivalence of bipartite quantum states and simultaneous orthogonal equivalence is thoroughly investigated and strengthened. It is proved that local unitary equivalence can be studied through simultaneous similarity under projective orthogonal transformations, and four parametrization independent algorithms are proposed to judge when two density matrices on ℂ{sup d{sub 1}} ⊗ ℂ{sup d{sub 2}} are locally unitary equivalent in connection with trace identities, Kronecker pencils, Albert determinants and Smith normal forms.

Awareness of pharmaceutical cost-assistance programs among inner-city seniors.

PubMed

Federman, Alex D; Safran, Dana Gelb; Keyhani, Salomeh; Cole, Helen; Halm, Ethan A; Siu, Albert L

2009-04-01

Lack of awareness may be a significant barrier to participation by low- and middle-income seniors in pharmaceutical cost-assistance programs. The goal of this study was to determine whether older adults' awareness of 2 major state and federal pharmaceutical cost-assistance programs was associated with the seniors' ability to access and process information about assistance programs. Data were gathered from a cross-sectional study of independently living, English- or Spanish-speaking adults aged > or =60 years. Participants were interviewed in 30 community-based settings (19 apartment complexes and 11 senior centers) in New York, New York. The analysis focused on adults aged > or =65 years who lacked Medicaid coverage. Multivariable logistic regression was used to model program awareness as a function of information access (family/social support, attendance at senior or community centers and places of worship, viewing of live health insurance presentations, instrumental activities of daily living, site of medical care, computer use, and having a proxy decision maker for health insurance matters) and information-processing ability (education level, English proficiency, health literacy, and cognitive function). The main outcome measure was awareness of New York's state pharmaceutical assistance program (Elderly Pharmaceutical Insurance Coverage [EPIC

Systematic review of factors affecting pharmaceutical expenditures.

PubMed

Mousnad, Mohamed Awad; Shafie, Asrul Akmal; Ibrahim, Mohamed Izham

2014-06-01

To systematically identify the main factors contributing to the increase in pharmaceutical expenditures. A systematic search of published studies was conducted utilising major widely used electronic databases using the search terms 'factors,' 'financing,' 'pharmaceutical,' and 'expenditures.' To be included, the studies needed to: (1) measure at least one of the following outcomes: total growth in pharmaceutical expenditures, price growth or quantity growth; (2) mention a clear method for analysing the impact of factors affecting the increases in drug expenditures; (3) be written in English. Nonprimary articles that were published only as an abstract, a review, a commentary or a letter were excluded. From a total of 2039 studies, only 25 were included in the full review. The main determinant categories that were identified in the review were factors related to price, utilisation, therapeutic choice, demand and health care system. The major cost drivers were found to be changes in drug quantities and therapies as well as new drugs. It is important for policymakers to understand pharmaceutical spending trends and the factors that influence them in order to formulate effective cost containment strategies and design optimum drug policy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Measuring patients' satisfaction with pharmaceutical services at a public hospital in Qatar.

PubMed

Khudair, Imran Fahmi; Raza, Syed Asif

2013-01-01

The aim of this paper is to study pharmacy service impact on patient satisfaction and to determine what factors saliently link with pharmaceutical service performance at Hamad General Hospital. A patient satisfaction questionnaire was designed using the literature and consultation with Hamad General Hospital medical experts. The questionnaire contained 22 items that focused on five influencing factors: promptness; attitude; supply; location; medication education; and respondent demographic aspects. A total of 220 respondents completed the questionnaire. An exploratory factor analysis was used to group items and a structural equation model was developed to test causality between five factors along with their influence on patient satisfaction. The study establishes statistical evidence that patient satisfaction is positively influenced by service promptness, pharmacist attitude, medication counseling, pharmacy location and waiting area. Several socio-demographic characteristics have statistically different effect on satisfaction, notably: gender; marital status; health status; age; educational level; and ethnicity. However, medication supply did not influence patient satisfaction. Pharmaceutical services are recognized as an essential healthcare-system component. Their impact on customer satisfaction has been investigated in many countries; however, there is no such study in Qatar. The findings identify pharmaceutical service performance indicators and provide guidelines to improve Qatari pharmaceutical services.

Testing the performance of pure spectrum resolution from Raman hyperspectral images of differently manufactured pharmaceutical tablets.

PubMed

Vajna, Balázs; Farkas, Attila; Pataki, Hajnalka; Zsigmond, Zsolt; Igricz, Tamás; Marosi, György

2012-01-27

Chemical imaging is a rapidly emerging analytical method in pharmaceutical technology. Due to the numerous chemometric solutions available, characterization of pharmaceutical samples with unknown components present has also become possible. This study compares the performance of current state-of-the-art curve resolution methods (multivariate curve resolution-alternating least squares, positive matrix factorization, simplex identification via split augmented Lagrangian and self-modelling mixture analysis) in the estimation of pure component spectra from Raman maps of differently manufactured pharmaceutical tablets. The batches of different technologies differ in the homogeneity level of the active ingredient, thus, the curve resolution methods are tested under different conditions. An empirical approach is shown to determine the number of components present in a sample. The chemometric algorithms are compared regarding the number of detected components, the quality of the resolved spectra and the accuracy of scores (spectral concentrations) compared to those calculated with classical least squares, using the true pure component (reference) spectra. It is demonstrated that using appropriate multivariate methods, Raman chemical imaging can be a useful tool in the non-invasive characterization of unknown (e.g. illegal or counterfeit) pharmaceutical products. Copyright © 2011 Elsevier B.V. All rights reserved.

Widespread, routine occurrence of pharmaceuticals in sewage effluent, combined sewer overflows and receiving waters.

PubMed

Kay, Paul; Hughes, Stephen R; Ault, James R; Ashcroft, Alison E; Brown, Lee E

2017-01-01

Research addressing the occurrence, fate and effects of pharmaceuticals in the aquatic environment has expanded rapidly over the past two decades, primarily due to the development of improved chemical analysis methods. Significant research gaps still remain, however, including a lack of longer term, repeated monitoring of rivers, determination of temporal and spatial changes in pharmaceutical concentrations, and inputs from sources other than wastewater treatment plants (WWTPs), such as combined sewer overflows (CSOs). In addressing these gaps it was found that the five pharmaceuticals studied were routinely (51-94% of the time) present in effluents and receiving waters at concentrations ranging from single ng to μg L -1 . Mean concentrations were in the tens to hundreds ng L -1 range and CSOs appear to be a significant source of pharmaceuticals to water courses in addition to WWTPs. Receiving water concentrations varied throughout the day although there were no pronounced peaks at particular times. Similarly, concentrations varied throughout the year although no consistent patterns were observed. No dissipation of the study compounds was found over a 5 km length of river despite no other known inputs to the river. In conclusion, pharmaceuticals are routinely present in semi-rural and urban rivers and require management alongside more traditional pollutants. Copyright © 2016 Elsevier Ltd. All rights reserved.

A prospective before-and-after trial of an educational intervention about pharmaceutical marketing.

PubMed

Agrawal, Sacha; Saluja, Inderpal; Kaczorowski, Janusz

2004-11-01

There is increasing evidence that physicians may be compromised by their interactions with the pharmaceutical industry. The authors aimed to develop and determine the effect of an educational intervention to inform family medicine residents about pharmaceutical marketing. Confidential, self-administered questionnaires were administered to family medicine residents at McMaster University, Hamilton, Canada, immediately before and after a two-part, 2.5-hour educational intervention. The curriculum consisted of (1) a faculty-led debate and discussion of a systematic review of physician-pharmaceutical industry interactions, and (2) an interactive workshop that included a presentation highlighting key empirical findings, a video illustrating techniques to optimize pharmaceutical sales representatives' visits, and small- and large-group problem-based discussions. Residents were asked about their attitudes toward five marketing strategies: drug samples, industry-sponsored continuing medical education, one-on-one interactions with sales representatives, free meals, and gifts worth less than CAN $10. A total of 37 residents responded to both questionnaires. After the intervention residents had more cautious attitudes, rating marketing strategies on a five-point Likert scale as less ethically appropriate (-0.41, p < .05) and less valuable to patients or useful to the resident (-0.39, p < .05), and reporting less intention to use them in the future (-0.44, p < .01). This intervention appears to have promoted more cautious attitudes toward pharmaceuticals marketing. Its long-term sustainability and effect on behavior remain unknown.

[Medical economics research on awareness of community pharmacists about raising pharmaceutical questions regarding prescriptions issued by physicians].

PubMed

Shikamura, Yoshiaki; Oyama, Akiko; Takahashi, Junichi; Akagi, Yuuki; Negishi, Kenichi; Ijyuin, Kazushige; Kamimura, Naoki; Aoyama, Takao

2012-01-01

This study examined the impact of pharmaceutical inquiries regarding prescriptions on drug costs by surveying the actual condition of inquiries at 13 pharmacies. The study also investigated the significance of inquiries from a medical economics perspective by calculating the medical cost savings realized by preventing adverse drug reactions (ADRs). As a result, the total change in drug costs for the 13 pharmacies after pharmaceutical inquiries represented an increase of ¥9,018/month. However, upon recalculating the cost of drugs by assuming that those with an "Incomplete entry in the prescription (compared with previous prescription, etc.)" should in fact have been prescribed, and excluding them, the total drug costs for the 13 pharmacies is decreased to ¥154,743/month, translating to a cost-savings of ¥7.2/prescription. The study then undertook a comprehensive assessment based on the Diagnosis Procedure Combination (DPC) system to determine the total medical cost-savings for 5 patients in whom ADRs could have occurred if the prescriptions had not been modified as a result of pharmaceutical inquiries. The obtained figure of ¥1,188,830 suggests that pharmaceutical inquiries contribute to reduced medical costs. The findings of this study indicate that pharmaceutical inquiries regarding prescriptions by staff pharmacists not only ensure the proper delivery of drug therapy to patients, but are also effective from a medical economics perspective.

