WorldWideScience

Sample records for model pharmaceutical powders

  1. Quantification of Tribocharging of Pharmaceutical Powders in V-Blenders: Experiments, Multiscale Modeling, and Simulations.

    Science.gov (United States)

    Naik, Shivangi; Hancock, Bruno; Abramov, Yuriy; Yu, Weili; Rowland, Martin; Huang, Zhonghui; Chaudhuri, Bodhisattwa

    2016-04-01

    Pharmaceutical powders are very prone to electrostatic charging by colliding and sliding contacts. In pharmaceutical formulation processes, particle charging is often a nuisance and can cause problems in the manufacture of products, such as affecting powder flow, fill, and dose uniformity. For a fundamental understanding of the powder triboelectrification, it is essential to study charge transfer under well-defined conditions. Hence, all experiments in the present study were conducted in a V-blender located inside a glove box with a controlled humidity of 20%. To understand tribocharging, different contact surfaces, namely aluminum, Teflon, poly methyl methacrylate, and nylon were used along with 2 pharmaceutical excipients and 2 drug substances. For the pharmaceutical materials, the work function values were estimated using MOPAC, a semiempirical molecular orbital package which has been previously used for the solid-state studies and molecular structure predictions. For a mechanistic understanding of tribocharging, a discrete element model incorporating charge transfer and electrostatic forces was developed. An effort was made to correlate tribocharging of pharmaceutical powders to properties such as cohesive energy density and surface energy. The multiscale model used is restricted as it considers only spherical particles with smooth surfaces. It should be used judiciously for other experimental assemblies because it does not represent a full validation of a tightly integrated model.

  2. Understanding the influence of powder flowability, fluidization and de-agglomeration characteristics on the aerosolization of pharmaceutical model powders.

    Science.gov (United States)

    Zhou, Qi Tony; Armstrong, Brian; Larson, Ian; Stewart, Peter J; Morton, David A V

    2010-08-11

    The aim of this study was to investigate the influence of the intrinsic inter-particulate cohesion of model pharmaceutical powders on their aerosolization from a dry powder inhaler. Two cohesive poly-disperse lactose powders with median particle sizes of around 4 and 20 microm were examined. The results showed that after dry coating with magnesium stearate, their flowability, fluidization and de-agglomeration behaviours could be substantially improved, as indicated by powder rheometry, shear testing and laser diffraction aerosol testing. This was achieved by reducing their cohesiveness via surface modification. In contrast to some previous reports, this study demonstrated how powder aerosolization may be improved more significantly and consistently (for widely varying air flow rates) by substantially reducing their inter-particulate cohesive forces. This study contributes to the understanding of the relationship between intrinsic cohesive nature and bulk properties such as flowability, fluidization and de-agglomeration and its impact on their aerosolization, which is fundamental and critical in the optimal design of dry powder inhaler formulations. The intensive mechanical dry coating technique also demonstrated a promising potential to improve aerosolization efficiency of fine cohesive model powders.

  3. Transport and deposition of cohesive pharmaceutical powders in human airway

    Science.gov (United States)

    Wang, Yuan; Chu, Kaiwei; Yu, Aibing

    2017-06-01

    Pharmaceutical powders used in inhalation therapy are in the size range of 1-5 microns and are usually cohesive. Understanding the cohesive behaviour of pharmaceutical powders during their transportation in human airway is significant in optimising aerosol drug delivery and targeting. In this study, the transport and deposition of cohesive pharmaceutical powders in a human airway model is simulated by a well-established numerical model which combines computational fluid dynamics (CFD) and discrete element method (DEM). The van der Waals force, as the dominant cohesive force, is simulated and its influence on particle transport and deposition behaviour is discussed. It is observed that even for dilute particle flow, the local particle concentration in the oral to trachea region can be high and particle aggregation happens due to the van der Waals force of attraction. It is concluded that the deposition mechanism for cohesive pharmaceutical powders, on one hand, is dominated by particle inertial impaction, as proven by previous studies; on the other hand, is significantly affected by particle aggregation induced by van der Waals force. To maximum respiratory drug delivery efficiency, efforts should be made to avoid pharmaceutical powder aggregation in human oral-to-trachea airway.

  4. Thermal properties of food and pharmaceutical powders

    Science.gov (United States)

    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. Process monitoring and modeling of a continuous pharmaceutical from powder to tablet process Line using a mass & energy balance

    DEFF Research Database (Denmark)

    Beer, Thomas De; Mortier, Séverine Thérèse F.C.; Gernaey, Krist

    2014-01-01

    The intention to shift from batch to continuous production processes within the pharmaceutical industry enhances the need to monitor and control the process in-line and real-time to continuously guarantee the end-product quality. Mass and energy balances have been successfully applied to a drying...

  6. Analysis of the surface energy of pharmaceutical powders by inverse gas chromatography.

    Science.gov (United States)

    Grimsey, Ian M; Feeley, Jane C; York, Peter

    2002-02-01

    The behavior of pharmaceutical solids, during either processing or use, can be noticeably affected by the surface energetics of the constituent particles. Several techniques exist to measure the surface energy, for example, sessile drop, and dynamic contact angle measurements. Inverse gas chromatography (IGC) is an alternative technique where the powder surface is characterized by the retention behavior of minute quantities of well-characterized vapors that are injected into a column containing the material of interest. Recently published articles using IGC on pharmaceutical powders have ranged from linking surface energetic data with triboelectric charging to studying the effect of surface moisture on surface energetics. Molecular modelling has also recently been used to explore the links between IGC data and the structural and chemical factors that influence surface properties, thereby achieving predictive knowledge regarding powder behavior during processing. In this minireview, the reported applications of IGC in the analysis of pharmaceutical powders are summarized and the major findings highlighted.

  7. Effect of contamination of pharmaceutical equipment on powder triboelectrification.

    Science.gov (United States)

    Eilbeck, J; Rowley, G; Carter, P A; Fletcher, E J

    2000-02-15

    Triboelectrification of pharmaceutical powders may cause problems during processing and manufacture due to adhesion/cohesion effects. The aim of this work was to investigate the role of adhered particles and moisture as contact surface contaminants on the electrostatic charging of size fractionated lactose, following contact with a surface, i.e. stainless steel, typically used in pharmaceutical process and manufacturing operations. Replicated experimental runs without cleaning the contact surface showed a successive decrease in the net electronegative charge due to adhered lactose particles. Removal of these contaminating particles by different cleaning methods had a considerable effect on the charge after triboelectrification. The charge on the lactose samples was found to decrease when humidity in the cyclone apparatus was increased from 2 to 100% relative humidity. These results clearly demonstrate that moisture, particulate contamination and method of cleaning of processing equipment during pharmaceutical manufacturing operations may influence the electrostatic behaviour of powders.

  8. Bulk characterization of pharmaceutical powders by low-pressure compression.

    Science.gov (United States)

    Sørensen, Arne Hagsten; Sonnergaard, Jørn Møller; Hovgaard, Lars

    2005-01-01

    Low-pressure compression of pharmaceutical powders using small amounts of sample (50 mg) was evaluated as an alternative to traditional bulk powder characterization by tapping volumetry. Material parameters were extrapolated directly from the compression data and by fitting with the Walker, the Kawakita, and the Log-Exp compression models. The compression-derived material parameters were compared to the poured and tapped density and the Compressibility Index determined by tapping. The repeatability of the compression-derived parameters was generally high, supporting their potential for characterization purposes. Significant correlation was demonstrated between several of the compression and tapping-derived parameters. The discriminative power of the low-pressure compression test was discussed using the compressed density at 0.2 MPa, correlated with the tapped density, and the relative Walker coefficient, correlated with the Compressibility Index, as examples. The compressed density at 0.2 MPa and the relative Walker coefficient demonstrated excellent discriminative power, superior to the discriminative power of the correlated tapping derived parameters. The low-pressure compression test was concluded to provide a cost-effective and sensitive alternative to traditional tapping volumetry.

