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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. 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.

  4. 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.

  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. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  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. 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.

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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 .

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. [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.

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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)

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. How experimental design can improve the validation process. Studies in pharmaceutical analysis.

    PubMed

    Furlanetto, S; Orlandini, S; Mura, P; Sergent, M; Pinzauti, S

    2003-11-01

    A critical discussion about the possibility of improving the method validation process by means of experimental design is presented. The reported multivariate strategies concern the evaluation of the performance parameters robustness and intermediate precision, and the optimisation of bias and repeatability. In particular, accuracy and precision improvement constitutes a special subset of experimental design in which the bias and the relative standard deviation of the assay are optimised. D-optimal design was used in order to plan experiments for this aim. The analytical methods considered were capillary electrophoresis, HPLC, adsorptive stripping voltammetry and differential pulse polarography. All methods were applied to real pharmaceutical analysis problems.

  5. 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.

  6. [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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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…

  20. 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…

  1. 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.

  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. 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.

  4. 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.

  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. 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.

  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. 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

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. Improving vegetable oil properties for lubrication methods

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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....

  20. 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.

  1. [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.

  2. 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.

  3. 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.

  4. 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.

  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. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  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. 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

  16. 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.

  17. 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.

  18. [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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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...

  19. 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...

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  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. 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.

  9. 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.

  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. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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

    2017-01-03

    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.

  4. [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.

  5. 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

  6. 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

  7. Nano hydroxyapatite-coated implants improve bone nanomechanical properties.

    PubMed

    Jimbo, R; Coelho, P G; Bryington, M; Baldassarri, M; Tovar, N; Currie, F; Hayashi, M; Janal, M N; Andersson, M; Ono, D; Vandeweghe, S; Wennerberg, A

    2012-12-01

    Nanostructure modification of dental implants has long been sought as a means to improve osseointegration through enhanced biomimicry of host structures. Several methods have been proposed and demonstrated for creating nanotopographic features; here we describe a nanoscale hydroxyapatite (HA)-coated implant surface and hypothesize that it will hasten osseointegration and improve its quality relative to that of non-coated implants. Twenty threaded titanium alloy implants, half prepared with a stable HA nanoparticle surface and half grit-blasted, acid-etched, and heat-treated (HT), were inserted into rabbit femurs. Pre-operatively, the implants were morphologically and topographically characterized. After 3 weeks of healing, the samples were retrieved for histomorphometry. The nanomechanical properties of the surrounding bone were evaluated by nanoindentation. While both implants revealed similar bone-to-implant contact, the nanoindentation demonstrated that the tissue quality was significantly enhanced around the HA-coated implants, validating the postulated hypothesis.

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. [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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  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. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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)

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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...

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  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. 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.

  11. 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.

  12. 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

  13. 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...

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. 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…

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. [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.

  11. 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

  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. Improving the cold flow properties of biodiesel by fractionation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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. ...

  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. 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.

  16. 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.

  17. 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.

  18. [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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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…

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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)

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  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. 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...

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. [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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. Improvement of High Temperature Mechanical Property by Precipitation Hardening of Reduced Activation Ferritic/Martensitic Steels

    SciTech Connect

    Sakasegawa, H.; Kohyama, A.; Katoh, Y.; Tamura, M.; Khono, Y.; Kimura, A.

    2003-07-15

    Reduced Activation Ferritic/Martensitic steels (RAFs) are leading candidates for blanket and first wall structures of the D-T fusion reactors. Recently, in order to achieve better efficiency of energy conversion by using RAFs in advanced blanket systems, improvement of high temperature mechanical property of RAFs is desired. In this work, experimental alloys, FETA-series (Fe-Ta-C or N) steels, were prepared to observe precipitation hardening mechanism by MX-type particles at elevated temperatures in detail. According to the results, innovative improvement of creep property can be achieved by applying of precipitation hardening by very fine TaX (X=C, N) particles. With increasing tantalum content, finer dispersion of MX-type particles, dislocation structures and sub-grain structures were observed by TEM (Transmission Electron Microscopy). These fine structures contributed to the improvement of creep property.

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  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. 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.

  13. 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%.

  14. 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.

  15. 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

  16. 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…

  17. 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...

  18. 77 FR 44515 - Airport Improvement Program (AIP): Policy Regarding Access to Airports From Residential Property

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-30

    ... Federal Aviation Administration 14 CFR Chapter I Airport Improvement Program (AIP): Policy Regarding Access to Airports From Residential Property AGENCY: Federal Aviation Administration (FAA), DOT. ACTION... policy, based on Federal law, concerning through-the-fence access to a federally obligated airport...

  19. Peroxidase mediated conjugation of corn fibeer gum and bovine serum albumin to improve emulsifying properties

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  20. 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.

  1. 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

  2. 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.

  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. 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…

  5. 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.

  6. 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

  7. 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...

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  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. 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.

  14. 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.

  15. [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.

  16. 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.

  17. [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.

  18. 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.

  19. 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

  20. [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.

  1. 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

  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. 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.

  4. 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.

  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. 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.

  7. 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

  8. Pharmaceutical and biomedical potential of surface engineered dendrimers.

    PubMed

    Satija, Jitendra; Gupta, Umesh; Jain, Narendra Kumar

    2007-01-01

    Dendrimers are hyperbranched, globular, monodisperse, nanometric polymeric architecture, having definite molecular weight, shape, and size (which make these an inimitable and optimum carrier molecule in pharmaceutical field). Dendritic architecture is having immense potential over the other carrier systems, particularly in the field of drug delivery because of their unique properties, such as structural uniformity, high purity, efficient membrane transport, high drug pay load, targeting potential, and good colloidal, biological, and shelf stability. Despite their enormous applicability in different areas, the inherent cytotoxicity, reticuloendothelial system (RES) uptake, drug leakage, immunogenicity, and hemolytic toxicity restricted their use in clinical applications, which is primarily associated with cationic charge present on the periphery due to amine groups. To overcome this toxic nature of dendrimers, some new types of nontoxic, biocompatible, and biodegradable dendrimers have been developed (e.g., polyester dendrimer, citric acid dendrimer, arginine dendrimer, carbohydrate dendrimers, etc.). The surface engineering of parent dendrimers is graceful and convenient strategy, which not only shields the positive charge to make this carrier more biomimetic but also improves the physicochemical and biological behavior of parent dendrimers. Thus, surface modification chemistry of parent dendrimers holds promise in pharmaceutical applications (such as solubilization, improved drug encapsulation, enhanced gene transfection, sustained and controlled drug release, intracellular targeting) and in the diagnostic field. Development of multifunctional dendrimer holds greater promise toward the biomedical applications because a number of targeting ligands determine specificity in the same manner as another type of group would secure stability in biological milieu and prolonged circulation, whereas others facilitate their transport through cell membranes. Therefore, as a

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. PHARMACEUTICALS AND PERSONAL CARE PRODUCTS ...

    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

  15. OVERVIEW OF PHARMACEUTICALS AND PERSONAL ...

    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

  16. ORIGINS AND RAMIFICATIONS 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

  17. PHARMACEUTICALS IN SOURCE WATER - OVERVIEW ...

    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

  18. INTRODUCTION TO PHARMACEUTICALS AND PERSONAL ...

    EPA Pesticide Factsheets

    There is no abstract 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. Subtask 3: T

  19. PHARMACEUTICAL AND PERSONAL CARE PRODUCTS ...

    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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Pharmaceutical applications of vibrational chemical imaging and chemometrics: a review.

    PubMed

    Gendrin, C; Roggo, Y; Collet, C

    2008-11-04

    The emergence of chemical imaging (CI) has gifted spectroscopy an additional dimension. Chemical imaging systems complement chemical identification by acquiring spatially located spectra that enable visualization of chemical compound distributions. Such techniques are highly relevant to pharmaceutics in that the distribution of excipients and active pharmaceutical ingredient informs not only a product's behavior during manufacture but also its physical attributes (dissolution properties, stability, etc.). The rapid image acquisition made possible by the emergence of focal plane array detectors, combined with publication of the Food and Drug Administration guidelines for process analytical technology in 2001, has heightened interest in the pharmaceutical applications of CI, notably as a tool for enhancing drug quality and understanding process. Papers on the pharmaceutical applications of CI have been appearing in steadily increasing numbers since 2000. The aim of the present paper is to give an overview of infrared, near-infrared and Raman imaging in pharmaceutics. Sections 2 and 3 deal with the theory, device set-ups, mode of acquisition and processing techniques used to extract information of interest. Section 4 addresses the pharmaceutical applications.

  5. ENVIRONMENTAL STEWARDSHIP OF PHARMACEUTICALS ...

    EPA Pesticide Factsheets

    The occurrence of pharmaceuticals and personal care products (PPCPS) as environmental pollutants is a multifaceted issue whose scope continues to become better delineated since the escalation of conceited attention beginning in the 1980s. PPCPs typically occur as trace environmental pollutants (primarily in surface but also in ground waters) as a result of their widespread, continuous, combined usage in a broad range of human and veterinary therapeutic activities and practices. With respect to the risk-assessment paradigm the growing body of published work has focused primarily on the origin and occurrence of these substances. Comparatively less is known about human and ecological exposure, and even less about the documented or potential hazards associated with trace exposure to these anthropogenic substances, many of which are highly bioactive and perpetually present in many aquatic locales. 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/m

  6. Biricodar. Vertex Pharmaceuticals.

    PubMed

    Dey, Saibal

    2002-05-01

    Vertex is developing biricodar as a chemosensitizing agent designed to restore the effectiveness of chemotherapeutic agents in tumor multidrug resistance. By November 1998, phase II trials had commenced for biricodar, in combination with chemotherapy, for five common cancer indications: breast, ovarian, soft-tissue sarcomas, small cell lung cancer and prostate cancer. Phase II trials were ongoing in January 2002. By March 2000, Vertex was the sole developer of biricodar, as an agreement made in 1996 with BioChem Pharma (now Shire Pharmaceuticals), for the development and marketing of biricodar in Canada was terminated. Biricodar is the free base compound, which also has a citrate salt analog known as VX-710-3. Vertex has published three patents, WO-09615101, WO-09636630 and WO-09736869, disclosing derivatives of biricodar that are claimed for the treatment of multidrug resistant protein and P-glycoprotein-mediated multidrug resistant tumors. In January 2002, a Banc of America analyst report forecast that biricodar had a 30% chance of reaching the market with a launch date in the second half of 2005, with peak sales estimated at $250 million.

  7. OSI-774 OSI Pharmaceuticals.

    PubMed

    Norman, P

    2001-02-01

    OSI-774 (formerly CP-358774), a quinazoline derivative, is an orally active epidermal growth factor receptor (EGFR) inhibitor which was originally under joint development by Pfizer and OSI Pharmaceuticals (formerly Oncogene Science) for the potential treatment of cancer (eg, ovarian, non-small cell lung cancer (NSCLC) and head and neck). It is being evaluated in phase II trials [304305], [372201]. On 8 January 2001, OSI announced that it had signed an agreement with Roche and Genentech for the global co-development and marketing of OSI-774. The agreement with Genentech covers the United States, that with Roche the rest of the world [395371], [395526]. In June 2000, OSI gained all development and marketing rights for OSI-774 following Pfizer's merger with Warner-Lambert [371439]. In September 2000, Pfizer transferred the IND dossierfor OSI-774 to OSI ahead of the timeline agreed in the June 2000 development and marketing rights agreement [383786]. The phase II trials will assess OSI-774 both as a single agent and in combination with existing chemotherapy regimens [347783]. Phase III trials are expected to be initiated in 2001 [347783]. In October 2000, Lehman Brothers predicted that OSI-774 would move into pivotal trials in thefirst half of 2001 and that the drug would be launched in 2003. The analysts also estimated worldwide sales of US $66 million, $285 million and $461 million in 2003, 2004 and 2005, respectively, and peak sales in excess of US $500 million [395189].

  8. PHARMACEUTICALS AS UBIQUITOUS POLLUTANTS ...

    EPA Pesticide Factsheets

    Those chemical pollutants that are regulated under various international, federal, and state programs represent but a small fraction of the universe of chemicals that occur in the environment as a result of both natural processes and human influence. Although this galaxy of targeted chemicals might be minuscule compared with the universe of both known and yet-to-be identified chemicals, an implicit assumption is that these selective lists of chemicals are responsible for the most significant share of risk with respect to environmental or economic impairment or to human health. Pharmaceuticals and personal care products (PPCPs) comprise a particularly large and diverse array of unregulated pollutants that occur in the environment from the combined activities and actions of multitudes of individuals as well as from veterinary and agricultural use. Although the concentration of any individual PPCP rarely ever exceeds the sub-ppm level (if present in drinking water, concentrations of individual PPCPs are generally less than the ppt-ppb level), evidence is accumulating that these trace-Ievel pollutants are ubiquitous, they can have a continuous presence regardless of environmental half-lives ( e.g., where sanitary wastewaters enter the environment), and the numbers of distinct and varied chemical entities could be extremely large (given that thousands are in commercial use). The research focused on in the subtasks is the development and application of state-of the-ar

  9. 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.

  10. Prioritizing pharmaceuticals in municipal wastewater

    EPA Science Inventory

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

  11. [PICS: pharmaceutical inspection cooperation scheme].

    PubMed

    Morénas, J

    2009-01-01

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

  12. Laser irradiation to produce amorphous pharmaceuticals.

    PubMed

    Titapiwatanakun, Varin; Tankul, Junlathip; Basit, Abdul W; Gaisford, Simon

    2016-11-30

    Using a high-power CO2 laser to irradiate powder beds, it was possible to induce phase transformation to the amorphous state. Irradiation of a model drug, indometacin, resulted in formation of a glass. Varying the settings of the laser (power and raster speed) was shown to change the physicochemical properties of the glasses produced and all irradiated glasses were found to be more stable than a reference glass produced by melt-quenching. Irradiation of a powder blend of paracetamol and polyvinylpyrrolidone K30 was found to produce a solid amorphous dispersion. The results suggest that laser-irradiation might be a useful method for making amorphous pharmaceuticals.

  13. Globalization in the pharmaceutical industry, Part II.

    PubMed

    Casadio Tarabusi, C; Vickery, G

    1998-01-01

    This is the second of a two-part report on the pharmaceutical industry. Part II begins with a discussion of foreign direct investment and inter-firm networks, which covers international mergers, acquisitions, and minority participation; market shares of foreign-controlled firms; international collaboration agreements (with a special note on agreements in biotechnology); and licensing agreements. The final section of the report covers governmental policies on health and safety regulation, price regulation, industry and technology, trade, foreign investment, protection of intellectual property, and competition.

  14. 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 micelles. All-together, a new strategy to improve nanomedicine delivery to tumor was provided by optimizing both nanomedicine size and the tumor microenvironment simultaneously, and it will have great potential in clinics for tumor treatment. PMID:27566585

  15. 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.

  16. Dropwise additive manufacturing of pharmaceutical products for solvent-based dosage forms.

    PubMed

    Hirshfield, Laura; Giridhar, Arun; Taylor, Lynne S; Harris, Michael T; Reklaitis, Gintaras V

    2014-02-01

    In recent years, the US Food and Drug Administration has encouraged pharmaceutical companies to develop more innovative and efficient manufacturing methods with improved online monitoring and control. Mini-manufacturing of medicine is one such method enabling the creation of individualized product forms for each patient. This work presents dropwise additive manufacturing of pharmaceutical products (DAMPP), an automated, controlled mini-manufacturing method that deposits active pharmaceutical ingredients (APIs) directly onto edible substrates using drop-on-demand (DoD) inkjet printing technology. The use of DoD technology allows for precise control over the material properties, drug solid state form, drop size, and drop dynamics and can be beneficial in the creation of high-potency drug forms, combination drugs with multiple APIs or individualized medicine products tailored to a specific patient. In this work, DAMPP was used to create dosage forms from solvent-based formulations consisting of API, polymer, and solvent carrier. The forms were then analyzed to determine the reproducibility of creating an on-target dosage form, the morphology of the API of the final form and the dissolution behavior of the drug over time. DAMPP is found to be a viable alternative to traditional mass-manufacturing methods for solvent-based oral dosage forms.

  17. 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.

  18. Quantitative on-line preconcentration-liquid chromatography coupled with tandem mass spectrometry method for the determination of pharmaceutical compounds in water.

    PubMed

    Idder, Salima; Ley, Laurent; Mazellier, Patrick; Budzinski, Hélène

    2013-12-17

    One of the current environmental issues concerns the presence and fate of pharmaceuticals in water bodies as these compounds may represent a potential environmental problem. The characterization of pharmaceutical contamination requires powerful analytical method able to quantify these pollutants at very low concentration (few ng L(-1)). In this work, a multi-residue analytical methodology (on-line solid phase extraction-liquid chromatography-triple quadrupole mass spectrometry using positive and negative electrospray ionization) has been developed and validated for 40 multi-class pharmaceuticals and metabolites for tap and surface waters. This on-line SPE method was very convenient and efficient compared to classical off-line SPE method because of its shorter total run time including sample preparation and smaller sample volume (1 mL vs up to 1 L). The optimized method included several therapeutic classes as lipid regulators, antibiotics, beta-blockers, non-steroidal anti-inflammatories, antineoplastic, etc., with various physicochemical properties. Quantification has been achieved with the internal standards. The limits of detection are between 0.7 and 15 ng L(-1) for drinking waters and 2-15 ng L(-1) for surface waters. The inter-day precision values are below 20% for each studied level. The improvement and strength of the analytical method has been verified along a monitoring of these 40 pharmaceuticals in Isle River, a French stream located in the South West of France. During this survey, 16 pharmaceutical compounds have been detected.

  19. Chain alignment for improved properties - Optimization of PLA and PHB-V by crystallization and reinforcement

    NASA Astrophysics Data System (ADS)

    Moser, K.; Bergmann, B.; Diemert, J.; Elsner, P.

    2014-05-01

    In this paper two promising ways to improve the material characteristics of PLA and PHB-V are presented by showing their positive effects on mechanical, optical, and thermal properties. The optimization is achieved by increasing the crystallization from the melt of the polymer chains and the other by means of a reinforcement of the matrices by bio-based materials. In the case of crystallization specific nucleating agents and optimized process parameters promote optimized crystallization conditions and lead particularly in toughness to significant improvements. In addition to crystallization the introduction of cellulose-based reinforcing materials is also a good alternative to improve the ductility of a biopolymer matrix considerably. Due to their polar surface structure cellulose fibres are favouring a very good interaction to the also polar biopolymers. In addition, the polar surfaces of both materials results in very homogeneous dispersion within the compound.

  20. Coupling membrane separation and photocatalytic oxidation processes for the degradation of pharmaceutical pollutants.

    PubMed

    Martínez, F; López-Muñoz, M J; Aguado, J; Melero, J A; Arsuaga, J; Sotto, A; Molina, R; Segura, Y; Pariente, M I; Revilla, A; Cerro, L; Carenas, G

    2013-10-01

    The coupling of membrane separation and photocatalytic oxidation has been studied for the removal of pharmaceutical pollutants. The retention properties of two different membranes (nanofiltration and reverse osmosis) were assessed. Comparable selectivity on the separation of pharmaceuticals were observed for both membranes, obtaining a permeate stream with concentrations of each pharmaceutical below 0.5 mg L(-)(1) and a rejected flux highly concentrated (in the range of 16-25 mg L(-)(1) and 18-32 mg L(-)(1) of each pharmaceutical for NF-90 and BW-30 membranes, respectively), when an initial stream of six pharmaceuticals was feeding to the membrane system (10 mg L(-)(1) of each pharmaceutical). The abatement of concentrated pharmaceuticals of the rejected stream was evaluated by means of heterogeneous photocatalytic oxidation using TiO2 and Fe2O3/SBA-15 in presence of hydrogen peroxide as photo-Fenton system. Both photocatalytic treatments showed remarkable removals of pharmaceutical compounds, achieving values between 80 and 100%. The nicotine was the most refractory pollutant of all the studied pharmaceuticals. Photo-Fenton treatment seems to be more effective than TiO2 photocatalysis, as high mineralization degree and increased nicotine removal were attested. This work can be considered an interesting approach of coupling membrane separation and heterogeneous photocatalytic technologies for the successful abatement of pharmaceutical compounds in effluents of wastewater treatment plants.

  1. Development of Problem Sets for K-12 and Engineering on Pharmaceutical Particulate Systems

    ERIC Educational Resources Information Center

    Savelski, Mariano J.; Slater, C. Stewart; Del Vecchio, Christopher A.; Kosteleski, Adrian J.; Wilson, Sarah A.

    2010-01-01

    Educational problem sets have been developed on structured organic particulate systems (SOPS) used in pharmaceutical technology. The sets present topics such as particle properties and powder flow and can be integrated into K-12 and college-level curricula. The materials educate students in specific areas of pharmaceutical particulate processing,…

  2. Cellulose nanowhiskers and fiber alignment greatly improve mechanical properties of electrospun prolamin protein fibers.

    PubMed

    Wang, Yixiang; Chen, Lingyun

    2014-02-12

    Electrospun fibers from natural polymers must possess appropriate mechanical properties if they are to be functional in numerous applications. In this research, two convenient physical approaches were applied to reinforce the assembled hordein/zein electrospun nanofabrics: incorporation of surface-modified cellulose nanowhiskers (SCN) and fiber alignment. The mechanical properties and stability of the modified fibers were tested in relation to fiber morphology and structure as characterized by scanning electron microscopy, transmission electron microscopy, Fourier-transform infrared spectroscopy, and Raman spectroscopy. SCN modified by quaternary ammonium salt were well-dispersed in hordein/zein networks, leading to fibers with significantly improved mechanical properties and water resistance. With the addition of 3 wt % SCN, the tensile strength and Young's modulus of hordein/zein fibers increased from 4.36 ± 0.29 to 7.79 ± 0.36 MPa and from 195.80 ± 13.02 to 396.64 ± 18.33 MPa, respectively, and the elongation at break was retained because of the formation of a percolating network of SCN. The alignment of electrospun fibers strengthened the hordein/zein nanofabrics in both tangential and normal directions to 17.26 ± 1.41 and 14.02 ± 0.74 MPa, respectively, by not only altering the piling up pattern, but also by promoting phase separation and improved interactions. When applying both of the reinforcing methods, the tensile strength of hordein/zein fibers was further enhanced to 21.99 ± 1.19 MPa, stronger than that of cancellous bones (5-10 MPa). All the reinforced fibers exhibited a reduced burst effect in phosphate-buffered saline (PBS) while releasing the incorporated bioactive molecule in a controlled manner. These physically reinforced prolamin protein fibers possessed significantly improved mechanical properties and may have potential to be used as tissue engineering scaffold materials or natural delivery systems for biomedical applications.

  3. The role of marketing in pharmaceutical research and development.

    PubMed

    Calfee, John E

    2002-01-01

    Pharmaceutical marketing, which is primarily targeted at physicians, has been criticised because it may distort physician prescribing and thus potentially raise costs and/or worsen health. An alternative view, presented in this paper, is that successful marketing of pharmaceuticals can improve consumer welfare by increasing incentives for research and development (R&D) investment and by providing guidance to R&D to make it more consistent with consumer preferences. There are a number of arguments that support this view, despite impediments to pharmaceutical marketing such as the prohibited dissemination of off-label information in the US, difficulties in estimating potential pharmaceutical demand, and the long time lag between demand assessment and the introduction of new drugs. For example, physicians are often slow to modify their prescribing practices, even when new evidence-based practice guidelines are issued by prestigious organisations. Pharmaceutical promotion is likely to be particularly valuable because information plays a key role, is highly technical, and can change rapidly. Even consumer advertising can potentially improve health, for example, by improving patient compliance with drug therapy. In addition to disseminating information about the benefits of new therapies, an essential (and perhaps unique) role for pharmaceutical promotion is to encourage physicians and payers to pay closer attention to consumer needs (i.e. willingness to pay) for new medical technology. Moreover, successful marketing of pharmaceuticals increases the returns from R&D, thus increasing incentives to explore consumer demand and to contribute to basic research on the role of drug therapy. Consumer benefits from this process may be very large.

  4. Improved Force Field Model for the Deep Eutectic Solvent Ethaline: Reliable Physicochemical Properties.

    PubMed

    Ferreira, Elisabete S C; Voroshylova, Iuliia V; Pereira, Carlos M; D S Cordeiro, M Natália

    2016-09-13

    In this work, we combined various parameters found in the literature for the choline cation, chloride anion, and ethylene glycol to set up force field models (FFMs) for a eutectic mixture, namely, ethaline (1:2 choline chloride/ethylene glycol (ChCl:2EG)). The validation of these models was carried out on the basis of physical and chemical properties, such as the density, expansion coefficient, enthalpy of vaporization, self-diffusion coefficients, isothermal compressibility, surface tension, and shear viscosity. After the initial evaluation of the FFMs, a refinement was found necessary and accomplished by taking into account polarization effects in a mean-field manner. This was achieved by rescaling the electrostatic charges of the ions based on partial charges derived from ab initio molecular dynamics (MD) simulations of the bulk system. Classical all-atom MD simulations performed over a large range of temperatures (298.15-373.15 K) using the refined FFMs clearly showed improved results, allowing a better prediction of experimental properties. Specific structural properties (radial distribution functions and hydrogen bonding) were then analyzed in order to support the adequacy of the proposed refinement. The final selected FFM leads to excellent agreement between simulated and experimental data on dynamic and structural properties. Moreover, compared to the previously reported force field model (Perkins, S. L.; Painter, P.; Colina, C. M. Experimental and Computational Studies of Choline Chloride-Based Deep Eutectic Solvents. J. Chem. Eng. Data 2014, 59, 3652-3662), a 10% improvement in simulated transport properties, i.e., self-diffusion coefficients, was achieved. The isothermal compressibility, surface tension, and shear viscosity for ethaline are accessed in MD simulations for the first time.