Quality of pharmaceutical advertising and gender bias in medical journals (1998-2008): a review of the scientific literature.

PubMed

Cambronero Saiz, Belén; Ruiz Cantero, María Teresa; Papí Gálvez, Natalia

2012-01-01

To review the scientific literature on pharmaceutical advertising aimed at health professionals in order to determine whether gender bias has decreased and the quality of information in pharmaceutical advertising has improved over time. We performed a content analysis of original articles dealing with medical drug promotion (1998-2008), according to quality criteria such as (a) the number, validity and accessibility of bibliographic references provided in pharmaceutical advertising and (b) the extent to which gender representations were consistent with the prevalence of the diseases. Databases: PUBMED, Medline, Scopus, Sociological Abstract, Eric and LILACS. We reviewed 31 articles that analyzed advertising in medical journals from 1975-2005 and were published between 1998 and 2008. We found that the number of references used to support pharmaceutical advertising claims increased from 1975 but that 50% of these references were not valid. There was a tendency to depict men in paid productive roles, while women appeared inside the home or in non-occupational social contexts. Advertisements for psychotropic and cardiovascular drugs overrepresented women and men respectively. The use of bibliographic references increased between 1998 and 2008. However, representation of traditional male-female roles was similar in 1975 and 2005. Pharmaceutical advertisements may contribute to reinforcing the perception that certain diseases are associated with the most frequently portrayed sex. Copyright © 2011 SESPAS. Published by Elsevier Espana. All rights reserved.

Development of a gas chromatography method for the determination of isotretinoin and its degradation products in pharmaceuticals.

PubMed

Lima, Eliana Martins; Diniz, Danielle G Almeida; Antoniosi-Filho, Nelson R

2005-07-15

This paper describes the development of a gas chromatography (GC) method used for the assay of isotretinoin in its isolated form and in pharmaceutical formulations. Isotretinoin soft and hard gelatin capsules were prepared with various excipients. The performance of the proposed gas chromatography method was compared to that of traditional high performance liquid chromatography (HPLC) systems for this substance, and the GC parameters were established based on several preliminary tests, including thermal analysis of isotretinoin. Results showed that gas chromatography-flame ionization detector (GC-FID) exhibited a separation efficiency superior to that of HPLC, particularly for separating isotretinoin degradation products. This method was proven to be effectively applicable to stability evaluation assays of isotretinoin and isotretinoin based pharmaceuticals.

Selection of solubility parameters for characterization of pharmaceutical excipients.

PubMed

Adamska, Katarzyna; Voelkel, Adam; Héberger, Károly

2007-11-09

The solubility parameter (delta(2)), corrected solubility parameter (delta(T)) and its components (delta(d), delta(p), delta(h)) were determined for series of pharmaceutical excipients by using inverse gas chromatography (IGC). Principal component analysis (PCA) was applied for the selection of the solubility parameters which assure the complete characterization of examined materials. Application of PCA suggests that complete description of examined materials is achieved with four solubility parameters, i.e. delta(2) and Hansen solubility parameters (delta(d), delta(p), delta(h)). Selection of the excipients through PCA of their solubility parameters data can be used for prediction of their behavior in a multi-component system, e.g. for selection of the best materials to form stable pharmaceutical liquid mixtures or stable coating formulation.

Adsorption characteristics of selected pharmaceuticals and an endocrine disrupting compound-Naproxen, carbamazepine and nonylphenol-on activated carbon.

PubMed

Yu, Zirui; Peldszus, Sigrid; Huck, Peter M

2008-06-01

The adsorption of two representative pharmaceutically active compounds (PhACs) (naproxen and carbamazepine) and one endocrine disrupting compound (nonylphenol) were evaluated on two types of activated carbon. When determining their isotherms at environmentally relevant concentration levels, it was found that at this low concentration range (10-800 ng/L), removals of the target compounds were contrary to expectations based on their hydrophobicity. Nonylphenol (log K(ow) 5.8) was most poorly adsorbed, whereas carbamazepine (log K(ow) 2.45) was most adsorbable. Nonylphenol Freundlich isotherms at this very low concentration range had a much higher 1/n compared to isotherms at much higher concentrations. This indicates that extrapolation from an isotherm obtained at a high concentration range to predict the adsorption of nonylphenol at a concentration well below the range of the original isotherm, leads to a substantial overestimation of its removals. Comparison of isotherms for the target compounds to those for other conventional micropollutants suggested that naproxen and carbamazepine could be effectively removed by applying the same dosage utilized to remove odorous compounds (geosmin and MIB) at very low concentrations. The impact of competitive adsorption by background natural organic matter (NOM) on the adsorption of the target compounds was quantified by using the ideal adsorbed solution theory (IAST) in combination with the equivalent background compound (EBC) approach. The fulfilment of the requirements for applying the simplified IAST-EBC model, which leads to the conclusion that the percentage removal of the target compounds at a given carbon dosage is independent of the initial contaminant concentration, was confirmed for the situation examined in the paper. On this basis it is suggested that the estimated minimum carbon usage rates (CURs) to achieve 90% removal of these emerging contaminants would be valid at concentrations of less than 500 ng/L in natural water.

Production of cocrystals in an excipient matrix by spray drying.

PubMed

Walsh, David; Serrano, Dolores R; Worku, Zelalem Ayenew; Norris, Brid A; Healy, Anne Marie

2018-01-30

Spray drying is a well-established scale-up technique for the production of cocrystals. However, to the best of our knowledge, the effect of introducing a third component into the feed solution during the spray drying process has never been investigated. Cocrystal formation in the presence of a third component by a one-step spray drying process has the potential to reduce the number of unit operations which are required to produce a final pharmaceutical product (e.g. by eliminating blending with excipient). Sulfadimidine (SDM), a poorly water soluble active pharmaceutical ingredient (API), and 4-aminosalicylic acid (4ASA), a hydrophilic molecule, were used as model drug and coformer respectively to form cocrystals by spray drying in the presence of a third component (excipient). The solubility of the cocrystal in the excipient was measured using a thermal analysis approach. Trends in measured solubility were in agreement with those determined by calculated Hansen Solubility Parameter (HSP) values. The ratio of cocrystal components to excipient was altered and cocrystal formation at different weight ratios was assessed. Cocrystal integrity was preserved when the cocrystal components were immiscible with the excipient, based on the difference in Hansen Solubility Parameters (HSP). For immiscible systems (difference in HSP > 9.6 MPa 0.5 ), cocrystal formation occurred even when the proportion of excipient was high (90% w/w). When the excipient was partly miscible with the cocrystal components, cocrystal formation was observed post spray drying, but crystalline API and coformer were also recovered in the processed powder. An amorphous dispersion was formed when the excipient was miscible with the cocrystal components even when the proportion of excipient used as low (10% w/w excipient). For selected spray dried cocrystal-excipient systems an improvement in tableting characteristics was observed, relative to equivalent physical mixtures. Copyright © 2017 Elsevier B.V. All rights reserved.

Application of an innovative design space optimization strategy to the development of liquid chromatographic methods to combat potentially counterfeit nonsteroidal anti-inflammatory drugs.

PubMed

Mbinze, J K; Lebrun, P; Debrus, B; Dispas, A; Kalenda, N; Mavar Tayey Mbay, J; Schofield, T; Boulanger, B; Rozet, E; Hubert, Ph; Marini, R D

2012-11-09

In the context of the battle against counterfeit medicines, an innovative methodology has been used to develop rapid and specific high performance liquid chromatographic methods to detect and determine 18 non-steroidal anti-inflammatory drugs, 5 pharmaceutical conservatives, paracetamol, chlorzoxazone, caffeine and salicylic acid. These molecules are commonly encountered alone or in combination on the market. Regrettably, a significant proportion of these consumed medicines are counterfeit or substandard, with a strong negative impact in countries of Central Africa. In this context, an innovative design space optimization strategy was successfully applied to the development of LC screening methods allowing the detection of substandard or counterfeit medicines. Using the results of a unique experimental design, the design spaces of 5 potentially relevant HPLC methods have been developed, and transferred to an ultra high performance liquid chromatographic system to evaluate the robustness of the predicted DS while providing rapid methods of analysis. Moreover, one of the methods has been fully validated using the accuracy profile as decision tool, and was then used for the quantitative determination of three active ingredients and one impurity in a common and widely used pharmaceutical formulation. The method was applied to 5 pharmaceuticals sold in the Democratic Republic of Congo. None of these pharmaceuticals was found compliant to the European Medicines Agency specifications. Copyright © 2012 Elsevier B.V. All rights reserved.

Pharmaceutical occurrence in groundwater and surface waters in forests land-applied with municipal wastewater.