  9. Quantification of the compactibility of pharmaceutical powders

    DEFF Research Database (Denmark)

    Sonnergaard, Jørn

    2006-01-01

    force normalized with the dimension of the tablet and termed the specific crushing strength, SCS. The proposed model: SCS = Cp * P + b estimates the slope of the regression line Cp as a dimensionless compactibility parameter and is reported with the corresponding standard deviation S. The linear region...... of the compactibility profile is selected using the 95% predictability limits bordering the regression line. Eleven different materials were tested and acceptable fits to the linear model were observed in all cases. The ability of the model to discriminate between the investigated materials is excellent, in cases where...

  10. Bulk characterization of pharmaceutical powders by low-pressure compression

    DEFF Research Database (Denmark)

    Sørensen, A.H.; Sonnergaard, Jørn; Hovgaard, L.

    2005-01-01

    for characterization purposes. Significant correlation was demonstrated between several of the compression and tapping-derived parameters. The discriminative power of the low-pressure compression test was discussed using the compressed density at 0.2 MPa, correlated with the tapped density, and the relative Walker...... coefficient, correlated with the Compressibility Index, as examples. The compressed density at 0.2 MPa and the relative Walker coefficient demonstrated excellent discriminative power, superior to the discriminative power of the correlated tapping derived parameters. The low-pressure compression test......Low-pressure compression of pharmaceutical powders using small amounts of sample (50 mg) was evaluated as an alternative to traditional bulk powder characterization by tapping volumetry. Material parameters were extrapolated directly from the compression data and by fitting with the Walker...

  11. The effect of lubricants on powder flowability for pharmaceutical application.

    Science.gov (United States)

    Morin, Garett; Briens, Lauren

    2013-09-01

    Pharmaceutical tablets are manufactured through a series of batch steps finishing with compression into a form using a tablet press. Lubricants are added to the powder mixture prior to the tabletting step to ensure that the tablet is ejected properly from the press. The addition of lubricants also affects tablet properties and can affect the behavior of the powder mixture. The objective of this research was to investigate the effect of lubricants on powder flowability as flowability into the tablet press is critical. Four lubricants (magnesium stearate, magnesium silicate, stearic acid, and calcium stearate) were mixed, in varying amounts, with spray-dried lactose. In addition, magnesium stearate was also mixed with placebo granules from a high-shear granulator. Measurements based on avalanche behavior indicated flowability potential and dynamic density and were more sensitive to changes in the mixture and provided a more accurate and reproducible indication of flowability than traditional static measurements. Of the tested lubricants, magnesium stearate provided the best increase in flowability even in the low amounts commonly added in formulations.

  12. Influence of process parameters on the preparation of pharmaceutical films by electrostatic powder deposition.

    Science.gov (United States)

    Prasad, Leena Kumari; LaFountaine, Justin S; Keen, Justin M; Williams, Robert O; McGinity, James W

    2016-12-30

    Electrostatic powder deposition (ESPD) has been developed as a solvent-free method to prepare pharmaceutical films. The aim of this work was to investigate the influence of process parameters during (1) electrostatic powder deposition, (2) curing, and (3) removal of the film from the substrate on the properties of the film. Polyethylene oxide (PEO) was used as the model polymer and stainless steel 316 as the substrate. Deposition efficiency (i.e. deposited weight) was measured with varying charging voltage, gun tip to substrate distance, and environmental humidity. Scanning electron microscopy was utilized to assess film formation, and adhesive and mechanical strength of films were measured with varying cure temperature and time. Adhesive strength was measured for films prepared on substrates of varying surface roughness. When deposition was performed at low humidity conditions, 25%RH, process parameters did not significantly affect deposition behavior. At 40%RH, increasing deposition efficiency with decreasing gun tip to substrate distance and increasing voltage (up to 60kV) was observed. Complete film formation was seen by 30min at 80°C, compared to lower curing temperatures and times. All films were readily removed from the substrates. The results show the ESPD process can be modified to produce films with good mechanical properties (e.g. tensile strength>0.06MPa), suggesting it is a promising dry powder process for preparing pharmaceutical films.

  13. Assessment of Pharmaceutical Powder Flowability using Shear Cell-Based Methods and Application of Jenike's Methodology.

    Science.gov (United States)

    Jager, Paul D; Bramante, Tommasina; Luner, Paul E

    2015-11-01

    Jenike's approach to hopper design for a large-scale (3150 L) conical hopper was applied to pharmaceutical powders to evaluate flow issues, such as funnel flow or cohesive arching. Seven grades of microcrystalline cellulose (MCC) and six powder blends were tested. A Schulze Ring Shear Tester measured the flow function, wall friction (using stainless steel coupons with a #2B or #8 finish) and compressibility. Hopper Index (HI, maximum hopper angle required for mass flow) and Arching Index (AI, minimum hopper outlet size to prevent cohesive arch formation) were computed using Mathcad(©) . For MCC, a linear relationship was observed between median particle size and the Jenike flow function coefficient. A curvilinear relationship was observed for powder blends indicating more complex flow behavior than based on median particle size alone. Powder bulk density had a minimal effect on AI for MCC grades. Overestimation of AI can occur with this method for pharmaceutical powders because the true shape of the flow function is not defined at very low consolidation pressures and linear extrapolation becomes unrepresentative. This instrumental limitation underscores the need for a precise and accurate test method to determine powder flow functions at very low levels of consolidation stress for pharmaceutical applications.

  14. On Identification of Critical Material Attributes for Compression Behaviour of Pharmaceutical Diluent Powders.

    Science.gov (United States)

    Zhang, Jianyi; Wu, Chuan-Yu; Pan, Xin; Wu, Chuanbin

    2017-07-23

    As one of the commonly-used solid dosage forms, pharmaceutical tablets have been widely used to deliver active drugs into the human body, satisfying patient's therapeutic requirements. To manufacture tablets of good quality, diluent powders are generally used in formulation development to increase the bulk of formulations and to bind other inactive ingredients with the active pharmaceutical ingredients (APIs). For formulations of a low API dose, the drug products generally consist of a large fraction of diluent powders. Hence, the attributes of diluents become extremely important and can significantly influence the final product property. Therefore, it is essential to accurately characterise the mechanical properties of the diluents and to thoroughly understand how their mechanical properties affect the manufacturing performance and properties of the final products, which will build a sound scientific basis for formulation design and product development. In this study, a comprehensive evaluation of the mechanical properties of the widely-used pharmaceutical diluent powders, including microcrystalline cellulose (MCC) powders with different grades (i.e., Avicel PH 101, Avicel PH 102, and DG), mannitol SD 100, lactose monohydrate, and dibasic calcium phosphate, were performed. The powder compressibility was assessed with Heckel and Kawakita analyses. The material elastic recovery during decompression and in storage was investigated through monitoring the change in the dimensions of the compressed tablets over time. The powder hygroscopicity was also evaluated to examine the water absorption ability of powders from the surroundings. It was shown that the MCC tablets exhibited continuous volume expansion after ejection, which is believed to be induced by (1) water absorption from the surrounding, and (2) elastic recovery. However, mannitol tablets showed volume expansion immediately after ejection, followed by the material shrinkage in storage. It is anticipated that

