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Sample records for improved pharmaceutical properties

  1. Eutectics as improved pharmaceutical materials: design, properties and characterization.

    PubMed

    Cherukuvada, Suryanarayan; Nangia, Ashwini

    2014-01-28

    Eutectics are a long known class of multi-component solids with important and useful applications in daily life. In comparison to other multi-component crystalline solids, such as salts, solid solutions, molecular complexes and cocrystals, eutectics are less studied in terms of molecular structure organization and bonding interactions. Classically, a eutectic is defined based on its low melting point compared to the individual components. In this article, we attempt to define eutectics not just based on thermal methods but from a structural organization view point, and discuss their microstructures and properties as organic materials vis-a-vis solid solutions and cocrystals. The X-ray crystal structure of a cocrystal is different from that of the individual components whereas the unit cell of a solid solution is similar to that of one of the components. Eutectics are closer to the latter species in that their crystalline arrangement is similar to the parent components but they are different with respect to the structural integrity. A solid solution possesses structural homogeneity throughout the structure (single phase) but a eutectic is a heterogeneous ensemble of individual components whose crystal structures are like discontinuous solid solutions (phase separated). Thus, a eutectic may be better defined as a conglomerate of solid solutions. A structural analysis of cocrystals, solid solutions and eutectics has led to an understanding that materials with strong adhesive (hetero) interactions between the unlike components will lead to cocrystals whereas those having stronger cohesive (homo/self) interactions will more often give rise to solid solutions (for similar structures of components) and eutectics (for different structures of components). We demonstrate that the same crystal engineering principles which have been profitably utilized for cocrystal design in the past decade can now be applied to make eutectics as novel composite materials, illustrated by

  2. Exploration of crystal simulation potential by fluconazole isomorphism and its application in improvement of pharmaceutical properties

    NASA Astrophysics Data System (ADS)

    Thakur, Amitha; Kumar, Dinesh; Thipparaboina, Rajesh; Shastri, Nalini R.

    2014-11-01

    Control of crystal morphology during crystallization is a paramount challenge in pharmaceutical processing. Hence, there is need to introduce computational methods for morphology prediction to manage production cost of drugs and improve related pharmaceutical and biopharmaceutical properties. Layer docking approach with molecular dynamics opens a new avenue for crystal habit prediction in presence of solvent. In the present study, attempts were made to correlate predicted and experimental crystal habits of fluconazole considering solvent interactions using layer docking approach. Simulated results from layer docking approach with methanol as solvent gave two dominant facets (0 1 1) and (1 0 1) with a surface area 22.43% and 19.82% respectively, which were in agreement with the experimental results. Experimentally grown modified crystal habit of fluconazole in methanol showed enhanced dissolution rate (p<0.05) when compared to plain drug. This was attributed to the increased surface area on the specified facets caused by interactions with the solvent. Furthermore, Differential Scanning Calorimetry, Fourier Transform Infrared (FTIR) Spectroscopy and powder X-ray Diffraction of recrystallized samples confirmed only a habit change and absence of any polymorphs, hydrates or solvates. Flow and compressibility of fluconazole recrystallized in methanol was significantly improved when compared to plain drug. This study demonstrates a methodical approach using computational tools for prediction and modification of crystal habit, to enhance dissolution of poorly soluble drugs, for future pharmaceutical applications.

  3. Pharmaceutical Cocrystals and Their Physicochemical Properties

    PubMed Central

    2009-01-01

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

  4. Creating an antibacterial with in vivo efficacy: synthesis and characterization of potent inhibitors of the bacterial cell division protein FtsZ with improved pharmaceutical properties.

    PubMed

    Haydon, David J; Bennett, James M; Brown, David; Collins, Ian; Galbraith, Greta; Lancett, Paul; Macdonald, Rebecca; Stokes, Neil R; Chauhan, Pramod K; Sutariya, Jignesh K; Nayal, Narendra; Srivastava, Anil; Beanland, Joy; Hall, Robin; Henstock, Vincent; Noula, Caterina; Rockley, Chris; Czaplewski, Lloyd

    2010-05-27

    3-Methoxybenzamide (1) is a weak inhibitor of the essential bacterial cell division protein FtsZ. Alkyl derivatives of 1 are potent antistaphylococcal compounds with suboptimal drug-like properties. Exploration of the structure-activity relationships of analogues of these inhibitors led to the identification of potent antistaphylococcal compounds with improved pharmaceutical properties.

  5. Thermal properties of food and pharmaceutical powders

    NASA Astrophysics Data System (ADS)

    Abiad, Mohamad Ghassan

    Foods and pharmaceuticals are complex systems usually exposed to various environmental conditions during processing and thus storage, stability, functionality and quality are key attributes that deserve careful attention. The quality and stability of foods and pharmaceuticals are mainly affected by environmental conditions such as temperature, humidity, time, and processing conditions (e.g. shear, pressure) under which they may undergo physical and/or chemical transformations. Glass transition as well as other thermal properties is a key to understand how external conditions affect physical changes of such materials. Development of new materials and understanding the physico-chemical behavior of existing ones require a scientific foundation that translates into safe and high quality foods, improved quality of pharmaceuticals and nutraceuticals with lower risk to patients and functional efficacy of polymers used in food and medicinal products. This research provides an overview of the glass transition and other thermal properties and introduces novel methods developed to characterize such properties.

  6. Discovery of pyrazine carboxamide CB1 antagonists: the introduction of a hydroxyl group improves the pharmaceutical properties and in vivo efficacy of the series.

    PubMed

    Ellsworth, Bruce A; Wang, Ying; Zhu, Yeheng; Pendri, Annapurna; Gerritz, Samuel W; Sun, Chongqing; Carlson, Kenneth E; Kang, Liya; Baska, Rose A; Yang, Yifan; Huang, Qi; Burford, Neil T; Cullen, Mary Jane; Johnghar, Susan; Behnia, Kamelia; Pelleymounter, Mary Ann; Washburn, William N; Ewing, William R

    2007-07-15

    Structure-activity relationships for a series of pyrazine carboxamide CB1 antagonists are reported. Pharmaceutical properties of the series are improved via inclusion of hydroxyl-containing sidechains. This structural modification sufficiently improved ADME properties of an orally inactive series such that food intake reduction was achieved in rat feeding models. Compound 35 elicits a 46% reduction in food intake in ad libidum fed rats 4-h post-dose.

  7. Improvement of some pharmaceutical properties of drugs by cyclodextrin complexation. 4. Chlorpromazine hydrochloride.

    PubMed

    Ammar, H O; Ghorab, M; el-Nahhas, S A; Omar, S M; Ghorab, M M

    1995-12-01

    The potentiality of interaction of chlorpromazine hydrochloride (CPZ) with beta-cyclodextrin (beta-CD) was investigated by spectrophotometry, vapour pressure osmometry and DSC thermograms. The results revealed a very strong evidence for molecular interaction between CPZ and beta-CD. The continuous variation method was used to elucidate the stoichiometry of such interaction by spectrophotometric as well as vapour pressure measurements. Both types of data revealed the formation of a 1:1 complex. The stability constant of the complex was determined at different temperatures by the vapour pressure osmometric method. The enthalpy and entropy of interaction were evaluated and the results indicate that the interaction is exothermic. The CPZ/beta-CD complex was prepared, lyophilized and photochemical stability of the drug, its physical mixture with beta-CD as well as the prepared complex was investigated at different pH-values in presence of different buffer systems. The results revealed that the stability of the drug is greatly improved in presence of beta-CD and the great dependency of stability on the pH of the solution is decreased in presence of beta-CD. The partition coefficient of CPZ and its complex with beta-CD was determined. The data reveal a higher p.c. of the complex compared to the parent drug. The effect of beta-CD on the bioavailability of CPZ was investigated by measuring the miotic response intensity in volunteers receiving a single oral dose of the drug, drug/beta-CD physical mixture or complex. The results revealed a distinct improvement of the biological performance of CPZ by beta-CD as evidenced by an increased intensity of drug action and its duration as well as augmenting its bioavailability without affecting the time for maximum effect.

  8. Improving environmental risk assessment of human pharmaceuticals.

    PubMed

    Ågerstrand, Marlene; Berg, Cecilia; Björlenius, Berndt; Breitholtz, Magnus; Brunström, Björn; Fick, Jerker; Gunnarsson, Lina; Larsson, D G Joakim; Sumpter, John P; Tysklind, Mats; Rudén, Christina

    2015-05-05

    This paper presents 10 recommendations for improving the European Medicines Agency's guidance for environmental risk assessment of human pharmaceutical products. The recommendations are based on up-to-date, available science in combination with experiences from other chemical frameworks such as the REACH-legislation for industrial chemicals. The recommendations concern: expanding the scope of the current guideline; requirements to assess the risk for development of antibiotic resistance; jointly performed assessments; refinement of the test proposal; mixture toxicity assessments on active pharmaceutical ingredients with similar modes of action; use of all available ecotoxicity studies; mandatory reviews; increased transparency; inclusion of emission data from production; and a risk management option. We believe that implementation of our recommendations would strengthen the protection of the environment and be beneficial to society. Legislation and guidance documents need to be updated at regular intervals in order to incorporate new knowledge from the scientific community. This is particularly important for regulatory documents concerning pharmaceuticals in the environment since this is a research field that has been growing substantially in the last decades.

  9. An overview of pharmaceutical cocrystals as intellectual property.

    PubMed

    Trask, Andrew V

    2007-01-01

    This review article focuses on the interaction among certain scientific, legal, and regulatory aspects of pharmaceutical crystal forms. The article offers an analysis of pharmaceutical cocrystals as patentable inventions by drawing upon recent scientific developments in the field. Several potential commercial advantages of pharmaceutical cocrystals are highlighted, and a number of recent court decisions involving salient issues are summarized. The article provides an outlook on how the developing field of cocrystallization may impact the pharmaceutical intellectual property landscape.

  10. Pharmaceutical and Toxicological Properties of Engineered Nanomaterials for Drug Delivery

    PubMed Central

    Palombo, Matthew; Deshmukh, Manjeet; Myers, Daniel; Gao, Jieming; Szekely, Zoltan; Sinko, Patrick J.

    2014-01-01

    Novel engineered nanomaterials (ENMs) are being developed to enhance therapy. The physicochemical properties of ENMs can be manipulated to control/direct biodistribution and target delivery, but these alterations also have implications for toxicity. It is well known that size plays a significant role in determining ENM effects since simply nanosizing a safe bulk material can render it toxic. However, charge, shape, rigidity, and surface modifications also have a significant influence on the biodistribution and toxicity of nanoscale drug delivery systems (NDDSs). In this review, NDDSs are considered in terms of platform technologies, materials, and physical properties that impart their pharmaceutical and toxicological effects. Moving forward, the development of safe and effective nanomedicines requires standardized protocols for determining the physical characteristics of ENMs as well as assessing their potential long-term toxicity. When such protocols are established, the remarkable promise of nanomedicine to improve the diagnosis and treatment of human disease can be fulfilled. PMID:24160695

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

    PubMed

    Horstkotte, Elke; Odoerfer, Kathrin I

    2012-12-01

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

  12. Does Intellectual Property Restrict Output? An Analysis of Pharmaceutical Markets*

    PubMed Central

    Lakdawalla, Darius; Philipson, Tomas

    2013-01-01

    Standard normative analysis of intellectual property focuses on the balance between incentives for research and the static welfare costs of reduced price-competition from monopoly. However, static welfare loss from patents is not universal. While patents restrict price competition, they may also provide static welfare benefits by improving incentives for marketing, which is a form of non-price competition. We show theoretically how stronger marketing incentives mitigate, and can even offset, the static costs of monopoly pricing. Empirical analysis in the pharmaceutical industry context suggests that, in the short-run, patent expirations reduce consumer welfare as a result of decreased marketing effort. In the long-run, patent expirations do benefit consumers, but by 30% less than would be implied by the reduction in price alone. The social value of monopoly marketing to consumers alone is roughly on par with its costs to firms. PMID:25221349

  13. Does Intellectual Property Restrict Output? An Analysis of Pharmaceutical Markets.

    PubMed

    Lakdawalla, Darius; Philipson, Tomas

    2012-02-01

    Standard normative analysis of intellectual property focuses on the balance between incentives for research and the static welfare costs of reduced price-competition from monopoly. However, static welfare loss from patents is not universal. While patents restrict price competition, they may also provide static welfare benefits by improving incentives for marketing, which is a form of non-price competition. We show theoretically how stronger marketing incentives mitigate, and can even offset, the static costs of monopoly pricing. Empirical analysis in the pharmaceutical industry context suggests that, in the short-run, patent expirations reduce consumer welfare as a result of decreased marketing effort. In the long-run, patent expirations do benefit consumers, but by 30% less than would be implied by the reduction in price alone. The social value of monopoly marketing to consumers alone is roughly on par with its costs to firms.

  14. Quantitative structure-property relationships in pharmaceutical research - Part 2.

    PubMed

    Grover; Singh; Bakshi

    2000-02-01

    Part one of this two-part review described the advantages and limitations of quantitative structure-property relationships (QSPR), and offered an overview of the components involved in the development of correlations1. Part two provides a discussion of a few notable examples of relationships with organoleptic, physicochemical and pharmaceutical properties.

  15. Improvement of Clinical Skills through Pharmaceutical Education and Clinical Research.

    PubMed

    Ishizaki, Junko

    2017-01-01

     Professors and teaching staff in the field of pharmaceutical sciences should devote themselves to staying abreast of relevant education and research. Similarly those in clinical pharmacies should contribute to the advancement of pharmaceutical research and the development of next generation pharmacists and pharmaceuticals. It is thought that those who work in clinical pharmacies should improve their own skills and expertise in problem-finding and -solving, i.e., "clinical skills". They should be keen to learn new standard treatments based on the latest drug information, and should try to be in a position where collecting clinical information is readily possible. In the case of pharmacists in hospitals and pharmacies, they are able to aim at improving their clinical skills simply through performing their pharmaceutical duties. On the other hand, when a pharmaceutical educator aims to improve clinical skills at a level comparable to those of clinical pharmacists, it is necessary to devote or set aside considerable time for pharmacist duties, in addition to teaching, which may result in a shortage of time for hands-on clinical practice and/or in a decline in the quality of education and research. This could be a nightmare for teaching staff in clinical pharmacy who aim to take part in such activities. Nonetheless, I believe that teaching staff in the clinical pharmacy area could improve his/her clinical skills through actively engaging in education and research. In this review, I would like to introduce topics on such possibilities from my own experiences.

  16. Pharmaceuticals' sorptions relative to properties of thirteen different soils.

    PubMed

    Kodešová, Radka; Grabic, Roman; Kočárek, Martin; Klement, Aleš; Golovko, Oksana; Fér, Miroslav; Nikodem, Antonín; Jakšík, Ondřej

    2015-04-01

    Transport of human and veterinary pharmaceuticals in soils and consequent ground-water contamination are influenced by many factors, including compound sorption on soil particles. Here we evaluate the sorption isotherms for 7 pharmaceuticals on 13 soils, described by Freundlich equations, and assess the impact of soil properties on various pharmaceuticals' sorption on soils. Sorption of ionizable pharmaceuticals was, in many cases, highly affected by soil pH. The sorption coefficient of sulfamethoxazole was negatively correlated to soil pH, and thus positively related to hydrolytic acidity and exchangeable acidity. Sorption coefficients for clindamycin and clarithromycin were positively related to soil pH and thus negatively related to hydrolytic acidity and exchangeable acidity, and positively related to base cation saturation. The sorption coefficients for the remaining pharmaceuticals (trimethoprim, metoprolol, atenolol, and carbamazepine) were also positively correlated with the base cation saturation and cation exchange capacity. Positive correlations between sorption coefficients and clay content were found for clindamycin, clarithromycin, atenolol, and metoprolol. Positive correlations between sorption coefficients and organic carbon content were obtained for trimethoprim and carbamazepine. Pedotransfer rules for predicting sorption coefficients of various pharmaceuticals included hydrolytic acidity (sulfamethoxazole), organic carbon content (trimethoprimand carbamazepine), base cation saturation (atenolol and metoprolol), exchangeable acidity and clay content (clindamycin), and soil active pH and clay content (clarithromycin). Pedotransfer rules, predicting the Freundlich sorption coefficients, could be applied for prediction of pharmaceutical mobility in soils with similar soil properties. Predicted sorption coefficients together with pharmaceutical half-lives and other imputes (e.g., soil-hydraulic, geological, hydro-geological, climatic) may be used for

  17. Pharmaceutical cocrystals, salts and multicomponent systems; intermolecular interactions and property based design.

    PubMed

    Berry, David J; Steed, Jonathan W

    2017-03-23

    As small molecule drugs become harder to develop and less cost effective for patient use, efficient strategies for their property improvement become increasingly important to global health initiatives. Improvements in the physical properties of Active Pharmaceutical Ingredients (APIs), without changes in the covalent chemistry, have long been possible through the application of binary component solids. This was first achieved through the use of pharmaceutical salts, within the last 10-15years with cocrystals and more recently coamorphous systems have also been consciously applied to this problem. In order to rationally discover the best multicomponent phase for drug development, intermolecular interactions need to be considered at all stages of the process. This review highlights the current thinking in this area and the state of the art in: pharmaceutical multicomponent phase design, the intermolecular interactions in these phases, the implications of these interactions on the material properties and the pharmacokinetics in a patient.

  18. Design, synthesis, and analysis of a polyethelene glycol-modified (PEGylated) small molecule inhibitor of integrin {alpha}4{beta}1 with improved pharmaceutical properties.

    PubMed

    Pepinsky, R B; Lee, W-C; Cornebise, M; Gill, A; Wortham, K; Chen, L L; Leone, D R; Giza, K; Dolinski, B M; Perper, S; Nickerson-Nutter, C; Lepage, D; Chakraborty, A; Whalley, E T; Petter, R C; Adams, S P; Lobb, R R; Scott, D M

    2005-02-01

    Integrin alpha4beta1 plays an important role in inflammatory processes by regulating the migration of leukocytes into inflamed tissues. Previously, we identified BIO5192 [2(S)-{[1-(3,5-dichloro-benzenesulfonyl)-pyrrolidine-2(S)-carbonyl]-amino}-4-[4-methyl-2(S)-(methyl-{2-[4-(3-o-tolyl-ureido)-phenyl]-acetyl}-amino)-pentanoylamino]-butyric acid], a highly selective and potent (K(D) of 9 pM) small molecule inhibitor of alpha4beta1. Although BIO5192 is efficacious in various animal models of inflammatory disease, high doses and daily treatment of the compound are needed to achieve a therapeutic effect because of its relatively short serum half-life. To address this issue, polyethylene glycol modification (PEGylation) was used as an approach to improve systemic exposure. BIO5192 was PEGylated by a targeted approach in which derivatizable amino groups were incorporated into the molecule. Two sites were identified that could be modified, and from these, five PEGylated compounds were synthesized and characterized. One compound, 2a-PEG (K(D) of 19 pM), was selected for in vivo studies. The pharmacokinetic and pharmacodynamic properties of 2a-PEG were dramatically improved relative to the unmodified compound. The PEGylated compound was efficacious in a rat model of experimental autoimmune encephalomyelitis at a 30-fold lower molar dose than the parent compound and required only a once-a-week dosing regimen compared with a daily treatment for BIO5192. Compound 2a-PEG was highly selective for alpha4beta1. These studies demonstrate the feasibility of PEGylation of alpha4beta1-targeted small molecules with retention of activity in vitro and in vivo. 2a-PEG, and related compounds, will be valuable reagents for assessing alpha4beta1 biology and may provide a new therapeutic approach to treatment of human inflammatory diseases.

  19. Improving Pharmaceutical Protein Production in Oryza sativa

    PubMed Central

    Kuo, Yu-Chieh; Tan, Chia-Chun; Ku, Jung-Ting; Hsu, Wei-Cho; Su, Sung-Chieh; Lu, Chung-An; Huang, Li-Fen

    2013-01-01

    Application of plant expression systems in the production of recombinant proteins has several advantages, such as low maintenance cost, absence of human pathogens, and possession of complex post-translational glycosylation capabilities. Plants have been successfully used to produce recombinant cytokines, vaccines, antibodies, and other proteins, and rice (Oryza sativa) is a potential plant used as recombinant protein expression system. After successful transformation, transgenic rice cells can be either regenerated into whole plants or grown as cell cultures that can be upscaled into bioreactors. This review summarizes recent advances in the production of different recombinant protein produced in rice and describes their production methods as well as methods to improve protein yield and quality. Glycosylation and its impact in plant development and protein production are discussed, and several methods of improving yield and quality that have not been incorporated in rice expression systems are also proposed. Finally, different bioreactor options are explored and their advantages are analyzed. PMID:23615467

  20. Structure-Property Relationships of Solids in Pharmaceutical Processing

    NASA Astrophysics Data System (ADS)

    Chattoraj, Sayantan

    Pharmaceutical development and manufacturing of solid dosage forms is witnessing a seismic shift in the recent years. In contrast to the earlier days when drug development was empirical, now there is a significant emphasis on a more scientific and structured development process, primarily driven by the Quality-by-Design (QbD) initiatives of US Food and Drug Administration (US-FDA). Central to such an approach is the enhanced understanding of solid materials using the concept of Materials Science Tetrahedron (MST) that probes the interplay between four elements, viz., the structure, properties, processing, and performance of materials. In this thesis work, we have investigated the relationships between the structure and those properties of pharmaceutical solids that influence their processing behavior. In all cases, we have used material-sparing approaches to facilitate property assessment using very small sample size of materials, which is a pre-requisite in the early stages of drug development when the availability of materials, drugs in particular, is limited. The influence of solid structure, either at the molecular or bulk powder levels, on crystal plasticity and powder compaction, powder flow, and solid-state amorphization during milling, has been investigated in this study. Through such a systematic evaluation, we have captured the involvement of structure-property correlations within a wide spectrum of relevant processing behaviors of pharmaceutical solids. Such a holistic analysis will be beneficial for addressing both regulatory and scientific issues in drug development.

  1. Crystalline mesophases: Structure, mobility, and pharmaceutical properties.

    PubMed

    Shalaev, Evgenyi; Wu, Ke; Shamblin, Sheri; Krzyzaniak, Joseph F; Descamps, Marc

    2016-05-01

    Crystalline mesophases, which are commonly classified according to their translational, orientational, and conformational order as liquid crystals, plastic crystals, and conformationally disordered crystals, represent a common state of condensed matter. As an intermediate state between crystalline and amorphous materials, crystalline mesophases resemble amorphous materials in relation to their molecular mobility, with the glass transition being their common property, and at the same time possessing a certain degree of translational periodicity (with the exception of nematic phase), with corresponding narrow peaks in X-ray diffraction patterns. For example, plastic crystals, which can be formed both by near-spherical molecules and molecules of lower symmetry, such as planar or chain molecules, can have both extremely sharp X-ray diffraction lines and exhibit glass transition. Fundamentals of structural arrangements in mesophases are compared with several types of disorder in crystalline materials, as well as with short-range ordering in amorphous solids. Main features of the molecular mobility in crystalline mesophases are found to be generally similar to amorphous materials, although some important differences do exist, depending on a particular type of mobility modes involved in relaxation processes. In several case studies reviewed, chemical stability appears to follow the extent of disorder, with the stability of crystalline mesophase found to be intermediate between amorphous (least stable) and crystalline (most stable) materials. Finally, detection of crystalline mesophases during manufacturing of two different types of dosage forms is discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Effects of Manufacturing Conditions on Pharmaceutical Properties of Petrolatum Ointment.

    PubMed

    Ashizuka, Yuki; Horisawa, Eijiro

    2016-08-01

    Oleaginous white petrolatum ointment (WP ointment) is one of the most commonly used dosage forms in the preparation of topical products. In general, WP ointments containing medium chain fatty acid triglycerides (MCT) are manufactured through a process of melting, mixing, agitating, and cooling. To investigate the pharmaceutical properties of WP ointments in greater detail, we examined manufacturing factors which could potentially influence the pharmaceutical properties of the finished product. WP ointment samples containing 10% MCT were stirred with a homogenizer and a paddle mixer at 65°C, then the homogenizer was stopped. Next, the paddle-mixer was stopped at several planned temperature points at which different samples were taken. Each sample was then cooled under the following planned conditions: rapid-cooling [-50°C/h] and slow-cooling [-7.5°C/h]. The pharmaceutical properties of each WP ointment sample, along with the appearance (Optical/digital microscope), hardness (Rheometer), and bleeding ability (100 Mesh wire-net cone) were measured. Then, release profiles were performed with a WP ointment using the model active ingredient Vitamin D. As a result, high hardness, low bleeding ability and low release profile were observed in the WP ointment samples that were manufactured under the condition of stopping the paddle-mixer at 40°C. However, the influence of cooling speed was observed to affect only hardness. Through optical microscopic observation, it was found that the appearance of WP ointment samples differed depending on the conditions under which they were manufactured. In this study, it was clear that the pharmaceutical properties of WP ointment samples were particularly influenced by the paddle-mixer stopping temperature.

  3. Impact of soil properties on selected pharmaceuticals adsorption in soils

    NASA Astrophysics Data System (ADS)

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

    2014-05-01

    The presence of human and veterinary pharmaceuticals in the environment has been recognized as a potential threat. Pharmaceuticals may contaminate soils and consequently surface and groundwater. Study was therefore focused on the evaluation of selected pharmaceuticals adsorption in soils, as one of the parameters, which are necessary to know when assessing contaminant transport in soils. The goals of this study were: (1) to select representative soils of the Czech Republic and to measure soil physical and chemical properties; (2) to measure adsorption isotherms of selected pharmaceuticals; (3) to evaluate impact of soil properties on pharmaceutical adsorptions and to propose pedotransfer rules for estimating adsorption coefficients from the measured soil properties. Batch sorption tests were performed for 6 selected pharmaceuticals (beta blockers Atenolol and Metoprolol, anticonvulsant Carbamazepin, and antibiotics Clarithromycin, Trimetoprim and Sulfamethoxazol) and 13 representative soils (soil samples from surface horizons of 11 different soil types and 2 substrates). The Freundlich equations were used to describe adsorption isotherms. The simple correlations between measured physical and chemical soil properties (soil particle density, soil texture, oxidable organic carbon content, CaCO3 content, pH_H2O, pH_KCl, exchangeable acidity, cation exchange capacity, hydrolytic acidity, basic cation saturation, sorption complex saturation, salinity), and the Freundlich adsorption coefficients were assessed using Pearson correlation coefficient. Then multiple-linear regressions were applied to predict the Freundlich adsorption coefficients from measured soil properties. The largest adsorption was measured for Clarithromycin (average value of 227.1) and decreased as follows: Trimetoprim (22.5), Metoprolol (9.0), Atenolol (6.6), Carbamazepin (2.7), Sulfamethoxazol (1.9). Absorption coefficients for Atenolol and Metoprolol closely correlated (R=0.85), and both were also

  4. Pharmaceutical Technology Assessment for Managed Care: Current Practice and Suggestions for Improvement

    DTIC Science & Technology

    2001-01-01

    Together, these developments have caused managed care organizations to realize that making good decisions on new pharmaceuticals is to their immediate...financial and clinical benefit. Accordingly, many have expressed interest in improving their ability to evaluate new pharmaceuticals .

  5. Intellectual property rights: An overview and implications in pharmaceutical industry.

    PubMed

    Saha, Chandra Nath; Bhattacharya, Sanjib

    2011-04-01

    Intellectual property rights (IPR) have been defined as ideas, inventions, and creative expressions based on which there is a public willingness to bestow the status of property. IPR provide certain exclusive rights to the inventors or creators of that property, in order to enable them to reap commercial benefits from their creative efforts or reputation. There are several types of intellectual property protection like patent, copyright, trademark, etc. Patent is a recognition for an invention, which satisfies the criteria of global novelty, non-obviousness, and industrial application. IPR is prerequisite for better identification, planning, commercialization, rendering, and thereby protection of invention or creativity. Each industry should evolve its own IPR policies, management style, strategies, and so on depending on its area of specialty. Pharmaceutical industry currently has an evolving IPR strategy requiring a better focus and approach in the coming era.

  6. Intellectual property rights: An overview and implications in pharmaceutical industry

    PubMed Central

    Saha, Chandra Nath; Bhattacharya, Sanjib

    2011-01-01

    Intellectual property rights (IPR) have been defined as ideas, inventions, and creative expressions based on which there is a public willingness to bestow the status of property. IPR provide certain exclusive rights to the inventors or creators of that property, in order to enable them to reap commercial benefits from their creative efforts or reputation. There are several types of intellectual property protection like patent, copyright, trademark, etc. Patent is a recognition for an invention, which satisfies the criteria of global novelty, non-obviousness, and industrial application. IPR is prerequisite for better identification, planning, commercialization, rendering, and thereby protection of invention or creativity. Each industry should evolve its own IPR policies, management style, strategies, and so on depending on its area of specialty. Pharmaceutical industry currently has an evolving IPR strategy requiring a better focus and approach in the coming era. PMID:22171299

  7. [Regulation, innovation, and improvement of health care. The pharmaceutical sector].

    PubMed

    López-Casasnovas, Guillem

    2008-01-01

    The paper comments on present and future scenarios for the pharmaceutical sector in Spain, framed a highly regulated system. So far the drug industry has evolved under the short term public financial constraints for additional health care spending and the long term efforts to innovate. This has not proved to offer a stable setting for the relationship between the industry and Health Authorities. The author offers from the economic analysis and a subjective appraisal from his experience some recommendations for regulatory changes in order to better align the incentives of the parts for improving the health system as a whole. The basic point is that 'consumption levels' (quantities) and not (unit costs) are the main challenge to tackle today in our Public Health Care system, and for this the decentralisation of financial responsibility is not in itself 'the' problem but it may well be a part of the solution.

  8. Improving a pharmaceutical purchasing and inventory control system.

    PubMed

    Rubin, H; Keller, D D

    1983-01-01

    A method by which a pharmacy department improved its purchasing and inventory control system is described. System changes to the computerized inventory control system included implementation of a formulary, affiliation with a group purchasing association, and transfer of specified purchasing and inventory control functions to the technical staff of the purchasing department. Pharmacy maintained the decision-making authority over all vendors and dosage forms of drug products. Optimal results were achieved when the purchasing department's pharmacy buyer position was staffed with an employee who had previous experience as a clerical worker in the pharmacy. The authors state that this system has proved to be an effective, cost efficient method of purchasing and inventory control of pharmaceuticals in their hospital.

  9. Pharmaceutical Salts of Carvedilol: Polymorphism and Physicochemical Properties.

    PubMed

    Hiendrawan, Stevanus; Widjojokusumo, Edward; Veriansyah, Bambang; Tjandrawinata, Raymond R

    2016-09-06

    We report novel pharmaceutical salts of an anti-hypertensive drug carvedilol (CVD) with pharmaceutically acceptable salt formers, including oxalic acid (OXA), fumaric acid (FUMA), benzoic acid (BZA), and mandelic acid (MDA) via conventional solvent evaporation technique. The pKa difference between CVD and selected acids was greater than 3, thus suggesting salt formation. Two polymorphic forms of CVD/MDA salts and one p-Dioxane solvate of CVD/FUMA salt were also reported in this paper. The salts were characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). Stability of the salts was assessed by storage at 40°C/75% RH for 1 month. All CVD salts exhibited higher solubility in phosphate buffer solution pH 6.8 compared to the parent drug CVD and showed good stability in accelerated ICH conditions at 40°C/75% RH for 1 month. CVD/FUMA salt showed the highest solubility (1.78 times). Based on thermal analysis and slurry experiment, it was found that CVD/MDA polymorphs were related monotropically with Form 1 as the stable form. The results suggested that salt formation could be an alternative method to improve CVD solubility.

  10. Antisolvent precipitation of novel xylitol-additive crystals to engineer tablets with improved pharmaceutical performance.

    PubMed

    Kaialy, Waseem; Maniruzzaman, Mohammad; Shojaee, Saeed; Nokhodchi, Ali

    2014-12-30

    The purpose of this work was to develop stable xylitol particles with modified physical properties, improved compactibility and enhanced pharmaceutical performance without altering polymorphic form of xylitol. Xylitol was crystallized using antisolvent crystallization technique in the presence of various hydrophilic polymer additives, i.e., polyethylene glycol (PEG), polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA) at a range of concentrations. The crystallization process did not influence the stable polymorphic form or true density of xylitol. However, botryoidal-shaped crystallized xylitols demonstrated different particle morphologies and lower powder bulk and tap densities in comparison to subangular-shaped commercial xylitol. Xylitol crystallized without additive and xylitol crystallized in the presence of PVP or PVA demonstrated significant improvement in hardness of directly compressed tablets; however, such improvement was observed to lesser extent for xylitol crystallized in the presence of PEG. Crystallized xylitols produced enhanced dissolution profiles for indomethacin in comparison to original xylitol. The influence of additive concentration on tablet hardness was dependent on the type of additive, whereas an increased concentration of all additives provided an improvement in the dissolution behavior of indomethacin. Antisolvent crystallization using judiciously selected type and concentration of additive can be a potential approach to prepare xylitol powders with promising physicomechanical and pharmaceutical properties.

  11. Pharmaceutical cocrystals: an overview.

    PubMed

    Qiao, Ning; Li, Mingzhong; Schlindwein, Walkiria; Malek, Nazneen; Davies, Angela; Trappitt, Gary

    2011-10-31

    Pharmaceutical cocrystals are emerging as a new class of solid drugs with improved physicochemical properties, which has attracted increased interests from both industrial and academic researchers. In this paper a brief and systematic overview of pharmaceutical cocrystals is provided, with particular focus on cocrystal design strategies, formation methods, physicochemical property studies, characterisation techniques, and recent theoretical developments in cocrystal screening and mechanisms of cocrystal formations. Examples of pharmaceutical cocrystals are also summarised in this paper.

  12. The impact of the legal regime of intellectual property protection in the pharmaceutical market.

    PubMed

    Pashkov, Vitaliy M; Golovanova, Iryna A; Olefir, Andrii A

    2016-01-01

    the functioning of the healthcare industry in any country is impossible without providing enough medicines for patient care. This problem can best be resolved only when the majority of drugs, especially vital, will be made at national plants (industry). In this context, competition from generic drugs is the most optimal strategy to reduce drug's prices. the paper should examine how the legal regime of intellectual property affects the availability of medicines for people and identify ways of supporting breakthrough inventions and counter ≪unreal innovations≫. for the purpose of study were generalized information from the scientific journals of medical and legal perspective, monographs by using a set of scientific methods. Namely under systematic approach have been analyzed the problems of pharmaceutical market, ways of producing generic and original drugs. Comparative legal method was useful for learning features of flexible mechanisms of the TRIPS Agreement and market regulation of medicines in the world. based on the research was found that developed countries with strong pharmaceutical industry are interested in maximizing the protection of intellectual property rights, including importing countries. Flexible mechanisms of the TRIPS Agreement can be useful for developing countries. thus, successful development of pharmaceutical industry and health care should be accompanied by the following measures: - improvement of public health must be recognized as a main task of government policy; - substantial state support aimed at increasing the availability of drugs in the domestic market and the strengthening of export potential; - decrease patent protection of medicines and stimulate market launch of generic copies.

  13. The impact of the legal regime of intellectual property protection in the pharmaceutical market.

    PubMed

    Pashkov, Vitaliy M; Golovanova, Iryna A; Olefir, Andrii A

    the functioning of the healthcare industry in any country is impossible without providing enough medicines for patient care. This problem can best be resolved only when the majority of drugs, especially vital, will be made at national plants (industry). In this context, competition from generic drugs is the most optimal strategy to reduce drug's prices. the paper should examine how the legal regime of intellectual property affects the availability of medicines for people and identify ways of supporting breakthrough inventions and counter ≪unreal innovations≫. for the purpose of study were generalized information from the scientific journals of medical and legal perspective, monographs by using a set of scientific methods. Namely under systematic approach have been analyzed the problems of pharmaceutical market, ways of producing generic and original drugs. Comparative legal method was useful for learning features of flexible mechanisms of the TRIPS Agreement and market regulation of medicines in the world. based on the research was found that developed countries with strong pharmaceutical industry are interested in maximizing the protection of intellectual property rights, including importing countries. Flexible mechanisms of the TRIPS Agreement can be useful for developing countries. thus, successful development of pharmaceutical industry and health care should be accompanied by the following measures: - improvement of public health must be recognized as a main task of government policy; - substantial state support aimed at increasing the availability of drugs in the domestic market and the strengthening of export potential; - decrease patent protection of medicines and stimulate market launch of generic copies.

  14. Enhancing the pharmaceutical properties of protein drugs by ancestral sequence reconstruction

    PubMed Central

    Zakas, Philip M.; Brown, Harrison C.; Knight, Kristopher; Meeks, Shannon L.; Spencer, H. Trent; Gaucher, Eric A.; Doering, Christopher B.

    2016-01-01

    Optimization of a protein’s pharmaceutical properties is usually carried out by rational design and/or directed evolution. Here we test an alternative approach based on ancestral sequence reconstruction. Using available genomic sequence data on coagulation factor VIII and predictive models of molecular evolution, we engineer protein variants with improved activity, stability. biosynthesis potential, and reduced inhibition by clinical anti-drug antibodies. In principle, this approach can be applied to any protein drug based on a conserved gene sequence. PMID:27669166

  15. [Patents in pharmaceutical industry: between ethics and property rights].

    PubMed

    Martínez Cárdenas, Edgar E

    2003-01-01

    The article presents a reflection on one of the greater challenges which the contemporary State is confronted with, related to guaranteeing the effective application of the fundamental rights, besides having to solve the conflicts that arise due to the rivalry between either fundamental rights or between some of these and others known as second or third generation rights. The conflict between the protection to the intellectual property rights, as in the case of the patents of the pharmaceutical multinationals, and the fundamental right to life is considered. It is observed that the interests of these companies have prevailed, as if the fundamental value to protect was the profit of these multinationals, or their efficiency, and not the right to health of the individuals which bears a direct relation with the right to the life. This situation is aggravated still more when the State, instead of being on the side of the weaker and offering him protection, safeguards the stronger who abuse of their dominant position, exerting the monopoly on the production of many essential medicines.

  16. Innovative pharmaceutical development based on unique properties of nanoscale delivery formulation

    PubMed Central

    Mozhi, Anbu; Zhang, Xu; Zhao, Yuanyuan; Xue, Xiangdong; Hao, Yanli; Zhang, Xiaoning; Wang, Paul C.; Liang, Xing-Jie

    2014-01-01

    The advent of nanotechnology has reignited interest in the field of pharmaceutical science for the development of nanomedicine. Nanomedicinal formulations are nanometer-sized carrier materials designed for increasing the drug tissue bioavailability, thereby improving the treatment of systemically applied chemotherapeutic drugs. Nanomedicine is a new approach to deliver the pharmaceuticals through different routes of administration with safer and more effective therapies compared to conventional methods. To date, various kinds of nanomaterials have been developed over the years to make delivery systems more effective for the treatment of various diseases. Even though nanomaterials have significant advantages due to their unique nanoscale properties, there are still significant challenges in the improvement and development of nanoformulations with composites and other materials. Here in this review, we highlight the nanomedicinal formulations aiming to improve the balance between the efficacy and the toxicity of therapeutic interventions through different routes of administration and how to design nanomedicine for safer and more effective ways to improve the treatment quality. We also emphasize the environmental and health prospects of nanomaterials for human health care. PMID:23860639

  17. Innovative pharmaceutical development based on unique properties of nanoscale delivery formulation

    NASA Astrophysics Data System (ADS)

    Kumar, Anil; Chen, Fei; Mozhi, Anbu; Zhang, Xu; Zhao, Yuanyuan; Xue, Xiangdong; Hao, Yanli; Zhang, Xiaoning; Wang, Paul C.; Liang, Xing-Jie

    2013-08-01

    The advent of nanotechnology has reignited interest in the field of pharmaceutical science for the development of nanomedicine. Nanomedicinal formulations are nanometer-sized carrier materials designed for increasing the drug tissue bioavailability, thereby improving the treatment of systemically applied chemotherapeutic drugs. Nanomedicine is a new approach to deliver the pharmaceuticals through different routes of administration with safer and more effective therapies compared to conventional methods. To date, various kinds of nanomaterials have been developed over the years to make delivery systems more effective for the treatment of various diseases. Even though nanomaterials have significant advantages due to their unique nanoscale properties, there are still significant challenges in the improvement and development of nanoformulations with composites and other materials. Here in this review, we highlight the nanomedicinal formulations aiming to improve the balance between the efficacy and the toxicity of therapeutic interventions through different routes of administration and how to design nanomedicine for safer and more effective ways to improve the treatment quality. We also emphasize the environmental and health prospects of nanomaterials for human health care.

  18. Improving Patient's Primary Medication Adherence: The Value of Pharmaceutical Counseling.

    PubMed

    Leguelinel-Blache, Géraldine; Dubois, Florent; Bouvet, Sophie; Roux-Marson, Clarisse; Arnaud, Fabrice; Castelli, Christel; Ray, Valérie; Kinowski, Jean-Marie; Sotto, Albert

    2015-10-01

    Quality of transitions of care is one of the first concerns in patient safety. Redesigning the discharge process to incorporate clinical pharmacy activities could reduce the incidence of postdischarge adverse events by improving medication adherence. The present study investigated the value of pharmacist counseling sessions on primary medication adherence after hospital discharge.This study was conducted in a 1844-bed hospital in France. It was divided in an observational period and an interventional period of 3 months each. In both periods, ward-based clinical pharmacists performed medication reconciliation and inpatient follow-up. In interventional period, initial counseling and discharge counseling sessions were added to pharmaceutical care. The primary medication adherence was assessed by calling community pharmacists 7 days after patient discharge.We compared the measure of adherence between the patients from the observational period (n = 201) and the interventional period (n = 193). The rate of patients who were adherent increased from 51.0% to 66.7% between both periods (P < 0.01). When discharge counseling was performed (n = 78), this rate rose to 79.7% (P < 0.001). The multivariate regression performed on data from both periods showed that age of at least 78 years old, and 3 or less new medications on discharge order were predictive factors of adherence. New medications ordered at discharge represented 42.0% (n = 1018/2426) of all medications on discharge order. The rate of unfilled new medications decreased from 50.2% in the observational period to 32.5% in the interventional period (P < 10). However, patients included in the observational period were not significantly more often readmitted or visited the emergency department than the patients who experienced discharge counseling during the interventional period (45.3% vs. 46.2%; P = 0.89).This study highlights that discharge counseling sessions are essential to improve

  19. Determination of flow properties of pharmaceutical powders by near infrared spectroscopy.

    PubMed

    Sarraguça, Mafalda C; Cruz, Ana V; Soares, Sandra O; Amaral, Helena R; Costa, Paulo C; Lopes, João A

    2010-08-01

    The physical properties of pharmaceutical powders are of upmost importance in the pharmaceutical industry. The knowledge of their flow properties is of critical significance in operations such as blending, tablet compression, capsule filling, transportation, and in scale-up operations. Powders flow properties are measured using a number of parameters such as, angle of repose, compressibility index (Carr's index) and Hausner ratio. To estimate these properties, specific and expensive equipment with time-consuming analysis is required. Near infrared spectroscopy is a fast and low-cost analytical technique thoroughly used in the pharmaceutical industry in the quantification and qualification of products. To establish the potential of this technique to determine the parameters associated with the flow properties of pharmaceutical powders, blended powders based on paracetamol as the active pharmaceutical ingredient were constructed in pilot scale. Spectra were recorded on a Fourier-transform near infrared spectrometer in reflectance mode. The parameters studied were the angle of repose, aerated and tapped bulk density. The correlation between the reference method values and the near infrared spectrum was performed by partial least squares and optimized in terms of latent variables using cross-validation. The near infrared based properties predictions were compared with the reference methods results. Prediction errors, which varied between 2.35% for the angle of repose, 2.51% for the tapped density and 3.18% for the aerated density, show the potential of NIR spectroscopy in the determination of physical properties affecting the flowability of pharmaceutical powders.

  20. General practitioners and pharmaceutical sales representatives: quality improvement research

    PubMed Central

    Spurling, Geoffrey; Mansfield, Peter

    2007-01-01

    Background and objective Interaction between pharmaceutical sales representatives (PSRs) and general practitioners (GPs) may have an adverse impact on GP prescribing and therefore may be ethically questionable. This study aimed to evaluate the interactions between PSRs and GPs in an Australian general practice, and develop and evaluate a policy to guide the interaction. Methods Doctors' prescribing, diaries, practice promotional material and samples were audited and a staff survey undertaken. After receiving feedback, the staff voted on practice policy options. The resulting policy was evaluated 3 and 9 months. Results Prior to the intervention, GPs spent on average 40 min/doctor/month with PSRs. There were 239 items of promotional material in the practice and 4660 tablets in the sample cupboard. These were reduced by 32% and 59%, respectively, at 3 months after policy adoption and the reduction was sustained at 9 months. Vioxx was the most common drug name in promotional material. Staff adopted a policy of reduced access to PSRs including: reception staff not to make appointments for PSRs or accept promotional material; PSRs cannot access sample cupboards; GPs wishing to see PSRs may do so outside consulting hours. At 3 and 9 months, most staff were satisfied with the changes. Promotional items/room were not significantly reduced at 3 months (−4.0 items/room ; 95% CI −6.61 to −1.39; p = 0.066) or 9 months (−2.63 items/room; 95% CI −5.86 to 0.60; p = 0.24). Generic prescribing significantly increased at 3 months (OR 2.28, 95% CI 1.31 to 3.86; p = 0.0027) and 9 months (OR 2.07, 95% CI 1.13 to 3.82; p = 0.016). Conclusion There was a marked reduction in interactions with PSRs with majority staff satisfaction and improved prescribing practices. The new policy will form part of the practice's orientation package. Reception staff give PSRs a letter explaining the policy. It is hoped that the extra 40 min/doctor of

  1. Effect of colloidal silica on rheological properties of common pharmaceutical excipients.

    PubMed

    Majerová, Diana; Kulaviak, Lukáš; Růžička, Marek; Štěpánek, František; Zámostný, Petr

    2016-09-01

    In pharmaceutical industry, the use of lubricants is mostly based on historical experiences or trial and error methods even these days. It may be demanding in terms of the material consumption and may result in sub-optimal drug composition. Powder rheology enables more accurate monitoring of the flow properties and because the measurements need only a small sample it is perfectly suitable for the rare or expensive substances. In this work, rheological properties of four common excipients (pregelatinized maize starch, microcrystalline cellulose, croscarmellose sodium and magnesium stearate) were studied by the FT4 Powder Rheometer, which was used for measuring the compressibility index by a piston and flow properties of the powders by a rotational shear cell. After an initial set of measurements, two excipients (pregelatinized maize starch and microcrystalline cellulose) were chosen and mixed, in varying amounts, with anhydrous colloidal silicon dioxide (Aerosil 200) used as a glidant. The bulk (conditioned and compressed densities, compressibility index), dynamic (basic flowability energy) and shear (friction coefficient, flow factor) properties were determined to find an optimum ratio of the glidant. Simultaneously, the particle size data were obtained using a low-angle laser light scattering (LALLS) system and scanning electron microscopy was performed in order to examine the relationship between the rheological properties and the inner structure of the materials. The optimum of flowability for the mixture composition was found, to correspond to empirical findings known from general literature. In addition the mechanism of colloidal silicone dioxide action to improve flowability was suggested and the hypothesis was confirmed by independent test. New findings represent a progress towards future application of determining the optimum concentration of glidant from the basic characteristics of the powder in the pharmaceutical research and development. Copyright

  2. Intellectual Property and the Pharmaceutical Scientist: An Industry Perspective.

    ERIC Educational Resources Information Center

    Reilly, William J., Jr.

    1989-01-01

    Three issues are discussed: (1) conflict between the pharmaceutical industry and academe; (2) how and why some companies contract their research efforts to colleges; and (3) how colleges can increase their percentage of industry monies available for contract research. (Author/MSE)

  3. Intellectual Property and the Pharmaceutical Scientist: An Industry Perspective.

    ERIC Educational Resources Information Center

    Reilly, William J., Jr.

    1989-01-01

    Three issues are discussed: (1) conflict between the pharmaceutical industry and academe; (2) how and why some companies contract their research efforts to colleges; and (3) how colleges can increase their percentage of industry monies available for contract research. (Author/MSE)

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

    PubMed Central

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

    2017-01-01

    Tablets have been choice of manufacturers over the years due to their comparatively low cost of manufacturing, packaging, shipping, and ease of administration; also have better stability and can be considered virtually tamper proof. A major challenge in formulation development of the tablets extends from lower solubility of the active agent to the elaborated manufacturing procedures for obtaining a compressible granular material. Moreover, the validation and documentation increases, as the numbers of steps increases for an industrially acceptable granulation process. Spherical crystallization (SC) is a promising technique, which encompass the crystallization, agglomeration, and spheronization phenomenon in a single step. Initially, two methods, spherical agglomeration, and emulsion solvent diffusion, were suggested to get a desired result. Later on, the introduction of modified methods such as crystallo-co-agglomeration, ammonia diffusion system, and neutralization techniques overcame the limitations of the older techniques. Under controlled conditions such as solvent composition, mixing rate and temperature, spherical dense agglomerates cluster from particles. Application of the SC technique includes production of compacted spherical particles of drug having improved uniformity in shape and size of particles, good bulk density, better flow properties as well as better solubility so SC when used on commercial scale will bring down the production costs of pharmaceutical tablet and will increase revenue for the pharmaceutical industries in the competitive market. This review summarizes the technologies available for SC and also suggests the parameters for evaluation of a viable product. PMID:28405573

  5. Pharmaceutical salt of BM635 with improved bioavailability.

    PubMed

    Poce, Giovanna; Consalvi, Sara; Cocozza, Martina; Fernandez-Menendez, Raquel; Bates, Robert H; Ortega Muro, Fátima; Barros Aguirre, David; Ballell, Lluis; Biava, Mariangela

    2017-03-01

    BM635 is a small molecule endowed with outstanding anti-mycobacterial activity (minimum inhibitory concentration of 0.12μM against M. tuberculosis H37Rv) identified during a hit-to-lead campaign. Its poor aqueous solubility together with its high lipophilicity led to low exposure in vivo. Indeed, the half-life in vivo of BM635 was 1h, allowing a reasonable maximum concentration (Cmax=1.62μM) and a moderate bioavailability (46%). The present study aimed to develop salt forms of BM635 with pharmaceutically accepted hydrochloric, methanesulphonic, phosphoric, tartaric, and citric acids to overcome these drawbacks. BM635 salts (BM635-HCl, BM635-Mes, BM635-PA, BM635-TA and BM635-CA) were evaluated for physicochemical as well as biopharmaceutical attributes.

  6. Effects of soil properties on the uptake of pharmaceuticals into earthworms.

    PubMed

    Carter, Laura J; Ryan, Jim J; Boxall, Alistair B A

    2016-06-01

    Pharmaceuticals can enter the soil environment when animal slurries and sewage sludge are applied to land as a fertiliser or during irrigation with contaminated water. These pharmaceuticals may then be taken up by soil organisms possibly resulting in toxic effects and/or exposure of organisms higher up the food chain. This study investigated the influence of soil properties on the uptake and depuration of pharmaceuticals (carbamazepine, diclofenac, fluoxetine and orlistat) in the earthworm Eisenia fetida. The uptake and accumulation of pharmaceuticals into E. fetida changed depending on soil type. Orlistat exhibited the highest pore water based bioconcentration factors (BCFs) and displayed the largest differences between soil types with BCFs ranging between 30.5 and 115.9. For carbamazepine, diclofenac and fluoxetine BCFs ranged between 1.1 and 1.6, 7.0 and 69.6 and 14.1 and 20.4 respectively. Additional analysis demonstrated that in certain treatments the presence of these chemicals in the soil matrices changed the soil pH over time, with a statistically significant pH difference to control samples. The internal pH of E. fetida also changed as a result of incubation in pharmaceutically spiked soil, in comparison to the control earthworms. These results demonstrate that a combination of soil properties and pharmaceutical physico-chemical properties are important in terms of predicting pharmaceutical uptake in terrestrial systems and that pharmaceuticals can modify soil and internal earthworm chemistry which may hold wider implications for risk assessment. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Intellectual property and pharmaceutical drugs: an ethical analysis.

    PubMed

    De George, Richard T

    2005-10-01

    The pharmaceutical industry has in recent years come under attack from an ethical point of view concerning its patents and the non-accessibility of life-saving drugs for many of the poor in both less developed countries and in the United States. The industry has replied with economic and legal justifications for its actions. The result has been a communication gap between the industry on the one hand and poor nations and American critics on the other. This paper attempts to present and evaluate the arguments on all sides and suggests a possible way out of the current impasse. It attempts to determine the ethical responsibility of the drug industry in making drugs available to the needy, while at the same time developing the parallel responsibilities of individuals, governments, and NGOs. It concludes with the suggestion that the industry develop an international code for its self-regulation.

  8. Process analytical technology in the pharmaceutical industry: a toolkit for continuous improvement.

    PubMed

    Scott, Bradley; Wilcock, Anne

    2006-01-01

    Process analytical technology (PAT) refers to a series of tools used to ensure that quality is built into products while at the same time improving the understanding of processes, increasing efficiency, and decreasing costs. It has not been widely adopted by the pharmaceutical industry. As the setting for this paper, the current pharmaceutical manufacturing paradigm and PAT guidance to date are discussed prior to the review of PAT principles and tools, benefits, and challenges. The PAT toolkit contains process analyzers, multivariate analysis tools, process control tools, and continuous improvement/knowledge management/information technology systems. The integration and implementation of these tools is complex, and has resulted in uncertainty with respect to both regulation and validation. The paucity of staff knowledgeable in this area may complicate adoption. Studies to quantitate the benefits resulting from the adoption of PAT within the pharmaceutical industry would be a valuable addition to the qualitative studies that are currently available.

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

    PubMed

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

    2015-06-01

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

  10. Drug delivery systems improve pharmaceutical profile and facilitate medication adherence.

    PubMed

    Wertheimer, Albert I; Santella, Thomas M; Finestone, Albert J; Levy, Richard A

    2005-01-01

    Innovations in dosage forms and dose delivery systems across a wide range of medications offer substantial clinical advantages, including reduced dosing frequency and improved patient adherence; minimized fluctuation of drug concentrations and maintenance of blood levels within a desired range; localized drug delivery; and the potential for reduced adverse effects and increased safety. The advent of new large-molecule drugs for previously untreatable or only partially treatable diseases is stimulating the development of suitable delivery systems for these agents. Although advanced formulations may be more expensive than conventional dosage forms, they often have a more favorable pharmacologic profile and can be cost-effective. Inclusion of these dosage forms on drug formulary lists may help patients remain on therapy and reduce the economic and social burden of care.

  11. Structured pharmaceutical care improves the health-related quality of life of patients with asthma.

    PubMed

    Anum, Philip O; Anto, Berko P; Forson, Audrey G

    2017-01-01

    Asthma as a chronic health condition can be controlled when in addition to clinical care, adequate education and support is provided to enhance self-management. Like many other chronic health conditions improved self-management positively impacts the health-related quality of life (HRQoL). It can therefore be said that a well-structured pharmaceutical care delivery that addresses the issues related to patient education and support towards self-management stands a good chance of positively impacting asthma control. This study evaluated the impact of a structured pharmaceutical care delivery on asthma control. A prospective pre-/post- intervention study of a single cohort of 77 adult out-patients visiting specialist asthma clinics in Ghana were assessed for HRQoL and peak expiratory flow rates (PEFR) one month after pharmaceutical care intervention. Pharmaceutical care intervention covered education on the health condition, pharmacotherapy and self-management issues as well as correction of inhaler-use technique, where necessary and when to urgently seek medical care. The mean difference of the HRQoL and PEFR values were subjected to paired samples t-test analysis. Delivery of a structured pharmaceutical care led to a significant improvement in asthma specific quality of life and PEFR. The mean paired difference of the HRQoL for a cohort of patients with asthma post- pharmaceutical care intervention was 0.697(95% CI: 0.490 - 0.900) at t = 6.85 (p < 0.05). The mean paired difference for PEFR post intervention was 17.533 (95% CI: 2.876 - 32.190) at t = 2.384 (p = 0.02). This study identified important challenges with both the pharmacologic and the non-pharmacologic management of adult asthma patients. Inadequate inhaler-use skills, widespread occurrence of preventable adverse events and irregular use of preventer medicines were prevalent among patients. At one month after pharmaceutical care intervention, patients with asthma in a cohort follow-up study

  12. 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.

  13. Quantitative mineralogical properties (morphology-chemistry-structure) of pharmaceutical grade kaolinites and recommendations to regulatory agencies.

    PubMed

    Dogan, Meral; Dogan, A Umran; Aburub, Aktham; Botha, Alta; Wurster, Dale Eric

    2012-02-01

    The physical and chemical characteristics of kaolinite (kaolin) may be variable, and minor amounts of other clay minerals, nonclay minerals, and other impurities may affect the properties of kaolinites. Thus specific technical properties of pharmaceutical grade kaolinites become very important because these clays are used in medical applications, e.g., as pharmaceutical excipients, and will be consumed by humans. Seven pharmaceutical grade kaolinite specimens were used in this study: K1004, KA105, 2242-01, K2-500, Acros, Acros-mono, and KX0007-1. In addition, two kaolinites from the Clay Minerals Society Source Clays, KGa-1b and KGa-2, were used for comparison purposes. The Acros-mono and 2242-01 kaolinites contained minor amounts of illite, which was demonstrated both compositionally and structurally by using inductively coupled plasma spectroscopy and powder X-ray diffraction. The KX0007-1 kaolinite powder was found to be heavily contaminated with quartz, cristobalite, and alunite. Crystal structure computations also showed excess Si in its tetrahedral site, and the mineral no longer has the typical kaolinite crystal structure. These widely-used industrial standards should be quantitatively characterized morphologically, compositionally, and structurally. Results of the mineralogical characteristics should be clearly labeled on the pharmaceutical grade kaolinites and reported to the relevant regulatory agencies.

  14. Amorphous pharmaceutical solids.

    PubMed

    Vranić, Edina

    2004-07-01

    Amorphous forms are, by definition, non-crystalline materials which possess no long-range order. Their structure can be thought of as being similar to that of a frozen liquid with the thermal fluctuations present in a liquid frozen out, leaving only "static" structural disorder. The amorphous solids have always been an essential part of pharmaceutical research, but the current interest has been raised by two developments: a growing attention to pharmaceutical solids in general, especially polymorphs and solvates and a revived interest in the science of glasses and the glass transition. Amorphous substances may be formed both intentionally and unintentionally during normal pharmaceutical manufacturing operations. The properties of amorphous materials can be exploited to improve the performance of pharmaceutical dosage forms, but these properties can also give rise to unwanted effects that need to be understood and managed in order for the systems to perform as required.

  15. A strategy to improve skills in pharmaceutical supply management in East Africa: the regional technical resource collaboration for pharmaceutical management.

    PubMed

    Matowe, Lloyd; Waako, Paul; Adome, Richard Odoi; Kibwage, Isaac; Minzi, Omary; Bienvenu, Emile

    2008-12-23

    International initiatives such as the Global Fund to Fight AIDS, Tuberculosis and Malaria, the President's Emergency Plan for AIDS Relief and the President's Malaria Initiative have significantly increased availability and access to medicines in some parts of the developing world. Despite this, however, skills remain limited on quantifying needs for medications and ordering, receiving and storing medications appropriately; recording medications inventories accurately; distributing medications for use appropriately; and advising patients on how to use medications appropriately. The Regional Technical Resource Collaboration for Pharmaceutical Management (RTRC) has been established to help address the problem of skills shortage in pharmaceutical management in East Africa. The initiative brings together academic institutions from four East African countries to participate in skills-building activities in pharmaceutical supply management. The initiative targeted the institutions' ability to conduct assessments of pharmaceutical supply management systems and to develop and implement effective skills-building programmes for pharmaceutical supply chain management. Over a two-year period, the RTRC succeeded in conducting assessments of pharmaceutical supply management systems and practices in Kenya, Rwanda, Tanzania and Uganda. In 2006, the RTRC participated in a materials-development workshop in Kampala, Uganda, and contributed to the development of comprehensive HIV/AIDS pharmaceutical management training materials; these materials are now widely available in all four countries. In Tanzania and Uganda the RTRC has been involved with the training of health care workers in HIV/AIDS pharmaceutical management. In Kenya, Tanzania and Uganda the RTRC has been conducting operations research to find solutions to their countries' skills-shortage problems. Some of the interventions tested include applying and evaluating the effectiveness of a novel skills-building approach for

  16. Managing the interface with marketing to improve delivery of pharmacovigilance within the pharmaceutical industry.

    PubMed

    Edwards, Brian

    2004-01-01

    The pharmaceutical industry is under pressure to improve the scientific quality of its decisions concerning the benefit and risks of its products while ensuring compliance with acceptable standards of marketing. All those in a pharmaceutical company who currently work within pharmacovigilance should be encouraged to lead from the front to examine ongoing marketing activities to see how they can be adapted more towards pharmacovigilance and risk management. The current irony is that the personnel who have the greatest influence on benefit-risk decisions of a product are not necessarily those who acknowledge that they are performing pharmacovigilance. Indeed, for all concerned, whether their orientation is scientific and commercial, effective communication with prescribers and consumers usually underpins product success. Also, a substantial 'marketing' budget is culturally acceptable for the pharmaceutical industry so it is logical to assume that resource for postmarketing activity is often made available. Given these realities, I suggest we should strive for an integrated marketing and risk-management plan based on the best available evidence and that being fully aware and in control of the safety issues for your products is the best way to commercialise them successfully. This approach can still be consistent with other corporate responsibilities such as trying to reduce the financial burden of product development. If this article stimulates further debate about how the pharmaceutical industry can more effectively organise resources and operations to support pharmacovigilance, risk management, and marketing, then it will have achieved its purpose.

  17. [Rheologic properties of some pharmaceutical excipients in drug forms and cosmetic preparation technology].

    PubMed

    Tsagareishvili, G V; Bashura, A A; Alekseeva, M A; Bashura, G S

    2012-06-01

    The establishment of mechanisms and principles of the formation of deformation (fracture) of spatial structure of bentonite solutions and various solutions and disperse systems is one or the most important problems of modern pharmaceutical technology. The article presents the results of a long-term research of influence of high-molecular compounds and surfactants on the properties of designed dosage drug forms and cosmetic preparation. Research data, as the basis for drug combinations "gel" with dekamitoksin, extract Aesculus hippocastanum L and probiotics.

  18. Chemometric evaluation of pharmaceutical properties of antipyrine granules by near-infrared spectroscopy.

    PubMed

    Otsuka, Makoto; Mouri, Yoshifumi; Matsuda, Yoshihisa

    2003-01-01

    The purpose of this research was to apply near-infrared (NIR) spectroscopy with chemometrics to predict the change of pharmaceutical properties of antipyrine granules during granulation by regulation of the amount of water added. The various kinds of granules (mean particle size, 70-750 microm) were obtained from the powder mixture (1 g of antipyrine, 6 g of hydroxypropylcellulose, 140 g of lactose, and 60 g of potato starch) by regulation of the added water amount (11-19 wt/wt%) in a high-speed mixer. The granules were characterized by mean particle size, angle of repose, compressibility, tablet porosity, and tablet hardness as parameters of pharmaceutical properties. To predict the pharmaceutical properties, NIR spectra of the granules were measured and analyzed by principal component regression (PCR) analysis. The mean particle size of the granules increased from 81 micro m to 650 micro m with an increase in the amount of water, and it was possible to make larger spherical granules with narrow particle size distribution using a high-speed mixer. Angle of repose, compressibility, and porosity of the tablets decreased with an increase of added water, but tablet hardness increased. The independent calibration models to evaluate particle size, angle of repose, and tablet porosity and hardness were established by using PCR based on NIR spectra of granules, respectively. The correlation coefficient constants of calibration curves for prediction of mean particle size, angle of repose, tablet porosity, and tablet hardness were 0.9109, 0.8912, 0.7437, and 0.8064, respectively. It is possible that the pharmaceutical properties of the granule, such as mean particle size, angle of repose, tablet porosity, and tablet hardness, could be predicted by an NIR-chemometric method.

  19. How to improve R&D productivity: the pharmaceutical industry's grand challenge.

    PubMed

    Paul, Steven M; Mytelka, Daniel S; Dunwiddie, Christopher T; Persinger, Charles C; Munos, Bernard H; Lindborg, Stacy R; Schacht, Aaron L

    2010-03-01

    The pharmaceutical industry is under growing pressure from a range of environmental issues, including major losses of revenue owing to patent expirations, increasingly cost-constrained healthcare systems and more demanding regulatory requirements. In our view, the key to tackling the challenges such issues pose to both the future viability of the pharmaceutical industry and advances in healthcare is to substantially increase the number and quality of innovative, cost-effective new medicines, without incurring unsustainable R&D costs. However, it is widely acknowledged that trends in industry R&D productivity have been moving in the opposite direction for a number of years. Here, we present a detailed analysis based on comprehensive, recent, industry-wide data to identify the relative contributions of each of the steps in the drug discovery and development process to overall R&D productivity. We then propose specific strategies that could have the most substantial impact in improving R&D productivity.

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

    PubMed

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

    2007-11-01

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

  1. Quantitative structure property relationships for the adsorption of pharmaceuticals onto activated carbon.

    PubMed

    Dickenson, E R V; Drewes, J E

    2010-01-01

    Isotherms were determined for the adsorption of five pharmaceutical residues, primidone, carbamazepine, ibuprofen, naproxen and diclofenac, to Calgon Filtrasorb 300 powdered activated carbon (PAC). The sorption behavior was examined in ultra-pure and wastewater effluent organic matter (EfOM) matrices, where more sorption was observed in the ultra-pure water for PAC doses greater than 10 mg/L suggesting the presence of EfOM hinders the sorption of the pharmaceuticals to the PAC. Adsorption behaviors were described by the Freundlich isotherm model. Quantitative structure property relationships (QSPRs) in the form of polyparameter linear solvation energy relationships were developed for simulating the Freundlich adsorption capacity in both ultra-pure and EfOM matrices. The significant 3D-based descriptors for the QSPRs were the molar volume, polarizability and hydrogen-bond donor parameters.

  2. Nanomechanical properties of selected single pharmaceutical crystals as a predictor of their bulk behaviour.

    PubMed

    Egart, Mateja; Janković, Biljana; Lah, Nina; Ilić, Ilija; Srčič, Stanko

    2015-02-01

    The main goal of this research was to assess the mechanical properties of APIs' polymorphic forms at the single-crystal level (piroxicam, famotidine, nifedipine, olanzapine) in order to predict their bulk deformational attributes, which are critical for some pharmaceutical technology processes. The mechanical properties of oriented single crystals were determined using instrumented nanoindentation (continuous stiffness measurement). All polymorphic forms investigated were previously identified using a combination of calorimetric and spectroscopic techniques. Mechanical properties such as Young's modulus and indentation hardness were consistent with the molecular packing of the polymorphic forms investigated with respect to crystal orientation. For mechanically interlocked structures, characteristic of most polymorphic forms, response of single crystals to indentation was isotropic. The material's bulk elastic properties can be successfully predicted by measuring Young's modulus of single crystals because a good linear correlation with a bulk parameter such as the tablets' elastic relaxation index was determined. The results confirm the idea that the intrinsic mechanical properties of pharmaceutical crystals (Young's modulus) largely control and anticipate their deformational behavior during tablet compression. Young's modulus and indentation hardness represent a very valuable and effective tool in preformulation studies for describing materials' mechanical attributes, which are important for technological processes in which materials are exposed to deformation.

  3. Improving Energy Efficiency in Pharmaceutical ManufacturingOperations -- Part I: Motors, Drives and Compressed Air Systems

    SciTech Connect

    Galitsky, Christina; Chang, Sheng-chien; Worrell, Ernst; Masanet,Eric

    2006-04-01

    In Part I of this two-part series, we focus on efficient use of motors, drives and pumps, both for process equipment and compressed air systems. Pharmaceutical manufacturing plants in the U.S. spend nearly $1 billion each year for the fuel and electricity they need to keep their facilities running (Figure 1, below). That total that can increase dramatically when fuel supplies tighten and oil prices rise, as they did last year. Improving energy efficiency should be a strategic goal for any plant manager or manufacturing professional working in the drug industry today. Not only can energy efficiency reduce overall manufacturing costs, it usually reduces environmental emissions, establishing a strong foundation for a corporate greenhouse-gas-management program. For most pharmaceutical manufacturing plants, Heating, Ventilation and Air Conditioning (HVAC) is typically the largest consumer of energy, as shown in Table 1 below. This two-part series will examine energy use within pharmaceutical facilities, summarize best practices and examine potential savings and return on investment. In this first article, we will focus on efficient use of motors, drives and pumps, both for process equipment and compressed air systems. Part 2, to be published in May, will focus on overall HVAC systems, building management and boilers.