PubMed

McEachran, Andrew D; Shea, Damian; Bodnar, Wanda; Nichols, Elizabeth Guthrie

2016-04-01

The occurrence and fate of pharmaceutical and personal care products in the environment are of increasing public importance because of their ubiquitous nature and documented effects on wildlife, ecosystems, and potentially humans. One potential, yet undefined, source of entry of pharmaceuticals into the environment is via the land application of municipal wastewater onto permitted lands. The objective of the present study is to determine the extent to which pharmaceuticals are mitigated by or exported from managed tree plantations irrigated with municipal wastewater. A specific focus of the present study is the presence of pharmaceutical compounds in groundwater and surface water discharge. The study site is a municipality that land-applies secondary treated wastewater onto 930 hectares of a 2000-hectare managed hardwood and pine plantation. A suite of 33 pharmaceuticals and steroid hormones was targeted in the analysis, which consisted of monthly grab sampling of groundwater, surface water, and wastewater, followed by concentration and cleanup via solid phase extraction and separation, detection, and quantification via liquid chromatography coupled with tandem mass spectrometry. More than one-half of all compounds detected in irrigated wastewater were not present in groundwater and subsequent surface water. However, antibiotics, nonsteroidal anti-inflammatory drugs, caffeine, and other prescription and over-the-counter drugs remained in groundwater and were transported into surface water at concentrations up to 10 ng/L. These results provide important documentation for pharmaceutical fate and transport in forest systems irrigated with municipal wastewater, a previously undocumented source of environmental entry. © 2015 SETAC.

Estimating the sorption of pharmaceuticals based on their pharmacological distribution.

PubMed

Williams, Mike; Ong, Poh L; Williams, Desmond B; Kookana, Rai S

2009-12-01

Pharmaceuticals released into aquatic systems are expected to sorb to sediments to varying degrees. Their sorption is likely to influence their fate and, ultimately, the risk they pose to aquatic organisms. This has led to the European Medicines Agency requiring an assessment of affinity to solids, using batch sorption methods, for the environmental risk assessment (ERA) of new human medicines. However, a large body of data is generated before pharmaceuticals are released onto the market, including their extent of distribution throughout the human body, measured by the volume of distribution (VD). In the present study, batch sorption experiments were undertaken using 12 different soils and sediments to determine whether VD was a good indicator of experimental Kd values for 21 pharmaceuticals. The r2 values obtained from the regressions ranged from 0.39 to 0.76 (with a median value of 0.5) and all regressions were found to be significant. The use of this more comprehensive set of soils and sediments was consistent with previous studies comparing VD and Kd, despite the Kd values of the selected pharmaceuticals varying greatly between soils. The relationship between Kd and VD was greatly improved when zwitterionic antibiotics and carbamazepine were not included, possibly due to complex sorption or pharmacokinetic behavior. There are likely to be a number of factors affecting the sorption of pharmaceuticals that cannot be explained by VD. However, further work may elucidate how these factors can be accounted for, enabling VD to be effectively used to facilitate the ERA of human pharmaceuticals with already available information.

Residues of pharmaceutical products in recycled organic manure produced from sewage sludge and solid waste from livestock and relationship to their fermentation level.

PubMed

Motoyama, Miki; Nakagawa, Shuhei; Tanoue, Rumi; Sato, Yuri; Nomiyama, Kei; Shinohara, Ryota

2011-07-01

In recent years, sludge generated in sewage treatment plants (STPs) and solid waste from livestock being utilized is useful for circulation of nourishment in farmlands as recycled organic manure (ROM). In this study, we determined the residue levels and patterns of 12 pharmaceutical products generated by human activity in the ROMs produced from human waste sludge (HWS), sewage sludge (SS), cattle manure (CM), poultry manure (PM), swine manure (SM) and horse manure (HM). The kind and number of pharmaceutical products detected in ROMs were different. Fluoroquinolones (FQs) were detected at high levels in HWS and SS samples. In addition, the detection frequency and concentration levels of sulfonamides (SAs) in PM and SM were high. Moreover, high concentrations of chlortetracycline (CTC) were found in only SM. These differences reflect specific adherence adsorption of the pharmaceutical products to different livestock and humans. Moreover, it was found that the concentrations of pharmaceutical products and fermentation levels of ROMs had significant positive correlation (r=0.41, p=0.024). When the fermentation test of ROM was conducted in a rotary fermentor in a lab scale test, the residue levels of pharmaceutical products decreased effectively except carbamazepine (CBZ). The rates of decrease were in the case of tetracyclines (TCs): 85-92%, FQs: 81-100%, erythromycine: 67%, SAs: 79-95%, trimethoprim: 86% and CBZ: 37% by 30 d. Pharmaceutical products that can be decomposed by fermentation process at the lowest impact of residual antibiotic activities may therefore be considered as environmentally friendly medicines. Copyright © 2011 Elsevier Ltd. All rights reserved.

Septonex-tetraphenylborate screen-printed ion selective electrode for the potentiometric determination of Septonex in pharmaceutical preparations.

PubMed

Mohamed, Gehad G; El-Shahat, M F; Al-Sabagh, A M; Migahed, M A; Ali, Tamer Awad

2011-04-07

A screen-printed electrode (SPE) was fabricated for the determination of 1-(ethoxycarbonyl)pentadecyltrimethylammonium bromide (Septonex) based on the use of Septonex-tetraphenylborate as the electroactive substance, and o-nitrophenyloctylether (o-NPOE) as the plasticizing agent. The electrode passes a near-Nernstian cationic slope of 59.33 ± 0.85 mV from activity between pH values of 2 to 9 with a lower detection limit of 9×10(-7) M and response time of about 5 s and exhibits an adequate shelf-life of 6 months. The method was applied for the determination of Septonex in pharmaceutical preparations. A percentage recovery of 99.88% was obtained with RSD=1.24%. The electrode was successfully applied in the determination of Septonex in laboratory-prepared samples by direct potentiometric, calibration curve and standard addition methods. Potentiometric titration of Septonex with sodium tetraphenylborate and phosphotungstic acid as a titrant was monitored with the modified screen-printed electrode as an end-point indicator electrode. Selectivity coefficients for Septonex relative to a number of potential interfering substances were determined. The sensor was highly selective for Septonex over a large number of compounds. Selectivity coefficient data for some common ions show negligible interference; however, cetyltrimethylammonium bromide and iodide ions interfere significantly. The analytical usefulness of the proposed electrode was evaluated by its application in the determination of Septonex in laboratory-prepared pharmaceutical samples with satisfactory results. The results obtained with the fabricated sensor are comparable with those obtained by the British Pharmacopeia method. © The Royal Society of Chemistry 2011

The gap between legal rules and practice in advertising non-registered pharmaceutical products. A new method of analysis.

PubMed

Wieringa, N F; de Meijer, A H; Schutjens, M D; Vos, R

1992-12-01

The market of non-registered pharmaceutical products is growing fast in number and overall costs, not only in the Netherlands, but also in other European countries. These products often give the impression that the consumer may expect 'an effect as from a drug'. Legally, there is a clear distinction between 'drugs' and 'commodities' in the Netherlands; the question is whether legislation and practice concur. In an investigation we analysed texts of advertisements for non-registered pharmaceutical products published in a popular magazine. A method was developed, based on the legal definition of a drug and jurisprudence, to determine in a qualitative and quantitative way the application of medicinal claims. It transpired that in 65% of the analysed advertisements explicit or implicit claims were made. These products should therefore be subject to drugs legislation. Thus, in the Netherlands there is a gap between legislation and practice in advertising non-registered pharmaceutical products.

Pharmaceutical aspects of salt and cocrystal forms of APIs and characterization challenges.

PubMed

Cerreia Vioglio, Paolo; Chierotti, Michele R; Gobetto, Roberto

2017-08-01

In recent years many efforts have been devoted to the screening and the study of new solid-state forms of old active pharmaceutical ingredients (APIs) with salification or co-crystallization processes, thus modulating final properties without changing the pharmacological nature. Salts, hydrates/solvates, and cocrystals are the common solid-state forms employed. They offer the intriguing possibility of exploring different pharmaceutical properties for a single API in the quest of enhancing the final drug product. New synthetic strategies and advanced characterization techniques have been recently proposed in this hot topic for pharmaceutical companies. This paper reviews the recent progresses in the field particularly focusing on the characterization challenges encountered when the nature of the solid-state form must be determined. The aim of this article is to offer the state-of-the-art on this subject in order to develop new insights and to promote cooperative efforts in the fascinating field of API salt and cocrystal forms. Copyright © 2017 Elsevier B.V. All rights reserved.

Environmental risk assessment of selected pharmaceuticals in Turkey.

PubMed

Oğuz, Merve; Mihçiokur, Hamdi

2014-07-01

In this study, environmental risks of selected pharmaceuticals were investigated to assess potential hazards. Ciprofloxacin, Clarithromycin, Cefuroxime axetil, antibiotics, Benzalkoniuman antiseptic, Paracetamol, an analgesic, and Naproxen, an anti-inflammatory, were selected due to their high rate of usage in Turkey. Ciprofloxacin was found to have the highest risk due to its high PEC/PNEC ratio (28.636). Benzalkonium, Paracetamol and Clarithromycin have a potential to cause environmental hazards. The biodegradation and biological concentration factors (BCF) of the drugs were also determined using EPA/STWIN and EPA/BCFWIN programs. The results illustrated that these pharmaceuticals are nonbiodegradable in wastewater treatment plants. The BCFs of Benzalkonium and Clarithromycin were found to be very high, 70.790 L/kg and 56.490 L/kg, respectively. It was suggested that alternative treatment methods other than biological ones should be investigated for these pharmaceuticals because of their low biodegradability. Also, unnecessary use of antibiotics is supposed to be discouraged to reduce environmental hazards. Copyright © 2014 Elsevier B.V. All rights reserved.