  15. On Identification of Critical Material Attributes for Compression Behaviour of Pharmaceutical Diluent Powders

    Directory of Open Access Journals (Sweden)

    Jianyi Zhang

    2017-07-01

    Full Text Available As one of the commonly-used solid dosage forms, pharmaceutical tablets have been widely used to deliver active drugs into the human body, satisfying patient’s therapeutic requirements. To manufacture tablets of good quality, diluent powders are generally used in formulation development to increase the bulk of formulations and to bind other inactive ingredients with the active pharmaceutical ingredients (APIs. For formulations of a low API dose, the drug products generally consist of a large fraction of diluent powders. Hence, the attributes of diluents become extremely important and can significantly influence the final product property. Therefore, it is essential to accurately characterise the mechanical properties of the diluents and to thoroughly understand how their mechanical properties affect the manufacturing performance and properties of the final products, which will build a sound scientific basis for formulation design and product development. In this study, a comprehensive evaluation of the mechanical properties of the widely-used pharmaceutical diluent powders, including microcrystalline cellulose (MCC powders with different grades (i.e., Avicel PH 101, Avicel PH 102, and DG, mannitol SD 100, lactose monohydrate, and dibasic calcium phosphate, were performed. The powder compressibility was assessed with Heckel and Kawakita analyses. The material elastic recovery during decompression and in storage was investigated through monitoring the change in the dimensions of the compressed tablets over time. The powder hygroscopicity was also evaluated to examine the water absorption ability of powders from the surroundings. It was shown that the MCC tablets exhibited continuous volume expansion after ejection, which is believed to be induced by (1 water absorption from the surrounding, and (2 elastic recovery. However, mannitol tablets showed volume expansion immediately after ejection, followed by the material shrinkage in storage. It is

  16. Application of Response Surface Methodology to Estimate the Design Space of Pharmaceutical Diluents for Dispensing Powdered Formulations.

    Science.gov (United States)

    Miyazaki, Yasunori; Takayama, Kozo; Uchino, Tomonobu; Kagawa, Yoshiyuki

    2016-01-01

    Scientific approaches for dispensation are important for the quality and efficacy of drug treatments. Therefore, for the dispensation of powdered medicines, we have developed a powder blending method using a planetary centrifugal mixer (PCM) to replace the empirical manual method involving a mortar and pestle. The aim of this study was to optimize the formulation of pharmaceutical diluents for dispensing powdered medicines, using PCM. The diluents, composed of powdered lactose, crystalline lactose, and corn starch were assigned to a {3,2}-Simplex Lattice design. Then, the designed diluents were blended with model powders, such as carbazochrome sodium sulfonate powder, rifampicin capsule contents, and crushed sulfasarazine tablets, at ratios of 1 : 4, 1 : 1, and 4 : 1 using PCM at 800 rpm for 60 s at a 20% filling rate. The mixtures were examined for content uniformity relative standard deviation (RSD) and flowability angle of repose (AOR). Response surface methodology was applied to optimize the formulation with the smallest RSD and AOR, and then the design space of desired diluents was estimated. On the basis of the design space, crystalline lactose, the mixture of lactose powder and crystalline lactose at a ratio of 1 : 4, and the mixture of corn starch and crystalline lactose at a ratio of 1 : 4, were suitable diluents for the powdered formulation, the content of the capsules, and the crushed tablets, respectively. The selected diluents were successfully applied to other model medicines showing a sufficient RSD and AOR. This technique could contribute to the development of scientific approaches for dispensation.

  17. A novel electrostatic dry powder coating process for pharmaceutical dosage forms: immediate release coatings for tablets.

    Science.gov (United States)

    Qiao, Mingxi; Zhang, Liqiang; Ma, Yingliang; Zhu, Jesse; Chow, Kwok

    2010-10-01

    An electrostatic dry powder coating process for pharmaceutical solid dosage forms was developed for the first time by electrostatic dry powder coating in a pan coater system. Two immediate release coating compositions with Opadry® AMB and Eudragit® EPO were successfully applied using this process. A liquid plasticizer was sprayed onto the surface of the tablet cores to increase the conductivity of tablet cores to enhance particle deposition, electrical resistivity reduced from greater than 1×10(13)Ωm to less than 1×10(9)Ωm, and to lower the glass transition temperature (T(g)) of the coating polymer for film forming in the pan coater. The application of liquid plasticizer was followed by spraying charged coating particles using an electrostatic charging gun to enhance the uniform deposition on tablet surface. The coating particles were coalesced into a thin film by curing at an acceptable processing temperature as formation was confirmed by SEM micrographs. The results also show that the optimized dry powder coating process produces tablets with smooth surface, good coating uniformity and release profile that are comparable to that of the tablet cores. The data also suggest that this novel electrostatic dry powder coating technique is an alternative to aqueous- or solvent-based coating process for pharmaceutical products. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

  18. Effect of milling temperatures on surface area, surface energy and cohesion of pharmaceutical powders.

    Science.gov (United States)

    Shah, Umang V; Wang, Zihua; Olusanmi, Dolapo; Narang, Ajit S; Hussain, Munir A; Tobyn, Michael J; Heng, Jerry Y Y

    2015-11-10

    Particle bulk and surface properties are influenced by the powder processing routes. This study demonstrates the effect of milling temperatures on the particle surface properties, particularly surface energy and surface area, and ultimately on powder cohesion. An active pharmaceutical ingredient (API) of industrial relevance (brivanib alaninate, BA) was used to demonstrate the effect of two different, but most commonly used milling temperatures (cryogenic vs. ambient). The surface energy of powders milled at both cryogenic and room temperatures increased with increasing milling cycles. The increase in surface energy could be related to the generation of surface amorphous regions. Cohesion for both cryogenic and room temperature milled powders was measured and found to increase with increasing milling cycles. For cryogenic milling, BA had a surface area ∼ 5× higher than the one obtained at room temperature. This was due to the brittle nature of this compound at cryogenic temperature. By decoupling average contributions of surface area and surface energy on cohesion by salinization post-milling, the average contribution of surface energy on cohesion for powders milled at room temperature was 83% and 55% at cryogenic temperature.

  19. Advances in Compression and Binding Characteristics of Pharmaceutical Powders%药物粉体压缩与结合特性研究进展

    Institute of Scientific and Technical Information of China (English)

    杜焰; 冯怡; 徐德生; 赵立杰

    2012-01-01

    OBJECTIVE The physical properties of pharmaceutical powders and their compression and binding characteristics have a significant impact on quality of solid dosage. Understanding of comprehensive properties of pharmaceutical powders is helpful to improve production process of solid dosage. METHODS This article reviewed the research of compression and binding properties of pharmaceutical powder from different aspects. The new applied research on characteristic parameters of pharmaceutical powders was evaluated. So the relevant mathematical models were described in case that mathematical models were widely used in the compression process all over the world. RESULTS From the study on the prediction of pharmaceutical powders' compression behavior, we could found that the mechanical properties of pharmaceutical powders could be described by binding index, hardness, tensile strength, Young's modulus and other parameters.They could be used to guide the production. CONCLUSION Understanding and grasping the comprehensive properties of powders was the key point during our formulation design, product development and solving practical production problems.%目的 药物粉体物理性质与其压缩与结合特性对固体制剂的质量具有重大影响,对于药用粉体综合特性的理解目的在于改进制剂生产工艺.方法 本文从不同角度对有关药物粉体的压缩与结合特性的研究进行了综述,对于药物粉体的特性参数最新应用研究进行评价.国内外的研究在药用粉体的压缩过程中多使用数学模型,因此对相关数学模型进行了阐述.结果 对于药物粉体的压缩行为预测研究发现,药用粉体的机械特性一般可以用压合指数、硬度、抗张强度、杨氏模量等参数描述,从而指导生产.结论 掌握和理解粉体压缩与结合特性,是处方设计、产品研发以及解决生产中可能存在的实际问题的关键.