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

    PubMed

    Gryl, Marlena

    2015-08-01

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

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

    PubMed Central

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

    2009-01-01

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

  6. Prediction of solubility curves and melting properties of organic and pharmaceutical compounds.

    PubMed

    Nordström, Fredrik L; Rasmuson, Ake C

    2009-02-15

    The relationships between solubility, temperature dependence of solubility, melting temperature and melting enthalpy are investigated for the purpose of finding relations that can significantly reduce the need for experimental work in the selection of the solvent for processing of organic fine chemicals and pharmaceuticals. The relationships are investigated theoretically and by evaluation of experimental data for 41 organic and pharmaceutical compounds comprising a total of 115 solubility curves in organic and aqueous solvents. The work considers (i) selection of the equation for correlation of solubility data based on thermodynamic considerations and ability to predict melting properties of the solute from solubility data, (ii) prediction of the temperature dependence of solubility, and (iii) prediction of solubility curves in new solvents. While it is a simple task to find an equation to obtain a decent fit of experimental solubility data, it is more challenging to find relations that are sufficiently sound thermodynamically to allow for extrapolation to the melting temperature. However, with a proper choice of equation it is shown that the melting temperature of the solute can readily be predicted from solubility data in organic solvents (average accuracy of -5K, standard deviation of 26K). Relationships are identified by which the entire solubility curve can be predicted of the compound in a new solvent using only the melting properties and a single solubility data point in that solvent.

  7. Non-destructive determination of anisotropic mechanical properties of pharmaceutical solid dosage forms.

    PubMed

    Akseli, I; Hancock, B C; Cetinkaya, C

    2009-07-30

    The mechanical property anisotropy of compacts made from four commercially available pharmaceutical excipient powders (microcrystalline cellulose, lactose monohydrate, ascorbic acid, and aspartame) was evaluated. The speed of pressure (longitudinal) waves in the uni-axially compressed cubic compacts of each excipient in the three principle directions was determined using a contact ultrasonic method. Average Young's moduli of each compact in the axial (x) and radial (y and z) directions were characterized. The contact ultrasonic measurements revealed that average Young's modulus values vary with different testing orientations which indicate Young's modulus anisotropy in the compacts. The extent of Young's modulus anisotropy was quantified by using a dimensionless ratio and was found to be significantly different for each material (microcrystalline cellulose>lactose>aspartame>ascorbic acid). It is also observed that using the presented contact method, compacts at high solid fraction (0.857-0.859) could be differentiated than those at the solid fraction of 0.85 in their groups. The presented contact ultrasonic method is an attractive tool since it has the advantages of being sensitive to solid fraction ratio, non-destructive, requiring small amount of material and rapid. It is noteworthy that, since the approach provides insight into the performance of common pharmaceutical materials and fosters increased process knowledge, it can be applied to broaden the understanding of the effect of the mechanical properties on the performance (e.g., disintegration profiles) of solid oral dosage forms.

  8. Using information technology for an improved pharmaceutical care delivery in developing countries. Study case: Benin.

    PubMed

    Edoh, Thierry Oscar; Teege, Gunnar

    2011-10-01

    One of the problems in health care in developing countries is the bad accessibility of medicine in pharmacies for patients. Since this is mainly due to a lack of organization and information, it should be possible to improve the situation by introducing information and communication technology. However, for several reasons, standard solutions are not applicable here. In this paper, we describe a case study in Benin, a West African developing country. We identify the problem and the existing obstacles for applying standard ECommerce solutions. We develop an adapted system approach and describe a practical test which has shown that the approach has the potential of actually improving the pharmaceutical care delivery. Finally, we consider the security aspects of the system and propose an organizational solution for some specific security problems.

  9. Pharmaceutical pricing: a review of proposals to improve access and affordability of prescription drugs.

    PubMed

    Tironi, Paula

    2010-01-01

    This article discusses how pharmaceutical innovation achieves remarkable improvements in human health but a significant portion of the U.S. population cannot afford prescription drugs. The author examines ways that patent protection, generics, supply chain complexity, and the cost of innovation and promotion affect access and affordability. The author then looks at the influences of marketing strategies and industry trends such as the patent cliff and pipeline for new drugs, innovations in biotechnology and genomics, comparative effectiveness analysis, and payor and employer strategies on drug prices. An analysis of reform proposals in the context of industry trends suggests that promoting generic drug use and availability through education, prohibiting authorized generics, and restricting the practice of developing follow-on drugs and discontinuing the original formulations upon patent expiration could improve access and affordability most quickly and significantly.

  10. [Rising attention to the market to ratio meet demand of improving efficiency of pharmaceutical circulation--based on complicated variety and specification of drugs].

    PubMed

    Chen, Zhaoxing; Sun, Lihua

    2010-05-01

    Analyzing the complicated variety and specification of drugs and the objective demand of pharmaceutical circulation, to seek out the key factors in improving the efficiency of pharmaceutical circulation, for putting forward suggestions to promote the development of pharmaceutical circulation in China. The conclusion is drawed from industrial organization theory and successful experience of foreign countries, high market attention met with the demand of complicated variety and specification of drugs in pharmaceutical circulation.

  11. Improving pharmaceutical innovation by building a more comprehensive database on drug development and use.

    PubMed

    Daniel, Gregory W; Cazé, Alexis; Romine, Morgan H; Audibert, Céline; Leff, Jonathan S; McClellan, Mark B

    2015-02-01

    New drugs and biologics have had a tremendous impact on the treatment of many diseases. However, available measures suggest that pharmaceutical innovation has remained relatively flat, despite substantial growth in research and development spending. We review recent literature on pharmaceutical innovation to identify limitations in measuring and assessing innovation, and we describe the framework and collaborative approach we are using to develop more comprehensive, publicly available metrics for innovation. Our research teams at the Brookings Institution and Deerfield Institute are collaborating with experts from multiple areas of drug development and regulatory review to identify and collect comprehensive data elements related to key development and regulatory characteristics for each new molecular entity approved over the past several decades in the United States and the European Union. Subsequent phases of our effort will add data on downstream product use and patient outcomes and will also include drugs that have failed or been abandoned in development. Such a database will enable researchers to better analyze the drivers of drug innovation, trends in the output of new medicines, and the effect of policy efforts designed to improve innovation.

  12. Use of Fenton oxidation to improve the biodegradability of a pharmaceutical wastewater.

    PubMed

    Tekin, Huseyin; Bilkay, Okan; Ataberk, Selale S; Balta, Tolga H; Ceribasi, I Haluk; Sanin, F Dilek; Dilek, Filiz B; Yetis, Ulku

    2006-08-21

    The applicability of Fenton's oxidation to improve the biodegradability of a pharmaceutical wastewater to be treated biologically was investigated. The wastewater was originated from a factory producing a variety of pharmaceutical chemicals. Treatability studies were conducted under laboratory conditions with all chemicals (having COD varying from 900 to 7000 mg/L) produced in the factory in order to determine the operational conditions to utilize in the full-scale treatment plant. Optimum pH was determined as 3.5 and 7.0 for the first (oxidation) and second stage (coagulation) of the Fenton process, respectively. For all chemicals, COD removal efficiency was highest when the molar ratio of H(2)O(2)/Fe(2+) was 150-250. At H(2)O(2)/Fe(2+) ratio of 155, 0.3M H(2)O(2) and 0.002 M Fe(2+), provided 45-65% COD removal. The wastewater treatment plant that employs Fenton oxidation followed by aerobic degradation in sequencing batch reactors (SBR), built after these treatability studies provided an overall COD removal efficiency of 98%, and compliance with the discharge limits. The efficiency of the Fenton's oxidation was around 45-50% and the efficiency in the SBR system which has two reactors each having a volume of 8m(3) and operated with a total cycle time of 1 day, was around 98%, regarding the COD removal.

  13. Regulating pharmaceutical markets: improving efficiency and controlling costs in the UK.

    PubMed

    Walley, Tom; Mrazek, Monique; Mossialos, Elias

    2005-01-01

    UK government policy on pharmaceuticals is broadly integrated across the whole of health care policy. In the early 1990s, cost containment was emphasized, through budget holding by doctors to ensure clinical acceptability. From 2000 onwards, increased government funding for the NHS has allowed expansion of services and prescribing in areas of public health importance, but has been coupled with increased accountability and ambitious targets for the process of care and health outcomes. Standards for care are set in national guidelines including those from the National Institute for Clinical Excellence (NICE). NICE recommends or rejects new technologies to the NHS for their clinical value and cost effectiveness. Although following its advice is mandatory, evidence so far suggests that it has been only partly successful at improving services and eliminating variations. GP prescribing is monitored by Primary Care Organisations (PCO) which also hold the medicines budget. They may provide incentives to GPs for meeting targets in quality or expenditure. The UK government regulates the prices of generics but not of branded medicines; instead it regulates the profitability of the pharmaceutical industry. This arrangement seems to have been successful both at maintaining a major employer and export earner, and in limiting high drug expenditure.

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

    NASA Astrophysics Data System (ADS)

    Valenzano, Loredana

    2013-03-01

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

  15. Pharmaceutical services cost analysis using time-driven activity-based costing: A contribution to improve community pharmacies' management.

    PubMed

    Gregório, João; Russo, Giuliano; Lapão, Luís Velez

    2016-01-01

    The current financial crisis is pressing health systems to reduce costs while looking to improve service standards. In this context, the necessity to optimize health care systems management has become an imperative. However, little research has been conducted on health care and pharmaceutical services cost management. Pharmaceutical services optimization requires a comprehensive understanding of resources usage and its costs. This study explores the development of a time-driven activity-based costing (TDABC) model, with the objective of calculating the cost of pharmaceutical services to help inform policy-making. Pharmaceutical services supply patterns were studied in three pharmacies during a weekday through an observational study. Details of each activity's execution were recorded, including time spent per activity performed by pharmacists. Data on pharmacy costs was obtained through pharmacies' accounting records. The calculated cost of a dispensing service in these pharmacies ranged from €3.16 to €4.29. The cost of a counseling service when no medicine was supplied ranged from €1.24 to €1.46. The cost of health screening services ranged from €2.86 to €4.55. The presented TDABC model gives us new insights on management and costs of community pharmacies. This study shows the importance of cost analysis for health care services, specifically on pharmaceutical services, in order to better inform pharmacies' management and the elaboration of pharmaceutical policies. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Self-care Improvement After a Pharmaceutical Intervention in Elderly Type 2 Diabetic Patients.

    PubMed

    Nascimentoa, Tania; Braz, Nídia; Gomes, Eurico; Fernandez-Arche, Angeles; De La Puerta, Rocio

    2015-01-01

    Diabetes mellitus involves long-term complications that affect diabetic patients' quality of life. The best way to prevent these complications is that patients achieve good metabolic control. In order to reach this goal, patients are requested to acquire daily behaviours (self-care). Such behaviours are sometimes hard to adhere, because they require changes in habits acquired over time. The aim of the present study is to evaluate the improvement on self-care after a pharmaceutical intervention on home regime patients. We performed a controlled experimental comparative study with a follow up of 6 months, on 87 patients, randomized in control group (n=43) and intervention group (n=44). We accessed sociodemographic and clinical data (glycaemic profile), as well as adherence to drug therapy and self-assessed care (before/after). In the intervention group, mean age was 74.2±5.4 years, and the median time of T2DM diagnosis was 14.7±8.5 years. At the end of study, the decrease in fasting blood glucose was higher in the intervention group patients than that observed in the control group (50.2mg/dL), with statistically significant difference (p<0.05), as well as the decrease verified in HbA1c. In self-care adherence, alterations in the levels of adherence of the general nutrition and physical exercise dimensions became evident, with an increase in the number of days of adherence. On medication adherence statistically significant alterations (p<0.05) were also recorded. We can conclude that an individualized pharmaceutical intervention can improve self-care behaviours, as well as medication adherence, contributing to better metabolic control.

  17. Deformation properties of pharmaceutical excipients determined using an in-die and out-die method.

    PubMed

    Ilić, Ilija; Govedarica, Biljana; Šibanc, Rok; Dreu, Rok; Srčič, Stane

    2013-03-25

    This study investigated deformation mechanisms of some commonly used pharmaceutical fillers, such as microcrystalline cellulose, lactose, dicalcium phosphate, isomalt and cornstarch, using a combination of the in-die and out-die method with the Heckel and Walker models. The tableting mixtures contained of 98.5% (w/w) filler, the rest consisted of dry binder and an antiadhesive agent. Our results showed that plasticity and elasticity may be considered independent deformation properties as highly plastic materials (microcrystalline cellulose, cornstarch) also exhibited high elasticity. Particular emphasis was placed on explaining the differences observed between the in-die and out-die method-comparison revealed that the differences are a consequence of the material's elastic properties. Larger error of in-die results can be expected for more elastic materials, and thus in-die Heckel should be used with some considerations. In contrast, the Walker model was found to be more robust and smaller differences were observed between the two methods. We consider the most correct results to have been obtained by the out-die approach, which excludes the elastic properties of the material evaluated. An excellent correlation between elastic determination at the single-particle level and multiple-particle scale was demonstrated, suggesting a great potential of nanoscale determination of a material's mechanical properties for better elucidation of deformation mechanisms. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Improving the Practical Education of Chemical and Pharmaceutical Engineering Majors in Chinese Universities

    ERIC Educational Resources Information Center

    Zhao, Feng-qing; Yu, Yi-feng; Ren, Shao-feng; Liu, Shao-jie; Rong, Xin-yu

    2014-01-01

    Practical education in chemical engineering has drawn increasing attention in recent years. This paper discusses two approaches to teaching and learning about experiments among upper-level chemical and pharmaceutical engineering majors in China. On the basis of years of experience in teaching chemical and pharmaceutical engineering, we propose the…

  19. Improving the Practical Education of Chemical and Pharmaceutical Engineering Majors in Chinese Universities

    ERIC Educational Resources Information Center

    Zhao, Feng-qing; Yu, Yi-feng; Ren, Shao-feng; Liu, Shao-jie; Rong, Xin-yu

    2014-01-01

    Practical education in chemical engineering has drawn increasing attention in recent years. This paper discusses two approaches to teaching and learning about experiments among upper-level chemical and pharmaceutical engineering majors in China. On the basis of years of experience in teaching chemical and pharmaceutical engineering, we propose the…

  20. Significant Improvement in Sleep in People with Intellectual Disabilities Living in Residential Settings by Non-Pharmaceutical Interventions

    ERIC Educational Resources Information Center

    Hylkema, T.; Vlaskamp, C.

    2009-01-01

    Background: Although about 15 to 50 percent of people with intellectual disabilities (ID) living in residential settings suffer from sleep problems, scant attention is paid to these problems. Most available studies focus on pharmaceutical solutions. In this study we focus on improving sleep in people with intellectual disabilities living in…

  1. Significant Improvement in Sleep in People with Intellectual Disabilities Living in Residential Settings by Non-Pharmaceutical Interventions

    ERIC Educational Resources Information Center

    Hylkema, T.; Vlaskamp, C.

    2009-01-01

    Background: Although about 15 to 50 percent of people with intellectual disabilities (ID) living in residential settings suffer from sleep problems, scant attention is paid to these problems. Most available studies focus on pharmaceutical solutions. In this study we focus on improving sleep in people with intellectual disabilities living in…

  2. Energy Efficiency Improvement and Cost Saving Opportunities for the Pharmaceutical Industry. An ENERGY STAR Guide for Energy and Plant Managers

    SciTech Connect

    Galitsky, Christina; Galitsky, Christina; Chang, Sheng-chieh; Worrell, Ernst; Masanet, Eric

    2008-03-01

    The U.S. pharmaceutical industry consumes almost $1 billion in energy annually. Energy efficiency improvement is an important way to reduce these costs and to increase predictable earnings, especially in times of high energy price volatility. There are a variety of opportunities available at individual plants in the U.S. pharmaceutical industry to reduce energy consumption in a cost-effective manner. This Energy Guide discusses energy efficiency practices and energy efficient technologies that can be implemented at the component, process, system, and organizational levels. A discussion of the trends, structure, and energy consumption characteristics of the U.S. pharmaceutical industry is provided along with a description of the major process steps in the pharmaceutical manufacturing process. Expected savings in energy and energy-related costs are given for many energy efficiency measures, based on case study data from real-world applications in pharmaceutical and related facilities worldwide. Typical measure payback periods and references to further information in the technical literature are also provided, when available. The information in this Energy Guide is intended to help energy and plant managers reduce energy consumption in a cost-effective manner while meeting regulatory requirements and maintaining the quality of products manufactured. At individual plants, further research on the economics of the measures?as well as their applicability to different production practices?is needed to assess potential implementation of selected technologies.

  3. A Critical Review of Properties and Analytical Methods for the Determination of Oxytetracyline in Biological and Pharmaceutical Matrices.

    PubMed

    Sversut, Rúbia Adrieli; da Silva, Adriane Andrade; Cardoso, Teófilo Fernando Mazon; Kassab, Nájla Mohamad; do Amaral, Marcos Serrou; Salgado, Hérida Regina Nunes

    2017-03-04

    Antibiotics have an unquestionable importance in the treatment of many infections. Oxytetracycline is an antibiotic belonging to the class of tetracyclines, available for use in human and veterinary medicine. Development of analytical methods that prove the quality and efficacy of these drugs is fundamentally important to the pharmaceutical industry. In this context, the research presents an overview of the analytical profile of oxytetracycline, describing its chemical and pharmacological properties, and analytical methods for quantification of this drug in biological samples and pharmaceutical products. Oxytetracycline can be analyzed in these matrices by many types of methodologies. However, high-performance liquid chromatography is the most widely used, being recommended by official compendia. This kind of study can be useful to support the development of new efficient and sustainable analytical methods that may be utilized in the quality control routine of oxytetracycline in pharmaceutical products and pharmacokinetic monitoring in biological samples.

  4. Pharmaceutical properties of calycosin, the major bioactive isoflavonoid in the dry root extract of Radix astragali.

    PubMed

    Gao, JunQing; Liu, Zong Jun; Chen, Tao; Zhao, DeQiang

    2014-09-01

    Radix astragali (Fabaceae astragalus propinquus Schischkin) is a Chinese medicinal herb traditionally used for the treatment of several diseases. Calycosin is the major bioactive chemical in the dry root extract of this medical plant. This work presents a brief overview of recent reports on the potential effects of calycosin on several diseases and the possible mechanisms of action of this chemical. This review gathers information from the scientific literature (before 1 June 2013) that was compiled from various databases, such as Science Direct, PubMed, Google Scholar, and Scopus. The potential pharmaceutical properties of calycosin in the treatment of tumors, inflammation, stroke, and cardiovascular diseases have gained increasing attention in the recent years. The literature survey showed that calycosin exhibits promising effects for the treatment of several diseases and that these effects may be due to its isoflavonoid and phytoestrogenic properties. The effects of calycosin most likely result from its interaction with the ER receptors on the cell membrane and the modulation of the MAPK signaling pathway. Calycosin exhibits great potential as a therapeutic drug and may be a successful example of the standardization and modernization of traditional Chinese herbal medicine.

  5. Cyclodextrins in pharmaceutical formulations I: structure and physicochemical properties, formation of complexes, and types of complex.

    PubMed

    Jambhekar, Sunil S; Breen, Philip

    2016-02-01

    Cyclodextrins are cyclic oligosaccharides that have been recognized as pharmaceutical adjuvants for the past 20 years. The molecular structure of these glucose derivatives, which approximates a truncated cone, bucket, or torus, generates a hydrophilic exterior surface and a nonpolar interior cavity. Cyclodextrins can interact with appropriately sized drug molecules to yield an inclusion complex. These noncovalent inclusion complexes offer a variety of advantages over the noncomplexed form of a drug. Cyclodextrins are primarily used to enhance the aqueous solubility, physical chemical stability, and bioavailability of drugs. Their other applications include preventing drug-drug interactions, converting liquid drugs into microcrystalline powders, minimizing gastrointestinal and ocular irritation, and reducing or eliminating unpleasant taste and smell. Here, we discuss the physical chemical properties of various cyclodextrins, including the effects of substitutions on these properties. Additionally, we report on the regulatory status of their use, commercial products containing cyclodextrins, toxicological considerations, and the forces involved in complex formation. We also highlight the types of complex formed and discuss the methods used to determine the types of complex present.

  6. Improvement of time in therapeutic range with warfarin by pharmaceutical intervention.

    PubMed

    Víquez-Jaikel, Alvaro; Victoria Hall-Ramírez; Ramos-Esquivel, Allan

    2017-02-01

    Background Anticoagulation therapy with warfarin is highly effective for prevention and treatment of thromboembolic disorders. Nevertheless, its management is challenging especially in developing countries, where the medical access is difficult and patient education is poor. Objective To determine the effect of pharmaceutical intervention (PI) on the time in therapeutic range (TTR) of a group of anticoagulated patients from our referral center. Method A group of consecutive outpatients previously treated by usual medical care underwent PI. The intervention consisted in the identification and avoidance of food and drug interactions, the confection of medication schedule charts and education to patients regarding side effects and drug monitoring. Mean TTR before and after PI was compared through the Wilcoxon test for repeated measures. Regression analyses were performed to assess the relationship between a TTR level under 65% and potential explanatory variables. Results Mean TTR before PI was 37.4 ± 23.5% and after PI it raised to 67.0 ± 24.9%. Mean change in TTR was +29.5% (95% CI 14.5-44.6; p < 0.001). Before PI only 4 patients had TTR values above 65%, in contrast to 18 patients after PI. Conclusion Our findings support the efficacy of PI to improve TTR values in patients treated with warfarin.

  7. Patent and intellectual property rights related to pharmaceuticals: global future perspectives: Japan.

    PubMed

    Komatani, Takeshi S

    2016-07-01

    The Japanese patent system is reviewed and summarized from pharmaceutical industrial point of view. Current systems and practice are introduced and current problems in pharma patent are discussed, and perspective for future patent system in the field of pharmaceutical industry is discussed and proposed.

  8. High-throughput NIR-chemometric methods for determination of drug content and pharmaceutical properties of indapamide tablets.

    PubMed

    Tomuta, Ioan; Rus, Lucia; Iovanov, Rares; Rus, Luca Liviu

    2013-10-01

    This paper describes the development, validation and application of NIR-chemometric methods for API content and pharmaceutical characterization (disintegration time and crushing strength) of indapamide intact tablets. Development of the method for chemical characterization was performed on samples corresponding to 80, 90, 100, 110 and 120% of indapamide content and for pharmaceutical characterization on samples prepared at nine different compression forces (covering the interval 7-45 kN). NIR spectra of prepared tablets were recorded in transmission mode, and partial least-squares followed by leave-one-out cross-validation were used to develop models for the prediction of the drug content and the pharmaceutical properties of tablets. All developed models were validated in terms of trueness, precision and accuracy. No statistical differences were found between results predicted by NIR-chemometric methods and the ones determined by reference methods. Therefore, the developed NIR-chemometric methods meet the requirements of a high-throughput method for the determination of drug content, pharmaceutical properties of indapamide tablets.

  9. Transglycosylated stevia and hesperidin as pharmaceutical excipients: dramatic improvement in drug dissolution and bioavailability.

    PubMed

    Uchiyama, Hiromasa; Tozuka, Yuichi; Imono, Masaaki; Takeuchi, Hirofumi

    2010-10-01

    The capability of transglycosylated materials, α-glycosyltransferase-treated stevia (Stevia-G) and α-glycosyl hesperidin (Hsp-G), to enhance the bioavailability of poorly water-soluble drugs was investigated. Spray-dried particles (SDPs) of drug/transglycosylated material, such as, flurbiprofen (FP)/Stevia-G, probucol (PRO)/Stevia-G, FP/Hsp-G, and PRO/Hsp-G were prepared. All SDPs showed pronounced improvement in both dissolution rate and apparent drug solubility. The amount of dissolved PRO was significantly improved to that of untreated PRO crystals when prepared as SDPs of PRO/Stevia-G or PRO/Hsp-G. There was no cytotoxicity to Caco-2 cells at levels of 10% Stevia-G or Hsp-G solution. Values for the area under the plasma concentration-time curve (AUC) of untreated PRO, SDPs of PRO/Hsp-G and PRO/Stevia-G after oral administration to rats were 4.94±2.06, 26.08±4.52 and 48.79±9.97μgh/mL, respectively. Interestingly, AUC values in cases of the FP system were in the order of untreated FPpharmaceutical excipient. Copyright © 2010 Elsevier B.V. All rights reserved.

  10. Understanding solid-state properties of triglycerides used in pharmaceutical and food microencapsulation.

    PubMed

    Elviri, Lisa; Mangia, Mattia; Menabeni, Roberta; Della Bella, Andrea; Camellini, Claudia; Beltrami, Diego; Arduini, Lauro; Bettini, Ruggero

    2015-01-01

    Hydrophobic materials, in particular hydrogenated vegetable oils, HVO, are extensively used as coating materials in food and pharmaceutical systems. Correct application of these coatings requires an evaluation of their behaviour as a function of various parameters such as melting temperature, solubility, concentration and/or pH. The purpose of this study was to assess the physico-chemical properties of an HVO in terms of composition, crystallisation, phase transition and polymorphism using a variety of analytical techniques, such as electrospray mass spectrometry (ESI-MS), differential scanning calorimetry (DSC) and X-ray diffraction (XRD). High-resolution ESI-MS allowed establishment of the HVO main composition of long-chain triglycerides (average molecular weight 1183 Da). DSC results showed that thermal history determines the formation of at least two polymorphs of HVO, namely two different crystal forms, assigned as form α, melting point (m.p.) 48 °C, and form β', m.p. 60 °C. A third polymorph, the more thermodynamically stable β-form, having a melting point at 62 °C, is obtained by solution-mediated re-crystallisation. Phase transformation paths were investigated by isothermal DSC experiments, which evidenced that the α-form is kinetically stable at temperatures lower than 25 °C. These data are of particular interest in practical applications such as spray freezing or pan coating where significant heat transfer phenomena are involved.

  11. The impact of roller compaction and tablet compression on physicomechanical properties of pharmaceutical excipients.

    PubMed

    Iyer, Raman Mahadevan; Hegde, Shridhar; Dinunzio, James; Singhal, Dharmendra; Malick, Waseem

    2014-08-01

    Material properties play a significant role in pharmaceutical processing. The impact of roller compaction (RC) and tablet compression on solid fraction (SF), tensile strength (TS) and flexural modulus (FM) of Avicel DG [co-processed excipient with 75% microcrystalline cellulose (MCC) and 25% anhydrous dibasic calcium phosphate (DCPA)], lactose and 1:1 Mixture of the two was studied. Materials were roller compacted at different force and roller type and compressed into tablets over a range of compression pressures (CP). SF, TS and FM were determined for ribbons and tablets. Roller force was a significant variable affecting SF while roller type was not. Both SF and TS of tablets increased with CP with Avicel DG exhibiting greater TS than that of 1:1 Mixture while tablets of lactose had the lowest TS. The TS of tablets decreased exponentially with tablet porosity. Ribbon of Avicel DG had higher TS and lower SF than lactose and greater reworkability. This is attributed to plastic deformation of MCC resulting in high degree of bonding and fragmentation of DCPA that fills the void spaces during tablet compression. The lack of significant increase in SF and low tablet TS for lactose upon compression is likely due to its brittle fragmentation and some elastic recovery as shown by the high FM.

  12. Multivariate analysis in the pharmaceutical industry: enabling process understanding and improvement in the PAT and QbD era.

    PubMed

    Ferreira, Ana P; Tobyn, Mike

    2015-01-01

    In the pharmaceutical industry, chemometrics is rapidly establishing itself as a tool that can be used at every step of product development and beyond: from early development to commercialization. This set of multivariate analysis methods allows the extraction of information contained in large, complex data sets thus contributing to increase product and process understanding which is at the core of the Food and Drug Administration's Process Analytical Tools (PAT) Guidance for Industry and the International Conference on Harmonisation's Pharmaceutical Development guideline (Q8). This review is aimed at providing pharmaceutical industry professionals an introduction to multivariate analysis and how it is being adopted and implemented by companies in the transition from "quality-by-testing" to "quality-by-design". It starts with an introduction to multivariate analysis and the two methods most commonly used: principal component analysis and partial least squares regression, their advantages, common pitfalls and requirements for their effective use. That is followed with an overview of the diverse areas of application of multivariate analysis in the pharmaceutical industry: from the development of real-time analytical methods to definition of the design space and control strategy, from formulation optimization during development to the application of quality-by-design principles to improve manufacture of existing commercial products.

  13. The Chinese pharmaceutical market at the crossroads: pro-competition solutions to improve access, quality and affordability.

    PubMed

    Wang, Y Richard

    2005-01-01

    The Chinese pharmaceutical market is large in absolute size (the second largest in Asia), but it faces similar problems to those that plague other developing countries, such as a lack of adequate patent protection, low pharmaceutical spending per capita, but high pharmaceutical expenditure as a proportion of total medical spending, and a lack of health insurance coverage. In this article, the pros and cons of two pro-competition policy proposals for China are explored. The first proposal is to follow the E5 guideline of the International Conference on Harmonisation and waive unnecessary local clinical trials for global new drugs that have been approved by the US Food and Drug Administration or the European Medicines Agency (except for drugs for which there is a real possibility of there being ethnic differences in patient responses). The second proposal is to tighten the standards for generic drugs and approve only bioequivalent ones. While the first proposal encourages price competition between similar compounds in the same therapeutic class, the second proposal enhances generic competition for off-patent drugs. Working together, these two proposals would improve access to and the quality and affordability of pharmaceuticals in China.

  14. 30 years of pharmaceutical cost-utility analyses: growth, diversity and methodological improvement.

    PubMed

    Neumann, Peter J; Fang, Chi-Hui; Cohen, Joshua T

    2009-01-01

    To review and critically evaluate published cost-utility analyses (CUAs) pertaining to pharmaceuticals for the past 3 decades. We examined data from the Tufts Medical Center Cost-Effectiveness Analysis Registry (www.cearegistry.org), which contains detailed information on English-language CUAs and their ratios (in $US, year 2008 values) published in peer-reviewed journals. We summarized study features using descriptive statistics for articles published from 1976 to 2006. Changes in study methodology over time were analysed by trend test. Analysis of ratios was restricted to those published from 2000 to 2006 from studies that correctly discounted future costs and benefits. Factors associated with having a favourable value (defined to be more than the median for all included ratios) were identified by logistic regression. Of 1393 CUAs published through 2006, 640 (45.9%) pertained to pharmaceuticals. The proportion of CUAs that focussed on pharmaceuticals increased from 34% for the period 1990-5 to 47% for the period 2001-5. Investigations with a US perspective accounted for 51% of all CUAs, although this proportion has decreased over time. The UK perspective investigations accounted for nearly 16% of all studies, and this portion has increased over time. About 24% of all CUAs were sponsored by industry, 48% were sponsored by non-industry sources, and 28% did not disclose their funding. Adherence to good methodological practices is roughly similar for studies with industry and non-industry sponsorship. Adherence to these practices has increased over time. Among the 1969 ratios meeting our inclusion criteria, the median value was $US22 000 per QALY. Logistic regression revealed that, while controlling for the intervention category (e.g. pharmaceutical, medical device, screening), ratios were more likely to be favourable if they were from studies sponsored by a pharmaceutical or device manufacturer (OR 1.53; 95% CI 1.07, 2.19). Ratios for pharmaceutical CUAs were less

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

    PubMed

    Gadade, Dipak Dilip; Pekamwar, Sanjay Sudhakar

    2016-12-01

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

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

    PubMed Central

    Gadade, Dipak Dilip; Pekamwar, Sanjay Sudhakar

    2016-01-01

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

  17. Quantitative Systems Pharmacology can reduce attrition and improve productivity in pharmaceutical research and development.

    PubMed

    Leil, Tarek A; Bertz, Richard

    2014-01-01

    The empirical hypothesis generation and testing approach to pharmaceutical research and development (R&D), and biomedical research has proven very effective over the last half-century; resulting in tremendous increases productivity and the rates of approval for new drug applications at the Food and Drug Administration (FDA). However, as discovery of new therapeutic approaches for diseases with unmet medical need becomes more challenging, the productivity and efficiency of the traditional approach to drug discovery and development is diminishing. Innovative approaches are needed, such as those offered by Quantitative Systems Pharmacology (QSP) modeling and simulation. This "systems" approach to modeling and simulation can be used to guide the hypothesis generation and testing process in pharmaceutical R&D, in a manner similar to its adoption in other industries in the past. Embedding QSP into the existing processes within pharmaceutical discovery and development will be required in order to realize the full beneficial impact of this innovative approach.

  18. Quantitative Systems Pharmacology can reduce attrition and improve productivity in pharmaceutical research and development

    PubMed Central

    Leil, Tarek A.; Bertz, Richard

    2014-01-01

    The empirical hypothesis generation and testing approach to pharmaceutical research and development (R&D), and biomedical research has proven very effective over the last half-century; resulting in tremendous increases productivity and the rates of approval for new drug applications at the Food and Drug Administration (FDA). However, as discovery of new therapeutic approaches for diseases with unmet medical need becomes more challenging, the productivity and efficiency of the traditional approach to drug discovery and development is diminishing. Innovative approaches are needed, such as those offered by Quantitative Systems Pharmacology (QSP) modeling and simulation. This “systems” approach to modeling and simulation can be used to guide the hypothesis generation and testing process in pharmaceutical R&D, in a manner similar to its adoption in other industries in the past. Embedding QSP into the existing processes within pharmaceutical discovery and development will be required in order to realize the full beneficial impact of this innovative approach. PMID:25426074

  19. Pharmaceutical properties of two ethenzamide-gentisic acid cocrystal polymorphs: Drug release profiles, spectroscopic studies and theoretical calculations.

    PubMed

    Sokal, Agnieszka; Pindelska, Edyta; Szeleszczuk, Lukasz; Kolodziejski, Waclaw

    2017-04-30

    The aim of this study was to evaluate the stability and solubility of the polymorphic forms of the ethenzamide (ET) - gentisic acid (GA) cocrystals during standard technological processes leading to tablet formation, such as compression and excipient addition. In this work two polymorphic forms of pharmaceutical cocrystals (ETGA) were characterized by (13)C and (15)N solid-state nuclear magnetic resonance and Fourier transformed infrared spectroscopy. Spectroscopic studies were supported by gauge including projector augmented wave (GIPAW) calculations of chemical shielding constants.Polymorphs of cocrystals were easily identified and characterized on the basis of solid-state spectroscopic studies. ETGA cocrystals behaviour during direct compressionand tabletting with excipient addition were tested. In order to choose the best tablet composition with suitable properties for the pharmaceutical industry dissolution profile studies of tablets containing polymorphic forms of cocrystals with selected excipients were carried out. Copyright © 2017. Published by Elsevier B.V.

  20. Physicochemical and Antimicrobial Properties of Cocoa Pod Husk Pectin Intended as a Versatile Pharmaceutical Excipient and Nutraceutical

    PubMed Central

    Adi-Dako, Ofosua; Frimpong Manso, Samuel; Boakye-Gyasi, Mariam EL; Sasu, Clement; Pobee, Mike

    2016-01-01

    The physicochemical and antimicrobial properties of cocoa pod husk (CPH) pectin intended as a versatile pharmaceutical excipient and nutraceutical were studied. Properties investigated include pH, moisture content, ash values, swelling index, viscosity, degree of esterification (DE), flow properties, SEM, FTIR, NMR, and elemental content. Antimicrobial screening and determination of MICs against test microorganisms were undertaken using agar diffusion and broth dilution methods, respectively. CPH pectin had a DE of 26.8% and exhibited good physicochemical properties. Pectin had good microbiological quality and exhibited pseudoplastic, shear thinning behaviour, and high swelling capacity in aqueous media. The DE, FTIR, and NMR results were similar to those of previous studies and supported highly acetylated low methoxy pectin. CPH pectin was found to be a rich source of minerals and has potential as a nutraceutical. Pectin showed dose-dependent moderate activity against gram positive and gram negative microorganisms but weak activity against Listeria spp. and A. niger. The MICs of pectin ranged from 0.5 to 4.0 mg/mL, with the highest activity against E. coli and S. aureus (MIC: 0.5–1.0 mg/mL) and the lowest activity against A. niger (MIC: 2.0–4.0 mg/mL). The study has demonstrated that CPH pectin possesses the requisite properties for use as a nutraceutical and functional pharmaceutical excipient. PMID:27066294

  1. An investigation of the physico-mechanical properties of pharmaceutical compounds by compaction simulator and nano-indentation

    NASA Astrophysics Data System (ADS)

    Bordawekar, Mangesh

    In early development, pharmaceutical formulation scientists are often faced with challenges of developing robust and scalable formulations in extremely stringent timelines based on limited API quantities. Hence, tablet formulation development would benefit significantly from tools that enable predictive analysis based on limited quantities of API to enable selection of excipients with appropriate physico-mechanical properties that would result in robust and scalable formulations. With the recent technological advances, especially in sensor technologies, tools such as the compaction simulator, and instrumented nanoindentation offer hitherto unavailable means of assessing material properties with limited quantities. The goal of this work was to evaluate the physico-mechanical properties of selected pharmaceutical excipients and active pharmaceutical ingredients using a macro-scale analysis technique (compaction simulator), and a micro-scale analysis technique (nanoindentation tester) and compare the results obtained from these techniques in order to determine whether a rank order correlation exists between the two. Excipients representing diverse physic-mechanical properties, and a group of APIs were selected for the study. For the compaction simulator studies, tablets were uniaxially compressed using a flat faced 11.28mm round tooling on the STYLCAM® 200R compaction simulator, to a target final porosity at two different cam speeds (5 rpm and 25 rpm). The force displacement profiles, plastic, elastic, and total compression energies, plasticity index, energy density and the Heckel plots were determined for each compact. These compacts were further analyzed with a Berkovich geometry indenter. The plasticity index, hardness, elastic modulus, as well as creep and relaxation were determined from the force-displacement profiles. The nature of force-displacement curves was studied to differentiate compounds based on predominant mechanisms of deformation. Compaction

  2. Review of the pharmaceutical properties and clinical effects of the topical NSAID formulation, diclofenac epolamine.

    PubMed

    Rainsford, K D; Kean, W F; Ehrlich, G E

    2008-10-01

    Topical formulations of non-steroidal anti-inflammatory drugs (NSAIDs), in particular diclofenac (DI), have become popular for treating various acute and chronic painful inflammatory conditions. To perform a literature review of (1) the use of topical NSAIDs; (2) the pharmaceutical, pharmacokinetic and pharmacodynamic properties of a medicated plaster (patch) containing diclofenac epolamine (DI-EP, Flector Tissugel, Flector patch) compared with other formulations of topical NSAIDs; and (3) evaluation of the clinical findings from studies with this novel DI-EP patch. (1) Pharmacokinetic studies involved determination of DI from DI-EP and separately epolamine (EP) and the epoxide metabolite (N-oxide-EP) in laboratory animals and humans; the latter being the major metabolite in humans. About 2% of DI is absorbed by the skin in humans and is excreted in the urine. Maximum plasma concentrations of 17.4 ng/mL DI are reached at 5.4 hours (approximate steady state conditions); the plasma elimination half-time (t(1/2)) being 26.4 hours. Low systemic levels of DI and EP are produced from DI-EP. Pronounced accumulation of DI occurs in the muscle layers and in synovial fluids of arthritic patients; (2) No significant toxicity occurs from EP nor N-oxide-EP, while that of oral DI-EP was similar to that from DI; and (3) In acute musculoskeletal conditions (sprains, tendonitis and sports injuries) and osteoarthritis DI-EP patches control pain and signs of joint or physical injury compared with placebo controls by 3-5 days with almost complete pain relief at 14 days. DI-EP was shown to have equivalent therapeutic effect to another DI diethylammonium gel formulation (Voltaren Emulgel). There were no reports of serious adverse events in the gastro-intestinal (GI) tract, kidneys or liver from DI-EP. Mild GI symptoms and skin reactions occur in 2 and 10% of patients, respectively. The patch delivery of DI in DI-EP affords controlled delivery of the active drug in contrast to that from

  3. The influence of excipients on physical and pharmaceutical properties of oral lyophilisates containing a pregabalin-acetaminophen combination.

    PubMed

    Chiriac, Aurica P; Diaconu, Alina; Nita, Loredana E; Tudorachi, Nita; Mititelu-Tartau, Liliana; Creteanu, Andreea; Dragostin, Oana; Rusu, Daniela; Popa, Gratiela

    2017-05-01

    The purpose of the study was to investigate and characterize the oral lyophilisates containing the pregabalin-acetaminophen drug combination and as xcipients mannitol with microcrystalline cellulose or hydroxypropyl methylcellulose, in order to conclude upon drug-excipient interactions and their stability implications, impact of excipients on drug release and on the physicochemical and mechanical properties of the pharmaceutical formulations. The oral tablets were made by using a Christ freeze-dryer alpha 2-4-LSC lyophilizer, and evaluated for stability, drug-excipient compatibility and homogeneity of the prepared pharmaceutical formulations. The formulations were evaluated for in vivo absorption in rabbits by histopathological exams. FTIR and thermogravimetric analyses, DLS technique, SEM and NIR-CI studies confirmed the compatibility between compounds. From the determined physical and biochemical parameters of the formulations it was established that they are stable, homogeneous, and meet the conditions for orally disintegrating tablets. In the case of the investigated pharmaceutical formulations the study evidenced the assembling through physical bonds between the excipients and the 'codrug' complex, which do not affect the release of the bioactive compounds.

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

    PubMed

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

    2012-07-01

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

  5. Relating emulsion stability to interfacial properties for pharmaceutical emulsions stabilized by Pluronic F68 surfactant.

    PubMed

    Powell, Kristin Conrad; Damitz, Robert; Chauhan, Anuj

    2017-04-15

    We explore mechanisms of emulsion stability for several systems using Pluronic F68 and a range of oils commonly used in pharmaceutics and cosmetics. We report measurements of dynamic emulsion drop size, zeta potential, and creaming time, as well as dynamic interfacial tension and interfacial viscoelasticity. Experiments show that with 1wt% Pluronic F68, soybean oil emulsions were the most stable with no creaming over six months, followed by isopropyl myristate, octanoic acid, and then ethyl butyrate. The eventual destabilization occurred due to the rising of large drops which formed through Ostwald ripening and coalescence. While Ostwald ripening is important, it is not the dominant destabilization mechanism for the time scale of interest in pharmaceutical emulsions. The more significant destabilization mechanism, coalescence, is reduced through surfactant adsorption, which decreases surface tension, increases surface elasticity, and adds a stearic hindrance to collisions. Though the measured values of elasticity obtained using a standard oscillatory pendant drop method did not correlate to emulsion stability, this is because the frequencies for the measurements were orders of magnitude below those relevant to coalescence in emulsions. However, we show that the high frequency elasticity obtained by fitting the surface tension data to a Langmuir isotherm has very good correlation with the emulsion stability, indicating that the elasticity of the interface plays a key role in stabilizing these pharmaceutical formulations. Further, this study highlights how these important high frequency elasticity values can be easily estimated from surface isotherms. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Improving vegetable oil properties for lubrication methods

    USDA-ARS?s Scientific Manuscript database

    The inherent problems of vegetable oils, such as poor oxidation and low-temperature properties, can be improved by attaching functional groups at the sites of unsaturation through chemical modifications. In this article, you will see how functionalization helps overcome these disadvantages....

  7. Effects of rotational speed on the hydrodynamic properties of pharmaceutical antibodies measured by analytical ultracentrifugation sedimentation velocity.

    PubMed

    Krayukhina, Elena; Uchiyama, Susumu; Fukui, Kiichi

    2012-09-29

    Analytical ultracentrifugation sedimentation velocity (AUC-SV) has recently become one of the most important tools for the measurement of hydrodynamic properties of proteins. Although a number of studies using AUC-SV as applied to pharmaceutical antibodies have been conducted, the effect of rotational speed on molecular properties has not been systematically examined. The present study aimed to elucidate the influence of rotational speed on the hydrodynamic parameters of pharmaceutical antibodies. A monoclonal and a polyclonal antibody were studied by using AUC-SV at 5 different rotor speeds, and the acquired data were analyzed either by using the computer programs SEDFIT or UltraScan. The frictional ratio of the studied antibodies decreased at high rotor speeds, resulting in underestimation of molecular weight. The frictional ratio value of the monoclonal antibody measured at the low rotor speed was consistent with that of human immunoglobulin G1 computed from its three-dimensional structure. The best agreement between the measured molecular weight and the value calculated from the antibody sequence was achieved at the lower rotor speed. Similar to the results obtained using antibodies, AUC-SV analysis of human serum albumin revealed that the frictional ratio and apparent molecular weight behave in a speed-dependent manner. We deduced that the findings were mainly attributable to the hydrostatic pressure in the analytical ultracentrifuge. The current study implies that rotor speed should be carefully considered in antibody studies using AUC-SV. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Improved low-power semiconductor diode lasers for light activation of pharmaceutical agents

    NASA Astrophysics Data System (ADS)

    Lee, Susanne M.; Mueller, Eduard K.; Van de Workeen, Brian C.; Mueller, Otward M.

    2001-05-01

    In photodynamic therapy, a photosensitizing dye is injected into the patient and the die accumulates in tumor tissue. The cancer cells are then destroyed by absorbing light of a specific wavelength, usually around 630 nm. One of the strong advantages of this therapy is that it destroys only malignant cells and causes less morbidity than standard treatments like surgery and radiotherapy. There are several other techniques that also utilize light activation of pharmaceutical agents in treatment of cancers such as breast cancer. One method of supplying this light activation is through the use of diode lasers, which are constantly finding new application in all fields of medicine. However these lasers tend to be limited by their high cost per watt and multiple wavelength output. Cryogenically cooling such lasers provides higher power output and therefore longer device lifetime. We report quantification of these results from laser power meter and photospectrometer data.

  9. Comparison of solute-binding properties of plastic materials used as pharmaceutical product containers.

    PubMed

    Jenke, Dennis; Couch, Tom; Gillum, Amy

    2010-01-01

    Material/water equilibrium binding constants (E(b)) were determined for 11 organic solutes and 2 plastic materials commonly used in pharmaceutical product containers (plasticized polyvinyl chloride and polyolefin). In general, solute binding by the plasticized polyvinyl chloride material was greater, by nearly an order of magnitude, than the binding by the polyolefin (on an equal weight basis). The utilization of the binding constants to facilitate container compatibility assessments (e.g., drug loss by container binding) for drug-containing products is discussed.

  10. Hydrogels 2.0: improved properties with nanomaterial composites for biomedical applications.

    PubMed

    Memic, Adnan; Alhadrami, Hani A; Hussain, M Asif; Aldhahri, Musab; Al Nowaiser, Fozia; Al-Hazmi, Faten; Oklu, Rahmi; Khademhosseini, Ali

    2015-12-23

    The incorporation of nanomaterials in hydrogels (hydrated networks of crosslinked polymers) has emerged as a useful method for generating biomaterials with tailored functionality. With the available engineering approaches it is becoming much easier to fabricate nanocomposite hydrogels that display improved performance across an array of electrical, mechanical, and biological properties. In this review, we discuss the fundamental aspects of these materials as well as recent developments that have enabled their application. Specifically, we highlight synthesis and fabrication, and the choice of nanomaterials for multifunctionality as ways to overcome current material property limitations. In addition, we review the use of nanocomposite hydrogels within the framework of biomedical and pharmaceutical disciplines.

  11. [Specificities of patent protection in the pharmaceutical industry: modalities and traits of intellectual property].

    PubMed

    Jannuzzi, Anna Haydée Lanzillotti; Vasconcellos, Alexandre Guimarães; de Souza, Cristina Gomes

    2008-06-01

    Different forms of protection for inventions in the pharmaceutical industry point to strategies for the perpetuation of patent protection. Based on a literature review showing the specificities of patenting in the industry, the article provides a brief history of drug patents in Brazil, a discussion of patentable and non-patentable inventions, and the modalities and traits of patent protection that aim to extend the temporary monopoly granted under the patent. Such strategies include patents targeting polimorphs and optical isomers of drugs and drug combinations and specific clinical preparations, increasingly present in the drug patent claims filed by pharmaceutical companies. The study's objective is to discuss the specificities of drug patent claims in order to help develop expertise in the area and discuss the impact of expanding the scope of patent protection. In conclusion, while the tendency to expand towards more a permissive protective scope could produce opportunities for Brazilian national inventors, it could also be harmful to a policy for access to medicines.

  12. Removal of caffeine from pharmaceutical wastewater by adsorption: influence of NOM, textural and chemical properties of the adsorbent.

    PubMed

    Álvarez-Torrellas, Silvia; Rodríguez, Araceli; Ovejero, Gabriel; Gómez, José María; García, Juan

    2016-01-01

    This work involves the study of the influence of textural and chemical adsorbent properties on natural organic matter (NOM) removal and the simultaneous adsorption of caffeine and NOM in pharmaceutical wastewater. The performance of a microporous activated carbon, Calgon F400, a synthesized mesoporous carbon from peach stones and a commercial sepiolite in the removal of NOM of a WWTP effluent, and the competitive adsorption of caffeine/NOM were evaluated. It was evidenced that the microporous structure of the adsorbents significantly conditioned the removal of NOM, finding that F400 activated carbon (microporous volume of 0.46 cm(3) g(-1)) led to a NOM removal of 45%. The presence of NOM in the aqueous medium led to worse adsorption parameters, including adsorption capacity at breakthrough time, mass transfer zone length and fractional bed utilization. Additionally, an overshooting in the Total Organic Carbon concentration (TOC/TOC0 = 1.05) was observed in the sepiolite adsorption fixed-bed experiment, due to the displacement of the background NOM. The tested adsorbents were efficient in the removal of caffeine from a pharmaceutical wastewater, finding a competitive effect between the target compound and the background NOM for the active sites.

  13. Engineered particles demonstrate improved flow properties at elevated drug loadings for direct compression manufacturing.

    PubMed

    Trementozzi, Andrea N; Leung, Cheuk-Yui; Osei-Yeboah, Frederick; Irdam, Erwin; Lin, Yiqing; MacPhee, J Michael; Boulas, Pierre; Karki, Shyam B; Zawaneh, Peter N

    2017-03-08

    Optimizing powder flow and compaction properties are critical for ensuring a robust tablet manufacturing process. The impact of flow and compaction properties of the active pharmaceutical ingredient (API) becomes progressively significant for higher drug load formulations, and for scaling up manufacturing processes. This study demonstrated that flow properties of a powder blend can be improved through API particle engineering, without critically impacting blend tabletability at elevated drug loadings. In studying a jet milled API (D50=24μm) and particle engineered wet milled API (D50=70μm and 90μm), flow functions of all API lots were similarly poor despite the vast difference in average particle size (ffc<4). This finding strays from the common notion that powder flow properties are directly correlated to particle size distribution. Upon adding excipients, however, clear trends in flow functions based on API particle size were observed. Wet milled API blends had a much improved flow function (ffc>10) compared with the jet milled API blends. Investigation of the compaction properties of both wet and jet milled powder blends also revealed that both jet and wet milled material produced robust tablets at the drug loadings used. The ability to practically demonstrate this uncommon observation that similarly poor flowing APIs can lead to a marked difference upon blending is important for pharmaceutical development. It is especially important in early phase development during API selection, and is advantageous particularly when material-sparing techniques are utilized.

  14. Improving the performance of an aerobic membrane bioreactor (MBR) treating pharmaceutical wastewater with powdered activated carbon (PAC) addition.

    PubMed

    Kaya, Yasemin; Bacaksiz, A Murat; Golebatmaz, Ugur; Vergili, Ilda; Gönder, Z Beril; Yilmaz, Gulsum

    2016-04-01

    In this study, the effects of organic loading rate (OLR) and the addition of powdered activated carbon (PAC) on the performance and membrane fouling of MBR were conducted to treat real pharmaceutical process wastewater. Over 145 days of operation, the MBR system was operated at OLRs ranging from 1 to 2 kg COD m(-3) day(-1) without sludge wasting. The addition of PAC provided an improvement in the flux, despite an increase in the OLR:PAC ratio. The results demonstrated that the hybrid PAC-MBR system maintained a reduced amount of membrane fouling and steadily increased the removal performance of etodolac. PAC addition reduced the deposition of extracellular polymeric substance and organic matter on the membrane surface and resulted an increase in COD removal even at higher OLRs with low PAC addition. Membrane fouling mechanisms were investigated using combined adsorption fouling models. Modified fouling index values and normalized mass transfer coefficient values indicated that predominant fouling mechanism was cake adsorption.

  15. Transition of care: A set of pharmaceutical interventions improves hospital discharge prescriptions from an internal medicine ward.

    PubMed

    Neeman, Marine; Dobrinas, Maria; Maurer, Sophie; Tagan, Damien; Sautebin, Annelore; Blanc, Anne-Laure; Widmer, Nicolas

    2017-03-01

    Continuity of care between hospitals and community pharmacies needs to be improved to ensure medication safety. This study aimed to evaluate whether a set of pharmaceutical interventions to prepare hospital discharge facilitates the transition of care. This study took place in the internal medicine ward and in surrounding community pharmacies. The intervention group's patients underwent a set of pharmaceutical interventions during their hospital stay: medication reconciliation at admission, medication review, and discharge planning. The two groups were compared with regards to: number of community pharmacist interventions, time spent on discharge prescriptions, and number of treatment changes. Comparison between the groups showed a much lower (77% lower) number of community pharmacist interventions per discharge prescription in the intervention (n=54 patients) compared to the control group (n=64 patients): 6.9 versus 1.6 interventions, respectively (p<0.0001); less time working on discharge prescriptions; less interventions requiring a telephone call to a hospital physician. The number of medication changes at different steps was also significantly lower in the intervention group: 40% fewer (p<0.0001) changes between hospital admission and discharge, 66% fewer (p<0.0001) between hospital discharge and community pharmacy care, and 25% fewer (p=0.002) between community pharmacy care and care by a general practitioner. An intervention group underwent significantly fewer medication changes in subsequent steps in the transition of care after a set of interventions performed during their hospital stay. Community pharmacists had to perform fewer interventions on discharge prescriptions. Altogether, this improves continuity of care. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  16. Predictive evaluation of pharmaceutical properties of direct compression tablets containing theophylline anhydrate during storage at high humidity by near-infrared spectroscopy.

    PubMed

    Otsuka, Yuta; Yamamoto, Masahiro; Tanaka, Hideji; Otsuka, Makoto

    2015-01-01

    Theophylline anhydrate (TA) in tablet formulation is transformed into monohydrate (TH) at high humidity and the phase transformation affected dissolution behavior. Near-infrared spectroscopic (NIR) method is applied to predict the change of pharmaceutical properties of TA tablets during storage at high humidity. The tablet formulation containing TA, lactose, crystalline cellulose and magnesium stearate was compressed at 4.8 kN. Pharmaceutical properties of TA tables were measured by NIR, X-ray diffraction analysis, dissolution test and tablet hardness. TA tablet was almost 100% transformed into TH after 24 hours at RH 96%. The pharmaceutical properties of TA tablets, such as tablet hardness, 20 min dissolution amount (D20) and increase of tablet weight (TW), changed with the degree of hydration. Calibration models for TW, tablet hardness and D20 to predict the pharmaceutical properties at high-humidity conditions were developed on the basis of the NIR spectra by partial least squares regression analysis. The relationships between predicted and actual measured values for TW, tablet hardness and D20 had straight lines, respectively. From the results of NIR-chemometrics, it was confirmed that these predicted models had high accuracy to monitor the tablet properties during storage at high humidity.

  17. PICA Variants with Improved Mechanical Properties

    NASA Technical Reports Server (NTRS)

    Thornton, Jeremy; Ghandehari, Ehson M.; Fan, Wenhong; Stackpoole, Margaret; Chavez-Garcia, Jose

    2011-01-01

    Phenolic Impregnated Carbon Ablator (PICA) is a member of the family of Lightweight Ceramic Ablators (LCAs) and was developed at NASA Ames Research Center as a thermal protection system (TPS) material for the Stardust mission probe that entered the Earth s atmosphere faster than any other probe or vehicle to date. PICA, carbon fiberform base and phenolic polymer, shows excellent thermal insulative properties at heating rates from about 250 W/sq cm to 1000 W/sq cm. The density of standard PICA - 0.26 g/cu cm to 0.28 g/cu cm - can be changed by changing the concentration of the phenolic resin. By adding polymers to the phenolic resin before curing it is possible to significantly improve the mechanical properties of PICA without significantly increasing the density.

  18. Pharmaceutical solid dispersion technology: a strategy to improve dissolution of poorly water-soluble drugs.

    PubMed

    Kumar, Shobhit; Gupta, Satish K

    2013-08-01

    Oral bioavailability is the major problem when a poorly water-soluble active agent is delivered via oral route. To overcome such problems, solid dispersion systems have been demonstrated in literature to enhance the dissolution property of poorly water-soluble drugs. In the present review, the important aspects to be considered during preparation of solid dispersion systems viz., properties of polymer and preparation techniques of solid dispersion which affect the dissolution rate are discussed. Formulation and evaluation techniques for solid dispersions have been described. The final section of article highlights the recent patents and studies related to solid dispersion systems.

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

    PubMed

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

    2014-09-10

    This study investigates the extent to which single-crystal mechanical properties of selected active ingredients (famotidine, nifedipine, olanzapine, piroxicam) influence their bulk compressibility and compactibility. Nanomechanical attributes of oriented single crystals were determined with instrumented nanoindentation, and bulk deformational properties were assessed with the Walker and Heckel models as well as the elastic relaxation index. Good correlations were established between bulk and single-crystal plasticity parameters: the Walker coefficient and indentation hardness. The Walker model showed more practical value for evaluating bulk deformational properties of the APIs investigated because their properties differed more distinctly compared to the Heckel model. In addition, it was possible to predict the elastic properties of the materials investigated at the bulk level because a correlation between the elastic relaxation index and compliance was established. The value of using indentation hardness for crystalline APIs was also confirmed because their compactibility at the bulk level was able to be predicted. Mechanically interlocked structures were characteristic of most polymorphic forms investigated, resulting in single crystals having isotropic mechanical properties. It was revealed that in such cases good correlations between single and bulk mechanical properties can be expected. The results imply that innate crystal deformational properties define their compressibility and compactibility properties to a great extent. Copyright © 2014. Published by Elsevier B.V.

  20. Lorentz contact resonance spectroscopy for nanoscale characterisation of structural and mechanical properties of biological, dental and pharmaceutical materials.

    PubMed

    Khanal, Dipesh; Dillon, Eoghan; Hau, Herman; Fu, Dong; Ramzan, Iqbal; Chrzanowski, Wojciech

    2015-12-01

    Scanning probe microscopy has been widely used to obtain topographical information and to quantify nanostructural properties of different materials. Qualitative and quantitative imaging is of particular interest to study material-material interactions and map surface properties on a nanoscale (i.e. stiffness and viscoelastic properties). These data are essential for the development of new biomedical materials. Currently, there are limited options to map viscoelastic properties of materials at nanoscale and at high resolutions. Lorentz contact resonance (LCR) is an emerging technique, which allows mapping viscoelasticity of samples with stiffness ranging from a few hundred Pa up to several GPa. Here we demonstrate the applicability of LCR to probe and map the viscoelasticity and stiffness of 'soft' (biological sample: cell treated with nanodiamond), 'medium hard' (pharmaceutical sample: pMDI canister) and 'hard' (human teeth enamel) specimens. The results allowed the identification of nanodiamond on the cells and the qualitative assessment of its distribution based on its nanomechanical properties. It also enabled mapping of the mechanical properties of the cell to demonstrate variability of these characteristics in a single cell. Qualitative imaging of an enamel sample demonstrated variations of stiffness across the specimen and precise identification of enamel prisms (higher stiffness) and enamel interrods (lower stiffness). Similarly, mapping of the pMDI canister wall showed that drug particles were adsorbed to the wall. These particles showed differences in stiffness at nanoscale, which suggested variations in surface composition-multiphasic material. LCR technique emerges as a valuable tool for probing viscoelasticity of samples of varying stiffness's.

  1. Ion Implantatiion Improves Bearing-Surface Properties

    NASA Technical Reports Server (NTRS)

    Misra, M. S.; Kustas, F. M.

    1985-01-01

    Selected ions fired into rolling elements to increase resistance to rolling-contact fatique. Mask strips confine implantation to 105 degree arcs on cylindrical surfaces. Specimens kept cool by copper block through which refrigerant is circulated. Implanting nitrogen or titanium ions in metals improves resistance to fatigue, corrosion, and wear without altering bulk properties. Unlike such surface treatments as conventional nitriding, conventional carburizing, and coating, ion implantation is low-temperature process, requires no finishing operations, and produces highly-alloyed surface layer. Implantation process also helps conserve such strategic materials as chromium and cobalt by using them only where needed.

  2. First report about pharmaceutical properties and phytochemicals analysis of Rosa abyssinica R. Br. ex Lindl. (Rosaceae).

    PubMed

    Moustafa, Mahmoud Fawzy; Alrumman, Sulaiman Abdullah

    2015-11-01

    In vitro antimicrobial efficacy of seven solvent extracts from leaves and hips of Saudi Arabian weed Rosa abyssinica against a variety of human pathogenic bacteria and Candida species have been evaluated using well diffusion methods. Phytochemicals present in the leaves and hips of Rosa abyssinica has been characterized using Gas Chromatogram Mass spectrometry analysis. The extracts comparative efficacy against tested microbes gained from the fresh and dry leaves exhibited more prominent activity than fresh and dry hips. The methanol, chloroform, petroleum ether, acetone and diethyl ether extracts have a greater lethal effect on pathogenic microbes than hot water extracts, while cold-water extracts showed no activity. Twenty-four phytochemicals have been characterized from ethanol extract of the leaves of Rosa abyssinica and fifteen from hips by GC-MS. The major compounds detected in the leaves were squalene (38.21%), ethane, 1,1-diethoxy- (9.65%), β-D-glucopyranose, 1,6-anhydro- (8.55%), furfural (5.50%) and 2-furancarboxaldehyde 5-(hydroxymethyl)- (5.19%). The major compounds in the hips were 2-furancarboxaldehyde 5-(hydroxymethyl)- (51.27%), β-D-glucopyranose, 1,6-anhydro- (8.18%), 4H-pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl- (7.42%), 2,5-furandione, dihydro-3-methylene- (6.79%) and furfural (5.99%). Current findings indicate that extract from leaves and hips of Rosa abyssinica and the bioactive components present could be used as pharmaceutical agents.

  3. Modeling of the solution interaction properties of plastic materials used in pharmaceutical product container systems.

    PubMed

    Jenke, Dennis; Couch, Tom; Gillum, Amy; Sadain, Salma

    2009-01-01

    Material/water equilibrium binding constants (Eb) were determined for 14 organic solutes and 17 plastic raw materials that could be used in pharmaceutical product container systems. Correlations between the measured binding constants and the organic solute's octanol/water and hexane/water partition coefficients were obtained. In general, while the materials examined exhibited a wide range of binding characteristics, the tested materials by and large fell within two broad classes: (1) those that were octanol-like in their binding characteristics, and (2) those that were hexane-like. Materials of the same class (e.g., polypropylenes) generally had binding models that were very similar. Rank ordering of the materials in terms of their magnitude of drug binding (least binding to most binding) was as follows: polypropylene < polyethylene < polyamide < styrene-ethylene-butylene-styrene < copolyester ether elastomer approximately equal to amine-terminated poly fatty acid amide polymer. The utilization of the developed models to estimate drug loss via sorption by the container is discussed.

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

    PubMed

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

    2012-07-01

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

  5. Framework for continuous quality improvement in the provision of pharmaceutical care.

    PubMed

    Gitlow, H S; Melby, M J

    1991-09-01

    Implementation of the continuous quality improvement (CQI) process by health-care organizations is described. CQI involves a chain of events: Improvement in quality leads to decreased costs because of less rework, fewer mistakes, fewer delays, and better use of people and materials; productivity improves; better quality and lower price facilitate capturing the market, staying in business, and providing more jobs. The implementation of CQI within an organization involves the development, standardization, and deployment of standard methods and the use of daily management, cross-functional management, policy management, departmental management, and quality control circles to maintain, improve, or innovate standard methods. An organization's standard methods, key indicators (indicators for measuring performance of the organization's key functions), and standards emanate from its vision and mission statements and midterm and short-term strategic plans. In a quality control audit, an agreed-upon method, as monitored through a key indicator, is used to measure a result against an established standard; when a problem is detected, a quality control diagnosis is conducted and the method is changed if necessary. Use of this process requires the creation of standard methods for all important aspects of the organization's services, including operations, clinical services, and training of personnel. Health-care managers can use the principles of CQI in assessing the quality of care provided.

  6. The dilemma of intellectual property rights for pharmaceuticals: the tension between ensuring access of the poor to medicines and committing to international agreements.

    PubMed

    Cohen, Jillian Clare; Illingworth, Patricia

    2003-05-01

    In this paper, we provide an overview of how the outcomes of the Uruguay Round affected the application of pharmaceutical intellectual property rights globally. Second, we explain how specific pharmaceutical policy tools can help developing states mitigate the worst effects of the TRIPS Agreement. Third, we put forward solutions that could be implemented by the World Bank to help overcome the divide between creating private incentives for research and development of innovative medicines and ensuring access of the poor to medicine. Fourth, we evaluate these solutions on the basis of utilitarian considerations and urge that equitable pricing is morally preferable to the other solutions.

  7. Prediction of the Carcinogenic Potential of Human Pharmaceuticals Using Repeated Dose Toxicity Data and Their Pharmacological Properties

    PubMed Central

    van der Laan, Jan Willem; Buitenhuis, Wenny H. W.; Wagenaar, Laura; Soffers, Ans E. M. F.; van Someren, Eugene P.; Krul, Cyrille A. M.; Woutersen, Ruud A.

    2016-01-01

    In an exercise designed to reduce animal use, we analyzed the results of rat subchronic toxicity studies from 289 pharmaceutical compounds with the aim to predict the tumor outcome of carcinogenicity studies in this species. The results were obtained from the assessment reports available at the Medicines Evaluation Board of the Netherlands for 289 pharmaceutical compounds that had been shown to be non-genotoxic. One hundred forty-three of the 239 compounds not inducing putative preneoplastic lesions in the subchronic study did not induce tumors in the carcinogenicity study [true negatives (TNs)], whereas 96 compounds were categorized as false negatives (FNs) because tumors were observed in the carcinogenicity study. Of the remaining 50 compounds, 31 showed preneoplastic lesions in the subchronic study and tumors in the carcinogenicity study [true positives (TPs)], and 19 only showed preneoplastic lesions in subchronic studies but no tumors in the carcinogenicity study [false positives (FPs)]. In addition, we then re-assessed the prediction of the tumor outcome by integrating the pharmacological properties of these compounds. These pharmacological properties were evaluated with respect to the presence or absence of a direct or indirect proliferative action. We found support for the absence of cellular proliferation for 204 compounds (TN). For 67 compounds, the presence of cellular hyperplasia as evidence for proliferative action could be found (TP). Therefore, this approach resulted in an ability to predict non-carcinogens at a success rate of 92% and the ability to detect carcinogens at 98%. The combined evaluation of pharmacological and histopathological endpoints eventually led to only 18 unknown outcomes (17 categorized as FN and 1 as FP), thereby enhancing both the negative and positive predictivity of an evaluation based upon histopathological evaluation only. The data show the added value of a consideration of the pharmacological properties of compounds in

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

    PubMed

    Awa, Kimie; Shinzawa, Hideyuki; Ozaki, Yukihiro

    2015-08-01

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

  9. [Evolution of the international intellectual property rights system: patent protection for the pharmaceutical industry and access to medicines].

    PubMed

    Chaves, Gabriela Costa; Oliveira, Maria Auxiliadora; Hasenclever, Lia; de Melo, Luiz Martins

    2007-02-01

    This article discusses the evolution of the international intellectual property rights system in three phases and the implications for public health, especially for the implementation of policies for access to medicines. During the first phase, characterized by the Paris and Berne Convention, signatory countries defined which technological fields should be protected (or not). Under the second phase, with the enforcement of the WTO TRIPS Agreement, countries are obliged to grant patent protection for all technological fields, including for the pharmaceutical industry. Within their national legislations, countries also have the opportunity to implement access to TRIPS flexibilities for medicines. With the third phase, characterized by the negotiation and signing of bilateral and regional free trade agreements, countries will have to implement TRIPS-plus provisions which may have negative implications for the TRIPS flexibilities as well as for policies for access to medicines. The authors conclude that the currently proposed international intellectual property rights system favors patent-holder rights and that a balance is needed between patent holders' and health rights.

  10. Cocrystallization and amorphization induced by drug-excipient interaction improves the physical properties of acyclovir.