Ontogenetic dietary shifts and bioaccumulation of diphenhydramine in Mugil cephalus from an urban estuary.

PubMed

Haddad, Samuel P; Du, Bowen; Scott, W Casan; Saari, Gavin N; Breed, Christopher; Kelly, Martin; Broach, Linda; Chambliss, C Kevin; Brooks, Bryan W

2017-06-01

Though bioaccumulation of pharmaceuticals has received attention in inland waters, studies of pharmaceutical bioaccumulation in estuarine and marine systems are limited. Further, an understanding of pharmaceutical bioaccumulation across size classes of organisms displaying ontogenetic feeding shifts is lacking. We selected the striped mullet, Mugil cephalus, a euryhaline and eurythermal species that experiences dietary shifts with age, to identify whether a model base, diphenhydramine, accumulated in a tidally influenced urban bayou. We further determined whether diphenhydramine accumulation differed among size classes of striped mullet over a two year study period. Stable isotope analysis identified that ontogenetic feeding shifts of M. cephalus occurred from juveniles to adults. However, bioaccumulation of diphenhydramine did not significantly increase across age classes of M. cephalus but corresponded to surface water levels of the pharmaceutical, which suggests inhalational uptake to diphenhydramine was more important for bioaccumulation than dietary exposure in this urban estuary. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impact of distance education on academic performance in a pharmaceutical care course

PubMed Central

Bem, Tamires; Carneiro, Mára Lucia Fernandes; de Castro, Mauro Silveira

2017-01-01

The objective of this study was to compare the performance of pharmacy students from a Pharmaceutical Care course, taught in both distance education (DE) and campus-based formats using active methodologies. For two semesters, students (n = 82) taking the course studied half the subject in the distance education format and half in person. Questionnaires were applied at the beginning of the semester aimed to outline the demographic profile of the students. Their grade in the course was evaluated to determine their performance. The Module 1 (Information on Medication) average on the campus-based was 7.1225 and on DE was 7.5519, (p = 0.117). The Module 2 (Pharmaceutical Services) average on the campus-based was 7.1595 and on distance education was 7.7025, (p = 0.027*). There was a difference in learning outcomes in the Pharmaceutical Care Course between face-to-face and distant education. Therefore, the student performance was better in the distance education module, indicating distance education can be satisfactorily used in Pharmacy Programs. PMID:28384362

Occurrence and seasonal variations of 25 pharmaceutical residues in wastewater and drinking water treatment plants.

PubMed

Kot-Wasik, A; Jakimska, A; Śliwka-Kaszyńska, M

2016-12-01

Thousands of tons of pharmaceuticals are introduced into the aqueous environment due to their incomplete elimination during treatment process in wastewater treatment plants (WWTPs) and water treatment plants (WTPs). The presence of pharmacologically active compounds in the environment is of a great interest because of their potential to cause negative effects. Furthermore, drugs can undergo different processes leading to the formation of new transformation products, which may be more toxic than the parent compound. In light of these concerns, within the research a new, rapid and sensitive analytical procedure for the determination of a wide range of pharmaceuticals from different classes using solid phase extraction (SPE) and high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) technique in different water samples was developed. This methodology was applied to investigate the occurrence, removal efficiency of 25 pharmaceuticals during wastewater and drinking water treatment, and seasonal variability in the amount of selected pharmaceuticals in WWTP and WTP over a year. The most often detected analytes in water samples were carbamazepine (100 % of samples) and ibuprofen (98 % of samples), concluding that they may be considered as pollution indicators of the aqueous environment in tested area. Highly polar compound, metformin, was determined at very high concentration level of up to 8100 ng/L in analyzed water samples. Drugs concentrations were much higher in winter season, especially for non-steroidal inflammatory drugs (NSAIDs) and caffeine, probably due to the inhibited degradation related to lower temperatures and limited sunlight. Carbamazepine was found to be the most resistant drug to environmental degradation and its concentrations were at similar levels during four seasons.

30 CFR 7.10 - MSHA acceptance of equivalent non-MSHA product safety standards.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false MSHA acceptance of equivalent non-MSHA product... General § 7.10 MSHA acceptance of equivalent non-MSHA product safety standards. (a) MSHA will accept non...) [Reserved] (d) After MSHA has determined that non-MSHA product safety standards are equivalent and has...

30 CFR 7.10 - MSHA acceptance of equivalent non-MSHA product safety standards.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false MSHA acceptance of equivalent non-MSHA product... General § 7.10 MSHA acceptance of equivalent non-MSHA product safety standards. (a) MSHA will accept non...) [Reserved] (d) After MSHA has determined that non-MSHA product safety standards are equivalent and has...

30 CFR 7.10 - MSHA acceptance of equivalent non-MSHA product safety standards.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false MSHA acceptance of equivalent non-MSHA product... General § 7.10 MSHA acceptance of equivalent non-MSHA product safety standards. (a) MSHA will accept non...) [Reserved] (d) After MSHA has determined that non-MSHA product safety standards are equivalent and has...

30 CFR 7.10 - MSHA acceptance of equivalent non-MSHA product safety standards.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false MSHA acceptance of equivalent non-MSHA product... General § 7.10 MSHA acceptance of equivalent non-MSHA product safety standards. (a) MSHA will accept non...) [Reserved] (d) After MSHA has determined that non-MSHA product safety standards are equivalent and has...

30 CFR 7.10 - MSHA acceptance of equivalent non-MSHA product safety standards.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false MSHA acceptance of equivalent non-MSHA product... General § 7.10 MSHA acceptance of equivalent non-MSHA product safety standards. (a) MSHA will accept non...) [Reserved] (d) After MSHA has determined that non-MSHA product safety standards are equivalent and has...

The impact of pharmaceutical innovation on premature cancer mortality in Canada, 2000-2011.

PubMed

Lichtenberg, Frank R

2015-09-01

The premature cancer mortality rate has been declining in Canada, but there has been considerable variation in the rate of decline across cancer sites. I analyze the effect that pharmaceutical innovation had on premature cancer mortality in Canada during the period 2000-2011, by investigating whether the cancer sites that experienced more pharmaceutical innovation had larger declines in the premature mortality rate, controlling for changes in the incidence rate. Premature mortality before age 75 is significantly inversely related to the cumulative number of drugs registered at least 10 years earlier. Since mean utilization of drugs that have been marketed for less than 10 years is only one-sixth as great as mean utilization of drugs that have been marketed for at least a decade, it is not surprising that premature mortality is strongly inversely related only to the cumulative number of drugs that had been registered at least ten years earlier. Premature mortality before age 65 and 55 is also strongly inversely related to the cumulative number of drugs that had been registered at least ten years earlier. None of the estimates of the effect of incidence on mortality are statistically significant. Controlling for the cumulative number of drugs, the cumulative number of chemical subgroups does not have a statistically significant effect on premature mortality. This suggests that drugs (chemical substances) within the same class (chemical subgroup) are not therapeutically equivalent. During the period 2000-2011, the premature (before age 75) cancer mortality rate declined by about 9 %. The estimates imply that, in the absence of pharmaceutical innovation during the period 1985-1996, the premature cancer mortality rate would have increased about 12 % during the period 2000-2011. A substantial decline in the "competing risk" of death from cardiovascular disease could account for this. The estimates imply that pharmaceutical innovation during the period 1985-1996 reduced the number of years of potential life lost to cancer before age 75 in 2011 by 105,366. The cost per life-year before age 75 gained from previous pharmaceutical innovation is estimated to have been 2730 USD. Most of the previously-registered drugs were off-patent by 2011, but evidence suggests that, even if these drugs had been sold at branded rather than generic prices, the cost per life-year gained would have been below 11,000 USD, a figure well below even the lowest estimates of the value of a life-year gained. The largest reductions in premature mortality occur at least a decade after drugs are registered, when their utilization increases significantly. This suggests that, if Canada is to obtain substantial additional reductions in premature cancer mortality in the future (a decade or more from now) at a modest cost, pharmaceutical innovation (registration of new drugs) is needed today.

A simple calculation method for determination of equivalent square field.

PubMed

Shafiei, Seyed Ali; Hasanzadeh, Hadi; Shafiei, Seyed Ahmad

2012-04-01

Determination of the equivalent square fields for rectangular and shielded fields is of great importance in radiotherapy centers and treatment planning software. This is accomplished using standard tables and empirical formulas. The goal of this paper is to present a formula based on analysis of scatter reduction due to inverse square law to obtain equivalent field. Tables are published by different agencies such as ICRU (International Commission on Radiation Units and measurements), which are based on experimental data; but there exist mathematical formulas that yield the equivalent square field of an irregular rectangular field which are used extensively in computation techniques for dose determination. These processes lead to some complicated and time-consuming formulas for which the current study was designed. In this work, considering the portion of scattered radiation in absorbed dose at a point of measurement, a numerical formula was obtained based on which a simple formula was developed to calculate equivalent square field. Using polar coordinate and inverse square law will lead to a simple formula for calculation of equivalent field. The presented method is an analytical approach based on which one can estimate the equivalent square field of a rectangular field and may be used for a shielded field or an off-axis point. Besides, one can calculate equivalent field of rectangular field with the concept of decreased scatter radiation with inverse square law with a good approximation. This method may be useful in computing Percentage Depth Dose and Tissue-Phantom Ratio which are extensively used in treatment planning.

