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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. Improvement of Pharmaceutical Properties of Isoprenoid Compounds through the Formation of Cyclodextrin Pseudorotaxane-Like Supramolecules.

    PubMed

    Higashi, Taishi; Tanaka, Haruki; Yoshimatsu, Ayumi; Ikeda, Haruna; Arima, Kanako; Honjo, Masatoshi; Iwamoto, Chihiro; Motoyama, Keiichi; Arima, Hidetoshi

    2016-01-01

    The purpose of this study was to design cyclodextrin (CyD)-based pseudorotaxane-like supramolecular complexes with various isoprenoid compounds, such as reduced coenzyme Q10 (R-CoQ10), squalene, tocotrienol, and teprenone, and to evaluate their pharmaceutical properties. Squalene, tocotrienol, and teprenone formed precipitates with β-CyD and γ-CyD in aqueous solution, whereas R-CoQ10 formed precipitates with γ-CyD aqueous solution. The results of powder X-ray diffraction and (1)H-NMR analyses indicated that these precipitates are derived from pseudorotaxane-like supramolecular complexes. The photostability of teprenone was markedly improved by complexation with CyDs, especially in the γ-CyD system. In addition, the dispersion rates of teprenone in the γ-CyD system were higher than those in the β-CyD system, compared with the corresponding physical mixtures. In conclusion, pharmaceutical properties such as photostability and dispersion rates of isoprenoid compounds were improved by the formation of pseudorotaxane-like supramolecular complexes with β-CyD and/or γ-CyD. PMID:26852798

  3. Improved blend and tablet properties of fine pharmaceutical powders via dry particle coating.

    PubMed

    Huang, Zhonghui; Scicolone, James V; Han, Xi; Davé, Rajesh N

    2015-01-30

    The improvements in the flow and packing of fine pharmaceutical powder blends due to dry coating of micronized acetaminophen (mAPAP, ∼11μm), a model poorly flowing drug, are quantified. Poor flow and packing density of fine excipients (∼20μm) allowed testing the hypothesis that dry coating of cohesive API may counteract poor flow and packing of fine pharmaceutical powder blends. Further, fine excipients could improve compaction and reduce segregation tendency. It was found that flow function coefficient (FFC) and bulk density enhancements for 10%, 30%, and 60% (w/w), API loading blends with dry coated API are significantly higher than those without coated silica. At the highest API loading, for which coarser excipients were also used as reference, the flow and packing of dry coated mAPAP blends were significantly increased regardless of the excipient particle size, exceeding those of a well compacting excipient, Avicel 102. In addition, tensile strength of tablets with fine excipients was significantly higher, indicating improved compactibility. These results show for the first time that dry coating of fine, cohesive API powder leads to significantly improved flow and packing of high API loading blends consisting of fine excipients, while achieving improved tablet compactibility, suggesting suitability for direct compaction. PMID:25475016

  4. 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.

  5. Pharmaceutical cocrystals: along the path to improved medicines.

    PubMed

    Duggirala, Naga K; Perry, Miranda L; Almarsson, Örn; Zaworotko, Michael J

    2016-01-14

    Cocrystals, a long known but understudied class of crystalline solids, have attracted interest from crystal engineers and pharmaceutical scientists in the past decade and are now an integral part of the preformulation stage of drug development. This is largely because cocrystals that contain a drug molecule, pharmaceutical cocrystals, can modify physicochemical properties without the need for covalent modification of the drug molecule. This review presents a brief history of cocrystals before addressing recent advances in design, discovery and development of pharmaceutical cocrystals that have occurred since an earlier review published in 2004. We address four aspects of cocrystals: nomenclature; design using hydrogen-bonded supramolecular synthons; methods of discovery and synthesis; development of pharmaceutical cocrystals as drug products. Cocrystals can be classified into molecular cocrystals (MCCs) that contain only neutral components (coformers) and ionic cocrystals (ICCs), which are comprised of at least one ionic coformer that is a salt. That cocrystals, especially ICCs, offer much greater diversity in terms of composition and properties than single component crystal forms and are amenable to design makes them of continuing interest. Seven recent case studies that illustrate how pharmaceutical cocrystals can improve physicochemical properties and clinical performance of drug substances, including a recently approved drug product based upon an ICC, are presented. PMID:26565650

  6. Purified guar galactomannan as an improved pharmaceutical excipient.

    PubMed

    Gebert, M S; Friend, D R

    1998-08-01

    The purpose of this study was to assess certain pharmaceutical attributes of guar galactomannan, a hydrocolloid polysaccharide obtained from the endosperm of the leguminous plant Cyamopsis tetragonolobus (L.), following purification using both literature procedures and new processes. Experiments were performed to measure viscosity, hydration rate, tablet hardness, and dissolution profiles of guar galactomannan both before and after purification. The viscosity of an aqueous 1% purified galactomannan solution is typically 40-50% higher than its unpurified guar galactomannan precursor. The hydration rate of an aqueous 1% purified galactomannan solution increases by 100% after purification. These physicochemical changes resulted in improvements in pharmaceutical properties such as better stir speed independence in both tablet and capsule dissolution profiles and improved tablet hardness. For instance, time to 50% dissolution of ranitidine HCl from capsules containing unpurified guar gum was 0.4 and 1.8 hr at 20 and 40 rpm, respectively, using USP Apparatus II. Using the same amount of purified guar gum and the same conditions (20 and 40 rpm), these values were increased to 2.9 and 3.8 hr, respectively. These data demonstrate a reduced effect of changing agitation conditions and the need for less guar gum to sustain the release of a water-soluble drug. Tablet hardness of purified guar gum (particle size < 75 microns) was about 7 kP and the same unpurified guar gum of equal particle size and hydration gave a hardness of less than 1 kP. PMID:9742552

  7. 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

  8. 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

  9. 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. PMID:23013408

  10. 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

  11. 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

  12. 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.

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

    PubMed

    Ashizuka, Yuki; Horisawa, Eijiro

    2016-08-01

    Oleaginous white petrolatum ointment (WP ointment) is one of the most commonly used dosage forms in the preparation of topical products. In general, WP ointments containing medium chain fatty acid triglycerides (MCT) are manufactured through a process of melting, mixing, agitating, and cooling. To investigate the pharmaceutical properties of WP ointments in greater detail, we examined manufacturing factors which could potentially influence the pharmaceutical properties of the finished product. WP ointment samples containing 10% MCT were stirred with a homogenizer and a paddle mixer at 65°C, then the homogenizer was stopped. Next, the paddle-mixer was stopped at several planned temperature points at which different samples were taken. Each sample was then cooled under the following planned conditions: rapid-cooling [-50°C/h] and slow-cooling [-7.5°C/h]. The pharmaceutical properties of each WP ointment sample, along with the appearance (Optical/digital microscope), hardness (Rheometer), and bleeding ability (100 Mesh wire-net cone) were measured. Then, release profiles were performed with a WP ointment using the model active ingredient Vitamin D. As a result, high hardness, low bleeding ability and low release profile were observed in the WP ointment samples that were manufactured under the condition of stopping the paddle-mixer at 40°C. However, the influence of cooling speed was observed to affect only hardness. Through optical microscopic observation, it was found that the appearance of WP ointment samples differed depending on the conditions under which they were manufactured. In this study, it was clear that the pharmaceutical properties of WP ointment samples were particularly influenced by the paddle-mixer stopping temperature. PMID:27193304

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

    PubMed

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

    2016-05-01

    Crystalline mesophases, which are commonly classified according to their translational, orientational, and conformational order as liquid crystals, plastic crystals, and conformationally disordered crystals, represent a common state of condensed matter. As an intermediate state between crystalline and amorphous materials, crystalline mesophases resemble amorphous materials in relation to their molecular mobility, with the glass transition being their common property, and at the same time possessing a certain degree of translational periodicity (with the exception of nematic phase), with corresponding narrow peaks in X-ray diffraction patterns. For example, plastic crystals, which can be formed both by near-spherical molecules and molecules of lower symmetry, such as planar or chain molecules, can have both extremely sharp X-ray diffraction lines and exhibit glass transition. Fundamentals of structural arrangements in mesophases are compared with several types of disorder in crystalline materials, as well as with short-range ordering in amorphous solids. Main features of the molecular mobility in crystalline mesophases are found to be generally similar to amorphous materials, although some important differences do exist, depending on a particular type of mobility modes involved in relaxation processes. In several case studies reviewed, chemical stability appears to follow the extent of disorder, with the stability of crystalline mesophase found to be intermediate between amorphous (least stable) and crystalline (most stable) materials. Finally, detection of crystalline mesophases during manufacturing of two different types of dosage forms is discussed. PMID:27067607

  15. 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

  16. Influence of mannitol concentration on the physicochemical, mechanical and pharmaceutical properties of lyophilised mannitol.

    PubMed

    Kaialy, Waseem; Khan, Usman; Mawlud, Shadan

    2016-08-20

    Mannitol is a pharmaceutical excipient that is receiving increased popularity in solid dosage forms. The aim of this study was to provide comparative evaluation on the effect of mannitol concentration on the physicochemical, mechanical, and pharmaceutical properties of lyophilised mannitol. The results showed that the physicochemical, mechanical and pharmaceutical properties of lyophilised mannitol powders are strong functions of mannitol concentration. By decreasing mannitol concentration, the true density, bulk density, cohesivity, flowability, netcharge-to-mass ratio, and relative degree of crystallinity of LM were decreased, whereas the breakability, size distribution, and size homogeneity of lyophilised mannitol particles were increased. The mechanical properties of lyophilised mannitol tablets improved with decreasing mannitol concentration. The use of lyophilised mannitol has profoundly improved the dissolution rate of indomethacin from tablets in comparison to commercial mannitol. This improvement exhibited an increasing trend with decreasing mannitol concentration. In conclusion, mannitols lyophilised from lower concentrations are more desirable in tableting than mannitols from higher concentrations due to their better mechanical and dissolution properties. PMID:27242312

  17. 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. PMID:22171299

  18. 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

  19. Viscoelastic properties and compaction behaviour of pharmaceutical particulate materials

    NASA Astrophysics Data System (ADS)

    Tsardaka, Ekaterini D.

    1990-01-01

    The viscoelastic behaviour of particulate solids is of major relevance in powder compaction. When designing a pharmaceutical tablet formulation, it is highly undesirable for the tablet properties to be markedly affected by changes in compaction rate on different tablet presses, if problems are to be avoided during scale-up and manufacture. In order to be able to predict and minimise the time-dependent deformation of pharmaceutical powders, a full understanding of such behaviour is needed. For comparative purposes, a range of materials with differing compaction properties were studied. Heckel plots were extended in order to study the consolidation behaviour of materials during compression, decompression and after ejection. A number of derived parameters were proposed as a useful means of assessing the viscoelastic characteristics of materials. The mechanical properties of the tablets produced were assessed by means of both a diametral loading test and a direct tension test, in order to study the homogeneity of tablets with respect to strength and toughness. Fitting stress relaxation data to a hyperbolic equation enabled the asymptotic value of relaxed stress and the rate of stress relaxation at short times to be determined. Creep analysis was found to be a most useful method in quantifying the viscoelastic properties of materials. Creep experiments were used to separately quantify the ability of a material to undergo elastic, viscoelastic and plastic deformation at constant stress. Analysis of the viscoelastic compliance provided a time constant and an equilibrium value. Spectral analysis of the creep data was an alternative method of studying viscoelastic behaviour, since analysis in the frequency domain revealed hidden periodicities of mechanisms possibly related to viscoelastic behaviour. A detailed study of several forms of modified starch addressed factors which may influence its viscoelastic behaviour, including manufacturing process variables such as particle

  20. 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. PMID:25447824

  1. Improvement of flow and bulk density of pharmaceutical powders using surface modification.

    PubMed

    Jallo, Laila J; Ghoroi, Chinmay; Gurumurthy, Lakxmi; Patel, Utsav; Davé, Rajesh N

    2012-02-28

    Improvement in flow and bulk density, the two most important properties that determine the ease with which pharmaceutical powders can be handled, stored and processed, is done through surface modification. A limited design of experiment was conducted to establish a standardized dry coating procedure that limits the extent of powder attrition, while providing the most consistent improvement in angle of repose (AOR). The magnetically assisted impaction coating (MAIC) was considered as a model dry-coater for pharmaceutical powders; ibuprofen, acetaminophen, and ascorbic acid. Dry coated drug powders were characterized by AOR, particle size as a function of dispersion pressure, particle size distribution, conditioned bulk density (CBD), Carr index (CI), flow function coefficient (FFC), cohesion coefficient using different instruments, including a shear cell in the Freeman FT4 powder rheometer, and Hansen flowability index. Substantial improvement was observed in all the measured properties after dry coating relative to the uncoated powders, such that each powder moved from a poorer to a better flow classification and showed improved dispersion. The material intrinsic property such as cohesion, plotted as a function of particle size, gave a trend similar to those of bulk flow properties, AOR and CI. Property improvement is also illustrated in a phase map of inverse cohesion (or FFC) as a function of bulk density, which also indicated a significant positive shift due to dry coating. It is hoped that such phase maps are useful in manufacturing decisions regarding the need for dry coating, which will allow moving from wet granulation to roller compaction or to direct compression based formulations. PMID:22197769

  2. 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.

  3. 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

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

    PubMed

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

    2016-09-01

    In pharmaceutical industry, the use of lubricants is mostly based on historical experiences or trial and error methods even these days. It may be demanding in terms of the material consumption and may result in sub-optimal drug composition. Powder rheology enables more accurate monitoring of the flow properties and because the measurements need only a small sample it is perfectly suitable for the rare or expensive substances. In this work, rheological properties of four common excipients (pregelatinized maize starch, microcrystalline cellulose, croscarmellose sodium and magnesium stearate) were studied by the FT4 Powder Rheometer, which was used for measuring the compressibility index by a piston and flow properties of the powders by a rotational shear cell. After an initial set of measurements, two excipients (pregelatinized maize starch and microcrystalline cellulose) were chosen and mixed, in varying amounts, with anhydrous colloidal silicon dioxide (Aerosil 200) used as a glidant. The bulk (conditioned and compressed densities, compressibility index), dynamic (basic flowability energy) and shear (friction coefficient, flow factor) properties were determined to find an optimum ratio of the glidant. Simultaneously, the particle size data were obtained using a low-angle laser light scattering (LALLS) system and scanning electron microscopy was performed in order to examine the relationship between the rheological properties and the inner structure of the materials. The optimum of flowability for the mixture composition was found, to correspond to empirical findings known from general literature. In addition the mechanism of colloidal silicone dioxide action to improve flowability was suggested and the hypothesis was confirmed by independent test. New findings represent a progress towards future application of determining the optimum concentration of glidant from the basic characteristics of the powder in the pharmaceutical research and development. PMID:27163240

  5. Improving efficiencies in pharmaceutical distribution channels using the economic order quantity model.

    PubMed

    Sullivan, D L; Schommer, J C

    1993-01-01

    The purpose of this study was to investigate empirically the potential cost savings to a pharmaceutical wholesaler using the Economic Order Quantity (EOQ) model. This model allows for calculating the order quantity that minimizes both ordering and holding costs. A regional pharmaceutical wholesaler was selected for a case analysis study using the EOQ model. Eleven brand name products were randomly selected for the analysis. The average yearly cost savings using EOQ was $31.92 per product. The potential yearly cost savings based on 8500 brand name stock-keeping units was $271,320. Using EOQ can therefore assist pharmaceutical wholesalers in minimizing holding and ordering costs and improve efficiency for pharmaceutical distribution channels. PMID:8111811

  6. 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)

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

    PubMed

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

    2016-11-01

    Sorption is a key factor in determining the persistence, attenuation and bioavailability of sediment-associated contaminants. However, our understanding of the sorption behaviour of pharmaceuticals in sediments is poor. In this study, we investigated the sorption behaviour of a diverse set of pharmaceuticals in a range sediment types. Sorption affinity of pharmaceuticals for all sediments was found to increase in the order mefenamic acidpharmaceuticals. Multiple linear regression analysis was therefore used to develop new models for estimating sorption of individual pharmaceuticals based on sediment properties. The analyses indicated that sorption is related to properties such as Log Dow of a compound in the sediment (lipophilicity corrected for the sediment pH), cation exchange capacity, clay%, organic carbon content and exchangeable Ca(2+), although, with the exception of atenolol, robust relationships between sediment properties and sorption were not obtained. Overall, the results demonstrate how complex the processes are that drive the sorption of pharmaceuticals in sediments and highlight the need for generation of further experimental data and further model development work. PMID:27270139

  8. 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. PMID:27049789

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

    PubMed

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

    2015-06-01

    Ginkgo biloba is an attractive and traditional medicinal plant, and has been widely used as a phytomedicine in the prevention and treatment of cardiovascular and cerebrovascular diseases. Flavonoids and terpene lactones are the major bioactive components of Ginkgo, whereas the ginkgolic acids (GAs) with strong allergenic properties are strictly controlled. In this study, we tested the content of flavonoids and GAs under ultraviolet-B (UV-B) treatment and performed comparative proteomic analyses to determine the differential proteins that occur upon UV-B radiation. That might play a crucial role in producing flavonoids and GAs. Our phytochemical analyses demonstrated that UV-B irradiation significantly increased the content of active flavonoids, and decreased the content of toxic GAs. We conducted comparative proteomic analysis of both whole leaf and chloroplasts proteins. In total, 27 differential proteins in the whole leaf and 43 differential proteins in the chloroplast were positively identified and functionally annotated. The proteomic data suggested that enhanced UV-B radiation exposure activated antioxidants and stress-responsive proteins as well as reduced the rate of photosynthesis. We demonstrate that UV-B irradiation pharmaceutically improved the metabolic ingredients of Ginkgo, particularly in terms of reducing GAs. With high UV absorption properties, and antioxidant activities, the flavonoids were likely highly induced as protective molecules following UV-B irradiation. PMID:25604066

  10. Review: Chios mastic gum: a plant-produced resin exhibiting numerous diverse pharmaceutical and biomedical properties.