  20. Continuous powder feeding for pharmaceutical solid dosage form manufacture: a short review.

    Science.gov (United States)

    Blackshields, Caroline A; Crean, Abina M

    2017-06-21

    There has been a noticeable shift from pharmaceutical batch processing towards a more continuous mode of manufacture for solid oral dosage forms. Continuous solid oral dose processes would not be possible in the absence of a highly accurate feeding system. The performance of feeders defines the content of formulations and is therefore a critical operation in continuous manufacturing of solid dosage forms. It was the purpose of this review to review the role of the initial powder feeding step in a continuous manufacturing process. Different feeding mechanisms are discussed with a particular emphasis on screw controlled loss in weight (LIW) feeding. The importance of understanding the physical properties of the raw materials and its impact on the feeding process is reviewed. Prior knowledge of materials provides an initial indication of how the powders will behave through processing and facilitates in the selection of the most suitable (i) feeder (capacity), (ii) feeding mechanism, and (iii) in the case of screw feeder - screw type. The studies identified in this review focus on the impact of material on powder feeding performance.

  1. Identification of Polymorphic Forms of Active Pharmaceutical Ingredient in Low-Concentration Dry Powder Formulations by Synchrotron X-Ray Powder Diffraction.

    Science.gov (United States)

    Egusa, Kenji; Okazaki, Fumiaki; Schiewe, Joerg; Werthmann, Ulrike; Wolkenhauer, Markus

    2017-09-13

    The identification of different (pseudo) polymorphs of an active pharmaceutical ingredient in dry powder formulations is of importance during development and entire product lifecycle, e.g., quality control. Whereas determination of polymorphic differences of pure substances is rather easy, in dry powder formulations, it is generally difficult and the difficulties increase particularly, if the substance of interest is present only in low concentrations in the formulation. Such a formulation is Spiriva(®) inhalation powder (Boehringer Ingelheim), which contains only 0.4 w/w% of the active pharmaceutical ingredient tiotropium bromide monohydrate in a matrix of α-lactose monohydrate as excipient. In this study, identification of 0.4 w/w% tiotropium bromide in the dry powder formulation was examined by X-ray powder diffraction (XRPD) using a synchrotron radiation source and the results were compared with the conventional laboratory XRPD measurements. The detection limit of tiotropium bromide by the laboratory XRPD was around 2-5 w/w%, and hence, detection of 0.4 w/w% tiotropium bromide was impossible. The synchrotron XRPD was capable to detect significantly lower level of tiotropium bromide by at least an order of magnitude. Four different polymorphic forms of tiotropium bromide present at 0.4 w/w% concentration in lactose powder blends were unambiguously identified by the synchrotron XRPD method.

  2. Computational modelling for dry-powder inhalers

    NARCIS (Netherlands)

    Kröger, Ralf; Woolhouse, Robert; Becker, Michael; Wachtel, Herbert; de Boer, Anne; Horner, Marc

    2012-01-01

    Computational fluid dynamics (CFD) is a simulation tool used for modelling powder flow through inhalers to allow optimisation both of device design and drug powder. Here, Ralf Kröger, Consulting Senior CFD Engineer, ANSYS Germany GmbH; Marc Horner, Lead Technical Services Engineer, Healthcare, ANSYS

  3. Computational modelling for dry-powder inhalers

    NARCIS (Netherlands)

    Kröger, Ralf; Woolhouse, Robert; Becker, Michael; Wachtel, Herbert; de Boer, Anne; Horner, Marc

    2012-01-01

    Computational fluid dynamics (CFD) is a simulation tool used for modelling powder flow through inhalers to allow optimisation both of device design and drug powder. Here, Ralf Kröger, Consulting Senior CFD Engineer, ANSYS Germany GmbH; Marc Horner, Lead Technical Services Engineer, Healthcare,

  4. Design of a fluid energy single vessel powder processor for pharmaceutical use.

    Science.gov (United States)

    Kay, G R; Staniforth, J N; Tobyn, M J; Horrill, M D; Newnes, L B; MacGregor, S A; Li, M; Atherton, G; Lamming, R C; Hajee, D W

    1999-04-30

    This study introduces a motionless novel single vessel powder processor designed to carry out all of the unit operations in the preparation of powders for tableting. The processor used controllable fluid dynamics to provide the energy for each unit operation. The vessel design was evaluated using a computational fluid dynamics model which indicated the flow necessary for the intended processing operations to take place. The processor performance was evaluated experimentally for two unit processes: particle size reduction and dry powder mixing. The processor was found capable of reducing the size of lactose granules from a median particle diameter of 459 microm to a median particle diameter of 182 microm within 5 min under optimal process conditions. It was found that a formulation containing lactose granules (373 microm median particle diameter) and a model drug, sodium chloride (30 microm), could be mixed to an improved degree of homogeneity in comparison with equivalent powders blended using a conventional turbulent tumbling technique. It was concluded that a processor having controllable fluid dynamics offered the potential to perform multi-task processing of powders.

  5. Near infrared spectroscopic calibration models for real time monitoring of powder density.

    Science.gov (United States)

    Román-Ospino, Andrés D; Singh, Ravendra; Ierapetritou, Marianthi; Ramachandran, Rohit; Méndez, Rafael; Ortega-Zuñiga, Carlos; Muzzio, Fernando J; Romañach, Rodolfo J

    2016-10-15

    Near infrared spectroscopic (NIRS) calibration models for real time prediction of powder density (tap, bulk and consolidated) were developed for a pharmaceutical formulation. Powder density is a critical property in the manufacturing of solid oral dosages, related to critical quality attributes such as tablet mass, hardness and dissolution. The establishment of calibration techniques for powder density is highly desired towards the development of control strategies. Three techniques were evaluated to obtain the required variation in powder density for calibration sets: 1) different tap density levels (for a single component), 2) generating different strain levels in powders blends (and as consequence powder density), through a modified shear Couette Cell, and 3) applying normal forces during a compressibility test with a powder rheometer to a pharmaceutical blend. For each variation in powder density, near infrared spectra were acquired to develop partial least squares (PLS) calibration models. Test samples were predicted with a relative standard error of prediction of 0.38%, 7.65% and 0.93% for tap density (single component), shear and rheometer respectively. Spectra obtained in real time in a continuous manufacturing (CM) plant were compared to the spectra from the three approaches used to vary powder density. The calibration based on the application of different strain levels showed the greatest similarity with the blends produced in the CM plant.

  6. Glass powder blended cement hydration modelling

    Science.gov (United States)

    Saeed, Huda

    .17, H/S ratio of 2.5 and N/S ratio of 0.18. In the second phase of this research, theoretical models are built using a modified version of an existing cement hydration modelling code, "CEMHYD3D", to simulate the chemical reaction of the activated glass powder hydration and glass powder in cement. The modified model, which is referred to as the "MOD-model" is further used to predict the types, compositions and quantities of reaction products. Furthermore, the glass powder hydration data, which is obtained experimentally, is incorporated into the MOD-model to determine the effect of adding glass powder to the paste on the process of cement hydration and resulting paste properties. Comparisons between theoretical and experimental results are made to evaluate the developed models. The MOD-model predictions have been validated using the experimental results, and were further used to investigate various properties of the hydrated glass powder cement paste. These properties include, for example, CH content of the paste, porosity, hydration degree of the glass powder and conventional C-S-H and GP CS-H contents. The results show that the MOD-model is capable of accurately simulating the hydration process of glass powder-blended cement paste and can be used to predict various properties of the hydrating paste.