    PubMed

    Masuda, Takaaki; Yoshihashi, Yasuo; Yonemochi, Etsuo; Fujii, Kotaro; Uekusa, Hidehiro; Terada, Katsuhide

    2012-01-17

    Although acyclovir is one of the most important antiviral drugs used today, there are several problems with its physical properties. The aim of this study is to prepare cocrystals or amorphous complex of acyclovir using drug-excipient interactions to improve the physical properties of the drug, especially its dissolution rate and transdermal absorption. Screening for formation of cocrystals and the presence of amorphous acyclovir was conducted with various pharmaceutical excipinents, with the use of the solution-crystallization method and liquid-assisted cogrinding. The potential cocrystalline phase and the amorphized complex were characterized by PXRD, TG/DTA, IR, DSC and HPLC techniques. The screening indicated that acyclovir formed novel cocrystals with tartaric acid and was amorphized with citric acid. The acyclovir-tartaric acid cocrystal (ACV-TA cocrystal) structure was determined from synchrotron X-ray powder diffraction data. T(g) of the amorphous acyclovir-citric acid compound (ACV-CA amorphous) was determined by DSC. The initial dissolution rate of the ACV-TA cocrystals was considerably faster than that of anhydrous acyclovir. In vitro skin permeation of ACV-CA amorphous from polyethylene glycol (PEG) ointment was remarkably higher than that of the crystalline acyclovir. We successfully improved the physical properties of acyclovir by the cocrystallization and amorphization techniques, using pharmaceutical excipients.

  11. Comprehensive summary--Predict-IV: A systems toxicology approach to improve pharmaceutical drug safety testing.

    PubMed

    Mueller, Stefan O; Dekant, Wolfgang; Jennings, Paul; Testai, Emanuela; Bois, Frederic

    2015-12-25

    This special issue of Toxicology in Vitro is dedicated to disseminating the results of the EU-funded collaborative project "Profiling the toxicity of new drugs: a non animal-based approach integrating toxicodynamics and biokinetics" (Predict-IV; Grant 202222). The project's overall aim was to develop strategies to improve the assessment of drug safety in the early stage of development and late discovery phase, by an intelligent combination of non animal-based test systems, cell biology, mechanistic toxicology and in silico modeling, in a rapid and cost effective manner. This overview introduces the scope and overall achievements of Predict-IV. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Intellectual Property and the Pharmaceutical Scientist: A View from the Other Side.

    ERIC Educational Resources Information Center

    Palmieri, Anthony III

    1989-01-01

    Issues in the debate over intellectual property are discussed by a former pharmacy professor who entered the pharmacy industry. Issues include patents and patent barriers, patent coverage, the academic misconception that industry has unlimited resources, and attitudes that defeat collaboration between industry and academe. (MSE)

  13. Abuse-deterrent formulations: transitioning the pharmaceutical market to improve public health and safety

    PubMed Central

    Worthy, Stacey L.; Barnes, Michael C.; Tarbell, Benjamin

    2015-01-01

    This article evaluates abuse-deterrent formulations (ADFs) as a method to reduce prescription drug abuse while ensuring access to vital medications for individuals with legitimate need; assesses the pros and cons of ADFs and the current state of ADF adoption in the market; and develops policy recommendations to transition the market to ADFs. Although abuse-deterrent technology is still in its nascent stages, ADFs have been proven to reduce prescription drug abuse and its consequences, and even an incremental reduction in abuse can have a significant impact on the nation by reducing the costly social, physical, mental, and public health problems resulting from abuse. Federal ADF policy does not reflect the urgency of the prescription drug abuse epidemic and does not go far enough toward changing the status quo. Policies must be implemented to encourage innovation and a market shift toward ADFs by ensuring any generic medication that references a branded ADF demonstrates that it does not have abuse-deterrent properties inferior to the branded ADF product. Policies must also require federal prescription drug benefit plans to cover ADFs to ensure consumers have access to such medications. PMID:25922655

  14. Improvement in Flavonoids and Phenolic Acids Production and Pharmaceutical Quality of Sweet Basil (Ocimum basilicum L.) by Ultraviolet-B Irradiation.

    PubMed

    Ghasemzadeh, Ali; Ashkani, Sadegh; Baghdadi, Ali; Pazoki, Alireza; Jaafar, Hawa Z E; Rahmat, Asmah

    2016-09-09

    -B treated leaves presented the highest DPPH activity and antiproliferative activity with a half-maximal inhibitory concentration (IC50) value of 56.0 and 40.8 µg/mL, respectively, over that of the control plants (78.0 and 58.2 µg/mL, respectively). These observations suggest that post-harvest irradiation with UV-B can be considered a promising technique to improve the healthy-nutritional and pharmaceutical properties of sweet basil leaves.

  15. Photorefractive polymer device with improved sensitizing property

    NASA Astrophysics Data System (ADS)

    Nguyen, Tam V.; Giang, Ha N.; Kinashi, K.; Sakai, W.; Tsutsumi, N.

    2015-09-01

    photorefractive (PR) application because of a fast hole mobility. In most of the previous studies, phenyl-C61-butyric acid methyl ester (PCBM) was used as a sensitizer. In this study, a high-performance charge generator perylene bisimide (PBI) is synthesized and added into the composite. PBI derivatives owning a large core of π-conjugated rings provide a high electron affinity and high charge carrier mobility. These features are promising to improve PR properties. To the best of our knowledge, it is the first time for using a combine of PCBM and PBI to improve the PR performance of PDAA-based composites. 2-(4-(azepan-1-yl)benzylidene)malononitrile (7-DCST) is used as a nonlinear optical chromophore. (4-diphenylamino)phenyl)methanol (TPAOH) is used as a plasticizer. Consequently, a diffraction efficiency of 76 % and a response time of 8 ms were obtained with 532 nm green laser under the electric field of 55 V μm-1. As a conclusion, the introduction of PBI is a promising approach for the photorefractive composite owning the video rate response.

  16. Mechanics of pharmaceutical pellets - Constitutive properties, deformation and breakage behavior(∗).

    PubMed

    Russell, Alexander; Šibanc, Rok; Dreu, Rok; Müller, Peter

    2017-09-15

    To ensure robust manufacturing of unit-based oral solid dosage forms with minimal structural imperfections and high mechanical reliability across subsequent processing unit operations (for e.g. withstanding mechanical stresses during coating, optional axial compression, handling, packaging, storage and transport conditions), process design should include consideration of precise limits of accurate micro, macro and bulk properties of the constituent pellets. This communication presents a comprehensive intricate database of micro-mechanical properties' and breakage probability distribution functions of pellets, illustrating the stiffening and strengthening effects of coatings and the softening and weakening effects of structural moisture. Further insights such as the (contact) history-dependent softening during decompression, strain hardening upon repeated stressing, strength recovery by drying and the fragmentation pattern by cracking are also presented. The contents herein are based on conveniently performable lab-scale diametrical compression measurements on model microcrystalline cellulose pellets - demonstrating feasibility of the approach and validity of the contribution. Copyright © 2017. Published by Elsevier Inc.

  17. Implementing Intellectual Property of Pharmaceuticals in Middle-Income Countries: A Case Study of Patent Regulation in Brazil.

    PubMed

    da Fonseca, Elize Massard; Bastos, Francisco Inácio

    2016-06-01

    The protection of pharmaceutical intellectual property (IP) rights is one of the most controversial debates in contemporary public health as countries have to balance incentives for drug development with the necessity of providing life-saving drugs. Compliance with IP protections is mandatory for members of the World Trade Organization (WTO). However, because of the costs associated with IP implementation we should expect late and/or poor implementation in middle-income countries. Surprisingly, this was not the case in Brazil. The country not only just fully implemented the WTO's requirement but declined the grace period granted for countries to adapt and included extra IP protections, going against a coalition of local industrialists and activists. Notwithstanding, as the consequences of IP regulations unfolds, Brazil also promoted new alliances that tailored and adjusted the regulations toward public health. We demonstrate that arguments of foreign pressure and lobbying are exaggerated and call attention to domestic shifts, long-term processes of regulatory decision, and political dynamics happening at the local level. By analyzing the case of Brazil, we provide a nuanced contribution to the discussion of IP implementation in middle-income countries and call attention to new models of government-society interactions in regulatory policy.

  18. The properties and the use of substituted benzofuroxans in pharmaceutical and medicinal chemistry: a comprehensive review.

    PubMed

    Jovené, Cyril; Chugunova, Elena A; Goumont, Régis

    2013-06-01

    Since the synthesis of 4,6-dinitrobenzofuroxan in 1899 by Drost, benzofuroxans have attracted particular attention. This peculiar series of compounds exhibit a broad spectrum of biological activity including antibacterial, antifungal, antileukemic, acaricide and immunodepressive properties. These works embrace a period of more than 50 years since the pioneering paper of Gosh and Whitehouse and papers in this major field of the heterocyclic chemistry are still published in 2013. The review has been built in two independent parts. The first one is directly dedicated to the structure of substituted benzofuroxans and will show many medicinal applications of these compounds such as nitric oxide-releasing abilities, induction of oxidative stress, potent anti-cancer agents, anti-chagas agent, target for antiamoebic agent, Ca2+ channel blockers or cytotoxic, mutagenic and genotoxic agent… The second part of this review will be in close connection with the use of benzofuroxans as synthetic precursors in the preparation of new biological compounds such as quinoxaline dioxide, benzimidazole and phenazine derivatives. The interaction of substituted benzofuroxans with electron rich heterocycles or carbanions is the key step in the synthesis of these new biological active compounds. These derivatives can be used as cytotoxic drugs, antimycobacterial agent and display anti-malarial, antileishmanial and antituberculosis activity. The nature of the substituent linked to the carbocyclic ring of benzofuroxan is of primary importance to understand the medicinal properties of this family of compounds. For example, when benzofuroxans are substituted by electron-releasing substituents, the chemical reactivity is transferred from the carbocyclic ring to the furoxan ring.

  19. Pharmaceutical Psychology.

    ERIC Educational Resources Information Center

    Dolinsky, Donna

    1979-01-01

    Defines areas that could comprise pharmaceutical psychology. The discussion includes a review of literature, outline of areas in pharmacy in which psychologists could become involved, description of a project involving the application of psychology to pharmacy, and analysis of the concept of pharmaceutical psychology. A 99-item bibliography is…

  20. Preparation of a novel positively charged nanofiltration composite membrane incorporated with silver nanoparticles for pharmaceuticals and personal care product rejection and antibacterial properties.

    PubMed

    Huang, Zhong-Hua; Yin, Yan-Na; Aikebaier, Gu-li-mi-la; Zhang, Yan

    2016-01-01

    A novel positively charged N-[(2-hydroxy-3-trimethylammonium)propyl] chloride chitosan (HTCC)-Ag/polyethersulfone (PES) composite nanofiltration membrane was easily prepared by coating the active layer, HTCC, onto PES as the support through epichlorohydrin as the cross-linking reagent and nano-Ag particles as the introduced inorganic components. Scanning election microscopy, X-ray photoelectron spectroscopy, atomic force microscopy, and X-ray diffraction were employed to characterize the morphology of the resultant membranes, of which the molecular weight cut-off was about 941 Da. At 25 °C, the pure water permeability is 16.27 L/h·m(2)·MPa. Our results showed that the rejection of pharmaceuticals and personal care products (PPCPs) followed the sequence: atenolol > carbamazepine > ibuprofen, confirming that the membranes were positively charged. The antibacterial properties of the membranes were compared to elucidate the existence of Ag nanoparticles which help to improve antibacterial activity against Gram-negative Escherichia coli (DH5α, Rosetta) and Gram-positive Bacillus subtilis. The inhibition zone diameters of HTCC-Ag/PES membranes towards E. coli DH5α, E. coli Rosetta and Bacillus subtilis were 17.77, 16.18, and 15.44 mm, respectively. It was found that HTCC-Ag/PES membrane has a better antibacterial activity against E. coli than against Bacillus subtilis, especially for E. coli DH5α.

  1. Modification of Propellant Binder Network for Improvement of Mechanical Properties

    DTIC Science & Technology

    1984-12-01

    Propellant November 1982 to Binder Network for 71 November 1984 Improvement of Mechanical Properties December 1984 Author: Polymer Research Institute 4...determine the possibility of improving mechanical properties of energetic propellants via bimodal and/or multimodal * binder network formation. * 3.0... mechanical properties . 4.5 Effect of Temperature Improvements in stress/strain properties of all the polymer/PEG 8000 bimodal systems tend to be griater at 25

  2. Tuning mechanical properties of pharmaceutical crystals with multicomponent crystals: voriconazole as a case study.

    PubMed

    Sanphui, Palash; Mishra, Manish Kumar; Ramamurty, Upadrasta; Desiraju, Gautam R

    2015-03-02

    Crystals of voriconazole, an antifungal drug, are soft in nature, and this is disadvantageous during compaction studies where pressure is applied on the solid. Crystal engineering is used to make cocrystals and salts with modified mechanical properties (e.g., hardness). Cocrystals with biologically safe coformers such as fumaric acid, 4-hydroxybenzoic acid, and 4-aminobenzoic acid and salts with hydrochloric acid and oxalic acid are prepared through solvent assisted grinding. The presence (salt) or absence (cocrystal) of proton transfer in these multicomponent crystals is unambiguously confirmed with single crystal X-ray diffraction. All the cocrystals have 1:1 stoichiometry, whereas salts exhibit variable stoichiometries such as HCl salt (1:2) and oxalate salts (1:1.5 and 1:1). The nanoindentation technique was applied on single crystals of the salts and cocrystals. The salts exhibit better hardness than the drug and cocrystals in the order salts ≫ drug > cocrystals. The molecular origin of this mechanical modulation is explained on the basis of slip planes in the crystal structure and relative orientations of the molecules with respect to the nanoindentation direction. The hydrochloride salt is the hardest solid in this family. This may be useful for tableting of the drug during formulation and in drug development.

  3. Characterisation of reversed-phase liquid chromatography stationary phases for the analysis of basic pharmaceuticals: eluent properties and comparison of empirical test methods.

    PubMed

    Vervoort, R J; Ruyter, E; Debets, A J; Claessens, H A; Cramers, C A; de Jong, G J

    2001-10-05

    The reversed-phase liquid chromatographic analysis of basic pharmaceuticals can be problematic. Both the properties of the eluent and the stationary phase can influence the chromatographic performance. Therefore selection of suitable experimental conditions for the analysis of basic compounds can be difficult. This paper shows that the organic modifier and the nature of the buffer influence the eluent properties. Moreover, the nature and amount of modifier also influence the basicity of the analytes. Investigations showed that the nature of the buffer can have a significant influence on retention and peak shape of basic compounds. Test procedures using basic analytes as test probes provided relevant information with respect to selecting columns to analyse basic pharmaceutical compounds. Test procedures using compounds like aniline, phenol and benzene were found to be less suitable.

  4. Mapping the solid-state properties of crystalline lysozyme during pharmaceutical unit-operations.

    PubMed

    Mohammad, Mohammad Amin; Grimsey, Ian M; Forbes, Robert T

    2015-10-10

    Bulk crystallisation of protein therapeutic molecules towards their controlled drug delivery is of interest to the biopharmaceutical industry. The complexity of biotherapeutic molecules is likely to lead to complex material properties of crystals in the solid state and to complex transitions. This complexity is explored using batch crystallised lysozyme as a model. The effects of drying and milling on the solid-state transformations of lysozyme crystals were monitored using differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), FT-Raman, and enzymatic assay. XRPD was used to characterise crystallinity and these data supported those of crystalline lysozyme which gave a distinctive DSC thermogram. The apparent denaturation temperature (Tm) of the amorphous lysozyme was ∼201 °C, while the Tm of the crystalline form was ∼187 °C. Raman spectra supported a more α-helix rich structure of crystalline lysozyme. This structure is consistent with reduced cooperative unit sizes compared to the amorphous lysozyme and is consistent with a reduction in the Tm of the crystalline form. Evidence was obtained that milling also induced denaturation in the solid-state, with the denatured lysozyme showing no thermal transition. The denaturation of the crystalline lysozyme occurred mainly through its amorphous form. Interestingly, the mechanical denaturation of lysozyme did not affect its biological activity on dissolution. Lysozyme crystals on drying did not become amorphous, while milling-time played a crucial role in the crystalline-amorphous-denatured transformations of lysozyme crystals. DSC is shown to be a key tool to monitor quantitatively these transformations. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Phosphorus recovery: minimization of amount of pharmaceuticals and improvement of purity in struvite recovered from hydrolysed urine.

    PubMed

    Kemacheevakul, Patiya; Chuangchote, Surawut; Otani, Sosuke; Matsuda, Tomonari; Shimizu, Yoshihisa

    2014-01-01

    Struvite (MgNH₄PO₄·6H₂O) is normally used as a fertilizer in agriculture, where struvite crystallization from hydrolysed human urine is a simple and reliable method for phosphorus (P) recovery. Human urine, however, contains high amount of pharmaceuticals, which may cause health risk for applications. This research investigates the possibility of decreasing the amount of pharmaceuticals (tetracycline, demeclocycline and oxytetracycline) in struvite crystals recovered from synthetic and human urines by focusing on storage time, and of increasing the quality of struvite production. Urines were stored for different times up to 15 days prior to recovery of phosphorus by two steps, spontaneous precipitation and struvite crystallization. The morphology of spontaneous precipitates and struvite crystals was observed. Spontaneous precipitation removed around 17-24% of phosphate from synthetic and human urines, while pharmaceuticals were removed with a quite high amount at a short storage time (5 days) and this amount decreased with increasing the storage time (10 and 15 days). Urines with>70% remaining phosphates were re-used for struvite crystallization by adding extra magnesium. It was found that maximum P-recovery efficiency could be achieved from struvite crystallization at 5-day storage time, 70% and 68% of remaining P in the separated supernatant from synthetic and human urines, respectively, whereas less than 1% pharmaceuticals remained in the struvite crystals from both samples. This indicates that the procedure in this work is a good method for phosphorus recovery, in which high struvite purity (>99%) is obtained with low amount of pharmaceuticals.

  6. Synthesis and structure-activity relationships of selective norepinephrine reuptake inhibitors (sNRI) with improved pharmaceutical characteristics.

    PubMed

    Pontillo, Joseph; Wu, Dongpei; Ching, Brett; Hudson, Sarah; Genicot, Marc J; Gao, Yinghong; Ewing, Todd; Fleck, Beth A; Gogas, Kathleen; Aparicio, Anna; Wang, Hua; Wen, Jenny; Wade, Warren S

    2008-12-01

    The design synthesis and SAR of a series of chiral ring-constrained norepinephrine reuptake inhibitors with improved physicochemical properties is described. Typical compounds are potent (IC(50)s<10 nM), selective against the other monoamine transporters, weak CYP2D6 inhibitors (IC(50)s>1 microM) and stable to oxidation by human liver microsomes. In addition, the compounds exhibit a favorable polarity profile.

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

    PubMed

    Arima, Hidetoshi; Motoyama, Keiichi; Higashi, Taishi

    2017-01-01

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

  8. Systematic screening of common wastewater-marking pharmaceuticals in urban aquatic environments: implications for environmental risk control.

    PubMed

    Zhou, Haidong; Zhang, Qingjun; Wang, Xuelian; Zhang, Qianqian; Ma, Lixin; Zhan, Yong

    2014-01-01

    In this report, we refer to pharmaceuticals that are widespread in the urban aquatic environment and that mainly originate from wastewater treatment plants or non-point source sewage as "wastewater-marking pharmaceuticals" (WWMPs). To some extent, they reflect the condition or trend of water contamination and also contribute to aquatic environmental risk assessment. The method reported here for screening typical WWMPs was proposed based on academic concerns about them and their concentrations present in the urban aquatic environment, as well as their properties of accumulation, persistence, eco-toxicity and related environmental risks caused by them. The screening system consisted of an initial screening system and a further screening system. In the former, pharmaceuticals were categorised into different evaluation levels, and in the latter, each pharmaceutical was given a normalised final evaluation score, which was the sum of every score for its properties of accumulation, persistence, eco-toxicity and environmental risk in the aquatic environment. The system was applied to 126 pharmaceuticals frequently detected in the aquatic environment. In the initial screening procedure, five pharmaceuticals were classified into the "high" category, 16 pharmaceuticals into the "medium" category, 15 pharmaceuticals into the "low" category and 90 pharmaceuticals into the "very low" category. Subsequently, further screening were conducted on 36 pharmaceuticals considered as being of "high", "medium" and "low" categories in the former system. We identified 7 pharmaceuticals with final evaluation scores of 1-10, 10 pharmaceuticals with scores of 11-15, 15 pharmaceuticals with scores from 16 to 20 and 4 pharmaceuticals with scores above 21. The results showed that this screening system could contribute to the effective selection of target WWMPs, which would be important for spatial-temporal dynamics, transference and pollution control of pharmaceuticals in the urban aquatic

  9. Multi-walled carbon nanotubes with selected properties for dynamic filtration of pharmaceuticals and personal care products.

    PubMed

    Wang, Yifei; Ma, Jing; Zhu, Jiaxin; Ye, Ning; Zhang, Xiaolei; Huang, Haiou

    2016-04-01

    In this study, multi-walled carbon nanotubes (MWCNT) with selected properties, including pristine MWCNT, hydroxylated MWCNT (H-MWCNT), thin-walled MWCNT with large inner diameter (L-MWCNT), aminated MWCNT, and high-purity MWCNT were investigated for dynamic removal of eight pharmaceuticals and personal care products (PPCP). The removal ratios of different PPCP by the pristine MWCNT followed a decreasing order of triclosan (0.93) > prometryn (0.71) > 4-acetylamino-antipyrine (0.67) > carbendazim (0.65) > caffeine (0.42) > ibuprofen (0.34) > acetaminophen (0.29) at 100 min of filtration. Similar or even higher PPCP removals were obtained for all PPCP as the influent concentration decreased, suggesting potential consistent PPCP removals at environmental PPCP concentrations. The removal ratio of acetaminophen was increased to 0.74 by using H-MWCNT. SRFA (Suwannee River fulvic acid) suppressed PPCP adsorption to MWCNT, to greater extents with increasing SRFA concentrations. The L-MWCNT, despite a large inner diameter of 52 ± 3 nm, did not provide better resistance to the competitive adsorption of SRFA than MWCNT with a small inner diameter of 10 ± 2 nm. Future research will be conducted to minimize the effect of SRFA and facilitate application of MWCNT to the treatment of PPCP-contaminated water. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Characterization and Quality Control of Pharmaceutical Cocrystals.

    PubMed

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

    2016-10-01

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

  11. Improving mechanical properties of desloratadine via multicomponent crystal formation.

    PubMed

    Ainurofiq, Ahmad; Mauludin, Rachmat; Mudhakir, Diky; Umeda, Daiki; Soewandhi, Sundani Nurono; Putra, Okky Dwichandra; Yonemochi, Etsuo

    2017-09-27

    We report the first multicomponent crystal of desloratadine, an important anti-histamine drug, with a pharmaceutically acceptable coformer of benzoic acid. The single crystal structure analysis revealed that this novel multicomponent crystal is categorized as salt due to the proton transfer from benzoic acid to the desloratadine molecule. By forming the salt multicomponent crystal, we demonstrated that the tabletability and plasticity of the multicomponent crystal was improved from the parent drug. In addition, neither capping nor lamination tendency was observed in the desloratadine-benzoic acid multicomponent crystal. The existence of a layered structure and slip planes are proposed to be associated with this improvement. The desloratadine-benzoate in this case shows an improved solubility in water and HCl 0.1N media and a better dissolution profile in water. However, the dissolution rate in HCl 0.1N media was found to be essentially indifference. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. The extended pharmaceutical enterprise.

    PubMed

    Cavalla, David

    2003-03-15

    The availability of widespread contractual services led to the birth of the virtual company in the 1990s. As the concept has matured, and the biotechnology sector diversified, interchange of intellectual property in the form of collaborative and license arrangements opens up still further the opportunities for outsourced forms of pharmaceutical R&D.

  13. Potent nonimmunosuppressive cyclophilin inhibitors with improved pharmaceutical properties and decreased transporter inhibition.

    PubMed

    Fu, Jiping; Tjandra, Meiliana; Becker, Christopher; Bednarczyk, Dallas; Capparelli, Michael; Elling, Robert; Hanna, Imad; Fujimoto, Roger; Furegati, Markus; Karur, Subramanian; Kasprzyk, Theresa; Knapp, Mark; Leung, Kwan; Li, Xiaolin; Lu, Peichao; Mergo, Wosenu; Miault, Charlotte; Ng, Simon; Parker, David; Peng, Yunshan; Roggo, Silvio; Rivkin, Alexey; Simmons, Robert L; Wang, Michael; Wiedmann, Brigitte; Weiss, Andrew H; Xiao, Linda; Xie, Lili; Xu, Wenjian; Yifru, Aregahegn; Yang, Shengtian; Zhou, Bo; Sweeney, Zachary K

    2014-10-23

    Nonimmunosuppressive cyclophilin inhibitors have demonstrated efficacy for the treatment of hepatitis C infection (HCV). However, alisporivir, cyclosporin A, and most other cyclosporins are potent inhibitors of OATP1B1, MRP2, MDR1, and other important drug transporters. Reduction of the side chain hydrophobicity of the P4 residue preserves cyclophilin binding and antiviral potency while decreasing transporter inhibition. Representative inhibitor 33 (NIM258) is a less potent transporter inhibitor relative to previously described cyclosporins, retains anti-HCV activity in cell culture, and has an acceptable pharmacokinetic profile in rats and dogs. An X-ray structure of 33 bound to rat cyclophilin D is reported.

  14. Some ozone advanced oxidation processes to improve the biological removal of selected pharmaceutical contaminants from urban wastewater.

    PubMed

    Espejo, Azahara; Aguinaco, Almudena; Amat, Ana M; Beltrán, Fernando J

    2014-01-01

    Removal of nine pharmaceutical compounds--acetaminophen (AAF), antipyrine (ANT), caffeine (CAF), carbamazepine (CRB), diclofenac (DCF), hydrochlorothiazide (HCT), ketorolac (KET), metoprolol (MET) and sulfamethoxazole (SMX)-spiked in a primary sedimentation effluent of a municipal wastewater has been studied with sequential aerobic biological and ozone advanced oxidation systems. Combinations of ozone, UVA black light and Fe(III) or Fe3O4 constituted the chemical systems. During the biological treatment (hydraulic residence time, HRT = 24 h), only AAF and CAF were completely eliminated, MET, SMX and HCT reached partial removal rates and the rest of compounds were completely refractory. With any ozone advanced oxidation process applied, the remaining pharmaceuticals disappear in less than 10 min. Fe3O4 or Fe(III) photocatalytic ozonation leads to 35% mineralization compared to 13% reached during ozonation alone after about 30-min reaction. Also, biodegradability of the treated wastewater increased 50% in the biological process plus another 150% after the ozonation processes. Both untreated and treated wastewater was non-toxic for Daphnia magna (D. magna) except when Fe(III) was used in photocatalytic ozonation. In this case, toxicity was likely due to the ferryoxalate formed in the process. Kinetic information on ozone processes reveals that pharmaceuticals at concentrations they have in urban wastewater are mainly removed through free radical oxidation.

  15. Design and quality control of a pharmaceutical formulation containing natural products with antibacterial, antifungal and antioxidant properties.

    PubMed

    Ordoñez, Adriana A L; Ordoñez, Roxana M; Zampini, Iris C; Isla, María I

    2009-08-13

    The aims of the present study were to determine the antibacterial and antifungal activity as well as mutagenicity of Sechium edule fluid extract and to obtain a pharmaceutical formulation with them. The extract exhibited antimicrobial activity against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae, Serratia marcescens, Morganella morganii, Acinetobacter baumannii, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Candida spp. and Aspergillus spp. isolated from clinical samples from two hospitals of Tucuman, Argentina. Non-toxicity and mutagenicity on both Salmonella typhimurium TA98 and TA 100 strains until 100 microg/plate were observed. A hydrogel with carbopol acrylic acid polymer containing S. edule fluid extract as antibacterial, antimycotic and antioxidant agent was obtained. Microbiological, physical and functional stability of pharmaceutical formulation conserved at room temperature for 1 year were determined. Addition of antioxidant preservatives to store the pharmaceutical formulation was not necessary. The semisolid system showed antimicrobial activity against all gram positive and gram negative bacteria and fungi assayed. The minimal inhibitory concentration (MIC) values ranged from 20 to 800 microg/mL. Its activity was compared with a pharmaceutical formulation containing commercial antibiotic and antifungal. A pseudoplastic behavior and positive thixotropy were observed. Our current finding shows an antimicrobial activity of hydrogel containing S. edule extract on a large range of gram negative and gram positive multi-resistant bacteria and fungi. This topical formulation may be used as antimycotic and as antibacterial in cutaneous infections.

  16. [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

  17. Finite element wavelets with improved quantitative properties

    NASA Astrophysics Data System (ADS)

    Nguyen, Hoang; Stevenson, Rob

    2009-08-01

    In [W. Dahmen, R. Stevenson, Element-by-element construction of wavelets satisfying stability and moment conditions, SIAM J. Numer. Anal. 37 (1) (1999) 319-352 (electronic)], finite element wavelets were constructed on polygonal domains or Lipschitz manifolds that are piecewise parametrized by mappings with constant Jacobian determinants. The wavelets could be arranged to have any desired order of cancellation properties, and they generated stable bases for the Sobolev spaces Hs for (or s<=1 on manifolds). Unfortunately, it appears that the quantitative properties of these wavelets are rather disappointing. In this paper, we modify the construction from the above-mentioned work to obtain finite element wavelets which are much better conditioned.

  18. Reservoir property grids improve with geostatistics

    SciTech Connect

    Vogt, J. . E and P Technology Dept.)

    1993-09-01

    Visualization software, reservoir simulators and many other E and P software applications need reservoir property grids as input. Using geostatistics, as compared to other gridding methods, to produce these grids leads to the best output from the software programs. For the purpose stated herein, geostatistics is simply two types of gridding methods. Mathematically, these methods are based on minimizing or duplicating certain statistical properties of the input data. One geostatical method, called kriging, is used when the highest possible point-by-point accuracy is desired. The other method, called conditional simulation, is used when one wants statistics and texture of the resulting grid to be the same as for the input data. In the following discussion, each method is explained, compared to other gridding methods, and illustrated through example applications. Proper use of geostatistical data in flow simulations, use of geostatistical data for history matching, and situations where geostatistics has no significant advantage over other methods, also will be covered.

  19. Improvement of mechanical properties of glass substrates

    NASA Astrophysics Data System (ADS)

    Karbay, Ismail Hakki Cengizhan; Budakoglu, Refika; Zayim, Esra Ozkan

    2015-12-01

    This paper aims to enhance the mechanical and optical properties of glass substrates with thin films by the sol-gel method. TiO2-SiO2 binary system and Ta2O5 were deposited on glass substrates with high transparency. Ring-on-ring flexure and scratch tests were the main mechanical characterization tests. Herein, we report that the thin films can be used to enhance the mechanical properties of the glass substrates efficiently and effectively. TiO2-SiO2 binary system shows more than two times and Ta2O5 thin films show nearly three times better ultimate strength in the ring-on-ring flexure test. Besides, Ta2O5 thin film samples show superior scratch resistance. Additionally, the finite element method was also used to check the conformity in the application of mechanical properties of composite materials. It is also worth noting that, the finite element method can be used to accurately analyze the mechanical stability of composite materials. The use of the finite element method can reduce the total number of experimental trials without losing reliability.

  20. Analyzing and improving viscoelastic properties of high density polyethylene

    NASA Astrophysics Data System (ADS)

    Ahmed, Reaj Uddin

    2011-12-01

    High Density Polyethylene (HDPE) is closely packed, less branched polyethylene having higher mechanical properties, chemical resistance, and heat resistance than Low Density Polyentylene (LDPE). Better properties and cost effectiveness make it an important raw material over LDPE in packaging industries. Stacked containers made of HDPE experience static loading and deformation strain during their storage period in a warehouse. As HDPE is a viscoelastic material, dimensional stability of stacked HDPE containers depends on time dependent properties such as creep and stress relaxation. Now, light weighting is a driving force in packaging industries, which results in lower production costs but performance of the product becomes a challenge. Proper understanding of the viscoelastic properties of HDPE, with relevant FE simulation can facilitate improved designs. This research involves understanding and improving viscoelastic properties, creep behavior, and stress relaxation of HDPE. Different approaches were carried out to meet the objectives. Organic filler CaCO3 was added to HDPE at increasing weight fractions and corresponding property changes were investigated. Annealing heat treatments were also carried out for potential property improvements. The effect of ageing was also investigated on both annealed and non annealed HDPE. The related performance of different water bottles against squeeze pressure was also characterized. Both approaches, incorporation of CaCO3 and annealing, showed improvements in the properties of HDPE over neat HDPE. This research aids finding the optimum solution for improving viscoelastic properties, stress relaxation, and creep behavior of HDPE in manufacturing.

  1. Application of feedback control and in situ milling to improve particle size and shape in the crystallization of a slow growing needle-like active pharmaceutical ingredient.

    PubMed

    Yang, Yang; Pal, Kanjakha; Koswara, Andy; Sun, Qingqing; Zhang, Yuqi; Quon, Justin; McKeown, Rahn; Goss, Charles; Nagy, Zoltan K

    2017-09-19

    Control of crystal size and shape is crucially important for crystallization process development in the pharmaceutical industries. In general crystals of large size and low aspect ratio are desired for improved downstream manufacturability. It can be extremely challenging to design crystallization processes that achieve these targets for active pharmaceutical ingredients (APIs) that have very slow growth kinetics and needle-like morphology. In this work, a batch cooling crystallization process for a GlaxoSmithKline patented API, which is characterized by very slow growth rate and needle morphology, was studied and improved using process analytical technology (PAT) based feedback control techniques and in situ immersion milling. Four specific approaches were investigated: Supersaturation control (SSC), direct nucleation control (DNC), sequential milling-DNC, and simultaneous milling-DNC. This is the first time that immersion wet milling is combined with feedback control in a batch crystallization process. All four approaches were found to improve crystal size and/or shape compared to simple unseeded or seeded linear cooling crystallizations. DNC provided higher quality crystals than SSC, and sequential and simultanesou milling-DNC approaches could reduce particle 2D aspect ratio without generating too much fines. In addition, an ultra-performance liquid chromatography (UPLC) system was used online as a novel PAT tool in the crystallization study. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Search for improved fluorinated stationary phases for separation of fluorine-containing pharmaceuticals from their desfluoro analogs.

    PubMed

    Regalado, Erik L; Makarov, Alexey A; McClain, Ray; Przybyciel, Matthew; Welch, Christopher J

    2015-02-06

    Evaluation of a several fluorine-containing stationary phases for the chromatographic separation of fluorine-containing pharmaceuticals from their corresponding desfluoro analogs revealed a number of perfluoroaryl and perfluoroalky stationary phases that afford good separations. These fluorous stationary phases exhibit greater retention for the fluorine-containing compounds relative to the H-containing analogs, consistent with a fluorophilic retention mechanism. While both perfluoroalkyl and perfluoroaryl stationary phases afford adequate resolution, the perfluoroaryl columns generally exhibit superior separation factor (α) and peak efficiency (N), resulting in faster baseline separations, with the Hypersil Gold PFP and Poroshell 120 PFP columns providing the best overall performance for the test group studied.

  3. Pharmaceutical companies' variation of drug prices within and among countries can improve long-term social well-being.

    PubMed

    Lichtenberg, Frank R

    2011-08-01

    Drug prices vary considerably across and within countries. On average, pharmaceutical companies charge lower prices in low-income countries than in industrialized nations. Manufacturers' ability to price products differently for different markets--a practice known as price discrimination--increases their profits overall. But it is also likely to result in greater investment in research and development, and therefore in more new drugs on the market. Although reducing price discrimination in order to cut costs might benefit consumers in the short run, it would harm them in the long run by reducing the number of new drugs developed.

  4. Endomorphin derivatives with improved pharmacological properties.

    PubMed

    Varamini, Pegah; Blanchfield, Joanne T; Toth, Istvan

    2013-01-01

    Centrally acting opioids, such as morphine, are the most frequently used analgesic agents for the treatment of severe pain. However, their usefulness is limited by the production of a range of adverse effects such as constipation, respiratory depression, tolerance and physical dependence. In addition, opioids generally exhibit poor efficacy against neuropathic pain. Endomorphin-1 and -2, two endogenous opioid peptides, have been shown to produce potent antinociception in rodent models of acute and neuropathic pain with less undesirable side effects than opioid alkaloids. However, native endomorphins are poorly suited to clinical applications without modifications. Like all small peptides, endomorphins suffer from poor metabolic stability and a relative inability to penetrate the gastro-intestinal mucosa and blood-brain-barrier. Since the discovery of endomorphins in 1997, a huge number of endomorphin analogs have been designed and synthesized with the aim of developing compounds with improved barrier penetration and resistance to enzymatic degradation. In this review we describe various strategies that have been adopted so far to conquer the major drawbacks associated with endomorphins. They include chemical modifications to produce locally or globally-restricted peptide analogs in addition to application of peptidase inhibitors, which is of minor importance compared to the former strategy. Diverse approaches that resulted in the design and synthesis of pharmacologically active endomorphin analogs with less adverse effects are also discussed giving an insight into the development of opioid peptides with an improved side effect profile.

  5. Improving Thermoelectric Properties of Nanowires Through Inhomogeneity

    NASA Astrophysics Data System (ADS)

    González, J. Eduardo; Sánchez, Vicenta; Wang, Chumin

    2016-10-01

    Inhomogeneity in nanowires can be present in the cross-section and/or by breaking the translational symmetry along the nanowire. In particular, the quasiperiodicity introduces an unusual class of electronic and phononic transport with a singular continuous eigenvalue spectrum and critically localized wave functions. In this work, the thermoelectricity in periodic and quasiperiodically segmented nanobelts and nanowires is addressed within the Boltzmann formalism by using a real-space renormalization plus convolution method developed for the Kubo-Greenwood formula, in which tight-binding and Born models are, respectively, used for the calculation of electric and lattice thermal conductivities. For periodic nanowires, we observe a maximum of the thermoelectric figure-of-merit (ZT) in the temperature space, as occurred in the carrier concentration space. This maximum ZT can be improved by introducing into nanowires periodically arranged segments and an inhomogeneous cross-section. Finally, the quasiperiodically segmented nanowires reveal an even larger ZT in comparison with the periodic ones.

  6. Improving Thermoelectric Properties of Nanowires Through Inhomogeneity

    NASA Astrophysics Data System (ADS)

    González, J. Eduardo; Sánchez, Vicenta; Wang, Chumin

    2017-05-01

    Inhomogeneity in nanowires can be present in the cross-section and/or by breaking the translational symmetry along the nanowire. In particular, the quasiperiodicity introduces an unusual class of electronic and phononic transport with a singular continuous eigenvalue spectrum and critically localized wave functions. In this work, the thermoelectricity in periodic and quasiperiodically segmented nanobelts and nanowires is addressed within the Boltzmann formalism by using a real-space renormalization plus convolution method developed for the Kubo-Greenwood formula, in which tight-binding and Born models are, respectively, used for the calculation of electric and lattice thermal conductivities. For periodic nanowires, we observe a maximum of the thermoelectric figure-of-merit ( ZT) in the temperature space, as occurred in the carrier concentration space. This maximum ZT can be improved by introducing into nanowires periodically arranged segments and an inhomogeneous cross-section. Finally, the quasiperiodically segmented nanowires reveal an even larger ZT in comparison with the periodic ones.

  7. Sale strategies of pharmaceutical companies in a "pharmerging" country: the problems will not improve if the gaps remain.

    PubMed

    Civaner, Murat

    2012-08-01

    This study aimed to examine the types of sales strategies used by pharmaceutical companies in a "pharmerging" market and to gain insight into the ways of avoiding the negative effects of these strategies. In-depth interviews were conducted with 22 physicians and company employees in the six largest cities of Turkey. The interviews were analyzed using content analysis. Various sales strategies, both legal and illegal, are universally applied. These methods target prescribers, patients, pharmacists, and society in general. Different types of companies, organizations, professionals, and science and ethical principles are used as means. Companies intervene immediately to prevent developments that may decrease sales, and exploit the educational and infrastructural needs. In contrast, physicians are overconfident about the effects of marketing and insufficiently educated on how to cope with the strategies and the drugs on the market, which make them vulnerable. Under these conditions, along with worldwide competition and economic volatility, policies that aim to set frameworks for pharmaceutical relationships have failed. Interventions are crucial, including instituting a national drug policy, minimizing the exposure to marketing, and addressing the educational and infrastructural needs of the prescribers. Without these interventions, gaps will continue to be exploited by companies for their own advantage, and the problems related to marketing will persist. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  8. Improving Search Properties in Genetic Programming

    NASA Technical Reports Server (NTRS)

    Janikow, Cezary Z.; DeWeese, Scott

    1997-01-01

    developed and implemented methods to use additional problem heuristics to fine-tune the searchable space, and to use typing information to further reduce the search space. Additional improvements have been proposed, but they are yet to be explored and implemented.

  9. Improving Search Properties in Genetic Programming

    NASA Technical Reports Server (NTRS)

    Janikow, Cezary Z.; DeWeese, Scott

    1997-01-01

    developed and implemented methods to use additional problem heuristics to fine-tune the searchable space, and to use typing information to further reduce the search space. Additional improvements have been proposed, but they are yet to be explored and implemented.

  10. 24 CFR 201.20 - Property improvement loan eligibility.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... least a one-half interest in one of the following: (i) Fee simple title to the real property; (ii) Lease... estimated cost. (2) The loan proceeds shall be used only to finance property improvements that substantially... the Secretary before making a loan. (3) The loan proceeds shall only be used to finance...

  11. 24 CFR 201.20 - Property improvement loan eligibility.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... least a one-half interest in one of the following: (i) Fee simple title to the real property; (ii) Lease... estimated cost. (2) The loan proceeds shall be used only to finance property improvements that substantially... the Secretary before making a loan. (3) The loan proceeds shall only be used to finance...

  12. Pharmaceutical virtue.

    PubMed

    Martin, Emily

    2006-06-01

    In the early history of psychopharmacology, the prospect of developing technologically sophisticated drugs to alleviate human ills was surrounded with a fervor that could be described as religious. This paper explores the subsequent history of the development of psychopharmacological agents, focusing on the ambivalent position of both the industry and its employees. Based on interviews with retired pharmaceutical employees who were active in the industry in the 1950s and 1960s when the major breakthroughs were made in the development of MAOIs and SSRIs, the paper explores the initial development of educational materials for use in sales campaigns. In addition, based on interviews with current employees in pharmaceutical sales and marketing, the paper describes the complex perspective of contemporary pharmaceutical employees who must live surrounded by the growing public vilification of the industry as rapacious and profit hungry and yet find ways to make their jobs meaningful and dignified. The paper will contribute to the understudied problem of how individuals function in positions that require them to be part of processes that on one description constitute a social evil, but on another, constitute a social good.

  13. The effectiveness of daily SMS reminders in pharmaceutical care of older adults on improving patients' adherence to antihypertensive medication (SPPA): study protocol for a randomized controlled trial.

    PubMed

    Haramiova, Zuzana; Stasko, Michal; Hulin, Martin; Tesar, Tomas; Kuzelova, Magdalena; Morisky, Donald M

    2017-07-18

    Despite a variety of efficient and cost-effective antihypertensive medication, hypertension remains a serious health and economic burden. High consumption of cardiovascular drugs in the Slovak Republic does result neither in better hypertension control nor in significant decrease in cardiovascular mortality. At the same time, Slovakia has alarmingly low patients' adherence to medication intake. Studies have shown the efficiency of short messaging service (SMS) reminders to improve patients' adherence and health outcomes at low costs. Since SMS is popular among Slovaks, this approach may be feasible also in Slovakia. The primary objective is to assess if daily SMS reminders of antihypertensive medication intake provided by pharmacists in addition to the standard pharmaceutical care increase the proportion of adherent older hypertensive ambulatory patients. The SPPA trial is a pragmatic randomized parallel group (1:1) trial in 300 older hypertensive patients carried out in community pharmacies in Slovakia. Trial pharmacies will be selected from all main regions of Slovakia. Trial intervention comprises daily personalized SMS reminders of medication intake embedded into usual pharmaceutical practice. The primary outcome is a combined adherence endpoint consisting of subjective self-reported medication adherence via the eight-item Morisky Medication Adherence Scale (MMAS-8) and objective pill count rate. Secondary outcomes include: change in the MMAS-8; comparison of adherence rates using pill count; change in systolic blood pressure; and patient satisfaction. Also, direct treatment costs will be evaluated and a cost-effectiveness analysis will be carried out. The SPPA trial engages community pharmacists and mobile health (mHealth) technologies via evidence-based pharmaceutical care to efficiently and cost-effectively addresses current main healthcare challenges: high prevalence of hypertension; overconsumption of cardiovascular medicines; low adherence to medication

  14. Improved high performance liquid chromatographic determination of ginsenosides in Panax ginseng-based pharmaceuticals using a diol column.

    PubMed

    Bonfill, Mercè; Casals, Isidre; Palazón, Javier; Mallol, Anna; Morales, Carmen

    2002-02-01

    A reversed-phase high-performance liquid chromatographic assay for the simultaneous quantitative determination of seven ginsenosides, Rb(1), Rb(2), Rc, Rd, Rg(1), Re and Rf in pharmaceutical preparations is described. Chromatographic separation was achieved in less than 20 min using a 250 x 4 mm Lichrospher, 5 microm, 100 A diol column with detection at 203 nm. The method was validated over the range of 2.5-20 ng/microL using a 20 microL sample volume. The average accuracy at five concentrations was 90-100%, and the within-day and between-day precision ranged from 1 to 7% expressed as coefficient of variation. The detection limit and the quantitation limit of the method were 20 and 50 ng injected for each ginsenoside, respectively. Copyright 2002 John Wiley & Sons, Ltd.

  15. An improved approach to measuring drug innovation finds steady rates of first-in-class pharmaceuticals, 1987-2011.

    PubMed

    Lanthier, Michael; Miller, Kathleen L; Nardinelli, Clark; Woodcock, Janet

    2013-08-01

    For more than a decade, industry analysts and policy makers have raised concerns about declining pharmaceutical innovation, citing declining numbers of new molecular entities (NMEs) approved in the United States each year. Yet there is little consensus on whether this is the best measure of "innovation." We examined NME approvals during 1987-2011 and propose the three distinct subcategories of NMEs--first-in-class, advance-in-class, and addition-to-class--to provide more nuanced and informative insights into underlying trends. We found that trends in NME approvals were largely driven by addition-to-class, or "me too," drug approvals, while first-in-class approvals remained fairly steady over the study period. Moreover, the higher proportion of first-in-class drug approvals over the most recent decade is an encouraging sign of the health of the industry as a whole.

  16. Effects of excipients on the tensile strength, surface properties and free volume of Klucel® free films of pharmaceutical importance

    NASA Astrophysics Data System (ADS)

    Gottnek, Mihály; Süvegh, Károly; Pintye-Hódi, Klára; Regdon, Géza

    2013-08-01

    The physicochemical properties of polymers planned to be applied as mucoadhesive films were studied. Two types of Klucel® hydroxypropylcellulose (LF and MF) were used as film-forming polymers. Hydroxypropylcellulose was incorporated in 2 w/w% with glycerol and xylitol as excipients and lidocaine base as an active ingredient at 5, 10 or 15 w/w% of the mass of the film-forming polymer. The free volume changes of the films were investigated by positron annihilation lifetime spectroscopy, the mechanical properties of the samples were measured with a tensile strength tester and contact angles were determined to assess the surface properties of the films. It was found that the Klucel® MF films had better physicochemical properties than those of the LF films. Klucel® MF as a film-forming polymer with lidocaine base and both excipients at 5 w/w% exhibited physicochemical properties and good workability. The excipients proved to exert strong effects on the physicochemical properties of the tested systems and it is very important to study them intensively in preformulation studies in the pharmaceutical technology in order to utilise their benefits and to avoid any disadvantageous effects.

  17. Trade, TRIPS, and pharmaceuticals.

    PubMed

    Smith, Richard D; Correa, Carlos; Oh, Cecilia

    2009-02-21

    The World Trade Organization's Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) set global minimum standards for the protection of intellectual property, substantially increasing and expanding intellectual-property rights, and generated clear gains for the pharmaceutical industry and the developed world. The question of whether TRIPS generates gains for developing countries, in the form of increased exports, is addressed in this paper through consideration of the importance of pharmaceuticals in health-care trade, outlining the essential requirements, implications, and issues related to TRIPS, and TRIPS-plus, in which increased restrictions are imposed as part of bilateral free-trade agreements. TRIPS has not generated substantial gains for developing countries, but has further increased pharmaceutical trade in developed countries. The unequal trade between developed and developing countries (ie, exporting and importing high-value patented drugs, respectively) raises the issue of access to medicines, which is exacerbated by TRIPS-plus provisions, although many countries have not even enacted provision for TRIPS flexibilities. Therefore this paper focuses on options that are available to the health community for negotiation to their advantage under TRIPS, and within the presence of TRIPS-plus.

  18. Transdermal Drug Delivery: Innovative Pharmaceutical Developments Based on Disruption of the Barrier Properties of the stratum corneum

    PubMed Central

    Zaid Alkilani, Ahlam; McCrudden, Maelíosa T.C.; Donnelly, Ryan F.

    2015-01-01

    The skin offers an accessible and convenient site for the administration of medications. To this end, the field of transdermal drug delivery, aimed at developing safe and efficacious means of delivering medications across the skin, has in the past and continues to garner much time and investment with the continuous advancement of new and innovative approaches. This review details the progress and current status of the transdermal drug delivery field and describes numerous pharmaceutical developments which have been employed to overcome limitations associated with skin delivery systems. Advantages and disadvantages of the various approaches are detailed, commercially marketed products are highlighted and particular attention is paid to the emerging field of microneedle technologies. PMID:26506371

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

    PubMed

    Kawakami, Kohsaku

    2012-05-01

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

  20. Recognizing misleading pharmaceutical marketing online.

    PubMed

    De Freitas, Julian; Falls, Brian A; Haque, Omar S; Bursztajn, Harold J

    2014-01-01

    In light of decision-making psychology, this article details how drug marketing operates across established and novel web domains and identifies some common misleading trends and influences on prescribing and patient-initiated medication requests. The Internet has allowed pharmaceutical marketing to become more salient than ever before. Although the Internet's growth has improved the dissemination of pharmaceutical information, it has also led to the increased influence of misleading pharmaceutical marketing. Such mismarketing is of concern, especially in psychiatry, since psychotropics generate considerable revenue for drug companies. In a climate of resource-limited drug regulation and time-strapped physicians, we recommend improving both independent monitoring and consumer awareness of Internet-enabled, potentially misleading, pharmaceutical marketing influences. © 2014 American Academy of Psychiatry and the Law.

  1. Comparison of the Solubilization Properties of Polysorbate 80 and Isopropanol/Water Solvent Systems for Organic Compounds Extracted from Three Pharmaceutical Packaging Configurations.

    PubMed

    Zdravkovic, Steven A

    2016-10-10

    It has been reported that the presence of polysorbate 80 in a pharmaceutical product's formulation may increase the number and/or amount of impurities leached from materials used during its manufacture, storage, and/or administration. However, it is uncertain if/how the solubilization properties of this surfactant compare to non-surfactant solvent systems. The goal of this study is to provide insight into this area of uncertainty by comparing the solubilization properties of polysorbate 80 to those of isopropanol/water solutions while in contact with a plasticized polyvinylchloride parenteral delivery bag, a single-use type manufacturing bag, and a polypropylene bottle. These properties were determined via a binding experiment, in which a set of model compounds was introduced into the solutions, and via an extraction experiment, in which compounds were extracted from the packaging material by the solutions. In both experiments, the amount of each compound present at equilibrium was assayed to determine the extent they were solubilized by the solution from the packaging material. Results from these experiments illustrate differences in the magnitude of solubilization obtained from solutions containing polysorbate 80 as compared to those composed of isopropanol/water. However, it was also demonstrated that their solubilization properties can be linked via a mathematical model. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Generic Selection Criteria for Safety and Patient Benefit [IV] - Physicochemical and pharmaceutical properties of brand-name and generic ketoprofen tapes.

    PubMed

    Wada, Yuko; Kihara, Maki; Nozawa, Mitsuru; Shimokawa, Ken-Ichi; Ishii, Fumiyoshi

    2015-06-01

    The physicochemical and pharmaceutical properties (pH, peel force, water-vapor permeability, and stretchability) of brand-name and generic ketoprofen products were evaluated and compared. The pHs of Mohrus as a brand-name product and Teikoku as a generic product were low (about 4). Among the other generic products, Patell and Nichi-Iko had a pH of about 4.3 while Frestol, Raynanon, BMD, and Touchron showed a pH of 4.6-5.2, which was in the pH range of normal healthy skin (4.5-6.5). The adhesive force was high (≥ 1.38) for Mohrus as a brand-name product as well as for Teikoku and Patell as generic products, but it was low (≤ 0.57) for the other 5 generic products. The water-vapor permeabilities of Mohrus as a brand-name product and Teikoku and Patell as generic products were low, being less than 1/6 of those for the other 5 generic products. Among the 5 generic products, BMD showed the highest water-vapor permeability (1,330 g/m²), and the other products also showed a value ≥ 1,100 g/m². The elongatedness of Mohrus was the lowest (15.5 cm), and that of Raynanon was the highest (24.5 cm); the difference was 9 cm. In this study, the physiochemical and pharmaceutical properties of ketoprofen tapes were clarified, which will allow pharmacists to provide products according to the needs of each patient when a brand-name product is changed to a generic one.

  3. 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.

  4. Ultrasound-assisted preparation of novel ibuprofen-loaded excipient with improved compression and dissolution properties.

    PubMed

    Gandhi, Paras; Patil, Sharvil; Aher, Suyog; Paradkar, Anant

    2016-10-01

    Most of the active pharmaceutical ingredients (APIs) suffer from a drawback of poor aqueous solubility. In addition to the same, some APIs show poor tabletting behavior creating problems in formulation development. Crystal engineering can be an efficient tool in rectification of such problems associated with the APIs. Thus present work deals with crystallization of ibuprofen (a model drug) onto the surface of dicalcium phosphate (DCP) particles using different techniques. The objective of the present work was to prepare ibuprofen-loaded DCP particles and further to analyze them for compressibility and dissolution behavior. Various crystallization techniques such as solvent evaporation (SE), melt crystallization (MC), melt sonocrystallization (MSC), antisolvent crystallization (AC), and antisolvent sonocrystallization (ASC) were screened for the preparation of ibuprofen-loaded DCP. Products obtained from different techniques were analyzed for physicochemical, micromeritic and compression properties. ASC technique was found to be suitable for preparing directly compressible ibuprofen-loaded DCP particles. The change in the crystal habit (needle to plate shape) of ibuprofen and its crystallization in miniscular form onto the surface of DCP particles showed significant improvement in the dissolution rate and compression properties of ibuprofen due to an increase in specific surface area when compared with ibuprofen crystallized by other techniques. Additionally, the tablets prepared from ASC powder did not require binder since ibuprofen acted as melt binder during compression. Directly compressible ibuprofen-loaded DCP particles can serve as an alternative for conventional ibuprofen tablets prepared by wet granulation technique.

  5. Pharmaceutical Analysis as a Branch of Pharmaceutics

    ERIC Educational Resources Information Center

    Connors, Kenneth A.

    1977-01-01

    Pharmaceutical analysis is incorporated into the pharmaceutics component of the undergraduate curriculum at the University of Wisconsin. Many collaborative demonstrations, lectures, and laboratory experiments can illustrate the close relationship between analysis and modern pharmacy practice. (Author/LBH)

  6. Glass Fiber Reinforced Polypropylene Mechanical Properties Enhancement by Adhesion Improvement

    PubMed Central

    Etcheverry, Mariana; Barbosa, Silvia E.

    2012-01-01

    Glass fibers (GF) are the reinforcement agent most used in polypropylene (PP) based composites, as they have good balance between properties and costs. However, their final properties are mainly determined by the strength and stability of the polymer-fiber interphase. Fibers do not act as an effective reinforcing material when the adhesion is weak. Also, the adhesion between phases can be easily degraded in aggressive environmental conditions such as high temperatures and/or elevated moisture, and by the stress fields to which the material may be exposed. Many efforts have been done to improve polymer-glass fiber adhesion by compatibility enhancement. The most used techniques include modifications in glass surface, polymer matrix and/or both. However, the results obtained do not show a good costs/properties improvement relationship. The aim of this work is to perform an accurate analysis regarding methods for GF/PP adhesion improvement and to propose a new route based on PP in-situ polymerization onto fibers. This route involves the modification of fibers with an aluminum alkyl and hydroxy-α-olefin and from there to enable the growth of the PP chains using direct metallocenic copolymerization. The adhesion improvements were further proved by fragmentation test, as well as by mechanical properties measurements. The strength and toughness increases three times and the interfacial strength duplicates in PP/GF composites prepared with in-situ polymerized fibers. PMID:28817025

  7. Nonmetallic impurities improve mechanical properties of vapor-deposited tungsten

    NASA Technical Reports Server (NTRS)

    Chin, J.; Weinberg, A. F.; Lindgren, J. R.

    1972-01-01

    Mechanical properties of vapor deposited tungsten are improved by selective incorporation of various nonmetallic impurities. Addition of trace quantities of carbon, nitrogen, or oxygen can significantly increase both low and high temperature yield strength without greatly affecting ductile-to-brittle transition temperature.

  8. Glass Fiber Reinforced Polypropylene Mechanical Properties Enhancement by Adhesion Improvement.

    PubMed

    Etcheverry, Mariana; Barbosa, Silvia E

    2012-06-18

    Glass fibers (GF) are the reinforcement agent most used in polypropylene (PP) based composites, as they have good balance between properties and costs. However, their final properties are mainly determined by the strength and stability of the polymer-fiber interphase. Fibers do not act as an effective reinforcing material when the adhesion is weak. Also, the adhesion between phases can be easily degraded in aggressive environmental conditions such as high temperatures and/or elevated moisture, and by the stress fields to which the material may be exposed. Many efforts have been done to improve polymer-glass fiber adhesion by compatibility enhancement. The most used techniques include modifications in glass surface, polymer matrix and/or both. However, the results obtained do not show a good costs/properties improvement relationship. The aim of this work is to perform an accurate analysis regarding methods for GF/PP adhesion improvement and to propose a new route based on PP in-situ polymerization onto fibers. This route involves the modification of fibers with an aluminum alkyl and hydroxy-α-olefin and from there to enable the growth of the PP chains using direct metallocenic copolymerization. The adhesion improvements were further proved by fragmentation test, as well as by mechanical properties measurements. The strength and toughness increases three times and the interfacial strength duplicates in PP/GF composites prepared with in-situ polymerized fibers.

  9. Effect of oxygenates blending with gasoline to improve fuel properties

    NASA Astrophysics Data System (ADS)

    Babazadeh Shayan, Soheil; Seyedpour, Seyed Morteza; Ommi, Fathollah

    2012-07-01

    The purpose of this paper is to study the effect of oxygenate additives into gasoline for the improvement of physicochemical properties of blends. Methyl Tertiary Butyl Ether (MTBE), Methanol, Tertiary butyl alcohol (TBA), and Tertiary amyl alcohol (TAA) blend into unleaded gasoline with various blended rates of 2.5%, 5%, 7.5%, 10%, 15%, and 20%. Physicochemical properties of blends are analyzed by the standard American Society of Testing and Materials (ASTM) methods. Methanol, TBA, and TAA increase density of the mixtures, but MTBE decreases density. The addition of oxygenates lead to a distortion of the base gasoline's distillation curves. The Reid vapor pressure (RVP) of gasoline is found to increase with the addition of the oxygenated compounds. All oxygenates improve both motor and research octane numbers. Among these four additives, TBA shows the best fuel properties.

  10. Optical Properties of Volcanic Ash: Improving Remote Sensing Observations

    NASA Astrophysics Data System (ADS)

    Whelley, P.; Colarco, P. R.; Aquila, V.; Krotkov, N. A.; Bleacher, J. E.; Garry, W. B.; Young, K. E.; Lima, A. R.; Martins, J. V.; Carn, S. A.

    2015-12-01

    Many times each year explosive volcanic eruptions loft ash into the atmosphere. Global travel and trade rely on aircraft vulnerable to encounters with airborne ash. Volcanic ash advisory centers (VAACs) rely on dispersion forecasts and satellite data to issue timely warnings. To improve ash forecasts model developers and satellite data providers need realistic information about volcanic ash microphysical and optical properties. In anticipation of future large eruptions we can study smaller events to improve our remote sensing and modeling skills so when the next Pinatubo 1991 or larger eruption occurs, ash can confidently be tracked in a quantitative way. At distances >100km from their sources, drifting ash plumes, often above meteorological clouds, are not easily detected from conventional remote sensing platforms, save deriving their quantitative characteristics, such as mass density. Quantitative interpretation of these observations depends on a priori knowledge of the spectral optical properties of the ash in UV (>0.3μm) and TIR wavelengths (>10μm). Incorrect assumptions about the optical properties result in large errors in inferred column mass loading and size distribution, which misguide operational ash forecasts. Similarly, simulating ash properties in global climate models also requires some knowledge of optical properties to improve aerosol speciation. Recent research has identified a wide range in volcanic ash optical properties among samples collected from the ground after different eruptions. The database of samples investigated remains relatively small, and measurements of optical properties at the relevant particle sizes and spectral channels are far from complete. Generalizing optical properties remains elusive, as does establishing relationships between ash composition and optical properties, which are essential for satellite retrievals. We are building a library of volcanic ash optical and microphysical properties. In this presentation we show

  11. Particle Engineering Via Mechanical Dry Coating in the Design of Pharmaceutical Solid Dosage Forms.

    PubMed

    Qu, Li; Morton, David A V; Zhou, Qi Tony

    2015-01-01

    Cohesive powders are problematic in the manufacturing of pharmaceutical solid dosage forms because they exhibit poor flowability, fluidization and aerosolization. These undesirable bulk properties of cohesive powders represent a fundamental challenge in the design of efficient pharmaceutical manufacturing processes. Recently, mechanical dry coating has attracted increasing attention as it can improve the bulk properties of cohesive powders in a cheaper, simpler, safer and more environment-friendly way than the existing solvent-based counterparts. In this review, mechanical dry coating techniques are outlined and their potential applications in formulation and manufacturing of pharmaceutical solid dosage forms are discussed. Reported data from the literature have shown that mechanical dry coating holds promise for the design of superior pharmaceutical solid formulations or manufacturing processes by engineering the interfaces of cohesive powders in an efficient and economical way.

  12. The Pharmaceutical Commons

    PubMed Central

    Lezaun, Javier

    2015-01-01

    In the last decade, the organization of pharmaceutical research on neglected tropical diseases has undergone transformative change. In a context of perceived “market failure,” the development of new medicines is increasingly handled by public-private partnerships. This shift toward hybrid organizational models depends on a particular form of exchange: the sharing of proprietary assets in general and of intellectual property rights in particular. This article explores the paradoxical role of private property in this new configuration of global health research and development. Rather than a tool to block potential competitors, proprietary assets function as a lever to attract others into risky collaborative ventures; instead of demarcating public and private domains, the sharing of property rights is used to increase the porosity of that boundary. This reimagination of the value of property is connected to the peculiar timescape of global health drug development, a promissory orientation to the future that takes its clearest form in the centrality of “virtual” business models and the proliferation of strategies of deferral. Drawing on the anthropological literature on inalienable possessions, we reconsider property’s traditional exclusionary role and discuss the possibility that the new pharmaceutical “commons” proclaimed by contemporary global health partnerships might be the precursor of future enclosures. PMID:25866425

  13. Improvement of physicochemical properties of an antiepileptic drug by salt engineering.

    PubMed

    Rahman, Ziyaur; Zidan, Ahmed S; Samy, Raghu; Sayeed, Vilayat A; Khan, Mansoor A

    2012-09-01

    The focus of the present investigation was to evaluate the feasibility of using cyclamic salt of lamotrigine in order to improve its solubility and intrinsic dissolution rate (IDR). The salt was prepared by solution crystallization method and characterized chemically by fourier transform infrared spectroscopy (FTIR), proton ((1)H) and carbon ((13)C) nuclear magnetic resonance (liquid and solid, NMR) spectroscopy, physically by powder X-ray diffraction (PXRD), thermally by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), physicochemically for solubility, IDR, solution and solid-state stability, and polymorphism by solution recrystallization and slurry conversion studies. The FTIR, NMR, PXRD, DSC, and TGA spectra and thermograms indicated the salt formation. The salt formation increased lamotrigine solubility by 19-fold and IDR by 4.9-fold in water. The solution and solid-state stability were similar to parent molecule and were resistant to polymorphic transformation. In conclusion, cyclamic salt of lamotrigine provides another potential avenue for the pharmaceutical development of lamotrigine with improved physicochemical properties especially for pediatric population. It is also possible that appropriate dosage forms can be formulated with much lower drug amount and better safety profile than existing products.

  14. Engineered disulfides improve mechanical properties of recombinant spider silk.

    PubMed

    Grip, S; Johansson, J; Hedhammar, M

    2009-05-01

    Nature's high-performance polymer, spider silk, is composed of specific proteins, spidroins, which form solid fibers. So far, fibers made from recombinant spidroins have failed in replicating the extraordinary mechanical properties of the native material. A recombinant miniature spidroin consisting of four poly-Ala/Gly-rich tandem repeats and a nonrepetitive C-terminal domain (4RepCT) can be isolated in physiological buffers and undergoes self assembly into macrofibers. Herein, we have made a first attempt to improve the mechanical properties of 4RepCT fibers by selective introduction of AA --> CC mutations and by letting the fibers form under physiologically relevant redox conditions. Introduction of AA --> CC mutations in the first poly-Ala block in the miniature spidroin increases the stiffness and tensile strength without changes in ability to form fibers, or in fiber morphology. These improved mechanical properties correlate with degree of disulfide formation. AA --> CC mutations in the forth poly-Ala block, however, lead to premature aggregation of the protein, possibly due to disulfide bonding with a conserved Cys in the C-terminal domain. Replacement of this Cys with a Ser, lowers thermal stability but does not interfere with dimerization, fiber morphology or tensile strength. These results show that mutagenesis of 4RepCT can reveal spidroin structure-activity relationships and generate recombinant fibers with improved mechanical properties.

  15. Improvement of Mechanical Properties in Natural Rubber with Organic Fillers

    NASA Astrophysics Data System (ADS)

    Gonzales-Fernandes, M.; Bastos, Andrade C. G.; Esper, F. J.; Valenzuela-Diaz, F. R.; Wiebeck, H.

    When added to polymeric matrices, organophilic clay transforms the performance of the resulting composites. A natural rubber matrix with different loads was prepared as bentonite chocolate B modified by sodification and treated with ammonium quaternary salt with cellulose charge, cardboard and palm fiber. After the mixture of natural rubber in a roller mill with the additives and subsequent addition of loads individually, plates were vulcanized for fabricating specimens. We measured the mechanical properties of traction and the interlayer distances analyzed by XRD. The aim of the paper is to show that the composite obtained improved in mechanical properties as compared to plates without the addition of loads.

  16. Enzymatic treatment of mechanical pulp fibers for improving papermaking properties.

    PubMed

    Wong, K K; Richardson, J D; Mansfield, S D

    2000-01-01

    Three enzyme preparations (crude cellulase, laccase, and proteinase) were evaluated for their potential to improve the papermaking properties of mechanical pulp. After treating a long fibre-rich fraction of the pulp with enzyme, the fibres were recombined with untreated fines for handsheet making and testing. None of the enzymes altered the retention of fines or the consolidation of the furnish mix during handsheet formation. All three enzymes increased tensile stiffness index, which is a measure of the initial resistance of the handsheets to strain. Only the laccase preparation, an enzyme that modifies pulp lignin, consistently increased fibre bonding to enhance other strength properties of the handsheets.

  17. Generic selection criteria for safety and patient benefit [V]: Comparing the pharmaceutical properties and patient usability of original and generic nasal spray containing ketotifen fumarate.

    PubMed

    Wada, Yuko; Ami, Shyoko; Nozawa, Mitsuru; Goto, Miho; Shimokawa, Ken-Ichi; Ishii, Fumiyoshi

    The pH, osmotic pressure (cryoscopy), viscosity, squeeze force, spray angle, and spraying frequency of nasal spray containing ketotifen fumarate (1 brand-name product and 8 generic products) were measured. Based on the results of pH measurement, all products were weakly acidic (4.0 to 5.1). For all products, the osmotic pressure ratio to physiological saline was approximately 1. The viscosity of various products ranged from approximately 1.0 to 1.5 mPa·s. The spray angle of drug solution differed among the products: minimum, 46 degrees (Sawai and Fusachol); and maximum, 68.7 degrees (Sekiton). In particular, TOA, Sawai, Fusachol, and TYK showed significantly smaller angles compared to Zaditen (brand-name product). Container properties varied among the products: minimum squeeze force, 19.0 N (Sekiton); and maximum squeeze force, 43.1 N (Sawai). Based on these results, although all the above products are identical in dosage form and active ingredient, the differences in pharmaceutical properties, such as container operations and drug-solution spraying/attachment, may markedly influence patients' subjective opinions.