    PubMed

    Dimas, Konstantinos S; Pantazis, Panayotis; Ramanujam, Rama

    2012-01-01

    Chios mastic gum (CMG) is a resin produced by the plant Pistacia lentiscus var. chia. CMG is used to extract the mastic gum essential oil (MGO). CMG and MGO consist of nearly 70 constituents and have demonstrated numerous and diverse biomedical and pharmacological properties including (a) eradication of bacteria and fungi that may cause peptic ulcers, tooth plaque formation and malodor of the mouth and saliva; (b) amelioration or dramatic reduction of symptoms of autoimmune diseases by inhibiting production of pro-inflammatory substances by activated macrophages, production of cytokines by peripheral blood mononuclear cells in patients with active Crohn's disease, and suppression of production of inflammatory cytokines and chemokines in an asthma model in mice; (c) protection of the cardiovascular system by effectively lowering the levels of total serum cholesterol, low-density lipoprotein and triglycerides in rats, and protection of low-density lipoprotein from oxidation in humans; (d) induction of apoptosis in human cancer cells in vitro and extensive inhibition of growth of human tumors xenografted in immunodeficient mice; and (e) improvement of symptoms in patients with functional dyspepsia. Collectively taken, these numerous and diverse medical and pharmaceutical properties of CMG and MGO warrant further research in an effort to enhance specific properties and identify specific constituent(s) that might be associated with each property. PMID:22949590

  11. 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. PMID:16358442

  12. Resveratrol: Biological and pharmaceutical properties as anticancer molecule.

    PubMed

    Hsieh, Tze-chen; Wu, Joseph M

    2010-01-01

    There is ample evidence that shows an inverse relationship between consumption of fruit/vegetable-rich diets and the risk of cancer at various anatomical sites. In this review, we will assess and summarize recent advances on cancer prevention by resveratrol, a natural stilbenoid present in red grapes, peanuts, some common drinks, and dietary supplements. We will focus on data published within the past few years on in vivo model tumor animal studies that reinforce the chemopreventive efficacy of resveratrol against a multitude of cancers, as well as on its sensitization/enhancing activities against tumor cells when used in combination with established chemotherapeutic and pharmaceutical agents. In addition, we will review examples resveratrol-target proteins, denoted RTPs, including the 24-kDa cytosolic protein quinone reductase 2 (NQO2) discovered in our laboratory that may confer resveratrol responsiveness to cancer cells. We will discuss the possible role of NQO2 in mediating cancer prevention by resveratrol. Our analysis of published data strengthen support that resveratrol displays novel roles in various cellular processes, and help to establish an expanded molecular framework for cancer prevention by resveratrol in vivo. PMID:20623546

  13. Characterization and adsorptive properties of pharmaceutical grade clays.

    PubMed

    Browne, J E; Feldkamp, J R; White, J L; Hem, S L

    1980-07-01

    The adsorption of tetracycline by clays commonly used in pharmacy can be predicted if the identity and character of the commerical clay sample are established. X-ray diffraction. IR spectroscopy, and chemical analysis were used to identify the clay component and any nonclay diluents present in a series of commerical pharmaceutical grade clays. The major clay components were montmorillonite, hectorite, attapulgite, saponite, and kaolinite. The clay structure, the nature of the exchangeable cation, and the presence of nonclay components are important factors affecting the tetracycline-clay interaction. In general, clay structures with a high surface charge lead to a greater interaction with the protonated form of tetracycline, while interaction with the zwitterionic form of tetracycline occurs in clay structures with minimal surface charge. The presence of multivalent, exchangeable cations on the clay surface diminishes interaction with the protonated form of tetracycline. Nonclay components such as calcite and dolomite increase the interactions of the zwitterionic and anionic forms of tetracycline with the clay. PMID:7391947

  14. [Examination of the properties of amphotensides with potential use as pharmaceuticals].

    PubMed

    Bialik, W

    1992-01-01

    Basic biological, surface-active and emulsifying properties of manufactured amphotensides in comparison with commercial products have been determined. It has been shown that the compounds investigated should be utilized as auxiliary substances in pharmaceutical technology. There is especially advisable to apply them as emulsifiers for o/w emulsions. PMID:8769083

  15. 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. PMID:15154832

  16. Pharmaceutical properties of freeze-dried formulations of egg albumin, several drugs and olive oil.

    PubMed

    Tsuji, Y; Kakegawa, H; Miyataka, H; Nishiki, M; Matsumoto, H; Satoh, T

    1996-04-01

    The freeze-dried ternary formulations of meclizine (MZ, an anti-motion sickness drug), prednisolone (PRED, an anti-inflammatory drug) and norfloxacin (NFLX, an anti-microbial drug) which are poorly water-soluble and are low bioavailability drugs, were prepared using egg albumin and olive oil. The powder X-ray diffractions, the dissolution rate and the bioavailabilities in vivo of these formulations were studied in comparison with each drug alone. By forming ternary formulations of these drugs, the dissolution rates of the drugs from the formulations were significantly improved compared with each drug alone. The results of their powder X-ray diffraction measurements showed that these drugs in the ternary formulations presented in an amorphous form, indicating increased dissolution rates. On the other hand, the plasma concentrations of these drugs increased significantly after oral administration in formulations to rats, except for the NFLX formulation, and the areas under the concentration-time curves (AUC) of the ternary formulations of MZ, PRED and NFLX were 2.1, 1.6 and 1.3 times those of the drugs alone, respectively. From these results, it was proven that formulations consisting of egg albumin, olive oil and poorly water-soluble drugs were useful preparations for improving the drug's disadvantageous pharmaceutical properties. PMID:9132174

  17. Excipient foods: designing food matrices that improve the oral bioavailability of pharmaceuticals and nutraceuticals.

    PubMed

    McClements, David Julian; Xiao, Hang

    2014-07-25

    The oral bioavailability of many lipophilic bioactive agents (pharmaceuticals and nutraceuticals) is limited due to various physicochemical and physiological processes: poor release from food or drug matrices; low solubility in gastrointestinal fluids; metabolism or chemical transformation within the gastrointestinal tract; low epithelium cell permeability. The bioavailability of these agents can be improved by specifically designing food matrices that control their release, solubilization, transport, metabolism, and absorption within the gastrointestinal tract. This article discusses the impact of food composition and structure on oral bioavailability, and how this knowledge can be used to design excipient foods for improving the oral bioavailability of lipophilic bioactives. Excipient foods contain ingredients or structures that may have no bioactivity themselves, but that are able to promote the bioactivity of co-ingested bioactives. These bioactives may be lipophilic drugs in pharmaceutical preparations (such as capsules, pills, or syrups) or nutraceuticals present within food matrices (such as natural or processed foods and beverages). PMID:24760211

  18. Characterization of tableting properties measured with a multi-functional compaction instrument for several pharmaceutical excipients and actual tablet formulations.

    PubMed

    Osamura, Takashi; Takeuchi, Yoshiko; Onodera, Risako; Kitamura, Masahiro; Takahashi, Yoshiteru; Tahara, Kohei; Takeuchi, Hirofumi

    2016-08-20

    Before designing tablet formulations, it is important to understand the "Tableting Properties" of excipients and API (active pharmaceutical ingredient) powders. Those properties refer to "Compressibility", "Compactability" and "Manufacturability", which are difficult to evaluate quantitatively. In this study, we aimed to evaluate the "Tableting Properties" by using a benchtop single-punch tablet press, developed recently to measure these parameters using a single device. In order to facilitate understanding of the results visually, we proposed a new plot, where the X-axis showed the tensile fracture stress and the Y-axis showed the ejection stress. This plot, which is composed of four regions, shows the combination of "Compactability" and "Manufacturability". We confirmed the ability of this device to evaluate the characteristics of typical pharmaceutical additives as a value of "Tableting Properties". Losartan potassium was used as an API, and Dilactose R and MCC as an excipient with good "Tableting Properties". The ejection stresses of losartan potassium and Dilactose R were very high. An increase in magnesium stearate shifted the point along the Y-axis in this plot, and it meant an improvement in "Manufacturability". It was confirmed that the device and plot are useful in designing formulations efficiently using a small amount of sample powders. PMID:27184101

  19. Synthesis and pharmaceutical properties of N-acyloxymethyl prodrugs of Allop with potential anti-trypanosomal activity.

    PubMed

    Gualdesi, M S; Ortiz, C S; Raviolo, M A

    2016-04-01

    We report herein the synthesis, and the physicochemical and pharmacokinetic properties of N-acyloxymethyl prodrugs of allopurinol (Allop) (2a-f). Allop is a compound with activity against Trypanosoma cruzi, a causative agent of Chagas disease. Its pathology leads to a huge number of infections and deaths per year, because in addition to many sufferers only having limited access to health services only an inefficient chemotherapy is available. Relevant pharmaceutical properties (pKa, stability, solubility, lipophilicity, in vitro permeability, binding protein, xanthine oxidase binding) were also determined. The results obtained showed that derivatives behave as prodrugs of Allop, since they exhibit improved physicochemical and pharmacokinetic properties relative to their precursor. This behavior turns these compounds into active reservoirs of Allop, and reduces its unfavorable characteristics, so 2a-f compounds are excellent candidates for the treatment of Chagas disease. This work is therefore an important contribution leading to the suppression of Chagas disease. PMID:26181622

  20. Intellectual property rights and the Canadian pharmaceutical marketplace: where do we go from here?

    PubMed

    Lexchin, Joel

    2005-01-01

    Patent protection for prescription drugs has a long and contentious history in Canada. Bills C-22 and C-91, passed as part of Canada's commitment to various trade deals, first weakened and then abolished compulsory licensing. In order to decide on a future course of action that Canada should take on intellectual property rights (IPRs), it is useful to review downstream effects that resulted from C-22 and C-91. This article examines changes to employment, Canada's balance of trade in pharmaceuticals, investment in research and development, and drug expenditures. The author then reviews the arguments advanced by the pharmaceutical industry in favor of stronger protection for IPRs, the recent complaints made against Canada at the World Trade Organization regarding pharmaceutical IPRs, and the continuing argument about the "evergreening" of patents. Also discussed are the second-draft text agreement of the Free Trade Area of the Americas, which will, if implemented, have significant repercussions for pharmaceutical IPRs in Canada, and some ways in which patents distort the marketplace for drugs. The article concludes with some alternative recommendations on the future of IPRs. PMID:15932005

  1. 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.

  2. 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. PMID:21519942

  3. 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. PMID:25646113

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

    PubMed

    Walley, Tom; Mrazek, Monique; Mossialos, Elias

    2005-01-01

    UK government policy on pharmaceuticals is broadly integrated across the whole of health care policy. In the early 1990s, cost containment was emphasized, through budget holding by doctors to ensure clinical acceptability. From 2000 onwards, increased government funding for the NHS has allowed expansion of services and prescribing in areas of public health importance, but has been coupled with increased accountability and ambitious targets for the process of care and health outcomes. Standards for care are set in national guidelines including those from the National Institute for Clinical Excellence (NICE). NICE recommends or rejects new technologies to the NHS for their clinical value and cost effectiveness. Although following its advice is mandatory, evidence so far suggests that it has been only partly successful at improving services and eliminating variations. GP prescribing is monitored by Primary Care Organisations (PCO) which also hold the medicines budget. They may provide incentives to GPs for meeting targets in quality or expenditure. The UK government regulates the prices of generics but not of branded medicines; instead it regulates the profitability of the pharmaceutical industry. This arrangement seems to have been successful both at maintaining a major employer and export earner, and in limiting high drug expenditure. PMID:16335083

  5. [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. PMID:22859452

  6. 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

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

    PubMed

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

    2009-07-30

    The mechanical property anisotropy of compacts made from four commercially available pharmaceutical excipient powders (microcrystalline cellulose, lactose monohydrate, ascorbic acid, and aspartame) was evaluated. The speed of pressure (longitudinal) waves in the uni-axially compressed cubic compacts of each excipient in the three principle directions was determined using a contact ultrasonic method. Average Young's moduli of each compact in the axial (x) and radial (y and z) directions were characterized. The contact ultrasonic measurements revealed that average Young's modulus values vary with different testing orientations which indicate Young's modulus anisotropy in the compacts. The extent of Young's modulus anisotropy was quantified by using a dimensionless ratio and was found to be significantly different for each material (microcrystalline cellulose>lactose>aspartame>ascorbic acid). It is also observed that using the presented contact method, compacts at high solid fraction (0.857-0.859) could be differentiated than those at the solid fraction of 0.85 in their groups. The presented contact ultrasonic method is an attractive tool since it has the advantages of being sensitive to solid fraction ratio, non-destructive, requiring small amount of material and rapid. It is noteworthy that, since the approach provides insight into the performance of common pharmaceutical materials and fosters increased process knowledge, it can be applied to broaden the understanding of the effect of the mechanical properties on the performance (e.g., disintegration profiles) of solid oral dosage forms. PMID:19426791

  8. Improvement of hairy root cultures and plants by changing biosynthetic pathways leading to pharmaceutical metabolites: strategies and applications.

    PubMed

    Ludwig-Müller, Jutta; Jahn, Linda; Lippert, Annemarie; Püschel, Joachim; Walter, Antje

    2014-11-01

    A plethora of bioactive plant metabolites has been explored for pharmaceutical, food chemistry and agricultural applications. The chemical synthesis of these structures is often difficult, so plants are favorably used as producers. While whole plants can serve as a source for secondary metabolites and can be also improved by metabolic engineering, more often cell or organ cultures of relevant plant species are of interest. It should be noted that only in few cases the production for commercial application in such cultures has been achieved. Their genetic manipulation is sometimes faster and the production of a specific metabolite is more reliable, because of less environmental influences. In addition, upscaling in bioreactors is nowadays possible for many of these cultures, so some are already used in industry. There are approaches to alter the profile of metabolites not only by using plant genes, but also by using bacterial genes encoding modifying enzymes. Also, strategies to cope with unwanted or even toxic compounds are available. The need for metabolic engineering of plant secondary metabolite pathways is increasing with the rising demand for (novel) compounds with new bioactive properties. Here, we give some examples of recent developments for the metabolic engineering of plants and organ cultures, which can be used in the production of metabolites with interesting properties. PMID:24699436

  9. 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…

  10. 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…

  11. 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.

  12. 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.

  13. 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. PMID:26686054

  14. Dielectric properties of pharmaceutical materials relevant to microwave processing: effects of field frequency, material density, and moisture content.

    PubMed

    Heng, Paul W S; Loh, Z H; Liew, Celine V; Lee, C C

    2010-02-01

    The rising popularity of microwaves for drying, material processing and quality sensing has fuelled the need for knowledge concerning dielectric properties of common pharmaceutical materials. This article represents one of the few reports on the density and moisture content dependence of the dielectric properties of primary pharmaceutical materials and their relevance to microwave-assisted processing. Dielectric constants (epsilon') and losses (epsilon'') of 13 pharmaceutical materials were measured over a frequency range of 1 MHz-1 GHz at 23 +/- 1 degrees C using a parallel-electrode measurement system. Effects of field frequency, material density and moisture content on dielectric properties were studied. Material dielectric properties varied considerably with frequency. At microwave frequencies, linear relationships were established between cube-root functions of the dielectric parameters [symbols: see text] and density which enabled dielectric properties of materials at various densities to be estimated by regression. Moisture content was the main factor that contributed to the disparities in dielectric properties and heating capabilities of the materials in a laboratory microwave oven. The effectiveness of a single frequency density-independent dielectric function for moisture sensing applications was explored and found to be suitable within low ranges of moisture contents for a model material. PMID:19708060

  15. 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. PMID:27334256

  16. The effects of relative humidity and super-disintegrant concentrations on the mechanical properties of pharmaceutical compacts.