  5. Improved functional properties of glycosylated soy protein isolate using D-glucose and xanthan gum.

    PubMed

    Li, Ruiqi; Hettiarachchy, Navam; Rayaprolu, Srinivas; Davis, Mike; Eswaranandam, Satchithanandam; Jha, Alok; Chen, Pengyin

    2015-09-01

    Functional properties of the soy protein need to improve to have better applications in food industry. Alkali extracted and acid precipitated soy protein isolate (SPI) was glycosylated using D-glucose (G) and Xanthan gum (X) via Maillard reaction to improve solubility. The effects of SPI to G and SPI to X ratios (SPI:G = 2:1, 1:1, and 1:2; SPI:X = 100:1 and 10:1) and incubation time (0, 6, 12, and 24 h) on the solubility and functional properties of glycosylated SPI were evaluated. The SPI:G ratio of 1:2 yielded a maximum degree of glycosylation of 71.1 %. The solubility of SPI after glycosylation significantly increased (P < 0.05) at pH 4.0-8.0 compared to SPI alone. Although the emulsion stability of glycosylated SPIs has not significantly increased (P > 0.05), the emulsifying activity improved significantly (P < 0.05). Glycosylation with SPI-X at a ratio of 10: 1 showed maximum emulsifying activity of 191.6 m(2)/g (SPI alone: 66.3 m(2)/g). Moreover, the SPI:X (ratio of 100:1) showed the maximum foaming activity (205 mL) compared to SPI alone (155 mL). The foaming stability of SPI (2.6 %) increased to 5.5 and 8.2 % when using xanthan gum at the ratio of 100:1 and 10:1, respectively. Glycosylated SPI with enhanced emulsifying and foaming properties has potential to improve the functional quality of the food products.

  6. Effects of Glycosylation on the Stability of Protein Pharmaceuticals

    PubMed Central

    SOLÁ, RICARDO J.; GRIEBENOW, KAI

    2008-01-01

    In recent decades, protein-based therapeutics have substantially expanded the field of molecular pharmacology due to their outstanding potential for the treatment of disease. Unfortunately, protein pharmaceuticals display a series of intrinsic physical and chemical instability problems during their production, purification, storage, and delivery that can adversely impact their final therapeutic efficacies. This has prompted an intense search for generalized strategies to engineer the long-term stability of proteins during their pharmaceutical employment. Due to the well known effect that glycans have in increasing the overall stability of glycoproteins, rational manipulation of the glycosylation parameters through glycoengineering could become a promising approach to improve both the in vitro and in vivo stability of protein pharmaceuticals. The intent of this review is therefore to further the field of protein glycoengineering by increasing the general understanding of the mechanisms by which glycosylation improves the molecular stability of protein pharmaceuticals. This is achieved by presenting a survey of the different instabilities displayed by protein pharmaceuticals, by addressing which of these instabilities can be improved by glycosylation, and by discussing the possible mechanisms by which glycans induce these stabilization effects. PMID:18661536

  7. Simulated gastrointestinal pH condition improves antioxidant properties of wheat and rice flours.

    PubMed

    Chan, Kim Wei; Khong, Nicholas M H; Iqbal, Shahid; Ismail, Maznah

    2012-01-01

    The present study was conducted to evaluate the antioxidant properties of wheat and rice flours under simulated gastrointestinal pH condition. After subjecting the wheat and rice flour slurries to simulated gastrointestinal pH condition, both slurries were centrifuged to obtain the crude phenolic extracts for further analyses. Extraction yield, total contents of phenolic and flavonoids were determined as such (untreated) and under simulated gastrointestinal pH condition (treated). 1,1-diphenyl-2-picrylhydrazyl radical (DPPH(•)) scavenging activity, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) radical cation (ABTS(•+)) scavenging activity, ferric reducing antioxidant power (FRAP), beta-carotene bleaching (BCB) and iron chelating activity assays were employed for the determination of antioxidant activity of the tested samples. In almost all of the assays performed, significant improvements in antioxidant properties (p < 0.05) were observed in both flours after treatment, suggesting that wheat and rice flours contain considerably heavy amounts of bound phenolics, and that their antioxidant properties might be improved under gastrointestinal digestive conditions.

  8. Improvement of the bio-functional properties of TiO2 nanotubes

    NASA Astrophysics Data System (ADS)

    Roguska, A.; Pisarek, M.; Belcarz, A.; Marcon, L.; Holdynski, M.; Andrzejczuk, M.; Janik-Czachor, M.

    2016-12-01

    Titanium oxide nanotubes with diameters from ca. 40-120 nm fabricated by the anodic oxidation of Ti at a constant voltage (10-28 V) were investigated to identify factors improving their bio-functional properties. Prepared substrates were subsequently annealed at 450 °C and 650 °C to obtain nanotubes having a crystalline structure, and were then examined by SEM, XRD, XPS, BET and contact angle measurement techniques. The thermally stabilized surfaces were subjected to bidirectional functionalization: by deposition of a thin layer of Ca-P and by loading with silver nanoparticles. Three factors were found to promote the proliferation of osteoblast (U2OS) cells: a larger nanotube diameter, a higher annealing temperature, and the presence of a thin Ca-P layer. Differentiation of these cells (by ALP test) was stimulated by a higher (650 °C) nanotube annealing temperature, but not by a thin Ca-P layer. The TiO2 nanotubes-modified samples exhibited noticeable antibacterial properties. Moreover, the additional deposition of Ag nanoparticles almost completely inhibited the survivability of S. epidermidis cells beyond 3 h of contact. In conclusion, TiO2 nanotubes-modified surfaces exhibit distinct bone forming ability and significant antibacterial properties, and can be easily functionalized by a thin Ca-P layer or nano-Ag deposition for further improvement of the above functionalities.

  9. Improving mechanical properties of carbon nanotube fibers through simultaneous solid-state cycloaddition and crosslinking.

    PubMed

    Lu, Xinyi; Hiremath, Nitilaksha; Hong, Kunlun; Evora, Maria C; Ranson, Victoria H; Naskar, Amit K; Bhat, Gajanan S; Kang, Nam-Goo; Mays, Jimmy W

    2017-04-07

    Individual carbon nanotubes (CNTs) exhibit exceptional mechanical properties. However, difficulties remain in fully realizing these properties in CNT macro-assemblies, because the weak inter-tube forces result in the CNTs sliding past one another. Herein, a simple solid-state reaction is presented that enhances the mechanical properties of carbon nanotube fibers (CNTFs) through simultaneous covalent functionalization and crosslinking. This is the first chemical crosslinking proposed without the involvement of a catalyst or byproducts. The specific tensile strength of CNTFs obtained from the treatment employing a benzocyclobutene-based polymer is improved by 40%. Such improvement can be attributed to a reduced number of voids, impregnation of the polymer, and the formation of covalent crosslinks. This methodology is confirmed using both multiwalled nanotube (MWNT) powders and CNTFs. Thermogravimetric analysis, differential scanning calorimetry, x-ray photoelectron spectroscopy, and transmission electron microscopy of the treated MWNT powders confirm the covalent functionalization and formation of inter-tube crosslinks. This simple one-step reaction can be applied to industrial-scale production of high-strength CNTFs.

  10. Combining phytoextraction and biochar addition improves soil biochemical properties in a soil contaminated with Cd.

    PubMed

    Lu, Huanping; Li, Zhian; Fu, Shenglei; Méndez, Ana; Gascó, Gabriel; Paz-Ferreiro, Jorge

    2015-01-01

    The main goal of phytoremediation is to improve ecosystem functioning. Soil biochemical properties are considered as effective indicators of soil quality and are sensitive to various environmental stresses, including heavy metal contamination. The biochemical response in a soil contaminated with cadmium was tested after several treatments aimed to reduce heavy metal availability including liming, biochar addition and phytoextraction using Amaranthus tricolor L. Two biochars were added to the soil: eucalyptus pyrolysed at 600 °C (EB) and poultry litter at 400 °C (PLB). Two liming treatments were chosen with the aim of bringing soil pH to the same values as in the treatments EB and PLB. The properties studied included soil microbial biomass C, soil respiration and the activities of invertase, β-glucosidase, β-glucosaminidase, urease and phosphomonoesterase. Both phytoremediation and biochar addition improved soil biochemical properties, although results were enzyme specific. For biochar addition these changes were partly, but not exclusively, mediated by alterations in soil pH. A careful choice of biochar must be undertaken to optimize the remediation process from the point of view of metal phytoextraction and soil biological activity.

  11. Improved antifouling properties of polyamide nanofiltration membranes by reducing the density of surface carboxyl groups.

    PubMed

    Mo, Yinghui; Tiraferri, Alberto; Yip, Ngai Yin; Adout, Atar; Huang, Xia; Elimelech, Menachem

    2012-12-18

    Carboxyls are inherent functional groups of thin-film composite polyamide nanofiltration (NF) membranes, which may play a role in membrane performance and fouling. Their surface presence is attributed to incomplete reaction of acyl chloride monomers during the membrane active layer synthesis by interfacial polymerization. In order to unravel the effect of carboxyl group density on organic fouling, NF membranes were fabricated by reacting piperazine (PIP) with either isophthaloyl chloride (IPC) or the more commonly used trimesoyl chloride (TMC). Fouling experiments were conducted with alginate as a model hydrophilic organic foulant in a solution, simulating the composition of municipal secondary effluent. Improved antifouling properties were observed for the IPC membrane, which exhibited lower flux decline (40%) and significantly greater fouling reversibility or cleaning efficiency (74%) than the TMC membrane (51% flux decline and 40% cleaning efficiency). Surface characterization revealed that there was a substantial difference in the density of surface carboxyl groups between the IPC and TMC membranes, while other surface properties were comparable. The role of carboxyl groups was elucidated by measurements of foulant-surface intermolecular forces by atomic force microscopy, which showed lower adhesion forces and rupture distances for the IPC membrane compared to TMC membranes in the presence of calcium ions in solution. Our results demonstrated that a decrease in surface carboxyl group density of polyamide membranes fabricated with IPC monomers can prevent calcium bridging with alginate and, thus, improve membrane antifouling properties.

  12. Improving mechanical properties of carbon nanotube fibers through simultaneous solid-state cycloaddition and crosslinking

    DOE PAGES

    Lu, Xinyi; Hiremath, Nitilaksha; Hong, Kunlun; ...

    2017-03-13

    Individual carbon nanotubes (CNTs) exhibit exceptional mechanical properties. However, difficulties remain in fully realizing these properties in CNT macro-assemblies, because the weak inter-tube forces result in the CNTs sliding past one another. Here in this study, a simple solid-state reaction is presented that enhances the mechanical properties of carbon nanotube fibers (CNTFs) through simultaneous covalent functionalization and crosslinking. This is the first chemical crosslinking proposed without the involvement of a catalyst or byproducts. The specific tensile strength of CNTFs obtained from the treatment employing a benzocyclobutene-based polymer is improved by 40%. Such improvement can be attributed to a reduced numbermore » of voids, impregnation of the polymer, and the formation of covalent crosslinks. This methodology is confirmed using both multiwalled nanotube (MWNT) powders and CNTFs. Thermogravimetric analysis, differential scanning calorimetry, x-ray photoelectron spectroscopy, and transmission electron microscopy of the treated MWNT powders confirm the covalent functionalization and formation of inter-tube crosslinks. This simple one-step reaction can be applied to industrial-scale production of high-strength CNTFs.« less

  13. Improving mechanical properties of carbon nanotube fibers through simultaneous solid-state cycloaddition and crosslinking

    NASA Astrophysics Data System (ADS)

    Lu, Xinyi; Hiremath, Nitilaksha; Hong, Kunlun; Evora, Maria C.; Ranson, Victoria H.; Naskar, Amit K.; Bhat, Gajanan S.; Kang, Nam-Goo; Mays, Jimmy W.

    2017-04-01

    Individual carbon nanotubes (CNTs) exhibit exceptional mechanical properties. However, difficulties remain in fully realizing these properties in CNT macro-assemblies, because the weak inter-tube forces result in the CNTs sliding past one another. Herein, a simple solid-state reaction is presented that enhances the mechanical properties of carbon nanotube fibers (CNTFs) through simultaneous covalent functionalization and crosslinking. This is the first chemical crosslinking proposed without the involvement of a catalyst or byproducts. The specific tensile strength of CNTFs obtained from the treatment employing a benzocyclobutene-based polymer is improved by 40%. Such improvement can be attributed to a reduced number of voids, impregnation of the polymer, and the formation of covalent crosslinks. This methodology is confirmed using both multiwalled nanotube (MWNT) powders and CNTFs. Thermogravimetric analysis, differential scanning calorimetry, x-ray photoelectron spectroscopy, and transmission electron microscopy of the treated MWNT powders confirm the covalent functionalization and formation of inter-tube crosslinks. This simple one-step reaction can be applied to industrial-scale production of high-strength CNTFs.

  14. Dense codes at high speeds: varying stimulus properties to improve visual speller performance.

    PubMed

    Geuze, Jeroen; Farquhar, Jason D R; Desain, Peter

    2012-02-01

    This paper investigates the effect of varying different stimulus properties on performance of the visual speller. Each of the different stimulus properties has been tested in previous literature and has a known effect on visual speller performance. This paper investigates whether a combination of these types of stimuli can lead to a greater improvement. It describes an experiment aimed at answering the following questions. (i) Does visual speller performance suffer from high stimulus rates? (ii) Does an increase in stimulus rate lead to a lower training time for an online visual speller? (iii) What aspect of the difference in the event related potential to a flash or a flip stimulus causes the increase in accuracy. (iv) Can an error-correcting (dense) stimulus code overcome the reduction in performance associated with decreasing target-to-target intervals? We found that higher stimulus rates can improve the visual speller performance and can lead to less time required to train the system. We also found that a proper stimulus code can overcome the stronger response to rows and columns, but cannot greatly improve speller performance.

  15. Effects of Constituent Properties on Performance Improvement of a Quenching and Partitioning Steel

    SciTech Connect

    Choi, Kyoo Sil; Hu, Xiaohua; Sun, Xin; Taylor, Mark D.; De Moor, Emmanuel; Speer, John; Matlock, David K.

    2014-04-01

    In this paper, a two-dimensional microstructure-based finite element modeling method is adopted to investigate the effects of material parameters of the constituent phases on the macroscopic tensile behavior of Q&P steel and then to do a computational materials design approach for its performance improvement. For this purpose, a model Q&P steel is first produced and various experiments are then performed to characterize the steel. Actual microstructure-based model is generated based on the information from EBSD, SEM and nano-indentation test, and the material properties for the constituent phases are determined based on the initial constituents’ properties from HEXRD test and the subsequent calibration of model prediction to tensile test results. Influence of various material parameters of the constituents on the macroscopic behaviors is then investigated by separately adjusting them by small amount. Based on the observation on the respective influence of constituents’ material parameters, a new set of material parameters are devised, which results in better performance in ductility. The results indicate that various material parameters may need to be concurrently adjusted in a cohesive way in order to improve the performance of Q&P steel. In summary, higher austenite stability, less strength difference between the phases, higher hardening exponents of the phases are generally beneficial for the performance improvement. The information from this study can be used to devise new Q&P heat-treating parameters to produce the Q&P steels with better performance.

  16. Improving the Compatibility and Mechanical Properties of Recycled Polymer Blends using Supercritical Carbon Dioxide

    NASA Astrophysics Data System (ADS)

    Fourman, Mitchell; Rafailovich, Miriam; Iraci, John Michael

    2011-03-01

    Supercritical Carbon Dioxide (scCO2) has been shown to decrease the interfacial tension between immiscible bulk polymer blends by Palermo et al. [Macromolecules 38 (22) 1980-1986, (2005)]. However, little work has been done to determine the efficacy of scCO2 on recycled materials. Here we show that scCO2 can be used to induce partial compatibility - and therefore improved mechanical properties - in bulk polymer blends using recycled materials. Blends of polymethyl methacrylate (PMMA), Ethylene vinyl acetate (EVA), and recycled Polyvinyl chloride (PVC) were created at different ratios using a CW Brabender twin screw extruder and exposed to scCO2. Dynamic Mechanical Analysis (DMA), Differential Scanning Calorimetry (DSC), Izod impact testing, and Instron tensile testing were used to measure the properties of blends before and after exposure. Results show improved strength and elasticity in bulk samples, with substantial improvement in modulus and impact factor within the ``density fluctuation ridge.'' Results suggest potential industrial and ecological benefits for scCO2. Supported in part by the Garcia NSF-MRSEC Center at the Department of Materials Science - Stony Brook University.

  17. Cross-linked chitosan improves the mechanical properties of calcium phosphate-chitosan cement.

    PubMed

    Aryaei, Ashkan; Liu, Jason; Jayatissa, Ahalapitiya H; Jayasuriya, A Champa

    2015-09-01

    Calcium phosphate (CaP) cements are highly applicable and valuable materials for filling bone defects by minimally invasive procedures. The chitosan (CS) biopolymer is also considered as one of the promising biomaterial candidates in bone tissue engineering. In the present study, some key features of CaP-CS were significantly improved by developing a novel CaP-CS composite. For this purpose, CS was the first cross-linked with tripolyphosphate (TPP) and then mixed with CaP matrix. A group of CaP-CS samples without cross-linking was also prepared. Samples were fabricated and tested based on the known standards. Additionally, the effect of different powder (P) to liquid (L) ratios was also investigated. Both cross-linked and uncross-linked CaP-CS samples showed excellent washout resistance. The most significant effects were observed on Young's modulus and compressive strength in wet condition as well as surface hardness. In dry conditions, the Young's modulus of cross-linked samples was slightly improved. Based on the presented results, cross-linking does not have a significant effect on porosity. As expected, by increasing the P/L ratio of a sample, ductility and injectability were decreased. However, in the most cases, mechanical properties were enhanced. The results have shown that cross-linking can improve the mechanical properties of CaP-CS and hence it can be used for bone tissue engineering applications.

  18. Electronic structures and optical properties of TiO2: Improved density-functional-theory investigation

    NASA Astrophysics Data System (ADS)

    Gong, Sai; Liu, Bang-Gui

    2012-05-01

    TiO2 has been recently used to realize high-temperature ferromagnetic semiconductors. In fact, it has been widely used for a long time as white pigment and sunscreen because of its whiteness, high refractive index, and excellent optical properties. However, its electronic structures and the related properties have not been satisfactorily understood. Here, we use Tran and Blaha's modified Becke-Johnson (TB-mBJ) exchange potential (plus a local density approximation correlation potential) within the density functional theory to investigate electronic structures and optical properties of rutile and anatase TiO2. Our comparative calculations show that the energy gaps obtained from mBJ method agree better with the experimental results than that obtained from local density approximation (LDA) and generalized gradient approximation (GGA), in contrast with substantially overestimated values from many-body perturbation (GW) calculations. As for optical dielectric functions (both real and imaginary parts), refractive index, and extinction coefficients as functions of photon energy, our mBJ calculated results are in excellent agreement with the experimental curves. Our further analysis reveals that these excellent improvements are achieved because mBJ potential describes accurately the energy levels of Ti 3d states. These results should be helpful to understand the high temperature ferromagnetism in doped TiO2. This approach can be used as a standard to understand electronic structures and the related properties of such materials as TiO2.

  19. Improvement in mechanical and barrier properties of polyethylene blown films using atomic layer deposition

    SciTech Connect

    Lee, Gyeong Beom; Hak Song, Seung; Wook Moon, Sung; Woo Kim, Jun; Hyung Shim, Joon; Choi, Byoung-Ho; Moo Heo, Young

    2014-01-15

    Recently, thin films deposited on polymer substrates have been widely utilized as encapsulation barriers in electronic applications such as flexible displays, packaging films, and organic light-emitting diodes. The barrier and mechanical properties of these films are critical aspects when using them for protecting the inner modules of electronic devices from environmental factors such as moisture, oxygen, and sunlight. In particular, polymers can be degraded or decomposed more easily than other materials under such environmental conditions. Therefore, polymer films can be deposited using thin functional materials; however, suitable deposition methods for polymers are scarce owing to many limitations such as low melting/glass transition temperature, thermal degradation, and oxidation. In this study, a thin alumina oxide film was deposited on a high-density polyethylene blown film by using atomic layer deposition. The mechanical and barrier properties of the alumina oxide film deposited on the polyethylene film were characterized by a microtensile test and water vapor transmission rate test. Process conditions such as process temperature, plasma surface treatment, and number of cycles were varied to ascertain the reliability of the thin alumina oxide film deposited on the high-density polyethylene blown film. The results showed that the barrier property of the deposited film improved upon the application of plasma surface treatment, and that its mechanical properties varied under different process conditions.

  20. White light-informed optical properties improve ultrasound-guided fluorescence tomography of photoactive protoporphyrin IX

    PubMed Central

    DSouza, Alisha V.; Kanick, Stephen C.; Davis, Scott C.; Pogue, Brian W.

    2013-01-01

    Abstract. Subsurface fluorescence imaging is desirable for medical applications, including protoporphyrin-IX (PpIX)-based skin tumor diagnosis, surgical guidance, and dosimetry in photodynamic therapy. While tissue optical properties and heterogeneities make true subsurface fluorescence mapping an ill-posed problem, ultrasound-guided fluorescence-tomography (USFT) provides regional fluorescence mapping. Here USFT is implemented with spectroscopic decoupling of fluorescence signals (auto-fluorescence, PpIX, photoproducts), and white light spectroscopy-determined bulk optical properties. Segmented US images provide a priori spatial information for fluorescence reconstruction using region-based, diffuse FT. The method was tested in simulations, tissue homogeneous and inclusion phantoms, and an injected-inclusion animal model. Reconstructed fluorescence yield was linear with PpIX concentration, including the lowest concentration used, 0.025  μg/ml. White light spectroscopy informed optical properties, which improved fluorescence reconstruction accuracy compared to the use of fixed, literature-based optical properties, reduced reconstruction error and reconstructed fluorescence standard deviation by factors of 8.9 and 2.0, respectively. Recovered contrast-to-background error was 25% and 74% for inclusion phantoms without and with a 2-mm skin-like layer, respectively. Preliminary mouse-model imaging demonstrated system feasibility for subsurface fluorescence measurement in vivo. These data suggest that this implementation of USFT is capable of regional PpIX mapping in human skin tumors during photodynamic therapy, to be used in dosimetric evaluations. PMID:23584445

  1. Mechanical properties improvement of silica aerogel through aging: Role of solvent type, time and temperature

    NASA Astrophysics Data System (ADS)

    Omranpour, H.; Dourbash, A.; Motahari, S.

    2014-05-01

    Effective parameters that enhance mechanical properties during aging were investigated in the present study. Silica aerogels were made from tetraethyl orthosilicate (TEOS), water, methanol and NH4F in molar ratio 1:4:8:2×10-3 using a one-step method. Different time, temperature and aging solvents in aging stage were studied. Subsequently, solvent exchange with n-hexane, modification under TMCS solution and ambient pressure drying (APD) were performed for all samples. The aerogels had densities within the range of 0.1 and 0.6 g/cm3. The FTIR, mechanical properties, density and BET results, porosity, pore volume, pore diameter and surface area of the samples, were discussed. The compression properties of the gel increased with the increase in the time and temperature of aging. It was observed that solvents with more polarity improved polymerization, which enhanced the mechanical properties of the related samples. However, the stresses and capillary forces of water during drying were so large that inhibited "spring-back effect" during APD, and consequently a collapsed silica network with higher density was fabricated. In other words, the specific compression strength and modulus declined drastically. For methanol, alcohols inhibit the reactions inconveniently causing more shrinkage. In aging by n-hexane, capillary pressure declined significantly and thereby shrinkage was eliminated and silica aerogels with low bulk densities (0.095 g/cm3), high specific surface areas (600 m2/g), and large pore volumes (2.6 cm3/g) were synthesized.

  2. Critical seeding density improves the properties and translatability of self-assembling anatomically shaped knee menisci.

    PubMed

    Hadidi, Pasha; Yeh, Timothy C; Hu, Jerry C; Athanasiou, Kyriacos A

    2015-01-01

    A recent development in the field of tissue engineering is the rise of all-biologic, scaffold-free engineered tissues. Since these biomaterials rely primarily upon cells, investigation of initial seeding densities constitutes a particularly relevant aim for tissue engineers. In this study, a scaffold-free method was used to create fibrocartilage in the shape of the rabbit knee meniscus. The objectives of this study were to: (i) determine the minimum seeding density, normalized by an area of 44 mm(2), necessary for the self-assembling process of fibrocartilage to occur; (ii) examine relevant biomechanical properties of engineered fibrocartilage, such as tensile and compressive stiffness and strength, and their relationship to seeding density; and (iii) identify a reduced, or optimal, number of cells needed to produce this biomaterial. It was found that a decreased initial seeding density, normalized by the area of the construct, produced superior mechanical and biochemical properties. Collagen per wet weight, glycosaminoglycans per wet weight, tensile properties and compressive properties were all significantly greater in the 5 million cells per construct group as compared to the historical 20 million cells per construct group. Scanning electron microscopy demonstrated that a lower seeding density results in a denser tissue. Additionally, the translational potential of the self-assembling process for tissue engineering was improved though this investigation, as fewer cells may be used in the future. The results of this study underscore the potential for critical seeding densities to be investigated when researching scaffold-free engineered tissues.