75 FR 33534 - Milk in the Northeast and Other Marketing Areas; Final Decision on Proposed Amendments to...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-14

... incorporates an equivalent 2.25 percent true milk protein criterion for determining if a product meets the... percent true milk protein criterion for determining if a product meets the compositional standard. The... solids and incorporates an equivalent 2.25 percent true milk protein criterion for determining whether a...

Rates of opioid dispensing and overdose after introduction of abuse-deterrent extended-release oxycodone and withdrawal of propoxyphene.

PubMed

Larochelle, Marc R; Zhang, Fang; Ross-Degnan, Dennis; Wharam, J Frank

2015-06-01

In the second half of 2010, abuse-deterrent extended-release oxycodone hydrochloride (OxyContin; Purdue Pharma) was introduced and propoxyphene was withdrawn from the US market. The effect of these pharmaceutical market changes on opioid dispensing and overdose rates is unknown. To evaluate the association between 2 temporally proximate changes in the opioid market and opioid dispensing and overdose rates. Claims from a large national US health insurer were analyzed, using an interrupted time series study design. Participants included an open cohort of 31.3 million commercially insured members aged 18 to 64 years between January 1, 2003, and December 31, 2012, with median follow-up of 20 months (last follow-up, December 31, 2012). Introduction of abuse-deterrent OxyContin (resistant to crushing or dissolving) on August 9, 2010, and market withdrawal of propoxyphene on November 19, 2010. Standardized opioid dispensing rates and prescription opioid and heroin overdose rates were the primary outcomes. We used segmented regression to analyze changes in outcomes from 30 quarters before to 8 quarters after the 2 interventions. Two years after the opioid market changes, total opioid dispensing decreased by 19% from the expected rate (absolute change, -32.2 mg morphine-equivalent dose per member per quarter [95% CI, -38.1 to -26.3]). By opioid subtype, the absolute change in dispensing by milligrams of morphine-equivalent dose per member per quarter at 2 years was -11.3 (95% CI, -12.4 to -10.1) for extended-release oxycodone, 3.26 (95% CI, 1.40 to 5.12) for other long-acting opioids, -8.19 (95% CI, -9.30 to -7.08) for propoxyphene, and -16.2 (95% CI, -18.8 to -13.5) for other immediate-release opioids. Two years after the market changes, the estimated overdose rate attributed to prescription opioids decreased by 20% (absolute change, -1.10 per 100,000 members per quarter [95% CI, -1.47 to -0.74]), but heroin overdose increased by 23% (absolute change, 0.26 per 100,000 members per quarter [95% CI, -0.01 to 0.53]). Opioid dispensing and prescription opioid overdoses decreased substantially after 2 major changes in the pharmaceutical market in late 2010. Pharmaceutical market interventions may have value in combatting the prescription opioid overdose epidemic, but heroin overdose rates continue to increase. Complementary strategies to identify and treat opioid abuse and addiction are urgently needed.

Time trends and determinants of pharmaceutical expenditure in China (1990-2009).

PubMed

Shi, Lizheng; Yang, Heidi Y; Cheng, Gang; Meng, Qingyue

2014-03-01

Pharmaceutical policy reform is currently one of the primary areas of health reform in China. The national pharmaceutical policy of China has multiple objectives: to develop the domestic pharmaceutical industry and encourage innovation, to control escalation of total pharmaceutical expenditures (TPE) which constitute a substantial component of total health expenditures (THE), and to ensure access to essential medicines for poor and uninsured patients. The current pharmaceutical system has been criticized for its high costs, questionable prescribing practices, and poor regulation of drug quality. This study aims to examine the time trends and influential factors of TPE in China. Data from the 2010 China National Health Accounts Report and the 2010 China Health Statistics Year Book were used in the analysis. Time trends of TPE as a share of THE (TPE/THE), of gross domestic product [GDP] (TPE/GDP), and the relationship between TPE/THE and GDP were examined. The growth of TPE was examined after adjusting for health care utilization and GDP. The determinants of the TPE/THE and the TPE/GDP between 1990 and 2009 were investigated by two time-series regression models including the amount of prescriptions dispensed (using proxy variables of health utilization), the price indices of medical services, and the price indices of pharmaceuticals during that time period. Descriptive analyses showed that TPE and THE grew consistently during the years 1990-2009. The ratio of the THE/GDP increased more rapidly in recent years than the TPE/GDP. Furthermore, outpatient pharmaceutical expenditures (PEs) per visit and hospital PEs per admission grew throughout the study period. The amount of outpatient visits did not show a significant growth pattern during the 1990s, despite rapid GDP growth during that period. The time-series models showed that the TPE/THE was negatively associated with GDP during the same year (p = 0.039), as well as the medical consumer price index [CPI] (p = 0.021). The TPE/GDP was influenced by the price index of prescriptions (p < 0.001) and the amount of health services utilization, including inpatient admissions (p = 0.012) and outpatient visits (p = 0.003). The cost escalations in PEs and health expenditures were concurrent with GDP growth. TPE has been the major source of financial burden for patients. Even though the rapid growth in China's economy may ameliorate the overall TPE burden, control of PEs is still a key for successful health system reform.

Green Pharmaceutical Analysis of Drugs Coformulated with Highly Different Concentrations Using Spiking and Manipulation of Their Ratio Spectra.

PubMed

Ayoub, Bassam M

2017-07-01

Introducing green analysis to pharmaceutical products is considered a significant approach to preserving the environment. This method can be an environmentally friendly alternative to the existing methods, accompanied by a validated automated procedure for the analysis of a drug with the lowest possible number of samples. Different simple spectrophotometric methods were developed for the simultaneous determination of empagliflozin (EG) and metformin (MT) by manipulating their ratio spectra in their application on a recently approved pharmaceutical combination, Synjardy tablets. A spiking technique was used to increase the concentration of EG in samples prepared from the tablets to allow for the simultaneous determination of EG with MT without prior separation. Validation parameters according to International Conference on Harmonization guidelines were acceptable over a concentration range of 2-12 μg/mL for both drugs using derivative ratio and ratio subtraction coupled with extended ratio subtraction. The optimized methods were compared using one-way analysis of variance and proved to be suitable as ecofriendly approaches for industrial QC laboratories.

Square Wave Voltammetric Determination of Diclofenac in Pharmaceutical Preparations and Human Serum

PubMed Central

Ciltas, Ulvihan; Yilmaz, Bilal; Kaban, Selcuk; Akcay, Bilge Kaan; Nazik, Gulsah

2015-01-01

In this study, a simple and reliable square wave voltammetric (SWV) method was developed and validated for determination of diclofenac in pharmaceutical preparations and human serum. The proposed method was based on electrooxidation of diclofenac at platinum electrode in 0.1 M TBAClO4/acetonitrile solution. The well-defined two oxidation peaks were observed at 0.87 and 1.27 V, respectively. Calibration curves that were obtained by using current values measured for second peak were linear over the concentration range of 1.5-17.5 μg mL-1 and 2-20 μg mL-1 in supporting electrolyte and serum, respectively. Precision and accuracy were also checked in all media. Intra- and inter-day precision values for diclofenac were less than 3.64, and accuracy (relative error) was better than 2.49%. Developed method in this study is accurate, precise and can be easily applied to Diclomec, Dicloflam and Voltaren tablets as pharmaceutical preparation. Also, the proposed technique was successfully applied to spiked human serum samples. No electroactive interferences from the endogenous substances were found in human serum. PMID:26330859

Square Wave Voltammetric Determination of Diclofenac in Pharmaceutical Preparations and Human Serum.

PubMed

Ciltas, Ulvihan; Yilmaz, Bilal; Kaban, Selcuk; Akcay, Bilge Kaan; Nazik, Gulsah

2015-01-01

In this study, a simple and reliable square wave voltammetric (SWV) method was developed and validated for determination of diclofenac in pharmaceutical preparations and human serum. The proposed method was based on electrooxidation of diclofenac at platinum electrode in 0.1 M TBAClO4/acetonitrile solution. The well-defined two oxidation peaks were observed at 0.87 and 1.27 V, respectively. Calibration curves that were obtained by using current values measured for second peak were linear over the concentration range of 1.5-17.5 μg mL(-1) and 2-20 μg mL(-1) in supporting electrolyte and serum, respectively. Precision and accuracy were also checked in all media. Intra- and inter-day precision values for diclofenac were less than 3.64, and accuracy (relative error) was better than 2.49%. Developed method in this study is accurate, precise and can be easily applied to Diclomec, Dicloflam and Voltaren tablets as pharmaceutical preparation. Also, the proposed technique was successfully applied to spiked human serum samples. No electroactive interferences from the endogenous substances were found in human serum.

QSPR studies on the photoinduced-fluorescence behaviour of pharmaceuticals and pesticides.