    PubMed

    Hersen-Delesalle, Christine; Leclerc, Bernard; Couarraze, Guy; Busignies, Virginie; Tchoreloff, Pierre

    2007-12-01

    The influence of the composition and the relative humidity on the properties of pharmaceutical compacts prepared from mixtures of three excipients and three super-disintegrants was evaluated. Various amounts of super-disintegrant and different conditions of relative humidity during the storage were used to study mechanistically the disintegration process and to connect it to compact's mechanical properties. Three point single beam test was used to measure tensile strength and Young's modulus of compacts containing various amount of disintegrant and stored under various relative humidity. The presence of moisture within pharmaceutical compacts containing a disintegrant influences drastically their mechanical properties. Then, the results are related to micro-cracks visualized by MEB. PMID:18097803

  17. Improved solid-state NMR quantifications of active principles in pharmaceutical formulations.

    PubMed

    Sanchez, Stéphanie; Ziarelli, Fabio; Viel, Stéphane; Delaurent, Corinne; Caldarelli, Stefano

    2008-08-01

    The facility of implementation reached by solid-state nuclear magnetic resonance (ssNMR) spectroscopy makes this technique increasingly popular in pharmaceutical sciences, and more specifically for the dosage of active principles in pharmaceutical formulations, since about 80% of the formulations currently available on the market are present in the solid form. In this case, analysis by MAS NMR allows faster and simplified protocols, as a solubilization step is not required. However, the specificity of the ssNMR experiments should be explicitly taken into account when designing an accurate measurement procedure. In this work we show that, by using a combination of external concentration referencing and a properly designed sample preparation optimized for quantitative determinations, quantification of active principles in pharmaceutical formulations can be performed with both speed and precision. The method is illustrated by reinvestigating the dosage of Meprobamate, an anxiolytic agent typically prescribed in case of anxiety or muscular soreness, present in a commercial formulation (Equanil). Specifically, with respect to previously proposed analytical protocols, the procedure outlined here allows fast quantification with excellent precision. PMID:18479881

  18. 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

  19. 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

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

    PubMed

    Adi-Dako, Ofosua; Ofori-Kwakye, Kwabena; Frimpong Manso, Samuel; Boakye-Gyasi, Mariam El; Sasu, Clement; Pobee, Mike

    2016-01-01

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

  1. Some pharmaceutical and inclusion properties of 2-hydroxybutyl-β-cyclodextrin derivative.

    PubMed

    Ishiguro, Takako; Morishita, Eri; Iohara, Daisuke; Hirayama, Fumitoshi; Wada, Koki; Motoyama, Keiichi; Arima, Hidetoshi; Uekama, Kaneto

    2011-10-31

    2-Hydroxybutyl-β-cyclodextrins (HB-β-CyDs) with different degrees of substitution (D.S.) were prepared and their physicochemical and biological properties and solubilizing abilities were studied and compared with those of 2-hydroxypropyl-β-cyclodextrin (HP-β-CyD). The surface activity of HB-β-CyD was higher than that of HP-β-CyD (D.S. 5.6) and increased with its concentration and D.S. The moisture sorption of HB-β-CyD (D.S. 5.5) was less than that of HP-β-CyD (D.S. 5.6), because of the introduction of hydrophobic hydroxybutyl groups in a molecule. The hemolytic activity (rabbit erythrocytes) decreased in the order of 2,6-di-O-methyl-β-cyclodextrin (DM-β-CyD)>methyl-β-cyclodextrin (M-β-CyD)>HB-β-CyD (D.S. 5.5)>β-CyD>HP-β-CyD (D.S. 5.6). The hemolytic activity of HB-β-CyD increased with D.S. and HB-β-CyD induced echinocyte (or crenation), as well as DM-β-CyD does. It was suggested from the solubility study of membrane components that HB-β-CyD interacted predominantly with cholesterol in erythrocytes, resulting in the hemolysis. The inclusion ability of HB-β-CyD was higher than that of HP-β-CyD (D.S. 5.6), especially for poorly water-soluble drugs with long linear structures such as biphenylylacetic acid and flurbiprofen (FP). For example, HB-β-CyD formed the inclusion complex with FP in a molar ratio of 1:1, by including the biphenyl moiety in the host cavity. The dissolution rate of FP/HB-β-CyD (D.S. 5.5) complex was faster than that of HP-β-CyD (D.S. 5.6) complex. The results suggested that HB-β-CyDs have considerable pharmaceutical potential and can work as a fast-dissolving carrier for poorly water-soluble drugs. PMID:21839823

  2. 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....

  3. [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. PMID:18545747

  4. 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. PMID:26593681

  5. Investigation and modelling approach of the mechanical properties of compacts made with binary mixtures of pharmaceutical excipients.

    PubMed

    Busignies, V; Leclerc, B; Porion, P; Evesque, P; Couarraze, G; Tchoreloff, P

    2006-08-01

    Three pharmaceutical excipients (microcrystalline cellulose, lactose, anhydrous calcium phosphate) and their binary mixtures were compacted to form compacts of various mean porosities. Some mechanical properties (Young's modulus, tensile strength and Brinell hardness) were studied on these compacts. The mechanical properties of the binary mixtures were not proportional to the mixture composition expressed in mass. More, for all the properties, a negative deviation was always observed from this linear relationship. In reference to a composition percolation phenomenon, critical mass fractions were detected from the graph mechanical property vs. mass composition of a mixture. The results obtained with Brinell hardness differed from the results of the Young's modulus and the tensile strength, i.e. the most plastic material in the binary mixture controlled the mixture behaviour. Secondly, a predictive model based on a statistical approach was proposed for the Young's modulus and the tensile strength. The validity of this model was verified on experimental data, and an interaction parameter used to characterize the affinity of the two compounds was calculated. Finally, the X-ray tomography technique was applied to the compacts of cellulose/phosphate mixtures to obtain cross-sections images of the compacts. The analysis of the cross-sections images allowed explaining the no linear relationship of the different mechanical properties results observed on these binary mixtures. PMID:16750353

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

    PubMed

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

    2015-12-25

    This special issue of Toxicology in Vitro is dedicated to disseminating the results of the EU-funded collaborative project "Profiling the toxicity of new drugs: a non animal-based approach integrating toxicodynamics and biokinetics" (Predict-IV; Grant 202222). The project's overall aim was to develop strategies to improve the assessment of drug safety in the early stage of development and late discovery phase, by an intelligent combination of non animal-based test systems, cell biology, mechanistic toxicology and in silico modeling, in a rapid and cost effective manner. This overview introduces the scope and overall achievements of Predict-IV. PMID:25450741

  7. Improving Pharmaceutical Aerosol Delivery During Noninvasive Ventilation: Effects of Streamlined Components

    PubMed Central

    Longest, P. Worth; Golshahi, Laleh; Hindle, Michael

    2013-01-01

    Aerosol delivery efficiency during noninvasive ventilation (NIV) is known to be low (~10%) and is associated with poor outcomes of aerosol therapy. The objective of this study was to demonstrate the benefit of redesigning ventilation circuit components using a streamlining approach to improve aerosol delivery during nasal high flow therapy in adults with a conventional-sized aerosol from a mesh nebulizer. The ventilation circuit consisted of a humidifier, mesh nebulizer, mixing T-connector (with 90° angle), 10 mm tubing, and nasal cannula interface. In vitro experiments and computational fluid dynamics analyses were used to evaluate depositional losses in a system of existing components and a newly proposed streamlined T-connector and cannula at flow rates of 30 and 45 LPM. Streamlined designs reduced deposition in the T-connector by a factor of 4. In the nasal cannula, the streamlined designs reduced depositional losses by factors of 1.25–2.0. With the streamlined designs, the highest emitted dose achieved was >40% for a conventional-sized aerosol at 30 LPM. Streamlined geometries offer an effective method to significantly improve the delivery of aerosols through components of NIV systems. This increase in delivery efficiency is important for new inhaled medications with narrow therapeutic windows, increased costs, or long delivery times. PMID:23423706

  8. The evaluation of the immunomodulating properties of ERA-63 a pharmaceutical with estrogenic activity.

    PubMed

    Janssen, G B; Penninks, A H; Knippels, L M J; van Zijverden, M; Spanhaak, S

    2008-08-28

    This paper describes studies performed with ERA-63 a low molecular weight pharmaceutical with intended immunomodulatory effects. Since this compound was also known to have estrogenic activity a non-conventional approach was taken in order to differentiate between estrogenic and non-estrogenic-induced immunomodulatory effects. EE was included not only for qualitative comparison (hazard identification) between immunomodulatory effects but also, in case of similar effects, to facilitate the extrapolation of the findings in the rat to anticipated effects in humans. After 28 days of treatment with dosages ranging from pharmacological up to clearly toxic levels for both compounds the immunotoxic potential was assessed by performing a T cell-dependent antibody response and a host resistance assay in rats. Selected ERA-63 dose levels (0.167-0.2, 1.67-2 and 16.7-20mg/kg) were expected to have comparable estrogenic activity to respective EE dose levels (0.05, 0.5 and 5mg/kg). General toxicity parameters reflecting estrogenic activity (i.e. decreased body- and organ weights of thymus and testis, and increased bilirubin and GGT levels) confirmed the comparable estrogenic activity for both compounds at the dose levels tested. Together with the comparable estrogen-related immune suppression (i.e. decreases in specific antibody responses and an increased susceptibility for Listeria monocytogenes infects) for both compounds, this indicates that available clinical data for EE facilitates the human risk assessment of ERA-63. PMID:18602456

  9. 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. PMID:26518012

  10. 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

  11. 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

    2016-01-01

    -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. PMID:27618000

  12. 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. PMID:26846538

  13. Ultrasound improves the renneting properties of milk.

    PubMed

    Liu, Zheng; Juliano, Pablo; Williams, Roderick P W; Niere, Julie; Augustin, Mary Ann

    2014-11-01

    The effects of ultrasound application on skim milk (10% w/w total solids at natural pH 6.7 or alkali-adjusted to pH 8.0) prior to the renneting of milk at pH 6.7 were examined. Skim milk, made by reconstituting skim milk powder, was sonicated at 20kHz and 30°C (dissipated power density 286kJkg(-1)) in an ultrasonic reactor. The rennet gelation time, curd firming rate, curd firmness, and the connectivity of the rennet gel network were improved significantly in rennet gels made from milk ultrasonicated at pH 8.0 and re-adjusted back to pH 6.7 compared to those made from milk sonicated at pH 6.7. These renneting properties were also improved in milk sonicated at pH 6.7 compared to those of the non-sonicated control milk. The improvements in renneting behavior were related to ultrasound-induced changes to the proteins in the milk. This study showed that ultrasonication has potential to be used as an intervention to manipulate the renneting properties of milk for more efficient manufacturing of cheese. PMID:24751292

  14. 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. PMID:26639478

  15. 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.

  16. 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.

  17. 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. PMID:25583304

  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. PMID:17221075

  19. Pharmaceutical cocrystals: walking the talk.

    PubMed

    Bolla, Geetha; Nangia, Ashwini

    2016-06-28

    Pharmaceutical cocrystals belong to a sub-class of cocrystals wherein one of the components is a drug molecule (or an active pharmaceutical ingredient, API) and the second is a benign food or drug grade additive (generally regarded as safe, GRAS). The two components are hydrogen-bonded in a fixed stoichiometric ratio in the crystal lattice. In the past decade, pharmaceutical cocrystals have demonstrated significant promise in their ability to modify the physicochemical and pharmacokinetic properties of drug substances, such as the solubility and dissolution rate, bioavailability, particle morphology and size, tableting and compaction, melting point, physical form, biochemical and hydration stability, and permeability. In this feature review, we highlight some prominent examples of drug cocrystals which exhibit variable hardness/softness and elasticity/plasticity depending on coformer selection, improvement of solubility and permeability in the same cocrystal, increase of the melting point for solid formulation, enhanced color performance, photostability and hydration stability, and a longer half-life. Cocrystals of flavanoids and polyphenols can make improved pharmaceuticals and also extend to the larger class of nutraceuticals. The application of crystal engineering to assemble ternary cocrystals expands this field to drug-drug cocrystals which may be useful in multi-drug resistance, mitigating side effects of drugs, or attenuating/enhancing drug action synergistically by rational selection. The advent of new techniques for structural characterization beyond the standard X-ray diffraction will provide a better understanding of drug phases which are at the borderline of crystalline-amorphous nature and even newer opportunities in the future. PMID:27278109

  20. 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. PMID:27185830

  1. 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. PMID:26845455

  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. PMID:27120646

  3. 24 CFR 201.20 - Property improvement loan eligibility.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 2 2013-04-01 2013-04-01 false Property improvement loan... AUTHORITIES TITLE I PROPERTY IMPROVEMENT AND MANUFACTURED HOME LOANS Eligibility and Disbursement Requirements § 201.20 Property improvement loan eligibility. (a) Borrower eligibility. (1) To be eligible for...

  4. 24 CFR 201.20 - Property improvement loan eligibility.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 2 2014-04-01 2014-04-01 false Property improvement loan... AUTHORITIES TITLE I PROPERTY IMPROVEMENT AND MANUFACTURED HOME LOANS Eligibility and Disbursement Requirements § 201.20 Property improvement loan eligibility. (a) Borrower eligibility. (1) To be eligible for...

  5. 24 CFR 201.20 - Property improvement loan eligibility.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 2 2012-04-01 2012-04-01 false Property improvement loan... AUTHORITIES TITLE I PROPERTY IMPROVEMENT AND MANUFACTURED HOME LOANS Eligibility and Disbursement Requirements § 201.20 Property improvement loan eligibility. (a) Borrower eligibility. (1) To be eligible for...

  6. Pharmaceutical properties of supramolecular assembly of co-loaded cardanol/triazole-halloysite systems.

    PubMed

    Massaro, Marina; Colletti, Carmelo G; Noto, Renato; Riela, Serena; Poma, Paola; Guernelli, Susanna; Parisi, Filippo; Milioto, Stefana; Lazzara, Giuseppe

    2015-01-30

    Halloysite nanotubes were explored as drug carrier for cardanol, which is considered as a promising natural anticancer active species. To this aim, besides the pristine nanoclay, a chemical modification of the nanocarrier was performed by attaching triazolium salts with different hydrophobicity at the outer surface of the hollow nanotubes. The interaction between cardanol and nanotubes was highlighted in solution by HPLC. This method proved the loading of the drug into the nanotubes. The solid dried complexes formed by pristine and modified halloysite with the cardanol were characterized by IR spectroscopy, thermogravimetric analysis as well as water contact angle to evidence the structure, thermal properties and wettability of the obtained materials. The kinetics of cardanol release as well as cell viability experiments provided promising results that put forward a new strategy for potential applications of cardanol as active antiproliferative molecule and clay nanotubes as drug carrier. PMID:25498322

  7. Medicinal properties of Hericium erinaceus and its potential to formulate novel mushroom-based pharmaceuticals.

    PubMed

    Jiang, Shengjuan; Wang, Songhua; Sun, Yujun; Zhang, Qiang

    2014-09-01

    Hericium erinaceus is an important mushroom with edible values and medicinal properties. Both the mycelium and the fruiting bodies contain many bioactive compounds with drug efficacy. Recent evidence demonstrates that it is helpful to various diseases, such as Alzheimer's disease, immunoregulatory, and many types of cancer. Furthermore, emerging pieces of evidence have shown that different active molecules in H. erinaceus have different functions on different organs in different diseases via the different mechanisms. Drawing on current research results, this review mainly focuses on the therapeutic effects of H. erinaceus on various diseases of multiple physiological systems, including the nervous system, digestive system, circulatory system, and immune system. This paper also discusses systematically the efficient protection of H. erinaceus against the diseases from the intricate experimental proofs by using the systematic viewpoints, which provides a framework for future research directions. PMID:25070597

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

    PubMed

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

    2015-03-01

    Crystals of voriconazole, an antifungal drug, are soft in nature, and this is disadvantageous during compaction studies where pressure is applied on the solid. Crystal engineering is used to make cocrystals and salts with modified mechanical properties (e.g., hardness). Cocrystals with biologically safe coformers such as fumaric acid, 4-hydroxybenzoic acid, and 4-aminobenzoic acid and salts with hydrochloric acid and oxalic acid are prepared through solvent assisted grinding. The presence (salt) or absence (cocrystal) of proton transfer in these multicomponent crystals is unambiguously confirmed with single crystal X-ray diffraction. All the cocrystals have 1:1 stoichiometry, whereas salts exhibit variable stoichiometries such as HCl salt (1:2) and oxalate salts (1:1.5 and 1:1). The nanoindentation technique was applied on single crystals of the salts and cocrystals. The salts exhibit better hardness than the drug and cocrystals in the order salts ≫ drug > cocrystals. The molecular origin of this mechanical modulation is explained on the basis of slip planes in the crystal structure and relative orientations of the molecules with respect to the nanoindentation direction. The hydrochloride salt is the hardest solid in this family. This may be useful for tableting of the drug during formulation and in drug development. PMID:25587626

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

    PubMed

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

    2015-10-10

    Bulk crystallisation of protein therapeutic molecules towards their controlled drug delivery is of interest to the biopharmaceutical industry. The complexity of biotherapeutic molecules is likely to lead to complex material properties of crystals in the solid state and to complex transitions. This complexity is explored using batch crystallised lysozyme as a model. The effects of drying and milling on the solid-state transformations of lysozyme crystals were monitored using differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), FT-Raman, and enzymatic assay. XRPD was used to characterise crystallinity and these data supported those of crystalline lysozyme which gave a distinctive DSC thermogram. The apparent denaturation temperature (Tm) of the amorphous lysozyme was ∼201 °C, while the Tm of the crystalline form was ∼187 °C. Raman spectra supported a more α-helix rich structure of crystalline lysozyme. This structure is consistent with reduced cooperative unit sizes compared to the amorphous lysozyme and is consistent with a reduction in the Tm of the crystalline form. Evidence was obtained that milling also induced denaturation in the solid-state, with the denatured lysozyme showing no thermal transition. The denaturation of the crystalline lysozyme occurred mainly through its amorphous form. Interestingly, the mechanical denaturation of lysozyme did not affect its biological activity on dissolution. Lysozyme crystals on drying did not become amorphous, while milling-time played a crucial role in the crystalline-amorphous-denatured transformations of lysozyme crystals. DSC is shown to be a key tool to monitor quantitatively these transformations. PMID:26068908

  10. Matrix deactivation: A general approach to improve stability of unstable and reactive pharmaceutical genotoxic impurities for trace analysis.