  7. Mechanistic modelling of the drying behaviour of single pharmaceutical granules

    DEFF Research Database (Denmark)

    Thérèse F.C. Mortier, Séverine; Beer, Thomas De; Gernaey, Krist

    2012-01-01

    The trend to move towards continuous production processes in pharmaceutical applications enhances the necessity to develop mechanistic models to understand and control these processes. This work focuses on the drying behaviour of a single wet granule before tabletting, using a six...... of b on the drying behaviour. Experimental data with the six-segmented fluidised bed dryer were collected to calibrate b. An exponential dependence on the drying air temperature was found. Independent experiments were done for the validation of the drying model.......-segmented fluidised bed drying system, which is part of a fully continuous from-powder-to-tablet manufacturing line. The drying model is based on a model described by Mezhericher et al. [1] and consists of two submodels. In the first drying phase (submodel 1), the surface water evaporates, while in the second drying...

  8. On-line monitoring of pharmaceutical production processes using Hidden Markov Model.

    Science.gov (United States)

    Zhang, Hui; Jiang, Zhuangde; Pi, J Y; Xu, H K; Du, R

    2009-04-01

    This article presents a new method for on-line monitoring of pharmaceutical production process, especially the powder blending process. The new method consists of two parts: extracting features from the Near Infrared (NIR) spectroscopy signals and recognizing patterns from the features. Features are extracted from spectra by using Partial Least Squares method (PLS). The pattern recognition is done by using Hidden Markov Model (HMM). A series of experiments are conducted to evaluate the effectiveness of this new method. In the experiments, wheat powder and corn powder are blended together at a set concentration. The proposed method can effectively detect the blending uniformity (the success rate is 99.6%). In comparison to the conventional Moving Block of Standard Deviation (MBSD), the proposed method has a number of advantages, including higher reliability, higher robustness and more transparent decision making. It can be used for effective on-line monitoring of pharmaceutical production processes.

  9. A GLUE uncertainty analysis of a drying model of pharmaceutical granules

    DEFF Research Database (Denmark)

    Mortier, Séverine Thérèse F.C.; Van Hoey, Stijn; Cierkens, Katrijn;

    2013-01-01

    A shift from batch processing towards continuous processing is of interest in the pharmaceutical industry. However, this transition requires detailed knowledge and process understanding of all consecutive unit operations in a continuous manufacturing line to design adequate control strategies...... uncertainty) originating from uncertainty in input data, model parameters, model structure, boundary conditions and software. In this paper, the model prediction uncertainty is evaluated for a model describing the continuous drying of single pharmaceutical wet granules in a six-segmented fluidized bed drying...... unit, which is part of the full continuous from-powder-to-tablet manufacturing line (Consigma™, GEA Pharma Systems). A validated model describing the drying behaviour of a single pharmaceutical granule in two consecutive phases is used. First of all, the effect of the assumptions at the particle level...

  10. Atmospheric freeze drying for the reduction of powder electrostatics of amorphous, low density, high surface area pharmaceutical powders.

    Science.gov (United States)

    O'Donnell, K P; Cai, Z; Schmerler, P; Williams, R O

    2013-02-01

    Amorphous itraconazole (ITZ) was prepared by Thin Film Freezing (TFF) utilizing 1,4-dioxane as the solvent with subsequent solvent removal via conventional tray lyophilization (ITZ LYO) or atmospheric freeze drying (ITZ AFD). ITZ AFD was prepared under various drying conditions to assess the influence of drying parameters on powder properties. XRD analysis confirmed all products were amorphous and DSC analysis revealed both drying processes resulted in the formation of the nematic mesophase of ITZ. SEM revealed a larger pore size and agglomerate size with fewer fine particles (i.e. less than 10 microns in diameter) for ITZ AFD compared to ITZ LYO. Residual solvent analysis revealed a primary drying temperature of -10°C resulted in residual solvent levels above the acceptable limits set by the International Conference on Harmonization as a result of microcollapse. Primary drying temperatures of less than -10°C resulted in acceptable residual solvent levels. The extent of microcollapse did not alter the macrostructure of the resulting powder. Powder flowability was determined to be similar for ITZ AFD and ITZ LYO based on Carr's index and the Hausner ratio, as well as by dynamic angle of repose. All powders displayed poor flowability. Chargeability measurements demonstrated a lower charge transfer for ITZ AFD powders compared to ITZ LYO due to a combination of factors including differences in residual solvent level, particle size, pore size, surface area, and fine particles content. The reduction in chargeability as a result of AFD is highly desirable because it allows for improved powder handling and use post-production.

  11. Development of a Reproducible Powder Characterization Method using a Powder Rheometer

    DEFF Research Database (Denmark)

    Søgaard, Søren Vinter; Allesø, Morten; Garnæs, Jørgen;

    2012-01-01

    In this study, a powder rheometer was used to measure flow characteristics of two pharmaceutical model powders. Precise measurements were obtained for one of the model powders whereas the results were less precise for the second powder. In conclusion, further work is needed to increase the mechan...

  12. Pharmaceutical aerosols deposition patterns from a Dry Powder Inhaler: Euler Lagrangian prediction and validation.

    Science.gov (United States)

    Ravi Kannan, Ravishekar; Przekwas, A J; Singh, Narender; Delvadia, Renishkumar; Tian, Geng; Walenga, Ross

    2017-04-01

    This study uses Computational Fluid Dynamics (CFD) to predict, analyze and validate the deposition patterns in a human lung for a Budesonide drug delivered from the Novolizer Dry Powder Inhaler device. We used a test case of known deposition patterns to validate our computational Euler Lagrangian-based deposition predictions. Two different lung models are used: (i) a basic ring-less trachea model and (ii) an advanced Human Zygote5 model. Unlike earlier attempts, the current simulations do not include the device in the computational domain. This greatly reduces the computational effort. To mimic the device, we model the inlet particle jet stream from the device as a spray entering the mouth in a conical fashion. Deposition studies in the various lung regions were performed. We were able to computationally predict and then demonstrate the enhanced deposition in the tracheal and first generation rings/ridges. The enhanced vorticity creation due to the ring structure and the geometrical design contributes to larger deposition in the Zygote5 model. These are in accord with existing data, unlike the ring-less model. Our validated results indicate the need to (i) introduce the ridges in the experimental casts and the CFD surface meshes to be anatomically consistent and obtain physiologically consistent depositions; (ii) introduce a factor to account for the recirculating lighter particles in empirical models.

  13. Characterization of cohesive powders for bulk handling and DEM modelling

    NARCIS (Netherlands)

    Thakur, S.C.; Imole, Olukayode Isaiah; Wojtkowski, Mateusz Bronislaw; Magnanimo, Vanessa; Montes, E.C.; Ramaioli, Marco; Ahmadian, H.; Ooi, J.Y.; Bischoff, M.; Ramm, E.; Onate, E; Owen, R.; Wriggers, P.

    2013-01-01

    The flow behaviour of granular materials is relevant for many industrial applications including the pharmaceutical, chemical, consumer goods and food industries. A key issue is the accurate characterisation of these powders under different loading conditions and flow regimes, for example in mixers,

  14. In Silico Models for Ecotoxicity of Pharmaceuticals.

    Science.gov (United States)

    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.

  15. Modeling of Powder Bed Manufacturing Defects

    Science.gov (United States)

    Mindt, H.-W.; Desmaison, O.; Megahed, M.; Peralta, A.; Neumann, J.