  3. Measurement of complex terahertz dielectric properties of polymers using an improved free-space technique

    NASA Astrophysics Data System (ADS)

    Chang, Tianying; Zhang, Xiansheng; Yang, Chuanfa; Sun, Zhonglin; Cui, Hong-Liang

    2017-04-01

    The complex dielectric properties of non-polar solid polymer materials were measured in the terahertz (THz) band by a free-space technique employing a frequency-extended vector network analyzer (VNA), and by THz time-domain spectroscopy (TDS). Mindful of THz wave’s unique characteristics, the free-space method for measurement of material dielectric properties in the microwave band was expanded and improved for application in the THz frequency region. To ascertain the soundness and utility of the proposed method, measurements of the complex dielectric properties of a variety of polymers were carried out, including polytetrafluoroethylene (PTFE, known also by the brand name Teflon), polypropylene (PP), polyethylene (PE), and glass fiber resin (Composite Stone). The free-space method relies on the determination of electromagnetic scattering parameters (S-parameters) of the sample, with the gated-reflect-line (GRL) calibration technique commonly employed using a VNA. Subsequently, based on the S-parameters, the dielectric constant and loss characteristic of the sample were calculated by using a Newtonian iterative algorithm. To verify the calculated results, THz TDS technique, which produced Fresnel parameters such as reflection and transmission coefficients, was also used to independently determine the dielectric properties of these polymer samples, with results satisfactorily corroborating those obtained by the free-space extended microwave technique.

  4. White light-informed optical properties improve ultrasound-guided fluorescence tomography of photoactive protoporphyrin IX

    NASA Astrophysics Data System (ADS)

    Flynn, Brendan P.; DSouza, Alisha V.; Kanick, Stephen C.; Davis, Scott C.; Pogue, Brian W.

    2013-04-01

    Subsurface fluorescence imaging is desirable for medical applications, including protoporphyrin-IX (PpIX)-based skin tumor diagnosis, surgical guidance, and dosimetry in photodynamic therapy. While tissue optical properties and heterogeneities make true subsurface fluorescence mapping an ill-posed problem, ultrasound-guided fluorescence-tomography (USFT) provides regional fluorescence mapping. Here USFT is implemented with spectroscopic decoupling of fluorescence signals (auto-fluorescence, PpIX, photoproducts), and white light spectroscopy-determined bulk optical properties. Segmented US images provide a priori spatial information for fluorescence reconstruction using region-based, diffuse FT. The method was tested in simulations, tissue homogeneous and inclusion phantoms, and an injected-inclusion animal model. Reconstructed fluorescence yield was linear with PpIX concentration, including the lowest concentration used, 0.025 μg/ml. White light spectroscopy informed optical properties, which improved fluorescence reconstruction accuracy compared to the use of fixed, literature-based optical properties, reduced reconstruction error and reconstructed fluorescence standard deviation by factors of 8.9 and 2.0, respectively. Recovered contrast-to-background error was 25% and 74% for inclusion phantoms without and with a 2-mm skin-like layer, respectively. Preliminary mouse-model imaging demonstrated system feasibility for subsurface fluorescence measurement in vivo. These data suggest that this implementation of USFT is capable of regional PpIX mapping in human skin tumors during photodynamic therapy, to be used in dosimetric evaluations.

  5. Improvement of polyvinyl alcohol properties by adding nanocrystalline cellulose isolated from banana pseudostems.

    PubMed

    Pereira, André Luís S; do Nascimento, Diego M; Souza Filho, Men de Sá M; Morais, João Paulo S; Vasconcelos, Niedja F; Feitosa, Judith P A; Brígida, Ana Iraidy S; Rosa, Morsyleide de F

    2014-11-04

    Cellulose nanocrystals (CNCs) isolated from banana pseudostems fibers (BPF) of the Pacovan variety were used as fillers in a polyvinyl alcohol (PVOH) matrix to yield a nanocomposite. The fibers from the external fractions of the BPF were alkaline bleached and hydrolyzed under acidic conditions (H2SO4 62% w/w, 70 min, 45 °C) to obtain CNCs with a length (L) of 135.0 ± 12.0 nm and a diameter (D) of 7.2 ± 1.9 nm to yield an aspect ratio (L/D) of 21.2. The CNCs were applied to PVOH films at different concentrations (0%, 1%, 3%, and 5% w/w, dry basis). With higher concentrations of CNCs, the water-vapor barrier of the films increased, while the optical properties changed very little. Increasing the concentration of the CNCs up to 3% significantly improved the mechanical properties of the nanocomposite.

  6. Improved mechanical and electrical properties in electrospun polyimide/multiwalled carbon nanotubes nanofibrous composites

    SciTech Connect

    Zha, Jun-Wei; Sun, Fang; Wang, Si-Jiao; Wang, Dongrui; Lin, Xiang; Dang, Zhi-Min; Chen, George

    2014-10-07

    Highly aligned polyimide (PI) and PI/multi-walled carbon nanotubes (PI/MWCNTs) nanofibrous composites by incorporating poly(ethylene oxide) as the dispersing medium were fabricated using electrospinning technique. The morphology, mechanical, and electrical properties of the electrospun nanofibrous composites were investigated. Scanning electron microscope showed that the functionalized MWCNTs (f-MWCNTs) were well dispersed and oriented along the nanofiber axis. Analysis of electrical properties indicated a remarkable improvement on the alternating current conductivity by introduction of the aligned f-MWCNTs. Besides, with addition of 3 vol. % f-MWCNTs, the obvious enhancement of tensile modulus and strength was achieved. Thus, the electrospun PI/MWCNTs nanofibrous composites have great potential applications in multifunctional engineering materials.

  7. Chemically Derived Dense Alumina-Zirconia Composites for Improved Mechanical and Wear Erosion Properties

    NASA Technical Reports Server (NTRS)

    1998-01-01

    As a result of this funded project high purity Zirconia-Toughened Alumina (ZTA) ceramic powders with and without yttria were produced using metal alkoxide precursors. ZTA ceramic powders with varying volume percents of zirconia were prepared (7, 15, and 22%). Aluminum tri-sec butoxide, zirconium propoxide, and yttrium isopropoxide were the reagents used. Synthesis conditions were varied to control the hydrolysis and the aging conditions for the sol to gel transition. FTIR analysis and rheological characterization were used to follow the structural evolution during the sol to gel transition. The greater extent of hydrolysis and the build-up of structure measured from viscoelastic properties were consistent. Heat treatment was conducted to produce submicron grain fully crystalline ZTA ceramic powders. This improved materials should have enhanced properties such strength, toughness, and wear resistance for advanced structural applications, for example engine components in high technology aerospace applications.

  8. [Improving global access to new vaccines: intellectual property, technology transfer, and regulatory pathways].

    PubMed

    Crager, Sara Eve

    2015-01-01

    The 2012 World Health Assembly Global Vaccine Action Plan called for global access to new vaccines within 5 years of licensure. Current approaches have proven insufficient to achieve sustainable vaccine pricing within such a timeline. Paralleling the successful strategy of generic competition to bring down drug prices, a clear consensus is emerging that market entry of multiple suppliers is a critical factor in expeditiously bringing down prices of new vaccines. In this context, key target objectives for improving access to new vaccines include overcoming intellectual property obstacles, streamlining regulatory pathways for biosimilar vaccines, and reducing market entry timelines for developing-country vaccine manufacturers by transfer of technology and know-how. I propose an intellectual property, technology, and know-how bank as a new approach to facilitate widespread access to new vaccines in low- and middle-income countries by efficient transfer of patented vaccine technologies to multiple developing-country vaccine manufacturers.

  9. Improved Relationships for the Thermodynamic Properties of Carbon Phases at Detonation Conditions

    NASA Astrophysics Data System (ADS)

    Stiel, Leonard; Baker, Ernest; Murphy, Daniel

    2013-06-01

    In order to improve the procedures utilized in the Jaguar thermochemical program for carbon, volumetric and heat capacity relationships have been developed for graphite, diamond, and liquid carbon forms. Available experimental thermodynamic property and Hugoniot data have been analyzed to establish optimum equations of state for the carbon phases. The appropriate carbon form or multiple forms at equilibrium results from the minimization of the Gibbs free energy of the system. The resulting relationships are utilized to examine the phase behavior of carbon at elevated temperatures and pressures. The behavior of metastable carbon states is optimized by analyses of Hugoniot data for hydrocarbons, and C-J and cylinder velocities for a database of CHNO explosives. The accuracy of the resulting relationships is demonstrated by comparisons for several properties, including the Hugoniot behavior of oxygen-deficient explosives at overdriven conditions.

  10. Improvement of the microstructure and mechanical properties of bioceramic scaffolds using electrohydrodynamic spraying with template modification.

    PubMed

    Muthutantri, Anushini I; Edirisinghe, Mohan J; Boccaccini, Aldo R

    2010-04-01

    Porous scaffolds play a key role in tissue engineering (TE) approaches and new processing methods and materials are constantly being developed to cater for the wide range of specifications and requirements. Electrospraying is a relatively new processing method used for producing open-pore scaffolds. In this work, the electrospraying technique was manipulated to make the process more efficient, and the effect of spraying time on the pore size and strut thickness of zirconia scaffolds was explored. Scaffolds of adequate pore size and interconnectivity, with an average compressive strength of approximately 7.5 MPa, by electrospraying for only 10 min are reported. The effect of modifying the sacrificial template on the microstructure and mechanical properties of the sintered scaffolds was also investigated. A combination of template surface hydroxylation and improved conductivity produced a thicker ceramic coating, leading to enhanced mechanical properties.

  11. Gamma-irradiation improves the color and antioxidant properties of Chaga mushroom (Inonotus obliquus) extract.

    PubMed

    Kim, Jae-Hun; Sung, Nak-Yun; Kwon, Sun-Kyu; Srinivasan, Periasamy; Song, Beom-Seok; Choi, Jong-Il; Yoon, Yohan; Kim, Jin Kyu; Byun, Myung-Woo; Kim, Mee-Ree; Lee, Ju-Woon

    2009-12-01

    The objective of this study was to evaluate the effect of ionizing radiation on color and antioxidative properties of Chaga mushroom (Inonotus obliquus) extract (CME). CME (10 mg/mL) was gamma-irradiated at 0, 3, 5, 7, and 10 kGy, and color, antioxidant activity, and total phenolic compound levels were then determined. The lightness and yellowness were increased (P < .05), and the redness was decreased (P < .05), as irradiation dose increased. The antioxidant parameters such as the 2-diphenyl-1-picrylhydrazyl, superoxide, and hydroxyl radical scavenging activities, ferric reducing/antioxidant power, and inhibition of lipid peroxidation increased as the irradiation dose increased. Also, the total phenolic compound levels of CME were increased (P < .05) by gamma-irradiation. These results suggest that gamma-irradiation could be considered a means for improving the antioxidant properties and the color of CME.

  12. Improving Global Access to New Vaccines: Intellectual Property, Technology Transfer, and Regulatory Pathways

    PubMed Central

    2014-01-01

    The 2012 World Health Assembly Global Vaccine Action Plan called for global access to new vaccines within 5 years of licensure. Current approaches have proven insufficient to achieve sustainable vaccine pricing within such a timeline. Paralleling the successful strategy of generic competition to bring down drug prices, a clear consensus is emerging that market entry of multiple suppliers is a critical factor in expeditiously bringing down prices of new vaccines. In this context, key target objectives for improving access to new vaccines include overcoming intellectual property obstacles, streamlining regulatory pathways for biosimilar vaccines, and reducing market entry timelines for developing-country vaccine manufacturers by transfer of technology and know-how. I propose an intellectual property, technology, and know-how bank as a new approach to facilitate widespread access to new vaccines in low- and middle-income countries by efficient transfer of patented vaccine technologies to multiple developing-country vaccine manufacturers. PMID:25211753

  13. Improved mechanical properties of HDPE/nano-alumina composite through silane coupling agent

    NASA Astrophysics Data System (ADS)

    Akmil, N.; Luqman, C. A.; Ahmad, M.; Zaman, K.

    2012-11-01

    The effect of silane coupling agent to mechanical properties of HDPE/nano-alumina composite was investigated. Nano-alumina used in this study was produced by using sol-gel method. The shape and size of nano-alumina were determined by using TEM. Prior to the usage of nano alumina as a filler in the polymer matrix, (3-methacryloxypropyl) trimethoxysilane (MPS) was used to functionalize the nanoparticles due to its bifunctional nature: hydrolysable group (-Si(OCH3)3) and unsaturated carbon-carbon double bond. The XRD result shows diffraction spectrum of the synthesized nano-alumina. In order to improve the mechanical properties of the composite, nanoalumina was treated with (3-methacryloxypropyl) trimethoxysilane (MPS). A high tensile strength, is achieved at 4 wt% of MPS.

  14. Improvement of luminescence properties of GaN buffer layer for fast nitride scintillator structures

    NASA Astrophysics Data System (ADS)

    Hubáček, T.; Hospodková, A.; Oswald, J.; Kuldová, K.; Pangrác, J.

    2017-04-01

    We have optimized technology of GaN buffer layer growth with respect to the application in fast scintillation structures. The deep defect luminescence so called yellow band (YB) with decay time up to tens of microseconds is undesired for these applications and should be suppressed or at least the ratio of intensities of excitonic to YB maximum has to be considerably increased. The required photoluminescence properties were achieved by optimization of growth parameters of nucleation and coalescence layer on sapphire substrate. We have shown that decrease of NH3 flow, decrease of coalescence temperature, increase of nucleation time and nucleation pressure lead to improvement of the structure and luminescence properties of the buffer layer. Results indicate a significant increased ratio of excitonic/YB luminescence intensity.

  15. Improving global access to new vaccines: intellectual property, technology transfer, and regulatory pathways.

    PubMed

    Crager, Sara Eve

    2014-11-01

    The 2012 World Health Assembly Global Vaccine Action Plan called for global access to new vaccines within 5 years of licensure. Current approaches have proven insufficient to achieve sustainable vaccine pricing within such a timeline. Paralleling the successful strategy of generic competition to bring down drug prices, a clear consensus is emerging that market entry of multiple suppliers is a critical factor in expeditiously bringing down prices of new vaccines. In this context, key target objectives for improving access to new vaccines include overcoming intellectual property obstacles, streamlining regulatory pathways for biosimilar vaccines, and reducing market entry timelines for developing-country vaccine manufacturers by transfer of technology and know-how. I propose an intellectual property, technology, and know-how bank as a new approach to facilitate widespread access to new vaccines in low- and middle-income countries by efficient transfer of patented vaccine technologies to multiple developing-country vaccine manufacturers.

  16. Application of bioethanol derived lignin for improving physico-mechanical properties of thermoset biocomposites.

    PubMed

    Bajwa, Dilpreet S; Wang, Xinnan; Sitz, Evan; Loll, Tyler; Bhattacharjee, Sujal

    2016-08-01

    Lignin is the most abundant of renewable polymers next to cellulose with a global annual production of 70million tons, largely produced from pulping and second generation biofuel industries. Low value of industrial lignin makes it an attractive biomaterial for wide range of applications. The study investigated the application of wheat straw and corn stover based lignin derived from ethanol production for use in thermoset biocomposites. The biocomposite matrix constituted a two component low viscosity Araldite(®)LY 8601/Aradur(®) 8602 epoxy resin system and the lignin content varied from 0 to 25% by weight fraction. The analysis of the physical and mechanical properties of the biocomposites show bioethanol derived lignin can improve selective properties such as impact strength, and thermal stability without compromising the modulus and strength attributes.

  17. Microlayer coextrusion process as a way to improve thermomechanical properties of ABS/PC blends

    NASA Astrophysics Data System (ADS)

    Sollogoub, C.; Grandmontagne, A.; Guinault, A.

    2011-05-01

    ABS/PC blends have always presented a great interest both in industrial and academic contexts, since they combine the most desirable properties of both ABS and PC. Melt blends are classically prepared using a twin screw extruder. In this study, ABS/PC blends of two compositions were prepared with two blending techniques: coextrusion mixing method (CM) and microlayer coextrusion method (MC), designed to better control the blend morphology, and then injection molded. SEM observations show that different blend morphologies have been obtained, depending on the blending technique. It was shown that microlayer coextrusion process can lead to orientated morphology phase (fibrillar and lamellar structures), whereas coextrusion mixing method leads only to nodular morphology. These morphologies have been correlated with thermomechanical properties (tensile tests and DMTA). Improved mechanical performances are achieved with the microlayer coextrusion process.

  18. Method of manipulating the chemical properties of water to improve the effectiveness of a desired process

    DOEpatents

    Hawthorne, Steven B.; Miller, David J.; Lagadec, Arnaud Jean-Marie; Hammond, Peter James; Clifford, Anthony Alan

    2002-01-01

    The method of the present invention is adapted to manipulate the chemical properties of water in order to improve the effectiveness of a desired process. The method involves heating the water in the vessel to subcritical temperatures between 100.degree. to 374.degree. C. while maintaining sufficient pressure to the water to maintain the water in the liquid state. Various physiochemical properties of the water can be manipulated including polarity, solute solubility, surface tension, viscosity, and the disassociation constant. The method of the present invention has various uses including extracting organics from solids and semisolids such as soil, selectively extracting desired organics from liquids, selectively separating organics using sorbent phases, enhancing reactions by controlling the disassociation constant of water, cleaning waste water, removing organics from water using activated carbon or other suitable sorbents, and degrading various compounds.

  19. Improvement of Structural and Mechanical Properties of Al-1100 Alloy via Friction Stir Processing

    NASA Astrophysics Data System (ADS)

    Mosallaee, M.; Dehghan, M.

    2014-10-01

    In the present study, the relationship between structural and mechanical properties of friction stir processed Al-1100 alloy and process parameters (tool rotation rate: ω and traverse speed: ν) was studied to get an better understanding and optimizing the friction stir processing (FSP) condition of this alloy. Microstructural studies revealed that increasing of ω up to 720 rpm resulted in grain refinement in the stirred zone (SZ), but higher increasing of ω caused grain growth in this zone. These variations of SZ grain size illustrated that the prevailing factor that determined the SZ grain size was plastic deformation at first and thereafter, peak temperature in the SZ. Mechanical properties investigations were in accordance with microstructural findings and illustrated that optimized FSP condition for Al-1100 alloy was 720 rpm and 20 mm/min. Optimized FSP condition resulted in a significant improvement of tensile strength and elongation up to 22 and 8% of those of base metal, respectively.

  20. Cavitation technology - a greener processing technique for the generation of pharmaceutical nanoemulsions.

    PubMed

    Sivakumar, Manickam; Tang, Siah Ying; Tan, Khang Wei

    2014-11-01

    Novel nanoemulsion-based drug delivery systems (DDS) have been proposed as alternative and effective approach for the delivery of various types of poorly water-soluble drugs in the last decade. This nanoformulation strategy significantly improves the cell uptake and bioavailability of numerous hydrophobic drugs by increasing their solubility and dissolution rate, maintaining drug concentration within the therapeutic range by controlling the drug release rate, and reducing systemic side effects by targeting to specific disease site, thus offering a better patient compliance. To date, cavitation technology has emerged to be an energy-efficient and promising technique to generate such nanoscale emulsions encapsulating a variety of highly potent pharmaceutical agents that are water-insoluble. The micro-turbulent implosions of cavitation bubbles tear-off primary giant oily emulsion droplets to nano-scale, spontaneously leading to the formation of highly uniform drug contained nanodroplets. A substantial body of recent literatures in the field of nanoemulsions suggests that cavitation is a facile, cost-reducing yet safer generation tool, remarkably highlighting its industrial commercial viability in the development of designing novel nanocarriers or enhancing the properties of existing pharmaceutical products. In this review, the fundamentals of nanoemulsion and the principles involved in their formation are presented. The underlying mechanisms in the generation of pharmaceutical nanoemulsion under acoustic field as well as the advantages of using cavitation compared to the conventional techniques are also highlighted. This review focuses on recent nanoemulsion-based DDS development and how cavitation through ultrasound and hydrodynamic means is useful to generate the pharmaceutical grade nanoemulsions including the complex double or submicron multiple emulsions.

  1. Development of pharmaceutical heroin preparations for medical co-prescription to opioid dependent patients.

    PubMed

    Klous, Marjolein G; Van den Brink, Wim; Van Ree, Jan M; Beijnen, Jos H

    2005-12-12

    Presently, there is a considerable interest in heroin-assisted treatment: co-prescription of heroin to certain subgroups of chronic, treatment-resistant, opioid dependent patients. In 2002, nine countries had planned (Australia, Belgium, Canada, France, Spain) or ongoing (Germany, The Netherlands, Switzerland, United Kingdom) clinical trials on this subject. These trials (and the routine heroin-assisted treatment programs that might result) will need pharmaceutical heroin (diacetylmorphine) to prescribe to the patients. Research into the development of pharmaceutical forms of heroin for prescription to addicts can benefit from the large amount of knowledge that already exists regarding this substance. Therefore, in this paper we review the physicochemical and pharmaceutical properties of diacetylmorphine and the clinically investigated routes of administration, as well as routes of administration utilised on the street in the context of developing pharmaceutical heroin formulations for prescription to addicts. Patient acceptability of the formulation is essential, because heroin-assisted treatment is aimed at treatment-resistant addicts, who often have to be encouraged to participate (or to maintain participation) in a treatment program. This means that the most suitable products would have pharmacokinetic profiles mimicking that of diacetylmorphine for injection, with rapid peak concentrations of diacetylmorphine and 6-acetylmorphine, ensuring the 'rush effect' and the sustained presence of morphine(-6-glucuronide) creating the prolonged euphoria. Diacetylmorphine for inhalation after volatilisation (via 'chasing the dragon') seems to be a suitable candidate, while intranasal and oral diacetylmorphine are currently thought to be unsuitable. However, oral and intranasal delivery systems might be improved and become suitable for use by heroin dependent patients.

  2. Engineering of PHB synthesis causes improved elastic properties of flax fibers.

    PubMed

    Wróbel-Kwiatkowska, Magdalena; Zebrowski, Jacek; Starzycki, Michał; Oszmiański, Jan; Szopa, Jan

    2007-01-01

    Flax stem is a source of fiber used by the textile industry. Flax fibers are separated from other parts of stems in the process called retting and are probably the first plant fibers used by man for textile purposes (1). Nowadays flax cultivation is often limited because of its lower elastic property compared to cotton fibers. Thus the goal of this study was to increase the flax fiber quality using a transgenic approach. Expression of three bacterial genes coding for beta-ketothiolase (phb A), acetoacetyl-CoA reductase (phb B), and PHB synthase (phb C) resulted in poly-beta-hydroxybutyrate (PHB) accumulation in the plant stem. PHB is known as a biodegradable thermoplastic displaying chemical and physical properties similar to those of conventional plastics (i.e., polypropylene). The fibers isolated from transgenic flax plants cultivated in the field and synthesizing PHB were then studied for biomechanical properties. All measured parameters, strength, Young's modulus, and energy for failure of flax fibers, were significantly increased. Thus the substantial improvement in elastic properties of fibers from the transgenic line has been achieved. Since the acetyl CoA, substrate for PHB synthesis, is involved not only for energy production but also for synthesis of many cellular constituents, the goal of this study was also the analysis of those metabolites, which interfere with plant physiology and thus fiber quality. The analyzed plants showed that reduction in lignin, pectin, and hemicellulose levels resulted in increased retting efficiency. A significant increase in phenolic acids was also detected, and this was the reason for improved plant resistance to pathogen infection. However, a slight decrease in crop production was detected.

  3. Improving Coastal Ocean Color Validation Capabilities through Application of Inherent Optical Properties (IOPs)

    NASA Technical Reports Server (NTRS)

    Mannino, Antonio

    2008-01-01

    Understanding how the different components of seawater alter the path of incident sunlight through scattering and absorption is essential to using remotely sensed ocean color observations effectively. This is particularly apropos in coastal waters where the different optically significant components (phytoplankton, detrital material, inorganic minerals, etc.) vary widely in concentration, often independently from one another. Inherent Optical Properties (IOPs) form the link between these biogeochemical constituents and the Apparent Optical Properties (AOPs). understanding this interrelationship is at the heart of successfully carrying out inversions of satellite-measured radiance to biogeochemical properties. While sufficient covariation of seawater constituents in case I waters typically allows empirical algorithms connecting AOPs and biogeochemical parameters to behave well, these empirical algorithms normally do not hold for case I1 regimes (Carder et al. 2003). Validation in the context of ocean color remote sensing refers to in-situ measurements used to verify or characterize algorithm products or any assumption used as input to an algorithm. In this project, validation capabilities are considered those measurement capabilities, techniques, methods, models, etc. that allow effective validation. Enhancing current validation capabilities by incorporating state-of-the-art IOP measurements and optical models is the purpose of this work. Involved in this pursuit is improving core IOP measurement capabilities (spectral, angular, spatio-temporal resolutions), improving our understanding of the behavior of analytical AOP-IOP approximations in complex coastal waters, and improving the spatial and temporal resolution of biogeochemical data for validation by applying biogeochemical-IOP inversion models so that these parameters can be computed from real-time IOP sensors with high sampling rates. Research cruises supported by this project provides for collection and

  4. Automatic conceptual indexing of French pharmaceutical theses.

    PubMed

    Mary, Vincent; Pouliquen, Bruno; Le Duff, Franck; Darmoni, Stefan J; Segui, Alain; Le Beux, Pierre

    2002-01-01

    French pharmaceutical theses are rarely quoted. If the main obstacles originate from language or access barriers, proper indexation could also be blamed. Manually extracted key-words don't necessary come from a structured thesaurus. In the following work, this manual indexing method is compared to an automated one, "Nomindex", based on UMLS. The automated method is improved by the addition of a relevance scoring system. The first indexing step consists of downloading, adapting and indexing theses in electronic format. Results will then be analyzed and sorted by relevance, through the comparison of classic statistical indices (noise, silence and relevance). It was assumed that the manually obtained key-words were always relevant. The silence of manual indexing is nevertheless high: seven new key-words are proposed by Nomindex, which results are mixed (10% of silence, but 50% of noise). These results are promising on the first experiment on pharmaceutical document without lexicon improvement. The indexing, if it is currently insufficient for a real life use, could easily be improved by specific updates of the lexicon.