    PubMed

    Sun, Mingjiang; Bai, Lin; Terfloth, Gerald J; Liu, David Q; Kord, Alireza S

    2010-05-01

    Trace analysis of unstable and reactive pharmaceutical genotoxic impurities (GTIs) is a challenging task in pharmaceutical analysis. Many method issues such as insufficient sensitivity, poor precision, and unusual (too high/low) spiking recovery are often directly related to analytes' instability. We report herein a matrix deactivation approach that chemically stabilizes these analytes for analytical method development. In contrast to the conventional chemical derivatization approach where the analytes are transformed into stable detectable species, the matrix deactivation approach chemically deactivates the hypothetical reactive species in the sample matrix. The matrix deactivation approach was developed on the premise that the instability of certain analytes at trace level is caused by reactions between the analytes and low level reactive species in the sample matrix. Thus, quenching the reactivity of the reactive species would be a key to stabilizing the unstable and reactive analytes. For example, electrophilic alkylators could be destabilized by nucleophiles or bases through either nucleophilic substitution or elimination reactions. One way to mask those reactive species is via protonation by adding acids to the diluent. Alternatively, one can use nucleophile scavengers to deplete reactive unknown species in the sample matrix completely, in analogy to the use of antioxidants and metal chelators to prevent oxidation in the analysis of compounds liable to oxidation. This paper reports the application of the matrix deactivation to the analyses of unstable and reactive pharmaceutical genotoxic impurities. Some of the methods have been used to support development of manufacturing processes for drug substances and a recent regulatory filing. PMID:20036478

  11. Genaissance pharmaceuticals, inc.

    PubMed

    Oestreicher, Paul

    2002-03-01

    Genaissance Pharmaceuticals, Inc. (Nasdaq: GNSC) is the world leader in the discovery and use of gene variation for the development of personalized medicines. In addition, the company has established partnerships with some of the world's top biopharmaceutical companies. The company has initiated the development of its own pipeline of products -- HAP Clozapine for schizophrenia and HAP Statin for cholesterol management -- utilizing its proprietary genetic markers. The company also markets its technology and clinical development skills to the pharmaceutical industry as a complete solution for improving the development, marketing and prescribing of drugs. PMID:11972448

  12. 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

    2015-02-01

    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. PMID:25595532

  13. Response properties of self-improving systems.

    PubMed

    Krakovsky, Andrey

    2016-04-01

    We observe that a sustained positivity (or negativity) of a system's second-order response will result in a directional change of the system's characteristics under the corresponding random exposure. We identify these changes with improvement (or decline) in the state of a system and introduce the concept of self-improving systems as systems which characteristics can sustainably improve under a random exposure. The resulting framework is of a general phenomenological nature and can be applied to complex systems across different areas of knowledge. PMID:27059562

  14. Response properties of self-improving systems

    NASA Astrophysics Data System (ADS)

    Krakovsky, Andrey

    2016-04-01

    We observe that a sustained positivity (or negativity) of a system's second-order response will result in a directional change of the system's characteristics under the corresponding random exposure. We identify these changes with improvement (or decline) in the state of a system and introduce the concept of self-improving systems as systems which characteristics can sustainably improve under a random exposure. The resulting framework is of a general phenomenological nature and can be applied to complex systems across different areas of knowledge.

  15. Development and characterization of naproxen-chitosan solid systems with improved drug dissolution properties.

    PubMed

    Mura, Paola; Zerrouk, Naima; Mennini, Natascia; Maestrelli, Francesca; Chemtob, Chantal

    2003-05-01

    The solubilizing and amorphizing properties toward naproxen (a poorly water-soluble antiinflammatory drug) of chitosan, an emerging pharmaceutical biopolymer, have been investigated. Solid binary systems at different drug/polymer ratios have been prepared according to different techniques (mixing, cogrinding, kneading, coevaporation) using chitosan at low (CS-L(w)) and medium (CS-M(w)) molecular weight, and tested for dissolution properties. Drug-carrier interactions were investigated in both the liquid and solid state, by phase solubility analysis, differential scanning calorimetry, X-ray powder diffractometry, FT-IR spectroscopy, and scanning electron microscopy. Drug dissolution parameters improved with increasing the polymer amount in the mixture, reaching the highest values at the 1:9 (w/w) drug/polymer ratio, and CS-L(w) was more efficacious than CS-M(w). Cogrinding was the most effective technique, showing the strongest amorphizing effect toward the drug and enabling an increase of more than ten times its relative dissolution rate. Coground mixtures at 3:7 (w/w) drug/polymer ratio were able to give directly compressed tablets which maintained unchanged the improved drug dissolution properties. Enhancer dissolution properties combined with its direct compression feasibility and antiulcerogenic action make CS-L(w) an optimal carrier for developing fast-release oral solid dosage forms of naproxen. PMID:12729863

  16. 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.

  17. Photochemical Mechanism of Riboflavin-Induced Degradation of Famotidine and a Suggested Pharmaceutical Strategy for Improving Photostability.

    PubMed

    Uchida, Atsushi; Onoue, Satomi; Ohtake, Hiroto; Seto, Yoshiki; Teramatsu, Tsuyoshi; Terajima, Tomoko; Oguchi, Toshio

    2016-02-01

    The present study aimed to clarify the mechanism of photodegradation of famotidine with riboflavin (FMT/RF), and to develop a photochemically stabilized formulation of FMT/RF. Photochemical properties of RF were characterized by UV-VIS spectral analysis, reactive oxygen species (ROS) assay, and photostability testing. Pharmacokinetic study was conducted in rats after intravenous administration of FMT (1 mg/kg) formulation containing RF (0.01 mg/kg). The UV-VIS spectral pattern of RF partly overlapped with the sunlight spectrum, and ROS generation from photoirradiated RF was remarkable; thus, RF had high photoreactive potential. In the photostability testing, after irradiation (250 W/m(2)), degradation rate for FMT in FMT/RF was ca. 11-fold higher than that in FMT alone. The addition of radical scavengers to FMT/RF led to attenuated photodegradation of FMT/RF; in particular, the addition of L-ascorbic acid (vitamin C; VC) to FMT/RF showed ca. 86% inhibition of the photodegradation of FMT/RF. The pharmacokinetic study on FMT indicated that the addition of VC (1 mg/kg) to FMT/RF had no significant impact on the pharmacokinetic behavior of FMT. These findings suggest that ROS-mediated photochemical reaction would be involved in the photodegradation pathway of FMT/RF, and the complementary use of VC might be an attractive approach to improve the photostability of FMT/RF. PMID:26505739

  18. Analyzing and improving viscoelastic properties of high density polyethylene

    NASA Astrophysics Data System (ADS)

    Ahmed, Reaj Uddin

    2011-12-01

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

  19. 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. PMID:19167054

  20. Recognizing misleading pharmaceutical marketing online.

    PubMed

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

    2014-01-01

    In light of decision-making psychology, this article details how drug marketing operates across established and novel web domains and identifies some common misleading trends and influences on prescribing and patient-initiated medication requests. The Internet has allowed pharmaceutical marketing to become more salient than ever before. Although the Internet's growth has improved the dissemination of pharmaceutical information, it has also led to the increased influence of misleading pharmaceutical marketing. Such mismarketing is of concern, especially in psychiatry, since psychotropics generate considerable revenue for drug companies. In a climate of resource-limited drug regulation and time-strapped physicians, we recommend improving both independent monitoring and consumer awareness of Internet-enabled, potentially misleading, pharmaceutical marketing influences. PMID:24986349

  1. Melding regulatory, pharmaceutical industry, and U.S. payer perspectives on improving approaches to heterogeneity of treatment effect in research and practice.

    PubMed

    Willke, Richard J; Crown, William; Del Aguila, Michael; Cziraky, Mark J; Khan, Zeba M; Migliori, Richard

    2013-01-01

    Effective pursuit of the science and management of heterogeneity of treatment effect (HTE) relies on the mutual understanding of the perspectives of, and collaboration among, the various stakeholders in health care. In this article, we compare, contrast, and endeavor to find areas of alignment across the perspectives of three such stakeholders -regulators, the biopharmaceutical and device industry, and U.S. payers. First, we discuss how evidence of HTE is generated and could be improved upon. For pharmaceuticals, much of the initial research is conducted by the pharmaceutical industry, guided by basic science but also delimited by potential markets, regulatory approval requirements, trial size considerations, and payer expectations for evidence of value. Once a drug is marketed, further evidence can be generated via combining trial data, conducting meta-analysis, and analyzing real-world results through observational research designs; we explore how these efforts can benefit from cooperation across these stakeholders. Second, we discuss the equally important utilization of HTE evidence so that physicians and patients have access to and can benefit from the learnings from this research. Research findings must be translated into actionable information and guidelines that can be incorporated into everyday practice. Doing so requires interaction and collaboration among all involved, based on facilitated communication as well as further evaluation research. We provide examples of several cross-sectorial initiatives that are under way in this area. Finally, we explore some economic aspects of HTE research as part of the drug development, marketing, and treatment process. Understanding the economic incentives present is fundamental to aligning those incentives to improve the availability and utilization of HTE evidence. Clear understandings among regulators, pharma, and payers about high-value targets, methods to efficiently generate and communicate information, and value

  2. Improving the electrical properties of graphene layers by chemical doping

    NASA Astrophysics Data System (ADS)

    Farooq Khan, Muhammad; Zahir Iqbal, Muhammad; Waqas Iqbal, Muhammad; Eom, Jonghwa

    2014-10-01

    Although the electronic properties of graphene layers can be modulated by various doping techniques, most of doping methods cost degradation of structural uniqueness or electrical mobility. It is matter of huge concern to develop a technique to improve the electrical properties of graphene while sustaining its superior properties. Here, we report the modification of electrical properties of single- bi- and trilayer graphene by chemical reaction with potassium nitrate (KNO3) solution. Raman spectroscopy and electrical transport measurements showed the n-doping effect of graphene by KNO3. The effect was most dominant in single layer graphene, and the mobility of single layer graphene was improved by the factor of more than 3. The chemical doping by using KNO3 provides a facile approach to improve the electrical properties of graphene layers sustaining their unique characteristics.

  3. 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.

  4. 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.

  5. Pharmaceutical Analysis as a Branch of Pharmaceutics

    ERIC Educational Resources Information Center

    Connors, Kenneth A.

    1977-01-01

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

  6. 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

  7. 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

  8. In Silico Models for Ecotoxicity of Pharmaceuticals.

    PubMed

    Roy, Kunal; Kar, Supratik

    2016-01-01

    Pharmaceuticals and their active metabolites are one of the significantly emerging environmental toxicants. The major routes of entry of pharmaceuticals into the environment are industries, hospitals, or direct disposal of unwanted or expired drugs made by the patient. The most important and distinct features of pharmaceuticals are that they are deliberately designed to have an explicit mode of action and designed to exert an effect on humans and other living systems. This distinctive feature makes pharmaceuticals and their metabolites different from other chemicals, and this necessitates the evaluation of the direct effects of pharmaceuticals in various environmental compartments as well as to living systems. In this background, the alarming situation of ecotoxicity of diverse pharmaceuticals have forced government and nongovernment regulatory authorities to recommend the application of in silico methods to provide quick information about the risk assessment and fate properties of pharmaceuticals as well as their ecological and indirect human health effects. This chapter aims to offer information regarding occurrence of pharmaceuticals in the environment, their persistence, environmental fate, and toxicity as well as application of in silico methods to provide information about the basic risk management and fate prediction of pharmaceuticals in the environment. Brief ideas about toxicity endpoints, available ecotoxicity databases, and expert systems employed for rapid toxicity predictions of ecotoxicity of pharmaceuticals are also discussed. PMID:27311470

  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. PMID:22588676

  10. Study of the Continuous Improvement Trend for Health, Safety and Environmental Indicators, after Establishment of Integrated Management System (IMS) in a Pharmaceutical Industry in Iran

    PubMed Central

    Mariouryad, Pegah; Golbabaei, Farideh; Nasiri, Parvin; Mohammadfam, Iraj

    2015-01-01

    Background Nowadays, organizations try to improve their services and consequently adopt management systems and standards which have become key parts in various industries. One of these management systems which have been noticed in the recent years is Integrated Management System that is the combination of quality, health, safety and environment management systems. Aim This study was conducted with the aim of evaluating the improvement trend after establishment of integrated management system for health, safety and environment indicators, in a pharmaceutical industry in Iran. Materials and Methods First, during several inspections in different parts of the industry, indicators that should have been noted were listed and then these indicators were organized in 3 domains of health, safety and environment in the form of a questionnaire that followed Likert method of scaling. Also, the weight of each index was resulted from averaging out of 30 managers and the viewpoints of the related experts in the field. Moreover, by checking the documents and evidence of different years (5 contemplation years of this study), the score of each indicator was determined by multiplying the weight and score of the indices and were finally analysed. Results Over 5 years, scores of health scope indicators, increased from 161.99 to 202.23. Score in the first year after applying the integrated management system establishment was 172.37 in safety part and in the final year increased to 197.57. The changes of environmental scope rates, from the beginning of the program up to the last year increased from 49.24 to 64.27. Conclusion Integrated management systems help organizations to improve programs to achieve their objectives. Although in this study all trends of health, safety and environmental indicator changes were positive, but at the same time showed to be slow. So, one can suggest that the result of an annual evaluation should be applied in planning future activities for the years ahead

  11. Optical properties of volcanic ash: improving remote sensing observations.

    NASA Astrophysics Data System (ADS)

    Whelley, Patrick; Colarco, Peter; Aquila, Valentina; Krotkov, Nickolay; Bleacher, Jake; Garry, Brent; Young, Kelsey; Rocha Lima, Adriana; Martins, Vanderlei; Carn, Simon

    2016-04-01

    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.