  18. The trends and constructive ambiguity in international agreements on intellectual property and pharmaceutical affairs: Implications for domestic legislations in low- and middle-income countries.

    PubMed

    Son, Kyung-Bok; Lee, Tae-Jin

    2017-06-06

    The purpose of this study is to analyse the trends in international agreements including Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS), Korea-United States Free Trade Agreements, and Trans-Pacific Partnership Agreements on intellectual property and pharmaceutical affairs with the updated framework. The study also assesses constructive ambiguity in international agreements, which might affect the implementation process through interpretation and domestic legislations. Five flexibility clauses and three TRIPS-plus provisions were selected, and presence of constructive ambiguity in the agreements was analysed to draw actual trends in international agreements. Flexibility provisions excluding compulsory licensing were not noticeably changed, and TRIPS-plus provisions including data exclusivity and patent linkage were expanded in scope or newly appeared, respectively. The clause regarding compulsory licensing, extension of the patent term, data exclusivity, and patent linkage showed unclear definitions or the lack of adequate explanations. With constructive ambiguity in those clauses, a country who wants to join international agreements in the near future could amend domestic legislations to minimise the detrimental effect of international agreements on access to medicines.

  19. Improvement of barrier properties of rotomolded PE containers with nanoclay

    SciTech Connect

    Jamshidi, Shadi; Sundararaj, Uttandaraman

    2015-05-22

    Polyethylene (PE) is widely used to make bulk containers in rotational molding process. The challenge in this study is to improve permeation resistance of PE to hydrocarbon solvents and gases. Adding organomodified clay improves the thermal, barrier and mechanical properties of PE. In fact, clay layers create a tortuous path against the permeant, yielding better barrier properties. Due to the non-polar hydrophobic nature of PE and polar hydrophilic structure of clay minerals, the compatibilizer plays a crucial role to enhance the dispersion level of clay in the matrix. In this study High Density Polyethylene (HDPE) and Linear Low Density Polyethylene (LLDPE) layered silicate nanocomposite were melt-compounded with two concentrations of organomodified clay (2 and 4 wt. %). The interaction between nanoclay, compatibilizer and rotomolding grade of PE were examined by using X-ray diffraction, transmission electron microscopy (TEM) and rheology test. Rheology was used to determine the performance of our material at low shear processing condition.

  20. Improvement of barrier properties of rotomolded PE containers with nanoclay

    NASA Astrophysics Data System (ADS)

    Jamshidi, Shadi; Sundararaj, Uttandaraman

    2015-05-01

    Polyethylene (PE) is widely used to make bulk containers in rotational molding process. The challenge in this study is to improve permeation resistance of PE to hydrocarbon solvents and gases. Adding organomodified clay improves the thermal, barrier and mechanical properties of PE. In fact, clay layers create a tortuous path against the permeant, yielding better barrier properties. Due to the non-polar hydrophobic nature of PE and polar hydrophilic structure of clay minerals, the compatibilizer plays a crucial role to enhance the dispersion level of clay in the matrix. In this study High Density Polyethylene (HDPE) and Linear Low Density Polyethylene (LLDPE) layered silicate nanocomposite were melt-compounded with two concentrations of organomodified clay (2 and 4 wt. %). The interaction between nanoclay, compatibilizer and rotomolding grade of PE were examined by using X-ray diffraction, transmission electron microscopy (TEM) and rheology test. Rheology was used to determine the performance of our material at low shear processing condition.

  1. Improvement of vehicle roll stability by varying suspension properties

    NASA Astrophysics Data System (ADS)

    Shim, Taehyun; Velusamy, Pradheep C.

    2011-02-01

    Vehicle roll dynamics are strongly influenced by suspension properties such as roll centre height, roll steer, and roll camber. In this paper, the effects of suspension properties on vehicle roll response have been investigated using a multi-body vehicle dynamics programme. Roll dynamics of a vehicle model with MacPherson (front) and multilink (rear) suspensions were evaluated for the fishhook manoeuvre and variations of its roll response due to changes in the suspension properties were assessed by quantitatively analysing the vehicle response through simulation. Critical suspension design parameters for vehicle roll dynamics were identified and adjusted to improve roll stability of the vehicle model with passive suspension. Design of experiments has been used for identifying critical hardpoints affecting the suspension parameters, and optimisation techniques were employed for parameter optimisation. This approach provides a viable alternative to costlier active control systems for economy-class vehicles.

  2. Nanostructured materials in electroanalysis of pharmaceuticals.

    PubMed

    Rahi, A; Karimian, K; Heli, H

    2016-03-15

    Basic strategies and recent developments for the enhancement of the sensory performance of nanostructures in the electroanalysis of pharmaceuticals are reviewed. A discussion of the properties of nanostructures and their application as modified electrodes for drug assays is presented. The electrocatalytic effect of nanostructured materials and their application in determining low levels of drugs in pharmaceutical forms and biofluids are discussed.

  3. Novel F-releasing Composite with Improved Mechanical Properties

    PubMed Central

    Ling, L.; Xu, X.; Choi, G.-Y.; Billodeaux, D.; Guo, G.; Diwan, R.M.

    2009-01-01

    In recent years, the authors have been developing novel fluoride-releasing dental composites containing ternary zirconium fluoride chelates. The aim of this study was to improve the physical and mechanical properties of these composites by improving the formulation of the monomers and photoinitiators. The hypothesis was that reduction of hydrophilic monomers and improvement of the photoinitiators could reduce water sorption and significantly increase the mechanical properties of the composite. The degree of conversion of the composites containing different compositions of photoinitiators was studied by Fourier transform near-infrared spectroscopy (FT-NIR). Ten experimental composites containing different compositions of ethoxylated bisphenol-A dimethacrylate (EBPADMA), 1,6-hexanediol dimethacrylate (HDDMA), triethylene glycol dimethacrylate (TEGDMA), and 2,2-bis[4-(2-hydroxy-3-methacryloyloxypropoxy)phenyl]-propane (BisGMA) were tested for flexural strength, viscosity, and water sorption. The experimental composite containing 20% synthesized fluoride-releasing monomer, 30% BisGMA, 30% EBPADMA, and 20% HDDMA showed significantly higher fluoride release and recharge, but physical and mechanical properties similar to those of the control composite containing 40% BisGMA, 40% EBPADMA, and 20% HDDMA. PMID:19131323

  4. Do changes to supply chains and procurement processes yield cost savings and improve availability of pharmaceuticals, vaccines or health products? A systematic review of evidence from low-income and middle-income countries.

    PubMed

    Seidman, Gabriel; Atun, Rifat

    2017-01-01

    Improving health systems performance, especially in low-resource settings facing complex disease burdens, can improve population health. Specifically, the efficiency and effectiveness of supply chains and procurement processes for pharmaceuticals, vaccines and other health products has important implications for health system performance. Pharmaceuticals, vaccines and other health products make up a large share of total health expenditure in low-income and middle-income countries (LMICs), and they are critical for delivering health services. Therefore, programmes which achieve cost savings on these expenditures may help improve a health system's efficiency, whereas programmes that increase availability of health products may improve a health system's effectiveness. This systematic review investigates whether changes to supply chains and procurement processes can achieve cost savings and/or improve the availability of drugs in LMICs. Using the PRISMA guidelines for systematic reviews, we searched PubMed, Embase, CINAHL and the Health Economic Evaluation Database to identify. We identified 1264 articles, of which 38 were included in our study. We found evidence that centralised procurement and tendering can achieve direct cost savings, while supply chain management programmes can reduce drug stock outs and increase drug availability for populations. This research identifies a broad set of programmes which can improve the ways that health systems purchase and delivery health products. On the basis of this evidence, policymakers and programme managers should examine the root causes of inefficiencies in pharmaceutical supply chain and procurement processes in order to determine how best to improve health systems performance in their specific contexts.

  5. Low-intermediate dose testosterone replacement therapy by different pharmaceutical preparations improves frailty score in elderly hypogonadal hyperglycaemic patients.

    PubMed

    Strollo, Felice; Strollo, Giovanna; Morè, Massimo; Magni, Paolo; Macchi, Chiara; Masini, Maria Angela; Carucci, Iarba; Celotti, Fabio; Ruscica, Massimiliano; Gentile, Sandro

    2013-06-01

    An open-label follow-up study of low-to-intermediate dose testosterone replacement therapy (TRT) was conducted in 64 overweight patients (aged 65-75 years) with late onset hypogonadism (LOH) and increased fasting plasma glucose (FPG). Patients were subdivided into four treatment groups: oral testosterone (T) (T undecanoate, 80 mg/d), transmucosal T (60 mg/d), transdermal T (30 mg/d) or no treatment (control), and evaluated at 0 and 6 months. FPG, hemoglobin (Hb), prostate-specific antigen (PSA) and total T were measured and the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) index was calculated. Body mass index (BMI), waist circumference, fitness level (6-min walking test), Aging Males' Symptoms (AMS) scale, handgrip strength and energy expenditure with physical activity (Minnesota questionnaire for Leisure Time Physical Activity (LTPA)) were evaluated and a "frailty score" (based on: grip strength, gait speed and LTPA) was calculated. T levels increased in all treatment groups; the oral T group had values still in the hypogonadal range (5.9 ± 1.1 nmol/L). PSA and Hb concentrations did not change in any group. BMI, waist circumference, FPG and HOMA-IR improved in all T-treated groups after 6 months, with a greater effect seen with transmucosal and transdermal T compared with oral T. This study indicates that low-to-intermediate dose TRT may be safely utilized in LOH patients to ameliorate somatic and psychological frailty symptoms in association with improved anthropometric and glycometabolic parameters in aging, overweight men with LOH and impaired fasting glucose.

  6. Pharmaceutical properties of a low-substituted hydroxypropyl cellulose (L-HPC) hydrogel as a novel external dressing.

    PubMed

    Ogawa, Atsushi; Nakayama, Sachie; Uehara, Mami; Mori, Yasuhiro; Takahashi, Mai; Aiba, Tetsuya; Kurosaki, Yuji

    2014-12-30

    Controlling the moisture balance between exudates and their transpiration from the surface of wounded skin is important for healing. Low-substituted hydroxypropyl cellulose (L-HPC) hydrogel sheets (HGSs) possessing high water retention and water vapor transmission properties were prepared by neutralizing the highly viscous alkaline liquid of 7-10% L-HPC. Glycerol-impregnated L-HPC hydrogel sheets (L-HPC G-HGSs) were obtained by exchanging aqueous liquid in L-HPC HGSs. The physical characteristics required for wound dressings, i.e., mechanical strength, adhesive strength, and water retention properties, as well as the water vapor transmission (WVT) properties of L-HPC HGSs and L-HPC G-HGSs were evaluated. The mechanical strengths of L-HPC HGSs were enhanced with increases in the L-HPC content. The impregnation of glycerol in L-HPC HGSs yielded a significantly elasticated sheet. The adhesive strengths of L-HPC HGSs were significantly lower than those of commercial medical dressings. Water retention in L-HPC HGSs after being stored for 2h at 37°C was approximately 50%. The WVT rate of 7% L-HPC HGS was approximately 40g/m(2)/h, which was markedly higher than that of silicone gel type medical dressings. In conclusion, L-HPC HGSs are promising dressings that maintain an adequate moisture balance by transpiring excessive wound exudates with less damage to the healing wound.

  7. Improved in silico prediction of carcinogenic potency (TD50) and the risk specific dose (RSD) adjusted Threshold of Toxicological Concern (TTC) for genotoxic chemicals and pharmaceutical impurities.

    PubMed

    Contrera, Joseph F

    2011-02-01

    The Threshold of Toxicological Concern (TTC) is a level of exposure to a genotoxic impurity that is considered to represent a negligible risk to humans. The TTC was derived from the results of rodent carcinogenicity TD50 values that are a measure of carcinogenic potency. The TTC currently sets a default limit of 1.5 μg/day in food contact substances and pharmaceuticals for all genotoxic impurities without carcinogenicity data. Bercu et al. (2010) used the QSAR predicted TD50 to calculate a risk specific dose (RSD) which is a carcinogenic potency adjusted TTC for genotoxic impurities. This promising approach is currently limited by the software used, a combination of MC4PC (www.multicase.com) and a Lilly Inc. in-house software (VISDOM) that is not available to the public. In this report the TD50 and RSD were predicted using a commercially available software, SciQSAR (formally MDL-QSAR, www.scimatics.com) employing the same TD50 training data set and external validation test set that was used by Bercu et al. (2010). The results demonstrate the general applicability of QSAR predicted TD50 values to determine the RSDs for genotoxic impurities and the improved performance of SciQSAR for predicting TD50 values.

  8. Petitioning the FDA to Improve Pharmaceutical, Device and Public Health Safety by Ordinary Citizens: A Descriptive Analysis

    PubMed Central

    Yang, Y. Tony; Cheng, Xi; Bian, John; Bennett, Charles L.

    2016-01-01

    The United States Constitution protects the right of citizens to petition the government for “a redress of grievances.” This right has important implications for citizens desiring to advance the public health by petitioning administrative agencies, such as the Food and Drug Administration, to take safety actions. We examined a total of 1,915 petitions filed between 2001 and 2013 to investigate the outcomes of citizen petitions that address public health concerns. We found that most petitions were filed by manufacturers against other manufacturers. Only 346 (18%) of all petitions were submitted by individuals and non-profit organizations, and 178 (87.3%) of these petitions with a final response were denied. On average, these petitions required 2.85 years for a final agency decision, and many decisions remain pending 10–13 years after their initial submission. The great majority of the approved requests included some form of risk communication, such as labeling changes, boxed warnings or placement of a drug into a Risk Evaluation and Mitigation Strategy. As a policy instrument to improve the safety of medical and food products, the citizen petition process requires sophisticated legal and scientific expertise, and may not represent a viable route for ordinary citizens to petition the FDA to “redress grievances.” PMID:27171162

  9. Investigation of process temperature and screw speed on properties of a pharmaceutical solid dispersion using corotating and counter-rotating twin-screw extruders.

    PubMed

    Keen, Justin M; Martin, Charlie; Machado, Augie; Sandhu, Harpreet; McGinity, James W; DiNunzio, James C

    2014-02-01

    The use of corotating twin screw hot-melt extruders to prepare amorphous drug/polymer systems has become commonplace. As small molecule drug candidates exiting discovery pipelines trend towards higher MW and become more structurally complicated, the acceptable operating space shifts below the drug melting point. The objective of this research is to investigate the extrusion process space, which should be selected to ensure that the drug is solubilized in the polymer with minimal thermal exposure, is critical in ensuring the performance, stability and purity of the solid dispersion. The properties of a model solid dispersion were investigated using both corotating and counter-rotating hot-melt twin-screw extruders operated at various temperatures and screw speeds. The solid state and dissolution performance of the resulting solid dispersions was investigated and evaluated in context of thermodynamic predictions from Flory-Huggins Theory. In addition, the residence time distributions were measured using a tracer, modelled and characterized. The amorphous content in the resulting solid dispersions was dependent on the combination of screw speed, temperature and operating mode. The counter-rotating extruder was observed to form amorphous solid dispersions at a slightly lower temperature and with a narrower residence time distribution, which also exhibited a more desirable shape. © 2013 Royal Pharmaceutical Society.

  10. Investigation of the photoionization properties of pharmaceutically relevant substances by resonance-enhanced multiphoton ionization spectroscopy and single-photon ionization spectroscopy using synchrotron radiation.

    PubMed

    Kleeblatt, Juliane; Ehlert, Sven; Hölzer, Jasper; Sklorz, Martin; Rittgen, Jan; Baumgärtel, Peter; Schubert, Jochen K; Zimmermann, Ralf

    2013-08-01

    The photoionization properties of the pharmaceutically relevant substances amantadine, diazepam, dimethyltryptamine, etomidate, ketamine, mescaline, methadone, and propofol were determined. At beamline U125/2-10m-NIM of the BESSY II synchrotron facility (Berlin, Germany) vacuum ultraviolet (VUV) photoionization spectra were recorded in the energy range 7.1 to 11.9 eV (174.6 to 104.2 nm), showing the hitherto unknown ionization energies and fragmentation appearance energies of the compounds under investigation. Furthermore, (1+1)-resonance-enhanced multiphoton ionization (REMPI) spectra of selected compounds (amantadine, diazepam, etomidate, ketamine, and propofol) were recorded by a continuous scan in the energy range between 3.6 and 5.7 eV (345 to 218 nm) using a tunable optical parametric oscillator (spectral resolution: 0.1 nm) laser system. The resulting REMPI wavelength spectra of these compounds are discussed and put into context with already known UV absorption data. Time-of-flight mass spectrometry was used for ion detection in both experiments. Finally, the implications of the obtained physical-chemical results for potential analytical applications are discussed. In this context, fast detection approaches for the considered compounds from breath gas using photoionization mass spectrometry and a rapid pre-concentration step (e.g., needle trap device) are of interest.

  11. New Rotary Table Providing Improved Mass Property Measurements

    NASA Astrophysics Data System (ADS)

    Messing, R.; Appolloni, M.; Sablerolle, S.; Tavares, A.; Hervieu, M.

    2014-06-01

    ESA Test Centre at ESTEC, Noordwijk is a unique place in Europe, which is geared to perform environmental tests on large spacecraft at system level. The Test Centre includes the whole environmental facilities family: shakers, acoustic chamber, mass properties measurement facilities, electro-magnetic compatibility facilities and thermal vacuum chambers.Center of gravity (CoG) measurements require at least two force measurements in combination with a mass measurement to determine the CoG in the horizontal x-y plane. To achieve more quickly two or more orientations of the specimen with respect to the force cell the Test Centre implemented a rotary table on top of its W50/M6 mass property machine. This paper focuses on the acceptance and implementation of the rotary table and how by its use the CoG measurements could be improved in terms of measurement time, measurement uncertainty and measurement reliability.

  12. Improved expanding ring technique for determining dynamic material properties.

    PubMed

    Liang, M Z; Li, X Y; Qin, J G; Lu, F Y

    2013-06-01

    An improved expanding ring experimental technique has been described to determine dynamic material properties under conditions approximating uniform one-dimensional tensile loading. There are mainly explosive expanding ring technique and electromagnetic expanding ring technique currently, for which exist many limitations in practical applications. The work reported herein is an attempt to overcome this difficulty by lateral efficiency loading produced by projectile, made of low-density material, impacting the same material filling. The lateral efficiency loading is a convenient and effective method, which allows materials to be in uniform uniaxial stress conditions at a high stress rate. The procedure is illustrated by experiments performed on 1100-0 aluminum rings.

  13. Targeting the Biophysical Properties of the Myeloma Initiating Cell Niches: A Pharmaceutical Synergism Analysis Using Multi-Scale Agent-Based Modeling

    PubMed Central

    Su, Jing; Zhang, Le; Zhang, Wen; Choi, Dong Song; Wen, Jianguo; Jiang, Beini; Chang, Chung-Che; Zhou, Xiaobo

    2014-01-01

    Multiple myeloma, the second most common hematological cancer, is currently incurable due to refractory disease relapse and development of multiple drug resistance. We and others recently established the biophysical model that myeloma initiating (stem) cells (MICs) trigger the stiffening of their niches via SDF-1/CXCR4 paracrine; The stiffened niches then promote the colonogenesis of MICs and protect them from drug treatment. In this work we examined in silico the pharmaceutical potential of targeting MIC niche stiffness to facilitate cytotoxic chemotherapies. We first established a multi-scale agent-based model using the Markov Chain Monte Carlo approach to recapitulate the niche stiffness centric, pro-oncogenetic positive feedback loop between MICs and myeloma-associated bone marrow stromal cells (MBMSCs), and investigated the effects of such intercellular chemo-physical communications on myeloma development. Then we used AMD3100 (to interrupt the interactions between MICs and their stroma) and Bortezomib (a recently developed novel therapeutic agent) as representative drugs to examine if the biophysical properties of myeloma niches are drugable. Results showed that our model recaptured the key experimental observation that the MBMSCs were more sensitive to SDF-1 secreted by MICs, and provided stiffer niches for these initiating cells and promoted their proliferation and drug resistance. Drug synergism analysis suggested that AMD3100 treatment undermined the capability of MICs to modulate the bone marrow microenvironment, and thus re-sensitized myeloma to Bortezomib treatments. This work is also the first attempt to virtually visualize in 3D the dynamics of the bone marrow stiffness during myeloma development. In summary, we established a multi-scale model to facilitate the translation of the niche-stiffness centric myeloma model as well as experimental observations to possible clinical applications. We concluded that targeting the biophysical properties of stem

  14. Reprint of "Characterisation and modelling of the thermorheological properties of pharmaceutical polymers and their blends using capillary rheometry: Implications for hot melt processing of dosage forms".

    PubMed

    Jones, David S; Margetson, Daniel N; McAllister, Mark S; Andrews, Gavin P

    2015-12-30

    Given the growing interest in thermal processing methods, this study describes the use of an advanced rheological technique, capillary rheometry, to accurately determine the thermorheological properties of two pharmaceutical polymers, Eudragit E100 (E100) and hydroxypropylcellulose JF (HPC) and their blends, both in the presence and absence of a model therapeutic agent (quinine, as the base and hydrochloride salt). Furthermore, the glass transition temperatures (Tg) of the cooled extrudates produced using capillary rheometry were characterised using Dynamic Mechanical Thermal Analysis (DMTA) thereby enabling correlations to be drawn between the information derived from capillary rheometry and the glass transition properties of the extrudates. The shear viscosities of E100 and HPC (and their blends) decreased as functions of increasing temperature and shear rates, with the shear viscosity of E100 being significantly greater than that of HPC at all temperatures and shear rates. All platforms were readily processed at shear rates relevant to extrusion (approximately 200-300s(-1)) and injection moulding (approximately 900s(-1)). Quinine base was observed to lower the shear viscosities of E100 and E100/HPC blends during processing and the Tg of extrudates, indicative of plasticisation at processing temperatures and when cooled (i.e. in the solid state). Quinine hydrochloride (20% w/w) increased the shear viscosities of E100 and HPC and their blends during processing and did not affect the Tg of the parent polymer. However, the shear viscosities of these systems were not prohibitive to processing at shear rates relevant to extrusion and injection moulding. As the ratio of E100:HPC increased within the polymer blends the effects of quinine base on the lowering of both shear viscosity and Tg of the polymer blends increased, reflecting the greater solubility of quinine within E100. In conclusion, this study has highlighted the importance of capillary rheometry in

  15. Bioaccumulation Behavior of Pharmaceuticals and Personal Care Products in Adult Zebrafish (Danio rerio): Influence of Physical-Chemical Properties and Biotransformation.

    PubMed

    Chen, Fangfang; Gong, Zhiyuan; Kelly, Barry C

    2017-09-11

    The factors influencing bioaccumulation of pharmaceuticals and personal care products (PPCPs) in aquatic organisms are not well understood. The present study involved a comprehensive laboratory investigation to assess the bioaccumulation behavior of several PPCPs in adult zebrafish (Danio rerio). The studied PPCPs included several ionogenic organic compounds (IOCs) such as weak acids and weak bases. Experiments involved two exposure groups (high and low) and a control group, with a 6 day aqueous exposure, followed by a 7 day depuration phase under flow-through conditions. Uptake rate constants (ku) ranged between 0.19 and 8610 L·kg(-1)·d(-1), while depuration rate constants (kd) ranged between 0.14 and 5.14 d(-1) in different fish tissues. Steady-state bioconcentration factor (BCFss) values varied widely among the studied PPCPs, ranging from 0.09 to 6,460. In many cases, BCFss values of individual PPCPs differed substantially among different fish tissues. Positive linear relationships were observed between log BCFss values and physical-chemical properties such as octanol-water distribution coefficients (log Dow), membrane-water distribution coefficients (log Dmw), albumin-water distribution coefficients (log DBSAw), and muscle protein-water distribution coefficients (log Dmpw), indicating the importance of lipid-, phospholipid-, and protein-water partitioning. The results also showed that for many PPCPs, the estimated whole-body metabolism rate constant (km) values were comparable to the observed depuration rate (kd), indicating that metabolism plays a major role in the overall elimination of these compounds in zebrafish. An exception was sertraline, which exhibited a kd value (0.4-0.5 d(-1)) that was much higher than the estimated whole-body km (0.03 d(-1)). Overall, the results help to better understand the influence of physical-chemical properties and biotransformation on bioaccumulation behavior of these contaminants of concern in aquatic organisms.

  16. Targeting the biophysical properties of the myeloma initiating cell niches: a pharmaceutical synergism analysis using multi-scale agent-based modeling.

    PubMed

    Su, Jing; Zhang, Le; Zhang, Wen; Choi, Dong Song; Wen, Jianguo; Jiang, Beini; Chang, Chung-Che; Zhou, Xiaobo

    2014-01-01

    Multiple myeloma, the second most common hematological cancer, is currently incurable due to refractory disease relapse and development of multiple drug resistance. We and others recently established the biophysical model that myeloma initiating (stem) cells (MICs) trigger the stiffening of their niches via SDF-1/CXCR4 paracrine; The stiffened niches then promote the colonogenesis of MICs and protect them from drug treatment. In this work we examined in silico the pharmaceutical potential of targeting MIC niche stiffness to facilitate cytotoxic chemotherapies. We first established a multi-scale agent-based model using the Markov Chain Monte Carlo approach to recapitulate the niche stiffness centric, pro-oncogenetic positive feedback loop between MICs and myeloma-associated bone marrow stromal cells (MBMSCs), and investigated the effects of such intercellular chemo-physical communications on myeloma development. Then we used AMD3100 (to interrupt the interactions between MICs and their stroma) and Bortezomib (a recently developed novel therapeutic agent) as representative drugs to examine if the biophysical properties of myeloma niches are drugable. Results showed that our model recaptured the key experimental observation that the MBMSCs were more sensitive to SDF-1 secreted by MICs, and provided stiffer niches for these initiating cells and promoted their proliferation and drug resistance. Drug synergism analysis suggested that AMD3100 treatment undermined the capability of MICs to modulate the bone marrow microenvironment, and thus re-sensitized myeloma to Bortezomib treatments. This work is also the first attempt to virtually visualize in 3D the dynamics of the bone marrow stiffness during myeloma development. In summary, we established a multi-scale model to facilitate the translation of the niche-stiffness centric myeloma model as well as experimental observations to possible clinical applications. We concluded that targeting the biophysical properties of stem

  17. Characterisation and modelling of the thermorheological properties of pharmaceutical polymers and their blends using capillary rheometry: Implications for hot melt processing of dosage forms.

    PubMed

    Jones, David S; Margetson, Daniel N; McAllister, Mark S; Andrews, Gavin P

    2015-09-30

    Given the growing interest in thermal processing methods, this study describes the use of an advanced rheological technique, capillary rheometry, to accurately determine the thermorheological properties of two pharmaceutical polymers, Eudragit E100 (E100) and hydroxypropylcellulose JF (HPC) and their blends, both in the presence and absence of a model therapeutic agent (quinine, as the base and hydrochloride salt). Furthermore, the glass transition temperatures (Tg) of the cooled extrudates produced using capillary rheometry were characterised using Dynamic Mechanical Thermal Analysis (DMTA) thereby enabling correlations to be drawn between the information derived from capillary rheometry and the glass transition properties of the extrudates. The shear viscosities of E100 and HPC (and their blends) decreased as functions of increasing temperature and shear rates, with the shear viscosity of E100 being significantly greater than that of HPC at all temperatures and shear rates. All platforms were readily processed at shear rates relevant to extrusion (approximately 200-300 s(-1)) and injection moulding (approximately 900 s(-1)). Quinine base was observed to lower the shear viscosities of E100 and E100/HPC blends during processing and the Tg of extrudates, indicative of plasticisation at processing temperatures and when cooled (i.e. in the solid state). Quinine hydrochloride (20% w/w) increased the shear viscosities of E100 and HPC and their blends during processing and did not affect the Tg of the parent polymer. However, the shear viscosities of these systems were not prohibitive to processing at shear rates relevant to extrusion and injection moulding. As the ratio of E100:HPC increased within the polymer blends the effects of quinine base on the lowering of both shear viscosity and Tg of the polymer blends increased, reflecting the greater solubility of quinine within E100. In conclusion, this study has highlighted the importance of capillary rheometry in

  18. Novel Ferroptosis Inhibitors with Improved Potency and ADME Properties.

    PubMed

    Hofmans, Sam; Vanden Berghe, Tom; Devisscher, Lars; Hassannia, Behrouz; Lyssens, Sophie; Joossens, Jurgen; Van Der Veken, Pieter; Vandenabeele, Peter; Augustyns, Koen

    2016-03-10

    Ferroptosis is a nonapoptotic, iron-catalyzed form of regulated necrosis that is critically dependent on glutathione peroxidase 4 (GPX4). It has been shown to contribute to liver and kidney ischemia reperfusion injury in mice. A chemical inhibitor discovered by high-throughput screening displayed inhibition of ferroptosis with nanomolar activity and was dubbed ferrostatin-1 (fer-1). Ferrostatins inhibit oxidative lipid damage, but suffer from inherent stability problems due to the presence of an ester moiety. This limits the application of these molecules in vivo, due to rapid hydrolysis of the ester into the inactive carboxylic acid. Previous studies highlighted the importance of the ethyl ester and suggested steric modifications of the ester for generating improved molecules. In this study, we report the synthesis of novel ferroptosis inhibitors containing amide and sulfonamide moieties with improved stability, single digit nanomolar antiferroptotic activity, and good ADME properties suitable for application in in vivo disease models.

  19. Improved Properties of Pb Based BLZT Ferroelectric Ceramics

    SciTech Connect

    Kumar, Parveen; Singh, Sangeeta; Juneja, J. K.; Raina, K. K.; Prakash, Chandra

    2011-11-22

    Present report is concerning with investigation of effect of different sintering profiles on Pb based BLZT ceramics. The material powder of selected composition (Ba{sub 0.795}La{sub 0.005}Pb{sub 0.20}Ti{sub 0.90}Zr{sub 0.10}O{sub 3}) was prepared by solid state reaction route and then powder was compacted in the form of circular discs. The discs were then sintered at different temperatures (1325 deg. C for 4h, 1325 deg. C for 15min+1200 deg. C for 4h). Improved dielectric and ferroelectric properties were observed for samples sintered at 1200 deg. C. Shifting in T{sub c} to higher temperature could be related to enhanced tetragonality, which was further confirmed by X-ray diffraction analysis. All these improvements evidences that there is less Pb loss in case of modified sintering profile.

  20. [Application of microwave irradiation technology to the field of pharmaceutics].

    PubMed

    Zhang, Xue-Bing; Shi, Nian-Qiu; Yang, Zhi-Qiang; Wang, Xing-Lin

    2014-03-01

    Microwaves can be directly transformed into heat inside materials because of their ability of penetrating into any substance. The degree that materials are heated depends on their dielectric properties. Materials with high dielectric loss are more easily to reach a resonant state by microwaves field, then microwaves can be absorbed efficiently. Microwave irradiation technique with the unique heating mechanisms could induce drug-polymer interaction and change the properties of dissolution. Many benefits such as improving product quality, increasing energy efficiency and reducing times can be obtained by microwaves. This paper summarized characteristics of the microwave irradiation technique, new preparation techniques and formulation process in pharmaceutical industry by microwave irradiation technology. The microwave technology provides a new clue for heating and drying in the field of pharmaceutics.

  1. Phosphonic Acid-Functionalized Polyurethane Dispersions with Improved Adhesion Properties.

    PubMed

    Breucker, Laura; Landfester, Katharina; Taden, Andreas

    2015-11-11

    A facile route to phosphorus-functionalized polyurethane dispersions (P-PUDs) with improved adhesion properties is presented. (Bis)phosphonic acid moieties serve as adhesion promoting sites that are covalently attached via an end-capping reaction to isocyanate-reactive polyurethane particles under aqueous conditions. The synthetic approach circumvents solubility issues, offers great flexibility in terms of polyurethane composition, and allows for the synthesis of semicrystalline systems with thermomechanical response due to reversible physical cross-linking. Differential scanning calorimetry (DSC) is used to investigate the effect of functionalization on the semicrystallinity. The end-capping conversion was determined via inductively-coupled plasma optical emission spectroscopy (ICP-OES) and was surprisingly found to be almost independent of the stoichiometry of reaction, suggesting an adsorption-dominated process. Particle charge detection (PCD) experiments reveal that a dense surface coverage of phosphonic acid groups can be attained and that, at high functionalization degrees, the phosphonic adhesion moieties are partially dragged inside the colloidal P-PUD particle. Quartz crystal microbalance with dissipation (QCMD) investigations conducted with hydroxyapatite (HAP) and stainless steel sensors as model surfaces show a greatly enhanced affinity of the aqueous P-PUDs and furthermore indicate polymer chain rearrangements and autonomous film formation under wet conditions. Due to their facile synthesis, significantly improved adhesion, and variable film properties, P-PUD systems such as the one described here are believed to be of great interest for multiple applications, e.g., adhesives, paints, anticorrosion, or dentistry.

  2. Injectable acrylic bone cements for vertebroplasty with improved properties.

    PubMed

    Carrodeguas, Raúl García; Lasa, Blanca Vázquez; Del Barrio, Julio San Román

    2004-01-15

    Currently commercially available acrylic bone cements lack adequate radiopacity and viscosity when they are used in percutaneous vertebroplasty (PVP). In this work improved formulations of radiopaque and injectable poly(methyl methacrylate) bone cements were prepared with different amounts (10-50 wt.%) of BaTiO3 or SrTiO3 particles as the radiopaque agent. Two sets of cements were prepared by using untreated or silanated radiopaque particles, respectively. The influence of the content and nature of the radiopaque agent as well as its silanation with 3-(trimethoxysilyl) propyl methacrylate (gamma-MPS), on the curing parameters, residual monomer content, radiopacity, mechanical properties, and injectability of the resulting materials, was examined. Doughing and setting times, maximum temperature, and compressive strength of all formulations fulfilled the requirements of standard specifications, with values of peak temperature in the range 57-72 degrees C and those of compressive strength between 114 and 135 MPa. Formulations containing at least 20 wt.% BaTiO3 or SrTiO3 had radiopacities equal to or greater than that corresponding to 2 mm of Al as required for surgical plastics. Injectability of any of the formulations provided 75-80 wt.% of the total mass manually injected through a conventional biopsy needle 4 min after mixing. Silanation of the BaTiO3 or SrTiO3 particles led to formulations with improved mechanical properties and injectability compared to those obtained with the untreated fillers.

  3. Flavonoid insertion into cell walls improves wood properties.

    PubMed

    Ermeydan, Mahmut A; Cabane, Etienne; Masic, Admir; Koetz, Joachim; Burgert, Ingo

    2012-11-01

    Wood has an excellent mechanical performance, but wider utilization of this renewable resource as an engineering material is limited by unfavorable properties such as low dimensional stability upon moisture changes and a low durability. However, some wood species are known to produce a wood of higher quality by inserting mainly phenolic substances in the already formed cell walls--a process so-called heartwood formation. In the present study, we used the heartwood formation in black locust (Robinia pseudoacacia) as a source of bioinspiration and transferred principles of the modification in order to improve spruce wood properties (Picea abies) by a chemical treatment with commercially available flavonoids. We were able to effectively insert hydrophobic flavonoids in the cell wall after a tosylation treatment for activation. The chemical treatment reduced the water uptake of the wood cell walls and increased the dimensional stability of the bulk spruce wood. Further analysis of the chemical interaction of the flavonoid with the structural cell wall components revealed the basic principle of this bioinspired modification. Contrary to established modification treatments, which mainly address the hydroxyl groups of the carbohydrates with hydrophilic substances, the hydrophobic flavonoids are effective by a physical bulking in the cell wall most probably stabilized by π-π interactions. A biomimetic transfer of the underlying principle may lead to alternative cell wall modification procedures and improve the performance of wood as an engineering material.

  4. Improved thermoelectric properties in heavily doped FeGa3

    NASA Astrophysics Data System (ADS)

    Ponnambalam, V.; Morelli, Donald T.

    2015-12-01

    FeGa3, a hybridization gap semiconductor, has been substituted with an n-type dopant Ge to form a series of compositions FeGa3-xGex. Electrical and thermal transport properties of these compositions have been studied. Change in carrier density (n) is evident from the Hall measurements. The carrier density (n) can be as high as ˜1021 cm-3 in these compositions. In order to study the role of heavy doping on the thermoelectric properties of FeGa3, an alloy series Fe1-yCoyGa3-xGex has also been synthesized with higher concentrations of Ge (x = 0.1-0.35) and Co (y = 0.1-0.5). From resistivity and Seebeck coefficient measurements, it appears that heavy doping is accomplished by the simultaneous substitutions of Ge and Co. The systematic change in both resistivity (ρ) and Seebeck coefficient (α) is possibly due to change in the carrier density (n). The power factor (PF) α2/ρ improves steadily with increasing carrier density and the best PF ˜1.1 mW/m K2 is observed for the heavily doped compositions at 875 K. In the alloy series Fe1-yCoyGa3-xGex, thermal conductivity is also reduced substantially due to point defect scattering. Due to higher power factors, the figure of merit ZT improves to 0.25 at 875 K for the heavily doped compositions.

  5. Improvement of thermoelectric properties of alkaline-earth hexaborides

    SciTech Connect

    Takeda, Masatoshi . E-mail: takeda@mech.nagaokaut.ac.jp; Terui, Manabu; Takahashi, Norihito; Ueda, Noriyoshi

    2006-09-15

    Thermoelectric (TE) and transport properties of alkaline-earth hexaborides were examined to investigate the possibility of improvement in their TE performance. As carrier concentration increased, electrical conductivity increased and the absolute value of the Seebeck coefficient decreased monotonically, while carrier mobility was almost unchanged. These results suggest that the electrical properties of the hexaboride depend largely on carrier concentration. Thermal conductivity of the hexaboride was higher than 10 W/m K even at 1073 K, which is relatively high among TE materials. Alloys of CaB{sub 6} and SrB{sub 6} were prepared in order to reduce lattice thermal conductivity. Whereas the Seebeck coefficient and electrical conductivity of the alloys were intermediate between those of CaB{sub 6} and SrB{sub 6} single phases, the thermal conductivities of the alloys were lower than those of both single phases. The highest TE performance was obtained in the vicinity of Ca{sub 0.5}Sr{sub 0.5}B{sub 6}, indicating that alloying is effective in improving the performance. - Graphical abstract: Thermoelectric figure-of-merit, ZT, for (Ca,Sr)B{sub 6} alloys. The highest ZT value of 0.35 at 1073 K was obtained due to effective reduction of thermal conductivity by alloying.

  6. Synthesis and evaluation of the structural and physicochemical properties of carboxymethyl pregelatinized starch as a pharmaceutical excipient

    PubMed Central

    Lefnaoui, Sonia; Moulai-Mostefa, Nadji

    2015-01-01

    A pregelatinized starch (PGS) was derivatized with sodium chloroacetate (SCA) in alcoholic medium under alkaline condition to produce carboxymethyl pregelatinized starch (CMPGS) with various degrees of substitution (DS). Influence of the molar ratio of SCA to the glucopyranose units (SCA/GU), reaction time, temperature and the amount of sodium hydroxide on the degree of substitution (DS) and the reaction efficiency (RE) was studied. An optimal concentration of 30% of NaOH, for a reaction time of 1 h at 50 °C and molar ratio (SCA/GU) equal to 1.0, yielded an optimal DS of 0.55 and a RE of 55%. SEM micrographs revealed that the carboxymethylation assigned the structural arrangement of CMPGS and caused the granular disintegration. Wide angle diffraction X-ray (XRD) showed that the crystallinity of starch was obviously varied after carboxymethylation. New bands in FTIR spectra at 1417 and 1603 cm−1 indicated the presence of carboxymethyl groups. The solubility and viscosity of CMPGS increased with an increase in the degree of modification. In order to investigate the influence of DS on physical and drug release properties, CMPGS obtained with DS in the range of 0.12–0.55 was evaluated as tablet excipient for sustained drug release. Dissolution tests performed in phosphate buffer (pH 6.8), with Ibuprofen as drug model (25% loading) showed that CMPGS seems suitable to be used as sustained release excipient since the drug release was driven over a period up to 8 h. The in vitro release kinetics studies revealed that all formulations fit well with Korsmeyer-Peppas model and the mechanism of drug release is non-Fickian diffusion. PMID:26702266

  7. Modified β-Cyclodextrin Inclusion Complex to Improve the Physicochemical Properties of Albendazole. Complete In Vitro Evaluation and Characterization

    PubMed Central

    García, Agustina; Leonardi, Darío; Salazar, Mario Oscar; Lamas, María Celina

    2014-01-01

    The potential use of natural cyclodextrins and their synthetic derivatives have been studied extensively in pharmaceutical research and development to modify certain properties of hydrophobic drugs. The ability of these host molecules of including guest molecules within their cavities improves notably the physicochemical properties of poorly soluble drugs, such as albendazole, the first chosen drug to treat gastrointestinal helminthic infections. Thus, the aim of this work was to synthesize a beta cyclodextrin citrate derivative, to analyze its ability to form complexes with albendazole and to evaluate its solubility and dissolution rate. The synthesis progress of the cyclodextrin derivative was followed by electrospray mass spectrometry and the acid-base titration of the product. The derivative exhibited an important drug affinity. Nuclear magnetic resonance experiments demonstrated that the tail and the aromatic ring of the drug were inside the cavity of the cyclodextrin derivative. The inclusion complex was prepared by spray drying and full characterized. The drug dissolution rate displayed exceptional results, achieving 100% drug release after 20 minutes. The studies indicated that the inclusion complex with the cyclodextrin derivative improved remarkably the physicochemical properties of albendazole, being a suitable excipient to design oral dosage forms. PMID:24551084

  8. Improving drug candidates by design: a focus on physicochemical properties as a means of improving compound disposition and safety.

    PubMed

    Meanwell, Nicholas A

    2011-09-19

    The development of small molecule drug candidates from the discovery phase to a marketed product continues to be a challenging enterprise with very low success rates that have fostered the perception of poor productivity by the pharmaceutical industry. Although there have been significant advances in preclinical profiling that have improved compound triaging and altered the underlying reasons for compound attrition, the failure rates have not appreciably changed. As part of an effort to more deeply understand the reasons for candidate failure, there has been considerable interest in analyzing the physicochemical properties of marketed drugs for the purpose of comparing with drugs in discovery and development as a means capturing recent trends in drug design. The scenario that has emerged is one in which contemporary drug discovery is thought to be focused too heavily on advancing candidates with profiles that are most easily satisfied by molecules with increased molecular weight and higher overall lipophilicity. The preponderance of molecules expressing these properties is frequently a function of increased aromatic ring count when compared with that of the drugs launched in the latter half of the 20th century and may reflect a preoccupation with maximizing target affinity rather than taking a more holistic approach to drug design. These attributes not only present challenges for formulation and absorption but also may influence the manifestation of toxicity during development. By providing some definition around the optimal physicochemical properties associated with marketed drugs, guidelines for drug design have been developed that are based largely on calculated parameters and which may readily be applied by medicinal chemists as an aid to understanding candidate quality. The physicochemical properties of a molecule that are consistent with the potential for good oral absorption were initially defined by Lipinski, with additional insights allowing further

  9. Biomimetic Hybridization of Kevlar into Silk Fibroin: Nanofibrous Strategy for Improved Mechanic Properties of Flexible Composites and Filtration Membranes.

    PubMed

    Lv, Lili; Han, Xiangsheng; Zong, Lu; Li, Mingjie; You, Jun; Wu, Xiaochen; Li, Chaoxu

    2017-08-22

    Silk, one of the strongest natural biopolymers, was hybridized with Kevlar, one of the strongest synthetic polymers, through a biomimetic nanofibrous strategy. Regenerated silk materials have outstanding properties in transparency, biocompatibility, biodegradability and sustainability, and promising applications as diverse as in pharmaceutics, electronics, photonic devices and membranes. To compete with super mechanic properties of their natural counterpart, regenerated silk materials have been hybridized with inorganic fillers such as graphene and carbon nanotubes, but frequently lose essential mechanic flexibility. Inspired by the nanofibrous strategy of natural biomaterials (e.g., silk fibers, hemp and byssal threads of mussels) for fantastic mechanic properties, Kevlar was integrated in regenerated silk materials by combining nanometric fibrillation with proper hydrothermal treatments. The resultant hybrid films showed an ultimate stress and Young's modulus two times as high as those of pure regenerated SF films. This is not only because of the reinforcing effect of Kevlar nanofibrils, but also because of the increasing content of silk β-sheets. When introducing Kevlar nanofibrils into the membranes of silk nanofibrils assembled by regenerated silk fibroin, the improved mechanic properties further enabled potential applications as pressure-driven nanofiltration membranes and flexible substrates of electronic devices.

  10. Genoproteomics-assisted improvement of Andrographis paniculata: toward a promising molecular and conventional breeding platform for autogamous plants affecting the pharmaceutical industry.

    PubMed

    Valdiani, Alireza; Talei, Daryush; Lattoo, Surrinder K; Ortiz, Rodomiro; Rasmussen, Søren Kjærsgaard; Batley, Jacqueline; Rafii, Mohd Yusop; Maziah, Mahmood; Sabu, Kallevettankuzhy K; Abiri, Rambod; Sakuanrungsirikul, Suchirat; Tan, Soon Guan

    2017-09-01

    plant production and, therefore, can be regarded as prospective breeding platforms for medicinal plants that have an autogamous mode of reproduction. Finally, this review suggests that novel site-directed genome editing approaches such as TALENs (Transcription Activator-Like Effector Nucleases) and CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein-9 nuclease) systems together with other new plant breeding technologies (NPBT) should simultaneously be taken into consideration for improvement of pharmaceutical plants.

  11. The pharmaceutical industry in Cuba.

    PubMed

    Tancer, R S

    1995-01-01

    Cuba has developed a relatively sophisticated pharmaceutical sector, originally to provide medicinal products for her own population and, more recently, to earn hard currency through exports. Cuba has achieved both of these goals despite the US trade embargo, which isolates Cuba from commercial relations with US firms. Cuba is opening its economy to firms from other countries through the use of joint ventures and other forms of cooperation. US firms are unable to avail themselves of these opportunities, and the opportunities are thus being lost. In the case of pharmaceuticals, the Cubans recognize that they need assistance, particularly in the areas of marketing and packaging. Allowing the participation of US firms in the Cuban pharmaceutical industry could enhance the possibility of improving worldwide health care.

  12. Soil hydraulic properties near saturation, an improved conductivity model

    NASA Astrophysics Data System (ADS)

    Børgesen, Christen D.; Jacobsen, Ole H.; Hansen, Søren; Schaap, Marcel G.

    2006-06-01

    The hydraulic properties near saturation can change dramatically due to the presence of macropores that are usually difficult to handle in traditional pore size models. The purpose of this study is to establish a data set on hydraulic conductivity near saturation, test the predictive capability of commonly used hydraulic conductivity models and give suggestions for improved models. Water retention and near saturated and saturated hydraulic conductivity were measured for a variety of 81 top and subsoils. The hydraulic conductivity models by van Genuchten [ van Genuchten, 1980. A closed-form equation for predicting the hydraulic conductivity of unsaturated soils. Soil Sci. Soc. Am. J. 44, 892-898.] (vGM) and Brooks and Corey, modified by Jarvis [ Jarvis, 1991. MACRO—A Model of Water Movement and Solute Transport in Macroporous Soils. Swedish University of Agricultural Sciences. Department of Soil Sciences. Reports and Dissertations 9.] were optimised to describe the unsaturated hydraulic conductivity in the range measured. Different optimisation procedures were tested. Using the measured saturated hydraulic conductivity in the vGM model tends to overestimate the unsaturated hydraulic conductivity. Optimising a matching factor ( k0) improved the fit considerably whereas optimising the l-parameter in the vGM model improved the fit only slightly. The vGM was improved with an empirical scaling function to account for the rapid increase in conductivity near saturation. Using the improved models, it was possible to describe both the saturated and the unsaturated hydraulic conductivity better than a previously published model by Jarvis. The pore size boundary of the macropores was found at a capillary pressure of -4 hPa corresponding to a circular pore diameter of 750 μm.

  13. Applications of polybenzoxazines for improvement in processability and property

    NASA Astrophysics Data System (ADS)

    Jin, Lin

    Polybenzoxazines obtained from the polymerization of benzoxazine monomers or oligomers has been used for various applications: to simplify the technology adopted for protection, to improve the processability of high performance material and to replace the environmental hazards in resins. Novel siloxane-containing benzoxazine oligomers with benzoxazine rings in the main chain have been synthesized and mixed with octasilane polyhedral silsesquioxane (OctaSilane POSS) and glass sphere to form a thermo-oxidatively stable coating on a carbon/carbon composite after polymerization and baking. The coating method is very simple and inexpensive compared with the conventional approaches, such as chemical vapor deposition. The effectiveness of the coating has also been demonstrated. A new class of benzoxazine-containing monomers, namely bis(benzoxazinemaleimide)s have been synthesized to improve the poor processability of bismaleimides. A new approach of using high boiling point nonpolar solvent has been developed to prepare the monomer, which is difficult to synthesize using the traditional method of synthesizing benzoxazines. In the meantime, by the combination of two types of polymers: benzoxazine and bismaleimides, high thermally stable thermosets with high Tg have been obtained. Benzoxazine monomers have also been introduced into vinyl ester resins to replace styrene for environmental concern. With the incorporation of allyl-containing benzoxazines, the dynamic mechanical property and the thermal stability of the resins have been improved, while the processability of the resin is maintained.

  14. To see, or not to see, that is the question: can public disclosure really improve transparency between medicine and the pharmaceutical industry?

    PubMed

    Smith, Geoffrey P

    2014-06-01

    To critically review the potential effect of the public reporting of pharmaceutical company payments to healthcare professionals on the relationship between medicine and industry. This review is based on an examination of the 'Transparency Model' put out recently for consultation by Medicines Australia. Public reporting in itself will neither sharpen the boundaries between medicine and the pharmaceutical industry nor restore public confidence. Focusing on payments for clinical research and on the larger payments to healthcare professionals would lead to a better understanding of the interplay between science and marketing. © The Royal Australian and New Zealand College of Psychiatrists 2014.

  15. Microstructure of Tablet-Pharmaceutical Significance, Assessment, and Engineering.

    PubMed

    Sun, Changquan Calvin

    2017-05-01

    To summarize the microstructure - property relationship of pharmaceutical tablets and approaches to improve tablet properties through tablet microstructure engineering. The main topics reviewed here include: 1) influence of material properties and manufacturing process parameters on the evolution of tablet microstructure; 2) impact of tablet structure on tablet properties; 3) assessment of tablet microstructure; 4) development and engineering of tablet microstructure. Microstructure plays a decisive role on important pharmaceutical properties of a tablet, such as disintegration, drug release, and mechanical strength. Useful information on mechanical properties of a powder can be obtained from analyzing tablet porosity-pressure data. When helium pycnometry fails to accurately measure true density of a water-containing powder, non-linear regression of tablet density-pressure data is a useful alternative method. A component that is more uniformly distributed in a tablet generally exerts more influence on the overall tablet properties. During formulation development, it is highly recommended to examine the relationship between any property of interest and tablet porosity when possible. Tablet microstructure can be engineered by judicious selection of formulation composition, including the use of the optimum solid form of the drug and appropriate type and amount of excipients, and controlling manufacturing process.

  16. Improvements in CVD diamond properties for radiotherapy dosimetry.

    PubMed

    De Angelis, C; Bucciolini, M; Casati, M; Løvik, I; Bruzzi, M; Lagomarsino, S; Sciortino, S; Onori, S

    2006-01-01

    The goal of this work was to compare the behaviour of a chemical vapour deposited (CVD) diamond sample, grown at the University of Florence using a local procedure, with that of a commercial CVD diamond. The comparison was performed exposing both systems to 25 MV photons and measuring the current response during irradiation. Properties of dosimetric interest such as stability of response, dose rate dependence and rise time were investigated. After a preliminary study, which evidenced better performances of the commercial device with respect to the local CVD diamond, the latter was irradiated with a high fluence of fast neutrons. As a result of the neutron treatment, the quality of the CVD home-made diamond has been improved to match with that of the commercial dosemeter.

  17. Polyimide-organosilicate hybrids with improved thermal and optical properties.

    PubMed

    Jung, Youngsuk; Byun, Sunjung; Park, Sungjun; Lee, Hyunmi

    2014-05-14

    Through hydrolysis and polycondensation of amino-silane with alkyl bridged silane, a new type of polysilsesquioxane (PSSQ) was obtained. Here we use amine functionalized silane and bis(silyl)ethane to synthesize alkyl chain linked PSSQ. Compared to conventional polyhedral oligomeric silsesquioxane (POSS), this new silane compound has both enhanced thermal stability and improved compatibility with poly(amic acid). Gelation of this silane compound with poly(amic acid) provides polyimide-organosilicate composite materials. We show that films made from solutions of the composites exhibit higher optical transparency and superior dimensional stability during thermal treatment than films of pure polyimide or of polyimide composites with conventional POSS. Bridging of POSS and chemical bonding between POSS and polyimide chains significantly enhance the physical properties. These results provide useful information for designing molecular architecture for the fabrication of high-performance plastic substrates in the future display devices.

  18. Mutagenizing brewing yeast strain for improving fermentation property of beer.

    PubMed

    Liu, Zengran; Zhang, Guangyi; Sun, Yunping

    2008-07-01

    A brewing yeast mutant with perfect sugar fermentation capacity was isolated by mutagenizing the Saccharomyces pastorianus transformant, which carries an integrated glucoamylase gene and has one copy of non-functional alpha-acetolactate synthase gene. The mutant was able to utilize maltotriose efficiently, and the maltotriose fermentability in YNB-2% maltotriose medium increased from 32.4% to 72.0% after 5 d in shaking culture. The wort fermentation test confirmed that the sugar fermentation property of the mutant was greatly improved, while its brewing performances were analogous to that of the wild-type strain and the characteristic trait of shortened beer maturation period was retained. Therefore, we believe that the brewing yeast mutant would benefit the beer industry and would be useful for low caloric beer production.

  19. Improving properties of Mg with Al–Cu additions

    SciTech Connect

    Rashad, Muhammad; Pan, Fusheng; Asif, Muhammad; Hussain, Shahid; Saleem, Muhammad

    2014-09-15

    The present work reports improvement in tensile properties of the Mg matrix reinforced with micron-sized copper–aluminum particulate hybrids. The Al–Cu particulate hybrids were incorporated into the Mg matrix through powder metallurgy method. The synthesized alloys exhibited homogeneously dispersed Mg{sub 2}Cu particles in the matrix, therefore leading to a 110% increase in yield strength (221 MPa) and a 72% enhancement in ultimate tensile strength (284 MPa) by addition of 1.0 wt.%Al–0.6 wt.%Cu particle hybrids. Optical microscopy, scanning election microscopy, transmission electron microscopy and X-ray diffraction were used to investigate the microstructure and intermetallic phases of the synthesized alloys. - Highlights: • Mg matrix is reinforced with Al–Cu particulate hybrids. • Powder metallurgic method is used to fabricate the alloys. • Tensile strength and ductility were increased simultaneously.

  20. Cyclization of conotoxins to improve their biopharmaceutical properties.

    PubMed

    Clark, Richard J; Akcan, Muharrem; Kaas, Quentin; Daly, Norelle L; Craik, David J

    2012-03-15

    Conotoxins are disulfide-rich peptides from the venoms of marine cone snails that are used in prey capture. Due to their exquisite potency and selectivity for different ion channels, receptors and transporters they have attracted much interest as leads in drug design. This article gives a brief background on conotoxins, describes their structures and highlights methods for synthetic cyclization to improve their biopharmaceutical properties. The proximity of the N and C termini of many conotoxins makes them particularly suitable for cyclization with linkers of on average five to seven amino acids. By linking the ends of conotoxins it is possible to significantly decrease their susceptibility to proteolysis without loss of their intrinsic biological activity. Here, the principles of conotoxin cyclization are illustrated with applications to the α- and χ- conotoxin classes, which have been implicated as leads for the treatment of pain and a range of other disorders including neuroprotection, schizophrenia, depression and cancer.

  1. Method to produce gamma titanium aluminide articles having improved properties

    SciTech Connect

    Youngwon Kim; Dimiduk, D.M.

    1993-07-13

    A method is described for producing articles of gamma titanium aluminide alloy having improved properties which comprises the steps of: (a) shaping said article at a temperature in the approximate range of about 130 C below the titanium-aluminum eutectoid temperature of said alloy to about 20 C below the alpha-transus temperature of said alloy; (b) heat treating the thus-shaped article at about the alpha transus temperature of said alloy for about 15 to 120 minutes; (c) cooling the heat-treated article at a rate of about 30 to 500 C per minute; and (d) aging the article at a temperature between about 750 and 1,050 C for about 4 to 300 hours.

  2. Improvement of cement concrete strength properties by carbon fiber additives

    NASA Astrophysics Data System (ADS)

    Nevsky, Andrey; Kudyakov, Konstantin; Danke, Ilia; Kudyakov, Aleksandr; Kudyakov, Vitaly

    2016-01-01

    The paper presents the results of studies of fiber-reinforced concrete with carbon fibers. The effectiveness of carbon fibers uniform distribution in the concrete was obtained as a result of its preliminary mechanical mixing in water solution with chemical additives. Additives are to be used in the concrete technology as modifiers at initial stage of concrete mix preparing. The technology of preparing of fiber-reinforced concrete mix with carbon fibers is developed. The superplasticizer is based on ether carboxylates as a separator for carbon fibers. The technology allows increasing of concrete compressive strength up to 43.4% and tensile strength up to 17.5% as well as improving stability of mechanical properties.

  3. Improvement in properties of plastic teeth by electron beam irradiation

    NASA Astrophysics Data System (ADS)

    Sano, Yuko; Ishikawa, Shun-ichi; Seguchi, Tadao

    2011-11-01

    Improvement of the comfort and esthetics of artificial plastic teeth is desirable for the recently increasing numbers of elderly in society. Plastic teeth made of polycarbonate (PC) were modified by electron beam (EB) irradiation under specific conditions, and the change in the chemical properties of the PC was investigated. The water absorption, glucose attachment, level of bis-phenol-A (BPA) extraction, maltose adhesion, and mucin adhesion on the PC teeth were measured before and after EB irradiation. EB irradiation to a dose of 3.5 kGy at 150 °C in a nitrogen gas atmosphere reduced the water absorption by 20%, glucose absorption by 40%, maltose adhesion by 20%, and the amount of various amino acids, formed as the hydrolysis products of mucin, adhering on the PC teeth were reduced by 60-99%. The BPA content was lower than the detection limit for analysis of both the original and the EB irradiated PC teeth.

  4. Ceramic Composite Intermediate Temperature Stress-Rupture Properties Improved Significantly

    NASA Technical Reports Server (NTRS)

    Morscher, Gregory N.; Hurst, Janet B.

    2002-01-01

    Silicon carbide (SiC) composites are considered to be potential materials for future aircraft engine parts such as combustor liners. It is envisioned that on the hot side (inner surface) of the combustor liner, composites will have to withstand temperatures in excess of 1200 C for thousands of hours in oxidizing environments. This is a severe condition; however, an equally severe, if not more detrimental, condition exists on the cold side (outer surface) of the combustor liner. Here, the temperatures are expected to be on the order of 800 to 1000 C under high tensile stress because of thermal gradients and attachment of the combustor liner to the engine frame (the hot side will be under compressive stress, a less severe stress-state for ceramics). Since these composites are not oxides, they oxidize. The worst form of oxidation for strength reduction occurs at these intermediate temperatures, where the boron nitride (BN) interphase oxidizes first, which causes the formation of a glass layer that strongly bonds the fibers to the matrix. When the fibers strongly bond to the matrix or to one another, the composite loses toughness and strength and becomes brittle. To increase the intermediate temperature stress-rupture properties, researchers must modify the BN interphase. With the support of the Ultra-Efficient Engine Technology (UEET) Program, significant improvements were made as state-of-the-art SiC/SiC composites were developed during the Enabling Propulsion Materials (EPM) program. Three approaches were found to improve the intermediate-temperature stress-rupture properties: fiber-spreading, high-temperature silicon- (Si) doped boron nitride (BN), and outside-debonding BN.

  5. Improving the mechanical properties of nano-hydroxyapatite

    NASA Astrophysics Data System (ADS)

    Khanal, Suraj Prasad

    Hydroxyapatite (HAp) is an ideal bioactive material that is used in orthopedics. Chemical composition and crystal structure properties of HAp are similar to the natural bone hence it promotes bone growth. However, its mechanical properties of synthetic HAp are not sufficient for major load-bearing bone replacement. The potential of improving the mechanical properties of synthetic hydroxyapatite (HAp) by incorporating carboxyl functionalized single walled carbon nanotubes (CfSWCNT) and polymerized epsilon-caprolactam (nylon) is studied. The fracture toughness, tensile strength, Young's modulus, stiffness and fracture energy were studied for a series of HAp samples with CfSWCNT concentrations varying from 0 to 1.5 wt. % without, and with nylon addition. X-ray diffraction (XRD), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM) and Differential Scanning Calorimetry (DSC) were used to characterize the samples. The fracture toughness and tensile test was performed under the standard protocol of ASTM D5045 and ASTM D638-02a respectively. Reproducible maximum values of (3.60 +/- 0.3) MPa.m1/2 for fracture toughness and 65.38 MPa for tensile strength were measured for samples containing 1 wt. % CfSWCNT and nylon. The Young's modulus, stiffness and fracture energy of the samples are 10.65 GPa, 1482.12 N/mm, and 644 J/m2 respectively. These values are comparable to those of the cortical bone. Further increase of the CfSWCNT content results to a decreased fracture toughness and tensile strength and formation of a secondary phase.

  6. Processed wastewater sludge for improvement of mechanical properties of concretes.

    PubMed

    Barrera-Díaz, Carlos; Martínez-Barrera, Gonzalo; Gencel, Osman; Bernal-Martínez, Lina A; Brostow, Witold

    2011-08-15

    Two problems are addressed simultaneously. One is the utilisation of sludge from the treatment of wastewater. The other is the modification of the mechanical properties of concrete. The sludge was subjected to two series of treatments. In one series, coagulants were used, including ferrous sulphate, aluminium sulphate or aluminium polyhydroxychloride. In the other series, an electrochemical treatment was applied with several starting values of pH. Then, concretes consisting of a cement matrix, silica sand, marble and one of the sludges were developed. Specimens without sludge were prepared for comparison. Curing times and aggregate concentrations were varied. The compressive strength, compressive strain at yield point, and static and dynamic elastic moduli were determined. Diagrams of the compressive strength and compressive strain at the yield point as a function of time passed through the minima as a function of time for concretes containing sludge; therefore, the presence of sludge has beneficial effects on the long term properties. Some morphological changes caused by the presence of sludge are seen in scanning electron microscopy. A way of utilising sludge is thus provided together with a way to improve the compressive strain at yield point of concrete. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Ni-Flash-Coated Galvannealed Steel Sheet with Improved Properties

    NASA Astrophysics Data System (ADS)

    Pradhan, D.; Dutta, M.; Venugopalan, T.

    2016-11-01

    In the last several years, automobile industries have increasingly focused on galvannealed (GA) steel sheet due to their superior properties such as weldability, paintability and corrosion protection. To improve the properties further, different coatings on GA have been reported. In this context, an electroplating process (flash coating) of bright and adherent Ni plating was developed on GA steel sheet for covering the GA defects and enhancing the performances such as weldability, frictional behavior, corrosion resistance and phosphatability. For better illustration, a comparative study with bare GA steel sheet has also been carried out. The maximum electroplating current density of 700 A/m2 yielded higher cathode current efficiency of 95-98%. The performances showed that Ni-coated (coating time 5-7 s) GA steel sheet has better spot weldability, lower dynamic coefficient of friction (0.07 in lubrication) and three times more corrosion resistance compared to bare GA steel sheet. Plate-like crystal of phosphate coating with size of 10-25 µm was obtained on the Ni-coated GA. The main phase in the phosphate compound was identified as hopeite (63.4 wt.%) along with other phases such as spencerite (28.3 wt.%) and phosphophyllite (8.3 wt.%).

  8. Stealth Properties to Improve Therapeutic Efficacy of Drug Nanocarriers

    PubMed Central

    Caliceti, Paolo

    2013-01-01

    Over the last few decades, nanocarriers for drug delivery have emerged as powerful tools with unquestionable potential to improve the therapeutic efficacy of anticancer drugs. Many colloidal drug delivery systems are underdevelopment to ameliorate the site specificity of drug action and reduce the systemic side effects. By virtue of their small size they can be injected intravenously and disposed into the target tissues where they release the drug. Nanocarriers interact massively with the surrounding environment, namely, endothelium vessels as well as cells and blood proteins. Consequently, they are rapidly removed from the circulation mostly by the mononuclear phagocyte system. In order to endow nanosystems with long circulation properties, new technologies aimed at the surface modification of their physicochemical features have been developed. In particular, stealth nanocarriers can be obtained by polymeric coating. In this paper, the basic concept underlining the “stealth” properties of drug nanocarriers, the parameters influencing the polymer coating performance in terms of opsonins/macrophages interaction with the colloid surface, the most commonly used materials for the coating process and the outcomes of this peculiar procedure are thoroughly discussed. PMID:23533769

  9. Enzymatic modification of egg lecithin to improve properties.

    PubMed

    Asomaning, Justice; Curtis, Jonathan M

    2017-04-01

    This research studied the enzymatic modification of egg yolk phospholipids and its effect on physicochemical properties. Egg yolk lipids were extracted with food grade ethanol and egg phospholipids (ePL) produced by deoiling with acetone. Vegetable oils were used to interesterify ePL utilizing Lipozyme®: sn-1,3 specific lipase. The enzymatic interesterification resulted in a single phase liquid product, whereas simple blending of the ePL and vegetable oil resulted in a product with two phases. In addition solid fat content decreased by 50% at -10°C and 94% at 35°C when compared with egg yolk lipids extract. A decrease in melting temperature resulted from the interesterification process. Interesterification improved emulsion stability index when used as an emulsifier in oil-in-water emulsion and compared to the native and soy lecithin. Enzyme reusability test showed retention of 63% activity after 10 cycles. Overall, the properties of native egg phospholipids were significantly enhanced in a potentially useful manner through interesterification. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Polysaccharides of Trametes versicolor Improve Bone Properties in Diabetic Rats.

    PubMed

    Chen, Chung-Hwan; Kang, Lin; Lo, Hui-Chen; Hsu, Tai-Hao; Lin, Fang-Yi; Lin, Yi-Shan; Wang, Zai-Jie; Chen, Shih-Tse; Shen, Chwan-Li

    2015-10-28

    This study investigates the effects of Trametes versicolor (L.:Fr.) Pilát (TVP, also known as Yunzhi) on bone properties in diabetic rats. Forty-five male Wistar rats (8 weeks old) were fed either a chow diet (control) or a high-fat diet throughout the study period of 28 days. Animals in the high-fat-diet group were injected with nicotinamide and streptozotocin to induce diabetes mellitus (DM). The DM rats were divided into a group receiving distilled water (vehicle) and another group receiving TVP at 0.1 g/kg weight by gavage. Relative to the vehicle group, TVP gavage lowered postprandial blood sugar (225 ± 18 mg/dL for TVP vs 292 ± 15 mg/dL for vehicle, p < 0.001) on day 26. Compared to the vehicle group, TVP mitigated DM-induced bone deterioration as determined by increasing bone volume of proximal tibia (22.8 ± 1.4% for TVP vs 16.8 ± 1.3% for vehicle, p = 0.003), trabecular number (p = 0.011), and femoral bone strength (11% in maximal load, 22% in stiffness, 14% in modulus, p < 0.001), and by reducing loss of femoral cortical porosity by 25% (p < 0.001). Our study demonstrates the protective effect of TVP on bone properties was mediated through, in part, the improvement of hyperglycemic control in DM animals.