  5. Advanced Technology for Improved Quantum Device Properties Using Highly Strained Materials

    DTIC Science & Technology

    1991-03-01

    Improved Quantum PE 61153N Device Properties Using Highly Strained Materials PE 1401N~R&T 414s 001-02 IN G. AUTHOR(S) (William J. Schaff , S.D. Offsey and...DECEMBER 15, 1989 CORNELL UNIVERSITY.......................... ITHACA, NY 14853-5401 PREPARED BY: WJ. Schaff ........ S.D. Offsey I - L.F. Eastman D ’’. i...Mandeville, R. Saito, P.J. Tasker, W.J. Schaff and L.F. Eastman, 12th IEEE/Comell Conference on’Advanced Concepts in High Speed Semiconductor Devices

  6. Research on the property improvement of PVC using red mud in industrial waste residue

    NASA Astrophysics Data System (ADS)

    Nie, Xiaopeng; Li, Xingang; Shuai, Songxian

    2015-07-01

    Red mud is a red solid power waste that is discharged in the aluminium refinery industry during production. It is a strong alkali and can be categorized as polluting industrial residue. How to make comprehensive use of red mud has become a worldwide issue. In this paper, we put red mud into PVC (polyvinyl chloride polymer), taking advantage of the complicated chemical properties of red mud derived from the Bayer process. The results are compared with silica fume, coal ash and calcium carbonate under the same experimental conditions, which shows that improvement of PVC plastication can be achieved by adding red mud.

  7. Improved retrievals of the optical properties of cirrus clouds by a combination of lidar methods.

    PubMed

    Cadet, Bertrand; Giraud, Vincent; Haeffelin, Martial; Keckhut, Philippe; Rechou, Anne; Baldy, Serge

    2005-03-20

    We focus on improvement of the retrieval of optical properties of cirrus clouds by combining two lidar methods. We retrieve the cloud's optical depth by using independently the molecular backscattering profile below and above the cloud [molecular integration (MI) method] and the backscattering profile inside the cloud with an a priori effective lidar ratio [particle integration (PI) method]. When the MI method is reliable, the combined MI-PI method allows us to retrieve the optimal effective lidar ratio. We compare these results with Raman lidar retrievals. We then use the derived optimal effective lidar ratio for retrieval with the PI method for situations in which the MI method cannot be applied.

  8. Improving predictions of root biomechanical properties, is age a better determinant than diameter?

    NASA Astrophysics Data System (ADS)

    Loades, Kenneth; Hallett, Paul; Lynch, Jonathan; Chimungu, Joseph; Bengough, Anthony

    2014-05-01

    Roots mechanically reinforce many soils. Root tensile strength and stiffness is critical for soil stabilisation with plants potentially providing civil engineers a 'green' alternative for soil stabilisation. Relatively little is known on factors influencing root tensile strength. Through a better understanding of these factors the adoption of 'green engineering' techniques by civil engineers will improve. Existing models are limited in their accuracy due to simplistic assumptions to derive root contributions to the resistance of soil to failure. Current models typically use relationships between strength and diameter, however, there are a number of other factors potentially influencing root biomechanical properties. The effects of root age on biomechanical properties have largely been overlooked. Barley (Hordeum vulgare) was grown under differing soil conditions, waterlogged, moderate mechanical impedance and in unimpeded, control, conditions. The root system was excavated and tensile tests performed on root sections along the length of each root axis. Root tensile strength increased with increasing distance along the root axes in control soil from 0.5 MPa to 7.0 MPa at a distance of 800mm from the root tip and from 1.0 Mpa to 8.0 MPa, 500mm from the root tip when under moderate mechanical impedance. Increases in strength were also observed when plants were subjected to waterlogging with tensile strength increasing from 1.0 MPa to 3.0 MPa, 200mm from the root tip. Young's modulus increased from ~10 MPa at the root tip to ~60 MPa 400mm and 800mm from the root tip in mechanically impeded and control treatments respectively. Distance from root tip explained over 47% of the variance in root tensile strength and 34% of root stiffness. Including root diameter in the model led to further improvements in predicting root properties, explaining ~54% of root strength variance and ~49% of root stiffness. Root age has been shown to improve predictions of root tensile strength

  9. Fabrication of flexible magnetic papers based on bacterial cellulose and barium hexaferrite with improved mechanical properties

    NASA Astrophysics Data System (ADS)

    Lim, Guh-Hwan; Lee, Jooyoung; Kwon, Nayoung; Bok, Shingyu; Sim, Hwansu; Moon, Kyoung-Seok; Lee, Sang-Eui; Lim, Byungkwon

    2016-09-01

    We report on a simple approach to fabricate mechanically robust magnetic cellulose papers containing M-type barium hexaferrite (BaFe12O19) nanoplates. BaFe12O19 nanoplates were synthesized by a hydrothermal method and then chemically functionalized by using a silane coupling agent. The magnetic cellulose papers prepared with the silane-treated BaFe12O19 nanoplates exhibited improved mechanical properties with tensile strength of 58.5 MPa and Young's modulus of 2.95 GPa.

  10. Effect of surface modified hydroxyapatite on the tensile property improvement of HA/PLA composite

    NASA Astrophysics Data System (ADS)

    Li, J.; Lu, X. L.; Zheng, Y. F.

    2008-11-01

    In this study, we modified the surface of hydroxyapatite (HA) particle by ring-opening polymerization of lactide (LA). The modified HA particles were characterized by IR and TGA. It was shown that LA could be graft-polymerized onto the surface of HA. A series of composites based on modified HA/PLA were further prepared and characterized. It indicated that the modified HA particles were well dispersed in PLA matrix than unmodified HA particles and the adhesion between HA particle and PLA matrix was improved. The modified HA/PLA composites showed good mechanical properties than that of unmodified HA/PLA.

  11. Explicit Runge-Kutta schemes for incompressible flow with improved energy-conservation properties

    NASA Astrophysics Data System (ADS)

    Capuano, F.; Coppola, G.; Rández, L.; de Luca, L.

    2017-01-01

    The application of pseudo-symplectic Runge-Kutta methods to the incompressible Navier-Stokes equations is discussed in this work. In contrast to fully energy-conserving, implicit methods, these are explicit schemes of order p that preserve kinetic energy to order q, with q > p. Use of explicit methods with improved energy-conservation properties is appealing for convection-dominated problems, especially in case of direct and large-eddy simulation of turbulent flows. A number of pseudo-symplectic methods are constructed for application to the incompressible Navier-Stokes equations and compared in terms of accuracy and efficiency by means of numerical simulations.

  12. [Bioequivalence studies of pharmaceutical preparations].

    PubMed

    Vetchý, D; Frýbortová, K; Rabisková, M; Danecková, H

    2007-01-01

    Bioequivalence studies are very important for the development of a pharmaceutical preparation in the pharmaceutical industry. Their rationale is the monitoring of pharmacokinetic and pharmacodynamic parameters after the administration of tested drugs. The target of such study is to evaluate the therapeutic compatibility of tested drugs (pharmaceutical equivalents or pharmaceutical alternatives). The importance of bioequivalence studies is increasing also due to the large growth of the production and consumption of generic products. Generic products represent approximately 50 % of the whole consumption in many European countries and USA. The search output of bioequivalence study is together with the pharmaceutical quality data of medical product one of the main part of the registration file submitted to a national regulatory authorities. The registration of generic products does not demand complicated and expensive clinical study contrary to original product. The comparison of the original and the generic product via bioequivalence study is suggested as sufficient. The aim of this article is to provide to a medical public a summary about the types of bioequivalence studies, their range, rules of their practise and let them gain their own attitude to this question.

  13. Fallow Effects on Improving Soil Properties and Decreasing Erosion: Atlantic Forest, Southeastern Brazil

    NASA Astrophysics Data System (ADS)

    Miranda, J. P.; Silva, L. M.; Lima, R. L.; Donagemma, G. K.; Bertolino, A. V. A.; Fernandes, N. F.; Correa, F. M.; Polidoro, J. C.; Tato, G.

    2009-04-01

    Soil tillage plays a major role in changing physical and hydrological properties of soils through time, and in consequence, in the dynamics of infiltration, soil water and erosion. In the hilly landscape of southeastern Brazil, many areas originally occupied by the Atlantic Forest (one the most threatened biomes on the planet) have been continuously transformed in the last decades into agricultural systems, usually associated with small farming properties. Traditionally, the agricultural activities in these areas incorporate rotational systems which include a fallow period, where previously farmed areas repose for at least five years. In some areas, vegetation grows so fast that after 7 or 8 years these sites may be considered by regulator agencies as forests, impeding their use again for farming. As a consequence, farmers tend to decrease the amount of time used fallow impeding the recovery of original soil properties, reducing in consequence the infiltration rate, and increasing the runoff and erosion. Currently, the Brazilian laws allow that the farmers use the fallow system for 10 years in areas where this technique has been used traditionally. So, a major issue here is for how long the farming plots should be left reposing. Therefore, this study aims both to characterize the effects of continuous farming on soil physical and hydrological properties, as well as to define the impacts of different fallow periods on the improvement of soil properties and in the reduction of runoff and erosion. The experiments were carried out in a cultivation site located at Bom Jardim city, close to Rio de Janeiro city. The area is situated at about 800m of elevation in the hilly steep topography of the Serra do Mar, a coast range in southeastern Brazil, with an average total annual rainfall of 2000 mm. In this study, carried out in a typical farm of the area, we compared the effects of 5 different soil usages on soil properties: banana, coffee, F2 (2-year fallow), F5 (5-year

  14. Intrinsic Tween 20 improves release and antilisterial properties of co-encapsulated nisin and thymol.

    PubMed

    Xiao, Dan; Gömmel, Christina; Davidson, P Michael; Zhong, Qixin

    2011-09-14

    Antimicrobial delivery systems have been proposed as potential solutions to improve effectiveness of antimicrobials in food matrixes by shielding antimicrobials from contacting food matrix components and releasing them continuously. In this work, spray-dried capsules were produced from zein solutions with the same concentrations of nisin and thymol but with varying Tween 20 contents for characterization of release kinetics of antimicrobials and antilisterial properties. At intermediate levels of Tween 20, sustained and more complete release of antimicrobials was observed at pH 6.0 and 8.0. Most capsule samples were more effective than free antimicrobials against Listeria monocytogenes in 2% reduced fat milk, and the best capsule treatment reduced the bacterial population by 2 log CFU/mL more than comparable free antimicrobials after 4 h incubation at 25 °C. Our work demonstrated that nonionic surfactant can be conveniently used to modulate characteristics of delivery systems to effectively improve antimicrobial functions in food systems.

  15. Improvement of mechanical properties by additive assisted laser sintering of PEEK

    SciTech Connect

    Kroh, M. Bonten, C.; Eyerer, P.

    2014-05-15

    The additive assisted laser sintering was recently developed at IKT: A carbon black (CB) additive is used to adjust the polymer's laser absorption behavior with the aim to improve the interconnection of sintered powder layers. In this paper a parameter study, Polyetheretherketone (PEEK) samples were prepared with different contents of carbon black and were laser sintered with varying thermal treatment. The samples were mechanically tested and investigated by optical light and transmission electron microscopy. An influence on the morphology at the border areas of particles and intersections of laser sintered layers was found. Depending on the viscosity of the raw material and CB content, different shapes of lamellae were observed. These (trans-) crystalline or polymorph structures, respectively, influence the thermal and mechanical behavior of the virgin PEEK. Moreover, the thermal treatment during the sintering process caused an improvement of mechanical properties like tensile strength and elongation at break.

  16. Improvement of Mechanical and Thermal Properties of CFRP Laminates Using Micro-Fibrillated Cellulose

    NASA Astrophysics Data System (ADS)

    Kim, Hyojin; Suzuki, Tadashi; Takemura, Kenichi

    The aim of this study is improvement of mechanical and thermal properties of plain woven carbon fiber (CF) reinforced epoxy with addition of MFC as the additive. Carbon fiber/epoxy laminates with addition 0.3, 0.5, 0.7 and 1wt% of MFC were characterized by flexural test, DSC and TMA. The result represented that the flexural strength improved slightly at 0.3 and 0.5 wt% of MFC, but flexural modulus was not changed, respectively. The glass transition temperature of MFC-CFRP laminates showed the increase according to increase of MFC addition at 0.7 and 1.0 wt%. The coefficient of thermal expansion was decrease by 0.7 wt% of MFC addition.

  17. Improvement in high stress abrasive wear property of steel by hardfacing

    SciTech Connect

    Kumar, S.; Mondal, D.P.; Khaira, H.K.; Jha, A.K.

    1999-12-01

    High stress abrasive wear behavior of mild steel, medium carbon steel, and hardfacing alloy has been studied to ascertain the extent of improvement in the wear properties after hardfacing of steel. High stress abrasive wear tests were carried out by sliding the specimen against the abrasive media consisting of silicon carbide particles, rigidly bonded on paper base and mounted on disk. Maximum wear was found in the case of mild steel followed by a medium carbon alloy steel and a hardfacing alloy. Different compositions of steels and constituent phases present led to different wear rates of the specimen. The extent of improvement in wear performance of steel due to hardfacing is quite appreciable (twice compared to mild steel). Microstructural examination of the wear surface has been carried out to understand the wear mechanism.

  18. Improvement of mechanical properties of fiber reinforced mortar using a linear optimization method

    NASA Astrophysics Data System (ADS)

    Kočí, V.; Černý, R.

    2017-02-01

    A linear optimization method is applied to improve mechanical properties of fiber reinforced cement mortar. Since this method is preferably used in other scientific disciplines, few preconditions are taken into account in advance, in order to accommodate it to the specifics related to building materials design. Defining physical limitations and accelerating the optimization process, the target values of optimization are reached in 21 days after 3 optimization steps. Within this relatively short time span, the compressive and bending strengths of fiber reinforced cement mortar increase from 36.9 to 52.2 MPa and from 9.1 to 10.1 MPa, respectively, while identical components are used. The improvements are achieved after preparation of only nine different mixtures, which is a very small number confirming the effectivity of this method in the field of building materials design.

  19. Improvement of reinforced concrete properties based on modified starch/polybutadiene nanocomposites.

    PubMed

    Saboktakin, Amin; Saboktakin, Mohammad Reza

    2014-09-01

    A novel polymer-modified cement concrete with carboxymethyl starch (CMS) and 1,4-cis polybutadiene (PBD) system by mixing polymer dispersions or redispersible polymer powders with the fresh mixture have been examined. In this paper, the addition of CMS-PBD powders in an aqueous solution is studied. Polymeric molecules are supplied on a molecular scale, improving the approach of the relatively large cement grains by the polymers. The chemical and mechanical properties of CMS-PBD-modified cement concrete have been studied. The additions of very small amounts of CMS-PBD polymeric system results in an improvement of the durability and the adhesion strength of the cementitious materials, which makes them appropriate as repair materials.

  20. Biocomposites of cellulose reinforced starch: improvement of properties by photo-induced crosslinking.

    PubMed

    Kumar, Annamalai Pratheep; Singh, Raj Pal

    2008-12-01

    In the present study, the composite films have been prepared from the aqueous dispersions of starch with microcrystalline cellulose using glycerol as plasticizer and irradiated under ultraviolet (UV) light using sodium benzoate as photo-sensitizer. Photo-crosslinking was characterized by measuring the water absorption under 100% relative humidity, swelling degree and gel fraction in dimethylsulphoxide (DMSO), upon irradiation time. Both, the incorporation of cellulose and photo-irradiation were found to decrease the water absorption, swelling in DMSO and increase the gel fraction. Thermal transitions indicated the anti-plasticization of amylopectin chains at the fiber/matrix interface. With increasing content of cellulose and photo-irradiation time, the tensile modulus and strength were found to improve. It is summarized that the combination of cellulose reinforcement and photo-crosslinking of matrix has improved the physical and mechanical properties.

  1. MOF-199: A simple strategy for improvement of crystallinity and photovoltaic property

    NASA Astrophysics Data System (ADS)

    Khajavian, Ruhollah; Ghani, Kamal

    2016-12-01

    In this study, thin films of MOF-199 were prepared using a Layer-by-Layer deposition approach and applied as sensitizing materials in TiO2-based solar cells. Our results indicate that by introducing 3,4-dihydroxybenzoic acid at the interface of TiO2-MOF via a simple surface modification step, TiO2 surface roughness is reduced and texture quality of MOF-199 polycrystalline film enhances along <111> crystallographic direction while the overall conversion efficiency of the cell increases as well. The improvement in Jsc could be a consequence of enhanced crystallinity, reduced surface roughness and enhanced light-harvesting properties of surface-modified photoanode. Dark I-V characteristics of the cells also indicate that the interfacial charge recombination at TiO2-MOF interface is inhibited upon introducing DHBA thus, Voc is improved.

  2. An Experimental Investigation towards Improvement of Thermoelectric Properties of Strontium Titanate Ceramics

    NASA Astrophysics Data System (ADS)

    Mehdizadeh Dehkordi, Arash

    The direct energy conversion between heat and electricity based on thermoelectric effects is a topic of long-standing interest in condensed matter materials science. Experimental and theoretical investigations in order to understand the mechanisms involved and to improve the materials properties and conversion efficiency have been ongoing for more than half a century. While significant achievements have been accomplished in improving the properties of conventional heavy element based materials (such as Bi2Te 3 and PbTe) as well as the discovery of new materials systems for the close-to-room temperature and intermediate temperatures, high-temperature applications of thermoelectrics is still limited to one materials system, namely SiGe. Recently, oxides have exhibited great potential to be investigated for high-temperature thermoelectric power generation. The objective of this dissertation is to synthesize and investigate both electronic and thermal transport in strontium titanate (SrTiO3) ceramics in order to experimentally realize its potential and to ultimately investigate the possibility of further improvement of the thermoelectric performance of this perovskite oxide for mid- to high temperature applications. Developing a synthesis strategy and tuning various synthesis parameters to benefit the thermoelectric transport form the foundation of this study. It is worth mentioning that the results of this study has been employed to prepare targets for pulsed-laser deposition (PLD) to study the thermoelectric properties of corresponding thin films and superlattice structures at Dr. Husam Alshareef's group at King Abdullah University of Science and Technology (KAUST), Saudi Arabia. Considering the broad range of functionality of SrTiO3, the findings of this work will surely benefit other fields of research and application of this functional oxide such as photoluminescence, ferroelectricity or mixed-ionic electronic conductivity. This dissertation will ultimately

  3. Inherent Anticipation in the Pharmaceutical and Biotechnology Industries.

    PubMed

    Goldman, Michael; Evans, Georgia; Zappia, Andrew

    2015-04-15

    Pharmaceutical and biotech research often involves discovering new properties of, or new methods to use, existing compositions. The doctrine of inherent anticipation, however, prevents the issuance and/or validity of a patent for discoveries deemed to have been implicitly disclosed in the prior art. This can be a barrier to patent rights in these technologies. Inherent anticipation therefore creates uncertainty for patent protection in the pharmaceutical and biotech sciences. Despite this uncertainty, Federal Circuit jurisprudence provides guidance on the boundaries of the inherent anticipation doctrine. In view of the case law, certain strategies may be employed to protect inventions that may potentially be viewed as inherent in the prior art.

  4. Pharmaceutical applications of mucoadhesion for the non-oral routes.

    PubMed

    Edsman, Katarina; Hägerström, Helene

    2005-01-01

    The adhesion of pharmaceutical formulations to the mucosal tissue offers the possibility of creating an intimate and prolonged contact at the site of administration. This prolonged residence time can result in enhanced absorption and, in combination with a controlled release of the drug, also improved patient compliance by reducing the frequency of administration. During the almost 30 years over which mucoadhesion has been studied, a considerable amount of knowledge has been gained, and much has been learned about the different mechanisms occurring at the formulation-mucus interface and the properties that affect these mechanisms. The in-vivo performance of a dosage form not only depends on the mechanisms occurring at the interface, but also on the properties of the total mucoadhesive complex: the dosage form, the mucosa and the interface between them. A wide variety of methods are used for studying mucoadhesion; some rather similar to the in-vivo situation and some mimicking the interface alone. In this review, the mucus surface, the methods used for the study of mucoadhesion, the different mechanisms involved in mucoadhesion and theories underpinning them have been described. The complexity of mucoadhesion when trying to systemize the subject will also be discussed. The last part of the review describes the buccal, nasal, ocular, vaginal and rectal routes and provides examples of what can be achieved in-vivo when using mucoadhesive formulations.

  5. Recombinant Wheat Endoplasmic Reticulum Oxidoreductin 1 Improved Wheat Dough Properties and Bread Quality.

    PubMed

    Liu, Guang; Wang, JingJing; Hou, Yi; Huang, Yan-Bo; Zhang, Ya-Ping; Li, Cunzhi; Li, Lin; Hu, Song-Qing

    2017-03-15

    Recombinant wheat endoplasmic reticulum oxidoreductin 1 (wEro1) with considerable ability was expressed in Escherichia coli. The functional roles of wEro1 in flour processing quality were investigated by farinographic, rheological, texture profile analysis, electrophoresis, size exclusion chromatography, scanning electron microscopy, and Fourier transform infrared spectroscopy. wEro1 exhibited an obvious oxidation activity of sulfhydryl groups in small molecule and protein. Addition of wEro1 could strengthen the processing quality of dough, indicated by the improved mixing characteristics, viscoelastic properties, and bread qualities. These improvement effects of wEro1 could be attributed to the formation of macromolecular gluten polymers and massive gluten networks by disulfide cross-linking. Additionally, the increased β-turn structure further demonstrated the enhancement of dough strength. Moreover, the amount of peroxide in dough was improved significantly from 2.36 to 2.82 μmol/g of flour with 0.15% wEro1 treatment. Therefore, the results suggested that wEro1 is a promising novel flour improver.

  6. Improvement of OLED properties with the AlN insulated layer

    NASA Astrophysics Data System (ADS)

    Liu, Chunling; Wang, Jin; Wang, Chunwu; Zhao, Lei; Jiang, Wenlong

    2010-11-01

    The thin aluminum nitride(AlN) film using as an insulating layer was inserted between the anode (ITO) and the NPB organic film in the organic light-emitting devices(OLED) for the structure being K9/ITO/AlN/NPB/Alq3/LiF/Al.The effect of the different thickness AlN film on the device performance was investigated. After optimization, improvement of OLEDs properties is biggest when the AlN film thickness is about 0.4nm.Such a structure with AlN layer facilitates the increase of current density and decrease of threshold voltage, resulting in an improved luminance and energy efficiency. The average luminance increased by about 30% and an improvement of 21.8% on the average current density. The lifetime experiment of the devices has proved an improvement on stability because of inserted AlN film. This phenomenon is mainly because of the insulating capability of the aluminum nitride coating and the passivation role of AlN film to the ITO surface. The processing is simple and high efficient, can be widely applied to the OLED devices.

  7. Chemistry in the Pharmaceutical Industry

    NASA Astrophysics Data System (ADS)

    Poindexter, Graham S.; Pendri, Yadagiri; Snyder, Lawrence B.; Yevich, Joseph P.; Deshpande, Milind

    This chapter will discuss the role of chemistry within the pharmaceutical industry. Although the focus will be upon the industry within the United States, much of the discussion is equally relevant to pharmaceutical companies based in other first world nations such as Japan and those in Europe. The major objective of the pharmaceutical industry is the discovery, development, and marketing of efficacious and safe drugs for the treatment of human disease. Of course drug companies do not exist as altruistic, charitable organizations but like other share-holder owned corporations within our capitalistic society must achieve profits in order to remain viable and competitive. Thus, there exists a conundrum between the dual goals of enhancing the quality and duration of human life and that of increasing stock-holder equity. Much has been written and spoken in the lay media about the high prices of prescription drugs and the hardships this places upon the elderly and others of limited income.

  8. Macro trends in pharmaceutical innovation.

    PubMed

    Cohen, Fredric J

    2005-04-01

    Extract: A lately recycled criticism of the pharmaceutical industry is that it is failing in its mission to innovate. In particular, critics question the industry's incentives to innovate, and they deride those innovations the industry makes as imitative. Industry advocates contend the opposite. The truth is that there are no generally accepted measures of innovation that would conclusively prove either side's point. However, I have found trends in several measures that support both sides of the innovation debate. Overall, the bulk of evidence suggests that the pharmaceutical industry continues to regard pioneering innovations as important (evidenced by the motivation, effort and ability of the industry to create such innovations). However, like other mature manufacturing industries, the pharmaceutical industry relies heavily on incremental innovations (what critics call "me-too" drugs) to sustain its profits. To a large extent, these incremental innovations are themselves medically beneficial and should be encouraged rather than dismissed as merely imitative.

  9. Planning and coordinating pharmaceutical purchasing.

    PubMed

    Buchanan, E C

    1984-09-01

    The planning and coordination of the pharmaceutical purchasing process are discussed. Planning for pharmaceutical purchasing should begin with decisions regarding why a purchasing policy is needed, what the institution's purchasing policy will be, and what departments will be involved in purchasing. General goals of purchasing and procedures for revising purchasing functions are presented, and the role of the pharmacy department, materials management, and other hospital departments in purchasing is discussed. Coordinating input on purchasing decisions from medical staff, administration, and clinical and technical pharmacy personnel to achieve purchasing goals and objectives is discussed. A well-designed pharmaceutical purchasing system provides for planned and scheduled purchases, competitive bidding, product standardization, group purchasing, information sharing, internal accountability, and quality assurance.