  12. Improving cochlear implant properties through conductive hydrogel coatings.

    PubMed

    Hassarati, Rachelle T; Dueck, Wolfram F; Tasche, Claudia; Carter, Paul M; Poole-Warren, Laura A; Green, Rylie A

    2014-03-01

    Conductive hydrogel (CH) coatings for biomedical electrodes have shown considerable promise in improving electrode mechanical and charge transfer properties. While they have desirable properties as a bulk material, there is limited understanding of how these properties translate to a microelectrode array. This study evaluated the performance of CH coatings applied to Nucleus Contour Advance cochlear electrode arrays. Cyclic voltammetry and biphasic stimulation were carried out to determine electrical properties of the coated arrays. Electrical testing demonstrated that CH coatings supported up to 24 times increase in charge injection limit. Reduced impedance was also maintained for over 1 billion stimulations without evidence of delamination or degradation. Mechanical studies performed showed negligible effect of the coating on the pre-curl structure of the Contour Advance arrays. Testing the coating in a model human scala tympani confirmed that adequate contact was maintained across the lateral wall. CH coatings are a viable, stable coating for improving electrical properties of the platinum arrays while imparting a softer material interface to reduce mechanical mismatch. Ultimately, these coatings may act to minimize scar tissue formation and fluid accumulation around electrodes and thus improve the electrical performance of neural implants. PMID:24608692

  13. 24 CFR 201.20 - Property improvement loan eligibility.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 2 2011-04-01 2011-04-01 false Property improvement loan eligibility. 201.20 Section 201.20 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR HOUSING-FEDERAL HOUSING COMMISSIONER, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT MORTGAGE...

  14. 24 CFR 201.20 - Property improvement loan eligibility.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Property improvement loan eligibility. 201.20 Section 201.20 Housing and Urban Development Regulations Relating to Housing and Urban... HOUSING AND URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND...

  15. 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.

  16. MULTIFUNCTIONAL AND STIMULI-SENSITIVE PHARMACEUTICAL NANOCARRIERS

    PubMed Central

    Torchilin, Vladimir

    2011-01-01

    Currently used pharmaceutical nanocarriers, such as liposomes, micelles, and polymeric nanoparticles, demonstrate a broad variety of useful properties, such as longevity in the body; specific targeting to certain disease sites; enhanced intracellular penetration; contrast properties allowing for direct carrier visualization in vivo; stimili-sensitivity, and others. Some of those pharmaceutical carriers have already made their way into clinic, while others are still under preclinical development. In certain cases, the pharmaceutical nanocarriers combine several of the listed properties. Long-circulating immunoliposomes capable of prolonged residence in the blood and specific target recognition represent one of examples of this kind. The engineering of multifunctional pharmaceutical nanocarriers combining several useful properties in one particle can significantly enhance the efficacy of many therapeutic and diagnostic protocols. This paper considers the current status and possible future directions in the emerging area of multifunctional nanocarriers with primary attention on the combination of such properties as longevity, targetability, intracellular penetration, contrast loading, and stimuli sensitivity. PMID:18977297

  17. 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

  18. UVA is the major contributor to the photodegradation of tretinoin and isotretinoin: Implications for development of improved pharmaceutical formulations.

    PubMed

    Tashtoush, Bassam M; Jacobson, Elaine L; Jacobson, Myron K

    2008-03-20

    The chemical stability of tretinoin (RA) and isotretinoin (13RA) in ethanol and dermatological cream preparations exposed to solar simulated light (SSL), UVA, and visible light has been studied. Photostability was monitored by an HPLC method that allowed simultaneous analysis of RA and 13RA, thus allowing photodegradation due to isomerization to other retinoids and photolysis to non-retinoid products to be monitored. Both retinoids undergo both isomerization and photolysis following SSL, UVA and visible light exposure but RA is more sensitive to photodegradation than 13RA. Degradation of both retinoids by photolysis is considerably greater in cream formulations than in ethanol and the photodegradation follows second order kinetics. Rate constants and half-lives for degradation of RA and 13RA in ethanol solution and cream preparations subjected to different light sources are reported. The UVA component of SSL is the major contributor to photodegradation. Since UVA penetrates deeply into skin, our results suggest that photodegradation of RA may contribute to the photosensitivity associated with RA therapy. Our studies suggest that development of improved formulations and the use of effective UVA sunscreens may reduce the side effects of RA therapy. PMID:18093761

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

    PubMed

    Chen, Brian K; 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

  20. 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

  1. Reprivatizing pharmaceutical supplies in Africa.

    PubMed

    Turshen, M

    2001-01-01

    Perhaps no part of the health system is as imperiled by neoliberal economic reforms as the public drug sector. The national bill for pharmaceuticals can claim one-third of a developing country's annual health budget. This article describes the essential drugs program created by WHO in the 1980s to protect financially reduced ministries of health from the high prices charged by multinational pharmaceutical companies. It describes the backlash from the World Bank and UNICEF, which launched the Bamako Initiative and other community financing schemes and revolving drug plans in which individuals, families or community groups buy drugs above the wholesale purchase price; clinics use the proceeds to maintain drug supplies and subsidize other health services. When this plan failed, the Bank proposed outright privatization of drug purchase and supply, returning power to the multinational suppliers. The article ends with a consideration of patents and the new intellectual property rights as they pertain to pharmaceutical production in Africa. PMID:11469153

  2. 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.

  3. 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.

  4. Improvement of thymol properties by complexation with cyclodextrins: in vitro and in vivo studies.

    PubMed

    Nieddu, Maria; Rassu, Giovanna; Boatto, Gianpiero; Bosi, Paolo; Trevisi, Paolo; Giunchedi, Paolo; Carta, Antonio; Gavini, Elisabetta

    2014-02-15

    Thymol, an effective agent for microbial diseases, has a low aqueous solubility and a strong bitter/irritating taste. These physicochemical characteristics need to be improved to develop pharmaceutical preparations. This study evaluates whether β-cyclodextrin and a copolymer based on dimethylaminoethyl methacrylate (DMAEMA) interact with thymol in order to control powderization, solubilization, and taste-masking properties. The thymol-β-cyclodextrin complex was prepared by co-precipitation and sealed-heating methods. The DMAEMA copolymer was mixed with the complex using a new approach, instead of spray coating, to decrease thymol volatility. In vivo studies were performed. Sealed-heating is a suitable method for including thymol in β-cyclodextrin with a good loading efficiency; thymol volatility control is achieved by mixing the complex with the DMAEMA copolymer. β-Cyclodextrin accelerates the in vivo thymol absorption rate compared with the free drug; the thymol half-life is still long. Therefore, a low number of administrations per day are required. Although bioavailability is unchanged with respect to free thymol, high doses could be administered of a selected formulation without compromising the compliance. Furthermore, thymol that is not absorbed is held along the intestine, where it can useful in the treatment and/or prevention of intestinal bacterial diseases. PMID:24507296

  5. 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

  6. 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. PMID:23876725

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

    PubMed

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

    2015-12-30

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

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

    PubMed Central

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

    2014-01-01

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

  9. Optimization of the cyclotide framework to improve cell penetration properties

    PubMed Central

    Huang, Yen-Hua; Chaousis, Stephanie; Cheneval, Olivier; Craik, David J.; Henriques, Sónia T.

    2015-01-01

    Cell penetrating peptides have been regarded as promising vectors to deliver hydrophilic molecules inside cells. Although they are great tools for research and have high potential as drug delivery systems, their application as drugs is impaired by their low stability in serum. Cyclotides, cyclic disulfide-rich peptides from plants, are ultra-stable molecules that have inspired applications in drug design as they can be used as scaffolds to stabilize linear bioactive sequences. Recently, they have also been shown to possess cell-penetrating properties. The combination of their remarkable stability and cell-penetrating properties opens new avenues for the application of peptides to bind to and inhibit intracellular proteins. Nevertheless, for a broader application of these molecules as vectors is of utmost importance to improve their cellular internalization efficiency. In this study we successfully modified MCoTI-II, one of the most widely studied cyclotide scaffolds in drug design, and improved its internalization properties. The internalization of the newly designed MCoTI-II is as efficient as the gold standard cell-penetrating peptide (CPP) TAT and maintains all the required features as a template to graft desired bioactivities. PMID:25709580

  10. New Skyrme interaction with improved spin-isospin properties

    NASA Astrophysics Data System (ADS)

    Roca-Maza, X.; Colò, G.; Sagawa, H.

    2012-09-01

    A correct determination of the spin-isospin properties of the nuclear effective interaction should lead to, among other improvements, an accurate description of the Gamow-Teller resonance (GTR). These nuclear excitations impact on a variety of physical processes: from the response in charge-exchange reactions of nuclei naturally present in the Earth, to the description of the stellar nucleosynthesis and of the pre-supernova explosion core-collapse evolution of massive stars in the Universe. A reliable description of the GTR provides also stringent tests for neutrinoless double-β decay calculations. We present a new Skyrme interaction as accurate as previous forces in the description of finite nuclei and of uniform matter properties around saturation density, and that accounts well for the GTR in 48Ca, 90Zr, and 208Pb, and the isobaric analog resonance and spin dipole resonance in 90Zr and 208Pb.

  11. 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

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

    PubMed

    Lefnaoui, Sonia; Moulai-Mostefa, Nadji

    2015-11-01

    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

  13. Improving satellite retrieved aerosol microphysical properties using GOCART data

    NASA Astrophysics Data System (ADS)

    Li, S.; Kahn, R.; Chin, M.; Garay, M. J.; Chen, L.; Liu, Y.

    2014-09-01

    The Multi-Angle Imaging Spectro-Radiometer (MISR) instrument on NASA's Terra satellite can provide more reliable Aerosol Optical Depth (AOD, τ) and more particle information, such as constraints on particle size (Angström exponent or ANG, α), particle shape, and single-scattering albedo (SSA, ω), than many other satellite instruments. However, MISR's ability to retrieve aerosol properties is weakened at low AOD levels. When aerosol-type information content is low, many candidate aerosol mixtures can match the observed radiances. We propose an algorithm to improve MISR aerosol retrievals by constraining MISR mixtures' ANG and absorbing AOD (AAOD) with Goddard Chemistry Aerosol Radiation and Transport (GOCART) model-simulated aerosol properties. To demonstrate this approach, we calculated MISR aerosol optical properties over the contiguous US from 2006 to 2009. Sensitivities associated with the thresholds of MISR-GOCART differences were analyzed according to the agreement between our results (AOD, ANG, and AAOD) and AErosol RObotic NETwork (AERONET) observations. Overall, our AOD has a good agreement with AERONET because the MISR AOD retrieval is not sensitive to different mixtures under many retrieval conditions. The correlation coefficient (r) between our ANG and AERONET improves to 0.45 from 0.29 for the MISR Version 22 standard product and 0.43 for GOCART when all data points are included. However, when only cases having AOD > 0.2, the MISR product itself has r ~ 0.40, and when only AOD > 0.2 and the best-fitting mixture are considered, r ~ 0.49. So as expected, the ANG improvement occurs primarily when the model constraint is applied in cases where the particle type information content of the MISR radiances is low. Regression analysis for AAOD shows that MISR Version 22 and GOCART misestimate AERONET by a ratio (mean retrieved AAOD to mean AERONET AAOD) of 0.5; our method improves this ratio to 0.74. Large discrepancies are found through an inter

  14. 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

  15. Modified β-cyclodextrin inclusion complex to improve the physicochemical properties of albendazole. complete in vitro evaluation and characterization.

    PubMed

    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

  16. 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.

  17. 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. PMID:23045363

  18. 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

  19. Pharmaceutical expenditure in Sweden.

    PubMed

    Henriksson, F; Hjortsberg, C; Rehnberg, C

    1999-05-01

    Recently, the responsibility for prescribed pharmaceuticals in Sweden was transferred from national level to the regional health authorities (county councils). The purpose was that a closer integration and balance between pharmaceuticals and other factors of production in health care should produce better opportunities for a cost-effective use of the total health care resources. The purpose of this paper is to present a deeper analysis of pharmaceuticals as a production factor in Sweden, mainly during the 1990s, and to discuss the future development and future policy decisions in Sweden. Pharmaceuticals have increased their share of total health care expenditure in Sweden, from about 9% in 1990 to about 14% in 1995. The Swedish pharmaceutical market can be divided into sub-markets, where the prescription sub-market accounts for the greater part of pharmaceutical expenditure. Further, a few disease categories account for a larger fraction of the cost of prescribed pharmaceuticals. The importance of pharmaceuticals as a production factor also differs between different age groups. Several factors are expected to contribute to a future increase in Swedish pharmaceutical expenditure, for instance an ageing population and the rapid introduction of expensive new pharmaceuticals. PMID:10538288

  20. Electron microscopy of pharmaceutical systems.

    PubMed

    Klang, Victoria; Valenta, Claudia; Matsko, Nadejda B

    2013-01-01

    During the last decades, the focus of research in pharmaceutical technology has steadily shifted towards the development and optimisation of nano-scale drug delivery systems. As a result, electron microscopic methods are increasingly employed for the characterisation of pharmaceutical systems such as nanoparticles and microparticles, nanoemulsions, microemulsions, solid lipid nanoparticles, different types of vesicles, nanofibres and many more. Knowledge of the basic properties of these systems is essential for an adequate microscopic analysis. Classical transmission and scanning electron microscopic techniques frequently have to be adapted for an accurate analysis of formulation morphology, especially in case of hydrated colloidal systems. Specific techniques such as environmental scanning microscopy or cryo preparation are required for their investigation. Analytical electron microscopic techniques such as electron energy-loss spectroscopy or energy-dispersive X-ray spectroscopy are additional assets to determine the elemental composition of the systems, but are not yet standard tools in pharmaceutical research. This review provides an overview of pharmaceutical systems of interest in current research and strategies for their successful electron microscopic analysis. Advantages and limitations of the different methodological approaches are discussed and recent findings of interest are presented. PMID:22921788

  1. 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.

  2. 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. PMID:26491881

  3. 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.

  4. Improved field emission property of graphene by laser irradiation

    NASA Astrophysics Data System (ADS)

    Cai, Wenbo; Zeng, Baoqing; Liu, Jianlong; Guo, Jing; Li, Nannan; Chen, Lei; Chen, Hongwei

    2013-11-01

    Graphene oxide (GO) can be reduced to graphene by either laser irradiation or thermal annealing. To improve the field emission (FE) property, a pulse CO2 laser has been employed to irradiate GO films prepared by electrophoretic deposition (EPD). By varying the laser irradiation time, we were able to fabricate emitters with varied field enhancement factor. It has been found that the FE properties of laser irradiated films with optimized time 15 s were better than that of thermal annealed samples. The turn-on field (Eto) at 0.01 mA/cm2 was reduced from 3.4 to 2.4 V/μm, and the threshold field (Eth) at 1 mA/cm2 was reduced from 6.8 to 5.1 V/μm. Scanning electron microscopy (SEM) was taken to reveal the change of morphology after laser ablation, and it shows that the laser irradiation made great deal of graphene edges vertical to the substrate, which remarkably enhanced the FE properties. This kind of effective and convenience method made the graphene films as a potential field emitter for vacuum microelectronic devices.

  5. 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. PMID:23764981

  6. Pharmaceutical care in smoking cessation.

    PubMed

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

    2015-01-01

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

  7. 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.

  8. Biological and Pharmaceutical Nanomaterials

    NASA Astrophysics Data System (ADS)

    Kumar, Challa S. S. R.

    2006-01-01

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

  9. Metrology in Pharmaceutical Industry - A Case Study

    NASA Astrophysics Data System (ADS)

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

    2016-07-01

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

  10. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-01-01

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

  12. 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.

  13. 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.

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

    PubMed

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

    2014-01-30

    This work reports on the structure and properties of novel nanocomposites composed of exfoliated montmorillonite clay blended with levan, a polysaccharide produced by Bacillus sp. Dry levan is very brittle, making it difficult to obtain stand-alone films. MMT-levan composites were prepared by solution blending in water, coating on plastic surfaces, partial drying at 50°C, and conditioning in air at 50-60% relative humidity. This process results in freestanding, transparent, and flexible films of pure levan and MMT-levan composites plasticized by 10-15 wt% water. XRD patterns from levan-MMT composites indicate an MMT interlayer spacing 0.62 nm greater than that of the starting MMT, suggesting re-stacking of MMT platelets coated by adsorbed, uncoiled levan molecules. FTIR results suggest that levan adheres to MMT via water-mediated hydrogen bonding between the levan's hydroxyl groups and MMT surface oxygens. MMT-levan composites have improved thermal stability and a well-defined glass transition temperature that increases with MMT loading. The tensile moduli of levan-MMT composites increase by as much as 480% relative to pure levan. The XRD and mechanical property results suggest that MMT reinforces levan through a filler network structure composed of MMT platelets bridged by adsorbed levan molecules, enhanced when the MMT loading becomes high enough (5-10wt% MMT) to induce an isotropic-nematic transition in MMT platelet orientation. PMID:24299812

  15. 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

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

    PubMed

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

    2011-08-15

    Two problems are addressed simultaneously. One is the utilisation of sludge from the treatment of wastewater. The other is the modification of the mechanical properties of concrete. The sludge was subjected to two series of treatments. In one series, coagulants were used, including ferrous sulphate, aluminium sulphate or aluminium polyhydroxychloride. In the other series, an electrochemical treatment was applied with several starting values of pH. Then, concretes consisting of a cement matrix, silica sand, marble and one of the sludges were developed. Specimens without sludge were prepared for comparison. Curing times and aggregate concentrations were varied. The compressive strength, compressive strain at yield point, and static and dynamic elastic moduli were determined. Diagrams of the compressive strength and compressive strain at the yield point as a function of time passed through the minima as a function of time for concretes containing sludge; therefore, the presence of sludge has beneficial effects on the long term properties. Some morphological changes caused by the presence of sludge are seen in scanning electron microscopy. A way of utilising sludge is thus provided together with a way to improve the compressive strain at yield point of concrete. PMID:21616593

  17. Mimicking mussel adhesion to improve interfacial properties in composites

    PubMed Central

    Hamming, L. M.; Fan, X. W.; Messersmith, P. B.; Brinson, L. C.