PubMed

López-Malo, D; Bueso-Bordils, J I; Duart, M J; Alemán-López, P A; Martín-Algarra, R V; Antón-Fos, G M; Lahuerta-Zamora, L; Martínez-Calatayud, J

2017-07-01

Fluorimetric analysis is still a growing line of research in the determination of a wide range of organic compounds, including pharmaceuticals and pesticides, which makes necessary the development of new strategies aimed at improving the performance of fluorescence determinations as well as the sensitivity and, especially, the selectivity of the newly developed analytical methods. In this paper are presented applications of a useful and growing tool suitable for fostering and improving research in the analytical field. Experimental screening, molecular connectivity and discriminant analysis are applied to organic compounds to predict their fluorescent behaviour after their photodegradation by UV irradiation in a continuous flow manifold (multicommutation flow assembly). The screening was based on online fluorimetric measurement and comprised pre-selected compounds with different molecular structures (pharmaceuticals and some pesticides with known 'native' fluorescent behaviour) to study their changes in fluorescent behaviour after UV irradiation. Theoretical predictions agree with the results from the experimental screening and could be used to develop selective analytical methods, as well as helping to reduce the need for expensive, time-consuming and trial-and-error screening procedures.

RP-HPLC Method Development and Validation for Determination of Eptifibatide Acetate in Bulk Drug Substance and Pharmaceutical Dosage Forms.

PubMed

Bavand Savadkouhi, Maryam; Vahidi, Hossein; Ayatollahi, Abdul Majid; Hooshfar, Shirin; Kobarfard, Farzad

2017-01-01

A new, rapid, economical and isocratic reverse phase high performance liquid chromatography (RP-HPLC) method was developed for the determination of eptifibatide acetate, a small synthetic antiplatelet peptide, in bulk drug substance and pharmaceutical dosage forms. The developed method was validated as per of ICH guidelines. The chromatographic separation was achieved isocratically on C18 column (150 x 4.60 mm i.d., 5 µM particle size) at ambient temperature using acetonitrile (ACN), water and trifluoroacetic acid (TFA) as mobile phase at flow rate of 1 mL/min and UV detection at 275 nm. Eptifibatide acetate exhibited linearity over the concentration range of 0.15-2 mg/mL (r 2 =0.997) with limit of detection of 0.15 mg/mL The accuracy of the method was 96.4-103.8%. The intra-day and inter-day precision were between 0.052% and 0.598%, respectively. The present successfully validated method with excellent selectivity, linearity, sensitivity, precision and accuracy was applicable for the assay of eptifibatide acetate in bulk drug substance and pharmaceutical dosage forms.

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

PubMed

Horkovics-Kovats, Stefan

2014-02-01

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

Measurements of elastic moduli of pharmaceutical compacts: a new methodology using double compaction on a compaction simulator.

PubMed

Mazel, Vincent; Busignies, Virginie; Diarra, Harona; Tchoreloff, Pierre

2012-06-01

The elastic properties of pharmaceutical powders play an important role during the compaction process. The elastic behavior can be represented by Young's modulus (E) and Poisson's ratio (v). However, during the compaction, the density of the powder bed changes and the moduli must be determined as a function of the porosity. This study proposes a new methodology to determine E and v as a function of the porosity using double compaction in an instrumented compaction simulator. Precompression is used to form the compact, and the elastic properties are measured during the beginning of the main compaction. By measuring the axial and radial pressure and the powder bed thickness, E and v can be determined as a function of the porosity. Two excipients were studied, microcrystalline cellulose (MCC) and anhydrous calcium phosphate (aCP). The values of E measured are comparable to those obtained using the classical three-point bending test. Poisson's ratio was found to be close to 0.24 for aCP with only small variations with the porosity, and to increase with a decreasing porosity for MCC (0.23-0.38). The classical approximation of a value of 0.3 for ν of pharmaceutical powders should therefore be taken with caution. Copyright © 2012 Wiley Periodicals, Inc.

New Spectrophotometric and Fluorimetric Methods for Determination of Fluoxetine in Pharmaceutical Formulations

PubMed Central

Darwish, Ibrahim A.; Amer, Sawsan M.; Abdine, Heba H.; Al-Rayes, Lama I.

2009-01-01

New simple and sensitive spectrophotometric and fluorimetric methods have been developed and validated for the determination of fluoxetine hydrochloride (FLX) in its pharmaceutical formulations. The spectrophotometric method was based on the reaction of FLX with 1,2-naphthoquinone-4-sulphonate (NQS) in an alkaline medium (pH 11) to form an orange-colored product that was measured at 490 nm. The fluorimetric method was based on the reaction of FLX with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) in an alkaline medium (pH 8) to form a highly fluorescent product that was measured at 545 nm after excitation at 490 nm. The variables affecting the reactions of FLX with both NQS and NBD-Cl were carefully studied and optimized. The kinetics of the reactions were investigated, and the reaction mechanisms were presented. Under the optimum reaction conditions, good linear relationships were found between the readings and the concentrations of FLX in the ranges of 0.3–6 and 0.035–0.5 μg mL−1 for the spectrophotometric and fluorimetric methods, respectively. The limits of detection were 0.1 and 0.01 μg mL−1 for the spectrophotometric and fluorimetric methods, respectively. Both methods were successfully applied to the determination of FLX in its pharmaceutical formulations. PMID:20107560

Anodic voltammetric behavior and determination of cefixime in pharmaceutical dosage forms and biological fluids.

PubMed

Golcu, Ayşegul; Dogan, Burcu; Ozkan, Sibel A

2005-10-15

The voltammetric behavior of cefixime was studied using cyclic, linear sweep, differential pulse and square wave voltammetric techniques. The oxidation of cefixime was irreversible and exhibited diffusion controlled process depending on pH. The oxidation mechanism was proposed and discussed. Different parameters were tested to optimize the conditions for the determination of cefixime. The dependence of current intensities and potentials on pH, concentration, scan rate, nature of the buffer was investigated. According to the linear relationship between the peak current and the concentration, differential pulse (DPV) and square wave (SWV) voltammetric methods for cefixime assay in pharmaceutical dosage forms and biological fluids were developed. For the determination of cefixime were proposed in acetate buffer at pH 4.5, which allows quantitation over the 6 x 10(-6)-2 x 10(-4)M range in supporting electrolyte and spiked serum sample; 8 x 10(-6)-2 x 10(-4)M range in urine sample; 6 x 10(-6)-1 x 10(-4)M range in breast milk samples for both techniques. The repeatability, reproducibility, precision and accuracy of the methods in all media were investigated. No electroactive interferences from the excipients and endogenous substances were found in the pharmaceutical dosage forms and in the biological samples, respectively.

The selective determination of sulfates, sulfonates, and phosphates in urine by capillary electrophoresis/mass spectrometry.

PubMed

Bunz, Svenja-Catharina; Neusüß, Christian

2013-01-01

Metabolite identification and metabolite profiling are of major importance in the pharmaceutical and clinical context. However, anions of biological relevance such as sulfates, sulfonates, and phosphates are rarely included in common techniques for metabolite studies. In this protocol, we demonstrate a unique method to selectively determine these anions. The method comprises a capillary electrophoresis separation using an acidic background electrolyte (pH ≤ 2) and anodic detection by mass spectrometry via negative electrospray ionization. In this way, only anions of strong acids like sulfates are determined. The selectivity for sulfur-containing species is proved based on the specific isotopic ratios. In conjunction with the accurate mass from the time-of-flight mass spectrometer, the presented method is well suited for clinical and pharmaceutical applications to identify possible metabolites and to quantify known metabolites.

Metabolic engineering: the ultimate paradigm for continuous pharmaceutical manufacturing.

PubMed

Yadav, Vikramaditya G; Stephanopoulos, Gregory

2014-07-01

Research and development (R&D) expenditures by pharmaceutical companies doubled over the past decade, yet candidate attrition rates and development times rose markedly during this period. Understandably, companies have begun downsizing their pipelines and diverting investments away from R&D in favor of manufacturing. It is estimated that transitioning to continuous manufacturing could enable companies to compete for a share in emerging markets. Accordingly, the model for continuous manufacturing that has emerged commences with the conversion of late-stage intermediates into the active pharmaceutical ingredient (API) in a series of continuous flow reactors, followed by continuous solid processing to form finished tablets. The use of flow reactions for API synthesis will certainly generate purer products at higher yields in shorter times compared to equivalent batch reactions. However, transitioning from batch to flow configuration simply alleviates transport limitations within the reaction milieu. As the catalogue of reactions used in flow syntheses is a subset of batch-based chemistries, molecules such as natural products will continue to evade drug prospectors. Also, it is uncertain whether flow synthesis can deliver improvements in the atom and energy economies of API production at the scales that would achieve the levels of revenue growth targeted by companies. Instead, it is argued that implementing metabolic engineering for the production of oxidized scaffolds as gateway molecules for flow-based addition of electrophiles is a more effective and scalable strategy for accessing natural product chemical space. This new paradigm for manufacturing, with metabolic engineering as its engine, would also permit rapid optimization of production variables and allow facile scale-up from gram to ton scale to meet material requirements for clinical trials, thus recasting manufacturing as a tool for discovery. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Medicine procurement and the use of flexibilities in the Agreement on Trade-Related Aspects of Intellectual Property Rights, 2001-2016.