  11. Montmorillonite-levan nanocomposites with improved thermal and mechanical properties.

    PubMed

    Chen, Xiaoming; Gao, Hongsheng; Ploehn, Harry J

    2014-01-30

    This work reports on the structure and properties of novel nanocomposites composed of exfoliated montmorillonite clay blended with levan, a polysaccharide produced by Bacillus sp. Dry levan is very brittle, making it difficult to obtain stand-alone films. MMT-levan composites were prepared by solution blending in water, coating on plastic surfaces, partial drying at 50°C, and conditioning in air at 50-60% relative humidity. This process results in freestanding, transparent, and flexible films of pure levan and MMT-levan composites plasticized by 10-15 wt% water. XRD patterns from levan-MMT composites indicate an MMT interlayer spacing 0.62 nm greater than that of the starting MMT, suggesting re-stacking of MMT platelets coated by adsorbed, uncoiled levan molecules. FTIR results suggest that levan adheres to MMT via water-mediated hydrogen bonding between the levan's hydroxyl groups and MMT surface oxygens. MMT-levan composites have improved thermal stability and a well-defined glass transition temperature that increases with MMT loading. The tensile moduli of levan-MMT composites increase by as much as 480% relative to pure levan. The XRD and mechanical property results suggest that MMT reinforces levan through a filler network structure composed of MMT platelets bridged by adsorbed levan molecules, enhanced when the MMT loading becomes high enough (5-10wt% MMT) to induce an isotropic-nematic transition in MMT platelet orientation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Do changes to supply chains and procurement processes yield cost savings and improve availability of pharmaceuticals, vaccines or health products? A systematic review of evidence from low-income and middle-income countries

    PubMed Central

    Atun, Rifat

    2017-01-01

    Introduction Improving health systems performance, especially in low-resource settings facing complex disease burdens, can improve population health. Specifically, the efficiency and effectiveness of supply chains and procurement processes for pharmaceuticals, vaccines and other health products has important implications for health system performance. Pharmaceuticals, vaccines and other health products make up a large share of total health expenditure in low-income and middle-income countries (LMICs), and they are critical for delivering health services. Therefore, programmes which achieve cost savings on these expenditures may help improve a health system's efficiency, whereas programmes that increase availability of health products may improve a health system's effectiveness. This systematic review investigates whether changes to supply chains and procurement processes can achieve cost savings and/or improve the availability of drugs in LMICs. Methods Using the PRISMA guidelines for systematic reviews, we searched PubMed, Embase, CINAHL and the Health Economic Evaluation Database to identify. Results We identified 1264 articles, of which 38 were included in our study. We found evidence that centralised procurement and tendering can achieve direct cost savings, while supply chain management programmes can reduce drug stock outs and increase drug availability for populations. Conclusions This research identifies a broad set of programmes which can improve the ways that health systems purchase and delivery health products. On the basis of this evidence, policymakers and programme managers should examine the root causes of inefficiencies in pharmaceutical supply chain and procurement processes in order to determine how best to improve health systems performance in their specific contexts. PMID:28589028

  13. Coamorphous atorvastatin calcium to improve its physicochemical and pharmacokinetic properties.

    PubMed

    Shayanfar, Ali; Ghavimi, Hamed; Hamishekar, Hamed; Jouyban, Abolghasem

    2013-01-01

    Atorvastatin calcium (ATC) is classified as class II (low solubility and high permeability) compound according to the biopharmaceutical classification system. The amorphous form of ATC possesses higher solubility, dissolution rate, and bioavailability than its crystalline form. Coamorphous drug system is a new and emerging method to prepare stable amorphous forms, in this case leading to the improved stability of ATC in dissolution medium. In this study, coamorphous form of ATC and nicotinamide (ATC-NIC) was prepared from solvent evaporation method and characterized using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR) and powder X-ray diffraction (PXRD). The intrinsic dissolution rate and solubility of ATC-NIC were determined along with plasma concentrations of ATC using HPLC after oral dosing in rats. The crystalline ATC was converted to coamorphous form revealing a molecular interaction between ATC and NIC. The intrinsic dissolution rate, solubility and plasma concentration of coamorphous ATC-NIC are higher than those of crystalline ATC. ATC-NIC coamorphous system showed greater solution stability than those reported in the literature for amorphous ATC. Coamorphous ATC-NIC has improved physicochemical and pharmacokinetic properties as compared to ATC. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

  14. Possibility of improvement of hemoglobin properties as biosensors' detection element

    NASA Astrophysics Data System (ADS)

    Martirosyan, A. S.; Vardapetyan, H. R.; Tiratsuyan, S. G.; Hovhannisyan, A. A.

    2010-04-01

    Biosensors are finding numerous applications in clinical diagnosis, drug discovery, biotechnology, environmental monitoring and etc. Hemoglobin (Hb), a natural heme containing protein, exhibits enzymatic activity towards hydrogen peroxide, which is possible to improve by altering the heme orientation and/or changing the microenvironment in the vicinity of the heme sites. It was shown that hypericin (HY), a naphthodianthrone from Hipericum perforatum and a potent photosensitizer, interacts with Hb and causes conformational changes of the protein. These results were gained both in dark and under visible light exposure by absorption and fluorescence spectroscopy. It was shown that photodynamic influence of HY leads to Hb absorption decrease at Soret band, depending on HY concentration and irradiation doze. Excitation of Hb/HY complexes leads to reduction of some emission peaks, correlating with the concentration of HY, incubation and irradiation time. The incubation and irradiation of complexes leads to an increase in electrophoretic mobility of Hb and its peroxidase activity. Under the HY influence Hb properties as a hydrogen peroxide detector could be improved and an effective determination of peroxide formation could be achieved. This makes Hb an attractive 'recognition' element for construction of third-generation biosensors.

  15. Wet-preserved hemp fibreboard properties improvement with veneering

    NASA Astrophysics Data System (ADS)

    Kirilovs, E.; Kukle, S.; Gusovius, H.-J.

    2015-03-01

    The initial research describes a new type of fiber boards for the furniture interior design, developed in cooperation with ATB (Leibniz-Institute for Agricultural Engineering) by using a new method of raw materials preparation and specific production technologies of ATB. The main raw materials are aerobically aged hemp stalks. The samples are made of hemp chips with a long preservation time and fastened together with the UF glue. Specimens are 8 mm thick and correspond to a medium-density fiberboard, fitting standard EN622. Due to the fact that non-veneered material can be used only in non-load-bearing constructions, material improving technologies were studied, such as increase of board density, increase of glue percentage, partially substitution of wet-preserved hemp chips with a dry hemp and/or wooden chips to equalize moisture content of obtained mixture. The particular article describes how the new material is veneered with the oak veneer obtaining three-ply composite board with the improved mechanical properties that allows to use these boards in a load-bearing constructions. Tests are performed with the veneered material to determine such parameters as static bending strength (MOR), modulus of elasticity in static bending (MOE), swelling in thickness and hardness.

  16. Pharmaceutical applications of hot-melt extrusion: part I.

    PubMed

    Crowley, Michael M; Zhang, Feng; Repka, Michael A; Thumma, Sridhar; Upadhye, Sampada B; Battu, Sunil Kumar; McGinity, James W; Martin, Charles

    2007-09-01

    Interest in hot-melt extrusion techniques for pharmaceutical applications is growing rapidly with well over 100 papers published in the pharmaceutical scientific literature in the last 12 years. Hot-melt extrusion (HME) has been a widely applied technique in the plastics industry and has been demonstrated recently to be a viable method to prepare several types of dosage forms and drug delivery systems. Hot-melt extruded dosage forms are complex mixtures of active medicaments, functional excipients, and processing aids. HME also offers several advantages over traditional pharmaceutical processing techniques including the absence of solvents, few processing steps, continuous operation, and the possibility of the formation of solid dispersions and improved bioavailability. This article, Part I, reviews the pharmaceutical applications of hot-melt extrusion, including equipment, principles of operation, and process technology. The raw materials processed using this technique are also detailed and the physicochemical properties of the resultant dosage forms are described. Part II of this review will focus on various applications of HME in drug delivery such as granules, pellets, immediate and modified release tablets, transmucosal and transdermal systems, and implants.

  17. Freeze Dried Quetiapine-Nicotinamide Binary Solid Dispersions: A New Strategy for Improving Physicochemical Properties and Ex Vivo Diffusion

    PubMed Central

    Al-Remawi, Mayyas Mohammad Ahmad

    2016-01-01

    Improving the physicochemical properties and oral bioavailability of quetiapine fumarate (QF) enabling enhanced antipsychotic attributes are the main aims of this research. The freeze dried solid dispersion strategy was adopted using nicotinamide (NIC) as highly soluble coformer. The prepared dispersions were characterized using scanning electron microscopy (SEM) differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). Static disc intrinsic dissolution rate and ex vivo diffusion through intestinal tissues were conducted and compared to pure quetiapine fumarate. The results demonstrated a highly soluble coamorphous system formed between quetiapine fumarate and nicotinamide at 1 : 3 molar ratio through H-bonding interactions. The results showed >14-fold increase in solubility of QF from the prepared dispersions. Increased intrinsic dissolution rate (from 0.28 to 0.603 mg cm−2 min−1) and faster flux rate through duodenum (from 0.027 to 0.041 mg cm−2 h−1) and jejunum (0.027 to 0.036 mg cm−2 h−1) were obtained. The prepared coamorphous dispersion proved to be effective in improving the drug solubility and dissolution rate and ex vivo diffusion. Therefore, binary coamorphous dispersions could be a promising solution to modify the physicochemical properties, raise oral bioavailability, and change the biopharmaceutics classification (BCS) of some active pharmaceutical ingredients. PMID:28042494

  18. [Spectral Analysis about the Pharmaceutical Cocrystal Formation of Piracetam and 3-Hydroxybenzoic Acid].

    PubMed

    Zhang, Hui-li; Xia, Yi; Hong, Zhi; Du, Yong

    2015-07-01

    Pharmaceutical cocrystal can improve physical and chemical properties of active pharmaceutical ingredient (API), meanwhile this feature has shown great potential in improving the pharmaceutical's properties and characteristics. In this study, cocrystal formation between piracetam and 3-hydroxybenzoic acid (3HBA) using grinding method has been characterized by Fourier transform infrared (FTIR), Raman and terahertz (THz) spectroscopical techniques. The vibrational modes of different motions are obtained by the assignment of the peaks in the spectra of the starting materials and the cocrystal components. FTIR, Raman and THz spectroscopical results show that the vibrational modes of the cocrystal are different from those of the starting materials. In addition, the dynamic process of the above cocrystal formation is investigated in-depth with Raman and THz spec- tra. Piracetam-3HBA cocrystal is formed pretty fast in first several minutes, and then the formation rate becomes slow. After 35 minutes, such formation process has been completed. The results offer the theoretical benchmark and unique means for real-time monitoring pharmaceutical cocrystal formation and also the corresponding quantitative analysis in the pharmaceutical field.

  19. Improving the mechanical properties of multiuse dental floss holders.

    PubMed

    Wolff, A; Staehle, H J

    2014-11-01

    This study was designed to determine the effect of using a tensioning device and various winding techniques on the tension of a polytetrafluorethylene (PTFE) floss in a multiuse holder. The hypothesis of this study is that the use of a tensioning device improves the handling and mechanical properties of floss holders. The floss holder was modified so that four different degrees of tension (single-/double-wound; with/without tensioning device) were obtained and tested in an in vitro model approximating dental proximal contact resistance. The following parameters were measured: (I) the force (N) necessary to pass through the proximal contact after the 30th passage, (II) the displacement of the floss (mm), (III) the loosening of the floss (offset, mm), (IV) the change in distance between the branches (mm). (I) passage force. All modifications reached 11 N (median). For the double-wound modification using the tensioning device, the smallest displacement (II) was 3.6 mm; the single-wound modification without the tensioning device had the highest displacement (7.6 mm, medians) (III). The offset of all four different modifications ranged between 0 and -2 mm (medians). For the modification without the tensioning device, there was a difference in offset of -2 mm (single-wound) and 0.5 mm (double-wound) (medians). Modifications with the tensioning device did not produce any offset differences. (IV) A change in distance between the branches between -3 mm and -2 mm, respectively (with the tensioning device), and 0 mm (without the tensioning device) was observed (median). The results indicated that double-wound floss and the use of a tensioning device both lead to a constant tension of the floss in the floss holder. Technical modifications such as those shown in this study should improve the mechanical properties of multiuse floss holders, which, in turn, could lead to more user-friendly floss holders and hence to higher user acceptance. © 2013 John Wiley & Sons A/S. Published

  20. Improved Rosetta Pedotransfer Estimation of Hydraulic Properties and Their Covariance

    NASA Astrophysics Data System (ADS)

    Zhang, Y.; Schaap, M. G.

    2014-12-01

    Quantitative knowledge of the soil hydraulic properties is necessary for most studies involving water flow and solute transport in the vadose zone. However, it is always expensive, difficult, and time consuming to measure hydraulic properties directly. Pedotransfer functions (PTFs) have been widely used to forecast soil hydraulic parameters. Rosetta is is one of many PTFs and based on artificial neural network analysis coupled with the bootstrap sampling method. The model provides hierarchical PTFs for different levels of input data for Rosetta (H1-H5 models, with higher order models requiring more input variables). The original Rosetta model consists of separate PTFs for the four "van Genuchten" (VG) water retention parameters and saturated hydraulic conductivity (Ks) because different numbers of samples were available for these characteristics. In this study, we present an improved Rosetta pedotransfer function that uses a single model for all five parameters combined; these parameters are weighed for each sample individually using the covariance matrix obtained from the curve-fit of the VG parameters to the primary data. The optimal number of hidden nodes, weights for saturated hydraulic conductivity and water retention parameters in the neural network and bootstrap realization were selected. Results show that root mean square error (RMSE) for water retention decreased from 0.076 to 0.072 cm3/cm3 for the H2 model and decreased from 0.044 to 0.039 cm3/cm3 for the H5 model. Mean errors which indicate variable matric potential-dependent bias were also reduced significantly in the new model. The RMSE for Ks increased slightly (H2: 0.717 to 0.722; H5: 0.581 to 0.594); this increase is minimal and a result of using a single model for water retention and Ks. Despite this small increase the new model is recommended because of its improved estimation of water retention, and because it is now possible to calculate the full covariance matrix of soil water retention

  1. Evolutionary engineering of Saccharomyces cerevisiae for improved industrially important properties.

    PubMed

    Cakar, Z Petek; Turanli-Yildiz, Burcu; Alkim, Ceren; Yilmaz, Ulkü

    2012-03-01

    This article reviews evolutionary engineering of Saccharomyces cerevisiae. Following a brief introduction to the 'rational' metabolic engineering approach and its limitations such as extensive genetic and metabolic information requirement on the organism of interest, complexity of cellular physiological responses, and difficulties of cloning in industrial strains, evolutionary engineering is discussed as an alternative, inverse metabolic engineering strategy. Major evolutionary engineering applications with S. cerevisiae are then discussed in two general categories: (1) evolutionary engineering of substrate utilization and product formation and (2) evolutionary engineering of stress resistance. Recent developments in functional genomics methods allow rapid identification of the molecular basis of the desired phenotypes obtained by evolutionary engineering. To conclude, when used alone or in combination with rational metabolic engineering and/or computational methods to study and analyze processes of adaptive evolution, evolutionary engineering is a powerful strategy for improvement in industrially important, complex properties of S. cerevisiae. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  2. A new approach to improve the properties of brazed joints

    SciTech Connect

    Zorc, B.; Kosec, L.

    2000-01-01

    Composite brazing filler metals improve mechanical properties of brazed joints. Application of a new, parallel-wire reinforcement, along with an appropriate working procedure, in the brazing of metallic materials offers solutions to several problems related to brazed joints. All reactions between constituents of the brazed joint are noteworthy. Joining of the reinforcement to the base metal without a brazing filler metal at the contact face between the reinforcement and the base metal is required. In this case, the reinforcement has a decisive influence on tensile strength, toughness and resistance to crack propagation in the reinforced brazed joint since the reinforcement is situated in the brazed-joint plane. Coalescence of the reinforcement with the base metal may be obtained in two ways, i.e., in some cases by diffusion brazing if the combination of the brazing filler metal, the base metal and the reinforcement permits, and in other cases by diffusion welding of the base metal and the reinforcement, in the latter case, the brazing filler metal is inert as far as the reinforcement and the base metal are concerned. In both cases, application of compressive force is required to permit coalescence of the reinforcement wire with the base metal over a large area.

  3. Improved Plasma Properties in RT-1 with a Levitated Coil

    NASA Astrophysics Data System (ADS)

    Saitoh, Haruhiko; Yoshida, Zensho; Ogawa, Yuichi; Morikawa, Junji; Watanabe, Sho; Yano, Yoshihisa; Suzuki, Junko

    2007-11-01

    Ring Trap-1 (RT-1) is a novel device to confine plasmas in a magnetosphere-like configuration generated by a superconducting internal conductor. The ring coil is excited with a permanent current of Ic=250kAT that is magnetically levitated in the chamber to minimize disturbances to the plasmas. The main scientific objective of RT-1 is to realize self-organized states of flowing plasmas with a very high beta value, where the thermal pressure of plasmas is balanced by the hydrodynamic pressure of a fast flow (S. M. Mahajan & Z. Yoshida, PRL 81, 4863 (1998), Z. Yoshida & S. M. Mahajan, PRL 88, 095001 (2002)). We have started a series of initial plasma experiments since 2006, and in this study, we focused on the improvements of plasma properties by the coil levitation. Hydrogen plasmas were generated by an 8.2GHz ECH system. When the coil was levitated, a line integrated electron density increased to ne=4x10^17m-2 and the peak density was close to the O-mode cut off density of the microwave. The beta value of the plasma was ˜3% and the pressure was mainly sustained by a high energy component of electrons. The magnetic surface configuration of RT-1 is also suitable for the confinement of non-neutral plasmas. Experiments on electron plasmas were conducted in RT-1 expanding the previous work in a normal conducting device.

  4. Pharmaceutical residues in tidal surface sediments of three rivers in southeastern China at detectable and measurable levels.

    PubMed

    Chen, Yongshan S; Yu, Shen; Hong, Youwei W; Lin, Qiaoying Y; Li, Hongbo B

    2013-12-01

    Pharmaceutical compounds were increasingly detected in environmental matrices but little is known whether these compounds would transport to coastal zones via watersheds. Three typical tidal rivers in southeastern China were selected and 15 surface sediment samples (0-10 cm) were collected along a 50-km tidal section of each river. Surface sediment samples were frozen-drying and then extracted for pharmaceutical compounds by an accelerated solvent extraction system. The pharmaceutical compounds in extracts were scanned using a high-performance liquid chromatography/tandern mass spectrometry (HPLC-MS/MS). Three hundred and thirty compounds from nine pharmaceutical groups were detected with signal-to-noise above three (detectable level) in the surface sediments, of which 186 compounds were with a signal-to-noise above ten (measurable level). Of all, 291 and 80 compounds were detectable and measurable in all the three rivers, respectively. The Jiulong River showed a high load of pharmaceutical compounds in surface sediment than other two rivers. Of the nine pharmaceutical groups, the antihistamines and detoxification group and anti-infective drug group contributed five dominant compounds in the surface sediments in all the three rivers. Natures of pharmaceutical compounds rather than the sediment properties (pH, EC, and total carbon content) might influence their residues. The incredible number and intensity of pharmaceutical residues were detected in tidal surface sediments of the three rivers indicating that the pharmaceutical contamination should be strongly considered in China. Source identification and eco-toxicity assessment should be taken into account in the future study. Therapeutic medicine managements need to be strictly improved at a watershed scale to reduce loads of pharmaceuticals into aquatic ecosystems.

  5. Use of Natural Gums and Mucilages as Pharmaceutical Excipients.

    PubMed

    Hamman, Hannlie; Steenekamp, Jan; Hamman, Josias

    2015-01-01

    Polysaccharide rich gums and mucilages are produced by different natural sources such as plants, animals and microbial organisms to fulfil structural and physiological functions. Their diverse structural compositions with a broad range of physicochemical properties make them useful for inclusion in dosage forms for different purposes such as to improve manufacturing processes and/or to facilitate drug delivery. A number of natural gums and mucilages have been investigated for inclusion in pharmaceutical formulations for a variety of reasons. The search for new excipients continues to be an active topic in dosage form design and drug delivery research. The aim of this review article is to give an overview of the chemical nature of natural gums and mucilages and to discuss their applications in the formulation of pharmaceutical dosage forms. Special emphasis will be placed on the use of gums and mucilages in novel drug delivery systems, such as modified release dosage forms and delivery systems that target specific sites of delivery.

  6. Pharmaceutical care in smoking cessation

    PubMed Central

    Marín Armero, Alicia; Calleja Hernandez, Miguel A; Perez-Vicente, Sabina; Martinez-Martinez, Fernando

    2015-01-01

    As a determining factor in various diseases and the leading known cause of preventable mortality and morbidity, tobacco use is the number one public health problem in developed countries. Facing this health problem requires authorities and health professionals to promote, via specific programs, health campaigns that improve patients’ access to smoking cessation services. Pharmaceutical care has a number of specific characteristics that enable the pharmacist, as a health professional, to play an active role in dealing with smoking and deliver positive smoking cessation interventions. The objectives of the study were to assess the efficacy of a smoking cessation campaign carried out at a pharmaceutical care center and to evaluate the effects of pharmaceutical care on patients who decide to try to stop smoking. The methodology was an open, analytical, pre–post intervention, quasi-experimental clinical study performed with one patient cohort. The results of the study were that the promotional campaign for the smoking cessation program increased the number of patients from one to 22, and after 12 months into the study, 43.48% of the total number of patients achieved total smoking cessation. We can conclude that advertising of a smoking cessation program in a pharmacy increases the number of patients who use the pharmacy’s smoking cessation services, and pharmaceutical care is an effective means of achieving smoking cessation. PMID:25678779

  7. Improved removal of estrogenic and pharmaceutical compounds in sewage effluent by full scale granular activated carbon: impact on receiving river water.

    PubMed

    Grover, D P; Zhou, J L; Frickers, P E; Readman, J W

    2011-01-30

    Sewage effluents are widely recognised as the main source of emerging contaminants, such as endocrine disrupting chemicals (EDCs) and pharmaceuticals in surface waters. A full-scale granular activated carbon (GAC) plant has been installed as an advanced technology for the removal of these contaminants, in a major sewage treatment works (STW) in South-West England as part of the UK National Demonstration Programme for EDCs. This study presented for the first time, an assessment of the impact of a recently commissioned, post-tertiary GAC plant in the removal of emerging contaminants in a working STW. Through regular sampling followed by solid-phase extraction and analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS), a significant reduction in the concentrations of steroidal estrogens was observed (>43-64%). In addition, significant reductions were observed for many of the pharmaceutical compounds such as mebeverine (84-99%), although the reduction was less dramatic for some of the more widely used pharmaceuticals analysed, including carbamazepine and propranolol (17-23%). Copyright © 2010 Elsevier B.V. All rights reserved.

  8. Does brand differentiate pharmaceuticals?

    PubMed

    Bednarik, Josef

    2005-12-01

    Role of marketing in pharmaceutical industry is increasing and inspiration by successful brands known from consumer goods market influenced pharmaceutical companies enough to switch their attention to branding initiatives. Still there is little evidence that pharmaceutical brands represent anything more than product only. This study aims to explore the area of branding in pharmaceutical industry. Central hypothesis of the research has been that brand and its emotional content differentiate pharmaceuticals as well as rational data derived from clinical studies. It has been tested by extensive review of available literature as well as by primary research focused on drivers of physicians' attitudes towards products and their influence on prescribing behavior. The research has been conducted in the sample of psychiatrists in the Czech Republic. No evidence about pharmaceutical brand exceeding value of product has been found in reviewed literature. Nevertheless, the primary research conducted in the sample of Czech psychiatrists indicates that emotional brand in pharmaceutical industry exists and enables author to draw a model of Customer/product life cycle that describes likely impact of functional, emotional and self-expressive benefits throughout pharmaceutical product's market presence. Pharmaceutical brand is likely to develop differently than the same of consumer goods products--it seems to be built predominantly on long-term positive experience. Marketing role in this process should lie in finding relevant product position and building brand identity compliant with real product capabilities.

  9. Biological and Pharmaceutical Nanomaterials

    NASA Astrophysics Data System (ADS)

    Kumar, Challa S. S. R.

    2006-01-01

    This first comprehensive yet concise overview of all important classes of biological and pharmaceutical nanomaterials presents in one volume the different kinds of natural biological compounds that form nanomaterials or that may be used to purposefully create them. This unique single source of information brings together the many articles published in specialized journals, which often remain unseen by members of other, related disciplines. Covering pharmaceutical, nucleic acid, peptide and DNA-Chitosan nanoparticles, the book focuses on those innovative materials and technologies needed for the continued growth of medicine, healthcare, pharmaceuticals and human wellness. For chemists, biochemists, cell biologists, materials scientists, biologists, and those working in the pharmaceutical and chemical industries.

  10. [Annual lifelong learning program for pharmaceutical care practice by the Gifu Pharmaceutical University].

    PubMed

    Sugiyama, Tadashi; Horiuchi, Tadashi; Tsuchiya, Teruo

    2011-01-01

    Knowledge and techniques involved in medical affairs have been steadily advancing. The lifelong learning programs supported by Gifu Pharmaceutical University are introduced. The 3 unique programs consist of (1) a lifelong learning program concerning recent medical topics provided by our university, (2) a reeducation program containing some lectures and practices concerning the most advanced knowledge and techniques on pharmacy and medicine, provided by co-organization of 3 public universities (Nagoya City University, University of Shizuoka, and Gifu Pharmaceutical University), and (3) an annual lifelong learning program promoted by Gifu Pharmaceutical University Pharmacy. Gifu Pharmaceutical University Pharmacy accommodates 100 prescriptions daily from hospitals. The annual lifelong learning programs held by our pharmacy have comprehensively provided practical knowledge and techniques on newly developed medicines, pharmaceutical care practice, pharmacotherapy, community pharmaceutics, and so on, for the last 10 years. Pharmacists should have full responsibility for pharmacotherapy as health care workers. The pharmacists should make a concerted effort to understand pharmacotherapy through pharmaceutical care practice by cooperation with community pharmacists, hospital pharmacists, and pharmaceutical associations. Our lifelong learning program has contributed to the improvement of pharmaceutical skills and communication among pharmacists, medical doctors, and other health care workers.

  11. Improving Thermomechanical Properties of SiC/SiC Composites

    NASA Technical Reports Server (NTRS)

    DiCarlo, James A.; Bhatt, Ramakrishna T.

    2006-01-01

    Today, a major thrust toward improving the thermomechanical properties of engine components lies in the development of fiber-reinforced silicon carbide matrix composite materials, including SiC-fiber/SiC-matrix composites. These materials are lighter in weight and capable of withstanding higher temperatures, relative to state-of-the-art metallic alloys and oxide-matrix composites for which maximum use temperatures are in the vicinity of 1,100 C. In addition, the toughness or damage tolerance of the SiC-matrix composites is significantly greater than that of unreinforced silicon-based monolithic ceramics. For successful application in advanced engine systems, the SiC-matrix composites should be able to withstand component service stresses and temperatures for the desired component lifetimes. Inasmuch as the high-temperature structural lives of ceramic materials are typically limited by creep-induced growth of flaws, a key property required of such composite materials is high resistance to creep under conditions of use. Also, the thermal conductivity of the materials should be as high as possible so as to minimize component thermal gradients and thermal stresses. A state-of-the-art SiC-matrix composite is typically fabricated in a three-step process: (1) fabrication of a component-shaped architectural preform reinforced by thermally stable high-performance fibers, (2) chemical-vapor infiltration (CVI) of a fiber-coating material such as boron nitride (BN) into the preform, and (3) infiltration of an SiC-based matrix into the remaining porosity in the preform. Generally, the matrices of the highest-performing composites are fabricated by initial use of a CVI SiC matrix component that is typically more thermally stable and denser than matrix components formed by processes other than CVI. As such, the initial SiC matrix component made by CVI provides better environmental protection to the coated fibers embedded within it. Also, the denser CVI SiC imparts to the

  12. Metrology in Pharmaceutical Industry - A Case Study

    NASA Astrophysics Data System (ADS)

    Yuvamoto, Priscila D.; Fermam, Ricardo K. S.; Nascimento, Elizabeth S.

    2016-07-01

    Metrology is recognized by improving production process, increasing the productivity, giving more reliability to the measurements and consequently, it impacts in the economy of a country. Pharmaceutical area developed GMP (Good Manufacture Practice) requeriments, with no introduction of metrological concepts. However, due to Nanomedicines, it is expected this approach and the consequent positive results. The aim of this work is to verify the level of metrology implementation in a Brazilian pharmaceutical industry, using a case study. The purpose is a better mutual comprehension by both areas, acting together and governmental support to robustness of Brazilian pharmaceutical area.

  13. A Review on Advanced Treatment of Pharmaceutical Wastewater

    NASA Astrophysics Data System (ADS)

    Guo, Y.; Qi, P. S.; Liu, Y. Z.

    2017-05-01

    The composition of pharmaceutical wastewater is complex, which is high concentration of organic matter, microbial toxicity, high salt, and difficult to biodegrade. After secondary treatment, there are still trace amounts of suspended solids and dissolved organic matter. To improve the quality of pharmaceutical wastewater effluent, advanced treatment is essential. In this paper, the classification of the pharmaceutical technology was introduced, and the characteristics of pharmaceutical wastewater effluent quality were summarized. The methods of advanced treatment of pharmaceutical wastewater were reviewed afterwards, which included coagulation and sedimentation, flotation, activated carbon adsorption, membrane separation, advanced oxidation processes, membrane separation and biological treatment. Meanwhile, the characteristics of each process were described.

  14. [Brief history of pharmaceutical standard system in China].

    PubMed

    Zhang, Jianwu; Xiao, Shiying; Dong, Guofeng; Liu, Wei; Di, Feng; Yang, Xujie

    2010-03-01

    Pharmaceutical standard system which belongs to an important part of national drug policies is an inevitable result of the development of pharmacy. There was a long standing of pharmaceutical standard system in China whose germination could be traced back to Qin and Han dynasties, and it had laid a solid foundation for the establishment and improvement of modern pharmaceutical standard system by continual accumulation from the past dynasties. Since the founding of new China, distinguished achievements had been obtained on pharmaceutical standardization working,and currently it is in a new developing stage. There was a brief description in this paper on the development history of pharmaceutical standard system in China.

  15. 26 CFR 1.1019-1 - Property on which lessee has made improvements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... buildings or made other improvements upon the leased property and the lease is terminated by forfeiture or... value of such property attributable to such buildings or improvements, the basis of each portion of such... lease B erected a building on the property. It was estimated that upon expiration of the lease...

  16. Improving surface and mechanical properties of alginate films by using ethanol as a co-solvent during external gelation.

    PubMed

    Li, Jiwei; He, Jinmei; Huang, Yudong; Li, Dalong; Chen, Xiaotong

    2015-06-05

    Alginate films were prepared by solution casting method and further ionically crosslinked in a calcium chloride (CaCl2) water solution containing different proportions (0-40% v/v) of ethanol as the co-solvent. The addition of ethanol into the CaCl2 water solution was found to improve the visual appearance, thickness, surface homogeneity, and mechanical properties of the films, which can be attributed to the reduced swelling degree of films during crosslinking process. Furthermore, Fourier transform infrared spectroscopy (FTIR) and energy dispersive spectroscopy (EDS) analysis indicated that the incorporation of ethanol into the crosslinking solution did not detract from the uniformity of crosslinking throughout the film matrix. However, the swelling degree and calcium content determination indicated that the Ca(2+) crosslinking degree decreased when the ethanol proportion exceeded 30% v/v. Consequently, this study introduces a green, efficient, and simple technique for the preparation of calcium alginate films with excellent surface appearance and mechanical properties for pharmaceutical products.

  17. Biosafe nanoscale pharmaceutical adjuvant materials.

    PubMed

    Jin, Shubin; Li, Shengliang; Wang, Chongxi; Liu, Juan; Yang, Xiaolong; Wang, Paul C; Zhang, Xin; Liang, Xing-Jie

    2014-09-01

    Thanks to developments in the field of nanotechnology over the past decades, more and more biosafe nanoscale materials have become available for use as pharmaceutical adjuvants in medical research. Nanomaterials possess unique properties which could be employed to develop drug carriers with longer circulation time, higher loading capacity, better stability in physiological conditions, controlled drug release, and targeted drug delivery. In this review article, we will review recent progress in the application of representative organic, inorganic and hybrid biosafe nanoscale materials in pharmaceutical research, especially focusing on nanomaterial-based novel drug delivery systems. In addition, we briefly discuss the advantages and notable functions that make these nanomaterials suitable for the design of new medicines; the biosafety of each material discussed in this article is also highlighted to provide a comprehensive understanding of their adjuvant attributes.

  18. Biosafe Nanoscale Pharmaceutical Adjuvant Materials

    PubMed Central

    Jin, Shubin; Li, Shengliang; Wang, Chongxi; Liu, Juan; Yang, Xiaolong; Wang, Paul C.; Zhang, Xin; Liang, Xing-Jie

    2014-01-01

    Thanks to developments in the field of nanotechnology over the past decades, more and more biosafe nanoscale materials have become available for use as pharmaceutical adjuvants in medical research. Nanomaterials possess unique properties which could be employed to develop drug carriers with longer circulation time, higher loading capacity, better stability in physiological conditions, controlled drug release, and targeted drug delivery. In this review article, we will review recent progress in the application of representative organic, inorganic and hybrid biosafe nanoscale materials in pharmaceutical research, especially focusing on nanomaterial-based novel drug delivery systems. In addition, we briefly discuss the advantages and notable functions that make these nanomaterials suitable for the design of new medicines; the biosafety of each material discussed in this article is also highlighted to provide a comprehensive understanding of their adjuvant attributes. PMID:25429253

  19. Pharmaceutical Education in Nigeria.

    ERIC Educational Resources Information Center

    Oyegbile, F. Rachel

    1988-01-01

    Nigeria has six pharmacy schools, most offering graduate programs. The undergraduate program is being expanded from four to five years. Although behavioral and clinical sciences are offered, emphasis is on the pharmaceutical sciences. Overall, pharmaceutical education is oriented toward hospice practice. (Author/MSE)

  20. Pharmaceutical research and development.

    PubMed

    McKercher, P L

    1992-01-01

    Some aspects of pharmaceutical research and development (R&D) are reviewed. The viability of major pharmaceutical manufacturers depends on their research and thus they commit substantial resources to R&D programs. Major pharmaceutical manufacturers in the United States employ about 40,000 R&D personnel, and worldwide pharmaceutical R&D expenditures reached $24 billion in 1990. The pharmaceutical industry is one of the most profitable; however, increasing prices of their products are often associated with increasing R&D costs, ignoring the many positive attributes of R&D. The Council on Competitiveness has recently proposed reforms in the approval process for new drugs, including accelerated approval, external review, and international cooperation. These reforms would help to preserve an R&D capability and a relatively unregulated pharmaceutical industry. Pharmaceutical R&D has made many important contributions, including increased life expectancy, the internationally competitive position of the US industry, and a positive balance of trade. However, a misunderstanding of the role of R&D could encourage development of policies and legislation detrimental to pharmaceutical R&D.

  1. Pharmaceutical Education in Poland

    ERIC Educational Resources Information Center

    Furmanowa, Miroslawa; Borke, Mitchell L.

    1978-01-01

    The content and organization of Poland's system of pharmaceutical education is described. Tables are presented of the subjects of the basic studies curriculum and the following areas of specialization: applied pharmacy, pharmaceutical analysis, clinical analysis, drug technology, herbal pharmacy, and bioanalysis and environmental studies. (SW)

  2. 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.

  3. Pharmaceutical Education in Nigeria.

    ERIC Educational Resources Information Center

    Oyegbile, F. Rachel

    1988-01-01

    Nigeria has six pharmacy schools, most offering graduate programs. The undergraduate program is being expanded from four to five years. Although behavioral and clinical sciences are offered, emphasis is on the pharmaceutical sciences. Overall, pharmaceutical education is oriented toward hospice practice. (Author/MSE)

  4. A thing patented is a thing divulged: Francis E. Stewart, George S. Davis, and the legitimization of intellectual property rights in pharmaceutical manufacturing, 1879-1911.

    PubMed

    Gabriel, Joseph M

    2009-04-01

    This article examines the efforts of pharmacist and physician Francis E. Stewart to legitimize the commercial introduction of new drugs by reinterpreting the ethical status of patent rights in pharmaceutical manufacturing. I argue that patents had long been understood by the orthodox medical community as an unethical form of medical monopoly and that, as a result, drug companies that marketed their goods primarily to physicians in the years immediately following the Civil War had little room to develop or introduce new products. In collaboration with George S. Davis and the pharmaceutical manufacturing firm Parke, Davis, & Company, Stewart worked to redefine patents as an ethical means of encouraging scientific and commercial innovation. In doing so, he sought to reconcile medical science and commerce so that they were mutually beneficial to one another. However, I also suggest that his efforts had an ironic effect in that they helped legitimatize a form of patent protection that Stewart himself came to believe to be unethical in nature.

  5. Pharmaceutical technology management--profitable business avenue.

    PubMed

    Puthli, Shivanand P

    2010-01-01

    Growing research expenditure, regulatory framework and generic erosion have forced pharmaceutical companies globally to resort to pharmaceutical technology management (PTM). Indeed, the pharmaceutical industry has witnessed the impact of innovative drug delivery and device technologies and their influence on business. PTM has given a new business insight with greater profits and enhancement of product franchise. Promising breakthrough technologies have not been able to reach a commercial platform largely owing to lack of capital at the preliminary stages of the product development program. Intellectual property plays a considerable role in protecting innovative technologies. Joint ventures and strategic alliances also become important for commercializing a new technology. The synergy of PTM with options of in-licensing is expected to infuse newer opportunities to the pharmaceutical business.

  6. FDA pharmaceutical quality oversight.

    PubMed

    Yu, Lawrence X; Woodcock, Janet

    2015-08-01

    The launch of the Center for Drug Evaluation and Research (CDER) Office of Pharmaceutical Quality (OPQ) is a milestone in FDA's efforts to assure that quality medicines are available to the American public. As a new super-office within CDER, OPQ is strategically organized to streamline regulatory processes, advance regulatory standards, align areas of expertise, and originate surveillance of drug quality. Supporting these objectives will be an innovative and systematic approach to product quality knowledge management and informatics. Concerted strategies will bring parity to the oversight of innovator and generic drugs as well as domestic and international facilities. OPQ will promote and encourage the adoption of emerging pharmaceutical technology to enhance pharmaceutical quality and potentially reinvigorate the pharmaceutical manufacturing sector in the United States. With a motto of "One Quality Voice," OPQ embodies the closer integration of review, inspection, surveillance, policy, and research for the purpose of strengthening pharmaceutical quality on a global scale.

  7. 77 FR 51948 - Airport Improvement Program (AIP): Policy Regarding Access to Airports From Residential Property...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-28

    ... Federal Aviation Administration 14 CFR Chapter 1 Airport Improvement Program (AIP): Policy Regarding Access to Airports From Residential Property; Correction AGENCY: Federal Aviation Administration (FAA... paragraph in the Proposed Policy Regarding Access to Airports From Residential Property that was...

  8. Defining pharmaceutical systems strengthening: concepts to enable measurement.

    PubMed

    Hafner, Tamara; Walkowiak, Helena; Lee, David; Aboagye-Nyame, Francis

    2017-05-01

    Pharmaceutical products are indispensable for improving health outcomes. An extensive body of work on access to and use of medicines has resulted in an assortment of tools measuring various elements of pharmaceutical systems. Until now however, there has been little attempt to conceptualize a pharmaceutical system as an entity and define its strengthening in a way that allows for measuring systems strengthening. The narrow focus of available tools limits their value in ascertaining which interventions result in stronger, more resilient systems. We sought to address this shortcoming by revisiting the current definitions, frameworks and assessment tools related to pharmaceutical systems. We conducted a comprehensive literature review and consulted with select pharmaceutical experts. On the basis of our review, we propose that a pharmaceutical system consists of all structures, people, resources, processes, and their interactions within the broader health system that aim to ensure equitable and timely access to safe, effective, quality pharmaceutical products and related services that promote their appropriate and cost-effective use to improve health outcomes. We further propose that pharmaceutical systems strengthening is the process of identifying and implementing strategies and actions that achieve coordinated and sustainable improvements in the critical components of a pharmaceutical system to make it more responsive and resilient and to enhance its performance for achieving better health outcomes. Finally, we established that, in addition to system performance and resilience, seven components of the pharmaceutical system are critical for measuring pharmaceutical systems strengthening: pharmaceutical products and related services; policy, laws and governance; regulatory systems; innovation, research and development, manufacturing, and trade; financing; human resources; and information. This work adds clarity to the concept of pharmaceutical systems and their

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

    PubMed

    Saal, C; Becker, A

    2013-07-16

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

  10. A highly improved method for sensitive determination of amitriptyline in pharmaceutical formulations using an unmodified carbon nanotube electrode in the presence of sulfuric acid.

    PubMed

    Duarte, Eduardo Henrique; dos Santos, William Pereira; Hudari, Felipe Fantinato; Bott Neto, José Luiz; Sartori, Elen Romão; Dall'Antonia, Luiz Henrique; Pereira, Arnaldo César; Tarley, César Ricardo Teixeira

    2014-09-01

    The present paper describes a novel, simple and reliable differential pulse voltammetric method for determining amitriptyline (AMT) in pharmaceutical formulations. It has been described for many authors that this antidepressant is electrochemically inactive at carbon electrodes. However, the procedure proposed herein consisted in electrochemically oxidizing AMT at an unmodified carbon nanotube paste electrode in the presence of 0.1 mol L(-1) sulfuric acid used as electrolyte. At such concentration, the acid facilitated the AMT electroxidation through one-electron transfer at 1.33 V vs. Ag/AgCl, as observed by the augmentation of peak current. Concerning optimized conditions (modulation time 5 ms, scan rate 90 mV s(-1), and pulse amplitude 120 mV) a linear calibration curve was constructed in the range of 0.0-30.0 μmol L(-1), with a correlation coefficient of 0.9991 and a limit of detection of 1.61 μmol L(-1). The procedure was successfully validated for intra- and inter-day precision and accuracy. Moreover, its feasibility was assessed through analysis of commercial pharmaceutical formulations and it has been compared to the UV-vis spectrophotometric method used as standard analytical technique recommended by the Brazilian Pharmacopoeia. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Early stage phase separation in pharmaceutical solid dispersion thin films under high humidity: improved spatial understanding using probe-based thermal and spectroscopic nanocharacterization methods.

    PubMed

    Qi, Sheng; Moffat, Jonathan G; Yang, Ziyi

    2013-03-04

    Phase separation in pharmaceutical solid dispersion thin films under high humidity is still poorly understood on the submicrometer scale. This study investigated the phase separation of a model solid dispersion thin film, felodipine-PVP K29/32, prepared by spin-coating and analyzed using probe-based methods including atomic force microscopy, nanothermal analysis, and photothermal infrared microspectroscopy. The combined use of these techniques revealed that the phase separation process occurring in the thin films under high humidity is different from that in dry conditions reported previously. The initial stage of phase separation is primarily initiated in the bulk of the films as amorphous drug domains. Drug migration toward the surface of the solid dispersion film was then observed to occur under exposure to increased humidity. PVP cannot prevent phase separation of felodipine under high humidity but can minimize the crystallization of amorphous felodipine domains in the solid dispersion thin films. This study demonstrates the unique abilities of these nanocharacterization methods for studying, in three dimensions, the phase separation of thin films for pharmaceutical applications.

  12. Recent developments, characteristics and potential applications of screen-printed electrodes in pharmaceutical and biological analysis.

    PubMed

    Couto, R A S; Lima, J L F C; Quinaz, M B

    2016-01-01

    Screen-printed electrodes (SPEs) have gone through significant improvements over the past few decades with respect to both their format and their printing materials. Thus, SPEs have been successfully applied for the in situ detection of a plethora of analytes in a wide range of sample matrixes due to their advantageous material properties, such as disposability, simplicity, and rapid responses. In particular, the development of electrochemical sensors based on SPEs for pharmaceutical analysis has received massive consideration since they enable the rapid screening of the pharmaceutical compounds in complex matrixes, requiring small volumes of samples and no pre-treatment steps. This review summarizes the design and the working principles of electrochemical sensors based on SPEs applied to the quantification of pharmaceutical and biological compounds.

  13. Component morphology, size, and compositional impact on pharmaceutical powder blend flowability

    NASA Astrophysics Data System (ADS)

    Goldfarb, David; Nakagawa, Hirotaka; Conway, Stephen

    2014-11-01

    Through analysis of particle morphology, particle size, and compositional influences, we present experimental case studies revealing unexpected transitions in flowability and cohesion of pharmaceutical powder blends. We explore interactions between the needle-like API (Active Pharmaceutical Ingredient) and the more spherical remaining components (excipients) in the blend to explain these transitions, and optimal concentrations are identified. A range of particle sizes, aspect ratios (for API), and compositions were examined. Surprisingly, under certain conditions, a blend with a low API concentration exhibits less cohesive flowability properties than a placebo blend containing no API. Effective volume and coordination number models are tested by investigation of particle geometry, particle contact, and Van der Waals force factors. These results should translate both to the improved understanding of mixed component morphology systems and to a novel approach towards pharmaceutical product formulation optimization.

  14. Modified Polypropylene with Improved Physical-Mechanical Properties

    NASA Astrophysics Data System (ADS)

    Chervakov, D. O.; Bashtanyk, P. I.; Burmistr, M. V.

    2015-03-01

    The use of mixtures of benzoyl peroxide and polysiloxane polyol compounds as polypropylene modifiers is suggested. It is established that, in such a way, its physical-mechanical properties can be changed purposefully.

  15. Data Properties Categorization to Improve Scientific Sensor Data Error Detection

    NASA Astrophysics Data System (ADS)

    Gallegos, I.; Gates, A.; Tweedie, C. E.

    2009-12-01

    Recent advancements in scientific sensor data acquisition technologies have increased the amount of data collected in near-real time. Although the need for error detection in such data sets is widely acknowledged, few organizations to date have automated random and systematic error detection. This poster presents the results of a broad survey of the literature on scientific sensor data collected through networks and environmental observatories with the aim of identifying research priorities needed for the development of automated error detection mechanisms. The key finding of this survey is that there appears to be no overarching consensus about error detection criteria in the environmental sciences and that this likely limits the development and implementation of automated error detection in this domain. The literature survey focused on identifying scientific projects from institutions that have incorporated error detection into their systems, the type of analyzed data, and the type of sensor error detection properties as defined by each project. The projects have mechanisms that perform error detection in both the field sites and data centers. The literature survey was intended to capture a representative sample of projects with published error detection criteria. Several scientific projects have included error detection, mostly as part of the system’s source code; however, error detection properties, which are embedded or hard-coded in the source code, are difficult to refine and require a software developer to modify the source code every time a new error detection property or a modification to an existing property is needed. An alternative to hard-coded error detection properties is an error-detection mechanism, independent of the system used to collect the sensor data, which will automatically detect errors in the supported type of data. Such a mechanism would allow scientists to specify and reuse error detection properties and uses the specified properties

  16. Soluble insulin analogs combining rapid- and long-acting hypoglycemic properties - From an efficient E. coli expression system to a pharmaceutical formulation.

    PubMed

    Mikiewicz, Diana; Bierczyńska-Krzysik, Anna; Sobolewska, Agnieszka; Stadnik, Dorota; Bogiel, Monika; Pawłowska, Monika; Wójtowicz-Krawiec, Anna; Baran, Piotr A; Łukasiewicz, Natalia; Romanik-Chruścielewska, Agnieszka; Sokołowska, Iwona; Stadnik, Jacek; Borowicz, Piotr; Płucienniczak, Grażyna; Płucienniczak, Andrzej

    2017-01-01

    The discovery of insulin led to a revolution in diabetes management. Since then, many improvements have been introduced to insulin preparations. The availability of molecular genetic techniques has enabled the creation of insulin analogs by changing the structure of the native protein in order to improve the therapeutic properties. A new expression vector pIBAINS for production of four recombinant human insulin (INS) analogs (GKR, GEKR, AKR, SR) was constructed and overexpressed in the new E. coli 20 strain as a fusion protein with modified human superoxide dismutase (SOD). The SOD gene was used as a signal peptide to enhance the expression of insulin. SOD::INS was manufactured in the form of insoluble inclusion bodies. After cleavage of the fusion protein with trypsin, the released insulin analogs were refolded and purified by reverse-phase high performance liquid chromatography (RP-HPLC). Elongation of chain A, described here for the first time, considerably improved the stability of the selected analogs. Their identity was confirmed with mass spectrometric techniques. The biological activity of the insulin derivatives was tested on rats with experimental diabetes. The obtained results proved that the new analogs described in this paper have the potential to generate prolonged hypoglycemic activity and may allow for even less frequent subcutaneous administration than once-a-day. When applied, all the analogs demonstrate a rapid onset of action. Such a combination renders the proposed biosynthetic insulin unique among already known related formulations.

  17. Soluble insulin analogs combining rapid- and long-acting hypoglycemic properties – From an efficient E. coli expression system to a pharmaceutical formulation

    PubMed Central

    Mikiewicz, Diana; Bierczyńska-Krzysik, Anna; Sobolewska, Agnieszka; Stadnik, Dorota; Bogiel, Monika; Pawłowska, Monika; Wójtowicz-Krawiec, Anna; Baran, Piotr A.; Łukasiewicz, Natalia; Romanik-Chruścielewska, Agnieszka; Sokołowska, Iwona; Stadnik, Jacek; Borowicz, Piotr; Płucienniczak, Grażyna; Płucienniczak, Andrzej

    2017-01-01

    The discovery of insulin led to a revolution in diabetes management. Since then, many improvements have been introduced to insulin preparations. The availability of molecular genetic techniques has enabled the creation of insulin analogs by changing the structure of the native protein in order to improve the therapeutic properties. A new expression vector pIBAINS for production of four recombinant human insulin (INS) analogs (GKR, GEKR, AKR, SR) was constructed and overexpressed in the new E. coli 20 strain as a fusion protein with modified human superoxide dismutase (SOD). The SOD gene was used as a signal peptide to enhance the expression of insulin. SOD::INS was manufactured in the form of insoluble inclusion bodies. After cleavage of the fusion protein with trypsin, the released insulin analogs were refolded and purified by reverse-phase high performance liquid chromatography (RP-HPLC). Elongation of chain A, described here for the first time, considerably improved the stability of the selected analogs. Their identity was confirmed with mass spectrometric techniques. The biological activity of the insulin derivatives was tested on rats with experimental diabetes. The obtained results proved that the new analogs described in this paper have the potential to generate prolonged hypoglycemic activity and may allow for even less frequent subcutaneous administration than once-a-day. When applied, all the analogs demonstrate a rapid onset of action. Such a combination renders the proposed biosynthetic insulin unique among already known related formulations. PMID:28296883

  18. Pharmaceutical pricing and reimbursement reforms in Greece.

    PubMed

    Yfantopoulos, John

    2008-02-01

    Pharmaceutical price regulation in Greece is centralized. The National Drug Organization (EOF) is the main regulatory authority functioning under the auspices of the Ministry of Health and Social Solidarity. In 2004, total pharmaceutical expenditure in Greece reached the level of 2.9 billion euro, of which 77.9% were public expenditure and the remaining 22.1% private. According to Organization for Economic Cooperation and Development (OECD) data the total per-capita expenditure on pharmaceutical care in Greece is among the lowest in Europe, representing 58% of the EU-12 average. In 1998, Greece introduced a reimbursement list, and the lowest reference pricing system among the 15 European Union member states with the purpose of controlling the growth of pharmaceutical expenditure. The measures proved to be ineffective since pharmaceutical expenditure, after a short-term reduction, continued to increase at similar rates to those before the introduction of price control mechanisms. The average annual increase of pharmaceutical expenditure in Greece over the period 1998-2003 was 7.9%, which is among the highest in the OECD countries (average 6.1%). New pharmaceutical legislation, no. 3457, was enacted on May 8th 2006, aiming at greater access to medicines, improvements to citizens' quality of life, effective and efficient utilization of health resources, transparency in public management, protecting public health, and maintaining long-term financial viability of the insurance system. The innovative aspect of the new legislation is the abolition of the positive list and the establishment of a rebate system granting the National Insurance Funds a rebate rate paid by the pharmaceutical companies. The purpose of this paper is twofold. First to assess the effectiveness of the positive list introduced in 1988 in Greece, using simple econometric models. Second to present the recent pharmaceutical reforms aimed at the introduction of a rebate system and establishing

  19. Behavior of selected pharmaceuticals in topsoil of Greyic Phaeozem

    NASA Astrophysics Data System (ADS)

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

    2014-05-01

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

  20. Improved austenitic stainless steel for high temperature applications. [Improved stress-rupture properties

    DOEpatents

    Not Available

    This invention describes a composition for an austenitic stainless steel which has been found to exhibit improved high temperature stress rupture properties. The composition of this alloy is about (in wt. %): 12.5 to 14.5 Cr; 14.5 to 16.5 Ni; 1.5 to 2.5 Mo; 1.5 to 2.5 Mn; 0.1 to 0.4 Ti; 0.02 to 0.08 C; 0.5 to 1.0 Si; 0.01 maximum, N; 0.02 to 0.08 P; 0.002 to 0.008 B; 0.004-0.010 S; 0.02-0.05 Nb; .01-.05 V; 0.005-0.02 Ta; 0.02-0.05 Al; 0.01-0.04 Cu; 0.02-0.05 Co; .03 maximum, As; 0.01 maximum, 0; 0.01 maximum, Zr; and with the balance of the alloy being essentially iron. The carbon content of the alloy is adjusted such that wt. % Ti/(wt. % C+wt. % N) is between 4 and 6, and most preferably about 5. In addition the sum of the wt. % P + wt. % B + wt. % S is at least 0.03 wt. %. This alloy is believed to be particularly well suited for use as fast breeder reactor fuel element cladding.

  1. Supercritical fluid technology: concepts and pharmaceutical applications.

    PubMed

    Deshpande, Praful Balavant; Kumar, G Aravind; Kumar, Averineni Ranjith; Shavi, Gopal Venkatesh; Karthik, Arumugam; Reddy, Meka Sreenivasa; Udupa, Nayanabhirama

    2011-01-01

    In light of environmental apprehension, supercritical fluid technology (SFT) exhibits excellent opportunities to accomplish key objectives in the drug delivery sector. Supercritical fluid extraction using carbon dioxide (CO(2)) has been recognized as a green technology. It is a clean and versatile solvent with gas-like diffusivity and liquid-like density in the supercritical phase, which has provided an excellent alternative to the use of chemical solvents. The present commentary provides an overview of different techniques using supercritical fluids and their future opportunity for the drug delivery industry. Some of the emerging applications of SFT in pharmaceuticals, such as particle design, drug solubilization, inclusion complex, polymer impregnation, polymorphism, drug extraction process, and analysis, are also covered in this review. The data collection methods are based on the recent literature related to drug delivery systems using SFT platforms. SFT has become a much more versatile and environmentally attractive technology that can handle a variety of complicated problems in pharmaceuticals. This cutting-edge technology is growing predominantly to surrogate conventional unit operations in relevance to the pharmaceutical production process. Supercritical fluid technology has recently drawn attention in the field of pharmaceuticals. It is a distinct conception that utilizes the solvent properties of supercritical fluids above their critical temperature and pressure, where they exhibit both liquid-like and gas-like properties, which can enable many pharmaceutical applications. For example, the liquid-like properties provide benefits in extraction processes of organic solvents or impurities, drug solubilization, and polymer plasticization, and the gas-like features facilitate mass transfer processes. It has become a much more versatile and environmentally attractive technology that can handle a variety of complicated problems in pharmaceuticals. This review is

  2. Improving the API dissolution rate during pharmaceutical hot-melt extrusion I: Effect of the API particle size, and the co-rotating, twin-screw extruder screw configuration on the API dissolution rate.

    PubMed

    Li, Meng; Gogos, Costas G; Ioannidis, Nicolas

    2015-01-15

    The dissolution rate of the active pharmaceutical ingredients in pharmaceutical hot-melt extrusion is the most critical elementary step during the extrusion of amorphous solid solutions - total dissolution has to be achieved within the short residence time in the extruder. Dissolution and dissolution rates are affected by process, material and equipment variables. In this work, we examine the effect of one of the material variables and one of the equipment variables, namely, the API particle size and extruder screw configuration on the API dissolution rate, in a co-rotating, twin-screw extruder. By rapidly removing the extruder screws from the barrel after achieving a steady state, we collected samples along the length of the extruder screws that were characterized by polarized optical microscopy (POM) and differential scanning calorimetry (DSC) to determine the amount of undissolved API. Analyses of samples indicate that reduction of particle size of the API and appropriate selection of screw design can markedly improve the dissolution rate of the API during extrusion. In addition, angle of repose measurements and light microscopy images show that the reduction of particle size of the API can improve the flowability of the physical mixture feed and the adhesiveness between its components, respectively, through dry coating of the polymer particles by the API particles.

  3. Pharmaceutical policy in China.

    PubMed

    Sun, Qiang; Santoro, Michael A; Meng, Qingyue; Liu, Caitlin; Eggleston, Karen

    2008-01-01

    Contradictory goals plague China's pharmaceutical policy. The government wants to develop the domestic pharmaceutical industry and has used drug pricing to cross-subsidize public hospitals. Yet the government also aims to control drug spending through price caps and profit-margin regulations to guarantee access even for poor patients. The resulting system has distorted market incentives, increased consumers' costs, and financially rewarded inappropriate prescribing, thus undermining public health. Pharmaceuticals account for about half of total health spending in China, representing 43 percent of spending per inpatient episode and 51 percent of spending per outpatient visit. Yet some essential medicines are unavailable or of questionable quality.

  4. Pharmaceuticals: pharmaceutical cost controls--2005. End of Year Issue Brief.

    PubMed

    Seay, Melicia; Varma, Priya

    2005-12-31

    The enactment of the Omnibus Budget Reconciliation Act of 1990 (OBRA '90) gave states the option of offering pharmaceutical benefits within their Medicaid programs. But the law placed restrictions on states' flexibility to control what prescriptions they would cover and required the states to reimburse outpatient prescription drugs from manufacturers that signed rebate agreements with the U.S. Department of Health and Human Services. Forty-nine states--Arizona is excluded, based on its program structure--and the District of Columbia currently offer prescription drug coverage under the Medicaid Drug Rebate Program. During the past four years, states all over the country have been plagued with revenue shortfalls in their state Medicaid budgets. While the fiscal situation improved for most states in the 2004 legislative session, many states still face budget pressures in 2005. Compounding existing budget pressures are threats from the Bush Administration to shift increased costs of the Medicaid program on to the states. All things considered, the economic pressure of funding Medicaid is at the top of legislative agendas in 2005. As in previous years, states are attempting to reduce costs to their Medicaid programs by seeking savings in their pharmaceutical programs. Prescription drug costs are highly attributed as a contributing factor to the fiscal climate of state Medicaid programs. Currently, prescription drug spending outpaces that of every other category of health care and drug prices are rising faster than inflation. In response, states are instituting a variety of pharmaceutical cost control measures such as creating preferred drug lists (PDLs), negotiating supplemental rebates, forming bulk purchasing pools, promoting generic drug substitution and implementing price controls. As prescription drug cost containment tools have gained acceptance and momentum, they continue to be controversial. This issue brief explores the debate, history, methodology, utilization

  5. Pharmaceutical optimization of lipid-based dosage forms for the improvement of taste-masking, chemical stability and solubilizing capacity of phenobarbital.

    PubMed

    Monteagudo, Ezequiel; Langenheim, Mariana; Salerno, Claudia; Buontempo, Fabián; Bregni, Carlos; Carlucci, Adriana

    2014-06-01

    Microemulsions (MEs) and self-emulsifying drug delivery systems (SEEDS) containing phenobarbital (Phe) were developed to improve its chemical stability, solubilizing capacity and taste-masking in oral liquid dosage forms. Cremophor® RH40 and Labrasol® were used as surfactants for the screening of ME regions, Capmul® MCM L, Captex® 355, Imwitor® 408, Myglyol® 840 and Isopropyl myristate were the oil phases assayed; Transcutol® P, Polyethylene-glycol 400, glycerol, Propylene-glycol and ethanol the cosurfactants. Phe stability assay was carried out (20:4:20:56% and 20:4:35:41% (w/w); surfactant:oily phase:cosurfactant:water) for both surfactants; only one containing ethanol showed significant dismissing in its drug content. Solubility capacity for these selected formulations were also evaluated, an amount between 17 and 58 mg/mL of Phe could be loaded. At last, an optimized ME formulation with Cremophor® RH40 20%, Capmul® MCM L 4%, PEG 400 35% and sucralose 2% (w/w) was chosen in order to optimize taste-masking using an electronic tongue. Strawberry along with banana and tutti-frutti flavors plus mint flavor proved to be the best ones. Labrasol-based pre-concentrates were tested for (micro)emulsifying properties; all of them resulted to behave as SEDDS. In summary, a rationale experimental design conducted to an optimized ME for Phe oral pediatric administration which was able to load 5-fold times the currently used dose (4 mg/mL), with no sign of physical or chemical instability and with improved taste; SEDDS for capsule filling were also obtained. The biopharmaceutical advantages described for these dosage forms encourage furthering in vivo evaluation.

  6. ENVIRONMENTAL STEWARDSHIP OF PHARMACEUTICALS ...

    EPA Pesticide Factsheets

    There is no abstract available for this product. If further information is requested, please refer to the bibliographic citation and contact the person listed under Contact field. The research focused on in the subtasks is the development and application of state-of the-art technologies to meet the needs of the public, Office of Water, and ORD in the area of Water Quality. Located In the subtasks are the various research projects being performed in support of this Task and more in-depth coverage of each project. Briefly, each project's objective is stated below.Subtask 1: To integrate state-of-the-art technologies (polar organic chemical integrative samplers, advanced solid-phase extraction methodologies with liquid chromatography/electrospray/mass spectrometry) and apply them to studying the sources and fate of a select list of PPCPs. Application and improvement of analytical methodologies that can detect non-volatile, polar, water-soluble pharmaceuticals in source waters at levels that could be environmentally significant (at concentrations less than parts per billion, ppb). IAG with USGS ends in FY05. APM 20 due in FY05.Subtask 2: Coordination of interagency research and public outreach activities for PPCPs. Participate on NSTC Health and Environment subcommittee working group on PPCPs. Web site maintenance and expansion, invited technical presentations, invited articles for peer-reviewed journals, interviews for media, responding to public inquiries. S

  7. PHARMACEUTICALS AS ENVIRONMENTAL ...

    EPA Pesticide Factsheets

    There is no abstract available for this product. If further information is requested, please refer to the bibliographic citation and contact the person listed under Contact field. The research focused on in the subtasks is the development and application of state-of the-art technologies to meet the needs of the public, Office of Water, and ORD in the area of Water Quality. Located In the subtasks are the various research projects being performed in support of this Task and more in-depth coverage of each project. Briefly, each project's objective is stated below.Subtask 1: To integrate state-of-the-art technologies (polar organic chemical integrative samplers, advanced solid-phase extraction methodologies with liquid chromatography/electrospray/mass spectrometry) and apply them to studying the sources and fate of a select list of PPCPs. Application and improvement of analytical methodologies that can detect non-volatile, polar, water-soluble pharmaceuticals in source waters at levels that could be environmentally significant (at concentrations less than parts per billion, ppb). IAG with USGS ends in FY05. APM 20 due in FY05.Subtask 2: Coordination of interagency research and public outreach activities for PPCPs. Participate on NSTC Health and Environment subcommittee working group on PPCPs. Web site maintenance and expansion, invited technical presentations, invited articles for peer-reviewed journals, interviews for media, responding to public inquiries. S

  8. GMK (Progenics Pharmaceuticals).

    PubMed

    Knutson, Keith L

    2002-01-01

    Progenics Pharmaceuticals is developing GMK vaccine (a ganglioside conjugate vaccine coupled to keyhole limpet hemocyanin and formulated with the adjuvant QS-21), licensed from the Memorial Sloan-Kettering Cancer Center, for the potential treatment of melanoma and other cancers [194258], [325284]. It was previously under co-development with Bristol-Myers Squibb, but in May 2001, all rights to the GMK vaccine were returned to Progenics [409168]. It was the first of a new class of ganglioside conjugate vaccine evaluated by Progenics [194258]. GMK vaccination induces antibodies against GM2 ganglioside capable of specifically killing melanoma cells. Melanoma patients with antibodies against GM2 ganglioside have significantly improved disease-free and overall survival compared to antibody-negative subjects. The vaccine is undergoing two phase III trials, the first comparing GMK to high-dose IFNalpha in melanoma patients with more serious disease and at a high risk of relapse, and the second, in collaboration with the European Organization for Research and Treatment of Cancer, comparing GMK (14 doses of GMK over three years) to no treatment other than close monitoring of malignant melanoma patients at immediate risk of relapse [409168]. In February 1999, Lehman Brothers predicted that the vaccine had a 50% probability of reaching market, with an estimated first launch date in 2002. The analysts predicted potential peak sales in 2008 of $150 million in the US and $100 million in the rest of the world at that time [319225]. In January 2000, Lehman Brothers expected that an NDA filing would take place in 2002, with possible launch of the vaccine in 2003. In addition, Lehman Brothers estimated potential peak sales at $500 million [357788]. In August 2000, Punk, Ziegel & Company predicted that Progenics Pharmaceuticals will become sustainably profitable in 2003 following the launch of GMK and PRO-542 in 2002 [390063]. In July 2001, Ladenburg Thalmann predicted a $257 million

  9. Do technical and commercial biases contribute to the pharmaceutical industry's productivity problems? An analysis of how reordering priorities can improve productivity.

    PubMed

    Fryburg, David A

    2010-09-01

    Of the many issues that contribute to the pharmaceutical industry's productivity problems, biases in the drug discovery and development (DDD) process should be included on the list. The dominant bias pervading the early DDD process is the requirement to identify and develop a commercializable molecule, long before the importance of the target in human disease is understood. That requirement filters out many potentially valuable projects. By changing the emphasis from identifying a commercializable molecule to using molecular tools to test the relevance of the mechanism in humans, the projected number of proofs of concept and subsequent launches could increase up to fivefold. Because this tool paradigm requires resources, one consideration is to form a consortium to share the burden, benefiting both the industry and patients in need. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. New benchmark to improve the photoelectrochemical properties of hematite

    NASA Astrophysics Data System (ADS)

    Singh, Aadesh P.; Tripathi, Ambuj; Shrivastav, Rohit; Dass, Sahab; Satsangi, Vibha R.

    2008-08-01

    Modification in the properties of material by swift heavy ion irradiation is an interesting area of research. It provides the researchers a new dimension of introducing desired changes to the behaviour of the material, which largely influence their PEC properties also. This communication describes a study on the swift heavy ion irradiation induced modification in the PEC properties of nanostructured hematite thin films. Thin films of nanostructured α-Fe2O3 prepared by spray-pyrolysis were irradiated with Si7+ ions at fluence ranging from 5x1012 to 4x1013 ions/cm2. After characterizing them for structural, morphological and optical parameters, photoelectrochemical response of the irradiated and unirradiated samples of hematite thin films in terms of photocurrent density as a function of different ions fluence, towards the solar splitting of water was studied. It was observed that ion fluence plays an important role in modifying the PEC properties of the material. Sample irradiated with 100 MeV Si7+ ions at fluence 2x1013 ions/cm2 exhibited the best photocurrent density.

  11. Improving the cold flow properties of biodiesel by fractionation

    USDA-ARS?s Scientific Manuscript database

    Production of biodiesel is increasing world-wide and contributing to the growing development of renewable alternative fuels. Biodiesel has many fuel properties such as density, viscosity, lubricity, and cetane number that make it compatible for combustion in compression-ignition (diesel) engines. ...

  12. Method of Improving the Storage Properties of Alkaline Detergent Compositions.

    DTIC Science & Technology

    The caking of powder detergent compositions in storage, with consequent loss of free flowing and granular characteristics, has been a serious problem...properties of detergent compositions by eliminating the caking thereof. A typical detergent composition in which the present invention could be

  13. Solid Solutions Formation: Improving the Thermoelectric Properties of Skutterudites

    NASA Technical Reports Server (NTRS)

    Borshchevsky, A.; Caillat, T.; Fleurial, J. P.

    1996-01-01

    Materials with skutterudite structure have been known for a long time. Some of them are semiconductors. A typical skutterudite is CoSb(sub 3) and its thermoelectric properties were partially studied in the 1960's. Recently, it has been discovered that many skutterudite compounds are thermoelectrics with promising future.

  14. Using glucosamine to improve the properties of photocrosslinked gelatin scaffolds.

    PubMed

    Suo, Hairui; Xu, Kedi; Zheng, Xiaoxiang

    2015-02-01

    The use of hydrogel-based cell transport scaffolds holds great promise in regenerative medicine, such as treating osteoarthritis. Gelatin and glucosamine are the ideal materials to be used in the hydrogel scaffolds for cartilage regeneration for they could act as compositions of cartilage. To overcome the weak strength of traditional gelatin hydrogels and down-regulate cell toxicity of glucosamine, gelatin and glucosamine molecules were grafted with acrylate groups and covalently crosslinked under photo-radiation to form hydrogels. Hydrogels with tuning physiochemical properties were produced according to different proportions of methacrylate gelatin (GelMA) and N-acryloyl glucosamine (AGA). The process of photocrosslinking was elaborated, and the hypothesis of increasing AGA concentration leading to higher strength of hydrogels was corroborated by testing rheological property and scanning micro-morphological features. A serial of properties, including smaller swelling ratio, lower gelatin dissolution and slower degradation of GelMA/AGA hydrogels with higher AGA concentration further proved our hypothesis. Moreover, AGA molecules showed less cytotoxicity than unmodified glucosamine molecules and the incorporation of AGA molecules in GelMA/AGA hydrogels upregulated cell adhesion and spreading on the hydrogel surface. All of these results indicated that addition of AGA molecules could significantly alter the physiochemical properties of GelMA/AGA hydrogels, which may have broad application prospects in the future.