    2009-01-01

    The macroscale properties of polymer-matrix composites depend immensely on the quality of the interaction between the reinforcement phase and the bulk polymer. This work presents a method to improve the interfacial adhesion between metal-oxides and a polymer matrix by performing surface-initiated polymerization (SIP) by way of a biomimetic initiator. The initiator was modeled after 3,4-dihydroxy-L-phenylalanine (dopa), an amino acid that is highly concentrated in mussel foot adhesive proteins. Mechanical pull out tests of NiTi and Ti-6Al-4V wires from poly (methyl methacrylate) (PMMA) were performed to directly test the interfacial adhesion. These tests demonstrated improvements in maximum interfacial shear stress of 116% for SIP-modified NiTi wires and 60% for SIP-modified Ti-6Al-4V wires over unmodified specimens. Polymer chain growth from the metal oxides was validated using x-ray photoemission spectroscopy (XPS), ellipsometry, scanning electron microscopy (SEM), and contact angle analysis. PMID:19578545

  18. 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.

  19. 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.

  20. 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.

  1. Herbicide and pharmaceutical relationships

    Technology Transfer Automated Retrieval System (TEKTRAN)

    For many years, virtually all pharmaceutical companies had an agrochemical division. This was partly to maximize the benefits of expensive chemical synthesis efforts by searching for many types of useful biological activities. Leads for pharmaceuticals and pesticides often overlap, in some cases l...

  2. Pharmaceutical Education in Poland

    ERIC Educational Resources Information Center

    Furmanowa, Miroslawa; Borke, Mitchell L.

    1978-01-01

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

  3. 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

  4. Amorphous calcium phosphate composites with improved mechanical properties

    PubMed Central

    O’Donnell, J.N.R.; Antonucci, J.M.; Skrtic, D.

    2008-01-01

    Hybridized zirconium amorphous calcium phosphate (ACP)-filled methacrylate composites make good calcium and phosphate releasing materials for anti-demineralizing/remineralizing applications with low mechanical demands. The objective of this study was to assess the effect of the particle size of the filler on the mechanical properties of these composites. Photo-curable resins were formulated from ethoxylated bisphenol A dimethacrylate, triethylene glycol dimethacrylate, 2-hydroxyethyl methacrylate and methacryloxyethyl phthalate. Camphorquinone and ethyl-4-N,N-dimethylaminobenzoate were utilized as components of the photoinitiator system. After 2 h of mechanical milling in isopropanol, an approximate 64 % reduction in the median particle diameter was observed [27.48 μm vs. 9.98 μm] for unmilled and milled wet ACP, respectively. Dry ACP showed a 43 % reduction in particle size from pre- to post-milling. As well as dry composites, those that had been immersed in aqueous media were evaluated for their Young’s Modulus, water sorption, biaxial tensile, three-point flexural and diametral tensile strength. Mechanically milling the filler increased the volume of fine particles in the composite specimens, resulting in a more homogeneous intra-composite distribution of ACP and a reduction in voids. In turn, less water diffused into the milled composites upon aqueous exposure, and they showed a marked improvement in biaxial flexure strength and a moderate improvement in flexural strength over composites with unmilled ACP. The demonstrated improvement in the mechanical stability of milled Zr-ACP composites may help in extending their dental applicability. PMID:18688290

  5. 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. PMID:26027494

  6. The transferability from rat subacute 4-week oral toxicity study to translational research exemplified by two pharmaceutical immunosuppressants and two environmental pollutants with immunomodulating properties.

    PubMed

    Kemmerling, Jessica; Fehlert, Ellen; Kuper, C Frieke; Rühl-Fehlert, Christine; Stropp, Gisela; Vogels, Jack; Krul, Cyrille; Vohr, Hans-Werner

    2015-07-15

    Exposure to chemicals may have an influence on the immune system. Often, this is an unwanted effect but in some pharmaceuticals, it is the intended mechanism of action. Immune function tests and in depth histopathological investigations of immune organs were integrated in rodent toxicity studies performed according to an extended OECD test guideline 407 protocol. Exemplified by two immunosuppressive drugs, azathioprine and cyclosporine A, and two environmental chemicals, hexachlorobenzene and benzo[a]pyrene, results of subacute rat studies were compared to knowledge in other species particular in humans. Although immune function has a high concordance in mammalian species, regarding the transferability from rodents to humans various factors have to be taken into account. In rats, sensitivity seems to depend on factors such as strain, sex, stress levels as well as metabolism. The two immunosuppressive drugs showed a high similarity of effects in animals and humans as the immune system was the most sensitive target in both. Hexachlorobenzene gave an inconsistent pattern of effects when considering the immune system of different species. In some species pronounced inflammation was observed, whereas in primates liver toxicity seemed more obvious. Generally, the immune system was not the most sensitive target in hexachlorobenzene-treatment. Immune function tests in rats gave evidence of a reaction to systemic inflammation rather than a direct impact on immune cells. Data from humans are likewise equivocal. In the case of benzo[a]pyrene, the immune system was the most sensitive target in rats. In the in vitro plaque forming cell assay (Mishell-Dutton culture) a direct comparison of cells from different species including rat and human was possible and showed similar reactions. The doses in the rat study had, however, no realistic relation to human exposure, which occurs exclusively in mixtures and in a much lower range. In summary, a case by case approach is necessary

  7. Another development in pharmaceuticals: an introduction.

    PubMed

    Streky, G

    1985-01-01

    The provision of appropriate medicines of the right kind, quality and quantity, and at reasonable prices is a central concern for any government. Simultaneously, there is increasing recognition of the serious problems inherent in the existing systems of pharmaceutical development, promotion, marketing, distribution and use in all countries and particularly in the 3rd World. The vast majority of people in most 3rd World countries have little or no access to effective and safe medicines. The Dag Hammarskjold Foundation organized a consultation on Another Development in Pharmaceuticals in June 1985. It was based on some papers commissioned for that occasion with a view to developing new approaches to fundamental problems in this field and involving both national and international actors and institutions. The basic concern of these papers was to place the debate on pharmaceuticals in its proper historical, contemporary and future context. The 5 major areas discussed were: 1) man and medicines: a historical perspective; 2) towards a healthy use of pharmaceuticals; 3) towards a healthy pharmaceutical industry by the year 2000; 4) 1st principles for the prescription, promotion and use of pharmaceuticals: towards a code of conduct; and 5) monitoring Another Development in Pharmaceuticals. 90% of the world's production of pharmaceuticals originates in the industrialized countries, which also accounts for 80% of the consumption. 3rd World countries have been supplied with a very inappropriate assortment of products by the pharmaceutical industry. There is a growing demand for improved practices that are conducive to health development. An international harmonization of regulatory standards is needed. PMID:12341048

  8. Improvement of the soy formate dehydrogenase properties by rational design.

    PubMed

    Kargov, I S; Kleimenov, S Y; Savin, S S; Tishkov, V I; Alekseeva, A A

    2015-06-01

    Previous experiments on substitution of the residue Phe290 to Asp, Asn and Ser in NAD(+)-dependent formate dehydrogenase from soya Glycine max (SoyFDH) showed important role of the residue in enzyme thermal stability and catalytic properties (Alekseeva et al. Prot. Eng. Des. Sel., 2012a; 25: :781-88). In this work, we continued site-directed mutagenesis experiments of the Phe290 and the residue was changed to Ala, Thr, Tyr, Glu and Gln. All amino acid changes resulted in increase of catalytic constant from 2.9 to 3.5-4.7 s(-1). The substitution Phe290Ala led to KM (NAD+) decrease from 13.3 to 8.6 μM, and substitutions Phe290Tyr and Phe290Glu resulted in decrease and increase of KM (HCOO-) from 1.5 to 0.9 and -2.9 mM, respectively. The highest improvement of catalytic properties was observed for SoyFDH Phe290Ala which showed 2-fold higher catalytic efficiency with both substrates. Stability of mutants was examined by study of thermal inactivation kinetics and differential scanning calorimetry (DSC). All five amino acids provided increase of thermal stability of mutant SoyFDH in comparison with wild-type enzyme. Mutant SoyFDH Phe290Glu showed the highest improvement-the stabilization effect was 43 at 56°C. The DSC data agree with results of thermal inactivation kinetics. Substitutions Phe290Tyr, Phe290Thr, Phe290Gln and Phe290Glu provided Tm value increase 0.6°-6.6°. SoyFDH Phe290Glu and previously prepared SoyFDH Phe290Asp show similar thermal stability as enzymes from Candida boidinii and Mycobacterium vaccae N10 and have higher catalytic efficiency with NAD(+) compared with all described FDHs. Therefore, these mutants are very perspective enzymes for coenzyme regeneration in processes of chiral synthesis with dehydrogenases. PMID:25744036

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

    NASA Astrophysics Data System (ADS)

    Zhang, Y.; Schaap, M. G.

    2014-12-01

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

  10. 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.

  11. 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

  12. 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. PMID:25448572

  13. 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.

  14. 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…

  15. 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

  16. Rejection of pharmaceuticals by forward osmosis membranes.

    PubMed

    Jin, Xue; Shan, Junhong; Wang, Can; Wei, Jing; Tang, Chuyang Y

    2012-08-15

    Rejection of four pharmaceutical compounds, carbamazepine, diclofenac, ibuprofen and naproxen, by forward osmosis (FO) membranes was investigated in this study. For the first time, the rejection efficiency of the pharmaceutical compounds was compared between commercial cellulose triacetate (CTA) based membranes and thin film composite (TFC) polyamide based membranes. The rejection behavior was related to membrane interfacial properties, physicochemical characteristics of the pharmaceutical molecules and feed solution pH. TFC polyamide membranes exhibited excellent overall performance, with high water flux, excellent pH stability and great rejection of all pharmaceuticals investigated (>94%). For commercial CTA based FO membranes, hydrophobic interaction between the compounds and membranes exhibited strong influence on their rejection under acidic conditions. The pharmaceuticals rejection was well correlated to their hydrophobicity (log D). Under alkaline conditions, both electrostatic repulsion and size exclusion contributed to the removal of deprotonated molecules. The pharmaceuticals rejection by CTA-HW membrane at pH 8 followed the order: diclofenac (99%)>carbamazepine (95%)>ibuprofen (93%) ≈ naproxen (93%). These results can be important for FO membrane synthesis, modification and their application in water purification. PMID:22640821

  17. 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. PMID:23607724

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

    PubMed

    Kaushik, Deepak; Dureja, Harish

    2014-04-01

    Taste masking is an important factor in the development of oral dosage forms containing bitter active pharmaceutical ingredients. Currently numerous techniques are being applied to overcome this problem. Realizing this, several researchers and pharmaceutical companies are now engaged in developing novel techniques to address the problem of taste masking evident by numerous patents filed in this area in recent times. In this review the most recent patents for taste masking are discussed and how these patents overcome the limitations of conventional approaches of taste masking is also highlighted. Novel techniques based on some recent patents such as nanohybrid, melt extrusion, non-complex cyclodextrin compositions and off taste masking are providing new realms to taste masking of bitter drugs. The present article also provides an overview of various patented platform technologies based on different techniques/mechanisms employed for taste masking. The unique features and principles of taste-masking approaches used in various patented technologies are also discussed. A better understanding of these new patents and patented technologies will help researchers and pharmaceutical industries to select the appropriate platform, or to develop innovative products with improved taste masking properties. PMID:24499438

  19. 26 CFR 301.6323(c)-2 - Protection for real property construction or improvement financing agreements.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... improvement financing agreements. 301.6323(c)-2 Section 301.6323(c)-2 Internal Revenue INTERNAL REVENUE... Collection General Provisions § 301.6323(c)-2 Protection for real property construction or improvement... property construction or improvement financing agreement entered into before the tax lien filing, and...

  20. 26 CFR 301.6323(c)-2 - Protection for real property construction or improvement financing agreements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... improvement financing agreements. 301.6323(c)-2 Section 301.6323(c)-2 Internal Revenue INTERNAL REVENUE... Collection General Provisions § 301.6323(c)-2 Protection for real property construction or improvement... property construction or improvement financing agreement entered into before the tax lien filing, and...

  1. 26 CFR 301.6323(c)-2 - Protection for real property construction or improvement financing agreements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... improvement financing agreements. 301.6323(c)-2 Section 301.6323(c)-2 Internal Revenue INTERNAL REVENUE... Collection General Provisions § 301.6323(c)-2 Protection for real property construction or improvement... property construction or improvement financing agreement entered into before the tax lien filing, and...

  2. Terahertz study on porosity and mass fraction of active pharmaceutical ingredient of pharmaceutical tablets.

    PubMed

    Bawuah, Prince; Tan, Nicholas; Tweneboah, Samuel Nana A; Ervasti, Tuomas; Axel Zeitler, J; Ketolainen, Jarkko; Peiponen, Kai-Erik

    2016-08-01

    In this study, terahertz time-domain spectroscopic (THz-TDS) technique has been used to ascertain the change in the optical properties, as a function of changing porosity and mass fraction of active pharmaceutical ingredient (API), of training sets of pharmaceutical tablets. Four training sets of pharmaceutical tablets were compressed with microcrystalline cellulose (MCC) excipient and indomethacin API by varying either the porosity, height, and API mass fraction or all three tablet parameters. It was observed, as far as we know, for the first time, that the THz time-domain and frequency-domain effective refractive index, as well as, the frequency-domain effective absorption coefficient both show linear correlations with the porosity and API mass fraction for training sets of real pharmaceutical tablets. We suggest that, the observed linear correlations can be useful in basic research and quality inspection of pharmaceutical tablets. Additionally, we propose a novel optical strain parameter, based on THz measurement, which yields information on the conventional strain parameter of a tablet as well as on the change of fill fraction of solid material during compression of porous pharmaceutical tablets. We suggest that the THz measurement and proposed method of data analysis, in addition to providing an efficient tool for basic research of porous media, can serve as one of the novel quality by design (QbD) implementation techniques to predict critical quality attributes (CQA) such as porosity, API mass fraction and strain of flat-faced pharmaceutical tablets before production. PMID:27288937

  3. A review of monitoring methods for pharmaceutical wet granulation.

    PubMed

    Hansuld, E M; Briens, L

    2014-09-10

    High-shear wet granulation is commonly used in the pharmaceutical industry to improve powder properties for downstream processes such as tabletting. Granule growth, however, is difficult to predict because the process is sensitive to raw material properties and operating conditions. Development of process analytical technologies is encouraged by regulatory bodies to improve process understanding and monitor quality online. The primary technologies investigated for high-shear wet granulation monitoring include power consumption, near-infrared spectroscopy, Raman spectroscopy, capacitance measurements, microwave measurements, imaging, focused beam reflectance measurements, spatial filter velocimetry, stress and vibration measurements, as well as acoustic emissions. This review summarizes relevant research related to each of these technologies and discusses the challenges associated with each approach as a possible process analytical technology tool for high-shear wet granulation. PMID:24950366

  4. 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

  5. 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.

  6. Optimization of microtubule affinity regulating kinase (MARK) inhibitors with improved physical properties.

    PubMed

    Sloman, David L; Noucti, Njamkou; Altman, Michael D; Chen, Dapeng; Mislak, Andrea C; Szewczak, Alexander; Hayashi, Mansuo; Warren, Lee; Dellovade, Tammy; Wu, Zhenhua; Marcus, Jacob; Walker, Deborah; Su, Hua-Poo; Edavettal, Suzanne C; Munshi, Sanjeev; Hutton, Michael; Nuthall, Hugh; Stanton, Matthew G

    2016-09-01

    Inhibition of microtubule affinity regulating kinase (MARK) represents a potentially attractive means of arresting neurofibrillary tangle pathology in Alzheimer's disease. This manuscript outlines efforts to optimize a pyrazolopyrimidine series of MARK inhibitors by focusing on improvements in potency, physical properties and attributes amenable to CNS penetration. A unique cylcyclohexyldiamine scaffold was identified that led to remarkable improvements in potency, opening up opportunities to reduce MW, Pgp efflux and improve pharmacokinetic properties while also conferring improved solubility. PMID:27491711

  7. Improving magnetic properties of ultrasmall magnetic nanoparticles by biocompatible coatings

    NASA Astrophysics Data System (ADS)

    Costo, R.; Morales, M. P.; Veintemillas-Verdaguer, S.