    2017-09-01

    Powder bed additive manufacturing offers unmatched capabilities. The deposition resolution achieved is extremely high enabling the production of innovative functional products and materials. Achieving the desired final quality is, however, hampered by many potential defects that have to be managed in due course of the manufacturing process. Defects observed in products manufactured via powder bed fusion have been studied experimentally. In this effort we have relied on experiments reported in the literature and—when experimental data were not sufficient—we have performed additional experiments providing an extended foundation for defect analysis. There is large interest in reducing the effort and cost of additive manufacturing process qualification and certification using integrated computational material engineering. A prerequisite is, however, that numerical methods can indeed capture defects. A multiscale multiphysics platform is developed and applied to predict and explain the origin of several defects that have been observed experimentally during laser-based powder bed fusion processes. The models utilized are briefly introduced. The ability of the models to capture the observed defects is verified. The root cause of the defects is explained by analyzing the numerical results thus confirming the ability of numerical methods to provide a foundation for rapid process qualification.

  16. Modeling powder encapsulation in dosator-based machines: I. Theory.

    Science.gov (United States)

    Khawam, Ammar

    2011-12-15

    Automatic encapsulation machines have two dosing principles: dosing disc and dosator. Dosator-based machines compress the powder to plugs that are transferred into capsules. The encapsulation process in dosator-based capsule machines was modeled in this work. A model was proposed to predict the weight and length of produced plugs. According to the model, the plug weight is a function of piston dimensions, powder-bed height, bulk powder density and precompression densification inside dosator while plug length is a function of piston height, set piston displacement, spring stiffness and powder compressibility. Powder densification within the dosator can be achieved by precompression, compression or both. Precompression densification depends on the powder to piston height ratio while compression densification depends on piston displacement against powder. This article provides the theoretical basis of the encapsulation model, including applications and limitations. The model will be applied to experimental data separately.

  17. SKIM MILK POWDER, WHEY POWDER AND MILK AND WHEY MIXTURES IN POWDER PRODUCED IN MINISPRAY DRYER:ISOTHERM ANALYSIS AND APPLICATION OF THE BET MODEL

    OpenAIRE

    Perrone, Ítalo Tuler; Carvalho, Antônio Fernandes de; Pereira, João Pablo Fortes; Stringueta, Paulo César; Silva, Paulo Henrique Fonseca da

    2013-01-01

    In this study whey powders and skim milk powder were produced in laboratory scale. Water vapor sorption for each powder was measured gravimetrically. The results of the isothermal adsorption were in agreement with the BET model and the quantities of water in the monolayer, obtained by the model, were less than the total quant ities of water in the powder s. Laboratory scale production of milk and whey powders showed that increasing whey percentage in the mixture of milk and whey before drying...

  18. A DEM contact model for history-dependent powder flows

    Science.gov (United States)

    Hashibon, Adham; Schubert, Raphael; Breinlinger, Thomas; Kraft, Torsten

    2016-11-01

    Die filling is an important part of the powder handling process chain that greatly influences the characteristic structure and properties of the final part. Predictive modelling and simulation of the die-filling process can greatly contribute to the optimization of the part and the whole production procedure, e.g. by predicting the resulting powder compaction structure as a function of filling process parameters. The rheology of powders can be very difficult to model especially if heterogeneous agglomeration or time-dependent consolidation effects occur. We present a new discrete element contact force model that enables modelling complex powder flow characteristics including direct time-dependent consolidation effects and load history-dependent cohesion to describe the filling process of complex, difficult to handle powders. The model is demonstrated for simple flow and an industrial powder flow.

  19. Discrete Modelling of Powder Dispersion in Dry Powder Inhalers - A Brief Review.

    Science.gov (United States)

    Tong, Zhenbo; Yu, Aibing; Chan, Hak-Kim; Yang, Runyu

    2015-01-01

    The performance of a dry powder inhaler (DPI) depends on powder properties as well as the air and particle flows in the device. The main principle of powder dispersion is to overcome the inter-particle cohesion using various dispersion/ de-agglomeration forces. While different dispersion mechanisms have been identified, their relative importance under different conditions is less clear. The lack of understanding of these mechanisms is a major obstacle to the advance of pharmaceutical powder aerosol technology. This paper briefly reviews our recent effort in developing a combined computational fluid dynamics (CFD) and discrete element method (DEM) approach to gain such pivotal information. Dispersions under various specifically designed conditions were simulated to exam the role of individual dispersion mechanism. The air and particle flows were analysed at the particle scale and linked to dispersion performance characterised by fine particle fraction (FPF). In addition, the dispersion mechanisms of both drug only and carrier based formulations in a commercial inhaler were studied. Our work shows that the approach has the potential to develop a theoretical framework for designing new DPIs.

  20. Racing to define pharmaceutical R&D external innovation models.

    Science.gov (United States)

    Wang, Liangsu; Plump, Andrew; Ringel, Michael

    2015-03-01

    The pharmaceutical industry continues to face fundamental challenges because of issues with research and development (R&D) productivity and rising customer expectations. To lower R&D costs, move beyond me-too therapies, and create more transformative portfolios, pharmaceutical companies are actively capitalizing on external innovation through precompetitive collaboration with academia, cultivation of biotech start-ups, and proactive licensing and acquisitions. Here, we review the varying innovation strategies used by pharmaceutical companies, compare and contrast these models, and identify the trends in external innovation. We also discuss factors that influence these external innovation models and propose a preliminary set of metrics that could be used as leading indicators of success.

  1. Removal of Trace Pharmaceuticals from Water using coagulation and powdered activated carbon as pretreatment to ultrafiltration membrane system.

    Science.gov (United States)

    Sheng, Chenguang; Nnanna, A G Agwu; Liu, Yanghe; Vargo, John D

    2016-04-15

    In this study, the efficacy of water treatment technologies: ultra-filtration (UF), powdered activated carbon (PAC), coagulation (COA) and a combination of these technologies (PAC/UF and COA/UF) to remove target pharmaceuticals (Acetaminophen, Bezafibrate, Caffeine, Carbamazepine, Cotinine, Diclofenac, Gemfibrozil, Ibuprofen, Metoprolol, Naproxen, Sulfadimethoxine, Sulfamethazine, Sulfamethoxazole, Sulfathiazole, Triclosan and Trimethoprim) was investigated. Samples of wastewater from municipal WWTPs were analyzed using direct aqueous injection High Performance Liquid Chromatography with Tandem Quadrupole Mass Spectrometric (LC/MS/MS) detection. On concentration basis, results showed an average removal efficiency of 29%, 50%, and 7%, respectively, for the UF, PAC dosage of 50ppm, and COA dosage of 10ppm. When PAC dosage of 100ppm was used as pretreatment to the combined PAC and UF in-line membrane system, a 90.3% removal efficiency was achieved. The removal efficiency of UF in tandem with COA was 33%, an increase of 4% compared with the single UF treatment. The adsorption effect of PAC combined with the physical separation process of UF revealed the best treatment strategy for removing pharmaceutical contaminant from water.

  2. Modeling the effects of pharmaceutical marketing

    NARCIS (Netherlands)

    Leeflang, P.S.H.; Wieringa, J.E.

    Successful innovation of prescription drugs requires a substantial amount of marketing support. There is, however, much concern about the effects of marketing expenditures on the demand of pharmaceutical products (Manchanda et al., Market Lett 16(3/4):293-308, 2005). For example, excessive marketing

  3. Modeling the effects of pharmaceutical marketing

    NARCIS (Netherlands)

    Leeflang, P.S.H.; Wieringa, J.E.