  10. Are Pharmaceutical Patents Protected By Human Rights?

    PubMed Central

    Millum, Joseph

    2016-01-01

    The International Bill of Rights enshrines a right to health, which includes a right to access essential medicines. This right frequently appears to conflict with the intellectual property regime that governs pharmaceutical patents. However, there is also a human right that protects creative works, including scientific productions. Does this right support intellectual property protections, even when they may negatively affect health? This article examines the recent attempt by the Committee on Economic, Social and Cultural Rights to resolve this issue and argues that it fails. This is problematic because it means defenders of the present patent regime can continue using human rights documents to support their position. I offer a new framework for resolving the problem by examining the values that underlie human rights. PMID:18974405

  11. Pharmaceutical applications of dynamic mechanical thermal analysis.

    PubMed

    Jones, David S; Tian, Yiwei; Abu-Diak, Osama; Andrews, Gavin P

    2012-04-01

    The successful development of polymeric drug delivery and biomedical devices requires a comprehensive understanding of the viscoleastic properties of polymers as these have been shown to directly affect clinical efficacy. Dynamic mechanical thermal analysis (DMTA) is an accessible and versatile analytical technique in which an oscillating stress or strain is applied to a sample as a function of oscillatory frequency and temperature. Through cyclic application of a non-destructive stress or strain, a comprehensive understanding of the viscoelastic properties of polymers may be obtained. In this review, we provide a concise overview of the theory of DMTA and the basic instrumental/operating principles. Moreover, the application of DMTA for the characterization of solid pharmaceutical and biomedical systems has been discussed in detail. In particular we have described the potential of DMTA to measure and understand relaxation transitions and miscibility in binary and higher-order systems and describe the more recent applications of the technique for this purpose.

  12. Self-emulsifying excipient platform for improving technological properties of alginate-hydroxypropylcellulose pellets.

    PubMed

    Mannina, Paolo; Segale, Lorena; Giovannelli, Lorella; Bonda, Andrea Foglio; Pattarino, Franco

    2016-02-29

    In this work, alginate, alginate-pectin and alginate-hydroxypropylcellulose pellets were produced by ionotropic gelation and characterized. Ibuprofen was selected as model drug; it was suspended in the polymeric solution in crystalline form or dissolved in a self-emulsifying phase and then dispersed into the polymeric solution. The self-emulsifying excipient platform composed of Labrasol (PEG-8 caprylic/capric glycerides) and d-α-tocopherol polyethylene glycol 1000 succinate (TPGS), able to solubilize the drug was used to improve the technological and biopharmaceutical properties of the alginate pellets. The pellets had diameters between 1317 and 2026 μm and a high drug content (>51%). DSC analysis showed the amorphous state of drug in the pellets containing the self-emulsifying phase. All the systems restricted drug release in conditions simulating the gastric environment and made the drug completely available at a pH value typical for the intestine. Only alginate-HPC systems containing the drug solubilized into the self-emulsifying phase showed the ability to partially control the release of ibuprofen at neutral pH. The self-emulsifying excipient platform is a useful tool to improve technological and biopharmaceutical properties of alginate-HPC pellets.

  13. Enzymic dephosphorylation of bovine casein to improve acid clotting properties and digestibility for infant formula.

    PubMed

    Li-Chan, E; Nakai, S

    1989-01-01

    To improve acid clotting properties, enzymic dephosphorylation of caseins with calf intestinal alkaline phosphatase (CAP) or potato acid phosphatase (PAP) was investigated. Greater dephosphorylation was achieved using alpha s1- or beta-casein as substrates, compared to whole casein or skim milk. Electrophoresis of PAP-modified caseins revealed bands with lower mobility and a multibanded pattern in the beta-casein region which was similar to that of human beta-casein. On the other hand, CAP modification produced electrophoretic bands having lower mobility of the beta-casein component, but with higher mobility in the alpha s1-casein component as well as increased net negative charge in the CAP-casein. PAP-casein formed a fine dispersion upon acidification to pH 4, with a microstructure similar to that of acidified human casein. Greater initial rates of hydrolysis by pepsin at pH 4 were observed for both CAP- and PAP-modified caseins, compared to bovine and human caseins. The rate and extent of hydrolysis remained high for CAP-casein but tended to level off with PAP-casein during sequential digestion with pepsin and pancreatin. There may be advantages in the use of partial dephosphorylation to improve acid clotting and digestibility properties of bovine casein for infant feeding.

  14. Improvement in the mechanical properties of PTFE bonded NdFeB magnets by heat treatment

    NASA Astrophysics Data System (ADS)

    Tattam, C.; Williams, A. J.; Hay, J. N.; Harris, I. R.; Tedstone, S. F.; Ashraf, M. M.

    1996-05-01

    Rotary forging has been used to produce high density bonded magnets using NdFeB based melt spun ribbons (MQP-D). The binder used was polytetrafluoroethylene (PTFE). A post-forging heat treatment at temperatures above the crystalline melting point of PTFE (˜ 340°C) has been seen to improve substantially the mechanical integrity of the compacts. Heat treatments that were undertaken in air resulted in oxidation of the magnets, but the extent of oxidation was reduced with increasing PTFE content, characterised by a greater retention of magnetic properties. This behaviour suggests that to some extent. PTFE is effective as a barrier to oxidation. By heat treating in a vacuum, an improvement of over 100% in the mechanical strength of the compacts could be obtained with little loss in the magnetic properties. The fracture surfaces of both as-forged and heat treated compacts have been examined using scanning electron microscopy and it appears that bonding between the melt spun ribbon (MQI) and PTFE occurs during heat treatment.

  15. Polylactic acid with improved heat deflection temperatures and self-healing properties for durable goods applications.

    PubMed

    Wertz, J T; Mauldin, T C; Boday, D J

    2014-11-12

    A method to recover fracture toughness after failure and increase thermal properties of polylactic acid (PLA) for use within durable goods applications is presented. Microcapsules were incorporated into PLA to form a composite material in which the microcapsules served the dual purpose of (1) releasing self-healing additives to fracture regions and (2) serving as nucleating agents to improve the PLA composite's thermal tolerance. Self-healing was achieved though embedment of dicyclopentadiene-filled microcapsules and Grubbs' first generation ruthenium metathesis catalyst, the former being autonomically released into damage volumes and undergoing polymerization in the presence of the catalyst. This approach led to up to 84% recovery of the polymer composite's initial fracture toughness. Additionally, PLA's degree of crystallinity and heat deflection temperature were improved by ∼ 11% and ∼ 21 °C, respectively, relative to nonfilled virgin PLA, owing to microcapsule-induced nucleation. The self-healing system developed here overcomes many property limitations of PLA that can potentially lead to its incorporation into various durable goods.

  16. Manipulating dispersion and distribution of graphene in PLA through novel interface engineering for improved conductive properties.

    PubMed

    Fu, Yu; Liu, Linshu; Zhang, Jinwen

    2014-08-27

    This study aimed to enhance the conductive properties of PLA nanocomposite by controlling the dispersion and distribution of graphene within the minor phase of the polymer blend. Functionalized graphene (f-GO) was achieved by reacting graphene oxide (GO) with various silanes under the aid of an ionic liquid. Ethylene/n-butyl acrylate/glycidyl methacrylate terpolymer elastomer (EBA-GMA) was introduced as the minor phase to tailor the interface of matrix/graphene through reactive compatibilization. GO particles were predominantly dispersed in PLA in a self-agglomerating pattern, while f-GO was preferentially located in the introduced rubber phase or at the PLA/EBA-GMA interfaces through the formation of the three-dimensional percolated structures, especially for these functionalized graphene with reactive groups. The selective localization of the f-GO also played a crucial role in stabilizing and improving the phase morphology of the PLA blend through reducing the interfacial tension between two phases. The establishment of the percolated network structures in the ternary system was responsible for the improved AC conductivity and better dielectric properties of the resulting nanocomposites.

  17. Multivalent pIX phage display selects for distinct and improved antibody properties

    PubMed Central

    Høydahl, Lene S.; Nilssen, Nicolay R.; Gunnarsen, Kristin S.; Pré, M. Fleur du; Iversen, Rasmus; Roos, Norbert; Chen, Xi; Michaelsen, Terje E.; Sollid, Ludvig M.; Sandlie, Inger; Løset, Geir Å.

    2016-01-01

    Phage display screening readily allows for the identification of a multitude of antibody specificities, but to identify optimal lead candidates remains a challenge. Here, we direct the antibody-capsid fusion away from the signal sequence-dependent secretory SEC pathway in E. coli by utilizing the intrinsic signal sequence-independent property of pIX to obtain virion integration. This approach was combined with the use of an engineered helper phage known to improve antibody pIX display and retrieval. By direct comparison with pIII display, we demonstrate that antibody display using this pIX system translates into substantially improved retrieval of desired specificities with favorable biophysical properties in de novo selection. We show that the effect was due to less E. coli host toxicity during phage propagation conferred by the lack of a signal sequence. This pIX combinatorial display platform provides a generic alternative route for obtaining good binders with high stability and may thus find broad applicability. PMID:27966617

  18. A numerical investigation on mechanical property improvement of styrene butadine rubber by static straight blade indentation

    NASA Astrophysics Data System (ADS)

    Setiyana, B.; Ismail, R.; Jamari, J.; Schipper, D. J.

    2016-04-01

    Mechanical property improvement of rubber is widely carried out by adding carbon black or silica as a filler in rubber. In general, this improvement aims on the increase of stiffness and abrasion resistance. By means of the static straight blade indentation technique, this paper studies the mechanical properties of Unfilled Styrene Butadiene Rubber (SBR-0) and Filled Styrene Butadiene Rubber that is compounded with carbon black (SBR-25). The numerical method applied was Finite Element Analysis (FEA) in which the rubber was modeled as a hyper-elastic material and indented by a blade indenter with various wedge angles i.e. 30, 45 and 60 degrees. At the same depth of indentation, the results showed that there was an increase in both rubber stiffness and maximum stress if the rubber was compounded. However, it is found that the rubber stiffness showed a regular slight increase, while the maximum stress experienced an irregularly significant increase. Especially for the 30 degree wedge angle, the maximum stress extremely increased at a certain depth of indentation.

  19. Structure-based improvement of the biophysical properties of immunoglobulin VH domains with a generalizable approach.

    PubMed

    Ewert, Stefan; Honegger, Annemarie; Plückthun, Andreas

    2003-02-18

    In a systematic study of V gene families carried out with consensus V(H) and V(L) domains alone and in combinations in the scFv format, we found comparatively low expression yields and lower cooperativity in equilibrium unfolding in antibody fragments containing V(H) domains of human germline families 2, 4, and 6. From an analysis of the packing of the hydrophobic core, the completeness of charge clusters, the occurrence of unsatisfied hydrogen bonds, and residues with low beta-sheet propensities, positive Phi angles, and exposed hydrophobic side chains, we pinpointed residues potentially responsible for the unsatisfactory properties of these germline-encoded sequences. Several of those are in common between the domains of the even-numbered subgroups, but do not occur in the odd-numbered ones. In this study, we have systematically exchanged those residues alone and in combination in two different scFvs using the V(H)6 framework, and we describe their effect on equilibrium stability and folding yield. We improved the stability by 20.9 kJ/mol and the expression yield by a factor of 4 and can now use these data to rationally engineer antibodies derived from this and similar germline families for better biophysical properties. Furthermore, we provide an improved design for libraries exploiting the significant additional diversity provided by these frameworks. Both antibodies studied here completely retain their binding affinity, demonstrating that the CDR conformations were not affected.

  20. Perovskite phase formation, microstructure and improvement of dielectric properties in iron-containing ferroelectrics

    NASA Astrophysics Data System (ADS)

    Fang, Bijun; Geng, Baoyou; Wei, Xianwen; Shan, Yuejin; Tezuka, Keitaro; Imoto, Hideo

    2006-08-01

    Pure perovskite-phase lead iron scandium niobate, Pb(Fe1/4Sc1/4Nb1/2)O3 (PFScN), ceramics have been prepared by a conventional solid-state reaction method via a B-site oxide mixing route. Although synthesis conditions have been tailored to optimization, strong frequency dispersion of the dielectric properties cannot be improved by modifying ceramic processing, which is considered as correlating to the nature of iron-containing ferroelectrics. Sintering in an O2 atmosphere and MnO2 and Li2CO3 dopings tend to decrease the dielectric loss of the iron-containing dielectrics. The strong frequency dispersion of the dielectric response and the abnormally recurrent increase of the dielectric constant and loss in the paraelectric region are correspondingly suppressed. This improvement of dielectric properties in the iron-containing ferroelectrics is interpreted by an electron compensation mechanism, in which the generation of donor electrons is based on different ionization paths.

  1. Multivalent pIX phage display selects for distinct and improved antibody properties.

    PubMed

    Høydahl, Lene S; Nilssen, Nicolay R; Gunnarsen, Kristin S; Pré, M Fleur du; Iversen, Rasmus; Roos, Norbert; Chen, Xi; Michaelsen, Terje E; Sollid, Ludvig M; Sandlie, Inger; Løset, Geir Å

    2016-12-14

    Phage display screening readily allows for the identification of a multitude of antibody specificities, but to identify optimal lead candidates remains a challenge. Here, we direct the antibody-capsid fusion away from the signal sequence-dependent secretory SEC pathway in E. coli by utilizing the intrinsic signal sequence-independent property of pIX to obtain virion integration. This approach was combined with the use of an engineered helper phage known to improve antibody pIX display and retrieval. By direct comparison with pIII display, we demonstrate that antibody display using this pIX system translates into substantially improved retrieval of desired specificities with favorable biophysical properties in de novo selection. We show that the effect was due to less E. coli host toxicity during phage propagation conferred by the lack of a signal sequence. This pIX combinatorial display platform provides a generic alternative route for obtaining good binders with high stability and may thus find broad applicability.

  2. Improvement of the Pharmacological Properties of Maize RIP by Cysteine-Specific PEGylation

    PubMed Central

    Au, Ka-Yee; Shi, Wei-Wei; Qian, Shuai; Zuo, Zhong; Shaw, Pang-Chui

    2016-01-01

    To improve the pharmacological properties of maize ribosome-inactivating protein (maize RIP) for targeting HIV-infected cells, the previously engineered TAT-fused active form of maize RIP (MOD) was further engineered for cysteine-directed PEGylation. In this work, two potential antigenic sites, namely Lys-78 and Lys-264, were identified. They were mutated to cysteine residue and conjugated with PEG5k or PEG20k. The resultant PEG derivatives of MOD variants were examined for ribosome-inactivating activity, circulating half-life and immunogenicity. Our results showed that MOD-PEG conjugates had two- to five-fold lower biological activity compared to the wild-type. Mutation of the two sites respectively did not decrease the anti-MOD IgG and IgE level in mice, but the conjugation of PEG did dramatically reduce the antigenicity. Furthermore, pharmacokinetics studies demonstrated that attachment of PEG20k prolonged the plasma half-life by five-fold for MOD-K78C and 17-fold for MOD-K264C, respectively. The site-specific mutation together with PEGylation therefore generated MOD derivatives with improved pharmacological properties. PMID:27763506

  3. Improved Measurement of Elastic Properties of Cells by Micropipette Aspiration and Its Application to Lymphocytes.

    PubMed

    Esteban-Manzanares, Gustavo; González-Bermúdez, Blanca; Cruces, Julia; De la Fuente, Mónica; Li, Qingxuan; Guinea, Gustavo V; Pérez-Rigueiro, José; Elices, Manuel; Plaza, Gustavo R

    2017-01-17

    Mechanical deformability of cells is an important property for their function and development, as well as a useful marker of cell state. The classical technique of micropipette aspiration allows single-cell studies and we provide here a method to measure the two basic mechanical parameters, elastic modulus and Poisson's ratio. The proposed method, developed from finite-element analysis of micropipette aspiration experiments, may be implemented in future technologies for the automated measurement of mechanical properties of cells, based on the micropipette aspiration technique or on the cell transit through flow constrictions. We applied this method to measure the elastic parameters of lymphocytes, in which the mechanical properties depend on their activation state. Additionally, we discuss in this work the accuracy of previous models to estimate the elastic modulus of cells, in particular the analytical model by Theret et al., widely used in the field. We show the necessity of using an improved model, taking into account the finite size of the cells, to obtain new insights that may remain hidden otherwise.

  4. Use of Mucor miehei lipase to improve functional properties of yolk-contaminated egg whites.

    PubMed

    Macherey, Laura N; Conforti, Frank D; Eigel, William; O'Keefe, Sean F

    2011-05-01

    Egg yolk contamination of egg whites continues to be a serious problem in the egg industry. The ability of egg whites to form stable and voluminous foams is greatly inhibited by yolk contamination, even at very low levels, between 0.01% and 0.2% w/w yolk in white. Experiments were conducted to determine if Mucor miehei lipase could regenerate the functional properties of yolk-contaminated egg whites. Lipase from M. miehei and colipase from porcine pancreas were added to yolk-contaminated (0.2%, w/w) egg white samples to hydrolyze triglycerides originating from egg yolk. Enzymatic hydrolysis of triacylglycerols was confirmed using thin-layer chromatography. Treatment of yolk-contaminated samples with lipase and colipase yielded significant (P < 0.05) improvements in a number of the functional properties, including the final foam volume, foam capacity, and foaming power. These functional properties showed complete restoration to control levels. However, foam stability and foam drainage levels were not statistically different from yolk-contaminated samples that had not been enzymatically treated. Enzyme-treated yolk-contaminated egg whites were also tested in angel food cakes. Enzyme-treated, yolk-contaminated egg whites performed similarly to non-yolk-contaminated control, and much better than yolk-contaminated sample in angel food cakes. The results show that most negative effects of yolk contamination can be reversed by treatment with Mucor miehei lipase and colipase.

  5. Improving the mechanical properties of collagen-based membranes using silk fibroin for corneal tissue engineering.

    PubMed

    Long, Kai; Liu, Yang; Li, Weichang; Wang, Lin; Liu, Sa; Wang, Yingjun; Wang, Zhichong; Ren, Li

    2015-03-01

    Although collagen with outstanding biocompatibility has promising application in corneal tissue engineering, the mechanical properties of collagen-based scaffolds, especially suture retention strength, must be further improved to satisfy the requirements of clinical applications. This article describes a toughness reinforced collagen-based membrane using silk fibroin. The collagen-silk fibroin membranes based on collagen [silk fibroin (w/w) ratios of 100:5, 100:10, and 100:20] were prepared by using silk fibroin and cross-linking by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide. These membranes were analyzed by scanning electron microscopy and their optical property, and NaCl and tryptophan diffusivity had been tested. The water content was found to be dependent on the content of silk fibroin, and CS10 membrane (loading 10 wt % of silk fibroin) performed the optimal mechanical properties. Also the suture experiments have proved CS10 has high suture retention strength, which can be sutured in rabbit eyes integrally. Moreover, the composite membrane proved good biocompatibility for the proliferation of human corneal epithelial cells in vitro. Lamellar keratoplasty shows that CS10 membrane promoted complete epithelialization in 35 ± 5 days, and their transparency is restored quickly in the first month. Corneal rejection reaction, neovascularization, and keratoconus are not observed. The composite films show potential for use in the field of corneal tissue engineering.

  6. Improved broadband and quasi-omnidirectional anti-reflection properties with biomimetic silicon nanostructures

    NASA Astrophysics Data System (ADS)

    Huang, Yi-Fan; Chattopadhyay, Surojit; Jen, Yi-Jun; Peng, Cheng-Yu; Liu, Tze-An; Hsu, Yu-Kuei; Pan, Ci-Ling; Lo, Hung-Chun; Hsu, Chih-Hsun; Chang, Yuan-Huei; Lee, Chih-Shan; Chen, Kuei-Hsien; Chen, Li-Chyong

    2007-12-01

    Nature routinely produces nanostructured surfaces with useful properties, such as the self-cleaning lotus leaf, the colour of the butterfly wing, the photoreceptor in brittlestar and the anti-reflection observed in the moth eye. Scientists and engineers have been able to mimic some of these natural structures in the laboratory and in real-world applications. Here, we report a simple aperiodic array of silicon nanotips on a 6-inch wafer with a sub-wavelength structure that can suppress the reflection of light at a range of wavelengths from the ultraviolet, through the visible part of the spectrum, to the terahertz region. Reflection is suppressed for a wide range of angles of incidence and for both s- and p-polarized light. The antireflection properties of the silicon result from changes in the refractive index caused by variations in the height of the silicon nanotips, and can be simulated with models that have been used to explain the low reflection from moth eyes. The improved anti-reflection properties of the surfaces could have applications in renewable energy and electro-optical devices for the military.

  7. Graphene-Alumina Nanocomposites with Improved Mechanical Properties for Biomedical Applications.

    PubMed

    Liu, Jian; Yang, Yang; Hassanin, Hany; Jumbu, Neeraj; Deng, Sunan; Zuo, Qian; Jiang, Kyle

    2016-02-03

    This paper presents a study on graphene platelet (GPL)-reinforced alumina (Al2O3) ceramic composites and the relationships between the loading of GPL and both mechanical properties and in vitro biocompatibility. Al2O3 powders with different GPL contents were prepared and sintered using a gas protected pressure-less furnace. The examination of the results shows the density of the composites varying from 99.2% to 95.6% with the loading of GPL from 0.75 to 1.48 vol %. Raman studies show that moderate agglomerations of GPLs occur during the ball milling process and graphitic defects were produced during the high temperature processing. Mechanical properties of the Al2O3 matrix are significantly improved by adding GPLs. A maximum increase of approximately 60% in flexural strength and 70% in fracture toughness are achieved by introducing 0.75 vol % GPLs. In the biocompatibility tests, it was found that cells directly seeding on top of GPL/Al2O3 samples showed better initial attachment (3 h after seeding) and viability (3 days after incubation) than the monolithic Al2O3, indicating that the GPL/Al2O3 composites have comparable or more favorable biocompatibility. The excellent mechanical and biomedical properties of the GPL/Al2O3 composites may enable them to be applied to a wide range of engineering and biomedical applications.

  8. Improvement of mechanical properties of pellet containing tablets by thermal treatment.

    PubMed

    Csobán, Zsombor; Kállai-Szabó, Barnabás; Kállai-Szabó, Nikolett; Sebe, István; Gordon, Péter; Antal, István

    2015-12-30

    Batches of partially spray-dried lactose tablets with three different initial tensile strength (∼20N, ∼35N, ∼50N) were made. Changes along a 24h long thermal treatment at 100°C in tensile strength, friability, individual mass, water content, disintegration time, average free volume and wetting properties were evaluated. Caffeine containing gastroresistant pellets were gained by drug layering and filmcoating of inert microcrystalline cellulose pellet cores in fluid bed equipment. Shape, size, mechanical properties, drug content and dissolution profile of the coated pellets were determined. Batches of pellet containing tablets with three different pellet-filler ratios were compressed where partially spray-dried lactose was used as a filler-binder material.Characteristics of pellet containing tablets were evaluated before and after a 24h long thermal treatment at 100°C. Results shown that the poor initial mechanical properties (friability, tensile strength) were improved by thermal exposure while there were no remarkable alterations in drug release profiles.

  9. High-Temperature Synthesis of Ordered Mesoporous Aluminosilicates from ZSM-5 Nanoseeds with Improved Acidic Properties.

    PubMed

    Vu, Xuan Hoan; Eckelt, Reinhard; Armbruster, Udo; Martin, Andreas

    2014-08-18

    Ordered mesoporous SBA-15 analogs with different Si/Al ratios were successfully prepared in a two-step process from self-assembly of ZSM-5 nanoseeds at high temperature in mildly acidic media (473 K, pH 3.5). The obtained products were characterized as SAXS, XRD, N₂ sorption, FTIR, TEM, NH₃-TPD, AAS and ICP. The results show that the initial Si/Al molar ratio of ZSM-5 precursors strongly affects the final materials' properties. A highly condensed, well-ordered mesoporous SBA-15 analog with improved hydrothermal stability and acidic properties can be prepared from low aluminum containing ZSM-5 precursors (Si/Al ≥ 20). Reducing the initial Si/Al molar ratio to 10, however, leads to the formation of a disordered mesoporous SBA-15 type material accompanied by degraded textural and acidic properties. The gas phase cracking of cumene, carried out as probe reaction to evaluate Brønsted acidity, reveals that an increased density of Brønsted acid sites has been achieved over the SBA-15 analogs compared to conventional Al-SBA-15 due to the preservation of zeolite building units in the mesopore walls of the SBA-15 analogs.

  10. Improvement on Physical Properties of Pullulan Films by Novel Cross-Linking Strategy.

    PubMed

    Chen, Chieh-Ting; Chen, Kuan-I; Chiang, Hsin-Han; Chen, Yu-Kuo; Cheng, Kuan-Chen

    2017-01-01

    Pullulan based films possess several advantages, including high transparency, low toxicity, good biodegradability, good mechanical properties, and low oxygen permeability, are preferable for food packaging. The application of pullulan films on food packaging, however, has inherent disadvantage of high water solubility. In this study, glutaraldehyde and glycerol were used as the cross-linking reagent and the plasticizer respectively to improve water resistance and physical properties of the pullulan films. Effects of cross-linking degree on physical properties, including water absorptions, swelling behaviors, water vapor permeability and tensile strengths of films were evaluated. FTIR results demonstrated that the pullulan films were successfully cross-linked by glutaraldehyde. The tensile strength of pullulan films could be enhanced significantly (P < 0.05) when glutaraldehyde was between 1% and 5% (w/w); nevertheless, the amount of glutaraldehyde above 20% (w/w) led to films brittleness. With the addition of glycerol as a plasticizer enhanced the extensibility of films as well as the hydrophilicity, resulting in higher water vapor permeability.