PubMed

't Hoen, Ellen Fm; Veraldi, Jacquelyn; Toebes, Brigit; Hogerzeil, Hans V

2018-03-01

Millions of people, particularly in low- and middle-income countries, lack access to effective pharmaceuticals, often because they are unaffordable. The 2001 Ministerial Conference of the World Trade Organization (WTO) adopted the Doha Declaration on the TRIPS (Trade-Related Aspects of Intellectual Property Rights) Agreement and Public Health. The declaration recognized the implications of intellectual property rights for both new medicine development and the price of medicines. The declaration outlined measures, known as TRIPS flexibilities, that WTO Members can take to ensure access to medicines for all. These measures include compulsory licensing of medicines patents and the least-developed countries pharmaceutical transition measure. The aim of this study was to document the use of TRIPS flexibilities to access lower-priced generic medicines between 2001 and 2016. Overall, 176 instances of the possible use of TRIPS flexibilities by 89 countries were identified: 100 (56.8%) involved compulsory licences or public noncommercial use licences and 40 (22.7%) involved the least-developed countries pharmaceutical transition measure. The remainder were: 1 case of parallel importation; 3 research exceptions; and 32 non-patent-related measures. Of the 176 instances, 152 (86.4%) were implemented. They covered products for treating 14 different diseases. However, 137 (77.8%) concerned medicines for human immunodeficiency virus infection and acquired immune deficiency syndrome or related diseases. The use of TRIPS flexibilities was found to be more frequent than is commonly assumed. Given the problems faced by countries today in procuring high-priced, patented medicines, the practical, legal pathway provided by TRIPS flexibilities for accessing lower-cost generic equivalents is increasingly important.

Biopharmaceutic Risk Assessment of Brand and Generic Lamotrigine Tablets.

PubMed

Vaithianathan, Soundarya; Raman, Siddarth; Jiang, Wenlei; Ting, Tricia Y; Kane, Maureen A; Polli, James E

2015-07-06

The therapeutic equivalence of generic and brand name antiepileptic drugs has been questioned by neurologists and the epilepsy community. A potential contributor to such concerns is pharmaceutical quality. The objective was to assess the biopharmaceutic risk of brand name Lamictal 100 mg tablets and generic lamotrigine 100 mg tablets from several manufacturers. Lamotrigine was characterized in terms of the Biopharmaceutics Classification System (BCS), including aqueous solubility and Caco-2 permeability. A panel of pharmaceutical quality tests was also performed on three batches of Lamictal, three batches of Teva generic, and one batch of each of four other generics: appearance, identity, assay, impurity, uniformity of dosage units, disintegration, dissolution, friability, and loss on drying. These market surveillance results indicate that all brand name and generic lamotrigine 100 mg tablets passed all tests and showed acceptable pharmaceutical quality and low biopharmaceutic risk. Lamotrigine was classified as a BCS class IIb drug, exhibiting pH-dependent aqueous solubility and dissolution. At pH 1.2 and 4.5, lamotrigine exhibited high solubility, whereas lamotrigine exhibited low solubility at pH 6.8, including non-sink dissolution. Lamotrigine showed high Caco-2 permeability. The apparent permeability (Papp) of lamotrigine was (73.7 ± 8.7) × 10(-6) cm/s in the apical-to-basolateral (AP-BL) direction and (41.4 ± 1.6) × 10(-6) cm/s in the BL-AP direction, which were higher than metoprolol's AP-BL Papp of (21.2 ± 0.9) × 10(-6) cm/s and BL-AP Papp of (34.6 ± 4.6) × 10(-6) cm/s. Overall, lamotrigine's favorable biopharmaceutics from a drug substance perspective and favorable quality characteristics from a tablet formulation perspective suggest that multisource lamotrigine tablets exhibit a low biopharmaceutic risk.

Medicine procurement and the use of flexibilities in the Agreement on Trade-Related Aspects of Intellectual Property Rights, 2001–2016

PubMed Central

Veraldi, Jacquelyn; Toebes, Brigit; Hogerzeil, Hans V

2018-01-01

Abstract Millions of people, particularly in low- and middle-income countries, lack access to effective pharmaceuticals, often because they are unaffordable. The 2001 Ministerial Conference of the World Trade Organization (WTO) adopted the Doha Declaration on the TRIPS (Trade-Related Aspects of Intellectual Property Rights) Agreement and Public Health. The declaration recognized the implications of intellectual property rights for both new medicine development and the price of medicines. The declaration outlined measures, known as TRIPS flexibilities, that WTO Members can take to ensure access to medicines for all. These measures include compulsory licensing of medicines patents and the least-developed countries pharmaceutical transition measure. The aim of this study was to document the use of TRIPS flexibilities to access lower-priced generic medicines between 2001 and 2016. Overall, 176 instances of the possible use of TRIPS flexibilities by 89 countries were identified: 100 (56.8%) involved compulsory licences or public noncommercial use licences and 40 (22.7%) involved the least-developed countries pharmaceutical transition measure. The remainder were: 1 case of parallel importation; 3 research exceptions; and 32 non-patent-related measures. Of the 176 instances, 152 (86.4%) were implemented. They covered products for treating 14 different diseases. However, 137 (77.8%) concerned medicines for human immunodeficiency virus infection and acquired immune deficiency syndrome or related diseases. The use of TRIPS flexibilities was found to be more frequent than is commonly assumed. Given the problems faced by countries today in procuring high-priced, patented medicines, the practical, legal pathway provided by TRIPS flexibilities for accessing lower-cost generic equivalents is increasingly important. PMID:29531417

Are pharmacological properties of anticoagulants reflected in pharmaceutical pricing and reimbursement policy? Out-patient treatment of venous thromboembolism and utilization of anticoagulants in Poland.

PubMed

Bochenek, T; Czarnogorski, M; Nizankowski, R; Pilc, A

2014-06-01

Pharmacotherapy with vitamin K antagonists (VKA) and low-molecular-weight heparins (LMWH) is a major cost driver in the treatment of venous thromboembolism (VTE). Major representatives of anticoagulants in Europe include: acenocoumarol and warfarin (VKA), enoxaparin, dalteparin, nadroparin, reviparin, parnaparin and bemiparin (LMWH). Aim of this report is to measure and critically assess the utilization of anticoagulants and other resources used in the out-patient treatment of VTE in Poland. To confront the findings with available scientific evidence on pharmacological and clinical properties of anticoagulants. The perspectives of the National Health Fund (NHF) and the patients were adopted, descriptive statistics methods were used. The data were gathered at the NHF and the clinic specialized in treatment of coagulation disorders. Non-pharmacological costs of treatment were for the NHF 1.6 times higher with VKA than with LMWH. Daily cost of pharmacotherapy with LMWH turned out higher than with VKA (234 times for the NHF, 42 times per patient). Within both LMWH and VKA the reimbursement due for the daily doses of a particular medication altered in the manner inversely proportional to the level of patient co-payment. Utilization of long-marketed and cheap VKA was dominated by LMWH, when assessed both through the monetary measures and by the actual volume of sales. Pharmaceutical reimbursement policy favored the more expensive equivalents among VKA and LMWH, whereas in the financial terms the patients were far better off when remaining on a more expensive alternative. The pharmaceutical pricing and reimbursement policy of the state should be more closely related to the pharmacological properties of anticoagulants.

Effect of sampling volume on dry powder inhaler (DPI)-emitted aerosol aerodynamic particle size distributions (APSDs) measured by the Next-Generation Pharmaceutical Impactor (NGI) and the Andersen eight-stage cascade impactor (ACI).

PubMed

Mohammed, Hlack; Roberts, Daryl L; Copley, Mark; Hammond, Mark; Nichols, Steven C; Mitchell, Jolyon P

2012-09-01

Current pharmacopeial methods for testing dry powder inhalers (DPIs) require that 4.0 L be drawn through the inhaler to quantify aerodynamic particle size distribution of "inhaled" particles. This volume comfortably exceeds the internal dead volume of the Andersen eight-stage cascade impactor (ACI) and Next Generation pharmaceutical Impactor (NGI) as designated multistage cascade impactors. Two DPIs, the second (DPI-B) having similar resistance than the first (DPI-A) were used to evaluate ACI and NGI performance at 60 L/min following the methodology described in the European and United States Pharmacopeias. At sampling times ≥2 s (equivalent to volumes ≥2.0 L), both impactors provided consistent measures of therapeutically important fine particle mass (FPM) from both DPIs, independent of sample duration. At shorter sample times, FPM decreased substantially with the NGI, indicative of incomplete aerosol bolus transfer through the system whose dead space was 2.025 L. However, the ACI provided consistent measures of both variables across the range of sampled volumes evaluated, even when this volume was less than 50% of its internal dead space of 1.155 L. Such behavior may be indicative of maldistribution of the flow profile from the relatively narrow exit of the induction port to the uppermost stage of the impactor at start-up. An explanation of the ACI anomalous behavior from first principles requires resolution of the rapidly changing unsteady flow and pressure conditions at start up, and is the subject of ongoing research by the European Pharmaceutical Aerosol Group. Meanwhile, these experimental findings are provided to advocate a prudent approach by retaining the current pharmacopeial methodology.

Water Quality in the Blue River Basin, Kansas City Metropolitan Area, Missouri and Kansas, July 1998 to October 2004

USGS Publications Warehouse

Wilkison, Donald H.; Armstrong, Daniel J.; Norman, Richard D.; Polton, Barry C.; Furlong, Edward T.; Zaugg, Steven D.