    2010-01-01

    Successful innovation of prescription drugs requires a substantial amount of marketing support. There is, however, much concern about the effects of marketing expenditures on the demand of pharmaceutical products (Manchanda et al., Market Lett 16(3/4):293-308, 2005). For example, excessive marketing

  4. Formulation of a Success Model in Pharmaceutical R&D

    Directory of Open Access Journals (Sweden)

    Hyunju Rachel Kim

    2014-03-01

    Full Text Available Recently, pharmaceutical R&D has been demanded to increase productivity in terms of time efficiency and innovation as well. There have been discontinuous challenges coming up in this industry, such as globalized R&D competition, stricter regulation, lengthy process of clinical trials, and so on. Considering external changes, high competition, and discontinuities in the industry, it is a good time to redefine the concept of success in pharmaceutical R&D. Thus, this article attempts to formulate a new success model in pharmaceutical R&D, through contextualizing the industry’s success factors.

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

    Science.gov (United States)

    Butler, Owen; Forder, James; Saunders, John

    2015-03-15

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

  6. Adsorptive Cathodic Stripping Voltammetric Determination of Cefoperazone in Bulk Powder, Pharmaceutical Dosage Forms, and Human Urine

    Science.gov (United States)

    Hoang, Vu Dang; Huyen, Dao Thi; Phuc, Phan Hong

    2013-01-01

    The electroreduction behaviour and determination of cefoperazone using a hanging mercury drop electrode were investigated. Cyclic voltammograms of cefoperazone recorded in universal Britton-Robinson buffers pH 3–6 exhibited a single irreversible cathodic peak. The process was adsorption-controlled. Britton-Robinson buffer 0.04 M pH 4.0 was selected as a supporting electrolyte for quantitative purposes by differential pulse and square wave adsorptive cathodic stripping voltammetry. The experimental voltammetric conditions were optimized using Central Composite Face design. A reduction wave was seen in the range from −0.7 to −0.8 V. These voltammetric techniques were successfully validated as per ICH guidelines and applied for the determination of cefoperazone in its single and sulbactam containing powders for injection and statistically comparable to USP-HPLC. They were further extended to determine cefoperazone in spiked human urine with no matrix effect. PMID:24109542

  7. Adsorptive Cathodic Stripping Voltammetric Determination of Cefoperazone in Bulk Powder, Pharmaceutical Dosage Forms, and Human Urine

    Directory of Open Access Journals (Sweden)

    Vu Dang Hoang

    2013-01-01

    Full Text Available The electroreduction behaviour and determination of cefoperazone using a hanging mercury drop electrode were investigated. Cyclic voltammograms of cefoperazone recorded in universal Britton-Robinson buffers pH 3–6 exhibited a single irreversible cathodic peak. The process was adsorption-controlled. Britton-Robinson buffer 0.04 M pH 4.0 was selected as a supporting electrolyte for quantitative purposes by differential pulse and square wave adsorptive cathodic stripping voltammetry. The experimental voltammetric conditions were optimized using Central Composite Face design. A reduction wave was seen in the range from −0.7 to −0.8 V. These voltammetric techniques were successfully validated as per ICH guidelines and applied for the determination of cefoperazone in its single and sulbactam containing powders for injection and statistically comparable to USP-HPLC. They were further extended to determine cefoperazone in spiked human urine with no matrix effect.

  8. Adsorptive cathodic stripping voltammetric determination of cefoperazone in bulk powder, pharmaceutical dosage forms, and human urine.

    Science.gov (United States)

    Hoang, Vu Dang; Huyen, Dao Thi; Phuc, Phan Hong

    2013-01-01

    The electroreduction behaviour and determination of cefoperazone using a hanging mercury drop electrode were investigated. Cyclic voltammograms of cefoperazone recorded in universal Britton-Robinson buffers pH 3-6 exhibited a single irreversible cathodic peak. The process was adsorption-controlled. Britton-Robinson buffer 0.04 M pH 4.0 was selected as a supporting electrolyte for quantitative purposes by differential pulse and square wave adsorptive cathodic stripping voltammetry. The experimental voltammetric conditions were optimized using Central Composite Face design. A reduction wave was seen in the range from -0.7 to -0.8 V. These voltammetric techniques were successfully validated as per ICH guidelines and applied for the determination of cefoperazone in its single and sulbactam containing powders for injection and statistically comparable to USP-HPLC. They were further extended to determine cefoperazone in spiked human urine with no matrix effect.

  9. The determination of crystal structures of active pharmaceutical ingredients from X-ray powder diffraction data: a brief, practical introduction, with fexofenadine hydrochloride as example.

    Science.gov (United States)

    Brüning, Jürgen; Schmidt, Martin U

    2015-06-01

    This study describes the general method for the determination of the crystal structures of active pharmaceutical ingredients (API) from powder diffraction data and demonstrates its use to determine the hitherto unknown crystal structure of fexofenadine hydrochloride, a third-generation antihistamine drug. Fexofenadine hydrochloride was subjected to a series of crystallisation experiments using re-crystallisation from solvents, gas diffusion, layering with an antisolvent and gel crystallisation. Powder diffraction patterns of all samples were recorded and inspected for polymorphism and for crystallinity. All samples corresponded to the same polymorph. The crystal structure was determined from an X-ray powder diffraction pattern using a real-space method with subsequent Rietveld refinement. The structure exhibits a two-dimensional hydrogen bond network. Crystal structures of API can be determined from X-ray powder diffraction data with good reliability. Fexofenadine exhibits only one polymorphic form, which is stabilised in the crystal by strong hydrogen bonds of the type (+)N-H···Cl(-), O-H···Cl(-), and between COOH groups. © 2015 Royal Pharmaceutical Society.

  10. Models for open innovation in the pharmaceutical industry.

    Science.gov (United States)

    Schuhmacher, Alexander; Germann, Paul-Georg; Trill, Henning; Gassmann, Oliver

    2013-12-01

    The nature of the pharmaceutical industry is such that the main driver for its growth is innovation. In view of the vast challenges that the industry has been facing for several years and, in particular, how to manage stagnating research and development (R&D) productivity, pharmaceutical companies have opened their R&D organizations to external innovation. Here, we identify and characterize four new types of open innovator, which we call 'knowledge creator', 'knowledge integrator', 'knowledge translator' and 'knowledge leverager', and which describe current open R&D models.

  11. Toward better understanding of powder avalanching and shear cell parameters of drug-excipient blends to design minimal weight variability into pharmaceutical capsules.

    Science.gov (United States)

    Nalluri, Venkateshwar Rao; Puchkov, Maxim; Kuentz, Martin

    2013-02-14

    Powder flow of mixtures is complex and not properly understood. The selection of drug-excipient blends with inadequate powder flow can lead to quality issues of the final dosage form. Therefore, this work aims at a better understanding of how changes in powder flow of binary blends can lead to weight variability in pharmaceutical capsule filling. We used image-analysis-based powder avalanching and shear cell testing to study blends of paracetamol and microcrystalline cellulose. A pilot-scale machine with dosator principle was employed for encapsulation. As a result, the powder flow properties improved generally with rising amounts of microcrystalline cellulose. However, a negative correlation was observed between avalanche angle and angle of internal friction. Results were discussed and percolation theory was considered to explain abrupt changes in the observed flow properties. This was particularly helpful for analysis of the capsule-filling data, since capsule weight variability displayed a threshold behavior as a function of the mixture fraction. The capsule weight variability correlated with the angle of internal friction as well as with the angle and the energy of avalanches. Based on the results we proposed a strategy of how to design minimal weight variability into powder-filled capsules.