  11. New Soft Magnetic Composites for electromagnetic applications with improved mechanical properties

    NASA Astrophysics Data System (ADS)

    Ferraris, Luca; Pošković, Emir; Franchini, Fausto

    2016-05-01

    The chance to move from 2D to 3D approach in the design of the electrical machines is made possible by the availability of Soft Magnetic Composites (SMC), iron based powders, insulated and pressed to realize shapes otherwise impossible with the traditional lamination sheets technology. Some commercial products are available on the market as "ready to press" powders, which presents good magnetic and energetic properties but are sometimes weak under the mechanical point of view; other products aim at improving this aspect but with considerable process complications and relative cost. The experience of the Authors in the realization of bonded magnets with the adoption of selected organic resins has been partly transferred in the research field of the SMC in order to investigate the possibility to obtain good mechanical properties maintaining the magnetic characteristics of the Insulated Iron Powder Compounds (I.I.P.C.) taken as reference. The paper presents the activity that has been carried out in the realization of SMC mixing iron powders and phenolic resin, in different weight percentages and mold pressures. The obtained results are considered satisfactory under the point of view of the compromise between magnetic and mechanical properties, considering also that the required productive process is simpler. The comparison of the obtained results with those related to commercial products encourages to carry on the research, also because of the reduced cost of the proposed SMC at parity (or better) performance.

  12. Possibility of tree selection and breeding for genetic improvement of wood properties of Gmelina arborea

    SciTech Connect

    Akachuku, A.E.

    1984-06-01

    Wood samples of Gmelina arborea were collected from Nigerian plantations. The wood density was measured with an X-ray densitometer. Fiber length was measured with a modified map measurer. Fiber proportion was determined with a modification of Ladell's (1959) randomized dot technique. Considerable between-tree differences were observed in wood density, fiber length, fiber proportion, and sizes of trees of the same age, planted at the same spacing within the same environment. The magnitude of within-tree variations in these wood properties was different in trees within the same plot. Some individual trees combined comparatively high density, fiber length, and fiber proportion with fast growth rate and uniform wood. There was sufficient phenotypic variation to encourage genetic improvement of the wood properties and growth rate by selecting and breeding trees with higher values of these traits. Tree selection should be based on a preliminary screening for tree form and volume growth followed by a second selection for the desired wood properties.

  13. High-Temperature Synthesis of Ordered Mesoporous Aluminosilicates from ZSM-5 Nanoseeds with Improved Acidic Properties

    PubMed Central

    Vu, Xuan Hoan; Eckelt, Reinhard; Armbruster, Udo; Martin, Andreas

    2014-01-01

    Ordered mesoporous SBA-15 analogs with different Si/Al ratios were successfully prepared in a two-step process from self-assembly of ZSM-5 nanoseeds at high temperature in mildly acidic media (473 K, pH 3.5). The obtained products were characterized as SAXS, XRD, N2 sorption, FTIR, TEM, NH3-TPD, AAS and ICP. The results show that the initial Si/Al molar ratio of ZSM-5 precursors strongly affects the final materials’ properties. A highly condensed, well-ordered mesoporous SBA-15 analog with improved hydrothermal stability and acidic properties can be prepared from low aluminum containing ZSM-5 precursors (Si/Al ≥ 20). Reducing the initial Si/Al molar ratio to 10, however, leads to the formation of a disordered mesoporous SBA-15 type material accompanied by degraded textural and acidic properties. The gas phase cracking of cumene, carried out as probe reaction to evaluate Brønsted acidity, reveals that an increased density of Brønsted acid sites has been achieved over the SBA-15 analogs compared to conventional Al-SBA-15 due to the preservation of zeolite building units in the mesopore walls of the SBA-15 analogs.

  14. Microstructural modification of pure Mg for improving mechanical and biocorrosion properties.

    PubMed

    Ahmadkhaniha, D; Järvenpää, A; Jaskari, M; Sohi, M Heydarzadeh; Zarei-Hanzaki, A; Fedel, M; Deflorian, F; Karjalainen, L P

    2016-08-01

    In this study, the effect of microstructural modification on mechanical properties and biocorrosion resistance of pure Mg was investigated for tailoring a load-bearing orthopedic biodegradable implant material. This was performed utilizing the friction stir processing (FSP) in 1-3 passes to refine the grain size. Microstructure was examined in an optical microscope and scanning electron microscope with an electron backscatter diffraction unit. X-ray diffraction method was used to identify the texture. Mechanical properties were measured by microhardness and tensile testing. Electrochemical impedance spectroscopy was applied to evaluate corrosion behavior. The results indicate that even applying a single pass of FSP refined the grain size significantly. Increasing the number of FSP passes further refined the structure, increased the mechanical strength and intensified the dominating basal texture. The best combination of mechanical properties and corrosion resistance were achieved after three FSP passes. In this case, the yield strength was about six times higher than that of the as-cast Mg and the corrosion resistance was also improved compared to that in the as-cast condition.

  15. Analysis of Compounded Pharmaceutical Products to Teach the Importance of Quality in an Applied Pharmaceutics Laboratory Course

    PubMed Central

    Pignato, Alyssa

    2014-01-01

    Objective. To assess the effectiveness of a product-analysis laboratory exercise in teaching students the importance of quality in pharmaceutical compounding. Design. Second-year pharmacy students (N=77) participated in a pharmaceutical compounding laboratory exercise and subsequently analyzed their final product using ultraviolet (UV) spectrometry. Assessment. Reflection, survey instruments, and quiz questions were used to measure how well students understood the importance of quality in their compounded products. Product analysis showed that preparations compounded by students had an error range of 0.6% to 140%, with an average error of 23.7%. Students’ reflections cited common sources of error, including inaccurate weighing, contamination, and product loss during both the compounding procedure and preparation of the sample for analysis. Ninety percent of students agreed that the exercise improved their understanding of the importance of quality in compounded pharmaceutical products. Most students (85.7%) reported that this exercise inspired them to be more diligent in their preparation of compounded products in their future careers. Conclusion. Integrating an analytical assessment during a pharmaceutical compounding laboratory can enhance students’ understanding of quality of compounded pharmaceutical products. It can also provide students a chance to reflect on sources of error to improve their compounding technique in the future. PMID:24761022

  16. High hydrostatic pressure modification of whey protein concentrate for improved functional properties.

    PubMed

    Lim, S-Y; Swanson, B G; Clark, S

    2008-04-01

    Whey protein concentrate (WPC) has many applications in the food industry. Previous research demonstrated that treatment of whey proteins with high hydrostatic pressure (HHP) can enhance solubility and foaming properties of whey proteins. The objective of this study was to use HHP to improve functional properties of fresh WPC, compared with functional properties of reconstituted commercial whey protein concentrate 35 (WPC 35) powder. Fluid whey was ultrafiltered to concentrate proteins and reconstituted to equivalent total solids (8.23%) as reconstituted commercial WPC 35 powder. Solutions of WPC were treated with 300 and 400 MPa (0- and 15-min holding time) and 600 MPa (0-min holding time) pressure. After HHP, the solubility of the WPC was determined at both pH 4.6 and 7.0 using UDY and BioRad protein assay methods. Overrun and foam stability were determined after protein dispersions were whipped for 15 min. The protein solubility was greater at pH 7.0 than at pH 4.6, but there were no significant differences at different HHP treatment conditions. The maintenance of protein solubility after HHP indicates that HHP-treated WPC might be appropriate for applications to food systems. Untreated WPC exhibited the smallest overrun percentage, whereas the largest percentage for overrun and foam stability was obtained for WPC treated at 300 MPa for 15 min. Additionally, HHP-WPC treated at 300 MPa for 15 min acquired larger overrun than commercial WPC 35. The HHP treatment of 300 MPa for 0 min did not improve foam stability of WPC. However, WPC treated at 300 or 400 MPa for 15 min and 600 MPa for 0 min exhibited significantly greater foam stability than commercial WPC 35. The HHP treatment was beneficial to enhance overrun and foam stability of WPC, showing promise for ice cream and whipping cream applications.

  17. Improvement of water barrier property of paperboard by coating application with biodegradable polymers.

    PubMed

    Han, Jaejoon; Salmieri, Stéphane; Le Tien, Canh; Lacroix, Monique

    2010-03-10

    Biopolymeric coatings were prepared and applied onto paperboard to improve its water barrier property. To prepare whey protein isolate (WPI)/cellulose-based films, WPI and glycerol were dissolved in water with glutaraldehyde (cross-linking agent) and cellulose xanthate. The solution was cast, dried, and insolubilized by entrapment of WPI in regenerated cellulose. Films were combined with beeswax (BW) into a bilayer coating system and then applied onto paperboard by heating compression. Another coating solution consisting of poly(vinyl butyral) (PVB)/zein was prepared by dissolving poly(vinyl alcohol) (PVA) and zein in 70% ethanol with glutaraldehyde and butyraldehyde (functionalization agent). The PVB/zein solution was applied onto paperboard after BW was sprayed. The structure of the PVB/zein-based coatings was analyzed by Fourier transform infrared spectroscopy (FTIR). The water vapor barrier property of coated paperboards was evaluated by water vapor transmission rate (WVTR) measurements. From the FTIR spectra, PVA functionalization after cross-linking and efficient acetalization into PVB were confirmed. WPI/cellulose and PVB/zein coating treatments improved the water barrier properties of paperboard by decreasing the WVTR by 77-78%. Although the BW coating was more efficient (decrease of WVTR by 89%), bilayer coatings composed of BW and polymer coatings had a stronger barrier effect with a decrease of WVTR to 92-95%, hence approaching commercial attributes required to ensure water vapor barrier in paperboard-based food containers (10 g/m(2).day). These results suggest that surface coating by biodegradable polymers may be utilized for the manufacture of paperboard containers in industrial applications.

  18. Cyclodextrin Inclusion Complex to Improve Physicochemical Properties of Herbicide Bentazon: Exploring Better Formulations

    PubMed Central

    Yáñez, Claudia; Cañete-Rosales, Paulina; Castillo, Juan Pablo; Catalán, Nicole; Undabeytia, Tomás; Morillo, Esmeralda

    2012-01-01

    The knowledge of the host-guest complexes using cyclodextrins (CDs) has prompted an increase in the development of new formulations. The capacity of these organic host structures of including guest within their hydrophobic cavities, improves physicochemical properties of the guest. In the case of pesticides, several inclusion complexes with cyclodextrins have been reported. However, in order to explore rationally new pesticide formulations, it is essential to know the effect of cyclodextrins on the properties of guest molecules. In this study, the inclusion complexes of bentazon (Btz) with native βCD and two derivatives, 2-hydroxypropyl-β-cyclodextrin (HPCD) and sulfobutylether-β-cyclodextrin (SBECD), were prepared by two methods: kneading and freeze-drying, and their characterization was investigated with different analytical techniques including Fourier transform infrared spectroscopy (FT-IR), differential thermal analysis (DTA), X-ray diffractometry (XRD) and differential pulse voltammetry (DPV). All these approaches indicate that Btz forms inclusion complexes with CDs in solution and in solid state, with a stoichiometry of 1∶1, although some of them are obtained in mixtures with free Btz. The calculated association constant of the Btz/HPCD complex by DPV was 244±19 M−1 being an intermediate value compared with those obtained with βCD and SBECD. The use of CDs significantly increases Btz photostability, and depending on the CDs, decreases the surface tension. The results indicated that bentazon forms inclusion complexes with CDs showing improved physicochemical properties compared to free bentazon indicating that CDs may serve as excipient in herbicide formulations. PMID:22952577

  19. Improvement of islet graft function using liraglutide is correlated with its anti‐inflammatory properties

    PubMed Central

    Langlois, A; Dal, S; Vivot, K; Mura, C; Seyfritz, E; Bietiger, W; Dollinger, C; Peronet, C; Maillard, E; Pinget, M; Jeandidier, N

    2016-01-01

    Background and Purpose Liraglutide improves the metabolic control of diabetic animals after islet transplantation. However, the mechanisms underlying this effect remain unknown. The objective of this study was to evaluate the anti‐inflammatory and anti‐oxidative properties of liraglutide on rat pancreatic islets in vitro and in vivo. Experimental Approach In vitro, rat islets were incubated with 10 μmol·L−1 liraglutide for 12 and 24 h. Islet viability functionality was assessed. The anti‐inflammatory properties of liraglutide were evaluated by measuring CCL2, IL‐6 and IL‐10 secretion and macrophage chemotaxis. The anti‐oxidative effect of liraglutide was evaluated by measuring intracellular ROS and the total anti‐oxidative capacity. In vivo, 1000 islets were cultured for 24 h with or without liraglutide and then transplanted into the liver of streptozotocin‐induced diabetic Lewis rats with or without injections of liraglutide. Effects of liraglutide on metabolic control were evaluated for 1 month. Key Results Islet viability and function were preserved and enhanced with liraglutide treatment. Liraglutide decreased CCL2 and IL‐6 secretion and macrophage activation after 12 h of culture, while IL‐10 secretion was unchanged. However, intracellular levels of ROS were increased with liraglutide treatment at 12 h. This result was correlated with an increase of anti‐oxidative capacity. In vivo, liraglutide decreased macrophage infiltration and reduced fasting blood glucose in transplanted rats. Conclusions and Implications The beneficial effects of liraglutide on pancreatic islets appear to be linked to its anti‐inflammatory and anti‐oxidative properties. These findings indicated that analogues of glucagon‐like peptide‐1 could be used to improve graft survival. PMID:27515367

  20. Understanding and Improving High-Temperature Structural Properties of Metal-Silicide Intermetallics

    SciTech Connect

    Bruce S. Kang

    2005-10-10

    The objective of this project was to understand and improve high-temperature structural properties of metal-silicide intermetallic alloys. Through research collaboration between the research team at West Virginia University (WVU) and Dr. J.H. Schneibel at Oak Ridge National Laboratory (ORNL), molybdenum silicide alloys were developed at ORNL and evaluated at WVU through atomistic modeling analyses, thermo-mechanical tests, and metallurgical studies. In this study, molybdenum-based alloys were ductilized by dispersing MgAl2O4 or MgO spinel particles. The addition of spinel particles is hypothesized to getter impurities such as oxygen and nitrogen from the alloy matrix with the result of ductility improvement. The introduction of fine dispersions has also been postulated to improve ductility by acting as a dislocation source or reducing dislocation pile-ups at grain boundaries. The spinel particles, on the other hand, can also act as local notches or crack initiation sites, which is detrimental to the alloy mechanical properties. Optimization of material processing condition is important to develop the desirable molybdenum alloys with sufficient room-temperature ductility. Atomistic analyses were conducted to further understand the mechanism of ductility improvement of the molybdenum alloys and the results showed that trace amount of residual oxygen may be responsible for the brittle behavior of the as-cast Mo alloys. For the alloys studied, uniaxial tensile tests were conducted at different loading rates, and at room and elevated temperatures. Thermal cycling effect on the mechanical properties was also studied. Tensile tests for specimens subjected to either ten or twenty thermal cycles were conducted. For each test, a follow-up detailed fractography and microstructural analysis were carried out. The test results were correlated to the size, density, distribution of the spinel particles and processing time. Thermal expansion tests were carried out using thermo

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

    PubMed

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

    2015-09-30

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

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

    EPA Science Inventory

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

  3. Technology of Ultrasonic Treatment of High-Viscosity Oil from Yarega Oilfield to Improve the Rheological Properties of Oil

    NASA Astrophysics Data System (ADS)

    Zemenkov, Y. D.; Zemenkova, M. Y.; Berg, V. I.; Gordievskaya, E. F.

    2016-10-01

    The article investigates the possibility of applying ultrasonic treatment oil from Yarega oilfield to improve of rheological properties, reduce oil viscosity in Russian pipeline transportation system, and increase its efficiency and performance. Created laboratory test bed of ultrasonic waves.

  4. 36 CFR 51.41 - If the concession contract grants a compensable interest in real property improvements, will the...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... contract is an outfitter and guide concession contract? 51.41 Section 51.41 Parks, Forests, and Public... Offeror § 51.41 If the concession contract grants a compensable interest in real property improvements... park area....

  5. 36 CFR 51.41 - If the concession contract grants a compensable interest in real property improvements, will the...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... contract is an outfitter and guide concession contract? 51.41 Section 51.41 Parks, Forests, and Public... Offeror § 51.41 If the concession contract grants a compensable interest in real property improvements... park area....

  6. 36 CFR 51.41 - If the concession contract grants a compensable interest in real property improvements, will the...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... contract is an outfitter and guide concession contract? 51.41 Section 51.41 Parks, Forests, and Public... Offeror § 51.41 If the concession contract grants a compensable interest in real property improvements... park area....

  7. 36 CFR 51.41 - If the concession contract grants a compensable interest in real property improvements, will the...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... contract is an outfitter and guide concession contract? 51.41 Section 51.41 Parks, Forests, and Public... Offeror § 51.41 If the concession contract grants a compensable interest in real property improvements... park area....

  8. Arginine deiminase: recent advances in discovery, crystal structure, and protein engineering for improved properties as an anti-tumor drug.

    PubMed

    Han, Rui-Zhi; Xu, Guo-Chao; Dong, Jin-Jun; Ni, Ye

    2016-06-01

    Arginine deiminase (ADI) is an important arginine-degrading enzyme with wide applications, in particular as an anti-cancer agent for the therapy of arginine-auxotrophic tumors. In recent years, novel ADIs with excellent properties have been identified from various organisms, and crystal structures of ADI were investigated. To satisfy the requirements of potential therapeutic applications, protein engineering has been performed to improve the activity and properties of ADIs. In this mini-review, we systematically summarized the latest progress on identification and crystal structure of ADIs, and protein engineering strategies for improved enzymatic properties, such as pH optimum, K m and k cat values, and thermostability. We also outlined the PEGylation of ADI for improved circulating half-life and immunogenicity, as well as their performance in clinical trials. Finally, perspectives on extracellular secretion and property improvement of ADI were discussed.

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

    EPA Science Inventory

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

  10. Improving root-zone soil properties for Trembling Aspen in a reconstructed mine-site soil

    NASA Astrophysics Data System (ADS)

    Dyck, M. F.; Sabbagh, P.; Bockstette, S.; Landhäusser, S.; Pinno, B.

    2014-12-01

    Surface mining activities have significantly depleted natural tree cover, especially trembling aspen (Populus tremuloides), in the Boreal Forest and Aspen Parkland Natural Regions of Alberta. The natural soil profile is usually destroyed during these mining activities and soil and landscape reconstruction is typically the first step in the reclamation process. However, the mine tailings and overburden materials used for these new soils often become compacted during the reconstruction process because they are subjected to high amounts of traffic with heavy equipment. Compacted soils generally have low porosity and low penetrability through increased soil strength, making it difficult for roots to elongate and explore the soil. Compaction also reduces infiltration capacity and drainage, which can cause excessive runoff and soil erosion. To improve the pore size distribution and water transmission, subsoil ripping was carried out in a test plot at Genesee Prairie Mine, Alberta. Within the site, six replicates with two treatments each, unripped (compacted) and ripped (decompacted), were established with 20-m buffers between them. The main objective of this research was to characterize the effects of subsoil ripping on soil physical properties and the longevity of those effects.as well as soil water dynamics during spring snowmelt. Results showed improved bulk density, pore size distribution and water infiltration in the soil as a result of the deep ripping, but these improvements appear to be temporary.

  11. Recent progress in low-voltage cathodoluminescent materials: synthesis, improvement and emission properties.

    PubMed

    Li, Guogang; Lin, Jun

    2014-01-01

    Nowadays there are several technologies used for flat panel displays (FPDs) and the development of FPDs with enhanced energy efficiency and improved display quality is strongly required. Field emission displays (FEDs) have been considered as one of the most promising next generation flat panel display technologies due to their excellent display performance and low energy consumption. For the development of FEDs, phosphors are irreplaceable components. In the past decade, the study of highly efficient low-voltage cathodoluminescent materials, namely FED phosphors, has become the focus of enhancing energy efficiency and realizing high-quality displays. This review summaries the recent progress in the chemical synthesis and improvement of novel, rare-earth and transition metal ions activated inorganic cathodoluminescent materials in powder and thin film forms. The discussion is focused on the modification of morphology, size, surface, composition and conductivity of phosphors and the corresponding effects on their cathodoluminescent properties. Special emphases are given to the selection of host and luminescent centers, the adjustment of emission colors through doping concentration optimization, energy transfer and mono- or co-doping activator ions, the improvement of chromaticity, color stability and color gamut as well as the saturation behavior and the degradation behavior of phosphors under the excitation of a low-voltage electron beam. Finally, the research prospects and future directions of FED phosphors are discussed with recommendations to facilitate the further study of new and highly efficient low-voltage cathodoluminescent materials.

  12. Sorghum mutant RG displays antithetic leaf shoot lignin accumulation resulting in improved stem saccharification properties

    PubMed Central

    2013-01-01

    Background Improving saccharification efficiency in bioenergy crop species remains an important challenge. Here, we report the characterization of a Sorghum (Sorghum bicolor L.) mutant, named REDforGREEN (RG), as a bioenergy feedstock. Results It was found that RG displayed increased accumulation of lignin in leaves and depletion in the stems, antithetic to the trend observed in wild type. Consistent with these measurements, the RG leaf tissue displayed reduced saccharification efficiency whereas the stem saccharification efficiency increased relative to wild type. Reduced lignin was linked to improved saccharification in RG stems, but a chemical shift to greater S:G ratios in RG stem lignin was also observed. Similarities in cellulose content and structure by XRD-analysis support the correlation between increased saccharification properties and reduced lignin instead of changes in the cellulose composition and/or structure. Conclusion Antithetic lignin accumulation was observed in the RG mutant leaf-and stem-tissue, which resulted in greater saccharification efficiency in the RG stem and differential thermochemical product yield in high lignin leaves. Thus, the red leaf coloration of the RG mutant represents a potential marker for improved conversion of stem cellulose to fermentable sugars in the C4 grass Sorghum. PMID:24103129

  13. Improving the installation of renewable heating technology in UK social housing properties through user centred design.

    PubMed

    Moore, Natalie; Haines, Victoria; Lilley, Debra

    2015-11-01

    Social housing organisations are increasingly installing renewable energy technologies, particularly for the provision of heating and hot water. To meet carbon reduction targets, uptake and installation must allow occupants to use the technology effectively. This paper describes research which investigated the service of installing heat pumps into UK social housing properties, from both landlords' and tenants' experiences. Adopting a user centred design approach, the research was in three phases: an exploration study to investigate landlords' and tenants' experiences of heat pump installation and use; refinement and development of the requirements for improved service delivery, primarily technology introduction and control; and the development and initial evaluation of an information leaflet as a key touchpoint in the service delivery. Recommendations for improved service delivery, to enable heat pumps to be accepted and used more effectively, are presented, as well as reflection on the process of applying user centred design in this context. In a relatively immature area of industry, installations to date have been heavily focused on technical aspects. This paper provides an insight into the human aspects of the service delivery of heat pumps in social housing, providing designers and social housing landlords with insight about how to improve the service.

  14. EXPERIMENTAL STUDY ON SHOCK RELIEF PROPERTY OF FALL PROTECTION SYSTEM BY IMPROVED SCAFFOLD SHEETING

    NASA Astrophysics Data System (ADS)

    Ohdo, Katsutoshi; Takanashi, Seiji; Hino, Yasumichi; Takahashi, Hiroki; Toyosawa, Yasuo

    The frequency of fall accidents is one of the most serious problems in construction industries, and the countermeasures, such as guidelines or regulation, etc., for falls from scaffolds have been tightened in Japan. These countermeasures particularly affect the decrease in the number of the fatal accidents by falls from scaffolds. However, the rate of such accidents from falls is still high in the construction industries. In order to reduce the falls, the scaffold sheeting, as a covering around the scaffolds to protect against falling construction materials (a method widely used in Japan), was improved for fall protection. In this study, the safety of the fall protection system by the improved sheeting and the regulation was compared by fall tests using a human dummy. Then, impact loads, which acted on the scaffolds, were measured and evaluated for the safety property. Form the results of the fall tests, it could be confirmed that the fall protection system by the improved scaffold sheeting was relieved the impact loads more than that by the Japanese regulation.

  15. Improving the installation of renewable heating technology in UK social housing properties through user centred design

    PubMed Central

    Moore, Natalie; Lilley, Debra

    2015-01-01

    Social housing organisations are increasingly installing renewable energy technologies, particularly for the provision of heating and hot water. To meet carbon reduction targets, uptake and installation must allow occupants to use the technology effectively. This paper describes research which investigated the service of installing heat pumps into UK social housing properties, from both landlords’ and tenants’ experiences. Adopting a user centred design approach, the research was in three phases: an exploration study to investigate landlords’ and tenants’ experiences of heat pump installation and use; refinement and development of the requirements for improved service delivery, primarily technology introduction and control; and the development and initial evaluation of an information leaflet as a key touchpoint in the service delivery. Recommendations for improved service delivery, to enable heat pumps to be accepted and used more effectively, are presented, as well as reflection on the process of applying user centred design in this context. In a relatively immature area of industry, installations to date have been heavily focused on technical aspects. This paper provides an insight into the human aspects of the service delivery of heat pumps in social housing, providing designers and social housing landlords with insight about how to improve the service. PMID:26539060

  16. Improved surface property of PVDF membrane with amphiphilic zwitterionic copolymer as membrane additive

    NASA Astrophysics Data System (ADS)

    Li, Jian-Hua; Li, Mi-Zi; Miao, Jing; Wang, Jia-Bin; Shao, Xi-Sheng; Zhang, Qi-Qing

    2012-06-01

    An attempt to improve hydrophilicity and anti-fouling properties of PVDF membranes, a novel amphiphilic zwitterionic copolymer poly(vinylidene fluoride)-graft-poly(sulfobetaine methacrylate) (PVDF-g-PSBMA) was firstly synthesized by atom transfer radical polymerization (ATRP) and used as amphiphilic copolymer additive in the preparation of PVDF membranes. The PVDF-g-PSBMA/PVDF blend membranes were prepared by immersion precipitation process. Fourier transform infrared attenuated reflection spectroscopy (FTIR-ATR) and X-ray photoelectronic spectroscopy (XPS) measurements confirmed that PSBMA brushes from amphiphilic additives were preferentially segregated to membrane-coagulant interface during membrane formation. The morphology of membranes was characterized by scanning electron microscopy (SEM). Water contact angle measurements showed that the surface hydrophilicity of PVDF membranes was improved significantly with the increasing of amphiphilic copolymer PVDF-g-PSBMA in cast solution. Protein static adsorption experiment and dynamic fouling resistance experiment revealed that the surface enrichment of PSBMA brush endowed PVDF blend membrane great improvement of surface anti-fouling ability.