  15. Controlling polypropylene rheological properties by promoting organic peroxide during extrusion with improved properties for automotive applications

    NASA Astrophysics Data System (ADS)

    Herlambang, Bayu; Sandytama

    2017-05-01

    Excellent stability and processability of Controlled-Rheology Polypropylene (CRPP) was mandatory parameters especially for automotive application. Selected organic peroxide which was used to control the rheology of PP should perform good stability in physical properties due to pre-process of compounding for automotive application. The common organic peroxide that widely used is 2,5-dimethyl-2,5-di-tert-butylperoxyhexane (DHBP). However, the problems that usually encountered are Melt Flow Index (MFI) stability, initial color, and the odor which come from decomposition process. Research and Development (RND) team of PT Chandra Asri Petrochemical, Tbk (CAP) did the study to change the type of organic peroxide to 3,6,9-triethyl-3,6,9,-trimethyl-l,4,7-triperoxonane (TETMTPA) which was intended to improve these inferiorities when using DHBP. The results indicate better MFT stability, better initial color, and less odor when using TETMTPA than DHBP. This superiority is very applicable particularly for automotive application. Detailed analysis about volatile decomposition product from both peroxide indicated CRPP with TETMTPA has lower volatile compound which result lower odor level than CRPP with DHBP.

  16. Ecotoxicology of human pharmaceuticals.

    PubMed

    Fent, Karl; Weston, Anna A; Caminada, Daniel

    2006-02-10

    Low levels of human medicines (pharmaceuticals) have been detected in many countries in sewage treatment plant (STP) effluents, surface waters, seawaters, groundwater and some drinking waters. For some pharmaceuticals effects on aquatic organisms have been investigated in acute toxicity assays. The chronic toxicity and potential subtle effects are only marginally known, however. Here, we critically review the current knowledge about human pharmaceuticals in the environment and address several key questions. What kind of pharmaceuticals and what concentrations occur in the aquatic environment? What is the fate in surface water and in STP? What are the modes of action of these compounds in humans and are there similar targets in lower animals? What acute and chronic ecotoxicological effects may be elicited by pharmaceuticals and by mixtures? What are the effect concentrations and how do they relate to environmental levels? Our review shows that only very little is known about long-term effects of pharmaceuticals to aquatic organisms, in particular with respect to biological targets. For most human medicines analyzed, acute effects to aquatic organisms are unlikely, except for spills. For investigated pharmaceuticals chronic lowest observed effect concentrations (LOEC) in standard laboratory organisms are about two orders of magnitude higher than maximal concentrations in STP effluents. For diclofenac, the LOEC for fish toxicity was in the range of wastewater concentrations, whereas the LOEC of propranolol and fluoxetine for zooplankton and benthic organisms were near to maximal measured STP effluent concentrations. In surface water, concentrations are lower and so are the environmental risks. However, targeted ecotoxicological studies are lacking almost entirely and such investigations are needed focusing on subtle environmental effects. This will allow better and comprehensive risk assessments of pharmaceuticals in the future.

  17. Quality Control of Pharmaceuticals

    PubMed Central

    Levi, Leo; Walker, George C.; Pugsley, L. I.

    1964-01-01

    Quality control is an essential operation of the pharmaceutical industry. Drugs must be marketed as safe and therapeutically active formulations whose performance is consistent and predictable. New and better medicinal agents are being produced at an accelerated rate. At the same time more exacting and sophisticated analytical methods are being developed for their evaluation. Requirements governing the quality control of pharmaceuticals in accordance with the Canadian Food and Drugs Act are cited and discussed. PMID:14199105

  18. Understanding pharmaceutical quality by design.

    PubMed

    Yu, Lawrence X; Amidon, Gregory; Khan, Mansoor A; Hoag, Stephen W; Polli, James; Raju, G K; Woodcock, Janet

    2014-07-01

    This review further clarifies the concept of pharmaceutical quality by design (QbD) and describes its objectives. QbD elements include the following: (1) a quality target product profile (QTPP) that identifies the critical quality attributes (CQAs) of the drug product; (2) product design and understanding including identification of critical material attributes (CMAs); (3) process design and understanding including identification of critical process parameters (CPPs), linking CMAs and CPPs to CQAs; (4) a control strategy that includes specifications for the drug substance(s), excipient(s), and drug product as well as controls for each step of the manufacturing process; and (5) process capability and continual improvement. QbD tools and studies include prior knowledge, risk assessment, mechanistic models, design of experiments (DoE) and data analysis, and process analytical technology (PAT). As the pharmaceutical industry moves toward the implementation of pharmaceutical QbD, a common terminology, understanding of concepts and expectations are necessary. This understanding will facilitate better communication between those involved in risk-based drug development and drug application review.

  19. Drug Information Residency Rotation with Pharmaceutical Industry.

    ERIC Educational Resources Information Center

    Cramer, Richard L.

    1986-01-01

    Program objectives of a drug information rotation at the Upjohn Company include improving communication between the pharmaceutical industry and hospital pharmacy/academia, exposing the resident to the challenges the industry encounters, improving proficiency in drug information practice, and providing insight into the working relationships of…

  20. Drug Information Residency Rotation with Pharmaceutical Industry.

    ERIC Educational Resources Information Center

    Cramer, Richard L.

    1986-01-01

    Program objectives of a drug information rotation at the Upjohn Company include improving communication between the pharmaceutical industry and hospital pharmacy/academia, exposing the resident to the challenges the industry encounters, improving proficiency in drug information practice, and providing insight into the working relationships of…

  1. Halogenases: A Biotechnological Alternative for the Synthesis of Halogenated Pharmaceuticals.

    PubMed

    Ayala, Marcela; Segovia, Lorenzo; Torres, Eduardo

    2016-01-01

    The role of halogen atoms in pharmaceutical compounds has been recently revised, due to the weak interaction through the so called "halogen bond" between small molecules and proteins or other biomacromolecules, which could be fundamental for binding at a particular site within the macromolecule. Moreover, thousands of natural halogenated compounds have been described to date, pointing to a functional role of halogen atoms in these compounds, as well as a diversity of halogenating enzymes involved in the synthesis of these halogenated metabolites. In this mini-review the different halogenases described to date are presented, particularly those catalyzing halogenation reactions with potential applications in the pharmaceutical field. Oxidative halogenases following an electrophilic halogenation mechanism are the oldest and best characterized halogenases; however, novel halogenases following a nucleophilic halogenation mechanism have been recently described. The catalytic properties as well as the selectivity of some of these enzymes can be modulated through protein engineering, both by single point mutations or by directed evolution; on the other hand, metabolic pathway engineering has been used to improve the production of halogenated metabolites, as well as to produce novel halogenated compounds, potentially important in the pharmaceutical field. Recent advances and prospective on the field of enzymatic halogenation are covered.

  2. Recent patents and patented technology platforms for pharmaceutical taste masking.

    PubMed

    Kaushik, Deepak; Dureja, Harish

    2014-04-01

    Taste masking is an important factor in the development of oral dosage forms containing bitter active pharmaceutical ingredients. Currently numerous techniques are being applied to overcome this problem. Realizing this, several researchers and pharmaceutical companies are now engaged in developing novel techniques to address the problem of taste masking evident by numerous patents filed in this area in recent times. In this review the most recent patents for taste masking are discussed and how these patents overcome the limitations of conventional approaches of taste masking is also highlighted. Novel techniques based on some recent patents such as nanohybrid, melt extrusion, non-complex cyclodextrin compositions and off taste masking are providing new realms to taste masking of bitter drugs. The present article also provides an overview of various patented platform technologies based on different techniques/mechanisms employed for taste masking. The unique features and principles of taste-masking approaches used in various patented technologies are also discussed. A better understanding of these new patents and patented technologies will help researchers and pharmaceutical industries to select the appropriate platform, or to develop innovative products with improved taste masking properties.

  3. Applications of Polymers as Pharmaceutical Excipients in Solid Oral Dosage Forms.

    PubMed

    Debotton, Nir; Dahan, Arik

    2017-01-01

    Over the last few decades, polymers have been extensively used as pharmaceutical excipients in drug delivery systems. Pharmaceutical polymers evolved from being simply used as gelatin shells comprising capsule to offering great formulation advantages including enabling controlled/slow release and specific targeting of drugs to the site(s) of action (the "magic bullets" concept), hence hold a significant clinical promise. Oral administration of solid dosage forms (e.g., tablets and capsules) is the most common and convenient route of drug administration. When formulating challenging molecules into solid oral dosage forms, polymeric pharmaceutical excipients permit masking undesired physicochemical properties of drugs and consequently, altering their pharmacokinetic profiles to improve the therapeutic effect. As a result, the number of synthetic and natural polymers available commercially as pharmaceutical excipients has increased dramatically, offering potential solutions to various difficulties. For instance, the different polymers may allow increased solubility, swellability, viscosity, biodegradability, advanced coatings, pH dependency, mucodhesion, and inhibition of crystallization. The aim of this article is to provide a wide angle prospect of the different uses of pharmaceutical polymers in solid oral dosage forms. The various types of polymeric excipients are presented, and their distinctive role in oral drug delivery is emphasized. The comprehensive know-how provided in this article may allow scientists to use these polymeric excipients rationally, to fully exploit their different features and potential influence on drug delivery, with the overall aim of making better drug products. © 2016 Wiley Periodicals, Inc.

  4. Human pharmaceutical products in the environment - the "problem" in perspective.

    PubMed

    Taylor, David; Senac, Thomas

    2014-11-01

    Concerns about the potential for significant environmental impact from residues of human pharmaceuticals emerged at the beginning of the 21st century. Since then there has been an exponential rise in the number of publications and conferences on this "problem". However, this intense focus on human pharmaceuticals is misplaced. Pharmaceuticals do not consist of a coherent group of substances with similar chemical, structural, biological or toxicological properties. Pharmaceuticals are only identifiable from their use: in other words substances can be divided into two classes, those that are used as pharmaceuticals and those for which a possible pharmaceutical use has not yet been discovered. For example, nitro-glycerine, Warfarin and dimethyl fumarate, initially sold respectively as an explosive, a rodenticide and a mould inhibitor have subsequently all been used as pharmaceuticals. As analytical science advances, an increasing range of environmental contaminants, including pharmaceuticals, is being identified at sub μgL(-1) concentrations. Although, human and environmental exposure to these contaminants will be low, all of them need to be subjected to risk assessment on a case by case basis. Many of these substances, including human pharmaceuticals, may have little, if any, impact on human health or the environment, however for some substances there may be a significant risk and in these cases appropriate action should be taken. However considering all human pharmaceuticals as a special case, isolated from the wider range of emerging contaminants, is scientifically unjustifiable and diverts resources away from the consideration of other substances that may be of considerably more significance.

  5. [Social change and Pharmaceutical Affairs Law (PAL)].

    PubMed

    Masuyama, Koichi; Isobe, Soichiro

    2010-01-01

    Former Japanese pharmaceutical laws, originally based on the Pharmaceutical Marketing and Handling Regulations enacted in 1874 were in operation for many years before World War II. However, in order to address several drug issues, such as poor drug quality and insufficiences regarding the role of pharmacists during the War, the laws needed to be unified and revised. In this paper, we analyzed the record of discussions held by the Imperial Diet on the bill for the Pharmaceutical Affairs Law (PAL) in 1943. This is also regarded as the origin of the current PAL (LawNo.145 in 1960). Through this analysis, we tried to clarify the relationship between the social change and the role of PAL in society. During the War, the bill was discussed, aiming at the improvement of both human resources who treated drugs, and the quality of drug materials. Diet members discussed three main points, namely, "the duty of pharmacists", "the mission of the Japan Pharmaceutical Association" and "the quality control of pharmaceutical products". Notably, the bill pharmacists are required not only to dispense drugs, a role they had previously, but also to manage drug and food hygiene through the quality control of pharmaceutical products and the inspection of food and drink, in order to improve the public health in Japan. Originally, the law was passed to deal with the extraordinary circumstances during the War, but through our analysis, we found that they proactively improved the role of the law to comply with various drug issues raised during the War, the rapid change of the pharmaceutical hygiene concept and the social transformation.

  6. GLP2-2G-XTEN: A Pharmaceutical Protein with Improved Serum Half-Life and Efficacy in a Rat Crohn’s Disease Model

    PubMed Central

    Alters, Susan E.; McLaughlin, Bryant; Spink, Benjamin; Lachinyan, Tigran; Wang, Chia-wei; Podust, Vladimir; Schellenberger, Volker; Stemmer, Willem P. C.

    2012-01-01

    Objectives Glucagon-like peptide 2 (GLP2) is an intestinal growth factor that has been shown to stimulate intestinal growth and reduce disease severity in preclinical models of short bowel syndrome and inflammatory bowel disease. Teduglutide, a recombinant human GLP2 variant (GLP2-2G), has increased half-life and stability as compared to the native GLP2 peptide, but still requires twice daily dosing in preclinical models and daily dosing in the clinic. The goal of this study was to produce and characterize the preclinical pharmacokinetic and therapeutic properties of GLP2-2G-XTEN, a novel, long-acting form of GLP2-2G. Methodology and Results A GLP2-2G-XTEN fusion protein with extended exposure profile was produced by genetic fusion of GLP2-2G peptide to XTEN, a long, unstructured, non-repetitive, hydrophilic sequence of amino acids. The serum half-life of GLP2-2G-XTEN in mice, rats and monkeys was 34, 38 and 120 hours, respectively. Intestinotrophic effects were demonstrated in normal rats, where GLP2-2G-XTEN administration resulted in a significant increase in both small intestine weight and length. Efficacy of the GLP2-2G-XTEN protein was compared to that of GLP2-2G peptide in a rat Crohn’s disease model, indomethacin-induced inflammation. Prophylactic administration of GLP2-2G-XTEN significantly increased the length, reduced the number of trans-ulcerations and adhesions, and reduced the TNFα content of the small intestine. GLP2-2G-XTEN demonstrated greater in vivo potency as compared to GLP2-2G peptide, and improvement in histopathology supported the GLP2-2G-XTEN treatment effects. Conclusions and Significance GLP2-2G-XTEN is intestinotrophic and demonstrates efficacy in a rat Crohn’s disease model requiring a lower molar dose and less frequent dosing relative to GLP2-2G peptide. Allometric scaling based on pharmacokinetics from mouse, rat and monkey projects a human half-life of 240 hours. These improvements in preclinical pharmacokinetics and dosing

  7. Nigerian geophagical clay: a traditional antidiarrheal pharmaceutical.

    PubMed

    Vermeer, D E; Ferrell, R E

    1985-02-08

    The chief geophagical clay entering the West African market system comes from the village of Uzalla, Nigeria. Village inhabitants ascribe antidiarrheal properties to the clay, and they use it in traditional medicinal preparations to counteract intestinal problems. Mineralogical analyses demonstrate a striking similarity between the Uzalla village clay and the clay in the commercial pharmaceutical Kaopectate.

  8. Improved Icephobic Properties on Surfaces with a Hydrophilic Lubricating Liquid.

    PubMed

    Ozbay, Salih; Yuceel, Cigdem; Erbil, H Yildirim

    2015-10-07

    Slippery liquid-infused porous surfaces were developed recently for icephobic surface applications. Perfluorinated liquids, silicone oil, hydrocarbon, and water were used as lubricating liquids to form a continuous layer on a suitable substrate to prevent icing. However, ice accretion performances of these surfaces have not been reported previously depending on the type of the lubricant. In this work, fluorinated aliphatics, polyalphaolefin, silicone oil, and decamethylcyclopenta siloxane were used as hydrophobic lubricants; water, ethylene glycol, formamide, and water-glycerine mixture were used as hydrophilic lubricants to be impregnated by hydrophobic polypropylene and hydrophilic cellulose-based filter paper surfaces; ice accretion, drop freezing delay time, and ice adhesion strength properties of these surfaces were examined; and the results were compared to those of the reference surfaces such as aluminum, copper, polypropylene, and polytetrafluoroethylene. An ice accretion test method was also developed to investigate the increase of the mass of formed ice gravimetrically by spraying supercooled water onto these surfaces at different subzero temperatures ranging between -1 and -5 °C. It was determined that hydrophilic solvents (especially a water-glycerine mixture) that impregnated hydrophilic porous surfaces would be a promising candidate for anti-icing applications at -2 °C and 56-83% relative humidity because ice accretion and ice adhesion strength properties of these surface decreased simultaneously in these conditions.

  9. Iron aluminide alloys with improved properties for high temperature applications

    DOEpatents

    McKamey, C.G.; Liu, C.T.

    1990-10-09

    An improved iron aluminide alloy of the DO[sub 3] type is described that has increased room temperature ductility and improved high elevated temperature strength. The alloy system further is resistant to corrosive attack in the environments of advanced energy conversion systems such as those using fossil fuels. The resultant alloy is relatively inexpensive as contrasted to nickel based and high nickel steels currently utilized for structural components. The alloy system consists essentially of 26--30 at. % aluminum, 0.5--10 at. % chromium, 0.02--0.3 at. % boron plus carbon, up to 2 at. % molybdenum, up to 1 at. % niobium, up to 0.5 at. % zirconium, up to 0.1 at. % yttrium, up to 0.5 at. % vanadium and the balance iron. 3 figs.

  10. Iron aluminide alloys with improved properties for high temperature applications

    DOEpatents

    McKamey, Claudette G.; Liu, Chain T.

    1990-01-01

    An improved iron aluminide alloy of the DO.sub.3 type that has increased room temperature ductility and improved high elevated temperature strength. The alloy system further is resistant to corrosive attack in the environments of advanced energy corrosion systems such as those using fossil fuels. The resultant alloy is relatively inexpensive as contrasted to nickel based and high nickel steels currently utilized for structural components. The alloy system consists essentially of 26-30 at. % aluminum, 0.5-10 at. % chromium, 0.02-0.3 at. % boron plus carbon, up to 2 at. % molybdenum, up to 1 at. % niobium, up to 0.5 at. % zirconium, up to 0.1 at. % yttrium, up to 0.5 at. % vanadium and the balance iron.

  11. Cardiac rehabilitation improves the blood plasma properties of cardiac patients.

    PubMed

    Gwoździński, Krzysztof; Pieniążek, Anna; Czepas, Jan; Brzeszczyńska, Joanna; Jegier, Anna; Pawlicki, Lucjan

    2016-11-01

    Cardiac rehabilitation (CR) improves exercise tolerance and general function. However, its effects on blood plasma in cardiac patients remain uncertain. Our aim was to examine the effect of comprehensive CR on the oxidative stress parameters and antioxidant plasma status in patients with coronary artery disease (CAD) after cardiac interventions. Exercise-based rehabilitation was established as ergometer training, adjusted for individual patients' physical efficiency. Training was repeated three times a week for two months. The standard biochemical (total cholesterol, HDL, LDL, triglycerides and erythrocyte sedimentation rate) and metabolic parameters (peak oxygen uptake [VO2] and peak workload) were determined. We assessed plasma viscosity, lipid peroxidation, carbonyl compounds levels, glutathione (GSH) and ascorbate (ASC) levels and the non-enzymatic antioxidant capacity of plasma in 12 patients with CAD before and after CR. Parameters were examined before exercise, immediately after exercise, and 1 h later. We also compared morphological and biochemical parameters of blood, as well as other parameters such as heart rate and blood pressure (resting and exercise), VO2max and peak workload (W) before and after CR. Before CR, a significant decrease in GSH concentration was observed 1 h after exercise. Conversely, after CR, GSH, and ASC levels remained unchanged immediately after exercise. However, ASC increased after CR after exercise and 1 h later in comparison to before CR. There was a significant increase in ferric reduction ability of plasma immediately after exercise after CR, when compared with before CR. CR improved several blood biochemical parameters, peak VO2, induced an increase in systolic blood pressure peak, and patients' peak workload. After CR, improvements were detected in oxidative stress parameters, except in the level of carbonyls. These changes may contribute to the increased functional heart capacity and better tolerance to exercise and

  12. Cultivation and characterization of bacterial isolates capable of degrading pharmaceutical and personal care products for improved removal in activated sludge wastewater treatment.

    PubMed

    Zhou, Nicolette A; Lutovsky, April C; Andaker, Greta L; Gough, Heidi L; Ferguson, John F

    2013-11-01

    Pharmaceutical and personal care products (PPCPs) discharged with wastewater treatment plant (WWTP) effluents are an emerging surface water quality concern. Biological transformation has been identified as an important removal mechanism during wastewater treatment. The aim of this research was the identification of bacteria with characteristics for potential bioaugmentation to enhance PPCP removal. We report here the cultivation and characterization of bacteria capable of degrading PPCPs to ng/L concentrations. An isolation approach was developed using serial enrichment in mineral medium containing 1 mg/L of an individual PPCP as the sole organic carbon source available to heterotrophs until the original activated sludge inocula was diluted to ~10(-8) of its initial concentration, followed by colony growth on solid R2A agar. Eleven bacteria were isolated, eight that could remove triclosan, bisphenol A, ibuprofen, or 17β-estradiol to below 10 ng/L, one that could remove gemfibrozil to below 60 ng/L, and two that could remove triclosan or E2, but not to ng/L concentrations. Most bacterial isolates degraded contaminants during early growth when grown utilizing rich carbon sources and were only able to degrade the PPCPs on which they were isolated. Seven of the bacterial isolates were sphingomonads, including all the triclosan and bisphenol A degraders and the ibuprofen degrader. The study results indicate that the isolated bacteria may have a positive influence on removal in WWTPs if present at sufficient concentrations and may be useful for bioaugmentation.

  13. Investigation of the physical-mechanical properties of Eudragit(®) RS PO/RL PO and their mixtures with common pharmaceutical excipients.

    PubMed

    Dave, Vivek S; Fahmy, Raafat M; Hoag, Stephen W

    2013-07-01

    Ammonio methacrylate copolymers Eudragit(®) RS PO and Eudragit® RL PO have found widespread use as key components in various types of extended release solid dosage forms. The deformation behavior of neat polymers and binary mixes was evaluated using Heckel Analysis, strain rate sensitivity, work of compaction and elastic recovery index. Additionally, the compact forming ability of neat materials and binary mixes were evaluated by analyzing their tabletability, compressibility and compactibility profiles. The Heckel analysis of both polymers exhibited a speed-sensitive deformation behavior typical to plastic materials. The yield values of the binary mixes of the polymers with microcrystalline cellulose revealed a linear relationship with the weight fractions of individual components. The yield values of binary mixes of both the polymers with dibasic calcium phosphate exhibited slight negative deviations from linearity. Both polymers exhibited axial relaxation after ejection typical of viscoelastic materials, as measured by the elastic recovery index values. The work of compaction and the elastic recovery index values of the binary mixtures were found to be linearly related to the weight fractions of the individual components thus, confirming ideal mixing behavior based on the composition. Addition of microcrystalline cellulose to both polymers significantly improved their tabletability and compactibility. The tensile strengths of the compacts prepared with neat materials and binary mixes with microcrystalline cellulose, dibasic calcium phosphate and lactose were the function of their solid fraction and independent of the tableting speeds tested; thus, validating compactibility as a reliable parameter in predicting acceptable tablet properties.

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

    PubMed

    Yamamoto, Keiji; Limwikrant, Waree; Moribe, Kunikazu

    2011-01-01

    The molecular states of active pharmaceutical ingredients (APIs) in pharmaceutical dosage forms strongly affect the properties and quality of a drug. Various important fundamental physicochemical studies were reviewed from the standpoint of molecular pharmaceutics. Mechanochemical effects were evaluated in mixtures of APIs and pharmaceutical additives. Amorphization, complex formation and nanoparticle formation are observed after grinding process depending on the combination of APIs and pharmaceutical additives. Sealed-heating method and mesoporous materials have been used to investigate drug molecular interactions in dosage forms. Molecular states have been investigated using powder X-ray diffraction, thermal analysis, IR, solid state fluorometry, and NMR. © 2011 Pharmaceutical Society of Japan

  15. Synthesis and pharmacokinetic property improvement of deuterated plinabulin 9

    NASA Astrophysics Data System (ADS)

    Zhao, Jianchun; Cheng, Hejuan; Sun, Tianwen; Wang, Shixiao; Ding, Zhongpeng; Dou, Guifang; Meng, Zhiyun; Guan, Huashi; Li, Wenbao

    2017-04-01

    Plinabulin, a potent microtubule-targeting agent, is derived from marine natural diketopiperazine `phenylahistin'. To develop novel plinabulin analogue that could display better pharmacokinetic properties and less side effects, deuterated plinabulin 9 was synthesized and evaluated in vitro and in vivo. In comparison with plinabulin, in vivo pharmacokinetic studies indicated that the deuterated derivative 9 could alter blood circulation behavior obviously, which was proved by increased area under the plasma concentration- time curve (AUC0-∞), reduced clearance (CL), and prolonged total body mean residence time (MRT). The derivative 9 also has higher inhibition rates against BxPC-3, Jurkat and A-431 tumor cell lines as compared with its prototype plinabulin. Therefore, the deuterated compound 9 might be developed as a potential agent for different cancer treatments.

  16. Novel Cyclic Biphalin Analogue with Improved Antinociceptive Properties

    PubMed Central

    2014-01-01

    Two novel opioid analogues have been designed by substituting the native d-Ala residues in position 2,2′ of biphalin with two residues of d-penicillamine or l-penicillamine and by forming a disulfide bond between the thiol groups. The so-obtained compound 9 containing d-penicillamines showed excellent μ/δ mixed receptor affinities (Kiδ = 5.2 nM; Kiμ = 1.9 nM), together with an efficacious capacity to trigger the second messenger and a very good in vivo antinociceptive activity, whereas product 10 was scarcely active. An explanation of the two different pharmacological behaviors of products 9 and 10 was found by studying their conformational properties. PMID:25221662

  17. Magnetic nanoparticles supported ionic liquids improve firefly luciferase properties.

    PubMed

    Noori, Ali Reza; Hosseinkhani, Saman; Ghiasi, Parisa; Akbari, Jafar; Heydari, Akbar

    2014-03-01

    Ionic liquids as neoteric solvents, microwave irradiation, and alternative energy source are becoming as a solvent for many enzymatic reactions. We recently showed that the incubation of firefly luciferase from Photinus pyralis with various ionic liquids increased the activity and stability of luciferase. Magnetic nanoparticles supported ionic liquids have been obtained by covalent bonding of ionic liquids-silane on magnetic silica nanoparticles. In the present study, the effects of [γ-Fe2O3@SiO2][BMImCl] and [γ-Fe2O3@SiO2][BMImI] were investigated on the structural properties and function of luciferase using circular dichroism, fluorescence spectroscopy, and bioluminescence assay. Enzyme activity and structural stability increased in the presence of magnetic nanoparticles supported ionic liquids. Furthermore, the effect of ingredients which were used was not considerable on K(m) value of luciferase for adenosine-5'-triphosphate and also K(m) value for luciferin.

  18. Hydroxyapatite reinforced collagen scaffolds with improved architecture and mechanical properties.

    PubMed

    Kane, Robert J; Weiss-Bilka, Holly E; Meagher, Matthew J; Liu, Yongxing; Gargac, Joshua A; Niebur, Glen L; Wagner, Diane R; Roeder, Ryan K

    2015-04-01

    Hydroxyapatite (HA) reinforced collagen scaffolds have shown promise for synthetic bone graft substitutes and tissue engineering scaffolds. Freeze-dried HA-collagen scaffolds are readily fabricated and have exhibited osteogenicity in vivo, but are limited by an inherent scaffold architecture that results in a relatively small pore size and weak mechanical properties. In order to overcome these limitations, HA-collagen scaffolds were prepared by compression molding HA reinforcements and paraffin microspheres within a suspension of concentrated collagen fibrils (∼ 180 mg/mL), cross-linking the collagen matrix, and leaching the paraffin porogen. HA-collagen scaffolds exhibited an architecture with high porosity (85-90%), interconnected pores ∼ 300-400 μm in size, and struts ∼ 3-100 μm in thickness containing 0-80 vol% HA whisker or powder reinforcements. HA reinforcement enabled a compressive modulus of up to ∼ 1 MPa, which was an order of magnitude greater than unreinforced collagen scaffolds. The compressive modulus was also at least one order of magnitude greater than comparable freeze-dried HA-collagen scaffolds and two orders of magnitude greater than absorbable collagen sponges used clinically. Moreover, scaffolds reinforced with up to 60 vol% HA exhibited fully recoverable elastic deformation upon loading to 50% compressive strain for at least 100,000 cycles. Thus, the scaffold mechanical properties were well-suited for surgical handling, fixation, and bearing osteogenic loads during bone regeneration. The scaffold architecture, permeability, and composition were shown to be conducive to the infiltration and differentiation of adipose-derive stromal cells in vitro. Acellular scaffolds were demonstrated to induce angiogenesis and osteogenesis after subcutaneous ectopic implantation by recruiting endogenous cell populations, suggesting that the scaffolds were osteoinductive.

  19. Polymer/Silicate Nanocomposites Developed for Improved Thermal Stability and Barrier Properties

    NASA Technical Reports Server (NTRS)

    Campbell, Sandi G.

    2001-01-01

    The nanoscale reinforcement of polymers is becoming an attractive means of improving the properties and stability of polymers. Polymer-silicate nanocomposites are a relatively new class of materials with phase dimensions typically on the order of a few nanometers. Because of their nanometer-size features, nanocomposites possess unique properties typically not shared by more conventional composites. Polymer-layered silicate nanocomposites can attain a certain degree of stiffness, strength, and barrier properties with far less ceramic content than comparable glass- or mineral-reinforced polymers. Reinforcement of existing and new polyimides by this method offers an opportunity to greatly improve existing polymer properties without altering current synthetic or processing procedures.

  20. Potent antimalarial 4-pyridones with improved physico-chemical properties.

    PubMed

    Bueno, José M; Manzano, Pilar; García, María C; Chicharro, Jesús; Puente, Margarita; Lorenzo, Milagros; García, Adolfo; Ferrer, Santiago; Gómez, Rubén M; Fraile, María T; Lavandera, José L; Fiandor, José M; Vidal, Jaume; Herreros, Esperanza; Gargallo-Viola, Domingo

    2011-09-15

    Antimalarial 4-pyridones are a novel class of inhibitors of the plasmodial mitochondrial electron transport chain targeting Cytochrome bc1 (complex III). In general, the most potent 4-pyridones are lipophilic molecules with poor solubility in aqueous media and low oral bioavailability in pre-clinical species from the solid dosage form. The strategy of introducing polar hydroxymethyl groups has enabled us to maintain the high levels of antimalarial potency observed for other more lipophilic analogues whilst improving the solubility and the oral bioavailability in pre-clinical species. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Stability studies needed to define the handling and transport conditions of sensitive pharmaceutical or biotechnological products.

    PubMed

    Ammann, Claude

    2011-12-01

    Many pharmaceutical or biotechnological products require transport using temperature-controlled systems to keep their therapeutic properties. There are presently no official guidelines for testing pharmaceutical products in order to define suitable transport specifications. After reviewing the current guidance documents, this paper proposes a methodology for testing pharmaceutical products and defining appropriate transport conditions.

  2. New pharmaceuticals reduce cost of illness.

    PubMed

    Hansen, R W

    1986-06-01

    The cost of illness includes not only the funds required to treat illness, but also the effect on the patient's quality of life. Recent concern about rising health costs have focused on the direct expenditures without noting that the cost of illness in terms of mortality and morbidity has declined significantly. Pharmaceuticals have played a major role in reducing the total cost of illness. Several studies of the cost-effectiveness of past introductions of vaccines and pharmaceuticals reveal large cost savings. Although the focus of most studies has been on major advances, the continuing process of less dramatic therapeutic improvements has significantly trimmed the cost of illness. Cost-benefit studies of new drugs or changes in drug use, while more difficult to perform, make it possible to influence the selection of therapy. Since pharmaceuticals represent less than 10% of total treatment costs, reduction in the cost of pharmaceutical products can only have a minor impact on the total cost of illness. Pharmaceuticals can reduce the cost of illness by providing alternative therapies that reduce direct treatment cost or improve the public health.

  3. [Fourcroy and pharmaceutical journals].

    PubMed

    Bonnemain, Bruno

    2011-04-01

    Cadet de Gassicourt wrote a brief Eloge of Fourcroy in January 1810 as he died in December of 1809. Fourcroy had a major role concerning the new ideas on the place of pharmacy at the beginning of the 19th century. Fourcroy has had a key influence for the start of several pharmaceutical journals that wanted to emphasize the link between the new chemistry and pharmacy. None of these journals created with him will survive and one has to wait for 1909 to see the creation, without Fourcroy, of a new pharmaceutical journal, the "Journal de Pharmacie" that will become "Journal de Pharmacie et des Sciences accessoires", then "Journal de Pharmacie et de Chimie", before taking the name of"Annales Pharmaceutiques Françaises", the present official journal of the French Academy of Pharmacy. In spite of the essential role of Fourcroy at the start of pharmaceutical journals, Cadet did not even mention it in his Eloge of 1810.

  4. Common physical properties among relational networks improve analogy aptness.

    PubMed

    Ruiz, Francisco J; Luciano, Carmen

    2015-05-01

    Relational frame theory (RFT) conceptualizes analogy as the establishment of a relation of coordination among common types of relations. This study provided an initial RFT analysis of analogy aptness. Twenty participants initially learned to respond to the structure of analogical tests after which they were trained on two separate relational networks, each consisting of three equivalence classes (Network: 1 F1-G1-H1, F2-G2-H2, F3-G3-H3; Network 2: M1-N1-O1, M2-N2-O2, M3-N3-O3). The node stimuli always appeared with color spots on their backgrounds (F1 and M1: yellow; F2 and M2: red; F3 and M3: blue). In the critical test, participants had to select the more correct response from two options: relating combinatorial relations of coordination with the same color in the node stimuli (e.g., relating G1H1 to N1O1) versus relating combinatorial relations with different colors in the node stimuli (e.g., relating G1H1 to N2O2). The colors of the node stimuli did not appear on the critical test. Ninety percent of participants selected the analogies with common color properties as the more correct ones. Practical implications of these findings are discussed.

  5. Properties and reliability of improved large acceptance optical fibers

    NASA Astrophysics Data System (ADS)

    Skutnik, Bolesh J.; Smith, Cheryl; Moran, Kelly; Bakhshpour, Kevin

    2006-02-01

    The high power diode laser systems with their laser diode bars and arrays not only require special fibers to couple directly to the diode emitters, but also require special fibers to couple from the laser to the application sites. These power delivery fibers are much larger than the internal fibers, but must be flexible, and have not only good strength but also good fatigue behavior. This is particularly important for industrial systems using robotic arms or robots to apply the high power laser energy to the treatment site. The optical properties of hard plastic clad silica (HPCS) fibers are well suited for the needs of delivery of high power from diode laser bars and arrays to an application site. New formulations for HPCS fibers have been developed which have demonstrated fibers with good mechanical strength in preliminary tests. A systematic study has been undertaken to determine the strength and fatigue behavior of three 'new' HPCS fibers and to compare them with results for earlier HPCS fibers. Benefits of stronger median dynamic strengths and tighter flaw distributions have been found. Short to medium length time to failure results, indicate that the static fatigue parameters of the new high numerical aperture (NA) optical fibers are at least as good as those for standard NA HPCS fibers, which is an advance from previous results on the older formulation clad fibers.

  6. Hydrolysis by Alcalase Improves Hypoallergenic Properties of Goat Milk Protein

    PubMed Central

    Yun, Sung-Seob; Lee, Won-Jae; Kim, Jin-Wook; Ha, Ho-Kyung; Yoo, Michelle

    2016-01-01

    Goat milk is highly nutritious and is consumed in many countries, but the development of functional foods from goat milk has been slow compared to that for other types of milk. The aim of this study was to develop a goat milk protein hydrolysate (GMPH) with enhanced digestibility and better hypoallergenic properties in comparison with other protein sources such as ovalbumin and soy protein. Goat milk protein was digested with four commercial food-grade proteases (separately) under various conditions to achieve the best hydrolysis of αs -casein and β-lactoglobulin. It was shown that treatment with alcalase (0.4%, 60℃ for 30 min) effectively degraded these two proteins, as determined by SDS-PAGE, measurement of nonprotein nitrogen content, and reverse-phase high-performance liquid chromatography. Hydrolysis with alcalase resulted in a significant decrease in β-lactoglobulin concentration (almost to nil) and a ~40% reduction in the level of αs-casein. Quantification of histamine and TNF-α released from HMC-1 cells (human mast cell line) showed that the GMPH did not induce an allergic response when compared to the control. Hence, the GMPH may be useful for development of novel foods for infants, the elderly, and convalescent patients, to replace cow milk. PMID:27621693

  7. Silver-containing mesoporous bioactive glass with improved antibacterial properties.

    PubMed

    Gargiulo, Nicola; Cusano, Angela Maria; Causa, Filippo; Caputo, Domenico; Netti, Paolo Antonio

    2013-09-01

    The aim of the present work is the study of the bacteriostatic/bactericidal effect of a silver-containing mesoporous bioactive glass obtained by evaporation-induced self-assembly and successive thermal stabilization. Samples of the manufactured mesophase were characterized by means of transmission electron microscopy and N₂ adsorption/desorption at 77 K, revealing structural and textural properties similar to SBA-15 mesoporous silica. Glass samples used for bioactivity experiments were put in contact with a standardized, commercially available cell culture medium instead of lab-produced simulated body fluid, and were then characterized by means of X-ray diffraction, field emission scanning electron microscopy and Fourier transform infrared spectroscopy. All these analyses confirmed the development of a hydroxyl carbonate apatite layer on glass particles. Moreover, the investigated mesostructure showed a very good antibacterial effect against S. aureus strain, with a strong evidence of bactericidal activity already registered at 0.5 mg/mL of glass concentration. A hypothesis about the mechanism by which Ag affects the bacterial viability, based on the intermediate formation of crystalline AgCl, was also taken into account. With respect to what already reported in the literature, these findings claim a deeper insight into the possible use of silver-containing bioactive glasses as multifunctional ceramic coatings for orthopedic devices.

  8. Chitosan fibers with improved biological and mechanical properties for tissue engineering applications.

    PubMed

    Albanna, Mohammad Z; Bou-Akl, Therese H; Blowytsky, Oksana; Walters, Henry L; Matthew, Howard W T

    2013-04-01

    The low mechanical properties of hydrogel materials such as chitosan hinder their broad utility for tissue engineering applications. Previous research efforts improved the mechanical properties of chitosan fiber through chemical and physical modifications; however, unfavorable toxicity effects on cells were reported. In this paper, we report the preparation of chitosan fibers with improved mechanical and biocompatibility properties. The structure-property relationships of extruded chitosan fibers were explored by varying acetic acid (AA) concentration, ammonia concentration, annealing temperature and degree of heparin crosslinking. Results showed that optimizing AA concentration to 2vol% improved fiber strength and stiffness by 2-fold. Extruding chitosan solution into 25wt% of ammonia solution reduced fiber diameters and improved fiber strength by 2-fold and stiffness by 3-fold, due to an increase in crystallinity as confirmed by XRD. Fiber annealing further reduced fiber diameter and improved fiber strength and stiffness as temperature increased. Chitosan fibers crosslinked with heparin had increased diameter but lower strength and stiffness properties and higher breaking strain values. When individual parameters were combined, further improvement in fiber mechanical properties was achieved. All mechanically improved fibers and heparin crosslinked fibers promoted valvular interstitial cells (VIC) attachment and growth over 10 day cultures. Our results demonstrate the ability to substantially improve the mechanical properties of chitosan fibers without adversely affecting their biological properties. The investigated treatments offer numerous advantages over previous physical/chemical modifications and thus are expected to expand the utility of chitosan fibers with tunable mechanical properties in various tissue engineering applications. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Improvement of the energetic properties of the GPR

    NASA Astrophysics Data System (ADS)

    Pochanin, Gennadiy P.; Ruban, Vadim P.; Kholod, Pavlo V.; Shuba, Alexander A.; Pochanin, Alexander G.; Orlenko, Alexander A.

    2014-05-01

    The necessary condition for the expansion of the impulse Ground Penetrating Radar (GPR) applications is to improve the GPR energy performance for the detection of signals on the background of noise. Digital signal processing techniques allow suppressing the noise largely, but they work only when the GPR is able to register the reflected signals. The majority of the modern GPRs use sampling receivers. They allow recording signals of a very short du- ration. However, very large energy losses are inherent to this method. To improve the signal to noise ratio it is possible to increase the power of the probing signal and to de- crease the noise level of the receiver. In GPR, the transmitting and receiving antennas are usually electrodynamically coupled because they are situated quite close to each other. The sensitive input circuit of the receiver does not allow the excess of the signal amplitude typically more than 1 V. Thus, the increase of the intensity of the probing signal is possible only up to a certain level. To overcome this limitation, it was proposed to design an antenna in such a way that the coupling between the transmitting and receiving sections was absent or minimal. A special method that provided the decoupling below -64 dB was invented (theoretically the isolation is absolute and frequency independent). In order to register as short as possible signals, researchers strive to make sample duration of the sampling converter as short as possible. However, the shorter the sample duration, the smaller the energy of the signal that can be received and the larger the noise. Due to the dispersive absorption of electromagnetic waves in the ground, the high-frequency part of the signal spectrum is attenuated faster than the low-frequency part. It makes no sense to expect the arrival of very short pulses from deep reflectors. Thus, it is possible to increase the duration of the samples at reception of the signals from the deep objects. The authors proposed to

  10. Matched molecular pairs as a guide in the optimization of pharmaceutical properties; a study of aqueous solubility, plasma protein binding and oral exposure.

    PubMed

    Leach, Andrew G; Jones, Huw D; Cosgrove, David A; Kenny, Peter W; Ruston, Linette; MacFaul, Philip; Wood, J Matthew; Colclough, Nicola; Law, Brian

    2006-11-16

    By identifying every pair of molecules that differ only by a particular, well-defined, structural transformation in a database of measured properties and computing the corresponding change in property, we obtain an overview of the effect that structural change has upon the property and set an expectation for what will happen when that transformation is applied elsewhere. The mean change indicates the expected magnitude of the change in the property and the number of cases in which the property increases give the probability that the structural transformation will cause the property to increase. Outliers indicate potential ways of avoiding the general trend. Comparing to changes in lipophilicity highlights structural transformations that have unusual effects, some of which can be explained by conformational changes. In this paper, we focus upon the effects on aqueous solubility, plasma protein binding and oral exposure of adding substituents to aromatic rings and methylating heteroatoms.

  11. Solid dispersions of efonidipine hydrochloride ethanolate with improved physicochemical and pharmacokinetic properties prepared with microwave treatment.

    PubMed

    Otsuka, Masafumi; Maeno, Yusuke; Fukami, Toshiro; Inoue, Motoki; Tagami, Tatsuaki; Ozeki, Tetsuya

    2016-11-01

    Drug absorption into the body is known to be greatly affected by the solubility of the drug itself. The active pharmaceutical ingredient efonidipine hydrochloride ethanolate (NZ-105) is a novel 1,4-dihydropyridine calcium antagonist that has a very low solubility in water. It is classified as a poorly soluble drug, and improvements in its solubility and higher bioavailability with oral administration are needed. In this study, employing microwave technology as a new means to improve solubility, we established a method for preparing solid dispersions using hydroxypropyl methylcellulose acetate succinate as a polymeric carrier and urea as a third component. This effective method has a treatment time of several minutes (simple) and does not require the use of organic solvents (low environmental impact). The third component, urea, acts to lower the melting point of NZ-105, which promotes amorphization. This greatly improves the solubility compared with the microwave-treated product of NZ-105/HPMC-AS binary system. The solid dispersion prepared with this method, in addition to evaluation in vitro, was tested in vivo using beagle dogs and shown to be effective from the eightfold improvement in absorption compared with NZ-105 alone based on the area under the curve. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Effect of a pharmaceutical cationic exchange resin on the properties of controlled release diphenhydramine hydrochloride matrices using Methocel K4M or Ethocel 7cP as matrix formers.

    PubMed

    Akkaramongkolporn, Prasert; Ngawhirunpat, Tanasait; Nunthanid, Jurairat; Opanasopit, Praneet

    2008-01-01

    This work was aimed at evaluating the effect of a pharmaceutical cationic exchange resin (Amberlite IRP-69) on the properties of controlled release matrices using Methocel K4M (HPMC) or Ethocel 7cP (EC) as matrix formers. Diphenhydramine hydrochloride (DPH), which was cationic and water soluble, was chosen as a model drug. HPMC- and EC-based matrices with varying amounts (0-40%w/w) of resin incorporation were prepared by a direct compression. Matrix properties including diameter, thickness, hardness, friability, surface morphology and drug release were evaluated. The obtained matrices were comparable in diameter and thickness regardless of the amount of resin incorporation. Increasing the incorporated resin decreased the hardness of HPMC- and EC-based matrices, correlating with the degree of rupturing on the matrix surfaces. The friability of HPMC-based matrices increased with increasing the incorporated resin, corresponding to their decreased hardness. In contrast, the EC-based matrices showed no significant change in friability in spite of decreasing hardness. The incorporated resin differently influenced DPH release from HPMC- and EC-based matrices in deionized water. The resin further retarded DPH release from HPMC-based matrices due to the gelling property of HPMC and the ion exchange property of the resin. In contrast, the release from EC-based matrices initially increased because of the disintegrating property of the resin, but thereafter declined due to the complex formation between released drug and dispersed resin via the ion exchange process. The release in ionic solutions was also described. In conclusion, the incorporated resin could alter the release and physical properties of matrices.

  13. Transient Hypoxia Improves Matrix Properties in Tissue Engineered Cartilage

    PubMed Central

    Yodmuang, Supansa; Gadjanski, Ivana; Chao, Pen-hsiu Grace; Vunjak-Novakovic, Gordana

    2014-01-01

    Adult articular cartilage is a hypoxic tissue, with oxygen tension ranging from <10% at the cartilage surface to <1% in the deepest layers. In addition to spatial gradients, cartilage development is also associated with temporal changes in oxygen tension. However, a vast majority of cartilage tissue engineering protocols involves cultivation of chondrocytes or their progenitors under ambient oxygen concentration (21% O2), that is, significantly above physiological levels in either developing or adult cartilage. Our study was designed to test the hypothesis that transient hypoxia followed by normoxic conditions results in improved quality of engineered cartilaginous ECM. To this end, we systematically compared the effects of normoxia (21% O2 for 28 days), hypoxia (5% O2 for 28 days) and transient hypoxia—reoxygenation (5% O2 for 7 days and 21% O2 for 21 days) on the matrix composition and expression of the chondrogenic genes in cartilage constructs engineered in vitro. We demonstrated that reoxygenation had the most effect on the expression of cartilaginous genes including COL2A1, ACAN, and SOX9 and increased tissue concentrations of amounts of glycosaminoglycans and type II collagen. The equilibrium Young’s moduli of tissues grown under transient hypoxia (510.01 ± 28.15 kPa) and under normoxic conditions (417.60 ± 68.46 kPa) were significantly higher than those measured under hypoxic conditions (279.61 ± 20.52 kPa). These data suggest that the cultivation protocols utilizing transient hypoxia with reoxygenation have high potential for efficient cartilage tissue engineering, but need further optimization in order to achieve higher mechanical functionality of engineered constructs. PMID:23203946

  14. Potentiometric behaviour of ion selective electrodes based on iron porphyrins: the influence of porphyrin substituents on the response properties and analytical determination of diclofenac in pharmaceutical formulations.

    PubMed

    Santos, Emília M G; Araújo, Alberto N; Couto, Cristina M C M; Montenegro, M Conceição B S M

    2006-11-16

    The potentiometric response characteristics of diclofenac selective electrodes based on Fe(III) tetraphenylporphyrin-chloride (Fe(III)TPP-Cl) and Fe(III) tetrakis(pentafluorophenyl)porphyrin-chloride (Fe(III)TPFPP-Cl) in different mediator solvents and ionic additives are compared. The sensitivity, working range, detection limit, response mechanism, and selectivity of the membrane sensor show a significant dependence on the type of carrier substituent and on the pH value of the sample solution. Studies performed with different amounts of cationic additive (tetra-n-octylammoniumbromide (TOABr)) and anionic additive (sodium tetraphenylborate (NaTPB)) in the membranes allowed the determination of the potentiometric mechanism of action of the used metalloporphyrins. For the analysis of real samples, Fe(III)TPFPP-Cl (type G), prepared in o-NPOE, incorporating 10 mol% of TOABr, was used. This potentiometric unit presented a linear response towards diclofenac concentrations between 10(-5) and 10(-2)mol l(-1) ( I=0.1 mol l(-1)) and slopes of about -59 mV dec(-1), exhibiting a response time of 10s in a buffered solution of ammonia-ammonium sulphate with pH 9.9. The potentiometric analysis of sodium diclofenac in pharmaceutical formulations was carried out by direct potentiometry and the obtained results were compared to those provided by HPLC, presenting relative errors inferior to 1.0%.

  15. Effects of Fenton treatment on the properties of effluent organic matter and their relationships with the degradation of pharmaceuticals and personal care products.

    PubMed

    Li, Wei; Nanaboina, Venkateswarlu; Zhou, Qixing; Korshin, Gregory V

    2012-02-01

    This study examined effects of Fenton oxidation on trace level pharmaceuticals and personal care products (PPCPs) commonly occurring in wastewater. The tested PPCPs included acetaminophen, atenolol, atrazine, carbamazepine, metoprolol, dilantin, DEET, diclofenac, pentoxifylline, oxybenzone, caffeine, fluoxetine, gemfibrozil, ibuprofen, iopromide, naproxen, propranolol, sulfamethoxazole, bisphenol-A and trimethoprim. Transformations of effluent organic matter (EfOM) caused by Fenton oxidation were also quantified. All tested PPCPs, except atrazine and iopromide, were completely removed by Fenton treatment carried out using a 20mg/L Fe (II) concentration and a 2.5 H(2)O(2)/Fe (II) molar ratio. Up to 30% on the total carbon concentration was removed during Fenton treatment which was accompanied by the oxidation of EfOM molecules and formation of oxidation products such as oxalic, formic and acetic acids and, less prominently, formaldehyde, acetaldehyde, propionaldehyde and glycolaldehyde. The absorbance of EfOM treated with Fenton reagent at varying Fe (II) concentration and contact time underwent a consistent decrease. The relative decrease of EfOM absorbance was strongly and unambiguously correlated with the removal of all tested PPCPs.

  16. Occurrence and distribution of pharmaceutically active and endocrine disrupting compounds in Singapore's marine environment: influence of hydrodynamics and physical-chemical properties.

    PubMed

    Bayen, Stéphane; Zhang, Hui; Desai, Malan Manish; Ooi, Seng Keat; Kelly, Barry C

    2013-11-01

    The fate and exposure risks of pharmaceutically active compounds (PhACs) and endocrine disrupting chemicals (EDCs) in marine environments are not well-understood. In this study we developed a multi-residue analytical method for quantifying concentrations of forty target compounds in seawater from Singapore. Analyses of samples (n = 24) from eight sites showed the occurrence of several compounds, including gemfibrozil (<0.09-19.8 ng/L), triclosan (<0.55-10.5 ng/L), carbamazepine (<0.28-10.9 ng/L) and ibuprofen (<2.2-9.1 ng/L). A 3D hydrodynamic model for Singapore was used to predict residence time (tR). Principal Components Analysis revealed a strong relationship between tR and contaminant concentrations. While source emissions are undoubtedly important, proximate distance to a wastewater treatment plant had little influence on concentrations. The site with the greatest tR, which exhibited the highest concentrations, is adjacent to Singapore's largest protected wetland reserve. The results highlight an important linkage between hydrodynamic behavior and contaminant exposure risks in complex coastal marine ecosystems.

  17. 77 FR 23272 - Proposed Information Collection; Comment Request: FHA Insured Title I Property Improvement and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-18

    ... URBAN DEVELOPMENT Proposed Information Collection; Comment Request: FHA Insured Title I Property... information: Title of Proposal: Title I Property Improvement and Manufactured Home Loan Programs. OMB Control Number, if applicable: 2502-0328. Description of the need for the information and proposed use: Title...

  18. Growth and wood properties of genetically improved loblolly pine: propagation type comparison and genetic parameters

    Treesearch

    Finto Antony; Laurence Schimleck; Lewis Jordan; Benjamin Hornsby; Joseph Dahlen; Richard Daniels; Alexander Clark; Luis Apiolaza; Dudley Huber

    2013-01-01

    The use of clonal varieties in forestry offers great potential to improve growth traits (quantity) and wood properties (quality) of loblolly pine (Pinus taeda L.). Loblolly pine trees established via somatic embryogenesis (clones), full-sib zygotic crosses, and half-sib zygotic open-pollinated families were sampled to identify variation in growth and wood properties...

  19. Military Base Realignments and Closures: Process for Reusing Property for Homeless Assistance Needs Improvements

    DTIC Science & Technology

    2015-03-01

    MILITARY BASE REALIGNMENTS AND CLOSURES Process for Reusing Property for Homeless Assistance Needs Improvements...information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this...COVERED 00-00-2015 to 00-00-2015 4. TITLE AND SUBTITLE Military Base Realignments and Closures: Process for Reusing Property for Homeless Assistance

  20. Method for improving the extraction properties of a tributyl phosphate solution

    DOEpatents

    Martin, Earl C.; Bruns, Lester E.

    1976-01-01

    A method for improving the extraction properties of a tributyl phosphate extractant used for reprocessing irradiated nuclear reactor fuel (Purex Process) containing degradation products of tributyl phosphate by contacting the extractant with diazomethane in a suitable solvent whereby the degradation products are esterified to triester phosphates which have extraction properties similar to those of tributyl phosphate.

  1. An Innovative Pharmaceutical Care Practical Course

    ERIC Educational Resources Information Center

    Bulatova, N. R.; Aburuz, S.; Yousef, A. M.

    2007-01-01

    The innovative practical course was developed to improve the students' ability to acquire pharmaceutical care skills. The primary components of the course were in-school training using small group discussions and hospital experience including identification, analysis, prevention and resolution of drug-therapy problems, patient counseling on their…

  2. An Innovative Pharmaceutical Care Practical Course

    ERIC Educational Resources Information Center

    Bulatova, N. R.; Aburuz, S.; Yousef, A. M.

    2007-01-01

    The innovative practical course was developed to improve the students' ability to acquire pharmaceutical care skills. The primary components of the course were in-school training using small group discussions and hospital experience including identification, analysis, prevention and resolution of drug-therapy problems, patient counseling on their…

  3. Oligonucleotide-based pharmaceuticals: Non-clinical and clinical safety signals and non-clinical testing strategies.

    PubMed

    Mustonen, Enni-Kaisa; Palomäki, Tiina; Pasanen, Markku

    2017-09-28

    Antisense oligonucleotides, short interfering RNAs (siRNAs) and aptamers are oligonucleotide-based pharmaceuticals with a promising role in targeted therapies. Currently, five oligonucleotide-based pharmaceuticals have achieved marketing authorization in Europe or USA and many more are undergoing clinical testing. However, several safety concerns have been raised in non-clinical and clinical studies. Oligonucleotides share properties with both chemical and biological pharmaceuticals and therefore they pose challenges also from the regulatory point of view. We have analyzed the safety data of oligonucleotides and evaluated the applicability of current non-clinical toxicological guidelines for assessing the safety of oligonucleotide-based pharmaceuticals. Oligonucleotide-based pharmaceuticals display a similar toxicological profile, exerting adverse effects on liver and kidney, evoking hematological alterations, as well as causing immunostimulation and prolonging the coagulation time. It is possible to extrapolate some of these effects from non-clinical studies to humans. However, evaluation strategies for genotoxicity testing of "non-natural" oligonucleotides should be revised. Additionally, the selective use of surrogates and prediction of clinical endpoints for non-clinically observed immunostimulation is complicated by its multiple potential manifestations, demanding improvements in the testing strategies. Utilizing more relevant and mechanistic-based approaches and taking better account of species differences, could possibly improve the prediction of relevant immunological/proinflammatory effects in humans. Copyright © 2017. Published by Elsevier Inc.

  4. Pharmaceutical Education in Thailand.

    ERIC Educational Resources Information Center

    Charupatanapong, Nawarut; Rascati, Karen L.

    1991-01-01

    The pharmaceutical education system in Thailand is described and compared to that of Great Britain. The program in Thailand is a five-year curriculum with a two-year prepharmacy natural sciences program. Students start internships after the fourth year. Neither country emphasizes undergraduate preclinical experience nor requires licensing…

  5. Reflections on Pharmaceutical Education.

    ERIC Educational Resources Information Center

    Smith, Robert E.

    1992-01-01

    A discussion of the implications of adopting a new example for pharmaceutical education focuses on the need to develop a new pharmacy college culture and on the faculty's role in addressing stated educational goals. Anticipated changes in staffing and faculty development and difficulties in reorganizing curricula are examined. (MSE)

  6. Free trade in pharmaceuticals.

    PubMed

    Outterson, M Kevin

    2004-09-06

    Provisions in the Australia-United States Free Trade Agreement (AUSFTA) may threaten the Australian Pharmaceutical Benefits Scheme (PBS), the "gold standard" of such programs worldwide. If Australia postpones passing of the US Free Trade Agreement Implementation Bill in the Senate, there will be opportunity for broader interests in both the United States and Australia to carefully study the agreement. The provisions of AUSFTA relating to the PBS are supposed to promote transparency, but the pharmaceutical manufacturers themselves (who are demanding transparency) do not reveal the content of their submissions to the Pharmaceutical Benefits Advisory Committee, or disclose all their financial relationships with researchers and policymakers. In AUSFTA, the "public health" language of affordable prescription drugs is missing and is replaced by language supporting "pharmaceutical innovation". Debate as to whether AUSFTA will force significant changes to the PBS, including higher drug prices, is currently under way in Australia. Perhaps the appropriate target of reforms should be the excessive US drug prices, and not the economically efficient Australian drug prices.

  7. Microbial factories for recombinant pharmaceuticals

    PubMed Central

    Ferrer-Miralles, Neus; Domingo-Espín, Joan; Corchero, José Luis; Vázquez, Esther; Villaverde, Antonio

    2009-01-01

    Most of the hosts used to produce the 151 recombinant pharmaceuticals so far approved for human use by the Food and Drug Administration (FDA) and/or by the European Medicines Agency (EMEA) are microbial cells, either bacteria or yeast. This fact indicates that despite the diverse bottlenecks and obstacles that microbial systems pose to the efficient production of functional mammalian proteins, namely lack or unconventional post-translational modifications, proteolytic instability, poor solubility and activation of cell stress responses, among others, they represent convenient and powerful tools for recombinant protein production. The entering into the market of a progressively increasing number of protein drugs produced in non-microbial systems has not impaired the development of products obtained in microbial cells, proving the robustness of the microbial set of cellular systems (so far Escherichia coli and Saccharomyces cerevisae) developed for protein drug production. We summarize here the nature, properties and applications of all those pharmaceuticals and the relevant features of the current and potential producing hosts, in a comparative way. PMID:19317892

  8. Kaolinite in pharmaceutics and biomedicine.

    PubMed

    Awad, Mahmoud E; López-Galindo, Alberto; Setti, Massimo; El-Rahmany, Mahmoud M; Iborra, César Viseras

    2017-09-22

    Kaolinite Al2Si2O5(OH)4 is an abundant and inexpensive geomaterial regarded as one of the most common clay minerals in the earth's crust and the most widespread phase among the other kaolin polymorphs (halloysite, dickite and nacrite). Structurally, it is a hydrous aluminum phyllosilicate member belonging to the dioctahedral 1:1 kaolin mineral group. The particle size of the pseudohexagonal kaolinite platelets is normally <2μm (if compared to a human red blood cell of a typical diameter 6.2-8.2μm or to a virus particle of about 50nm diameter). The kaolinite platelets, either stacked together with a common booklet-like shape in a highly ordered structure (well crystallized) or disordered structure (poorly crystallized), consist of layers considered as a strong dipole of hydrophobic siloxane surface dominated by negative charges, and the other hydrophilic aluminol surface carries positive charges. Kaolinite has been used in many pharmaceutical applications as excipient or active ingredient, because it exhibits excellent physical, chemical and surface physicochemical properties. In addition to their classical pharmaceutical uses, kaolinite and its derivatives have been recently considered as a promising material in many biomedical innovation areas such as drug, protein and gene delivery based on the high interaction capacities with organic and biochemical molecules, bioadhesion and cellular uptake. Pharmaceutical kaolin grades are considerably demanded for usage as excipient in formulations of solid and semi-solid dosage forms. The most important functionalities of kaolin used as excipient are reported as diluent, binder, disintegrant, pelletizing and granulating, amorphizing, particle film coating, emulsifying and suspending agent. Because of its uninjured bioactivity, kaolinite has been also used as active agent for treatment of some common diseases. It can be topically administered as hemostatic agent, dermatological protector, anti-inflammatory agent and in

  9. Multifaceted role of clay minerals in pharmaceuticals

    PubMed Central

    Khurana, Inderpreet Singh; Kaur, Satvinder; Kaur, Harpreet; Khurana, Rajneet Kaur

    2015-01-01

    The desirable physical and physiochemical properties of clay minerals have led them to play a substantial role in pharmaceutical formulations. Clay minerals like kaolin, smectite and palygorskite-sepiolite are among the world's most valuable industrial minerals and of considerable importance. The elemental features of clay minerals which caused them to be used in pharmaceutical formulations are high specific area, sorption capacity, favorable rheological properties, chemical inertness, swelling capacity, reactivity to acids and inconsiderable toxicity. Of course, these are highly cost effectual. This special report on clay minerals provides a bird's eye view of the chemical composition and structure of these minerals and their influence on the release properties of active medicinal agents. Endeavor has been made to rope in myriad applications depicting the wide acceptability of these clay minerals. PMID:28031881

  10. Multifaceted role of clay minerals in pharmaceuticals.

    PubMed

    Khurana, Inderpreet Singh; Kaur, Satvinder; Kaur, Harpreet; Khurana, Rajneet Kaur

    2015-11-01

    The desirable physical and physiochemical properties of clay minerals have led them to play a substantial role in pharmaceutical formulations. Clay minerals like kaolin, smectite and palygorskite-sepiolite are among the world's most valuable industrial minerals and of considerable importance. The elemental features of clay minerals which caused them to be used in pharmaceutical formulations are high specific area, sorption capacity, favorable rheological properties, chemical inertness, swelling capacity, reactivity to acids and inconsiderable toxicity. Of course, these are highly cost effectual. This special report on clay minerals provides a bird's eye view of the chemical composition and structure of these minerals and their influence on the release properties of active medicinal agents. Endeavor has been made to rope in myriad applications depicting the wide acceptability of these clay minerals.

  11. Active pharmaceutical management strategies of health insurance systems to improve cost-effective use of medicines in low- and middle-income countries: a systematic review of current evidence.

    PubMed

    Faden, Laura; Vialle-Valentin, Catherine; Ross-Degnan, Dennis; Wagner, Anita

    2011-05-01

    Health insurance systems have great potential to improve the cost-effective use of medicines by leveraging better provider prescribing, more cost-effective use by consumers, and lower prices from industry. Despite ample evidence from high-income countries, little is known about insurance system strategies targeting medicines in low- and middle-income countries (LMIC). This paper provides a critical review of the literature on these strategies and their impacts in LMIC. We conducted a systematic review of published peer-reviewed and grey literature and organized the insurance system strategies into four categories: medicines selection, purchasing, contracting and utilization management. In n=63 reviewed publications we found reasonable evidence supporting the use of insurance as an overall strategy to improve access to pharmaceuticals and outcomes in LMIC. Beyond this, most of the literature focused on provider contracting strategies to influence prescribing. There was very little evidence on medicines selection, purchasing, or utilization management strategies. There is a paucity of published evidence on the impact of insurance system strategies on improving the use of medicines in LMIC. The existing evidence is questionable since the majority of the published studies utilize weak study designs. This review highlights the need for well-designed studies to build an evidence base on the impact of medicines management strategies deployed by LMIC insurance programs. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  12. Synthesis, Radiolabeling, and Characterization of Plasma Protein-Binding Ligands: Potential Tools for Modulation of the Pharmacokinetic Properties of (Radio)Pharmaceuticals.

    PubMed

    Müller, Cristina; Farkas, Renáta; Borgna, Francesca; Schmid, Raffaella M; Benešová, Martina; Schibli, Roger

    2017-09-12

    The development of (radio)pharmaceuticals with favorable pharmacokinetic profiles is crucial for allowing the optimization of the imaging or therapeutic potential and the minimization of undesired side effects. The aim of this study was, therefore, to evaluate and compare three different plasma protein binders (PPB-01, PPB-02, and PPB-03) that are potentially useful in combination with (radio)pharmaceuticals to enhance their half-life in the blood. The entities were functionalized with a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator via a l-lysine and β-alanine linker moiety using solid-phase peptide chemistry and labeled with (177)Lu (T1/2 = 6.65 days), a clinically established radiometal. The binding capacities of these radioligands and (177)Lu-DOTA were evaluated using human plasma and solutions of human serum albumin (HSA), human α1-acid glycoprotein (α1-AGP), and human transthyretin (hTTR) by applying an ultrafiltration assay. (177)Lu-DOTA-PPB-01 and (177)Lu-DOTA-PPB-02 bound to a high and moderate extent to human plasma proteins (>90% and ∼70%, respectively), whereas the binding to hTTR was considered negligible (<10%). (177)Lu-DOTA-PPB-03 showed almost complete binding to human plasma proteins (>90%) with a high fraction bound to hTTR (∼50%). Plasma protein binding of the (177)Lu-DOTA complex, which was used as a control, was not observed (<1%). (177)Lu-DOTA-PPB-01 and (177)Lu-DOTA-PPB-02 were both displaced (>80%) from HSA by ibuprofen, specific for Sudlow's binding site II and coherent with the aromatic structures, and >80% by their respective binding entities. (177)Lu-DOTA-PPB-03 was displaced from hTTR by the site-marker l-thyroxine (>60%) and by its binding entity PPB-03* (>80%). All three radioligands were investigated with regard to the in vivo blood clearance in normal mice. (177)Lu-DOTA-PPB-01 showed the slowest blood clearance (T1/2,β: >15 h) followed by (177)Lu-DOTA-PPB-03 (T1/2,β: ∼2.33 h) and (177)Lu

  13. Electrostatics of Pharmaceutical Aerosols for Pulmonary Delivery.

    PubMed

    Lip Kwok, Philip Chi

    2015-01-01

    This paper provides a review on key research findings in the rapidly developing area of pharmaceutical aerosol electrostatics. Solids and liquids can become charged without electric fields, the former by contact or friction and the latter by flowing or spraying. Therefore, charged particles and droplets carrying net charges are produced from pharmaceutical inhalers (e.g. dry powder inhalers, metered dose inhalers, and nebulisers) due to the mechanical processes involved in aerosolisation. The charging depends on many physicochemical factors, such as formulation composition, solid state properties, inhaler material and design, and relative humidity. In silico, in vitro, and limited in vivo studies have shown that electrostatic charges may potentially influence particle deposition in the airways. However, the evidence is not yet conclusive. Furthermore, there are currently no regulatory requirements on the characterisation and control of the electrostatic properties of inhaled formulations. Besides the need for further investigations on the relationship between physicochemical factors and charging characteristics of the aerosols, controlled and detailed in vivo studies are also required to confirm whether charges can affect particle deposition in the airways. Since pharmaceutical aerosol electrostatics is a relatively new research area, much remains to be explored. Thus there is certainly potential for development. New findings in the future may contribute to the advancement of pharmaceutical aerosol formulations and respiratory drug delivery.

  14. Improving the mechanical properties of chitosan-based heart valve scaffolds using chitosan fibers.

    PubMed

    Albanna, Mohammad Z; Bou-Akl, Therese H; Walters, Henry L; Matthew, Howard W T

    2012-01-01

    Chitosan is being widely studied for tissue engineering applications due to its biocompatibility and biodegradability. However, its use in load-bearing applications is limited due to low mechanical properties. In this study, we investigated the effectiveness of a chitosan fiber reinforcement approach to enhancing the mechanical properties of chitosan scaffolds. Chitosan fibers were fabricated using a solution extrusion and neutralization method and incorporated into porous chitosan scaffolds. The effects of fiber/scaffold mass ratio, fiber mechanical properties and fiber length on scaffold mechanical properties were studied. The results showed that incorporating fibers improved scaffold strength and stiffness in proportion to the fiber/scaffold mass ratio. A fiber-reinforced, heart valve scaffold achieved leaflet tensile strength values of 220±17 kPa, comparable to the radial values of human pulmonary valve leaflets. Additionally, the effects of 2 mm fibers were found to be up to threefold greater than 10 mm fibers at identical mass ratios. Heparin crosslinking of fibers produced a reduction in fiber strength, and thus failed to produce additional improvements to fiber-reinforced scaffold properties. Despite this reduction in fiber strength, heparin-modified fibers still improved the mechanical properties of reinforced scaffolds, but to a lesser extent than unmodified fibers. The results demonstrate that chitosan fiber reinforcement can be used to achieve porous chitosan scaffold strength approaching that of tissue, and that fiber length and mechanical properties are important parameters in defining the degree of mechanical improvement.