2006-01-01

Water-quality data were collected from sites in the Blue River Basin from July 1998 to October. Sites upstream from wastewater-treatment plants or the combined sewer system area had lower concentrations of total nitrogen, phosphorus, organic wastewater compounds, and pharmaceuticals, and more diverse aquatic communities. Sites downstream from wastewater-treatment plants had the largest concentrations and loads of nutrients, organic wastewater compounds, and pharmaceuticals. Approximately 60 percent of the total nitrogen and phosphorus in Blue River originated from the Indian Creek, smaller amounts from the upper Blue River (from 28 to 16 percent), and less than 5 percent from Brush Creek. Nutrient yields from the Indian Creek and the middle Blue River were significantly greater than yields from the upper Blue River, lower Brush Creek, the outside control site, and other U.S. urban sites. Large concentrations of nutrients led to eutrophication of impounded Brush Creek reaches. Bottom sediment samples collected from impoundments generally had concentrations of organic wastewater and pharmaceutical compounds equivalent to or greater than, concentrations observed in streambed sediments downstream from wastewater-treatment plants. Bacteria in streams largely was the result of nonpoint-source contributions during storms. Based on genetic source-tracking, average contributions of in-stream Esherichia coli bacteria in the basin from dogs ranged from 26-32 percent of the total concentration, and human sources ranged from 28-42 percent. Macro invertebrate diversity was highest at sites with the largest percentage of upstream land use devoted to forests and grasslands. Declines in macro invertebrate community metrics were correlated strongly with increases in several, inter-related urbanization factors.

Water quality in the Blue River basin, Kansas City metropolitan area, Missouri and Kansas, July 1998 to October 2004

USGS Publications Warehouse

Wilkison, Donald H.; Armstrong, Daniel J.; Norman, Richard D.; Poulton, Barry C.; Furlong, Edward T.; Zaugg, Steven D.

2006-01-01

Water-quality data were collected from sites in the Blue River Basin from July 1998 to October. Sites upstream from wastewater-treatment plants or the combined sewer system area had lower concentrations of total nitrogen, phosphorus, organic wastewater compounds, and pharmaceuticals, and more diverse aquatic communities. Sites downstream from wastewater-treatment plants had the largest concentrations and loads of nutrients, organic wastewater compounds, and pharmaceuticals. Approximately 60 percent of the total nitrogen and phosphorus in Blue River originated from the Indian Creek, smaller amounts from the upper Blue River (from 28 to 16 percent), and less than 5 percent from Brush Creek. Nutrient yields from the Indian Creek and the middle Blue River were significantly greater than yields from the upper Blue River, lower Brush Creek, the outside control site, and other U.S. urban sites. Large concentrations of nutrients led to eutrophication of impounded Brush Creek reaches. Bottom sediment samples collected from impoundments generally had concentrations of organic wastewater and pharmaceutical compounds equivalent to or greater than, concentrations observed in streambed sediments downstream from wastewater-treatment plants. Bacteria in streams largely was the result of nonpoint-source contributions during storms. Based on genetic source-tracking, average contributions of in-stream Esherichia coli bacteria in the basin from dogs ranged from 26-32 percent of the total concentration, and human sources ranged from 28-42 percent. Macro invertebrate diversity was highest at sites with the largest percentage of upstream land use devoted to forests and grasslands. Declines in macro invertebrate community metrics were correlated strongly with increases in several, inter-related urbanization factors.

Determination of sulpiride in pharmaceutical preparations and biological fluids using a Cr (III) enhanced chemiluminescence method.

PubMed

Khan, Muhammad Naeem; Jan, Muhammad Rasul; Shah, Jasmin; Lee, Sang Hak; Kim, Young Ho

2013-01-01

A highly sensitive and simple method for identifying sulpiride in pharmaceutical formulations and biological fluids is presented. The method is based on increased chemiluminescence (CL) intensity of a luminol-H2O2 system in response to the addition of Cr (III) under alkaline conditions. The CL intensity of the luminol-H2O2-Cr (III) system was greatly enhanced by the addition of sulpiride and the CL intensity was proportional to the concentration of sulpiride in a sample solution. Various parameters affecting the CL intensity were systematically investigated and optimized for determination of the sulpiride in a sample. Under the optimum conditions, the CL intensity was proportional to the concentration of sulpiride in the range of 0.068-4.0 µg/mL, with a good correlation coefficient of 0.997. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 8.50 × 10(-6) µg/mL and 2.83 × 10(-5) µg/mL, respectively. The method presented here produced good reproducibility with a relative standard deviation (RSD) of 2.70% (n = 7). The effects of common excipients and metal ions were studied for their interference effect. The method was validated statistically through recovery studies and successfully applied for the determination of sulpiride in pure form, pharmaceutical preparations and spiked human plasma samples. The percentage recoveries were found to range from 99.10 to 100.05% for pure form, 98.12 to 100.18% for pharmaceutical preparations and 97.9 to 101.4% for spiked human plasma. Copyright © 2012 John Wiley & Sons, Ltd.

Potency Determination of Antidandruff Shampoos in Nystatin International Unit Equivalents

PubMed Central

Anusha Hewage, D. B. G.; Pathirana, W.; Pinnawela, Amara

2008-01-01

A convenient standard microbiological potency determination test for the antidandruff shampoos was developed by adopting the pharmacopoeial microbiological assay procedure of the drug nystatin. A standard curve was drawn consisting of the inhibition zone diameters vs. logarithm of nystatin concentrations in international units using the fungus Saccharomyces cerevisiae (yeast) strain National Collection of Type Culture (NCTC) 1071606 as the test organism. From the standard curve the yeast inhibitory potencies of the shampoos in nystatin international unit equivalents were determined from the respective inhibition zones of the test samples of the shampoos. Under test conditions four shampoo samples showed remarkable fungal inhibitory potencies of 10227, 10731, 12396 and 18211 nystatin international unit equivalents/ml while two shampoo samples had extremely feeble inhibitory potencies 4.07 and 4.37 nystatin international unit equivalents/ml although the latter two products claimed antifungal activity. The potency determination method could be applied to any antidandruff shampoo with any one or a combination of active ingredients. PMID:21394271

Chemical composition of barks from Quercus faginea trees and characterization of their lipophilic and polar extracts.

PubMed

Ferreira, Joana P A; Miranda, Isabel; Sousa, Vicelina B; Pereira, Helena

2018-01-01

The bark from Quercus faginea mature trees from two sites was chemically characterized for the first time. The barks showed the following composition: ash 14.6%, total extractives 13.2%, suberin 2.9% and lignin 28.2%. The polysaccharides were composed mainly of glucose and xylose (50.3% and 35.1% of all monosaccharides respectively) with 4.8% of uronic acids. The suberin composition was: ω-hydroxyacids 46.3% of total compounds, ɑ,ω-alkanoic diacids 22.3%, alkanoic acids 5.9%, alkanols 6.7% and aromatics 6.9% (ferulic acid 4.0%). Polar extracts (ethanol-water) had a high phenolic content of 630.3 mg of gallic acid equivalents (GAE)/g of extract, condensed tannins 220.7 mg of catechin equivalents (CE)/g extract, and flavonoids 207.7 mg CE/g of extract. The antioxidant activity was very high corresponding to 1567 mg Trolox equivalents/g of extract, and an IC50 of 2.63 μg extract/ml. The lipophilic extracts were constituted mainly by glycerol and its derivatives (12.3% of all compounds), alkanoic acids (27.8%), sterols (11.5%) and triterpenes (17.8%). In view of an integrated valorization, Quercus faginea barks are interesting sources of polar compounds including phenols and polyphenols with possible interesting bioactivities, while the sterols and triterpenes contained in the lipophilic extracts are also valuable bioactive compounds or chemical intermediates for specific high-value market niches, such as cosmetics, pharmaceuticals and biomedicine.

Chemical composition of barks from Quercus faginea trees and characterization of their lipophilic and polar extracts

PubMed Central

2018-01-01

The bark from Quercus faginea mature trees from two sites was chemically characterized for the first time. The barks showed the following composition: ash 14.6%, total extractives 13.2%, suberin 2.9% and lignin 28.2%. The polysaccharides were composed mainly of glucose and xylose (50.3% and 35.1% of all monosaccharides respectively) with 4.8% of uronic acids. The suberin composition was: ω-hydroxyacids 46.3% of total compounds, ɑ,ω-alkanoic diacids 22.3%, alkanoic acids 5.9%, alkanols 6.7% and aromatics 6.9% (ferulic acid 4.0%). Polar extracts (ethanol-water) had a high phenolic content of 630.3 mg of gallic acid equivalents (GAE)/g of extract, condensed tannins 220.7 mg of catechin equivalents (CE)/g extract, and flavonoids 207.7 mg CE/g of extract. The antioxidant activity was very high corresponding to 1567 mg Trolox equivalents/g of extract, and an IC50 of 2.63 μg extract/ml. The lipophilic extracts were constituted mainly by glycerol and its derivatives (12.3% of all compounds), alkanoic acids (27.8%), sterols (11.5%) and triterpenes (17.8%). In view of an integrated valorization, Quercus faginea barks are interesting sources of polar compounds including phenols and polyphenols with possible interesting bioactivities, while the sterols and triterpenes contained in the lipophilic extracts are also valuable bioactive compounds or chemical intermediates for specific high-value market niches, such as cosmetics, pharmaceuticals and biomedicine. PMID:29763441