    2015-02-01

    This paper deals with the effect of a biocompatible surface coating layer on the magnetic properties of ultrasmall iron oxide nanoparticles. Particles were synthesized by laser pyrolysis and fully oxidized to maghemite by acid treatment. The surface of the magnetic nanoparticles was systematically coated with either phosphonate (phosphonoacetic acid or pamidronic acid) or carboxylate-based (carboxymethyl dextran) molecules and the binding to the nanoparticle surface was analyzed. Magnetic properties at low temperature show a decrease in coercivity and an increase in magnetization after the coating process. Hysteresis loop displacement after field cooling is significantly reduced by the coating, in particular, for particles coated with pamidronic acid, which show a 10% reduction of the displacement of the loop. We conclude that the chemical coordination of carboxylates and phosphonates reduces the surface disorder and enhances the magnetic properties of ultrasmall maghemite nanoparticles.

  8. Improved piezoelectric properties of cellular polypropylene ferroelectrets by chemical modification

    NASA Astrophysics Data System (ADS)

    An, Zhenlian; Zhao, Min; Yao, Junlan; Zhang, Yewen; Xia, Zhongfu

    2009-06-01

    To improve the thermal stability of piezoelectricity of polypropylene (PP) ferroelectrets, chemical modification of the cellular PP film was performed via chromic acid oxidation and then hydrofluoric acid treatment. Deep chemical modification is achieved as indicated by the energy-dispersive X-ray analyses on the cross-section of the modified cellular PP film. The results of the isothermal decay for piezoelectric d 33-coefficient at 70°C indicate the improved thermal stability of piezoelectricity and the enhanced piezoelectric activity of the modified PP ferroelectrets. The former is attributed to the improvement of thermal stability of the charges trapped in the internal void surface layers as indicated by the thermally stimulated discharge measurements, while the latter results not only from the improved thermal stability of the charges but also from the reduction in Young’s modulus of the PP ferroelectrets due to the chemical modification as revealed by the dielectric resonance analyses.

  9. 27 CFR 70.233 - Protection for real property construction or improvement financing agreements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Protection for real property construction or improvement financing agreements. 70.233 Section 70.233 Alcohol, Tobacco Products... Limitations § 70.233 Protection for real property construction or improvement financing agreements. (a)...

  10. IMPROVED PHYSICAL PROPERTIES OF ZEIN USING GLYOXAL AS A CROSSLINKER

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effect of crosslinkers glyoxal, methylglyoxal and formaldehyde on physical properties of zein films was studied. Zein was solubilized in 90%(v/v) aqueous ethanol and the pH was adjusted with either hydrochloric acid or sodium hydroxide. Crosslinkers were added to 0.3, 1, 3 and 6%(w/w by zein w...

  11. 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. PMID:25248323

  12. IMPROVED PHYSICAL PROPERTIES OF ZEIN USING GLYOXAL AS A CROSSLINKER

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effect of crosslinkers glyoxal, methylglyoxal and formaldehyde on physical properties of zein films was studied. Crosslinker concentrations varied from 0.3 to 6% by zein weight. Films crosslinked with glyoxal and formaldehyde showed a significant increase in tensile strength under certain pH c...

  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. 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…

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

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Basis Rules of General Application § 1.1019-1 Property on which lessee has made improvements. In any case in which a lessee of real property has erected buildings... 1930 to B for a period of 25 years unimproved real property and in accordance with the terms of...

  16. GW-1000. GW Pharmaceuticals.

    PubMed

    Smith, Paul F

    2004-07-01

    GW Pharmaceuticals is developing GW-1000 (Sativex), a narrow ratio delta9-tetrahydrocannabinol:cannabidiol product for the potential treatment of multiple sclerosis, spinal cord injury, neurogenic pain and peripheral neuropathy. In March 2003, the company filed for approval for the treatment of MS with the UK Medicines Control Agency, and in May 2004, filed for new drug submission with Health Canada. PMID:15298072

  17. Free trade in pharmaceuticals.

    PubMed

    Outterson, M Kevin

    2004-09-01

    Provisions in the Australia-United States Free Trade Agreement (AUSFTA) may threaten the Australian Pharmaceutical Benefits Scheme (PBS), the "gold standard" of such programs worldwide. If Australia postpones passing of the US Free Trade Agreement Implementation Bill in the Senate, there will be opportunity for broader interests in both the United States and Australia to carefully study the agreement. The provisions of AUSFTA relating to the PBS are supposed to promote transparency, but the pharmaceutical manufacturers themselves (who are demanding transparency) do not reveal the content of their submissions to the Pharmaceutical Benefits Advisory Committee, or disclose all their financial relationships with researchers and policymakers. In AUSFTA, the "public health" language of affordable prescription drugs is missing and is replaced by language supporting "pharmaceutical innovation". Debate as to whether AUSFTA will force significant changes to the PBS, including higher drug prices, is currently under way in Australia. Perhaps the appropriate target of reforms should be the excessive US drug prices, and not the economically efficient Australian drug prices. PMID:15347274

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

    PubMed

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

    2013-07-01

    Ammonio methacrylate copolymers Eudragit(®) RS PO and Eudragit® RL PO have found widespread use as key components in various types of extended release solid dosage forms. The deformation behavior of neat polymers and binary mixes was evaluated using Heckel Analysis, strain rate sensitivity, work of compaction and elastic recovery index. Additionally, the compact forming ability of neat materials and binary mixes were evaluated by analyzing their tabletability, compressibility and compactibility profiles. The Heckel analysis of both polymers exhibited a speed-sensitive deformation behavior typical to plastic materials. The yield values of the binary mixes of the polymers with microcrystalline cellulose revealed a linear relationship with the weight fractions of individual components. The yield values of binary mixes of both the polymers with dibasic calcium phosphate exhibited slight negative deviations from linearity. Both polymers exhibited axial relaxation after ejection typical of viscoelastic materials, as measured by the elastic recovery index values. The work of compaction and the elastic recovery index values of the binary mixtures were found to be linearly related to the weight fractions of the individual components thus, confirming ideal mixing behavior based on the composition. Addition of microcrystalline cellulose to both polymers significantly improved their tabletability and compactibility. The tensile strengths of the compacts prepared with neat materials and binary mixes with microcrystalline cellulose, dibasic calcium phosphate and lactose were the function of their solid fraction and independent of the tableting speeds tested; thus, validating compactibility as a reliable parameter in predicting acceptable tablet properties. PMID:22994144

  19. In-vivo mechanical tissue property measurement for improved simulations

    NASA Astrophysics Data System (ADS)

    Ottensmeyer, Mark P.; Salisbury, J. Kenneth, Jr.

    2000-08-01

    Surgical training today, beyond what can be learned in didactic form or practice on animal or other models, is subject to the availability of appropriate training cases from which students can learn. This is especially true for battlefield surgery, as civilian hospitals may not expose doctors to frequent examples of relevant injuries. To provide a more uniform training experience, covering a standard suite of typical operations without relying on the misfortune of patients requiring surgery, many groups are developing computer-based surgical simulation systems. One of the current areas of development is the implementation of force and tactile (haptic) feedback in simulations. To create a model with realistic haptic feedback, knowledge of the material properties of the tissues in question is essential. While there is much data from tissue samples in vitro, the properties of living tissue in situ are mostly unknown. From the data that is available, it is clear that living tissue and tissue in vitro can have radically different mechanical properties. For this reason, our group is developing surgical tools that will be able to measure the force-displacement characteristics of a variety of tissues in living organisms. Taking these data over the range of frequencies relevant to haptic simulation provides information to extract stiffness and material damping parameters of different kinds of tissue. The tools are being designed for use during minimally invasive surgery, but will permit data to be acquired either during MIS or open procedures. Animal tests are expected to commence in early 2000, but the tools are being designed with safety considerations in mind for eventual use in humans. Data will be taken both for solid organs and for selected elements of the vasculature. These data will be used in simulation systems under development at the Center for Innovative Minimally Invasive Therapy at Massachusetts General Hospital and the Laboratory for Human and Machine Haptics

  20. 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.

  1. 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.

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

    PubMed

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

    2015-10-01

    Slippery liquid-infused porous surfaces were developed recently for icephobic surface applications. Perfluorinated liquids, silicone oil, hydrocarbon, and water were used as lubricating liquids to form a continuous layer on a suitable substrate to prevent icing. However, ice accretion performances of these surfaces have not been reported previously depending on the type of the lubricant. In this work, fluorinated aliphatics, polyalphaolefin, silicone oil, and decamethylcyclopenta siloxane were used as hydrophobic lubricants; water, ethylene glycol, formamide, and water-glycerine mixture were used as hydrophilic lubricants to be impregnated by hydrophobic polypropylene and hydrophilic cellulose-based filter paper surfaces; ice accretion, drop freezing delay time, and ice adhesion strength properties of these surfaces were examined; and the results were compared to those of the reference surfaces such as aluminum, copper, polypropylene, and polytetrafluoroethylene. An ice accretion test method was also developed to investigate the increase of the mass of formed ice gravimetrically by spraying supercooled water onto these surfaces at different subzero temperatures ranging between -1 and -5 °C. It was determined that hydrophilic solvents (especially a water-glycerine mixture) that impregnated hydrophilic porous surfaces would be a promising candidate for anti-icing applications at -2 °C and 56-83% relative humidity because ice accretion and ice adhesion strength properties of these surface decreased simultaneously in these conditions. PMID:26375386

  3. Extraction characterization and evaluation of selected mucilage as pharmaceutical excipient.

    PubMed

    Malviya, Rishabha

    2011-01-01

    Natural polymers have been used in different pharmaceutical formulations. They are easily available, non-toxic, biodegradable and cost effective to be used as pharmaceutical excipient. In present investigation mucilage was extracted from fruit of Hibiscus esculentus and further characterized to be used as pharmaceutical excipient. Tablets were prepared using four different concentrations (6.6%, 13.3%, 20%, 26.66%) of Hibiscus esculentus mucilage and potato starch to evaluate binding properties of mucilage. Results obtained from the micromeritic characterization and flow behavior showed that Hibiscus esculentus mucilage is a good candidate to be used as pharmaceutical excipient. Tablets prepared using mucilage showed relatively lesser friability than prepared with starch. It was found that release of drug from tablets prepared with mucilage was less as compared to prepared with starch. Findings of the different results easily predict the fact that mucilage obtained from Hibiscus esculentus has characteristics to be used as pharmaceutical excipient. PMID:22046826

  4. 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

  5. 2-Point microstructure archetypes for improved elastic properties

    NASA Astrophysics Data System (ADS)

    Adams, Brent L.; Gao, Xiang

    2004-01-01

    Rectangular models of material microstructure are described by their 1- and 2-point (spatial) correlation statistics of placement of local state. In the procedure described here the local state space is described in discrete form; and the focus is on placement of local state within a finite number of cells comprising rectangular models. It is illustrated that effective elastic properties (generalized Hashin Shtrikman bounds) can be obtained that are linear in components of the correlation statistics. Within this framework the concept of an eigen-microstructure within the microstructure hull is useful. Given the practical innumerability of the microstructure hull, however, we introduce a method for generating a sequence of archetypes of eigen-microstructure, from the 2-point correlation statistics of local state, assuming that the 1-point statistics are stationary. The method is illustrated by obtaining an archetype for an imaginary two-phase material where the objective is to maximize the combination C_{xxxx}^{*} + C_{xyxy}^{*}

  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. 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. PMID:22118906

  8. 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. PMID:25892119

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

    PubMed

    Jung, Tae-Hwan; Yun, Sung-Seob; Lee, Won-Jae; Kim, Jin-Wook; Ha, Ho-Kyung; Yoo, Michelle; Hwang, Hyo-Jeong; Jeon, Woo-Min; Han, Kyoung-Sik

    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. 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

  11. 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. PMID:26159653

  12. [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. PMID:25272516

  13. Dynamical properties and chaos synchronization of improved Colpitts oscillators

    NASA Astrophysics Data System (ADS)

    Kengne, J.; Chedjou, J. C.; Kenne, G.; Kyamakya, K.

    2012-07-01

    In this paper, the dynamics and synchronization of improved Colpitts oscillators designed to operate in ultrahigh frequency range are considered. The model is described by a continuous time four-dimensional autonomous system with an exponential nonlinearity. The system is integrated numerically and various bifurcation diagrams and corresponding graphs of largest 1D Lyapunov exponent are plotted to summarize different scenarios leading to chaos. It is found that the oscillator moves from the state of fixed point motion to chaos via the usual paths of period-doubling, intermittency and interior crisis routes when monitoring the bias (i.e. power supply) in tiny ranges. In order to promote chaos-based synchronization designs of this type of oscillators, a synchronization strategy based upon the design of a nonlinear state observer is successfully adapted. The suggested approach enables synchronization to be achieved via a scalar transmitted signal which represents a suitable feature for communication applications. Numerical simulations are performed to demonstrate the effectiveness and feasibility of the proposed technique.

  14. Tetrahydrobiopterin improves diastolic dysfunction by reversing changes in myofilament properties

    PubMed Central

    Jeong, Euy-Myoung; Monasky, Michelle M.; Gu, Lianzhi; Taglieri, Domenico M.; Patel, Bindiya G.; Liu, Hong; Wang, Qiongying; Greener, Ian; Dudley, Samuel C.; Solaro, R. John

    2013-01-01

    Despite the increasing prevalence of heart failure with preserved left ventricular function, there are no specific treatments, partially because the mechanism of impaired relaxation is incompletely understood. Evidence indicates that cardiac relaxation may depend on nitric oxide (NO), generated by NO synthase (NOS) requiring the co-factor tetrahydrobiopterin (BH4). Recently, we reported that hypertension-induced diastolic dysfunction was accompanied by cardiac BH4 depletion, NOS uncoupling, a depression in myofilament cross-bridge kinetics, and S-glutathionylation of myosin binding protein C (MyBP-C). We hypothesized that the mechanism by which BH4 ameliorates diastolic dysfunction is by preventing glutathionylation of MyBP-C and thus reversing changes of myofilament properties that occur during diastolic dysfunction. We used the deoxycorticosterone acetate (DOCA)-salt mouse model, which demonstrates mild hypertension, myocardial oxidative stress, and diastolic dysfunction. Mice were divided into two groups that received control diet and two groups that received BH4 supplement for 7 days after developing diastolic dysfunction at post-operative day 11. Mice were assessed by echocardiography. Left ventricular papillary detergent-extracted fiber bundles were isolated for simultaneous determination of force and ATPase activity. Sarcomeric protein glutathionylation was assessed by immunoblotting. DOCA-salt mice exhibited diastolic dysfunction that was reversed after BH4 treatment. Diastolic sarcomere length (DOCA-salt 1.70±0.01 vs. DOCA-salt+BH4 1.77±0.01 μm, P<0.001) and relengthening (relaxation constant, τ, DOCA-salt 0.28±0.02 vs. DOCA-salt+BH4 0.08±0.01, P<0.001) were also restored to control by BH4 treatment. pCa50 for tension increased in DOCA-salt compared to sham but reverted to sham levels after BH4 treatment. Maximum ATPase rate and tension cost (ΔATPase/ΔTension) decreased in DOCA-salt compared to sham, but increased after BH4 treatment. Cardiac My

  15. Properties of PMR Polyimide composites made with improved high strength graphite fibers

    NASA Technical Reports Server (NTRS)

    Vannucci, R. D.

    1980-01-01

    High strength, intermediate modulus graphite fibers were obtained from various commercial suppliers, and were used to fabricate PMR-15 and PMR-2 polyimide composites. The effects of the improved high strength graphite fibers on composite properties after exposure in air at 600 F were investigated. Two of the improved fibers were found to have an adverse effect on the long term performance of PMR composites. The influence of various factors such as fiber physical properties, surface morphology and chemical composition were also examined.

  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. Improvement of CuBr laser coherence properties

    NASA Astrophysics Data System (ADS)

    Astadjov, Dimo N.; Stoychev, Lyubomir I.; Sabotinov, Nikola V.