  15. Between confidentiality and scientific exchange: the place of publication in drug discovery and pharmaceutical research.

    PubMed

    Clozel, Martine

    2011-01-26

    To continue to improve life expectancy and quality of life, the discovery of innovative therapies should be among the prime goals of the life sciences. The large majority of the drugs that are discovered and successfully developed to the point of being used by patients come from the drug industry, but publications from this sector are rare among life sciences research publications. Publications in the field of pharmaceutical drug discovery should take into account the confidentiality inherent to the protection of the intellectual property rights of a discovery, but they are fundamentally important because they can enhance scientific knowledge, improve the care and safety of patients, provide information for prescribers, and educate the public about the pharmaceutical industry.

  16. Pharmaceutical care education in Kuwait: pharmacy students’ perspectives

    PubMed Central

    Katoue, Maram G.; Awad, Abdelmoneim I.; Schwinghammer, Terry L.; Kombian, Samuel B.

    2014-01-01

    Background Pharmaceutical care is defined as the responsible provision of medication therapy to achieve definite outcomes that improve patients’ quality of life. Pharmacy education should equip students with the knowledge, skills, and attitudes they need to practise pharmaceutical care competently. Objective To investigate pharmacy students’ attitudes towards pharmaceutical care, perceptions of their preparedness to perform pharmaceutical care competencies, opinions about the importance of the various pharmaceutical care activities, and the barriers to its implementation in Kuwait. Methods A descriptive, cross-sectional survey of pharmacy students (n=126) was conducted at Faculty of Pharmacy, Kuwait University. Data were collected via a pre-tested self-administered questionnaire. Descriptive statistics including percentages, medians and means Likert scale rating (SD) were calculated and compared using SPSS, version 19. Statistical significance was accepted at a p value of 0.05 or lower. Results The response rate was 99.2%. Pharmacy students expressed overall positive attitudes towards pharmaceutical care. They felt prepared to implement the various aspects of pharmaceutical care, with the least preparedness in the administrative/management aspects. Perceived pharmaceutical care competencies grew as students progressed through the curriculum. The students also appreciated the importance of the various pharmaceutical care competencies. They agreed/strongly agreed that the major barriers to the integration of pharmaceutical care into practice were lack of private counseling areas or inappropriate pharmacy layout (95.2%), lack of pharmacist time (83.3%), organizational obstacles (82.6%), and pharmacists’ physical separation from patient care areas (82.6%). Conclusion Pharmacy students’ attitudes and perceived preparedness can serve as needs assessment tools to guide curricular change and improvement. Student pharmacists at Kuwait University understand and

  17. Two-phase chromium-niobium alloys exhibiting improved mechanical properties at high temperatures

    DOEpatents

    Liu, Chain T.; Takeyama, Masao

    1994-01-01

    The specification discloses chromium-niobium alloys which exhibit improved mechanical properties at high temperatures in the range of 1250.degree. C. and improved room temperature ductility. The alloys contain a Cr.sub.2 Nb-rich intermetallic phase and a Cr-rich phase with an overall niobium concentration in the range of from about 5 to about 18 at. %. The high temperature strength is substantially greater than that of state of the art nickel-based superalloys for enhanced high temperature service. Further improvements in the properties of the compositions are obtained by alloying with rhenium and aluminum; and additional rare-earth and other elements.

  18. Two-phase chromium-niobium alloys exhibiting improved mechanical properties at high temperatures

    DOEpatents

    Liu, C.T.; Takeyama, Masao.

    1994-02-01

    The specification discloses chromium-niobium alloys which exhibit improved mechanical properties at high temperatures in the range of 1250 C and improved room temperature ductility. The alloys contain a Cr[sub 2]Nb-rich intermetallic phase and a Cr-rich phase with an overall niobium concentration in the range of from about 5 to about 18 at. %. The high temperature strength is substantially greater than that of state of the art nickel-based superalloys for enhanced high temperature service. Further improvements in the properties of the compositions are obtained by alloying with rhenium and aluminum; and additional rare-earth and other elements. 14 figures.

  19. Artificial neural networks: theoretical background and pharmaceutical applications: a review.

    PubMed

    Wesolowski, Marek; Suchacz, Bogdan

    2012-01-01

    In recent times, there has been a growing interest in artificial neural networks, which are a rough simulation of the information processing ability of the human brain, as modern and vastly sophisticated computational techniques. This interest has also been reflected in the pharmaceutical sciences. This paper presents a review of articles on the subject of the application of neural networks as effective tools assisting the solution of various problems in science and the pharmaceutical industry, especially those characterized by multivariate and nonlinear dependencies. After a short description of theoretical background and practical basics concerning the computations performed by means of neural networks, the most important pharmaceutical applications of neural networks, with suitable references, are demonstrated. The huge role played by neural networks in pharmaceutical analysis, pharmaceutical technology, and searching for the relationships between the chemical structure and the properties of newly synthesized compounds as candidates for drugs is discussed.

  20. SLIDE PRESENTATION--PHARMACEUTICALS AS ...

    EPA Pesticide Factsheets

    While pharmaceuticals are ubiquitous trace contaminants in the environment, thetypes, concentrations, and relative abundances of individual residues will vary depending on thegeographic locale and time of year, primarily a reflection of differing and varying prescribing andconsumption practices. The research focused on in the subtasks is the development and application of state-of the-art technologies to meet the needs of the public, Office of Water, and ORD in the area of Water Quality. Located In the subtasks are the various research projects being performed in support of this Task and more in-depth coverage of each project. Briefly, each project's objective is stated below.Subtask 1: To integrate state-of-the-art technologies (polar organic chemical integrative samplers, advanced solid-phase extraction methodologies with liquid chromatography/electrospray/mass spectrometry) and apply them to studying the sources and fate of a select list of PPCPs. Application and improvement of analytical methodologies that can detect non-volatile, polar, water-soluble pharmaceuticals in source waters at levels that could be environmentally significant (at concentrations less than parts per billion, ppb). IAG with USGS ends in FY05. APM 20 due in FY05.Subtask 2: Coordination of interagency research and public outreach activities for PPCPs. Participate on NSTC Health and Environment subcommittee working group on PPCPs. Web site maintenance and expansion, invited technical

  1. ABSTRACT PRESENTATION--PHARMACEUTICALS AS ...

    EPA Pesticide Factsheets

    Pharmaceuticals comprise a large and diverse array of contaminants that can occur in the environmentfrom the combined activities and actions of multitudes of individuals as well as from veterinary andagricultural use. The research focused on in the subtasks is the development and application of state-of the-art technologies to meet the needs of the public, Office of Water, and ORD in the area of Water Quality. Located In the subtasks are the various research projects being performed in support of this Task and more in-depth coverage of each project. Briefly, each project's objective is stated below.Subtask 1: To integrate state-of-the-art technologies (polar organic chemical integrative samplers, advanced solid-phase extraction methodologies with liquid chromatography/electrospray/mass spectrometry) and apply them to studying the sources and fate of a select list of PPCPs. Application and improvement of analytical methodologies that can detect non-volatile, polar, water-soluble pharmaceuticals in source waters at levels that could be environmentally significant (at concentrations less than parts per billion, ppb). IAG with USGS ends in FY05. APM 20 due in FY05.Subtask 2: Coordination of interagency research and public outreach activities for PPCPs. Participate on NSTC Health and Environment subcommittee working group on PPCPs. Web site maintenance and expansion, invited technical presentations, invited articles for peer-reviewed journals, interviews for med

  2. PHARMACEUTICALS IN THE ENVIRONMENT: SOURCES ...

    EPA Pesticide Factsheets

    An issue that began to receive more attention by environmental scientists in the late 1990s was the conveyancy of pharmaceuticals in the environment by way of their use in human and veterinary medical practices and personal care The research focused on in the subtasks is the development and application of state-of the-art technologies to meet the needs of the public, Office of Water, and ORD in the area of Water Quality. Located In the subtasks are the various research projects being performed in support of this Task and more in-depth coverage of each project. Briefly, each project's objective is stated below.Subtask 1: To integrate state-of-the-art technologies (polar organic chemical integrative samplers, advanced solid-phase extraction methodologies with liquid chromatography/electrospray/mass spectrometry) and apply them to studying the sources and fate of a select list of PPCPs. Application and improvement of analytical methodologies that can detect non-volatile, polar, water-soluble pharmaceuticals in source waters at levels that could be environmentally significant (at concentrations less than parts per billion, ppb). IAG with USGS ends in FY05. APM 20 due in FY05.Subtask 2: Coordination of interagency research and public outreach activities for PPCPs. Participate on NSTC Health and Environment subcommittee working group on PPCPs. Web site maintenance and expansion, invited technical presentations, invited articles for peer-reviewed journals, intervi

  3. EU pharmaceutical expenditure forecast

    PubMed Central

    Urbinati, Duccio; Rémuzat, Cécile; Kornfeld, Åsa; Vataire, Anne-Lise; Cetinsoy, Laurent; Aballéa, Samuel; Mzoughi, Olfa; Toumi, Mondher

    2014-01-01

    Background and Objectives With constant incentives for healthcare payers to contain their pharmaceutical budgets, forecasting has become critically important. Some countries have, for instance, developed pharmaceutical horizon scanning units. The objective of this project was to build a model to assess the net effect of the entrance of new patented medicinal products versus medicinal products going off-patent, with a defined forecast horizon, on selected European Union (EU) Member States’ pharmaceutical budgets. This model took into account population ageing, as well as current and future country-specific pricing, reimbursement, and market access policies (the project was performed for the European Commission; see http://ec.europa.eu/health/healthcare/key_documents/index_en.htm). Method In order to have a representative heterogeneity of EU Member States, the following countries were selected for the analysis: France, Germany, Greece, Hungary, Poland, Portugal, and the United Kingdom. A forecasting period of 5 years (2012–2016) was chosen to assess the net pharmaceutical budget impact. A model for generics and biosimilars was developed for each country. The model estimated a separate and combined effect of the direct and indirect impacts of the patent cliff. A second model, estimating the sales development and the risk of development failure, was developed for new drugs. New drugs were reviewed individually to assess their clinical potential and translate it into commercial potential. The forecast was carried out according to three perspectives (healthcare public payer, society, and manufacturer), and several types of distribution chains (retail, hospital, and combined retail and hospital). Probabilistic and deterministic sensitivity analyses were carried out. Results According to the model, all countries experienced drug budget reductions except Poland (+€41 million). Savings were expected to be the highest in the United Kingdom (−€9,367 million), France

  4. The pharmaceutical care in asthma - Polish and global perspective.

    PubMed

    Swieczkowski, Damian; Poniatowski, Patryk; Merks, Piotr; Jaguszewski, Milosz

    2016-01-01

    The pharmaceutical care is a pharmacist's contribution to the care of individual patients and leads to optimize the use of drugs. The pharmaceutical care may improve adherence, clinical effectiveness of providing therapy and improve the health-related quality of life. The conducted literature review confirmed that pharmaceutical care and advanced pharmaceutical services are clinical effective in asthma. The implementation of pharmaceutical care under Polish conditions is currently insufficient and remains challenging for the future. Herein we should admit, that the polish government has recently put an effort to appoint specially dedicated team establishing a program of reimbursed pharmaceutical care. This move should be considered as a new phase for amendments community pharmacy in Poland. The experience of different health care systems, including for instance United Kingdom, Australia or Canada, might be used in the process of changing Polish perspective. Herein, we have reviewed the literature and highlighted the services creating the program of pharmaceutical care in asthma. This unique work describes the complex nature of optimal pharmaceutical services emphasizing the strong necessity of multidimensional approach in this field.

  5. Pharmaceutical risk-sharing agreements.

    PubMed

    Cook, Joseph P; Vernon, John A; Manning, Richard

    2008-01-01

    Increased spending on pharmaceuticals continues to foster debate over healthcare policy. The increasing costs of bringing products to the market, as well as increased utilization of pharmaceuticals contribute to increased pharmaceutical expenditure; however, appropriate pharmaceutical use can, in certain cases, reduce overall healthcare costs. Nevertheless, the perception of high drug prices still puts pressure on pharmaceutical companies to build confidence in the proposition that their products are worth the additional expense. One potential approach to building this confidence, and maintaining investment incentives, is for the pharmaceutical company to share the risk of a situation in which there is uncertainty about whether the product is effective for the consumer and payer. Such risk-sharing arrangements for pharmaceuticals, like warranties, can be used to signal high quality when product quality is not fully observable. While there may be difficulties in devising such schemes for every product, such risk-sharing plans may become a staple feature of the market in the future.

  6. Improvements of physical, mechanical and biodegradation properties of polybutadiene rubber insulators by chitosan and silica nanoparticles.

    PubMed

    Saboktakin, Amin; Saboktakin, Mohammadreza

    2016-10-01

    1,4-cis-Polybutadiene rubber(1,4-cis pBR) as an insulation material is developing that will provide superior thermal insulation properties, flexibility, toughness by natural polymers such as chitosan(CS) and silica nanoparticles. This material is widely used in the insulation industries specially architecture. This research concerns physical, mechanical properties and also biodegradation of 1,4-cis pBR, which to be composed with the natural polymers such as CS. Silica nanoparticles were used as filler to improve the physical and mechanical properties of 1,4-cis pBR. To evaluating its physical and mechanical properties, stretching and bending and impact tests were used and the results show some improvement in these properties. Our observations show that temperature plays an important role as main factor in order to improve the mechanical properties of nanocomposites. Similar improvements in tensile modulus and strength have been observed for 1,4-cis pBR/CS-silica nanoparticles. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Thermoplastic impact property improvement in hybrid natural fibre epoxy composite bumper beam

    NASA Astrophysics Data System (ADS)

    Davoodi, M. M.; Sapuan, S. M.; Ali, Aidy; Ahmad, D.; Khalina, A.

    2010-05-01

    Utilization of thermoset resin as a bumper beam composite matrix is currently more dominated in car manufacturer suppliers, because of availability, easy processing, low material cost and production equipment investment. Moreover, low viscosity, shrinkage and excellent flow facilitate better fibre impregnation and proper surface resin wetting. Three-dimensional cross linking curing increase impact, creep and environmental stress cracking resistance properties. Low impact properties of natural fibre epoxy composite, are main issues in its employment for automotive structural components. Impact properties in epoxy composite bumper beam could be increased by modifying the resin, reinforcement and manufacturing process as well as geometry parameters such as cross section, thickness, added ribs and fixing method optimizations could strengthen impact resistance. There are two main methods, flexibilisation and toughening, as modifying the resin in order to improve the impact properties of epoxy composite, which form single phase or two-phase morphology to make modifier as epoxy or from separate phase to keep the thermo-mechanical properties. Liquid rubber, thermoplastic, core shell particle and rigid particle are different methods of toughening improvements. In this research, thermoplastic toughening has used to improve impact properties in hybrid natural fibre epoxy composite for automotive bumper beam and has achieved reasonable impact improvements.

  8. Electrostatics in pharmaceutical aerosols for inhalation.

    PubMed

    Wong, Jennifer; Chan, Hak-Kim; Kwok, Philip Chi Lip

    2013-08-01

    Electrostatics continues to play an important role in pharmaceutical aerosols for inhalation. Despite its ubiquitous nature, the charging process is complex and not well understood. Nonetheless, significant advances in the past few years continue to improve understanding and lead to better control of electrostatics. The purpose of this critical review is to present an overview of the literature, with an emphasis on how electrostatic charge can be useful in improving pulmonary drug delivery.

  9. Gray marketing of pharmaceuticals.

    PubMed

    Chaudhry, P E; Walsh, M G

    1995-01-01

    Pharmaceutical marketers in the European Union are constrained by regulated prices, opening up opportunities for gray marketers. The authors investigate the legal framework that regulates gray markets by summarizing and analyzing relevant European Court of Justice decisions that favor gray marketers and actually foster parallel trade. Before marketing managers can develop effective strategies in this marketplace, they must first understand the precedents of the legal system in which they will be operating.

  10. Wastage of pharmaceuticals.

    PubMed

    Hart, R J; Marshall, F S

    1976-12-04

    Wastage of pharmaceuticals was studied for three months at a 520-bed hospital in Suffolk. Drugs worth 1104 pounds were brought to the pharmacy for destruction. Only 40 pounds worth could be put back into stock. It is suggested that the use of blister-packing together with conservative prescribing, supply, and suitable storage of medicines could lead to important savings of drugs discarded each year in English hospitals, which from this study were estimated to cost in excess of 1 million pounds.

  11. [Questions about pharmaceutical expertise].

    PubMed

    Sauer, Fernand

    2012-01-01

    Over the last thirty years, many areas of expertise have developed in the pharmaceutical industry, from research and production to delivery to the patient. Strict European regulations and international best practice guidelines have shaped the expertise of pharmaceutical firms. Governments have set up health agencies to strengthen the supervision of private operators by recruiting in-house scientific experts and expert committees. The private and public sectors compete to recruit the best experts, and conflicts of interest must be addressed. The recent 'Mediator' (Benfluorex) case in France raises many questions about the potential failures of the health security system. Beyond the primary responsibility of the company, the main concern is off-label use. An effort to strengthen the legal framework and the tools used to collect, analyze and publicize pharmacovigilance data is currently underway at a national and European level. The competent authorities must restore public confidence through a more diligent and transparent handling of sensitive issues related to high-risk medicine. In a country where drug consumption is particularly high, doctors and pharmaceutical experts have been accused of becoming accustomed to risk and of loosing sight of the benefit to the patient. Health professionals in the private and public sectors must regain the appropriate health security reflexes to promote a more rational use of drugs.

  12. Pharmaceutical cocrystals: a novel approach for oral bioavailability enhancement of drugs.

    PubMed

    Chadha, Renu; Saini, Anupam; Arora, Poonam; Bhandari, Swati

    2012-01-01

    Solid dosage forms are by far the preferred drug delivery systems. However, these often face the problem of poor and erratic bioavailability during the drug development process. Numerous formulation strategies for drug delivery are currently under development, among which the solid forms such as polymorphs, solvates, salts, and cocrystals have been considered to be the most important for improving dissolution rate and bioavailability. Cocrystallization is a fairly new approach in pharmaceutical industry that can improve the solubility and, consequently, the bioactivity of the active pharmaceutical ingredient (API) without compromising its structural integrity. Pharmaceutical cocrystals have found their place in drug delivery, primarily due to their ability to produce alternative, viable solid forms when a more standard approach of salt and polymorph formation fails to deliver the desired objectives. Over the past few years, a number of papers have been published focusing on a broad range of subjects, from traditional crystal engineering to structure-property relationships of cocrystals. The present review, however, illustrates how the cocrystalline forms of APIs have improved their in vitro dissolution rate and in vivo bioavailability, often correlating well with their improved solubility as well.

  13. Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation.

    PubMed

    Patil, Hemlata; Tiwari, Roshan V; Repka, Michael A

    2016-02-01

    Hot-melt extrusion (HME) is a promising technology for the production of new chemical entities in the developmental pipeline and for improving products already on the market. In drug discovery and development, industry estimates that more than 50% of active pharmaceutical ingredients currently used belong to the biopharmaceutical classification system II (BCS class II), which are characterized as poorly water-soluble compounds and result in formulations with low bioavailability. Therefore, there is a critical need for the pharmaceutical industry to develop formulations that will enhance the solubility and ultimately the bioavailability of these compounds. HME technology also offers an opportunity to earn intellectual property, which is evident from an increasing number of patents and publications that have included it as a novel pharmaceutical formulation technology over the past decades. This review had a threefold objective. First, it sought to provide an overview of HME principles and present detailed engineered extrusion equipment designs. Second, it included a number of published reports on the application of HME techniques that covered the fields of solid dispersions, microencapsulation, taste masking, targeted drug delivery systems, sustained release, films, nanotechnology, floating drug delivery systems, implants, and continuous manufacturing using the wet granulation process. Lastly, this review discussed the importance of using the quality by design approach in drug development, evaluated the process analytical technology used in pharmaceutical HME monitoring and control, discussed techniques used in HME, and emphasized the potential for monitoring and controlling hot-melt technology.

  14. Improving the Dielectric Properties of Ethylene-Glycol Alkanethiol Self-Assembled Monolayers

    PubMed Central

    2014-01-01

    Self-assembled monolayers (SAMs) can be formed at the interface between solids and fluids, and are often used to modify the surface properties of the solid. One of the most widely employed SAM systems is exploiting thiol-gold chemistry, which, together with alkane-chain-based molecules, provides a reliable way of SAM formation to modify the surface properties of electrodes. Oligo ethylene-glycol (OEG) terminated alkanethiol monolayers have shown excellent antifouling properties and have been used extensively for the coating of biosensor electrodes to minimize nonspecific binding. Here, we report the investigation of the dielectric properties of COOH-capped OEG monolayers and demonstrate a strategy to improve the dielectric properties significantly by mixing the OEG SAM with small concentrations of 11-mercaptoundecanol (MUD). The monolayer properties and composition were characterized by means of impedance spectroscopy, water contact angle, ellipsometry and X-ray photoelectron spectroscopy. An equivalent circuit model is proposed to interpret the EIS data and to determine the conductivity of the monolayer. We find that for increasing MUD concentrations up to about 5% the resistivity of the SAM steadily increases, which together with a considerable decrease of the phase of the impedance, demonstrates significantly improved dielectric properties of the monolayer. Such monolayers will find widespread use in applications which depend critically on good dielectric properties such as capacitive biosensor. PMID:24447311

  15. Pharmaceutical care: the PCNE definition 2013.

    PubMed

    Allemann, Samuel S; van Mil, J W Foppe; Botermann, Lea; Berger, Karin; Griese, Nina; Hersberger, Kurt E

    2014-06-01

    Twenty-three years after Hepler and Strand published their well-known definition of Pharmaceutical Care (PhC), confusion remains about what the term includes and how to differentiate it from other terms. The board of the Pharmaceutical Care Network Europe (PCNE) felt the need to redefine PhC and to answer the question: "What is Pharmaceutical Care in 2013". The aims of this paper were to review existing definitions of PhC and to describe the process of developing a redefined definition. A literature search was conducted in the MEDLINE database (1964-January 2013). Keywords included "Pharmaceutical Care", "Medication (Therapy) Management", "Medicine Management", and "Pharmacist Care" in the title or abstract together with the term "defin*". To ease comparison between definitions, we developed a standardised syntax to paraphrase the definitions. During a dedicated meeting, a moderated discussion about the definition of PhC was organised. The initial literature search produced 186 hits, with eight unique PhC definitions. Hand searching identified a further 11 unique definitions. These 19 definitions were paraphrased using the standardised syntax (provider, recipient, subject, outcome, activities). Fourteen members of PCNE and 10 additional experts attended the moderated discussion. Working groups of increasing size developed intermediate definitions, which had similarities and differences to those retrieved in the literature search. At the end of the session, participants reached a consensus on a "PCNE definition of Pharmaceutical Care" reading: "Pharmaceutical Care is the pharmacist's contribution to the care of individuals in order to optimize medicines use and improve health outcomes". It was possible to paraphrase definitions of PhC using a standardised syntax focusing on the provider, recipient, subject, outcomes, and activities included in PhC practice. During a one-day workshop, experts in PhC research agreed on a definition, intended to be applicable for the

  16. An Improved Technique for dry Soil Moisture Release Curves to Determine Soil Mineralogical and Physical Properties

    NASA Astrophysics Data System (ADS)

    Campbell, G. S.; Campbell, C. S.; Cobos, D. R.

    2008-12-01

    Soil moisture release curves (MRC) or moisture sorption isotherms, which relate the amount of water in soil to its water potential or water activity, have many applications in soil physics and geotechnical engineering including determining soil water flow, specific surface area, swelling potential, and clay mineralogy and activity. Although research showing MRC for various soils dates back more than 50 years, limitations with the measurement technique have made developing MRC time consuming and inaccurate, especially in dry soils. Recently, an instrument was developed to create moisture sorption isotherms for various food and pharmaceutical products. The objective of this research was to investigate its use in soils for obtaining MRC in dry soils simply and accurately. Several different soil types were tested in the instrument from pure sand to bentonite and smectite clays. From the MRC of these soils, we were able to develop good correlations between actual and derived clay activity, surface area, and swelling potential. In addition, we were able to see hysteresis in dry soil water uptake for all soils, including sand. According to our tests, this new instrument will provide a powerful tool to investigate several soil physical properties simply and accurately.

  17. Wheat Gluten Blends with Maleic Anhydride-Functionalized Polyacrylate Cross-Linkers for Improved Properties.

    PubMed

    Diao, Cheng; Xia, Hongwei; Parnas, Richard S

    2015-10-14

    A family of polyacrylate-based cross-linkers was synthesized to maximize the toughness of high Tg, high modulus wheat gluten blends in the glassy state. Mechanical testing and damping measurements were conducted to provide an example where the work of fracture and strength of the blend substantially exceeds polystyrene while maintaining flexure stiffness in excess of 3 GPa. The new rubbery cross-linkers, polymethyl acrylate-co-maleic anhydride and polyethyl acrylate-co-maleic anhydride, improve WG mechanical properties and reduce water absorption simultaneously. MDSC, FTIR, HPLC, and NMR data confirmed the cross-linking reaction with wheat gluten. Flexural, DMA, and water absorption testing were carried out to characterize the property improvements. DMA was conducted to investigate the relationship between energy damping and mechanical property improvement. If the cross-linker damping temperature is close to the testing temperature, the entire sample exhibits high damping, toughness, and strength.

  18. Annealing-induced property improvements in 2-14-1 powders produced by inert gas atomization

    SciTech Connect

    Lewis, L.H.; Sellers, C.H.; Panchanathan, V.

    1996-04-01

    The effects of vacuum annealing on the phase constitution and magnetic properties of various size fractions of 3 alloy compositions produced by Inert-gas atomization (IGA) are examined. Annealing results in the oxidation of properitectic {alpha}-Fe formed during cooling of the melt, producing considerable improvement in the hard magnetic properties of the powders largely via the removal of lower-anisotropy magnetic reversal regions.

  19. Improved Conservation Properties for Particle-in-cell Simulations with Kinetic Electrons

    SciTech Connect

    J.L.V. Lewandowski

    2003-06-19

    It is shown that a simple algorithm which exactly segregates between adiabatic and non-adiabatic electrons in particle-in-cell simulations of drift modes yields excellent conservation properties (e.g. particle number, energy) compared to the conventional df scheme. The removal of the free streaming term in the evolution of the marker weight is shown to be responsible for the improved linear and nonlinear properties of the simulated plasma.

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

    PubMed

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

    2016-08-01

    In this study, terahertz time-domain spectroscopic (THz-TDS) technique has been used to ascertain the change in the optical properties, as a function of changing porosity and mass fraction of active pharmaceutical ingredient (API), of training sets of pharmaceutical tablets. Four training sets of pharmaceutical tablets were compressed with microcrystalline cellulose (MCC) excipient and indomethacin API by varying either the porosity, height, and API mass fraction or all three tablet parameters. It was observed, as far as we know, for the first time, that the THz time-domain and frequency-domain effective refractive index, as well as, the frequency-domain effective absorption coefficient both show linear correlations with the porosity and API mass fraction for training sets of real pharmaceutical tablets. We suggest that, the observed linear correlations can be useful in basic research and quality inspection of pharmaceutical tablets. Additionally, we propose a novel optical strain parameter, based on THz measurement, which yields information on the conventional strain parameter of a tablet as well as on the change of fill fraction of solid material during compression of porous pharmaceutical tablets. We suggest that the THz measurement and proposed method of data analysis, in addition to providing an efficient tool for basic research of porous media, can serve as one of the novel quality by design (QbD) implementation techniques to predict critical quality attributes (CQA) such as porosity, API mass fraction and strain of flat-faced pharmaceutical tablets before production. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. In vitro bone exposure to strontium improves bone material level properties.

    PubMed

    Cattani-Lorente, Maria; Rizzoli, René; Ammann, Patrick

    2013-06-01

    In rats treated with strontium ranelate, the ultimate load of intact bone is increased and associated with changes in microstructure and material level properties. Evaluation by micro-computed-tomography-based finite element analysis has shown that these changes independently contribute to the improvement of bone strength induced by strontium ranelate treatment. However, the mechanism by which Sr ion acts on bone material level properties remains unknown. The vertebrae of intact female rats were exposed overnight to 0.5, 1 or 2M chloride salt solutions of Sr, Ca and Ba. The latter two were used to assess the specificity of Sr. Bone material level properties were evaluated by measuring hardness, elastic modulus and working energy in a nanoindentation test. Wavelength dispersive X-ray spectroscopy provided semi-quantitative elemental analysis and mapping. Incubation with Sr rendered bone stiffer, harder and tougher. Among the divalent ions tested, Sr had the greatest effect. Sr affinity was also assessed on in vivo treated bone specimens. After in vitro exposure, the highest improvements were observed in ovariectomized rats. However, anti-osteoporotic treatments did not influence the capacity of Sr to modify bone material level properties. Our findings demonstrated that in vitro incubation with Sr selectively improved bone material level properties, which may contribute to the macroscopic increase of bone properties observed under Sr therapy.

  2. Improved gas sensing and dielectric properties of Fe doped hydroxyapatite thick films: Effect of molar concentrations

    SciTech Connect

    Mene, Ravindra U.; Mahabole, Megha P.; Mohite, K.C.; Khairnar, Rajendra S.

    2014-02-01

    Highlights: • We report improved gas sensing and dielectric characteristics of Fe ion exchanged HAp films. • Fe doped HAp film shows maximum gas response at relatively lower temperature. • Response and gas uptake capacity of sensors is improved for appropriate amount of Fe ions in HAp matrix. • Fe-HAp films exhibit remarkable improvement in dielectric properties compared to pure HAp. • Fe doped HAp films show significant improvement in gas sensing as well as in dielectric properties. - Abstract: In the present work Fe doped hydroxyapatite (Fe-HAp) thick films has been successfully utilized to improve the gas sensing as well as its dielectric properties. Initially, HAp nano powder is synthesized by chemical precipitation process and later on Fe ions are doped in HAp by ion exchange process. Structural and morphological modifications are observed by means of X-ray diffraction and scanning electron microscopy analysis. The sensing parameters such as operating temperature, response/recovery time and gas uptake capacity are experimentally determined. The Fe-HAp (0.05 M) film shows improved CO and CO{sub 2} gas sensing capacity at lower operating temperature compared to pure HAp. Moreover, variation of dielectric constant and dielectric loss for pure and Fe-HAp thick films are studied as a function of frequency in the range of 10 Hz–1 MHz. The study reveals that Fe doped HAp thick films improve the sensing and dielectric characteristics as compared to pure HAp.

  3. [Study thought of pharmaceutical preparations quality standards by dynamic quality control technology].

    PubMed

    Yu, Dan-Hong; Mao, Chen-Mei; Lv, Cheng-Zhe; Jin, Hui-Zhen; Yao, Xin; Jia, Xiao-Bin

    2014-07-01

    Pharmaceutical preparations, particularly as a "secret recipe" of traditional Chinese medicine in medical institutions, are the product of China's medical and health industry, and they are also an important means of competing of different medical institutions. Although pharmaceutical preparations have advantages and characteristics than institutes for drug and pharmaceutical companies, the quality standards of pharmaceutical preparations in medical institutions has not reached the desired level over the years. As we all know, the quality of pharmaceutical preparations is important to ensure the efficacy, especially under the environment of people pay more sttention on drug safety and effectiveness and contry increase emphasis on the stste of pharmaceutical preparations. In view of this, we will improve the grade, stability, and clinical efficacy of pharmaceutical preparations by the advanced equipment, testing instruments and the process dynamic quality control technology. Finally, we hope we can provide new ideas for the quality control of pharmaceutical preparations.

  4. Methods of improving mechanical and biomedical properties of Ca-Si-based ceramics and scaffolds.

    PubMed

    Wu, Chengtie

    2009-05-01

    CaSiO3 ceramics and porous scaffolds are regarded as potential materials for bone tissue regeneration owing to their excellent bioactivity. However, their low mechanical strength and high dissolution limit their further biomedical application. In this report, we introduce three methods to improve the mechanical and biomedical properties of CaSiO3 ceramics and scaffolds. Positive ions and polymer modification are two promising ways to improve the mechanical and biomedical properties of CaSiO3 ceramics and scaffolds for bone tissue regeneration.

  5. Dodecylamine functionalization of carbon nanotubes to improve dispersion, thermal and mechanical properties of polyethylene based nanocomposites

    NASA Astrophysics Data System (ADS)

    Ferreira, F. V.; Franceschi, W.; Menezes, B. R. C.; Brito, F. S.; Lozano, K.; Coutinho, A. R.; Cividanes, L. S.; Thim, G. P.

    2017-07-01

    This study presents the effect of dodecylamine (DDA) functionalization of carbon nanotubes (CNTs) on the thermo-physical and mechanical properties of high-density polyethylene (HDPE) based composites. Here, we showed that the functionalization with DDA improved the dispersion of the CNTs as well as the interfacial adhesion with the HDPE matrix via non-covalent interactions. The better dispersion and interaction of CNT in the HDPE matrix as a function of the surface chemistry was correlated with the improved thermo-physical and mechanical properties.

  6. Recommendations on the environmental risk assessment of pharmaceuticals: Effect characterization.

    PubMed

    Schmitt, Heike; Boucard, Tatiana; Garric, Jeanne; Jensen, John; Parrott, Joanne; Péry, Alexandre; Römbke, Jörg; Straub, Jürg Oliver; Hutchinson, Thomas H; Sánchez-Argüello, Paloma; Wennmalm, Ake; Duis, Karen

    2010-07-01

    The effects testing of pharmaceuticals consists of a tiered investigation of ecotoxicological endpoints. However, effects testing has to be performed only when the predicted environmental concentrations (PECs) of pharmaceuticals are above certain action limits. To study the appropriateness of these action limits, a literature search was performed for pharmaceuticals with predicted no-effect concentrations (PNECs) close to or below the action limits. Some human pharmaceuticals showed effects at concentrations ≤100 ng/L, mostly in nonstandard fish or invertebrate tests. In addition, antibiotics and parasiticides sometimes had effects at concentrations <10  mg/kg soil. To help in identifying pharmaceuticals that should undergo effects testing although their PECs are below the action limits, "however clauses" are postulated for pharmaceuticals that are potentially persistent, bioaccumulative, carcinogenic, mutagenic, or reproductively toxic. Effects testing should also be performed for pharmaceuticals that 1) affect target structures that are conserved across species, 2) have a high potency or a small therapeutic margin, 3) are from a new therapeutic class, and 4) are structurally similar to compounds with known effects. Furthermore, suggestions for improving the effects testing of pharmaceuticals are made. These include inter alia chronic effects testing as a general approach, the use of invertebrate tests including sexual reproduction, the application of endpoints reflecting the mode of action of the drug or known side effects, and the simulation of more realistic exposure conditions in terrestrial laboratory tests.

  7. Challenges in Translational Development of Pharmaceutical Cocrystals.

    PubMed

    Kale, Dnyaneshwar P; Zode, Sandeep S; Bansal, Arvind K

    2017-02-01

    The last 2 decades have witnessed increased research in the area of cocrystals resulting in deeper scientific understanding, increase in intellectual property landscape, and evolution in the regulatory environment. Pharmaceutical cocrystals have received significant attention as a new solid form on account of their ability to modulate poor physicochemical properties of drug molecules. However, pharmaceutical development of cocrystals could be challenging, thus limiting their translation into viable drug products. In the present commentary, the role of cocrystals in the modulation of material properties and challenges involved in the pharmaceutical development of cocrystals have been discussed. The major hurdles encountered in the development of cocrystals such as safety of coformers, unpredictable performance during dissolution and solubility in different media, difficulties in establishing in vitro-in vivo correlation, and polymorphism have been extensively discussed. The influence of selecting appropriate formulation and process design on these challenges has been discussed. Finally, a brief outline of cocrystals that are undergoing clinical development has also been presented. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  8. Chitin and Chitosan as Direct Compression Excipients in Pharmaceutical Applications

    PubMed Central

    Badwan, Adnan A.; Rashid, Iyad; Al Omari, Mahmoud M.H.; Darras, Fouad H.

    2015-01-01

    Despite the numerous uses of chitin and chitosan as new functional materials of high potential in various fields, they are still behind several directly compressible excipients already dominating pharmaceutical applications. There are, however, new attempts to exploit chitin and chitosan in co-processing techniques that provide a product with potential to act as a direct compression (DC) excipient. This review outlines the compression properties of chitin and chitosan in the context of DC pharmaceutical applications. PMID:25810109

  9. Process for improving mechanical properties of epoxy resins by addition of cobalt ions

    NASA Technical Reports Server (NTRS)

    Stoakley, D. M.; St.clair, A. K. (Inventor)

    1984-01-01

    A resin product useful as an adhesive, composite or casting resin is described as well as the process used in its preparation to improve its flexural strength mechanical property characteristics. Improved flexural strength is attained with little or no change in density, thermal stability or moisture resistance by chemically incorporating 1.2% to 10.6% by weight Co(3) ions in an epoxidized resin system.

  10. The impact of hot melt extrusion and spray drying on mechanical properties and tableting indices of materials used in pharmaceutical development.

    PubMed

    Iyer, Raman; Hegde, Shridhar; Zhang, Yu-E; Dinunzio, James; Singhal, Dharmendra; Malick, A; Amidon, Gregory

    2013-10-01

    The impact of melt extrusion (HME) and spray drying (SD) on mechanical properties of hypromellose acetate succinate (HPMCAS), copovidone, and their formulated blends was studied and compared with that of reference excipients. Tensile strength (TS), compression pressure (CP), elastic modulus (E), and dynamic hardness (Hd ) were determined along with Hiestand indices using compacts prepared at a solid fraction of ∼0.85. HPMCAS and copovidone exhibited lower Hd , lower CP, and lower E than the reference excipients and moderate TS. HPMCAS was found to be highly brittle based on brittle fracture index values. The CP was 24% and 61% higher for HPMCAS after SD and HME, respectively, than for unprocessed material along with a higher Hd . Furthermore, the TS of HPMCAS and copovidone decreased upon HME. Upon blending melt-extruded HPMCAS with plastic materials such as microcrystalline cellulose, the TS increased. These results suggest that SD and HME could impact reworkability by reducing deformation of materials and in case of HME, likely by increasing density due to heating and shear stress in a screw extruder. A somewhat similar effect was observed for the dynamic binding index (BId ) of the excipients and formulated blends. Such data can be used to quantitate the impact of processing on mechanical properties of materials during tablet formulation development. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  11. Removal of Pharmaceutical Residues by Ferrate(VI)

    PubMed Central

    Jiang, JiaQian; Zhou, Zhengwei

    2013-01-01

    Background Pharmaceuticals and their metabolites are inevitably emitted into the waters. The adverse environmental and human health effects of pharmaceutical residues in water could take place under a very low concentration range; from several µg/L to ng/L. These are challenges to the global water industries as there is no unit process specifically designed to remove these pollutants. An efficient technology is thus sought to treat these pollutants in water and waste water. Methodology/Major Results A novel chemical, ferrate, was assessed using a standard jar test procedure for the removal of pharmaceuticals. The analytical protocols of pharmaceuticals were standard solid phase extraction together with various instrumentation methods including LC-MS, HPLC-UV and UV/Vis spectroscopy. Ferrate can remove more than 80% of ciprofloxacin (CIP) at ferrate dose of 1 mg Fe/L and 30% of ibuprofen (IBU) at ferrate dose of 2 mg Fe/L. Removal of pharmaceuticals by ferrate was pH dependant and this was in coordinate to the chemical/physical properties of pharmaceuticals. Ferrate has shown higher capability in the degradation of CIP than IBU; this is because CIP has electron-rich organic moieties (EOM) which can be readily degraded by ferrate oxidation and IBU has electron-withdrawing groups which has slow reaction rate with ferrate. Promising performance of ferrate in the treatment of real waste water effluent at both pH 6 and 8 and dose range of 1–5 mg Fe/L was observed. Removal efficiency of ciprofloxacin was the highest among the target compounds (63%), followed by naproxen (43%). On the other hand, n-acetyl sulphamethoxazole was the hardest to be removed by ferrate (8% only). Conclusions Ferrate is a promising chemical to be used to treat pharmaceuticals in waste water. Adjusting operating conditions in terms of the properties of target pharmaceuticals can maximise the pharmaceutical removal efficiency. PMID:23409029

  12. Effects of copper and zinc ions on the germicidal properties of two popular pharmaceutical antiseptic agents cetylpyridinium chloride and povidone-iodine.

    PubMed

    Zeelie, J J; McCarthy, T J

    1998-03-01

    The effects of copper and zinc ions on the rate of killing of Gram-negative bacterium Pseudomonas aeruginosa, Gram-positive bacterium Staphylococcus aureus and fungal yeast Candida albicans by antiseptic agents cetylpyridinium chloride and povidone-iodine (Betadine) were investigated. In the 48 test cases copper and zinc ions clearly potentiated the antiseptic agents in 28 (58.3%) cases and exhibited an improved (not clear potentiation) activity in 15 (31.3%) cases. In five (10.4%) cases there was no change in the antiseptics' antimicrobial activity. In general zinc potentiated the antiseptic agents more than copper. If an 'improved activity' was the only criterion for this study, then a more rapid antimicrobial effect was observed in 43 out of the 48 test cases, i.e., 90%.

  13. Bolaamphiphiles: A Pharmaceutical Review

    PubMed Central

    Fariya, Mayur; Jain, Ankitkumar; Dhawan, Vivek; Shah, Sanket; Nagarsenker, Mangal S.

    2014-01-01

    The field of drug discovery is ever growing and excipients play a major role in it. A novel class of amphiphiles has been discussed in the review. The review focuses on natural as well as synthetic bolaamphiphiles, their chemical structures and importantly, their ability to self assemble rendering them of great use to pharmaceutical industry. Recent reports on their ability to be used in fabrication of suitable nanosized carriers for drug as well as genes to target site, has been discussed substantially to understand the potential of bolaamphiphiles in field of drug delivery. PMID:25671179

  14. Proposal and pharmacotechnical study of a modern dermo-pharmaceutical formulation for cold cream.

    PubMed

    Jiménez Soriano, M M; Fresno Contreras, M J; Sellés Flores, E

    1996-06-01

    Cold-Creams have been used since the times of Galen (II cA.D.) as dermo-pharmaceutical and cosmetic emulsions. This paper proposes a modern Cold-Creams formulation with variations to improve both the formula as well as the properties and applications of the traditional cerates. Basically, a modern self-emulsionable excipient with isopropyl myristate is proposed. This substance is completely analysed from the galenic and pharmaco-technical viewpoints and the analysis is completed with a study of cosmetic or dermo-pharmaceutical effectiveness and topical application on skin. The results clearly show the advantages of the new formula which are: it is easy and comfortable to prepare, very adequate for cosmetology with satisfactory stability and rheological qualities and a high degree of moisture/emollient power make it appropriate as a vehicle for the active principle in Dermopharmacy and Cosmetology.

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

    PubMed

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

    2007-12-27

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

  16. Relevance of variation in use of terminology to define generic pharmaceutical products.

    PubMed

    Fonseca, Elize Massard da

    2015-02-01

    The World Health Organization (WHO) promotes the use of generic drug policies to foster competition in the pharmaceutical sector, reduce drug prices, and increase access to therapeutic drugs. However, little is known about how countries implement these policies. This article describes different terminology adopted by national regulatory authorities to define generic versus proprietary drug products in developing countries, including those in Latin America, and challenges that arise in their application of WHO guidelines, such as labeling issues. The author concludes that variation in generics terminology in these countries is a result of institutional context (i.e., the public sector setting as well as the body of laws and regulations that exists in the country) and policy legacies, such as intellectual property regimes, and highlights the need for further analysis of pharmaceutical regulations to improve understanding of the barriers and political implications of generic drug policies.

  17. Experimental and theoretical investigation of the molecular structure, conformational stability, hyperpolarizability, electrostatic potential, thermodynamic properties and NMR spectra of pharmaceutical important molecule: 4‧-Methylpropiophenone

    NASA Astrophysics Data System (ADS)

    Karunakaran, V.; Balachandran, V.

    2014-07-01

    Combined experimental and theoretical studies have been performed on the structure and vibrational spectra (IR and Raman spectra) of 4‧-methylpropiophenone (MPP). The FT-IR and FT-Raman spectra of 4‧-methylpropiophenone (MPP) have been recorded in the region 4000-400 cm-1 and 3500-100 cm-1, respectively. The harmonic vibrational frequencies were calculated and the scaled values have been compared with experimental FT-IR and FT-Raman spectra. A detailed interpretation of the infrared and Raman spectra of MPP are also reported based on total energy distribution (TED). The observed and the calculated frequencies are found to be in good agreement. The 1H and 13C NMR chemical shifts have been calculated by Gauge-Independent Atomic Orbital (GIAO) method with B3LYP/6-311++G(d,p). The natural bond orbital (NBO), natural hybrid orbital (NHO) analysis and electronic properties, such as HOMO and LUMO energies, were performed by DFT approach. The calculated HOMO and LUMO energies show that charge transfer occurs within molecule. The first order hyperpolarizability (β0) of the novel molecular system and related properties (βtot, α0 and Δα) of MPP are calculated using DFT/6-311++G(d,p) method on the finite-field approach. The Mulliken charges, the values of electric dipole moment (μ) of the molecule were computed using DFT calculations. The thermodynamic functions of the title compound were also performed at the above method and basis set.

  18. A review of wood thermal pretreatments to improve wood composite properties

    Treesearch

    Manuel Raul Pelaez-Samaniego; Vikram Yadama; Eini Lowell; Raul. Espinoza-Herrera

    2013-01-01

    The objective of this paper is to review the published literature on improving properties of wood composites through thermal pretreatment of wood. Thermal pretreatment has been conducted in moist environments using hot water or steam at temperatures up to 180 and 230 ˚C, respectively, or in dry environments using inert gases at temperatures up to 240 ...

  19. The Acoustic Properties of Vowels: A Tool for Improving Articulation and Comprehension of English

    ERIC Educational Resources Information Center

    McCombs, Candalene J.

    2006-01-01

    Correct pronunciation is often a later step in the process of teaching English as a second language. However, a focus on the correct articulation of vowels can significantly improve listening and comprehension skills as well as articulatory skills. Vowels and consonants differ in their acoustic properties. Unlike consonants, vowel sounds are…

  20. Peroxidase mediated conjugation of corn fibeer gum and bovine serum albumin to improve emulsifying properties

    USDA-ARS?s Scientific Manuscript database

    The emulsifying properties of corn fiber gum (CFG), a naturally-occurring polysaccharide protein complex, were improved by kinetically controlled formation of hetero-covalent linkages with bovine serum albumin (BSA), using horseradish peroxidase. The formation of hetero-crosslinked CFG-BSA conjugate...

  1. 75 FR 57829 - Airport Improvement Program (AIP): Policy Regarding Access to Airports From Residential Property

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-22

    ... Federal Aviation Administration Airport Improvement Program (AIP): Policy Regarding Access to Airports... Proposed Policy Regarding Access to Airports From Residential Property that was published in the Federal... and clarify FAA policy concerning through-the-fence access to a Federally obligated airport from...

  2. Glycerol Tri-Ester Derivatives as Diluents to Improve Low Temperature Properties of Vegetable Oils

    USDA-ARS?s Scientific Manuscript database

    Large-scale production of biodiesel has led to a surplus of glycerol, so new commercial uses of this co-product are being sought. Twenty four vegetable oils were screened using glycerol tris (2-ethylhexanoate) [GTEH] as a diluent to improve the low temperature properties. Epoxidized soybean oil (E...

  3. Improved ice particle optical property simulations in the ultraviolet to far-infrared regime

    NASA Astrophysics Data System (ADS)

    Bi, Lei; Yang, Ping

    2017-03-01

    To derive the bulk radiative properties of ice clouds, aircraft contrails and snow grains, which are fundamental to atmospheric radiative transfer calculations in downstream applications, it is necessary to accurately simulate the scattering of light by individual ice particles. An ice particle optical property database reported in 2013 (hereafter, TAMUice2013) is updated (hereafter, TAMUice2016) to incorporate recent advances in computation of the optical properties of nonspherical particles. Specifically, we employ the invariant imbedding T-matrix (II-TM) method to compute the optical properties of particles with small to moderate size parameters. Both versions use the Improved Geometric Optics Method (IGOM) to compute the optical properties of large ice crystals, but TAMUice2016 improves the treatment of inhomogeneous waves inside the scattering particles in the case where ice is absorptive such as at infrared wavelengths. To bridge the gap between the extinction efficiencies computed from the II-TM and the IGOM, TAMUice2016 includes spectrally dependent higher order terms of the edge effect in addition to the first order counterpart considered in TAMUice2013. Furthermore, the differences between TAMUice2013 and TAMUice2016 are quantified with respect to the computation of the bulk optical properties of ice clouds.

  4. 2-Aminothiazoles with Improved Pharmacotherapeutic Properties for Treatment of Prion Disease

    PubMed Central

    Li, Zhe; Silber, B. Michael; Rao, Satish; Gever, Joel; Bryant, Clifford; Gallardo-Godoy, Alejandra; Dolghih, Elena; Widjaja, Kartika; Elepano, Manuel; Jacobson, Matthew P.; Renslo, Adam R.

    2014-01-01

    Recently, we described the aminothiazole lead (4-biphenyl-4-yl-thiazol-2-yl)-(6-methyl-pyridin-2-yl)-amine (1), which exhibits many desirable properties, including excellent stability in liver microsomes, oral bioavailability of ∼40% and high exposure in the brains of mice. Despite its good pharmacokinetic properties, compound 1 exhibited only modest potency in mouse neuroblastoma cells overexpressing the disease-causing prion protein PrPSc. Accordingly, we sought to identify analogs of 1 with improved antiprion potency in ScN2a-cl3 cells while retaining comparable or superior properties. We now report the discovery of improved lead compounds such as (6-methyl-pyridin-2-yl)-[4-(4-pyridin-3-yl-phenyl)-thiazol-2-yl]-amine (15) and cyclopropanecarboxylic acid (4-biphenyl-thiazol-2-yl)-amide (34), which exhibited brain exposure/EC50 ratios at least ten-fold greater than that of 1. PMID:23509039

  5. Improving the Mechanical Properties of Cu-15Ni-8Sn Alloys by Addition of Titanium.

    PubMed

    Zhao, Chao; Zhang, Weiwen; Wang, Zhi; Li, Daoxi; Luo, Zongqiang; Yang, Chao; Zhang, Datong

    2017-09-06

    The effect of Ti addition on the microstructure and mechanical properties of Cu-15Ni-8Sn alloys was investigated. Optical microscopy (OM), scanning electronic microscopy (SEM), and transmission electron microscopy (TEM) were used to determine grain size and distribution of the second phases in the alloys. The results indicate that the tensile properties of Cu-15Ni-8Sn alloys are improved significantly with Ti addition. Tensile elongation increased from 2.7% for the alloy without Ti to 17.9% for the alloy with 0.3% Ti, while tensile strength was maintained and even increased from 935 MPa to 1024 MPa. The improvement of the mechanical properties of Cu-15Ni-8Sn alloys by the addition of Ti is attributed to the grain refinement and suppression of discontinuous precipitation during heat treatment.

  6. 41 CFR 102-75.1040 - May Federal agencies abandon or destroy improvements on land or related personal property before...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... abandon or destroy improvements on land or related personal property before public notice is given of such proposed abandonment or destruction? 102-75.1040 Section 102-75.1040 Public Contracts and Property... PROPERTY 75-REAL PROPERTY DISPOSAL Abandonment, Destruction, or Donation to Public Bodies Abandonment...

  7. How can we improve sub 40 nm Transistor properties by using Ion implantation

    NASA Astrophysics Data System (ADS)

    Lee, Anbae; Jin, Seungwoo; Joo, Younghwan; Jang, Ilsik; Cha, Jaechun; Jeong, Kichel; Kang, Hyosang; Cho, Cjay; Jang, Jeonghoon; Hwang, Sunny

    2011-01-01

    To extend current process, it is required develop new implantation method. One of promising candidates are carbon implant, cold implant, or cold carbon implantation. To improve transistor properties, we have evaluated those implantation methods in Lightly doped drain (LDD), Source/Drain(S/D,P+ BF2, N+ As) and N+ add implant step. Carbon (C+) implantation could improve Short channel effect(SCE), cold implantation decrease Drain induced barrier lowering(DIBL), Sense and amplifer(S/A) mismatch and contact resistance. Cold carbon implant improved junction Breakdown voltage(BV). Optimization of process conditions and junction profiles is required for optimum device performance.

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

    PubMed

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

    2014-12-01

    As the demand for new drugs is rising, the pharmaceutical industry faces the quest of shortening development time, and thus, reducing the time to market. Environmental aspects typically still play a minor role within the early phase of process development. Nevertheless, it is highly promising to rethink, redesign, and optimize process strategies as early as possible in active pharmaceutical ingredient (API) process development, rather than later at the stage of already established processes. The study presented herein deals with a holistic life-cycle-based process optimization and intensification of a pharmaceutical production process targeting a low-volume, high-value API. Striving for process intensification by transfer from batch to continuous processing, as well as an alternative catalytic system, different process options are evaluated with regard to their environmental impact to identify bottlenecks and improvement potentials for further process development activities. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Deliquescence of pharmaceutical systems.

    PubMed

    Mauer, Lisa J; Taylor, Lynne S

    2010-12-01

    Deliquescence is a first order phase transition from solid to solution that occurs at a relative humidity (RH) that is characteristic to the crystalline compound. Such dissolution of active pharmaceutical ingredients and excipients can lead to detrimental physical and chemical instabilities. Furthermore, in systems containing more than one deliquescent component, the RH of the solid-solution transition will be lowered, leading to some level of dissolution at unexpectedly low RH conditions. Deliquescence lowering is independent of the ratio of the deliquescent components and therefore is of concern for any formulation containing two or more deliquescent compounds. Because chemical reactions occur much more readily in solution, deliquescence will enhance the degradation of labile APIs. RH fluctuations will lead to cycles of deliquescence and efflorescence (crystallization), which will contribute to particle agglomeration and caking. This review will address the phenomenon of deliquescence, the significance of deliquescence to pharmaceutical systems, measurement techniques, the kinetics and thermodynamics of deliquescence, the behavior of mixtures of deliquescent compounds (including phase diagrams and thermodynamics of binary systems), and consequences of deliquescence on chemical and physical stability.

  10. Pharmaceutical Education and the Translation of Pharmaceutical Care into Practice.

    ERIC Educational Resources Information Center

    Newton, Gail D.

    1991-01-01

    A systematic approach to reform of pharmaceutical education is seen as necessary to link intended outcomes of reform to a progressive and generally accepted mission of professional practice. Cooperation between pharmaceutical education, professional organizations, and regulatory agencies is viewed as necessary and refinement of professional…

  11. Pharmaceutical Education and the Translation of Pharmaceutical Care into Practice.

    ERIC Educational Resources Information Center

    Newton, Gail D.

    1991-01-01

    A systematic approach to reform of pharmaceutical education is seen as necessary to link intended outcomes of reform to a progressive and generally accepted mission of professional practice. Cooperation between pharmaceutical education, professional organizations, and regulatory agencies is viewed as necessary and refinement of professional…

  12. Improvements of reinforced silica aerogel nanocomposites thermal properties for architecture applications.

    PubMed

    Saboktakin, Amin; Saboktakin, Mohammad Reza

    2015-01-01

    An 1,4-cis polybutadiene rubber/carboxymethyl starch (CMS)-based silica aerogel nanocomposites as a insulation material was developed that will provide superior thermal insulation properties, flexibility, toughness, durability of the parent polymer, yet with the low density and superior insulation properties associated with the aerogels. In this study, reinforced 1,4-cis polybutadiene-CMS-silica aerogel nanocomposites were prepared from a silica aerogel with a surface area 710 m(2) g(-1), a pore size of 25.3 nm and a pore volume of 4.7 cm(3) g(-1). The tensile properties and dynamic mechanical properties of 1,4-cis polybutadiene/CMS nanocomposites were systematically enhanced at low silica loading. Similar improvements in tensile modulus and strength have been observed for 1,4-cis polybutadiene/CMS mesoporous silica aerogel nanocomposites.

  13. Improvement of adhesion properties of low density polyethylene (LDPE) substrate using atmospheric plasma

    SciTech Connect

    Sanchez-Nacher, L.; Garcia-Sanoguera, D.; Fenollar, O.; Balart, J.; Fombuena, V.

    2010-06-02

    In this work we have used atmospheric plasma technology on polyethylene surface with different treatment conditions. These modify surface pre-treatments on polyethylene, thus having a positive effect on overall surface activity of polymer surface and, consequently, adhesion properties can be remarkably improved. We have evaluated the influence of the nozzle/substrate distance and atmospheric plasma speed on wettability changes and adhesion properties. Wettability changes have been studied by contact angle measurements and subsequent surface energy calculation. Mechanical characterization of adhesion joints has been carried out in two different ways: peel and shear tensile test. The overall results show a remarkable increase in mechanical properties of adhesion joints for low nozzle/substrate distances and low speed. So plasma atmospheric technology is highly useful to increase adhesion properties of polypropylene.

  14. Improving ion-exchange membrane properties by the role of nanoparticles

    NASA Astrophysics Data System (ADS)

    Ariono, Danu; Khoiruddin

    2017-01-01

    Extensive application of synthetic ion-exchange membrane (IEM) in many areas has necessitated the improvement of their properties. Recently, the introduction of nanoparticles into polymeric membrane has attracted growing interest since the combination of both materials results in better properties. This well-known mixed-matrix membrane exhibits superior characteristics compared to an individual polymeric membrane. Properties of the nanoparticles such as electrical conductivity, hydrophilicity, and adsorption capacity can be utilized to produce the IEM with better physicochemical, electrochemical, and mechanical characteristics. The nanoparticles may also be used to achieve a specific characteristic such as an antibacterial property and monovalent ion permselectivity. In this paper, preparation, the role of inorganic materials and performance of mixed-matrix IEM are reviewed. In addition, challenges facing mixed-matrix IEM and strategies taken to overcome those challenges and future perspectives are discussed.

  15. Novel natural-product-like caged xanthones with improved druglike properties and in vivo antitumor potency.

    PubMed

    Wu, Yue; Hu, Mingyang; Yang, Li; Li, Xiang; Bian, Jinlei; Jiang, Fen; Sun, Haopeng; You, Qidong; Zhang, Xiaojin

    2015-06-15

    DDO-6101, a natural-product-like caged xanthone discovered previously in our laboratory based on the pharmacophoric scaffold of Garcinia natural product gambogic acid (GA), shows potent cytotoxicity in vitro but poor efficacy in vivo due to its poor druglike properties. In order to improve the druglike properties and in vivo cytotoxic potency, a novel series of 19 prenyl group-modified derivatives of DDO-6101 was synthesized and evaluated for their in vitro antitumor activity and druglike properties. The SAR and SPR information of these compounds was also obtained. In the light of the in vitro antitumor activity and druglike properties such as aqueous solubility and permeability, compound 6f (named as DDO-6306) was advanced into in vivo efficacy experiment. The results showed that DDO-6306 is more potent than DDO-6101 in vivo and is a promising antitumor candidate for further evaluation.

  16. Improvement in stability of superconducting coil by different mechanical properties of bobbins

    NASA Astrophysics Data System (ADS)

    Sekine, N.; Takao, T.; Kojo, Y.; Yamaguchi, Y.; Tada, S.; Takeo, M.; Sato, S.; Yamanaka, A.; Fukui, S.

    2003-10-01

    The Dyneema ® fiber reinforced plastic (DFRP) expands to a direction of the Dyneema fibers during cooling process. Therefore, a winding angle in Dyneema fibers of the DFRP bobbin manufactured by the filament winding method makes possible to control thermal expansion/contraction properties to the circumferential direction on the bobbin. Moreover, DFRP’s frictional coefficients are considerably low. These properties are extremely different from those of GFRP which is generally used as the spacers and the bobbins of superconducting coils. In this paper, the coils fabricated with DFRP and GFRP bobbins are examined in DC and AC operating experiments. When the coil was operated under DC current, the low frictional properties of the coils having DFRP bobbins improved the instability due to the wire motion, on the other hand, in case of AC operating test, the thermal expansion properties of DFRP bobbin could reduce the mechanical losses between the wire and the bobbin.

  17. Genetic Optimization of Training Sets for Improved Machine Learning Models of Molecular Properties.

    PubMed

    Browning, Nicholas J; Ramakrishnan, Raghunathan; von Lilienfeld, O Anatole; Roethlisberger, Ursula

    2017-04-06

    The training of molecular models of quantum mechanical properties based on statistical machine learning requires large data sets which exemplify the map from chemical structure to molecular property. Intelligent a priori selection of training examples is often difficult or impossible to achieve, as prior knowledge may be unavailable. Ordinarily representative selection of training molecules from such data sets is achieved through random sampling. We use genetic algorithms for the optimization of training set composition consisting of tens of thousands of small organic molecules. The resulting machine learning models are considerably more accurate: in the limit of small training sets, mean absolute errors for out-of-sample predictions are reduced by up to ∼75%. We discuss and present optimized training sets consisting of 10 molecular classes for all molecular properties studied. We show that these classes can be used to design improved training sets for the generation of machine learning models of the same properties in similar but unrelated molecular sets.

  18. Photoinduced electron transfer, improved nonlinear optical properties and photocurrent generation in polyaniline-graphite oxide hybrid

    NASA Astrophysics Data System (ADS)

    Remyamol, T.; Gopinath, Pramod; John, Honey

    2014-09-01

    Synergetic improvement in the optical limiting behaviour, as well as in the photocurrent generation, is observed when polyaniline is hybridized with graphite oxide (GO) by a simple in situ polymerization method. The noncovalent functionalization of polyaniline by GO is mainly by π-π interactions, hence the electronic structure of GO is maintained and crystallinity is restored in the hybrid. The hybrid material is fully characterized and the effect of the proportion of GO in the hybrid for the improvement in properties as compared to polyaniline is also studied. The nonlinear optical properties of the hybrid are studied by open aperture Z scan technique at 532 nm, in the nanosecond excitation domain. The photocurrent measurements of the films made by spin coating are also reported. The photoluminescence of polyaniline is significantly quenched in the hybrid, indicating light induced charge separation and electron transfer from polyaniline to GO, thereby improving the photocurrent generation and optical limiting behaviour.

  19. Metallurgical Mechanism and Niobium Effects on Improved Mechanical Properties in High Carbon Steels

    NASA Astrophysics Data System (ADS)

    Jansto, Steven G.

    The technological development of value-added applications for niobium (Nb) microalloyed structural steels has expanded into the high carbon long products sector. Micro additions of 0.005 to 0.020%Nb in various high carbon steel compositions have exhibited improved processing, such as wire drawability or formability during manufacturing, higher productivity at reduced operational cost as well as improved mechanical properties compared to traditional non-Nb bearing high carbon steels. Although the Nb solubility is limited in high carbon steels compared to low carbon steels, the optimized Nb content has been defined based on experimental results and now transferred into industrial operations. The Nb delays the pearlite transformation, hence resulting in a finer interlammelar spacing compared to traditional high carbon pearlitic steels. Consequently, the optimized Nb content leads to improved mechanical properties due to this finer interlamellar pearlite spacing. Opportunities exist to transfer this new Nb-technology into wire rods, bolts, rails and tire cord.

  20. Curcumin nanoparticles improve the physicochemical properties of curcumin and effectively enhance its antioxidant and antihepatoma activities.

    PubMed

    Yen, Feng-Lin; Wu, Tzu-Hui; Tzeng, Cheng-Wei; Lin, Liang-Tzung; Lin, Chun-Ching

    2010-06-23

    Curcumin (CUR), a natural polyphenol isolated from tumeric ( Curcuma longa ), has been documented to possess antioxidant and anticancer activities. Unfortunately, the compound has poor aqueous solubility, which results in poor bioavailability following high doses by oral administration. To improve the solubility of CUR, we developed a novel curcumin nanoparticle system (CURN) and investigated its physicochemical properties as well as its enhanced dissolution mechanism. Our results indicated that CURN improved the physicochemical properties of CUR, including a reduction in particle size and the formation of an amorphous state with hydrogen bonding, both of which increased the drug release of the compound. Moreover, in vitro studies indicated that CURN significantly enhanced the antioxidant and antihepatoma activities of CUR (P < 0.05). Consequently, we suggest that CURN can be used to reduce the dosage of CUR and improve its bioavailability and merits further investigation for therapeutic applications.

  1. Commentary: Why Pharmaceutical Scientists in Early Drug Discovery Are Critical for Influencing the Design and Selection of Optimal Drug Candidates.

    PubMed

    Landis, Margaret S; Bhattachar, Shobha; Yazdanian, Mehran; Morrison, John

    2017-07-28

    This commentary reflects the collective view of pharmaceutical scientists from four different organizations with extensive experience in the field of drug discovery support. Herein, engaging discussion is presented on the current and future approaches for the selection of the most optimal and developable drug candidates. Over the past two decades, developability assessment programs have been implemented with the intention of improving physicochemical and metabolic properties. However, the complexity of both new drug targets and non-traditional drug candidates provides continuing challenges for developing formulations for optimal drug delivery. The need for more enabled technologies to deliver drug candidates has necessitated an even more active role for pharmaceutical scientists to influence many key molecular parameters during compound optimization and selection. This enhanced role begins at the early in vitro screening stages, where key learnings regarding the interplay of molecular structure and pharmaceutical property relationships can be derived. Performance of the drug candidates in formulations intended to support key in vivo studies provides important information on chemotype-formulation compatibility relationships. Structure modifications to support the selection of the solid form are also important to consider, and predictive in silico models are being rapidly developed in this area. Ultimately, the role of pharmaceutical scientists in drug discovery now extends beyond rapid solubility screening, early form assessment, and data delivery. This multidisciplinary role has evolved to include the practice of proactively taking part in the molecular design to better align solid form and formulation requirements to enhance developability potential.

  2. Effect of poly ethylene glycol on the mechanical and thermal properties of bioactive poly(ε-caprolactone) melt extrudates for pharmaceutical applications.

    PubMed

    Douglas, P; Albadarin, Ahmad B; Sajjia, M; Mangwandi, Chirangano; Kuhs, Manuel; Collins, Maurice N; Walker, Gavin M

    2016-03-16

    This paper investigates the effects of polyethylene glycol (PEG), on the mechanical and thermal properties of nalidixic acid/poly ε-caprolactone (NA)/PCL blends prepared by hot melt extrusion. The blends were characterized by tensile and flexural analysis, dynamic mechanical analysis, differential scanning calorimetry, thermogravimetric analysis and X-ray diffraction. Results show that loading PEG in the PCL had a detrimental effect on the tensile strength and toughness of the blends, reducing them by 20-40%. The partial miscibility of the PCL-PEG system, causes an increase in Tg. While increases in the crystallinity is attributed to the plasticisation effect of PEG and the nucleation effect of NA. The average crystal size increased by 8% upon PEG addition. Experimental data indicated that the addition of NA caused loss of the tensile strength and toughness of PCL. Thermal analysis of the PCL showed that on addition of the thermally unstable NA, thermal degradation occurred early and was autocatalytic. However, the NA did benefit from the heat shielding provided by the PCL matrix resulting in more thermally stable NA particles. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Pharmaceutical new product development: the increasing role of in-licensing.

    PubMed

    Edwards, Nancy V

    2008-12-01

    Many pharmaceutical companies are facing a pipeline gap because of the increasing economic burden and uncertainty associated with internal research and development programs designed to develop new pharmaceutical products. To fill this pipeline gap, pharmaceutical companies are increasingly relying on in-licensing opportunities. New business development identifies new pharmaceuticals that satisfy unmet needs and are a good strategic fit for the company, completes valuation models and forecasts, evaluates the ability of the company to develop and launch products, and pursues in-licensing agreements for pharmaceuticals that cannot be developed internally on a timely basis. These agreements involve the transfer of access rights for patents, trademarks, or similar intellectual property from an outside company in exchange for payments. Despite the risks, in-licensing is increasingly becoming the preferred method for pharmaceutical companies with pipeline gaps to bring new pharmaceuticals to the clinician.

  4. Improving the outcomes of biopharmaceutical delivery via the subcutaneous route by understanding the chemical, physical and physiological properties of the subcutaneous injection site.