  17. Endocrine-Active Pharmaceuticals: An Environmental Concern?

    EPA Science Inventory

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

  18. Pharmaceutical and Medicine Manufacturing Sector (NAICS 3254)

    EPA Pesticide Factsheets

    Find environmental regulatory and compliance information for the pharmaceutical manufacturing sector, including essential uses of CFCs, NESHAP for pharmaceutical production, effluent guidelines for wastewater and management of hazardous waste.

  19. Pharmaceutical Research and Manufacturers of America

    MedlinePlus

    ... The New Era of Medicine SHARE THIS The Pharmaceutical Research and Manufacturers of America, PhRMA, represents the ... PhRMA Privacy Policy Terms of Service Site Map Pharmaceutical Research and Manufacturers of America® 950 F Street, ...

  20. Improvement of mechanical properties of polymeric composites: Experimental methods and new systems

    NASA Astrophysics Data System (ADS)

    Nguyen, Felix Nhanchau

    Filler- (e.g., particulate or fiber) reinforced structural polymers or polymeric composites have changed the way things are made. Today, they are found, for example, in air/ground transportation vehicles, sporting goods, ballistic barrier applications and weapons, electronic packaging, musical instruments, fashion items, and more. As the demand increases, so does the desire to have not only well balanced mechanical properties, but also light weight and low cost. This leads to a constant search for novel constituents and additives, new fabrication methods and analytical techniques. To achieve new or improved composite materials requires more than the identification of the right reinforcements to be used with the right polymer matrix at the right loading. Also, an optimized adhesion between the two phases and a toughened matrix system are needed. This calls for new methods to predict, modify and assess the level of adhesion, and new developments in matrix tougheners to minimize compromises in other mechanical/thermal properties. Furthermore, structural optimization, associated with fabrication (e.g., avoidance of fiber-fiber touching or particle aggregation), and sometimes special properties, such as electrical conductivity or magnetic susceptibility are necessary. Finally, the composite system's durability, often under hostile conditions, is generally mandatory. The present study researches new predictive and experimental methods for optimizing and characterizing filler-matrix adhesion and develops a new type of epoxy tougheners. Specifically, (1) a simple thermodynamic parameter evaluated by UNIFAC is applied successfully to screen out candidate adhesion promoters, which is necessary for optimization of the physio-chemical interactions between the two phases; (2) an optical-acoustical mechanical test assisted with an acoustic emission technique is developed to de-convolute filler debonding/delamination among many other micro failure events, and (3) novel core

  1. Using spectral subspaces to improve infrared spectroscopy prediction of soil properties

    NASA Astrophysics Data System (ADS)

    Sila, Andrew; Shepherd, Keith D.; Pokhariyal, Ganesh P.; Towett, Erick; Weullow, Elvis; Nyambura, Mercy K.

    2015-04-01

    We propose a method for improving soil property predictions using local calibration models trained on datasets in spectral subspaces rather that in a global space. Previous studies have shown that local calibrations based on a subset of spectra based on spectral similarity can improve model prediction performance where there is large population variance. Searching for relevant subspaces within a spectral collection to construct local models could result in models with high power and small prediction errors, but optimal methods for selection of local samples are not clear. Using a self-organizing map method (SOM) we obtained four mid-infrared subspaces for 1,907 soil sample spectra collected from 19 different countries by the Africa Soil Information Service. Subspace means for four sub-spaces and five selected soil properties were: pH, 6.0, 6.1, 6.0, 5.6; Mehlich-3 Al, 358, 974, 614, 1032 (mg/kg); Mehlich-3 Ca, 363, 1161, 526, 4276 (mg/kg); Total Carbon, 0.4, 1.1, 0.6, 2.3 (% by weight), and Clay (%), 16.8, 46.4, 27.7, 63.3. Spectral subspaces were also obtained using a cosine similarity method to calculate the angle between the entire sample spectra space and spectra of 10 pure soil minerals. We found the sample soil spectra to be similar to four pure minerals distributed as: Halloysite (n1=214), Illite (n2=743), Montmorillonite (n3=914) and Quartz (n4=32). Cross-validated partial least square regression models were developed using two-thirds of samples spectra from each subspace for the five soil properties.We evaluated prediction performance of the models using the root mean square error of prediction (RMSEP) for a one-third-holdout set. Local models significantly improved prediction performance compared with the global model. The SOM method reduced RMESP for total carbon by 10 % (global RMSEP = 0.41) Mehlich-3 Ca by 17% (global RMESP = 1880), Mehlich-3 Al by 21 % (global RMSEP = 206), and clay content by 6 % (global RMSEP = 13.6), but not for pH. Individual SOM

  2. Modeling picking on pharmaceutical tablets

    NASA Astrophysics Data System (ADS)

    Swaminathan, Shrikant

    Tablets are the most popular solid dosage form in the pharmaceutical industry because they are cheap to manufacture, chemically and mechanically stable and easy to transport and fairly easy to control dosage. Pharmaceutical tableting operations have been around for decades however the process is still not well understood. One of the common problems faced during the production of pharmaceutical tablets by powder compaction is sticking of powder to the punch face, This is known as 'sticking'. A more specialized case of sticking is picking when the powder is pulled away form the compact in the vicinity of debossed features. In the pharmaceutical industry, picking is solved by trial and error which is an expensive, labor intensive and time consuming affair. The objective of this work was to develop, validate, and implement a modeling framework for predicting picking in powder compacts. The model was developed in Abaqus a commercially available finite element package. The resulting model was used to investigate the influence of debossed feature geometry viz. the stroke angle and degree of pre-pick, and, influence of lubricant on picking. (Abstract shortened by ProQuest.).

  3. Financing pharmaceuticals in transition economies.

    PubMed

    Kanavos, P

    1999-06-01

    This paper (a) provides a methodological taxonomy of pricing, financing, reimbursement, and cost containment methodologies for pharmaceuticals; (b) analyzes complex agency relationships and the health versus industrial policy tradeoff; (c) pinpoints financing measures to balance safety and effectiveness of medicines and their affordability by publicly funded systems in transition; and (d) highlights viable options for policy-makers for the financing of pharmaceuticals in transition. Three categories of measures and their implications for pharmaceutical policy cost containing are analyzed: supply-side measures, targeting manufacturers, proxy demand-side measures, targeting physicians and pharmacists, and demand-side measures, targeting patients. In pursuing supply side measures, we explore free pricing for pharmaceuticals, direct price controls, cost-plus and cost pricing, average pricing and international price comparisons, profit control, reference pricing, the introduction of a fourth hurdle, positive and negative lists, and other price control measures. The analysis of proxy-demand measures includes budgets for physicians, generic policies, practice guidelines, monitoring the authorizing behavior of physicians, and disease management schemes. Demand-side measures explore the effectiveness of patient co-payments, the impact of allowing products over-the-counter and health promotion programs. Global policies should operate simultaneously on the supply, the proxy demand, and the demand-side. Policy-making needs to have a continuous long-term planning. The importation of policies into transition economy may require extensive and expensive adaptation, and/or lead to sub-optimal policy outcomes.

  4. Bioremediation of industrial pharmaceutical drugs.

    PubMed

    Mansour, Hedi Ben; Mosrati, Ridha; Barillier, Daniel; Ghedira, Kamel; Chekir-Ghedira, Leila

    2012-07-01

    Recently, attention has been drawn toward the occurrence of pharmaceuticals in the environment. In recent years, many reports have been made on the occurrence of the large, differentiated group of pharmaceuticals in wastewater (PW), surface water, ground water, and in soil. The pharmaceutical sector is currently expanding in Tunisia, with more than 34 industries. The aim of this work was to evaluate the ability of Pseudomonas putida mt-2 to treat PW. P. putida was very efficient in reducing chemical oxygen demand (COD), total dissolved solids (TDS), and turbidity of solution (85.5, 89.1, and 81.5%, respectively). Genotoxicity of effluent, before and after biodegradation, was evaluated in vivo in mouse bone marrow by assessing the percentage of cells bearing different chromosome aberrations. Results indicated that PW showed a significant ability to induce DNA damage. In addition, PW induced a remarkable lipid peroxidation (LPO) effect, however, activities of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were unchanged when treated with PW, compared to nontreated PW. This toxicity was imputed to the presence of pharmaceutical compounds in wastewater. However, chromosome aberration, as well as LPO of PW, were significantly reduced after bioremediation. Thus, the use of this strain for testing on the industrial scale seems possible and advantageous.

  5. Immunotoxicology in the pharmaceutical industry.

    PubMed Central

    Norbury, K C

    1982-01-01

    Development of an immunotoxicology program within the pharmaceutical industry is described. With few guidelines in the area and a multitude of factors to consider, a basic screen for evaluating immune competence in species routinely used in toxicologic studies has been proposed. The future of immunotoxicology depends upon the ability of the selected immune function tests to be predictive of human risk. PMID:7037389

  6. Patrick Couvreur: inspiring pharmaceutical innovation.

    PubMed

    Stanwix, Hannah

    2014-05-01

    Patrick Couvreur speaks to Hannah Stanwix, Managing Comissioning Editor: Professor Patrick Couvreur received his pharmacy degree from the Université Catholique de Louvain (Louvain-la-Neuve, Belgium) in 1972. He holds a PhD in pharmaceutical technology from the same university and completed a postdoctoral fellowship at the Eidgenössische Technische Hochschule (Zürich, Switzerland). Since 1984, Professor Couvreur has been Full Professor of Pharmacy at the Paris-Sud University (Paris, France) and was holder of the Chair of Innovation Technologique at the prestigious Collège de France (Paris, France). He has published more than 450 peer-reviewed articles and has an H-index of 73, with over 19,000 citations. Professor Coureur has been recognized by numerous national and international awards, including the 2004 Pharmaceutical Sciences World Congress Award, the prestigious Host Madsen Medal, the Prix Galien, the European Pharmaceutical Scientist Award 2011 from the European Federation of Pharmaceutical Sciences, the Médaille de l'Innovation from the Centre National de la Recherche Scientifique, and recently the European Inventor Award 2013 from the European Patent Office.

  7. Immunoassay Methods and their Applications in Pharmaceutical Analysis: Basic Methodology and Recent Advances.

    PubMed

    Darwish, Ibrahim A

    2006-09-01

    Immunoassays are bioanalytical methods in which the quantitation of the analyte depends on the reaction of an antigen (analyte) and an antibody. Immunoassays have been widely used in many important areas of pharmaceutical analysis such as diagnosis of diseases, therapeutic drug monitoring, clinical pharmacokinetic and bioequivalence studies in drug discovery and pharmaceutical industries. The importance and widespread of immunoassay methods in pharmaceutical analysis are attributed to their inherent specificity, high-throughput, and high sensitivity for the analysis of wide range of analytes in biological samples. Recently, marked improvements were achieved in the field of immunoassay development for the purposes of pharmaceutical analysis. These improvements involved the preparation of the unique immunoanalytical reagents, analysis of new categories of compounds, methodology, and instrumentation. The basic methodologies and recent advances in immunoassay methods applied in different fields of pharmaceutical analysis have been reviewed.

  8. Comprehension by older people of medication information with or without supplementary pharmaceutical pictograms.

    PubMed

    Ng, Annie W Y; Chan, Alan H S; Ho, Vincy W S

    2017-01-01

    This study examined the benefits of pharmaceutical pictograms for improving comprehension of medication information for older people. Fifty Hong Kong Chinese older people completed a medical information comprehension task for five drugs. Participants in the control group were presented with text labels while those in the experimental group were given the text labels plus supplementary pharmaceutical pictograms, and then all reported their understanding of the medication information conveyed. Lower educated older people had poorer understanding of medication information. The addition of pharmaceutical pictograms significantly improved the comprehension of medication information for older people. The majority of older people tested with pictograms favored adding pictograms to text and thought the pictograms were useful for conveying medical information rather than using written text alone. The findings suggested that pharmaceutical and health care professionals should include pharmaceutical pictograms on labels to better convey instructions on medication to older people.

  9. The supply of pharmaceuticals in humanitarian assistance missions: implications for military operations.

    PubMed

    Mahmood, Maysaa; Riley, Kevin; Bennett, David; Anderson, Warner

    2011-08-01

    In this article, we provide an overview of key international guidelines governing the supply of pharmaceuticals during disasters and complex emergencies. We review the World Health Organization's guidelines on pharmaceutical supply chain management and highlight their relevance for military humanitarian assistance missions. Given the important role of pharmaceuticals in addressing population health needs during humanitarian emergencies, a good understanding of how pharmaceuticals are supplied at the local level in different countries can help military health personnel identify the most appropriate supply options. Familiarity with international guidelines involved in cross-border movement of pharmaceuticals can improve the ability of military personnel to communicate more effectively with other actors involved in humanitarian and development spheres. Enhancing the knowledge base available to military personnel in terms of existing supply models and funding procedures can improve the effectiveness of humanitarian military operations and invite policy changes necessary to establish more flexible acquisition and funding regulations.

  10. The supply of pharmaceuticals in humanitarian assistance missions: implications for military operations.

    PubMed

    Mahmood, Maysaa; Riley, Kevin; Bennett, David; Anderson, Warner

    2011-01-01

    In this article, we provide an overview of key international guidelines governing the supply of pharmaceuticals during disasters and complex emergencies. We review the World Health Organization?s guidelines on pharmaceutical supply chain management and highlight their relevance for military humanitarian assistance missions. Given the important role of pharmaceuticals in addressing population health needs during humanitarian emergencies, a good understanding of how pharmaceuticals are supplied at the local level in different countries can help military health personnel identify the most appropriate supply options. Familiarity with international guidelines involved in cross-border movement of pharmaceuticals can improve the ability of military personnel to communicate more effectively with other actors involved in humanitarian and development spheres. Enhancing the knowledge base available to military personnel in terms of existing supply models and funding procedures can improve the effectiveness of humanitarian military operations and invite policy changes necessary to establish more flexible acquisition and funding regulations.

  11. A terahertz time-domain study on the estimation of opto-mechanical properties of pharmaceutical tablets using the Hashin-Shtrikman bounds for refractive index: a case study of microcrystalline cellulose and starch acetate compacts

    NASA Astrophysics Data System (ADS)

    Bawuah, Prince; Peiponen, Kai-Erik

    2016-06-01

    This work highlights the use of Hashin-Shtrikman (H-S) bounds in the prediction and verification of the effective refractive index, the height and the Young's modulus of given training sets of pharmaceutical compacts using the measured time delay of a THz pulse traversing the compacts. Set A consisted of 13 microcrystalline cellulose (MCC) compacts whereas set B was made up of 5 starch acetate (SA) compacts. MCC is a typical ingredient of many pharmaceutical tablets. In the case of the MCC compacts, tight and closely matched bounds were obtained between the experimental, the calculated upper, lower bound values for the effective refractive index, and the height values. This promising outcome has shown the high possibility of utilizing H-S bounds in the verification and prediction of the decision level of useful parameters, which can serve as a quality check for pharmaceutical tablets. For the SA compacts, although less tight bounds were observed, the experimental values for the effective refractive index and the Young's modulus were closely matched with the upper and the lower bounds, respectively. We therefore speculate based on the above observations that the MCC tablets contain an almost evenly distributed spherically shaped air voids whereas in the SA compacts, this assumption might not necessary be true.

  12. PNAUM: integrated approach to Pharmaceutical Services, Science, Technology and Innovation

    PubMed Central

    Gadelha, Carlos Augusto Grabois; Costa, Karen Sarmento; do Nascimento, José Miguel; Soeiro, Orlando Mário; Mengue, Sotero Serrate; da Motta, Márcia Luz; de Carvalho, Antônio Carlos Campos

    2016-01-01

    ABSTRACT This paper describes the development process of the Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos (PNAUM – National Survey on Access, Use and Promotion of Rational Use of Medicines) based on an integrated approach to pharmaceutical services, science, technology and innovation. It starts by contextualizing health and development in Brazil and features elements of the National Policy for Science, Technology and Innovation in Health in Brazil and the National Policy for Pharmaceutical Services. On presenting pharmaceutical policy guidelines, it stresses the lack of nationwide data. This survey, commissioned by the Brazilian Ministry of Health, has two components: household survey and evaluation of pharmaceutical services in primary care. The findings point to perspectives that represent, besides the enhancement of public policy for pharmaceutical services and public health, results of government action aimed at developing the economic and industrial health care complex to improve the health conditions of the Brazilian population. PMID:27982379

  13. A consideration of the patentability of enantiomers in the pharmaceutical industry in the United States.

    PubMed

    Miller, Chris P; Ullrich, John W

    2008-06-01

    During the last thirty years, concern over stereoselectivity of drug action has drawn a great deal of interest within the pharmaceutical field due to an improved understanding of the pharmacology and pharmacokinetics of enantiomers. Developing single enantiomers versus racemates or introducing a single enantiomer following the development of the racemic mixture appears to be the new trend. The intellectual property status of single enantiomers from racemates may be unclear. Drug discoverers and patent attorneys must examine the examples of the past to establish an appropriate pathway towards the development and intellectual property protection of chiral drugs. The review will focus on the patenting of an enantiomer in view of the prior art disclosure for the racemic mixture.

  14. Stability of Chitosan—A Challenge for Pharmaceutical and Biomedical Applications

    PubMed Central

    Szymańska, Emilia; Winnicka, Katarzyna

    2015-01-01

    Chitosan—one of the natural multifunctional polymers—due to its unique and versatile biological properties is regarded as a useful compound in medical and pharmaceutical technology. Recently, considerable research effort has been made in order to develop safe and efficient chitosan products. However, the problem of poor stability of chitosan-based systems restricts its practical applicability; thus, it has become a great challenge to establish sufficient shelf-life for chitosan formulations. Improved stability can be assessed by controlling the environmental factors, manipulating processing conditions (e.g., temperature), introducing a proper stabilizing compound, developing chitosan blends with another polymer, or modifying the chitosan structure using chemical or ionic agents. This review covers the influence of internal, environmental, and processing factors on the long-term stability of chitosan products. The aim of this paper is also to highlight the latest developments which enable the physicochemical properties of chitosan-based applications to be preserved upon storage. PMID:25837983

  15. Unhealthy marketing of pharmaceutical products: An international public health concern.

    PubMed

    Mulinari, Shai

    2016-05-01

    I consider the current state of pharmaceutical marketing vis-à-vis ethical and legal standards and advocate measures to improve it. There is abundant evidence of unethical or illicit marketing. It fuels growing concerns about undue corporate influence over pharmaceutical research, education, and consumption. The most extensive evidence of industry transgressions comes from the United States (US), where whistle-blowers are encouraged by financial rewards to help uncover illicit marketing and fraud. Outside the US increasing evidence of transgressions exists. Recently I have observed a range of new measures to align pharmaceutical marketing practices with ethical and legal standards. In the interest of public health, I highlight the need for additional and more profound reforms to ensure that information about medicines supports quality and resource-efficient care.

  16. Plant Metabolic Engineering Strategies for the Production of Pharmaceutical Terpenoids

    PubMed Central

    Lu, Xu; Tang, Kexuan; Li, Ping

    2016-01-01

    Pharmaceutical terpenoids belong to the most diverse class of natural products. They have significant curative effects on a variety of diseases, such as cancer, cardiovascular diseases, malaria and Alzheimer’s disease. Nowadays, elicitors, including biotic and abiotic elicitors, are often used to activate the pathway of secondary metabolism and enhance the production of target terpenoids. Based on Agrobacterium-mediated genetic transformation, several plant metabolic engineering strategies hold great promise to regulate the biosynthesis of pharmaceutical terpenoids. Overexpressing terpenoids biosynthesis pathway genes in homologous and ectopic plants is an effective strategy to enhance the yield of pharmaceutical terpenoids. Another strategy is to suppress the expression of competitive metabolic pathways. In addition, global regulation which includes regulating the relative transcription factors, endogenous phytohormones and primary metabolism could also markedly increase their yield. All these strategies offer great opportunities to enhance the supply of scarce terpenoids drugs, reduce the price of expensive drugs and improve people’s standards of living. PMID:27877181

  17. Pharmaceutical cocrystals: the coming wave of new drug substances.

    PubMed

    Brittain, Harry G

    2013-02-01

    Solid crystalline phases containing two cocrystallized components offer a new development pathway whereby one can potentially improve the physical characteristics (i.e., equilibrium solubility, dissolution rate, solid-state stability, etc.) of a drug substance that exhibits a profile that is less than desirable. In this commentary, the topic of pharmaceutical cocrystals will be briefly explored, and a short exposition of the solubility and dissolution rate advantages that have been realized in various systems will be provided. The Guidance for Industry document recently proposed by United States Food and Drug Administration will be outlined, and its requirements explained. Finally, the subset of pharmaceutical cocrystals that consist of a drug substance and a salt of that substance (termed a salt cocrystal) will be examined to illustrate this additional class of pharmaceutical cocrystals that may offer significant scientific and regulatory advantages.

  18. TOPICAL REVIEW: Prospects for improving the intrinsic and extrinsic properties of magnesium diboride superconducting strands

    NASA Astrophysics Data System (ADS)

    Collings, E. W.; Sumption, M. D.; Bhatia, M.; Susner, M. A.; Bohnenstiehl, S. D.

    2008-10-01

    The magnetic and transport properties of MgB2 films present performance goals yet to be attained for powder-processed bulk samples and conductors. Carbon-doped films have exhibited upper critical fields, μ0Hc2, as high as 60 T and a possible upper limit of more than twice this value has been predicted. Very high critical current densities, Jc, have also been measured for films, e.g. 25 MA cm-2 in the self-field and 7 kA cm-2 in 15 T. Such performance limits are still out of reach for even the best MgB2 magnet wire. In discussing the present status and prospects for improving the performance of powder-based wire we focus attention on (1) the intrinsic (intragrain) superconducting properties of MgB2—Hc2 and flux pinning, and (2) the factors that control the efficiency with which current is transported from grain to grain in the conductor, an extrinsic (intergrain) property. With regard to item (1), the role of dopants in Hc2 enhancement is discussed and examples presented. On the other hand their roles in increasing Jc, both via Hc2 enhancement as well as via direct fluxoid/pinning center interaction, are discussed and a comprehensive survey of Hc2 dopants and flux pinning additives is presented. Dopant selection, chemistry, methods of introduction (inclusion), and homogeneity of distribution (via the rounding of the superconducting electronic specific heat transition) are considered. Current transport through the powder-processed wire (an extrinsic property) is partially blocked by the inherent granularity of the material itself and the chemical or other properties of the intergrain surfaces. Overall porosity, including reduced density and intergranular blocking, is quantified in terms of the measured temperature dependence of the normal-state resistivity compared to that of a clean single crystal. Several experimental results are presented in terms of per cent effective cross-sectional area for current transport. These and other such results indicate that in

  19. Climate-Relevant Properties of Particles Generated by Traditional and Improved Wood Burning Cook Stoves

    NASA Astrophysics Data System (ADS)

    Roden, C. A.; Bond, T. C.; Conway, S.; Osorto Pinel, B.; Maccarty, N.; Still, D.

    2005-12-01

    Some 2-3 billion people in the world use biofuel as their primary energy source for domestic fuel needs. It is estimated that the combustion of biofuel generates 20% of all carbonaceous aerosols. Uncertainty about the quantity of negative (cooling) radiative forcing generated by aerosols contributes greatly to our lack of understanding of the complete climate picture. In order to facilitate measurements of poorly characterized aerosol sources at a wide range of potential sampling sites, we designed and built an Ambulatory, Real-time ANalyzer for Aerosols or ARANA. The ARANA measures the following real-time data: absorption at three wavelengths, scattering, CO concentration, and CO2 concentration. Additionally, the sampling system captures particles on filters for later analysis. The goals of this project are 1) to gain further understanding of the properties of aerosols generated from biofuels during actual cooking events, which may vary from laboratory testing 2) Determine the factors which govern the emissions from cookstoves so that we can represent these highly variable sources in emission models 3) quantitatively assess improved cookstoves, in order to improve the design and determine the lowest emission model. In Honduras during the summers of 2005 and 2004, we measured real-time emissions from four different improved cookstoves with five tests for each type of improved stove; as well as the emissions from 12 traditional Honduran cookstoves. We observed that particles produced during different combustion phases have very different optical properties. The fire startup and fuel addition phases generally produced the most aerosols, with large quantities of very dark particles having a single scatter albedo between 0.3 and 0.5. For most tests, the single scatter albedo averaged around 0.55 indicating that the primary particles are climate warming. We summarize the characteristics of the particles emitted during cooking events, examining the single scatter albedo

  20. Improving the Performance and Antifouling Properties of Thin-Film Composite Membranes for Water Separation Technologies

    NASA Astrophysics Data System (ADS)

    Tiraferri, Alberto

    Membrane-based water separation processes utilize semi-permeable membranes to retain dissolved solids and contaminants. Deployment of these technologies for desalination and wastewater reuse has the potential to sustainably increase the supply of potable, agricultural, and industrial water. Despite considerable development of semi-permeable membranes in the last decades, several design obstacles hampering their progress have yet to be overcome. Specifically, major membrane improvements are currently sought with respect to their performance and productivity, as well as their resistance to fouling. This dissertation research aims at the advancement of semi-permeable membranes by rational optimization of their design to: (i) understand and improve their transport properties and (ii) reduce fouling by organic molecules and delay biofouling by microorganisms. In particular, thin-film composite polyamide membranes for both reverse osmosis and forward osmosis processes are the main target of the investigation. The structural and physicochemical properties of thin-film composite membranes are both characterized and tailored through implementation of original techniques and novel functionalization protocols. The membrane structure and morphology are rationally modified to enhance the mass transport within the support layer. The influence of fabrication conditions on support layer formation and on its final structure is elucidated. The intricate interrelationship among the performance of the different layers of the composite membrane is highlighted and a new protocol is developed to characterize the transport properties of membranes deployed in forward osmosis processes. Novel approaches to impart targeted properties to the active surface of thin-film composite membranes are also proposed. The functionalization is achieved by exploiting the inherent moieties of the polyamide layer to irreversibly bind nanomaterials with desired properties. An experimental method to determine

  1. Improving the hydrogen storage properties of metal-organic framework by functionalization.

    PubMed

    Xia, Liangzhi; Liu, Qing; Wang, Fengling; Lu, Jinming

    2016-10-01

    Based on the structure of MOF-808, different substituents were introduced to replace hydrogen atom on the phenyl ring of MOF-808. The GCMC method was used to study the effect of functional groups on the hydrogen storage properties of MOF-808-X (X = -OH, -NO2, -CH3, -CN, -I). The H2 uptakes and isosteric heat of adsorption were simulated at 77 K. The results indicate that all these substituents have favorable impact on the hydrogen storage capacity, and -CN is found to be the most promising substituent to improve H2 uptake. These results may be helpful for the design of MOFs with higher hydrogen storage capacity. Graphical abstract Atomistic structures of MOFs. (a) The structures of MOF-808-X. (b) Model of organic linker. Atom color scheme: C, gray; H, white; O, red; X, palegreen (X = -OH, -NO2, -CH3, -CN, -I).