    2006-05-01

    Great improvement of CuBr laser beam spatial coherence was made by a special design of the laser resonator, the generalized diffraction filtered resonator. Utilizing it diffraction-limited beam divergence can be easily obtained throughout the laser pulse. Since the spatial coherence is in inverse relation with the beam divergence, decreasing the latter we increase the former. The temporal evolution of beam divergence for the more intense green (λ=510nm) laser line was measured within laser pulse of MO (master oscillator) CuBr laser system fitted with a stable plane-plane resonator (PPR), a confocal unstable resonator of positive branch (PBUR) and a generalized diffraction filtered resonator (GDFR). With the MOPA (master oscillator power amplifier) system only GDFR was used. The estimations were verified by direct coherence measurements by means of a reversal shear interferometer that was a modified Michelson interferometer. The estimations as well as the direct measurement of spatial coherence show that coherence degree increases from PPR through PBUR to GDFR. Moreover, with GDFR it is time-independent. With MOPA system the coherence degree goes up further. So the degree of coherence measured interferometrically with MO is: for PPR - 0.16, for PBUR - 0.28 and for GDFR - 0.36. For MOPA the measured degree of coherence reaches 0.65. The estimated and the measured coherence trends show similarity. Based on the Michelson interferometer and having just four optical components (a spherical lens, an optical wedge and two plane mirrors), a new rigid instrument for spatial coherence analysis of optical beams was introduced as well.

  18. 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...

  19. 27 CFR 70.233 - Protection for real property construction or improvement financing agreements.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2011-04-01 2011-04-01 false Protection for real... Limitations § 70.233 Protection for real property construction or improvement financing agreements. (a) In... after the tax lien filing, (2) Is on qualified property covered by the terms of a real...

  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. BLENDED FILMS OF NOVEL CASEIN WITH FOUR DIFFERENT CARRAGEENANS TO IMPROVE PROPERTIES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A novel CO2-precipitated casein (CO2CAS) forms films that are excellent oxygen barriers and moderate moisture barriers. CO2CAS films are strong, but elongation needs improvement. Blending biopolymers can improve properties of films. It is known that different types of carrageenans (kappa, iota, a...

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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. PMID:25915016

  7. Mechanochemistry of ibuprofen pharmaceutical.

    PubMed

    Andini, Salvatore; Bolognese, Adele; Formisano, Domenico; Manfra, Michele; Montagnaro, Fabio; Santoro, Luciano

    2012-07-01

    In this paper mechanochemistry has been studied in view of possible application to detoxification of expired pharmaceuticals. The experiments have been carried out with a commercial medication containing ibuprofen ((RS)-2-(4-(2-methylpropyl)phenyl)propanoic acid) which has been submitted to prolonged milling up to 40h. When Al(OH)(3) is used as co-reagent, the first degradation step induced by the mechanochemical treatment is an acid-base reaction with the ibuprofen carboxylic acid group. The subsequent degradation follows a complex pathway leading to 1-(4-isobutylphenyl)ethanone, 1-isobutyl-4-vinylbenzene and 2-(4-(3-methylbutan-2-yl)phenyl)propan-1-ol after 10h milling and, in addition, 1-(4-acetylphenyl)-2-methylpropan-1-one, 1-(4-(1-hydroxy-2-methylpropyl)phenyl)ethanone and 1-(4-(2-hydroxy-2-methylpropyl)phenyl)ethanone after 40h milling. The degradation reaction path and products have been identified by means of FT-IR spectroscopy, thin layer chromatography, NMR spectroscopy, mass spectroscopy and elemental analysis. The observed ibuprofen decarboxylation makes the drug simultaneously lose both its pharmaceutical activity and toxicity. PMID:22472100

  8. 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. PMID:27353394

  9. 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.

  10. Properties of PMR polyimide composites made with improved high strength graphite fibers

    NASA Technical Reports Server (NTRS)

    Vannucci, R. D.

    1980-01-01

    Recent graphite fiber developments have resulted in high strength, intermediate modulus graphite fibers having improved thermo-oxidative resistance. These improved fibers, obtained from various commercial suppliers, were used to fabricate PMR-15 and PMR-11 polyimide composites. Studies were performed to investigate the effects of the improved high strength graphite fibers on composite properties after exposure in air at 600 F. The use of the more oxidatively resistant fibers did not result in improved performance at 600 F. Two of the improved fibers were found to have an adverse effect on the long-term performance of PMR composites. The influence of various factors such as fiber physical properties, surface morphology and chemical composition are also discussed.

  11. 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. PMID:19041620

  12. 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

  13. 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

  14. Improving the Dielectric Properties of Ethylene-Glycol Alkanethiol Self-Assembled Monolayers

    PubMed Central

    2014-01-01

    Self-assembled monolayers (SAMs) can be formed at the interface between solids and fluids, and are often used to modify the surface properties of the solid. One of the most widely employed SAM systems is exploiting thiol-gold chemistry, which, together with alkane-chain-based molecules, provides a reliable way of SAM formation to modify the surface properties of electrodes. Oligo ethylene-glycol (OEG) terminated alkanethiol monolayers have shown excellent antifouling properties and have been used extensively for the coating of biosensor electrodes to minimize nonspecific binding. Here, we report the investigation of the dielectric properties of COOH-capped OEG monolayers and demonstrate a strategy to improve the dielectric properties significantly by mixing the OEG SAM with small concentrations of 11-mercaptoundecanol (MUD). The monolayer properties and composition were characterized by means of impedance spectroscopy, water contact angle, ellipsometry and X-ray photoelectron spectroscopy. An equivalent circuit model is proposed to interpret the EIS data and to determine the conductivity of the monolayer. We find that for increasing MUD concentrations up to about 5% the resistivity of the SAM steadily increases, which together with a considerable decrease of the phase of the impedance, demonstrates significantly improved dielectric properties of the monolayer. Such monolayers will find widespread use in applications which depend critically on good dielectric properties such as capacitive biosensor. PMID:24447311

  15. 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. PMID:26394179

  16. Improvement of mechanical properties of acrylic bone cement by fiber reinforcement.

    PubMed

    Saha, S; Pal, S

    1984-01-01

    Acrylic bone cement is significantly weaker and less stiff than compact bone. Bone cement is also weaker in tension than in compression. This limits its use in orthopaedics to areas where tensile stresses are minimum. We have attempted to improve the mechanical properties of PMMA by reinforcing it with metal wires, and graphite and aramid fibers. Normal, carbon fiber reinforced and aramid fiber reinforced bone cement specimens were tested in compression. Addition of a small percentage (1-2% by weight for carbon and up to 6% for aramid) of these fibers improved the mechanical properties significantly. Due to the improved mechanical properties of fiber reinforced bone cement, its clinical use may reduce the incidence of cement fracture and thus loosening of the prosthesis. PMID:6480622

  17. 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.

  18. Structured pharmaceutical analysis of the Systematic Tool to Reduce Inappropriate Prescribing is an effective method for final-year medical students to improve polypharmacy skills: a randomized controlled trial.

    PubMed

    Keijsers, Carolina J P W; van Doorn, Adriaan B D; van Kalles, Anouk; de Wildt, Dick J; Brouwers, Jacobus R B J; van de Kamp, Henrieke J; Jansen, Paul A F

    2014-07-01

    Medical students may not be adequately trained to prescribe appropriately to older adults with polypharmacy. This study addressed how to teach students to minimize inappropriate polypharmacy. Final-year medical students (N = 106) from two Dutch schools of medicine participated in this randomized controlled trial with a pre/posttest design. The Systematic Tool to Reduce Inappropriate Prescribing (STRIP) was used as the intervention. This medication review tool consists of five steps and is part of the Dutch multidisciplinary guideline on polypharmacy. Step two is a structured pharmaceutical analysis of drug use, assessed using six questions regarding undertreatment, ineffective treatment, overtreatment, potential adverse effects, contraindications or interactions, and dose adjustments. It is used in combination with the Screening Tool to Alert doctors to Right Treatment and the Screening Tool of Older Person's Prescriptions checklists. Students were asked to optimize the medication lists of real people, making use, or not, of the STRIP. The number of correct or potentially harmful decisions that the students made when revising the lists was determined by comparison with expert consensus. Students who used the STRIP had better scores than control students; they made more correct decisions (9.3 vs 7.0, 34%; P < .001, correlation coefficient (r) = 0.365) and fewer potentially harmful decisions (3.9 vs 5.6, -30%; P < .001, r = 0.386). E-learning did not have a different effect from that of non-E-learning methods. Students were satisfied with the method. The STRIP method is effective in helping final-year medical students improve their prescribing skills. PMID:24916615

  19. New insights in pharmaceutical analysis.

    PubMed

    Guillarme, Davy; Schappler, Julie; Boccard, Julien; Veuthey, Jean-Luc; Rudaz, Serge

    2012-01-01

    The research unit of pharmaceutical analytical chemistry (PAC) has been active in the field of separation sciences for many years. Liquid chromatography (LC) and its latest improvements such as ultra-high performance chromatography (UHPLC) and supercritical fluid chromatography (SFC) are deeply and thoroughly studied, from a fundamental viewpoint to its various application capabilities. Electro-driven separations such as capillary electrophoresis (CE) are also a major field of interest, especially for macromolecules, and low cost. All these techniques are investigated with various detection modes including mass spectrometry (MS) for various applications where high sensitivity and selectivity is needed. Extracting the relevant information from the overwhelming amount of data generated by modern analytical platforms has become an important issue for knowledge discovery in various research fields. The appropriate treatment of such data is therefore of crucial importance to provide valuable information. Numerous works in our research group have demonstrated the usefulness of statistical and mathematical methodologies to improve quality of the results. Therefore, well-established chemometric approaches (e.g. design of experiments, multivariate data analysis, etc.) are implemented to optimize the analytical process from method development to data analysis. PMID:22867546

  20. Pharmaceutical considerations of nitroglycerin

    SciTech Connect

    Yacobi, A.; Amann, A.H.; Baaske, D.M.

    1983-04-01

    During the past few years, there have been rapid changes in the pharmaceutical uses of nitroglycerin. New dosage forms and new delivery systems have become available, which have resulted in potential confusion to all concerned with the proper use of these systems. The goal of this review is to prevent confusion and to bring all the relevant information together. The various analytical techniques available for quality control of the dosage forms and for the study of the pharmacokinetics are reviewed, with the intent of enabling the reader to identify pertinent references rapidly. The interaction of nitroglycerin with packaging and plastic delivery devices is also reviewed so that the reader can make informed choices. Finally, the clinical pharmacy and pharmacokinetics are reviewed so as to bring the reader up to date in that area. After reading this article, the areas of nitroglycerin research that still need to be explored should be apparent.

  1. Pharmaceutical study of Yashadabhasma

    PubMed Central

    Bhojashettar, Santhosh; Jadar, P. G.; Rao, V. Nageswara

    2012-01-01

    Background: Rasashastra is a branch which deals with the pharmaceutics of Rasaoushadhis. Bhasmas are one among such Rasaoushadhis which are known for their low doses and fast action. A verse from Rasaratnasamuchchaya says that the bhasma prepared by using Mercury as media is of best quality. Materials and Methods: Following this principle, Yashadabhasma (Zinc calx) was prepared by subjecting it to Samanya shodhana (general purification method for all metals), Vishesha shodhana (specific putification method for Zinc), Jarana (roasting) and Marana (incineration) with Parada(Mercury) as a media under Gajaputa (classical heating system with 1000 cowdung cakes). Results and Conclusion: Yellow colored Yashadabhasma which passed all the classical bhasmaparikshas (tests for properly prepared calx) was obtained after two putas. The bhasma did not pass Nishchandratva(free from shining particles) test after 1stputa but was passed after giving it 2ndputa. PMID:23284213

  2. Improved instrumentation for monitoring the diurnal and seasonal cycles in the dielectric properties of forest canopies

    NASA Technical Reports Server (NTRS)

    Guerra, Abel G.; Mcdonald, Kyle C.; Way, Jobea

    1992-01-01

    The design and implementation of a dielectric measurement system that facilitates the automated and continuous in situ monitoring of the dielectric properties of several canopy constituents is presented. This system utilizes the same coaxial line reflection coefficient measurement technique as the portable dielectric probe (PDP) while incorporating several features that facilitate the automated monitoring of canopy dielectric properties. The new system is capable of continuously monitoring the dielectric properties of the canopy constituents in a near-simultaneous fashion. The implementation of a data logger as a user interface has increased the number of measurements that the instrument is able to store in memory while significantly improving system reliability.

  3. Improved carbides and new borides for HVOF and their coating properties

    SciTech Connect

    Froning, M.J.; Keller, H.

    1995-12-31

    In the presented paper, investigations on HVOF coatings produced from a new family of powders will be discussed. The influence of microstructure, composition and production methods will be discussed in view of powder properties and resulting coating properties. New boride powders and coatings will be compared with regard to their properties deposition, efficiency, hardness, surface roughness, bond strength, and wear against commercial WC-Co and cr3C2-NiCr coatings. Additionally, improved WC- and CrC-based powders and coatings will be compared with regard to oxidation and erosion resistance.

  4. 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.

  5. Experimental and theoretical investigation of the molecular structure, conformational stability, hyperpolarizability, electrostatic potential, thermodynamic properties and NMR spectra of pharmaceutical important molecule: 4'-methylpropiophenone.

    PubMed

    Karunakaran, V; Balachandran, V

    2014-07-15

    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 (1)H and (13)C 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. PMID:24657464

  6. 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.

  7. Novel Radiofrequency-Assisted Thermal Processing Improves the Gelling Properties of Standard Egg White Powder.

    PubMed

    Boreddy, Sreenivasula Reddy; Thippareddi, Harshavardhan; Froning, Glenn; Subbiah, Jeyamkondan

    2016-03-01

    Effect of radiofrequency (RF)-assisted thermal processing on quality and functional properties of high-foaming standard egg white powder (std. EWP, pH approximately 7.0) was investigated and compared with traditional processing (heat treatment in a hot room at 58 °C for at least 14 d). The RF-assisted thermal treatments were selected to meet the pasteurization requirements and to improve the functional properties of the std. EWP. The treatment conditions were: RF heating to 60, 70, 80, and 90 °C followed by holding in a hot air oven at those temperatures for different periods ranging from 4 h at 90 °C to 72 h at 60 °C. The quality (color and solubility) and functional properties (foaming properties: foaming capacity and foam stability; and gelling properties: water holding capacity and gel-firmness) of the std. EWP were investigated. RF-assisted thermal processing did not affect the color and solubility of std. EWP at any of the treatment conditions. In general, the foaming and gelling properties of RF-assisted thermally processed std. EWP increased with an increase in temperature and treatment duration. The optimal RF-assisted treatment conditions to produce std. EWP with similar functional properties as the traditionally processed (hot room processed) std. EWP were 90 °C for ≥8 h. These optimal conditions were similar to those for high gel egg white powder (HG-EWP, pH approximately 9.5). The RF-assisted thermal pasteurization improved the gelling properties of std. EWP to the levels of HG-EWP, leading to newer applications of this functionally improved safe product. The RF-assisted thermal processing allows the processor to produce a HG-EWP from std. EWP subsequent to processing while simultaneously pasteurizing the product, thus assuring the product safety. PMID:26869145

  8. 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

  9. Effect of poly ethylene glycol on the mechanical and thermal properties of bioactive poly(ε-caprolactone) melt extrudates for pharmaceutical applications.

    PubMed

    Douglas, P; Albadarin, Ahmad B; Sajjia, M; Mangwandi, Chirangano; Kuhs, Manuel; Collins, Maurice N; Walker, Gavin M

    2016-03-16

    This paper investigates the effects of polyethylene glycol (PEG), on the mechanical and thermal properties of nalidixic acid/poly ε-caprolactone (NA)/PCL blends prepared by hot melt extrusion. The blends were characterized by tensile and flexural analysis, dynamic mechanical analysis, differential scanning calorimetry, thermogravimetric analysis and X-ray diffraction. Results show that loading PEG in the PCL had a detrimental effect on the tensile strength and toughness of the blends, reducing them by 20-40%. The partial miscibility of the PCL-PEG system, causes an increase in Tg. While increases in the crystallinity is attributed to the plasticisation effect of PEG and the nucleation effect of NA. The average crystal size increased by 8% upon PEG addition. Experimental data indicated that the addition of NA caused loss of the tensile strength and toughness of PCL. Thermal analysis of the PCL showed that on addition of the thermally unstable NA, thermal degradation occurred early and was autocatalytic. However, the NA did benefit from the heat shielding provided by the PCL matrix resulting in more thermally stable NA particles. PMID:26794874

  10. Addition of cover crops enhances no-till potential for improving soil physical properties

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Interest in the use of cover crops (CC) is growing. Inclusion of CC may be a potential strategy to boost no-till performance by improving soil physical properties. To assess this potential, we utilized a wheat [Triticum aestivum (L.)]-grain sorghum [Sorghum bicolor (L.) Moench] rotation, four N rate...