    PubMed

    Kinnunen, Hanne M; Mrsny, Randall J

    2014-05-28

    Subcutaneous (SC) injection is currently the most common route of self-administering biopharmaceuticals such as proteins and peptides. While pharmaceutical scientists have acquired great skill in identifying formulations for these proteins and peptides with multi-year shelf life stability, the SC injection of these formulations can result in inconsistent or particularly low bioavailability outcomes. We hypothesise that upon injection, the chemical, physical and physiological properties of the subcutaneous tissue may play a crucial role in determining the therapeutic outcomes of SC injected biopharmaceuticals. We contend that physical and chemical stresses placed upon the injected protein or peptide as it transitions from the non-physiological environment of its formulation to the homeostatic conditions of the SC tissue can affect its fate following injection, and that by taking this environment into account when formulating, more precisely controlled release of SC injected biopharmaceuticals could be achieved. In this mini-review we describe how events that occur to an injected protein or peptide during this post-injection transition period could affect the diffusion of bioactive material to blood capillaries and lymphatic vessels. With this in mind, we have reviewed the chemical, physical and physiological attributes of the SC tissue and collated studies on how these properties are known to affect protein stability and diffusional properties. Finally, examples where the understanding of the properties of the SC tissue when formulating for SC injected biopharmaceuticals has improved the predictability of drug delivery via the SC route are discussed, with the need for novel tools for rational and informed formulation development highlighted. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Value of pharmaceuticals: ensuring the future of research and development.

    PubMed

    Serajuddin, Hamida K; Serajuddin, Abu T M

    2006-01-01

    To analyze the current situation under which the pharmaceutical industry is criticized for the production of drugs with potential adverse effects, the high prices of medicines, and aggressive marketing practices, and to provide a proposal to rectify the situation. Published books, pharmaceutical journals, Web of Science database using the search terms pharmaceutical, research, development, marketing, cost, and the Food and Drug Administration (FDA) Web site. Most breakthroughs in the treatment of diseases and prolongation of lives have come about through pharmaceuticals discovered and developed by the pharmaceutical industry. While the process of discovering and developing new pharmaceuticals is lengthy, costly, and lacking any assurance of success, investment in research and development by the U.S. pharmaceutical industry has increased progressively, reaching 51.3 billion dollars in 2005. Yet the annual number of FDA approvals of new molecular entities (NMEs) has gradually decreased over the past 10 years. Additionally, a large part of the patent life of a successful NME is consumed during this lengthy development phase. Few businesses, if any, have such long product gestation lives and risks. For these reasons, the pharmaceutical industry is often in a rush to recoup its investment before the product's patent expires, and this is the root cause of many criticisms against the pharmaceutical industry. To rectify the current situation, a new system is proposed under which innovator pharmaceutical companies would be allowed royalties for their products after the expiration of patents, in a manner similar to the way in which other intellectual properties (such as books, music, films) are protected by copyright. Such a system would allow pharmaceutical companies to continue research on new pharmaceutical products unimpeded by the patent clock. Given appropriate legislative or other facilitatory actions, a royalty-based system for the marketing of generic products after

  6. Effective executive management in the pharmaceutical industry.

    PubMed

    Tran, Hoang; Kleiner, Brian H

    2005-01-01

    Along with the boom in information technology and vast development in genomic and proteomic discoveries, the pharmaceutical and biotech industries have been provided the means and tools to create a new page in medicinal history. They are now able to alter the classic ways to cure complex diseases thanks to the completion of the human genome project. To be able to compete in this industry, pharmaceutical management has to be effective not only internally but also externally in socially acceptable conduct. The first department that requires focus is marketing and sales. As the main driving force to increase revenues and profits, marketing and sales employees should be highly motivated by compensation. Also, customer relationships should be maintained for long-term gain. As important as marketing, research and development requires the financial support as well as the critical decision making to further expand the product pipeline. Similarly, finance and technologies should be adequately monitored and invested to provide support as well as prepare for future expansion. On top of that, manufacturing processes and operations are operated per quality systems and FDA guidelines to ensure high quality. Human Resources, on the other hand, should carry the managing and motivation from upper management through systematic recruitment, adequate training, and fair compensation. Moreover, effective management in a pharmaceutical would also require the social welfare and charity to help patients who cannot afford the treatment as well as improving the organization's image. Last but not least, the management should also prepare for the globalization of the industry. Inevitably, large pharmaceutical companies are merging with each other or acquiring smaller companies to enhance the competitive advantages as well as expand their product mix. For effectiveness in a pharmaceutical industry, management should focus more than just the daily routine tasks and short-term goals. Rather, they

  7. Improving flow properties of ibuprofen by fluidized bed particle thin-coating.

    PubMed

    Ehlers, Henrik; Räikkönen, Heikki; Antikainen, Osmo; Heinämäki, Jyrki; Yliruusi, Jouko

    2009-02-23

    The surfaces of ibuprofen particles (d(50) 42 microm) were modified by coating the particles with diluted aqueous hydroxypropyl methylcellulose (HPMC) solution in an instrumentated top-spray fluid bed granulator. The objective was to evaluate whether an extremely thin polymer coating could be an alternative to granulation in enhancing powder flow and processing properties. The studied variables were inlet air temperature and spray rate. The treated powders showed a clear improvement in flow rate as measured with a flow meter designed for powders with poor flow properties. The particle size was determined using optical microscopy and image analysis. The particle size, size distribution and circularity of the treated and untreated ibuprofen batches showed no difference from each other. Consequently, the improvement in flow properties can be attributed to the trace amounts of hydroxypropyl methylcellulose applied onto the particle surfaces. In conclusion, fluidized bed particle thin-coating (PTC) alters the surface of ibuprofen powder particles and improves the flow properties of ibuprofen powder with changes in neither particle size, size distribution nor morphology.

  8. Improving mechanical and biological properties of macroporous HA scaffolds through composite coatings.

    PubMed

    Zhao, J; Lu, X; Duan, K; Guo, L Y; Zhou, S B; Weng, J

    2009-11-01

    Interconnected porous hydroxyapatite (HA) scaffolds are widely used for bone repair and replacement, owing to their ability to support the adhesion, transfer, proliferation and differentiation of cells. In the present study, the polymer impregnation approach was adopted to produce porous HA scaffolds with three-dimensional (3D) porous structures. These scaffolds have an advantage of highly interconnected porosity (approximately 85%) but a drawback of poor mechanical strength. Therefore, the as-prepared HA scaffolds were lined with composite polymer coatings in order to improve the mechanical properties and retain its good bioactivity and biocompatibility at the same time. The composite coatings were based on poly(D,L-lactide) (PDLLA) polymer solutions, and contained single component or combination of HA, calcium sulfate (CS) and chondroitin sulfate (ChS) powders. The effects of composite coatings on scaffold porosity, microstructure, mechanical property, in vitro mineralizing behavior, and cell attachment of the resultant scaffolds were investigated. The results showed that the scaffolds with composite coatings resulted in significant improvement in both mechanical and biological properties while retaining the 3D interconnected porous structure. The in vitro mineralizing behaviors were mainly related to the compositions of CS and ChS powders in the composite coatings. Excellent cell attachments were observed on the pure HA scaffold as well as the three types of composite scaffolds. These composite scaffolds with improved mechanical properties and bioactivities are promising bone substitutes in tissue engineering fields.

  9. Improvement of Polylactide Properties through Cellulose Nanocrystals Embedded in Poly(Vinyl Alcohol) Electrospun Nanofibers.

    PubMed

    López de Dicastillo, Carol; Garrido, Luan; Alvarado, Nancy; Romero, Julio; Palma, Juan Luis; Galotto, Maria Jose

    2017-05-11

    Electrospun nanofibers of poly (vinyl alcohol) (PV) were obtained to improve dispersion of cellulose nanocrystals (CNC) within hydrophobic biopolymeric matrices, such as poly(lactic acid) (PLA). Electrospun nanofibers (PV/CNC)n were successfully obtained with a final concentration of 23% (w/w) of CNC. Morphological, structural and thermal properties of developed CNC and electrospun nanofibers were characterized. X-ray diffraction and thermal analysis revealed that the crystallinity of PV was reduced by the electrospinning process, and the incorporation of CNC increased the thermal stability of biodegradable nanofibers. Interactions between CNC and PV polymer also enhanced the thermal stability of CNC and improved the dispersion of CNC within the PLA matrix. PLA materials with CNC lyophilized were also casted in order to compare the properties with materials based on CNC containing nanofibers. Nanofibers and CNC were incorporated into PLA at three concentrations: 0.5%, 1% and 3% (CNC respect to polymer weight) and nanocomposites were fully characterized. Overall, nanofibers containing CNC positively modified the physical properties of PLA materials, such as the crystallinity degree of PLA which was greatly enhanced. Specifically, materials with 1% nanofiber 1PLA(PV/CNC)n presented highest improvements related to mechanical and barrier properties; elongation at break was enhanced almost four times and the permeation of oxygen was reduced by approximately 30%.

  10. Improvement of Polylactide Properties through Cellulose Nanocrystals Embedded in Poly(Vinyl Alcohol) Electrospun Nanofibers

    PubMed Central

    López de Dicastillo, Carol; Garrido, Luan; Alvarado, Nancy; Romero, Julio; Palma, Juan Luis; Galotto, Maria Jose

    2017-01-01

    Electrospun nanofibers of poly (vinyl alcohol) (PV) were obtained to improve dispersion of cellulose nanocrystals (CNC) within hydrophobic biopolymeric matrices, such as poly(lactic acid) (PLA). Electrospun nanofibers (PV/CNC)n were successfully obtained with a final concentration of 23% (w/w) of CNC. Morphological, structural and thermal properties of developed CNC and electrospun nanofibers were characterized. X-ray diffraction and thermal analysis revealed that the crystallinity of PV was reduced by the electrospinning process, and the incorporation of CNC increased the thermal stability of biodegradable nanofibers. Interactions between CNC and PV polymer also enhanced the thermal stability of CNC and improved the dispersion of CNC within the PLA matrix. PLA materials with CNC lyophilized were also casted in order to compare the properties with materials based on CNC containing nanofibers. Nanofibers and CNC were incorporated into PLA at three concentrations: 0.5%, 1% and 3% (CNC respect to polymer weight) and nanocomposites were fully characterized. Overall, nanofibers containing CNC positively modified the physical properties of PLA materials, such as the crystallinity degree of PLA which was greatly enhanced. Specifically, materials with 1% nanofiber 1PLA(PV/CNC)n presented highest improvements related to mechanical and barrier properties; elongation at break was enhanced almost four times and the permeation of oxygen was reduced by approximately 30%. PMID:28492470

  11. Improved surface stability and biotin binding properties of streptavidin coating on polystyrene.

    PubMed

    Ylikotila, Johanna; Välimaa, Lasse; Takalo, Harri; Pettersson, Kim

    2009-05-01

    The ultimate nature of streptavidin to bind biotin tightly is widely utilized in many solid-phase based applications to provide a universal binding surface for biotinylated molecules. However, the preparation of the streptavidin coatings by passive adsorption may heavily alter the binding properties of native streptavidin and may not result in the best possible capture surface for demanding solid-phase assays. By introducing sulphydryl groups through primary amines in the protein, we have activated and conjugated native streptavidin into larger protein polymers resulting in high local binding density when coated on polystyrene. This thiolated streptavidin formed through chemical modification has improved adsorption properties and biotin binding capability, compared to the native streptavidin. When this thiolated streptavidin is coated on polystyrene, a dense surface is formed, which provides up to 3-fold increase in the biotin binding efficiency and improves the surface stability by minimizing the desorption of the adsorbed protein from the surface during incubation. Furthermore, this high-capacity surface is resistant to harsh chemical treatments, such as denaturing conditions or mild reducing conditions. The improved adsorption properties of the thiolated streptavidin allow the coating process to be performed with shorter incubation times (15min), still providing enhanced solid-phase properties, compared to a reference streptavidin surface.

  12. Improved electrical properties for Mn-doped lead-free piezoelectric potassium sodium niobate ceramics

    NASA Astrophysics Data System (ADS)

    Wang, Lingyan; Ren, Wei; Ma, Wenhui; Liu, Ming; Shi, Peng; Wu, Xiaoqing

    2015-09-01

    The un-doped and doped lead-free piezoelectric potassium sodium niobate (K0.5Na0.5NbO3, KNN) ceramics with different amounts of Mn were prepared. The decreased dielectric losses and the improved electrical properties were observed in the Mn-doped KNN ceramics. However, the variation of electrical properties with the Mn contents was not continuously. The 0.5 mol.% Mn-doped KNN ceramic shows the highest dielectric loss and the worst electrical properties. The KNN ceramics doped with less than and more than 0.5 mol.% Mn all show improved electrical properties. The change of lattice position of Mn ions in KNN ceramics was the main reason. When the Mn content is less than 0.5 mol.%, the Mn ions occupied the cation vacancies in A-site. When the Mn content is higher than 0.5 mol.%, the Mn ions entered B-site of KNN perovskite structure and formed the defect complexes ( MnNb ″ - VO ṡ ṡ ) and ( MnNb ' - VO ṡ ṡ - MnNb ' ). They both led to a lower defect concentration. However, When the Mn content is up to 1.5 mol.%, the electrical properties of KNN ceramic became degraded because of the accumulation of Mn oxides at grain boundaries.

  13. Designing a Pharmaceutical Care Curriculum.

    ERIC Educational Resources Information Center

    Perrier, Donald G.; And Others

    1995-01-01

    Guidelines for developing a pharmacy school curriculum based on the principle of pharmaceutical care and professional responsibility are offered, beginning with mission statements for profession, practice, and pharmaceutical education in general. The University of Toronto experience in designing such a curriculum is chronicled as an illustration…

  14. Rubisco catalytic properties of wild and domesticated relatives provide scope for improving wheat photosynthesis.

    PubMed

    Prins, Anneke; Orr, Douglas J; Andralojc, P John; Reynolds, Matthew P; Carmo-Silva, Elizabete; Parry, Martin A J

    2016-03-01

    Rubisco is a major target for improving crop photosynthesis and yield, yet natural diversity in catalytic properties of this enzyme is poorly understood. Rubisco from 25 genotypes of the Triticeae tribe, including wild relatives of bread wheat (Triticum aestivum), were surveyed to identify superior enzymes for improving photosynthesis in this crop. In vitro Rubisco carboxylation velocity (V c), Michaelis-Menten constants for CO2 (K c) and O2 (K o) and specificity factor (S c/o) were measured at 25 and 35 °C. V c and K c correlated positively, while V c and S c/o were inversely related. Rubisco large subunit genes (rbcL) were sequenced, and predicted corresponding amino acid differences analysed in relation to the corresponding catalytic properties. The effect of replacing native wheat Rubisco with counterparts from closely related species was analysed by modelling the response of photosynthesis to varying CO2 concentrations. The model predicted that two Rubisco enzymes would increase photosynthetic performance at 25 °C while only one of these also increased photosynthesis at 35 °C. Thus, under otherwise identical conditions, catalytic variation in the Rubiscos analysed is predicted to improve photosynthetic rates at physiological CO2 concentrations. Naturally occurring Rubiscos with superior properties amongst the Triticeae tribe can be exploited to improve wheat photosynthesis and crop productivity.

  15. Rubisco catalytic properties of wild and domesticated relatives provide scope for improving wheat photosynthesis

    PubMed Central

    Prins, Anneke; Orr, Douglas J.; Andralojc, P. John; Reynolds, Matthew P.; Carmo-Silva, Elizabete; Parry, Martin A. J.

    2016-01-01

    Rubisco is a major target for improving crop photosynthesis and yield, yet natural diversity in catalytic properties of this enzyme is poorly understood. Rubisco from 25 genotypes of the Triticeae tribe, including wild relatives of bread wheat (Triticum aestivum), were surveyed to identify superior enzymes for improving photosynthesis in this crop. In vitro Rubisco carboxylation velocity (V c), Michaelis–Menten constants for CO2 (K c) and O2 (K o) and specificity factor (S c/o) were measured at 25 and 35 °C. V c and K c correlated positively, while V c and S c/o were inversely related. Rubisco large subunit genes (rbcL) were sequenced, and predicted corresponding amino acid differences analysed in relation to the corresponding catalytic properties. The effect of replacing native wheat Rubisco with counterparts from closely related species was analysed by modelling the response of photosynthesis to varying CO2 concentrations. The model predicted that two Rubisco enzymes would increase photosynthetic performance at 25 °C while only one of these also increased photosynthesis at 35 °C. Thus, under otherwise identical conditions, catalytic variation in the Rubiscos analysed is predicted to improve photosynthetic rates at physiological CO2 concentrations. Naturally occurring Rubiscos with superior properties amongst the Triticeae tribe can be exploited to improve wheat photosynthesis and crop productivity. PMID:26798025

  16. Improved melt flow and physical properties of Mitsui Toatsu's LARC-TPI 1500 series polyimide

    NASA Technical Reports Server (NTRS)

    Ohta, Masahiro; Tamai, Shoji; Towell, T. W.; Johnston, N. J.; Saint Clair, T. L.

    1990-01-01

    The basic thermal properties and melt behavior of an improved form of LARC-TPI polyimide, LARC-TPI 1500, are investigated and compared with those of LARC-TPI 1000 and 2000. The LARC-TPI 1500 powders are thermally stable and melt processable. The absolute molecular weight of the polymer varies from 20,000 to 30,000, indicating recurring unit numbers of about 40-60. The melt flow properties of LARC-TPI 1500 are comparable to those of other engineering plastics, such as PEEK, PSU, and PES. The flexural modulus of injection molded parts of LARC-TPI 1500 is the highest among commercial thermoplastic polymers.

  17. Pharmaceutical study of Yashadabhasma.

    PubMed

    Bhojashettar, Santhosh; Jadar, P G; Rao, V Nageswara

    2012-01-01

    Rasashastra is a branch which deals with the pharmaceutics of Rasaoushadhis. Bhasmas are one among such Rasaoushadhis which are known for their low doses and fast action. A verse from Rasaratnasamuchchaya says that the bhasma prepared by using Mercury as media is of best quality. Following this principle, Yashadabhasma (Zinc calx) was prepared by subjecting it to Samanya shodhana (general purification method for all metals), Vishesha shodhana (specific putification method for Zinc), Jarana (roasting) and Marana (incineration) with Parada(Mercury) as a media under Gajaputa (classical heating system with 1000 cowdung cakes). Yellow colored Yashadabhasma which passed all the classical bhasmaparikshas (tests for properly prepared calx) was obtained after two putas. The bhasma did not pass Nishchandratva(free from shining particles) test after 1(st)puta but was passed after giving it 2(nd)puta.

  18. Pharmaceuticals in the environment: scientific evidence of risks and its regulation

    PubMed Central

    Küster, Anette; Adler, Nicole

    2014-01-01

    During the past two decades scientists, regulatory agencies and the European Commission have acknowledged pharmaceuticals to be an emerging environmental problem. In parallel, a regulatory framework for environmental risk assessment (ERA) of pharmaceutical products has been developed. Since the regulatory guidelines came into force the German Federal Agency (UBA) has been evaluating ERAs for human and veterinary pharmaceutical products before they are marketed. The results show that approximately 10% of pharmaceutical products are of note regarding their potential environmental risk. For human medicinal products, hormones, antibiotics, analgesics, antidepressants and antineoplastics indicated an environmental risk. For veterinary products, hormones, antibiotics and parasiticides were most often discussed as being environmentally relevant. These results are in good correlation with the results within the open scientific literature of prioritization approaches for pharmaceuticals in the environment. UBA results revealed that prospective approaches, such as ERA of pharmaceuticals, play an important role in minimizing problems caused by pharmaceuticals in the environment. However, the regulatory ERA framework could be improved by (i) inclusion of the environment in the risk–benefit analysis for human pharmaceuticals, (ii) improvement of risk management options, (iii) generation of data on existing pharmaceuticals, and (iv) improving the availability of ERA data. In addition, more general and integrative steps of regulation, legislation and research have been developed and are presented in this article. In order to minimize the quantity of pharmaceuticals in the environment these should aim to (i) improve the existing legislation for pharmaceuticals, (ii) prioritize pharmaceuticals in the environment and (iii) improve the availability and collection of pharmaceutical data. PMID:25405974

  19. Pharmaceuticals in the environment: scientific evidence of risks and its regulation.

    PubMed

    Küster, Anette; Adler, Nicole

    2014-11-19

    During the past two decades scientists, regulatory agencies and the European Commission have acknowledged pharmaceuticals to be an emerging environmental problem. In parallel, a regulatory framework for environmental risk assessment (ERA) of pharmaceutical products has been developed. Since the regulatory guidelines came into force the German Federal Agency (UBA) has been evaluating ERAs for human and veterinary pharmaceutical products before they are marketed. The results show that approximately 10% of pharmaceutical products are of note regarding their potential environmental risk. For human medicinal products, hormones, antibiotics, analgesics, antidepressants and antineoplastics indicated an environmental risk. For veterinary products, hormones, antibiotics and parasiticides were most often discussed as being environmentally relevant. These results are in good correlation with the results within the open scientific literature of prioritization approaches for pharmaceuticals in the environment. UBA results revealed that prospective approaches, such as ERA of pharmaceuticals, play an important role in minimizing problems caused by pharmaceuticals in the environment. However, the regulatory ERA framework could be improved by (i) inclusion of the environment in the risk-benefit analysis for human pharmaceuticals, (ii) improvement of risk management options, (iii) generation of data on existing pharmaceuticals, and (iv) improving the availability of ERA data. In addition, more general and integrative steps of regulation, legislation and research have been developed and are presented in this article. In order to minimize the quantity of pharmaceuticals in the environment these should aim to (i) improve the existing legislation for pharmaceuticals, (ii) prioritize pharmaceuticals in the environment and (iii) improve the availability and collection of pharmaceutical data.

  20. Bioplex technology: novel synthetic gene delivery pharmaceutical based on peptides anchored to nucleic acids.

    PubMed

    Simonson, Oscar E; Svahn, Mathias G; Törnquist, Elisabeth; Lundin, Karin E; Smith, C I E

    2005-01-01

    Non-viral gene delivery is an important approach in order to establish safe in vivo gene therapy in the clinic. Although viral vectors currently exhibit superior gene transfer efficacy, the safety aspect of viral gene delivery is a concern. In order to improve non-viral in vivo gene delivery we have designed a pharmaceutical platform called Bioplex (biological complex). The concept of Bioplex is to link functional entities via hybridising anchors, such as Peptide Nucleic Acids (PNA), directly to naked DNA. In order to promote delivery functional entities consisting of biologically active peptides or carbohydrates, are linked to the PNA anchor. The PNA acts as genetic glue and hybridises with DNA in a sequence specific manner. By using functional entities, which elicit receptor-mediated endocytosis, improved endosomal escape and enhance nuclear entry we wish to improve the transfer of genetic material into the cell. An important aspect is that the functional entities should also have tissue-targeting properties in vivo. Examples of functional entities investigated to date are the Simian virus 40 nuclear localisation signal to improve nuclear uptake and different carbohydrate ligands in order to achieve receptor specific uptake. The delivery system is also endowed with regulatory capability, since the release of functional entities can be controlled. The aim is to create a safe, pharmaceutically defined and stable delivery system for nucleic acids with enhanced transfection properties that can be used in the clinic.

  1. Identifying new persistent and bioaccumulative organics among chemicals in commerce II: pharmaceuticals.

    PubMed

    Howard, Philip H; Muir, Derek C G

    2011-08-15

    The goal of this study was to identify commercial pharmaceuticals that might be persistent and bioaccumulative (P&B) and that were not being considered in current wastewater and aquatic environmental measurement programs. We developed a database of 3193 pharmaceuticals from two U.S. Food and Drug Administration (FDA) databases and some lists of top ranked or selling drugs. Of the 3193 pharmaceuticals, 275 pharmaceuticals have been found in the environment and 399 pharmaceuticals were, based upon production volumes, designated as high production volume (HPV) pharmaceuticals. All pharmaceuticals that had reported chemical structures were evaluated for potential bioaccumulation (B) or persistence (P) using quantitative structure property relationships (QSPR) or scientific judgment. Of the 275 drugs detected in the environment, 92 were rated as potentially bioaccumulative, 121 were rated as potentially persistent, and 99 were HPV pharmaceuticals. After removing the 275 pharmaceuticals previously detected in the environment, 58 HPV compounds were identified that were both P&B and 48 were identified as P only. Of the non-HPV compounds, 364 pharmaceuticals were identified that were P&B. This study has yielded some interesting and probable P&B pharmaceuticals that should be considered for further study.

  2. Improvement of dissolution property of poorly water-soluble drug by supercritical freeze granulation.

    PubMed

    Sonoda, Ryoichi; Hara, Yuko; Iwasaki, Tomohiro; Watano, Satoru

    2009-10-01

    The dissolution property of the poorly water-soluble drug, flurbiprofen (FP) was improved by a novel supercritical freeze granulation using supercritical carbon dioxide. Supercritical freeze granulation was defined as a production method of the granulated substances by using the dry ice to generate intentionally for the rapid atomization of the supercritical carbon dioxide to the atmospheric pressure. This process utilized a rapid expansion of supercritical solutions (RESS) process with the mixture of the drug and lactose. In the supercritical freeze granulation, needle-like FP fine particles were obtained which adhered to the surface of lactose particles, which did not dissolve in supercritical carbon dioxide. The number of FP particles that adhered to the surface of particles decreased with an increase in the ratio of lactose added, leading to markedly improve the dissolution rate. This improvement was caused not only by the increase in the specific surface area but also the improvement of the dispersibility of FP in water. It is thus concluded that the supercritical freeze granulation is a useful technique to improve the dissolution property of the poorly water-soluble flurbiprofen.

  3. Explorations in the application of nanotechnology to improve the mechanical properties of composite materials

    NASA Astrophysics Data System (ADS)

    Yang, Cheng

    2007-12-01

    This thesis presents the research achievements on the design, preparation, characterization, and analysis of a series of composite materials. By studying the interface interaction of the composite materials using nanotechnology, we developed composite materials that achieve satisfactory mechanical properties in two classes of materials. Durable press (DP) natural textiles are important consumer products usually achieved by erosslinking the molecules in the textiles to achieve long-term wrinkle resistance, which, however, also leads to the simultaneous significant drop of mechanical properties. Herein, a series of polymeric nanoparticl es were investigated, the application of as little as ˜0.14 wt% addition of the nanoparticles improved the mechanical property of the DP cotton fabric by 56% in tearing resistance and 100% in abrasion resistance; the loss in recovery angle is negligible. The author also studied the enzyme-triggered DP treatments of silk fabrics, as a green process method. After the treatment of enzymes, excellent DP property was achieved with improved strain property. Injectable calcium phosphate powder containing acrylic bone cements are widely used in orthopedic surgery to fix artificial prostheses. However, the bending strength is still unsatisfactory. The author modified the surface of the strontium (Sr) containing hydroxyapatite (HA) filler powders with acrylolpamidronate in order to improve the overall mechanical performance of the bone cement composites. By adding 0.25 wt% of acrylolpamidronate to the Sr-HA nanopowders, more than 19% of the bending strength and more than 23% compression strength of the Sr-HA bone cement were improved. Biological evaluations revealed that these bone cement composites were biocompatible and bioactive in cell culture. The results obtained in this thesis work show an effective method to significantly enhance the mechanical properties of composite materials. Different from other available methods, by developing a

  4. Improving charge transport property and energy transfer with carbon quantum dots in inverted polymer solar cells

    SciTech Connect

    Liu, Chunyu; Chang, Kaiwen; Guo, Wenbin E-mail: chenwy@jlu.edu.cn Li, Hao; Shen, Liang; Chen, Weiyou E-mail: chenwy@jlu.edu.cn; Yan, Dawei E-mail: chenwy@jlu.edu.cn

    2014-08-18

    Carbon quantum dots (Cdots) are synthesized by a simple method and introduced into active layer of polymer solar cells (PSCs). The performance of doped devices was apparently improved, and the highest power conversion efficiency of 7.05% was obtained, corresponding to a 28.2% enhancement compared with that of the contrast device. The charge transport properties, resistance, impedance, and transient absorption spectrum are systematically investigated to explore how the Cdots affect on PSCs performance. This study reveals the importance of Cdots in enhancing the efficiency of PSCs and gives insight into the mechanism of charge transport improvement.

  5. Boron nitride nanotubes included thermally cross-linked gelatin-glucose scaffolds show improved properties.

    PubMed

    Şen, Özlem; Culha, Mustafa

    2016-02-01

    Boron nitride nanotubes (BNNTs) are increasingly investigated for their medical and biomedical applications due to their unique properties such as resistance to oxidation, thermal and electrical insulation, and biocompatibility. BNNTs can be used to enhance mechanical strength of biomedical structures such as scaffolds in tissue engineering applications. In this study, we report the use of BNNTs and hydroxylated BNNTs (BNNT-OH) to improve the properties of gelatin-glucose scaffolds prepared with electrospinning technique. Human dermal fibroblast (HDF) cells are used for the toxicity assessment and cell seeding studies. It is found that the addition of BNNTs into the scaffold does not influence cell viability, decreases the scaffold degradation rate, and improves cell attachment and proliferation compared to only-gelatin scaffold.

  6. Nanomechanical and Corrosion Properties of ZK60 Magnesium Alloy Improved by GD Ion Implantation

    NASA Astrophysics Data System (ADS)

    Tao, Xue Wei; Wang, Zhang Zhong; Zhang, Xiao Bo; Ba, Zhi Xin; Wang, Ya Mei

    2014-09-01

    Gadolinium (Gd) ion implantation with doses from 2.5 × 1016 to 1 × 1017 ions/cm2 into ZK60 magnesium alloy was carried out to improve its surface properties. X-ray photoelectron spectroscopy (XPS), nanoindenter, electrochemical workstation and scanning electron microscope (SEM) were applied to analyze the chemical composition, nanomechanical properties and corrosion characteristics of the implanted layer. The results indicate that Gd ion implantation produces a hybrid-structure protective layer composed of MgO, Gd2O3 and metallic Gd in ZK60 magnesium alloy. The surface hardness and modulus of the Gd implanted magnesium alloy are improved by about 300% and 100%, respectively with the dose of 1 × 1017 ions/cm2, while the slowest corrosion rate of the magnesium alloy in 3.5 wt.% NaCl solution is obtained with the dose of 5 × 1016 ions/cm2.

  7. ENGINEERED INTERFACE CHEMISTRY TO IMPROVE THE MECHANICAL PROPERTIES OF CARBON FIBER COMPOSITES CURED BY ELECTRON BEAM

    SciTech Connect

    Vautard, Frederic; Grappe, Hippolyte A.; Ozcan, Soydan

    2014-01-01

    A reactive sizing was designed to achieve high levels of interfacial adhesion and mechanical properties with a carbon fiber-acrylate system cured by electron beam (EB). The sizing was made of a partially cured epoxy sizing with a high density of pendant functional groups (acrylate functionality) able to generate a covalent bonding with the matrix. The interlaminar shear strength was clearly improved from 61 MPa to 81 MPa (+ 33 %) without any post-processing, reaching a similar value to the one obtained with the same system cured by a thermal treatment. Observation of the fracture profiles clearly highlighted a change in the fracture mechanism from a purely adhesive failure to a cohesive failure. Such improvements of the mechanical properties of carbon fiber composites cured by EB, without any post-cure, have not been reported previously to the best of our knowledge. This constitutes a breakthrough for the industrial development of composites EB curing.

  8. Improving conservation properties of a 5D gyrokinetic semi-Lagrangian code

    NASA Astrophysics Data System (ADS)

    Latu, Guillaume; Grandgirard, Virginie; Abiteboul, Jérémie; Crouseilles, Nicolas; Dif-Pradalier, Guilhem; Garbet, Xavier; Ghendrih, Philippe; Mehrenberger, Michel; Sarazin, Yanick; Sonnendrücker, Eric

    2014-11-01

    In gyrokinetic turbulent simulations, the knowledge of some stationary states can help reducing numerical artifacts. Considering long-term simulations, the qualities of the Vlasov solver and of the radial boundary conditions have an impact on the conservation properties. In order to improve mass and energy conservation mainly, the following methods are investigated: fix the radial boundary conditions on a stationary state, use a 4D advection operator that avoids a directional splitting, interpolate with a delta-f approach. The combination of these techniques in the semi-Lagrangian code gysela leads to a net improvement of the conservation properties in 5D simulations. Contribution to the Topical Issue "Theory and Applications of the Vlasov Equation", edited by Francesco Pegoraro, Francesco Califano, Giovanni Manfredi and Philip J. Morrison.

  9. [Pharmaceutical logistic in turnover of pharmaceutical products of Azerbaijan].

    PubMed

    Dzhalilova, K I

    2009-11-01

    Development of pharmaceutical logistic system model promotes optimal strategy for pharmaceutical functioning. The goal of such systems is organization of pharmaceutical product's turnover in required quantity and assortment, at preset time and place, at a highest possible degree of consumption readiness with minimal expenses and qualitative service. Organization of the optimal turnover chain in the region is offered to start from approximate classification of medicaments by logistic characteristics. Supplier selection was performed by evaluation of timeliness of delivery, quality of delivered products (according to the minimum acceptable level of quality) and time-keeping of time spending for orders delivery.

  10. Coating multilayer material with improved tribological properties obtained by magnetron sputtering

    NASA Astrophysics Data System (ADS)

    Mateescu, A. O.; Mateescu, G.; Balasoiu, M.; Pompilian, G. O.; Lungu, M.

    2017-02-01

    This work is based on the Patent no. RO 128094 B1, granted by the Romanian State Office for Inventions and Trademarks. The goal of the work is to obtain for investigations tribological coatings with multilayer structure with improved tribological properties, deposited by magnetron sputtering process from three materials (sputtering targets). Starting from compound chemical materials (TiC, TiB2 and WC), as sputtering targets, by deposition in argon atmosphere on polished stainless steel, we have obtained, based on the claims of the above patent, thin films of multilayer design with promising results regarding their hardness, elastic modulus, adherence, coefficient of friction and wear resistance. The sputtering process took place in a special sequence in order to ensure better tribological properties to the coating, comparing to those of the individual component materials. The tribological properties, such as the coefficient of friction, are evaluated using the tribometer test.

  11. Use of nickel to improve the mechanical properties of high oxygen underwater wet welds

    SciTech Connect

    Pope, A.M.; Teixeira, J.C.G.; Santos, V.R. dos; Paes, M.T.P.; Liu, S.

    1995-12-31

    The use of oxidizing electrodes for wet welding of offshore structural steels, in spite of their low susceptibility to hydrogen HAZ cracking, is limited, in part by the poor mechanical properties of their weld deposits. Low levels of carbon, manganese and other deoxidizers, together with high oxygen contents seems to be one of the reasons for this low performance. This work investigated the influence of nickel additions on the tensile strength and impact resistance of wet welds deposited at 1.1 m of water depth. It was found that maximum values of toughness and tensile strength occur for nickel contents between 2 and 3 weight percent. Nickel additions also had a strong effect in reducing the grain size of equiaxed ferrite in the reheated region of underwater wet welds thereby improving their mechanical properties. The deterioration of mechanical properties for nickel contents higher than 3 weight percent was attributed to weld metal solidification cracking.

  12. Improved efficient bounding method for DC contingency analysis using reciprocity properties

    SciTech Connect

    Carpentier, J.L.; Di Bono, P.J.; Tournebise, P.J. )

    1994-02-01

    The efficient bounding method for DC contingency analysis is improved using reciprocity properties. Knowing the consequences of the outage of a branch, these properties provide the consequences on that branch of various kinds of outages. This is used in order to reduce computation times and to get rid of some difficulties, such as those occurring when a branch flow is close to its limit before outage. Compensation, sparse vector, sparse inverse and bounding techniques are also used. A program has been implemented for single branch outages and tested on actual French EHV 650 bus network. Computation times are 60% of the Efficient Bounding method. The relevant algorithm is described in detail in the first part of this paper. In the second part, reciprocity properties and bounding formulas are extended for multiple branch outages and for multiple generator or load outages. An algorithm is proposed in order to handle all these cases simultaneously.

  13. Harnessing spectral property of dual wavelength white LED to improve vertical scanning interferometry.

    PubMed

    Chong, Wee Keat; Li, Xiang; Soh, Yeng Chai

    2013-07-01

    Unlike a conventional white light source that emits a continuous and broad spectrum of light, the dual wavelength white light emitting diode (LED) generates white light by mixing blue and yellow lights, so there are two distinct peaks in its intensity spectrum. Prior works had shown that the spectral property of the dual wavelength white LED can affect the vertical scanning interferometry negatively if the spectral effects are not compensated. In this paper, we shall examine this issue by modeling the spectral property and variation of the dual wavelength white LED, followed by investigating its effects on the interference signal of vertical scanning interferometry. Instead of compensating the spectral effects of the dual wavelength white LED, we harness its spectral property to improve the performance of a phase-based height reconstruction algorithm in vertical scanning interferometry.

  14. Discovery of Potent and Selective Tricyclic Inhibitors of Bruton's Tyrosine Kinase with Improved Druglike Properties.

    PubMed

    Wang, Xiaojing; Barbosa, James; Blomgren, Peter; Bremer, Meire C; Chen, Jacob; Crawford, James J; Deng, Wei; Dong, Liming; Eigenbrot, Charles; Gallion, Steve; Hau, Jonathon; Hu, Huiyong; Johnson, Adam R; Katewa, Arna; Kropf, Jeffrey E; Lee, Seung H; Liu, Lichuan; Lubach, Joseph W; Macaluso, Jen; Maciejewski, Pat; Mitchell, Scott A; Ortwine, Daniel F; DiPaolo, Julie; Reif, Karin; Scheerens, Heleen; Schmitt, Aaron; Wong, Harvey; Xiong, Jin-Ming; Xu, Jianjun; Zhao, Zhongdong; Zhou, Fusheng; Currie, Kevin S; Young, Wendy B

    2017-06-08

    In our continued effort to discover and develop best-in-class Bruton's tyrosine kinase (Btk) inhibitors for the treatment of B-cell lymphomas, rheumatoid arthritis, and systemic lupus erythematosus, we devised a series of novel tricyclic compounds that improved upon the druglike properties of our previous chemical matter. Compounds exemplified by G-744 are highly potent, selective for Btk, metabolically stable, well tolerated, and efficacious in an animal model of arthritis.

  15. Biaxial Stretch Improves Elastic Fiber Maturation, Collagen Arrangement, and Mechanical Properties in Engineered Arteries.

    PubMed

    Huang, Angela H; Balestrini, Jenna L; Udelsman, Brooks V; Zhou, Kevin C; Zhao, Liping; Ferruzzi, Jacopo; Starcher, Barry C; Levene, Michael J; Humphrey, Jay D; Niklason, Laura E

    2016-06-01

    Tissue-engineered blood vessels (TEVs) are typically produced using the pulsatile, uniaxial circumferential stretch to mechanically condition and strengthen the arterial grafts. Despite improvements in the mechanical integrity of TEVs after uniaxial conditioning, these tissues fail to achieve critical properties of native arteries such as matrix content, collagen fiber orientation, and mechanical strength. As a result, uniaxially loaded TEVs can result in mechanical failure, thrombus, or stenosis on implantation. In planar tissue equivalents such as artificial skin, biaxial loading has been shown to improve matrix production and mechanical properties. To date however, multiaxial loading has not been examined as a means to improve mechanical and biochemical properties of TEVs during culture. Therefore, we developed a novel bioreactor that utilizes both circumferential and axial stretch that more closely simulates loading conditions in native arteries, and we examined the suture strength, matrix production, fiber orientation, and cell proliferation. After 3 months of biaxial loading, TEVs developed a formation of mature elastic fibers that consisted of elastin cores and microfibril sheaths. Furthermore, the distinctive features of collagen undulation and crimp in the biaxial TEVs were absent in both uniaxial and static TEVs. Relative to the uniaxially loaded TEVs, tissues that underwent biaxial loading remodeled and realigned collagen fibers toward a more physiologic, native-like organization. The biaxial TEVs also showed increased mechanical strength (suture retention load of 303 ± 14.53 g, with a wall thickness of 0.76 ± 0.028 mm) and increased compliance. The increase in compliance was due to combinatorial effects of mature elastic fibers, undulated collagen fibers, and collagen matrix orientation. In conclusion, biaxial stretching is a potential means to regenerate TEVs with improved matrix production, collagen organization, and mechanical

  16. Two different electrical properties can improve transoceanic cable-route mapping

    USGS Publications Warehouse

    Wynn, J.; McGinnis, T.

    2001-01-01

    Induced polarization (IP) measurements made in the marine environment were investigated to map and remotely characterize the top 6-10 meters of the seafloor. The continuous resistivity profiling with cone-penetrometer tests, providing important information to engineers planning transoceanic cable routes, was also described. The IP effect and resistivity were identified as the two electric properties to improve transoceanic cable-route mapping. The measurement of IP and resistivity was found to depend on electrical current.

  17. Biaxial Stretch Improves Elastic Fiber Maturation, Collagen Arrangement, and Mechanical Properties in Engineered Arteries

    PubMed Central

    Huang, Angela H.; Balestrini, Jenna L.; Udelsman, Brooks V.; Zhou, Kevin C.; Zhao, Liping; Ferruzzi, Jacopo; Starcher, Barry C.; Levene, Michael J.; Humphrey, Jay D.

    2016-01-01

    Tissue-engineered blood vessels (TEVs) are typically produced using the pulsatile, uniaxial circumferential stretch to mechanically condition and strengthen the arterial grafts. Despite improvements in the mechanical integrity of TEVs after uniaxial conditioning, these tissues fail to achieve critical properties of native arteries such as matrix content, collagen fiber orientation, and mechanical strength. As a result, uniaxially loaded TEVs can result in mechanical failure, thrombus, or stenosis on implantation. In planar tissue equivalents such as artificial skin, biaxial loading has been shown to improve matrix production and mechanical properties. To date however, multiaxial loading has not been examined as a means to improve mechanical and biochemical properties of TEVs during culture. Therefore, we developed a novel bioreactor that utilizes both circumferential and axial stretch that more closely simulates loading conditions in native arteries, and we examined the suture strength, matrix production, fiber orientation, and cell proliferation. After 3 months of biaxial loading, TEVs developed a formation of mature elastic fibers that consisted of elastin cores and microfibril sheaths. Furthermore, the distinctive features of collagen undulation and crimp in the biaxial TEVs were absent in both uniaxial and static TEVs. Relative to the uniaxially loaded TEVs, tissues that underwent biaxial loading remodeled and realigned collagen fibers toward a more physiologic, native-like organization. The biaxial TEVs also showed increased mechanical strength (suture retention load of 303 ± 14.53 g, with a wall thickness of 0.76 ± 0.028 mm) and increased compliance. The increase in compliance was due to combinatorial effects of mature elastic fibers, undulated collagen fibers, and collagen matrix orientation. In conclusion, biaxial stretching is a potential means to regenerate TEVs with improved matrix production, collagen organization, and mechanical

  18. Ferrocene Containing Copolymers with Improved Electrostatic Dissipation Properties for Advanced Applications

    NASA Technical Reports Server (NTRS)

    Smith, T. M.; Nelson, G. L.

    2005-01-01

    Electrostatic dissipative polymers are used for a variety of functions. Typical methods utilized to transform electrically insulating polymers into either charge dissipative or conductive materials involve incorporating a conductive filler, conductive polymer, oxidizing the surface using plasma, or incorporating surfactants that act as surface wetting agents. Another approach is to synthesize a block copolymer that is expected to result in better electrical properties with minimal impacts to physical, fire, and thermal properties. One such block that can be added into the main chain of polymers is a diol terminated ferrocene oligomer, which is expected to impart electrostatic dissipative properties into the host polymer while concurrently improving the overall fire properties. Previous work with polyurethanes incorporating a ferrocene oligomer into the main chain resulted in much improved fire retardancy. In dealing with electrostatic dissipative materials the important questions are: how easily does the material charge and how quickly can the charge move to ground. One normally describes the materials conductivity, but conductivity only measures the fastest path for an electron not the slowest path. The slowest path is the one of interest, since it is left on the surface and thus can cause discharges. In order to assess ease of charging and decay times corona charge dissipation measurements can accurately assess these properties by introducing a charge on the surface of the material then measuring the surface voltage and the amount of charge deposited. The charge decay curve then will give an indication of a materials electrostatic dissipation properties. Normally, triboelectric testing can be performed, but results vary. Corona charge dissipation results are more repeatable.

  19. Controlling Pharmaceutical Crystallization with Designed Polymeric Heteronuclei

    PubMed Central

    2015-01-01

    To investigate the hypothesis that molecules acting as crystallization inhibitors in solution could be transformed into crystallization promoters, additives were synthesized that mimic the pharmaceuticals acetaminophen and mefenamic acid and also possess polymerizable functionality. It was found that, in solution, these additives face-selectively inhibit crystal growth and lead to overall slower crystal appearance. In contrast, when the tailor-made additives were incorporated into an insoluble polymer, the induction time for the onset of crystal formation for both pharmaceuticals was substantially decreased. This approach now allows for the synthesis of tailor-made polymers that decrease the induction time for crystal appearance and may find application in compounds that are resistant to crystallization or in improving the fidelity of heteronucleation approaches to solid form discovery. PMID:25521054

  20. Controlling pharmaceutical crystallization with designed polymeric heteronuclei.

    PubMed

    Pfund, Laura Y; Price, Christopher P; Frick, Jessica J; Matzger, Adam J

    2015-01-21

    To investigate the hypothesis that molecules acting as crystallization inhibitors in solution could be transformed into crystallization promoters, additives were synthesized that mimic the pharmaceuticals acetaminophen and mefenamic acid and also possess polymerizable functionality. It was found that, in solution, these additives face-selectively inhibit crystal growth and lead to overall slower crystal appearance. In contrast, when the tailor-made additives were incorporated into an insoluble polymer, the induction time for the onset of crystal formation for both pharmaceuticals was substantially decreased. This approach now allows for the synthesis of tailor-made polymers that decrease the induction time for crystal appearance and may find application in compounds that are resistant to crystallization or in improving the fidelity of heteronucleation approaches to solid form discovery.

  1. Synthesis and Characteristic of Xylan-grafted-polyacrylamide and Application for Improving Pulp Properties

    PubMed Central

    Xu, Gui-Bin; Kong, Wei-Qing; Sun, Run-Cang; Ren, Jun-Li

    2017-01-01

    Recently, more attentions have been focused on the exploration of hemicelluloses in the paper industry. In this work, xylan-grafted-polyacrylamide (xylan-g-PAM) biopolymers were synthesized by the graft copolymerization of xylan with acrylamide, and their interaction with fibers was also investigated to improve waste newspaper pulp properties with or without cationic fiber fines. The influences of synthesis conditions were studied on the grafting ratio and the grafting efficiency of biopolymers. Prepared biopolymers were characterized by FTIR, 13C NMR, TGA and rheology. It was found that the grafting of PAM on xylan was conductive to improve xylan properties, such as the solubility in water, rheological features, and thermal stability, and the maximum grafting ratio was achieved to 14.7%. Moreover, xylan-g-PAM could obviously enhance the mechanical properties of waste paper pulps. Xylan-g-PAM also played the dominant role in increasing the strength of paper in the combination with prepared cationic fine fibers. When the amounts of xylan-g-PAM and cationic fiber fines were 1.0 wt % and 0.5 wt %, the mechanical properties such as the tensile index was increased by 49.09%, tear index was increased by 36.54%, and the burst index was increased by 20.67%, when compared with the control handsheets. Therefore, xylan-g-PAM as the new biopolymer could be promising in the application of strength agents for the paper industry as well as cationic fiber fines. PMID:28825640

  2. Improved mechanical properties of A 508 class 3 steel for nuclear pressure vessel through steelmaking

    SciTech Connect

    Kim, J.T.; Kwon, H.K.; Kim, K.C.; Kim, J.M.

    1997-12-31

    The present work is concerned with the steelmaking practices which improve the mechanical properties of the A 508 class 3 steel for reactor pressure vessel. Three kinds of steelmaking practices were applied to manufacture the forged heavy wall shell for reactor pressure vessel, that is, the vacuum carbon deoxidation (VCD), modified VCD containing aluminum and silicon-killing. The segregation of the chemical elements through the thickness was quite small so that the variations of the tensile properties at room temperature were small and the anisotropy of the impact properties was hardly observed regardless of the steelmaking practices. The Charpy V-notch impact properties and the reference nil-ductile transition temperature by drop weight test were significantly improved by the modified VCD and silicon-killing as compared with those of the steel by VCD. Moreover, the plane strain fracture toughness values of the materials by modified VCD and silicon-killing practices was much higher than those of the steel by VCD. These were resulted from the fining of austenite grain size. It was observed that the grain size was below 20 {micro}m (ASTM No. 8.5) when using the modified VCD and silicon-killing, compared to 50 {micro}m (ASTM No. 7.0) when using VCD.

  3. Combined use of bile acids and aminoacids to improve permeation properties of acyclovir.

    PubMed

    Cirri, M; Maestrelli, F; Mennini, N; Mura, P

    2015-07-25

    The aim of this work was to develop a topical formulation with improved permeation properties of acyclovir. Ursodeoxycholic (UDC) and dehydrocholic (DHC) acids were tested as potential enhancers, alone or in combination with different aminoacids. Equimolar binary and ternary systems of acyclovir with cholic acids and basic, hydrophilic or hydrophobic aminoacids were prepared by co-grinding in a high vibrational micromill. Differential scanning calorimetry (DSC) was used to characterize the solid state of these systems, while their permeation properties were evaluated in vitro through a lipophilic artificial membrane. UDC was more than 2 times more effective than DHC in improving drug AUC and permeation rate. As for the ternary systems drug-UDC-aminoacid, only the combined use of l-lysine with UDC acid produced an evident synergistic effect in enhancing drug permeation properties, enabling an almost 3 and 8 times AUC increase compared to the binary UDC system or the pure drug, respectively. The best systems were selected for the development of topical cream formulations, adequately characterized and tested for in vitro drug permeation properties and stability on storage. The better performance revealed by acyclovir-UDC-l-lysine was mainly attributed to the formation of a more permeable activated system induced by the multicomponent co-grinding process.

  4. Optimization of factors to obtain cassava starch films with improved mechanical properties

    NASA Astrophysics Data System (ADS)

    Monteiro, Mayra; Oliveira, Victor; Santos, Francisco; Barros Neto, Eduardo; Silva, Karyn; Silva, Rayane; Henrique, João; Chibério, Abimaelle

    2017-08-01

    In this study, was investigated the optimization of the factors that significantly influenced the mechanical property improvement of cassava starch films through complete factorial design 23. The factors to be analyzed were cassava starch, glycerol and modified clay contents. A regression model was proposed by the factorial analysis, aiming to estimate the condition of the individual factors investigated in the optimum state of the mechanical properties of the biofilm, using the following statistical tool: desirability function and response surface. The response variable that delimits the improvement of the mechanical property of the biofilm is the tensile strength, such improvement is obtained by maximizing the response variable. The factorial analysis showed that the best combination of factor configurations to reach the best response was found to be: with 5g of cassava starch, 10% of glycerol and 5% of modified clay, both percentages in relation to the dry mass of starch used. In addition, the starch biofilm showing the lowest response contained 2g of cassava starch, 0% of modified clay and 30% of glycerol, and was consequently considered the worst biofilm.

  5. Improvements of Thermal, Mechanical, and Water-Resistance Properties of Polybenzoxazine/Boron Carbide Nanocomposites

    NASA Astrophysics Data System (ADS)

    Ramdani, Noureddine; Derradji, Mehdi; Wang, Jun; Mokhnache, El-Oualid; Liu, Wen-Bin

    2016-09-01

    Novel kinds of nanocomposites based on bisphenol A-aniline based polybenzoxazine matrix P(BA-a) and 0 wt.%-20 wt.% boron carbide (B4C) nanoparticles were produced and their properties were evaluated in terms of the nano-B4C content. The thermal conductivity of the P(BA-a) matrix was improved approximately three times from 0.18 W/m K to 0.86 W/m K at 20 wt.% nano-B4C loading, while its coefficient of thermal expansion (CTE) was deceased by 47% with the same nanofiller content. The microhardness properties were significantly improved by adding the B4C nanoparticles. At 20 wt.% of nano-B4C content, dynamic mechanical analysis (DMA) revealed a marked increase in the storage modulus and the glass transition temperature ( T g) of the nanocomposites, reaching 3.9 GPa and 204°C, respectively. Hot water uptake tests showed that the water-resistance of the polybenzoxazine matrix was increased by filling with nano-B4C nano-filler. The morphological analysis reflected that the improvements obtained in the mechanical and thermal properties are related to the uniform dispersion of the nano-B4C particles and their strong adhesion to the P(BA-a) matrix.

  6. Improvement of mechanical properties and life extension of high reliability structural components by laser shock processing

    NASA Astrophysics Data System (ADS)

    Ocaña, J. L.; Morales, M.; Porro, J. A.; Iordachescu, D.; Díaz, M.; Ruiz de Lara, L.; Correa, C.

    2011-05-01

    Profiting by the increasing availability of laser sources delivering intensities above 109 W/cm2 with pulse energies in the range of several Joules and pulse widths in the range of nanoseconds, laser shock processing (LSP) is being consolidating as an effective technology for the improvement of surface mechanical and corrosion resistance properties of metals and is being developed as a practical process amenable to production engineering. The main acknowledged advantage of the laser shock processing technique consists on its capability of inducing a relatively deep compression residual stresses field into metallic alloy pieces allowing an improved mechanical behaviour, explicitly, the life improvement of the treated specimens against wear, crack growth and stress corrosion cracking. Following a short description of the theoretical/computational and experimental methods developed by the authors for the predictive assessment and experimental implementation of LSP treatments, experimental results on the residual stress profiles and associated surface properties modification successfully reached in typical materials (specifically Al and Ti alloys) under different LSP irradiation conditions are presented. In particular, the analysis of the residual stress profiles obtained under different irradiation parameters and the evaluation of the corresponding induced surface properties as roughness and wear resistance are presented.

  7. A method to improve electrical properties of BiFeO3 thin films.

    PubMed

    Wu, Jiagang; Wang, John; Xiao, Dingquan; Zhu, Jianguo

    2012-03-01

    A method is used to improve the electrical properties of BiFeO(3) thin films by modifying the Bi content in ceramic targets, where all thin films were prepared on SrRuO(3)/Pt/TiO(2)/SiO(2)/Si(100) substrates by radio frequency sputtering. The Bi content in the ceramic target strongly affects the electrical properties of BiFeO(3) thin films. BiFeO(3) thin films prepared by using the ceramic target of Bi/Fe ≈ 1.15 with a molar ratio demonstrate a low leakage current density and a low dielectric loss. Moreover, a larger remanent polarization of 2P(r) ≈ 167.6 μC/cm(2) is also demonstrated for the BiFeO(3) thin films prepared by using the ceramic target of Bi/Fe ≈ 1.15, together with an improved fatigue behavior. Therefore, it is an effective way to improve the electrical properties of bismuth ferrite thin films by modifying the Bi content in ceramic targets. © 2012 American Chemical Society

  8. [Pharmaceuticals: a strategic national industry].

    PubMed

    Hollender, Louis

    2004-01-01

    Asked by Mme Nicole Fontaine, Delegate Minister of Industry, to help the government with its ongoing reflections on pharmaceutical industrial strategy, and the necessary autonomy of our country in the face of major commercial threats, a working group of the French National Academy of Medicine consulted representatives of five French and two foreign major drug companies. Their statements can be classified in four categories:--the first concerns new medications, which must be approved successively by three commissions, whose opinions are often delayed and influenced by economic considerations;--second, public and private research are both insufficient and are sometimes hindered by procedural restrictions,--third, the pharmaceutical industry is unable to deal with frequent and unforseeable political upheavals,--France does not adequately recognize the strategic importance of the pharmaceutical industry in the national economy. The Academy makes several recommendations: the French pharmaceutical industry should be considered as a national priority, the strategic importance of national pharmaceutical companies should be recognized, a multi-annual contract should be signed with manufacturers, clinical trials should be facilitated in France, relationships between the national pharmaceutical industry and public research structures should be reinforced, and an inter-ministerial Council on Pharmaceuticals should be created. This study was supplemented by a survey of veterinary medications, the results and conclusions of which are very similar to those outlined above for human medicines.

  9. Elemental Impurities in Pharmaceutical Excipients.

    PubMed

    Li, Gang; Schoneker, Dave; Ulman, Katherine L; Sturm, Jason J; Thackery, Lisa M; Kauffman, John F

    2015-12-01

    Control of elemental impurities in pharmaceutical materials is currently undergoing a transition from control based on concentrations in components of drug products to control based on permitted daily exposures in drug products. Within the pharmaceutical community, there is uncertainty regarding the impact of these changes on manufactures of drug products. This uncertainty is fueled in part by a lack of publically available information on elemental impurity levels in common pharmaceutical excipients. This paper summarizes a recent survey of elemental impurity levels in common pharmaceutical excipients as well as some drug substances. A widely applicable analytical procedure was developed and was shown to be suitable for analysis of elements that are subject to United States Pharmacopoeia Chapter <232> and International Conference on Harmonization's Q3D Guideline on Elemental Impurities. The procedure utilizes microwave-assisted digestion of pharmaceutical materials and inductively coupled plasma mass spectrometry for quantitative analysis of these elements. The procedure was applied to 190 samples from 31 different excipients and 15 samples from eight drug substances provided through the International Pharmaceutical Excipient Council of the Americas. The results of the survey indicate that, for the materials included in the study, relatively low levels of elemental impurities are present. © 2015 The Authors. Journal of Pharmaceutical Sciences published by Wiley Periodicals, Inc. and the American Pharmacists Association.

  10. [Chapter 1. A contemporary history of the Japanese pharmaceutical industry (1980-2010). A contemporary history of the Japanese Pharmaceutical Industry (1980-2010) Task Force].

    PubMed

    2014-01-01

    This publication, commemorating the sixty years since the founding of Japan Society for the History of Pharmacy (JSHP), provides an overview of the Japanese pharmaceutical industry over a thirty-year span from 1980 to 2010. In the first section, entitled Medical Evolution: The Growth Period for Pharmaceutical Products, and the second section, "Patient-Based Medicine: The Period of Information Prioritization, the following themes are examined. Changes in Drug Pricing Policies, Promotion of Bungyō (separation of prescription from dispensing), Measures to Improve the Safety of Pharmaceutical Products; Appropriate Use of Pharmaceutical Products, Drug Discovery: Changes in Pharmaceutical Product Development and Actual Conditions in the Domestic Launch of New Medicines; Marketing (Medical Representative) Reforms, Pharmaceutical Industry Mergers and Acquisitions, Internationalization of the Pharmaceutical Industry. The following papers are provided as further references to support the conclusions made in the sections above. Changes in Japanese Drug Discovery Technologies and Drug Development. Japan's Pharmaceutical Market and Shifts in Manufacturing and Sales. Changes in Clinical Trials in Japan and Appropriate Use of Pharmaceuticals. Internationalization of the Japanese Pharmaceutical Industry.

  11. Assimilation of remotely-sensed optical properties to improve marine biogeochemistry modelling

    NASA Astrophysics Data System (ADS)

    Ciavatta, Stefano; Torres, Ricardo; Martinez-Vicente, Victor; Smyth, Timothy; Dall'Olmo, Giorgio; Polimene, Luca; Allen, J. Icarus

    2014-09-01

    In this paper we evaluate whether the assimilation of remotely-sensed optical data into a marine ecosystem model improves the simulation of biogeochemistry in a shelf sea. A localized Ensemble Kalman filter was used to assimilate weekly diffuse light attenuation coefficient data, Kd(443) from SeaWiFs, into an ecosystem model of the western English Channel. The spatial distributions of (unassimilated) surface chlorophyll from satellite, and a multivariate time series of eighteen biogeochemical and optical variables measured in situ at one long-term monitoring site were used to evaluate the system performance for the year 2006. Assimilation reduced the root mean square error and improved the correlation with the assimilated Kd(443) observations, for both the analysis and, to a lesser extent, the forecast estimates, when compared to the reference model simulation. Improvements in the simulation of (unassimilated) ocean colour chlorophyll were less evident, and in some parts of the Channel the simulation of this data deteriorated. The estimation errors for the (unassimilated) in situ data were reduced for most variables with some exceptions, e.g. dissolved nitrogen. Importantly, the assimilation adjusted the balance of ecosystem processes by shifting the simulated food web towards the microbial loop, thus improving the estimation of some properties, e.g. total particulate carbon. Assimilation of Kd(443) outperformed a comparative chlorophyll assimilation experiment, in both the estimation of ocean colour data and in the simulation of independent in situ data. These results are related to relatively low error in Kd(443) data, and because it is a bulk optical property of marine ecosystems. Assimilation of remotely-sensed optical properties is a promising approach to improve the simulation of biogeochemical and optical variables that are relevant for ecosystem functioning and climate change studies.

  12. A composite athletic tape with hyperelastic material properties improves and maintains ankle support during exercise.

    PubMed

    Siegler, Sorin; Marchetto, Paul; Murphy, Daniel J; Gadikota, Hemanth R

    2011-12-01

    Controlled laboratory testing using a single-group, prospective, repeated-measures design. To compare the material properties of a hyperelastic athletic tape to a conventional tape and to compare the passive ankle support of these tapes before and after exercise. The near-linear material properties of conventional athletic tape may interfere with ankle motion, resulting in reduced athletic performance. Conventional athletic tape is also known to lose much of its initial support during exercise. It was assumed that a tape constructed of Kevlar fibers embedded in a silicon matrix would possess hyperelastic material properties that would improve ankle support. A tensile testing machine was used to determine the tensile material properties of 11 samples of conventional and hyperelastic tape. The ankles of 11 young, healthy athletes were taped, one ankle with conventional tape and the other ankle with hyperelastic tape. The passive ankle support of each tape was measured with an instrumented linkage (the ankle flexibility tester) before and after 30 minutes of exercise. The composite tape had a significantly higher load to failure than the conventional tape. It had significantly lower initial stiffness and higher late stiffness than conventional tape, thus demonstrating highly hyperelastic behavior. The hyperelastic tape maintained a significantly higher portion of its support during the 30 minutes of exercise than the conventional tape. Composite athletic tape with highly hyperelastic properties can be constructed and maintains a larger portion of its support during short-duration exercises (less than 30 minutes) than conventional athletic tape.

  13. Pharmaceutical industry and trade liberalization using computable general equilibrium model.

    PubMed

    Barouni, M; Ghaderi, H; Banouei, Aa

    2012-01-01

    Computable general equilibrium models are known as a powerful instrument in economic analyses and widely have been used in order to evaluate trade liberalization effects. The purpose of this study was to provide the impacts of trade openness on pharmaceutical industry using CGE model. Using a computable general equilibrium model in this study, the effects of decrease in tariffs as a symbol of trade liberalization on key variables of Iranian pharmaceutical products were studied. Simulation was performed via two scenarios in this study. The first scenario was the effect of decrease in tariffs of pharmaceutical products as 10, 30, 50, and 100 on key drug variables, and the second was the effect of decrease in other sectors except pharmaceutical products on vital and economic variables of pharmaceutical products. The required data were obtained and the model parameters were calibrated according to the social accounting matrix of Iran in 2006. The results associated with simulation demonstrated that the first scenario has increased import, export, drug supply to markets and household consumption, while import, export, supply of product to market, and household consumption of pharmaceutical products would averagely decrease in the second scenario. Ultimately, society welfare would improve in all scenarios. We presents and synthesizes the CGE model which could be used to analyze trade liberalization policy issue in developing countries (like Iran), and thus provides information that policymakers can use to improve the pharmacy economics.

  14. Pharmaceutical Industry and Trade Liberalization Using Computable General Equilibrium Model

    PubMed Central

    Barouni, M; Ghaderi, H; Banouei, AA

    2012-01-01

    Background Computable general equilibrium models are known as a powerful instrument in economic analyses and widely have been used in order to evaluate trade liberalization effects. The purpose of this study was to provide the impacts of trade openness on pharmaceutical industry using CGE model. Methods: Using a computable general equilibrium model in this study, the effects of decrease in tariffs as a symbol of trade liberalization on key variables of Iranian pharmaceutical products were studied. Simulation was performed via two scenarios in this study. The first scenario was the effect of decrease in tariffs of pharmaceutical products as 10, 30, 50, and 100 on key drug variables, and the second was the effect of decrease in other sectors except pharmaceutical products on vital and economic variables of pharmaceutical products. The required data were obtained and the model parameters were calibrated according to the social accounting matrix of Iran in 2006. Results: The results associated with simulation demonstrated that the first scenario has increased import, export, drug supply to markets and household consumption, while import, export, supply of product to market, and household consumption of pharmaceutical products would averagely decrease in the second scenario. Ultimately, society welfare would improve in all scenarios. Conclusion: We presents and synthesizes the CGE model which could be used to analyze trade liberalization policy issue in developing countries (like Iran), and thus provides information that policymakers can use to improve the pharmacy economics. PMID:23641393

  15. Development of hydrophilic GO-ZnO/PES membranes for treatment of pharmaceutical wastewater.

    PubMed

    Mahlangu, O T; Nackaerts, R; Mamba, B B; Verliefde, A R D

    2017-07-01

    Membrane application in water reclamation is challenged by fouling which deteriorates membrane performance in terms of permeate flux and solute rejection. Several studies focusing on antifouling membranes incorporated with nanoparticles have been carried out, but these membranes are not yet a viable solution due to their high energy requirements and inability to completely remove or degrade trace organic compounds (TOrCs). Therefore, this study aims at fabricating polyethersulfone (PES) membranes for treatment of pharmaceutical wastewater by using a unique membrane synthesis approach. PES membranes were synthesised by casting two different solutions before coagulation. Therefore, the synthesis technique was called 'double-casting phase inversion'. The membranes were impregnated with nanohybrid graphene oxide-zinc oxide (GO-ZnO) to increase their hydrophilicity, rejection of pharmaceuticals (by decreasing membrane-solute hydrophobic interactions), resistance to organic fouling and photodegradation properties. The addition of GO-ZnO increased membrane hydrophilicity and pure water permeability. The rejection of TOrCs and anti-fouling properties were also improved due to a reduction in membrane-solute and membrane-foulant hydrophobic interactions, respectively. In addition to improved TOrC rejection properties and resistance to fouling, GO-ZnO/PES membranes degraded Brilliant Black.

  16. Improving the physical properties crunchiness of potato crisps by pretreatment techniques and vacuum frying

    NASA Astrophysics Data System (ADS)

    Tran, Mai T. T.; Chen, Xiao Dong

    2013-08-01

    Vacuum frying with pre-treatment of potato crisps are potentially effective processes on the improving the crispness of potato crisps. Pre-drying and subsequent sugar dipping are considered as an advantageous process as the pre-treatment of potato crisps to reduce considerable amount of oil uptake. In this study, potato crisps were blanched, pre-dried, and dipped in the solution of sugar (23.07%, in 2 seconds) before vacuum frying at 120 °C, 110 °C with vacuum pressures, which is 150 mbars. The results were collected by testing the crispiness of the potato crisps with the three-point-support method and using an Instron Universal Testing Machine through the texture parameters: Maximum Peak Force; Slope of Initial Tangent, Hardness, Stiffness, Firmness, Modulus of Elasticity and Maximum Tensile Stress. There was a significant improving in physical properties of crisps observed. Crisps that had been pre- treatment and vacuum- fried at 110 °C (150 mbars) had much improving in crispness (50%) including the hardness (170%), stiffness (140%), firmness (50%) and modulus of elasticity (60%) compared with normal frying at 180 °C without pretreatment and vacuum frying. The effect of vacuum frying and the pre-treatment technique on the improving the physical properties of crisps was evaluated. The shrinkage of potato crisps after frying was also considered in this research. The color and microstructure of potato crisps with pre-treatments and vacuum frying have also been obtained.

  17. Optimization of the tumor microenvironment and nanomedicine properties simultaneously to improve tumor therapy

    PubMed Central

    Jiang, Ting; Wang, Lanting; Mei, Heng; Lu, Heng; Hu, Yu; Pang, Zhiqing

    2016-01-01

    Effective delivery of nanomedicines to tumor tissues depends on both the tumor microenvironment and nanomedicine properties. Accordingly, tumor microenvironment modification or advanced design of nanomedicine was emerging to improve nanomedicine delivery to tumors. However, few studies have emphasized the necessity to optimize the tumor microenvironment and nanomedicine properties simultaneously to improve tumor treatment. In the present study, imatinib mesylate (IMA) was used to normalize the tumor microenvironment including platelet-derived growth factor receptor-β expression inhibition, tumor vessel normalization, and tumor perfusion improvement as demonstrated by immunofluorescence staining. In addition, the effect of tumor microenvironment normalization on tumor delivery of nanomedicines with different sizes was carefully investigated. It was shown that IMA treatment significantly reduced the accumulation of nanoparticles (NPs) around 110 nm but enhanced the accumulation of micelles around 23 nm by in vivo fluorescence imaging experiment. Furthermore, IMA treatment limited the distribution of NPs inside tumors but increased that of micelles with a more homogeneous pattern. Finally, the anti-tumor efficacy study displayed that IMA pretreatment could significantly increase the therapeutic effects of paclitaxel-loaded micelle