  2. Gentamicin modified chitosan film with improved antibacterial property and cell biocompatibility.

    PubMed

    Liu, Yang; Ji, Peihong; Lv, Huilin; Qin, Yong; Deng, Linhong

    2017-05-01

    Gentamicin modified chitosan film (CS-GT) was produced using a three-step procedure comprising: (i) the chitosan solution was air-dried to form a chitosan (CS) film, (ii) using citric acid to generate the amide and carboxyl groups on the surface of CS, (iii) the CS with surface carboxyl groups was modified by grafting of gentamicin. After modification, this CS-GT film has excellent hydrophilicity and biocompatibility. It is very evident that the gentamicin grafting treatment significantly improves the antibacterial properties of the CS film. Our preliminary results suggest that this novel gentamicin modified chitosan film, which can be prepared in large quantities and at low cost, should have potential application in biomedical applications.

  3. Mo doped DLC nanocomposite coatings with improved mechanical and blood compatibility properties

    NASA Astrophysics Data System (ADS)

    Tang, X. S.; Wang, H. J.; Feng, L.; Shao, L. X.; Zou, C. W.

    2014-08-01

    Mo (molybdenum) doped diamond like carbon (Mo-DLC) coatings with improved mechanical and blood compatibility properties were deposited by closed field unbalanced magnetron sputtering. The undoped and Mo-doped DLC coatings were analyzed by various characterization techniques such as Raman spectra, Atomic force microscopy, and temperature-dependent frictional wear testing. The results showed that the Mo-DLC coating with low Mo concentration was a effective protective coating with reduced residual stress and increased cohesive strength, and kept good wear resistance at the ambient temperature of 500 °C. The blood compatibility of Mo-DLC coatings was investigated by platelet adhesion. The results showed that the amount of thrombus on the Mo-DLC nanocomposite coatings was much less than that of thrombus on pyrolytic carbon films. The Mo-DLC nanocomposite coatings would be a new kind of promising materials applied to artificial heart valve and endovascula stent.

  4. Improved photoluminescence property of CTAB assisted polyaniline-AlZnO nanocomposite

    SciTech Connect

    Mitra, Mousumi; Banerjee, Dipali; Kargupta, Kajari; Ganguly, Saibal

    2015-06-24

    Polyaniline-Al doped ZnO ((PANI-AlZnO:: 70:30) nanocomposite was prepared via in situ chemical oxidative polymerization, while the hexagonal powder of AlZnO was synthesized via sol-gel technique, using Hexadecyltrimethylammonium bromide (CTAB) as a capping agent. The prepared nanocomposite was characterized by High resolution transmission electron microscopy (HRTEM), EDAX, X-ray diffraction (XRD) and Fourier transforms infrared (FTIR) spectra. The optical property of the nanomaterials is examined by photoluminescence (PL) spectra analysis. The XRD pattern confirms the formation of Al doped ZnO as well as PANI. The HRTEM images of the composite showed the formation of hexagonal AlZnO embedded in polyaniline matrix. EDAX spectrum shows the compositional analysis of the nanocomposite. FTIR spectra confirm the formation of nanocomposite of PANI and hexagonal AlZnO. The PL intensity of the nanocomposite is improved as compared to pure AlZnO.

  5. Development of hybrid cotton/hydrogel yarns with improved absorption properties for biomedical applications.

    PubMed

    Pollini, Mauro; Paladini, Federica; Sannino, Alessandro; Maffezzoli, Alfonso

    2016-06-01

    Hyperhidrosis, or excessive sweating, is an overlooked and potentially disabling symptom, which is often seen in social anxiety disorder. In this work an innovative advanced textile material was developed for application in the management of excessive sweating, preparing a drying yarn providing improved comfort. Hybrid cotton/hydrogel yarns were obtained by combining cotton with superabsorbent hydrogels through an optimization study focused on the achievement of the most promising product in terms of absorption properties and resistance to washings. Swelling and washing tests were performed using different hydrogels, and the effect of an additional crosslinking on the materials was also evaluated by testing different solutions containing Al(3+) and Ca(2+) ions. Scanning electron microscopy and infrared spectroscopy analyses were adopted to characterize morphology and chemical structure of the hydrogels undergoing different production processes. The biocompatibility of the hybrid fabrics was demonstrated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide colorimetric assay (MTT) through the extract method.

  6. Fluorescence upconversion properties of a class of improved pyridinium dyes induced by two-photon absorption

    NASA Astrophysics Data System (ADS)

    Xu, Guibao; Hu, Dawei; Zhao, Xian; Shao, Zongshu; Liu, Huijun; Tian, Yupeng

    2007-06-01

    We report the fluorescence upconversion properties of a class of improved pyridinium toluene- p-sulfonates having donor- π-acceptor (D- π-A) structure under two-photon excitation at 1064 nm. The experimental results show that both the two-photon excited (TPE) fluorescence lifetime and the two-photon pumped (TPP) energy upconversion efficiency were increased with the enhancement of electron-donating capability of the donor in the molecule. It is also indicated that an overlong alkyl group tends to result in a weakened molecular conjugation, leading to a decreased two-photon absorption (TPA) cross section. By choosing the donor, we can obtain a longest fluorescence lifetime of 837 ps, a highest energy upconversion efficiency of ˜6.1%, and a maximum TPA cross-section of 8.74×10 -48 cm 4 s/photon in these dyes.

  7. Improvement of thermoelectric properties for half-Heusler TiNiSn by interstitial Ni defects

    SciTech Connect

    Hazama, Hirofumi; Matsubara, Masato; Asahi, Ryoji; Takeuchi, Tsunehiro

    2011-09-15

    We have synthesized off-stoichiometric Ti-Ni-Sn half-Heusler thermoelectrics in order to investigate the relation between randomly distributed defects and thermoelectric properties. A small change in the composition of Ti-Ni-Sn causes a remarkable change in the thermal conductivity. An excess content of Ni realizes a low thermal conductivity of 2.93 W/mK at room temperature while keeping a high power factor. The low thermal conductivity originates in the defects generated by an excess content of Ni. To investigate the detailed defect structure, we have performed first-principles calculations and compared with x ray photoemission spectroscopy measurement. Based on these analyses, we conclude that the excess Ni atoms randomly occupy the vacant sites in the half-Heusler structure, which play as phonon scattering centers, resulting in significant improvement of the figure of merit without any substitutions of expensive heavy elements, such as Zr and Hf.

  8. Shutdown-functionalized nonwoven separator with improved thermal and electrochemical properties for lithium-ion batteries

    NASA Astrophysics Data System (ADS)

    Kim, Youngkwon; Lee, Won-Yeol; Kim, Ki Jae; Yu, Ji-Sang; Kim, Young-Jun

    2016-02-01

    A shutdown-functionalized nonwoven separator (SFNS) with improved thermal and electrochemical stabilities is prepared by a simple dip coating method for use in lithium-ion battery (LiB) applications. The SFNS shows thermal stability at 200 °C, while providing shutdown functionality at approximately 140 °C, similar to commercial porous polyethylene separators. The surface-coated polymer prevents leakage current problems and in addition, shows air permeability values similar to that of bare nonwoven separators, while maintaining a thickness of about 20 μm, which is a desired attribute of effective separators for LiBs. The SFNS also shows increased electrolyte uptake and higher conductivity, compared to a bare polyethylene separator. Therefore, a cell with the SFNS exhibits higher discharge capacity and better cycle property than that with a porous polyethylene separator. These results suggest that SFNS is an effective separator for high-performance LiBs.

  9. Study for Reduction of Outgassing Property of Adsorbed Water Gas for Improved Surface Finished Titanium Material

    NASA Astrophysics Data System (ADS)

    Takeda, Masatoshi; Kurisu, Hiroki; Uchida, Takashi; Yamamoto, Setsuo; Ishizawa, Katsunobu; Nomura, Takeru; Eda, Takahiro; Murashige, Nobuyuki

    This paper addresses the development of the surface finishing for a titanium material and the study for the reduction of outgassing property of adsorbed water (H2O) molecules. Developed surface finishing is composed of the buffing for the reduction of the surface roughness and improved chemical polishing for the thick surface oxide layer compared with the chemical polishing so far. The surface roughness of the surface finished titanium material is reduced 35% and the thickness of the surface oxide layer increases by 30%. The total amount of thermal desorbed H2O gas for the new surface finished titanium is reduced 30%. It is considered that the origin for the decrease of the amount of desorption H2O gas is the reduction of the adsorption sites due to the decrease of the surface roughness and the reduction of adsorption energy of H2O gas due to the strong surface oxidation for a titanium material.

  10. Improved Mechanical Properties of Various Fabric-Reinforced Geocomposite at Elevated Temperature

    NASA Astrophysics Data System (ADS)

    Samal, Sneha; Phan Thanh, Nhan; Petríková, Iva; Marvalová, Bohadana

    2015-07-01

    This article signifies the improved performance of the various types of fabric reinforcement of geopolymer as a function of physical, thermal, mechanical, and heat-resistant properties at elevated temperatures. Geopolymer mixed with designed Si:Al ratios of 15.6 were synthesized using three different types of fabric reinforcement such as carbon, E-glass, and basalt fibers. Heat testing was conducted on 3-mm-thick panels with 15 × 90 mm surface exposure region. The strength of carbon-based geocomposite increased toward a higher temperature. The basalt-reinforced geocomposite strength decreased due to the catastrophic failure in matrix region. The poor bridging effect and dissolution of fabric was observed in the E-glass-reinforced geocomposite. At an elevated temperature, fiber bridging was observed in carbon fabric-reinforced geopolymer matrix. Among all the fabrics, carbon proved to be suitable candidate for the high-temperature applications in thermal barrier coatings and fire-resistant panels.

  11. Regulation of Isotopic Composition of Water - way of Improvement of Cosmonauts Drinking Water Functional Properties

    NASA Astrophysics Data System (ADS)

    Kulikova, Ekaterina; Utina, Dina; Vorozhtsova, Svetlana; Severyuhin, Yuri; Abrosimova, Anna; Sinyak, Yuri; Ivanov, Alexander

    The problem in providing drinking water to cosmonauts is solved - at this moment there is a task to improve the functional properties of the water. One of the perspectives of this trend is the use of light isotopic water. The animal studies have shown that long-term consumption of water with a depletion of deuterium and oxygen heavy isotopes accelerates the rise of mass non-irradiated mice, the phase fluctuations reducing or increasing hematological parameters were having adaptive nature. These fluctuations didn’t overcome values beyond the physiological norm of this type of animal. It is established that the therapeutic use of light isotopic water with 35 - 90 ppm in deuterium increases the survival of irradiated mice by an average of 30%, contributes to the preservation of irradiated animals body weight. Treatment of acute radiation sickness with light isotopic water stimulates hematopoietic recovery. At the same time, keeping mice drinking light isotopic water for 7 - 8 days before the irradiation (from 4 to 8.5 Gr) has no effect on the level of radio resistance. Longer keeping mice on light isotopic water, for 14 -21 days - reduction in life expectancy, animal mass, bone marrow cellularity and the level of white blood cells in irradiated animals is noted. It was established that keeping mice on light isotopic water for 14 days before exposure in experimental animals causes an increase in the mitotic index and the frequency of formation of aberrant mitosis after 24 hours of Co(60) gamma radiation in doses of 1 , 2, and 4 Gr. Thus, it is clear that the regulation of the isotopic composition of drinking water - way to improve its functional properties.

  12. Targeting the LRP5 pathway improves bone properties in a mouse model of osteogenesis imperfecta.

    PubMed

    Jacobsen, Christina M; Barber, Lauren A; Ayturk, Ugur M; Roberts, Heather J; Deal, Lauren E; Schwartz, Marissa A; Weis, MaryAnn; Eyre, David; Zurakowski, David; Robling, Alexander G; Warman, Matthew L

    2014-10-01

    The cell surface receptor low-density lipoprotein receptor-related protein 5 (LRP5) is a key regulator of bone mass and bone strength. Heterozygous missense mutations in LRP5 cause autosomal dominant high bone mass (HBM) in humans by reducing binding to LRP5 by endogenous inhibitors, such as sclerostin (SOST). Mice heterozygous for a knockin allele (Lrp5(p.A214V) ) that is orthologous to a human HBM-causing mutation have increased bone mass and strength. Osteogenesis imperfecta (OI) is a skeletal fragility disorder predominantly caused by mutations that affect type I collagen. We tested whether the LRP5 pathway can be used to improve bone properties in animal models of OI. First, we mated Lrp5(+/p.A214V) mice to Col1a2(+/p.G610C) mice, which model human type IV OI. We found that Col1a2(+/p.G610C) ;Lrp5(+/p.A214V) offspring had significantly increased bone mass and strength compared to Col1a2(+/p.G610C) ;Lrp5(+/+) littermates. The improved bone properties were not a result of altered mRNA expression of type I collagen or its chaperones, nor were they due to changes in mutant type I collagen secretion. Second, we treated Col1a2(+/p.G610C) mice with a monoclonal antibody that inhibits sclerostin activity (Scl-Ab). We found that antibody-treated mice had significantly increased bone mass and strength compared to vehicle-treated littermates. These findings indicate increasing bone formation, even without altering bone collagen composition, may benefit patients with OI.

  13. Targeting the LRP5 pathway improves bone properties in a mouse model of Osteogenesis Imperfecta

    PubMed Central

    Jacobsen, Christina M.; Barber, Lauren A.; Ayturk, Ugur M.; Roberts, Heather J.; Deal, Lauren E.; Schwartz, Marissa A.; Weis, MaryAnn; Eyre, David; Zurakowski, David; Robling, Alexander G.; Warman, Matthew L.

    2014-01-01

    The cell surface receptor low-density lipoprotein receptor-related protein 5 (LRP5) is a key regulator of bone mass and bone strength. Heterozygous missense mutations in LRP5 cause autosomal dominant high bone mass (HBM) in humans by reducing binding to LRP5 by endogenous inhibitors, such as sclerostin (SOST). Mice heterozygous for a knockin allele (Lrp5p.A214V) that is orthologous to a human HBM-causing mutation have increased bone mass and strength. Osteogenesis Imperfecta (OI) is a skeletal fragility disorder predominantly caused by mutations that affect type I collagen. We tested whether the LRP5 pathway can be used to improve bone properties in animal models of OI. First, we mated Lrp5+/p.A214V mice to Col1a2+/p.G610C mice, which model human type IV OI. We found that Col1a2+/p.G610C;Lrp5+/p.A214V offspring had significantly increased bone mass and strength compared to Col1a2+/p.G610C;Lrp5+/+ littermates. The improved bone properties were not due to altered mRNA expression of type I collagen or its chaperones, nor were they due to changes in mutant type I collagen secretion. Second, we treated Col1a2+/p.G610C mice with a monoclonal antibody that inhibits sclerostin activity (Scl-Ab). We found that antibody treated mice had significantly increased bone mass and strength compared to vehicle treated littermates. These findings indicate increasing bone formation, even without altering bone collagen composition, may benefit patients with OI. PMID:24677211

  14. Improvement of optical properties of TiO2 thin film treated with electron beam.

    PubMed

    Shin, Joong-Hyeok; Lee, Byung Cheol; Woo, Hee-Gweon; Hwang, Kwang Ha; Jun, Jin

    2013-03-01

    Nanocrystalline titanium dioxide (TiO2) thin films on silicon wafer substrates were prepared by sol-gel spin coating process. The prepared thin films were treated with electron beam (1.1 MeV, 300 kGy) at air atmosphere. The effects of electron-beam (EB) irradiation on the structural and optical properties of the TiO2 thin films were investigated. The structures of all the TiO2 thin films by XRD analysis showed an anatase phase, and the phase remained unchanged within the investigating range of EB treatment. The thickness of the titania thin film decreased slightly with EB treatment whereas the porosity increased. The EB treatment of TiO2 thin film can increase the proportion of Ti3+ in Ti2p at the thin film surface. The optical transmittance of the film in the wavelength ranges of above 380 nm increased after the EB treatment while its refractive index decreased with increasing EB dose. Therefore, improvement of the optical properties could be due to the change in both surface chemistry and morphology of the TiO2 thin films affected by EB irradiation.

  15. Peroxidase-mediated conjugation of corn fiber gum and bovine serum albumin to improve emulsifying properties.

    PubMed

    Liu, Yan; Qiu, Shuang; Li, Jinlong; Chen, Hao; Tatsumi, Eizo; Yadav, Madhav; Yin, Lijun

    2015-03-15

    The emulsifying properties of corn fiber gum (CFG), a naturally occurring polysaccharide-protein complex, was improved by kinetically controlled formation of hetero-covalent linkages with bovine serum albumin (BSA), using horseradish peroxidase (HRP). The formation of hetero-crosslinked CFG-BSA conjugates was confirmed using ultraviolet-visible and Fourier-transform infrared analyses. The optimum CFG-BSA conjugates were prepared at a CFG:BSA weight ratio of 10:1, and peroxidase:BSA weight ratio of 1:4000. Selected CFG-BSA conjugates were used to prepare oil-in-water emulsions; the emulsifying properties were better than those of emulsions stabilized with only CFG or BSA. Measurements of mean droplet sizes and zeta potentials showed that CFG-BSA-conjugate-stabilized emulsions were less susceptible to environmental stresses, such as pH changes, high K ionic strengths, and freeze-thaw treatments than CFG- or BSA-stabilized emulsions. These conjugates have potential applications as novel emulsifiers in food industry.

  16. Properties of Dopants in HfOx for Improving the Performance of Nonvolatile Memory

    NASA Astrophysics Data System (ADS)

    Duncan, Dan; Magyari-Köpe, Blanka; Nishi, Yoshio

    2017-03-01

    Doping is an increasingly popular technique for improving the characteristics of cutting-edge HfOx nonvolatile memory devices, but relatively few dopant species have been investigated. In this work, the properties of 50 different cation and anion dopants in HfOx are explored using density-functional theory and are corroborated with experimental data. Depending on the atomic species, dopants are found to preferentially form on either substitutional or interstitial lattice sites and to reduce the formation energy of oxygen vacancies in the surrounding oxide. The behavior of cation dopants in HfOx is also found to be well predicted by six properties: dopant valence, atomic radius, native-oxide enthalpy of formation, coordination number, magnetization, and charge transfer with the HfOx lattice. These results can be used to optimize dopant selection for tuning of the switching characteristics of HfOx -based resistance-change random-access-memory and conductive-bridge random-access-memory devices.

  17. Introducing improved structural properties and salt dependence into a coarse-grained model of DNA

    NASA Astrophysics Data System (ADS)

    Snodin, Benedict E. K.; Randisi, Ferdinando; Mosayebi, Majid; Šulc, Petr; Schreck, John S.; Romano, Flavio; Ouldridge, Thomas E.; Tsukanov, Roman; Nir, Eyal; Louis, Ard A.; Doye, Jonathan P. K.

    2015-06-01

    We introduce an extended version of oxDNA, a coarse-grained model of deoxyribonucleic acid (DNA) designed to capture the thermodynamic, structural, and mechanical properties of single- and double-stranded DNA. By including explicit major and minor grooves and by slightly modifying the coaxial stacking and backbone-backbone interactions, we improve the ability of the model to treat large (kilobase-pair) structures, such as DNA origami, which are sensitive to these geometric features. Further, we extend the model, which was previously parameterised to just one salt concentration ([Na+] = 0.5M), so that it can be used for a range of salt concentrations including those corresponding to physiological conditions. Finally, we use new experimental data to parameterise the oxDNA potential so that consecutive adenine bases stack with a different strength to consecutive thymine bases, a feature which allows a more accurate treatment of systems where the flexibility of single-stranded regions is important. We illustrate the new possibilities opened up by the updated model, oxDNA2, by presenting results from simulations of the structure of large DNA objects and by using the model to investigate some salt-dependent properties of DNA.

  18. Poly(3-hydroxybutyrate)/ZnO bionanocomposites with improved mechanical, barrier and antibacterial properties.

    PubMed

    Díez-Pascual, Ana M; Díez-Vicente, Angel L

    2014-06-17

    Poly(3-hydroxybutyrate) (PHB)-based bionanocomposites incorporating different contents of ZnO nanoparticles were prepared via solution casting technique. The nanoparticles were dispersed within the biopolymer without the need for surfactants or coupling agents. The morphology, thermal, mechanical, barrier, migration and antibacterial properties of the nanocomposites were investigated. The nanoparticles acted as nucleating agents, increasing the crystallization temperature and the degree of crystallinity of the matrix, and as mass transport barriers, hindering the diffusion of volatiles generated during the decomposition process, leading to higher thermal stability. The Young's modulus, tensile and impact strength of the biopolymer were enhanced by up to 43%, 32% and 26%, respectively, due to the strong matrix-nanofiller interfacial adhesion attained via hydrogen bonding interactions, as revealed by the FT-IR spectra. Moreover, the nanocomposites exhibited reduced water uptake and superior gas and vapour barrier properties compared to neat PHB. They also showed antibacterial activity against both Gram-positive and Gram-negative bacteria, which was progressively improved upon increasing ZnO concentration. The migration levels of PHB/ZnO composites in both non-polar and polar simulants decreased with increasing nanoparticle content, and were well below the current legislative limits for food packaging materials. These biodegradable nanocomposites show great potential as an alternative to synthetic plastic packaging materials especially for use in food and beverage containers and disposable applications.

  19. Poly(3-hydroxybutyrate)/ZnO Bionanocomposites with Improved Mechanical, Barrier and Antibacterial Properties

    PubMed Central

    Díez-Pascual, Ana M.; Díez-Vicente, Angel L.

    2014-01-01

    Poly(3-hydroxybutyrate) (PHB)-based bionanocomposites incorporating different contents of ZnO nanoparticles were prepared via solution casting technique. The nanoparticles were dispersed within the biopolymer without the need for surfactants or coupling agents. The morphology, thermal, mechanical, barrier, migration and antibacterial properties of the nanocomposites were investigated. The nanoparticles acted as nucleating agents, increasing the crystallization temperature and the degree of crystallinity of the matrix, and as mass transport barriers, hindering the diffusion of volatiles generated during the decomposition process, leading to higher thermal stability. The Young’s modulus, tensile and impact strength of the biopolymer were enhanced by up to 43%, 32% and 26%, respectively, due to the strong matrix-nanofiller interfacial adhesion attained via hydrogen bonding interactions, as revealed by the FT-IR spectra. Moreover, the nanocomposites exhibited reduced water uptake and superior gas and vapour barrier properties compared to neat PHB. They also showed antibacterial activity against both Gram-positive and Gram-negative bacteria, which was progressively improved upon increasing ZnO concentration. The migration levels of PHB/ZnO composites in both non-polar and polar simulants decreased with increasing nanoparticle content, and were well below the current legislative limits for food packaging materials. These biodegradable nanocomposites show great potential as an alternative to synthetic plastic packaging materials especially for use in food and beverage containers and disposable applications. PMID:24941255

  20. An experimental survey of additives for improving dehydrogenation properties of magnesium hydride

    NASA Astrophysics Data System (ADS)

    Zhou, Chengshang; Fang, Zhigang Zak; Sun, Pei

    2015-03-01

    The use of a wide range of additives has been known as an important method for improving hydrogen storage properties of MgH2. There is a lack of a standard methodology, however, that can be used to select or compare the effectiveness of different additives. A systematic experimental survey was carried out in this study to compare a wide range of additives including transitions metals, transition metal oxides, hydrides, intermetallic compounds, and carbon materials, with respect to their effects on dehydrogenation properties of MgH2. MgH2 with various additives were prepared by using a high-energy-high-pressure planetary ball milling method and characterized by using thermogravimetric analysis (TGA) techniques. The results showed that additives such as Ti and V-based metals, hydride, and certain intermetallic compounds have strong catalytic effects. Additives such as Al, In, Sn, Si showed minor effects on the kinetics of the dehydrogenation of MgH2, while exhibiting moderate thermodynamic destabilizing effects. In combination, MgH2 with both kinetic and thermodynamic additives, such as the MgH2-In-TiMn2 system, exhibited a drastically decreased dehydrogenation temperature.