  12. Business Model Innovation in the Pharmaceutical Industry

    DEFF Research Database (Denmark)

    Ahrensbach Rasmussen, Klement; Foss, Nicolai Juul

    of experimenting with business model. We distinguish between three ideal types, namely a traditionalist model (exemplified by Novo Nordisk), the full-blown service-oriented model (UCB Pharma) and the in-between model (LEO Pharma). We describe the changes to the organizational design and management processes...... that accompany the ongoing process of changing business models in these firms....

  13. Powder and other divided solids mixing. Scale-up and parametric study of a ribbon blender used in pharmaceutical powders mixing.

    Science.gov (United States)

    Côté, Pascal; Abatzoglou, Nicolas

    2006-02-01

    This work is aimed at evaluating the effect of ribbon blender operational parameters on mixture quality. Mix quality parameters and blend uniformity limits are enforced by regulatory bodies. These limits have served in this present work as targets for blending end-points. In a laboratory-scale model ribbon blender, built by scaling down a real industrial unit, powder mixtures composed of white and blue microcrystalline cellulose (MCC) were blended. Blend uniformity was evaluated using a statistical analysis method under various operating conditions such as loading patterns, blender filling percentage, impeller rotational speeds, and mixing times. It was shown that the filling percentage is the most influential mixing parameter. At high impeller rotational speed, the blending end-point was never reached during experimentation.

  14. A constitutive model for sintering of granulated ceramic powders

    Science.gov (United States)

    Shinagawa, K.; Hirashima, Y.

    1998-05-01

    Sintering behavior of granulated powder is investigated to develop a constitutive model for deformation analysis of ceramic powder compacts during sintering. Spray-dried alumina is compacted by CIPing (cold isostatic pressing) and sintered at various temperatures. Shrinkage and the change in grain size of the compacts during sintering are revealed in relation to the inhomogeneous microstructure consisting of fractured and unfractured granules as a consequence of the compaction. A constitutive model for the ceramic powder compacts having the internal structure is presented; The difference in grain growth in dense and sparse regions of the compacts is taken into consideration to the model. The results calculated by the model show good agreement with that obtained by experiment.

  15. Mouse models for atherosclerosis and pharmaceutical modifiers

    NARCIS (Netherlands)

    Zadelaar, A.S.M.; Kleemann, R.; Verschuren, L.; Vries-van der Weij, J. de; Hoorn, J. van der; Princen, H.M.; Kooistra, T.

    2007-01-01

    Atherosclerosis is a multifactorial highly-complex disease with numerous etiologies that work synergistically to promote lesion development. The ability to develop preventive and ameliorative treatments will depend on animal models that mimic the human subject metabolically and pathophysiologically

  16. Mouse models for atherosclerosis and pharmaceutical modifiers

    NARCIS (Netherlands)

    Zadelaar, A.S.M.; Kleemann, R.; Verschuren, L.; Vries-van der Weij, J. de; Hoorn, J. van der; Princen, H.M.; Kooistra, T.

    2007-01-01

    Atherosclerosis is a multifactorial highly-complex disease with numerous etiologies that work synergistically to promote lesion development. The ability to develop preventive and ameliorative treatments will depend on animal models that mimic the human subject metabolically and pathophysiologically

  17. Numerical modelling of cold compaction of metal powder

    DEFF Research Database (Denmark)

    Redanz, Pia

    1998-01-01

    model (J. Mech. Phys. Solids, 1992, 40(5), 1139-1162), developed by Fleck, Kuhr. and McMeeking, and a combination of the two models are used. The friction between the mould wall and the metal powder is modelled by a combination of Coulomb friction and a constant friction shear stress, since Coulomb...... friction is not realistic at high normal pressures. The finite element programme has been used to study the effects of friction, compaction method, and material parameters. Analyses for powder compacts of various geometries are presented to illustrate the method. (C) 1998 Elsevier Science Ltd. All rights...

  18. Ignition of Metal Powders in Combustion Products of Model Fuel

    Science.gov (United States)

    1974-11-13

    y AD/A-001 172 IGNITION OF METAL POWDERS IN COMBUSTION PRODUCTS OF MODEL FUEL A. K. Klyauzov, et al Foreign Technology...S. Air Force UNCLASSIFIED »b. s»ouc » "I»0«T TITLE IGNITION OF METAL POWDERS IN COMBUSTION PRODUCTS OF MODEL FUEL f* OCJCPIPTIVK NOTKI (Typ* o...report mnd Inclumiv «**»••) Translation S »UTMö«I|I ( Firn tSSS», rnlddl* Inltlml, faar .tarna; A. K. Klyauzov, M. M. Arsh, et al 6

  19. Multiscale Modeling of Powder Bed-Based Additive Manufacturing

    Science.gov (United States)

    Markl, Matthias; Körner, Carolin

    2016-07-01

    Powder bed fusion processes are additive manufacturing technologies that are expected to induce the third industrial revolution. Components are built up layer by layer in a powder bed by selectively melting confined areas, according to sliced 3D model data. This technique allows for manufacturing of highly complex geometries hardly machinable with conventional technologies. However, the underlying physical phenomena are sparsely understood and difficult to observe during processing. Therefore, an intensive and expensive trial-and-error principle is applied to produce components with the desired dimensional accuracy, material characteristics, and mechanical properties. This review presents numerical modeling approaches on multiple length scales and timescales to describe different aspects of powder bed fusion processes. In combination with tailored experiments, the numerical results enlarge the process understanding of the underlying physical mechanisms and support the development of suitable process strategies and component topologies.

  20. Analytical method (HPLC), validation used for identification and assay of the pharmaceutical active ingredient, Tylosin tartrate for veterinary use and its finite product Tilodem 50, hydrosoluble powder

    OpenAIRE

    2010-01-01

    In SC DELOS IMPEX ’96 SRL the quality of the active pharmaceutical ingredient (API) for the finite product Tilodem 50 - hydrosoluble powder was acomkplished in the respect of last European Pharmacopoeia.The method for analysis used in this purpose was the compendial method „Tylosin tartrate for veterinary use” in EurPh. in vigour edition and represent a variant developed and validation „in house”.The parameters which was included in the methodology validation for chromatographic method are th...

  1. A novel microwave sensor for real-time online monitoring of roll compacts of pharmaceutical powders online--a comparative case study with NIR.

    Science.gov (United States)

    Gupta, Anshu; Austin, John; Davis, Sierra; Harris, Michael; Reklaitis, Gintaras

    2015-05-01

    Control of particulate processes is hard to achieve because of the ease with which powders tend to segregate. Thus, proper sensing methods must be employed to ensure content uniformity during operation. The role of sensing schemes becomes even more critical while operating the process continuously as measurements are essential for implementation of feedback control (Austin et al. 2013. J Pharm Sci 102(6):1895-1904; Austin et al. 2014. Anal Chim Acta 819:82-93). A microwave sensor was developed and shown to be effective in online measurement of active pharmaceutical ingredient (API) concentration in a powder blend. During powder transport and hopper storage before processing, powder blends may segregate and cause quality deviations in the subsequent tableting operation. Therefore, it is critical to know the API concentration in the ribbons as the content uniformity is fixed once the ribbon is processed. In this study, a novel microwave sensor was developed that could provide measurement of a roller compacted ribbon's API concentration online, along with its density and moisture content. The results indicate that this microwave sensor is capable of increased accuracy compared with a commercially available near-IR probe for the determination of content uniformity and density in roller compacted ribbons online. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  2. Modelling of drying processes of pharmaceutical granules. Pharmaceutical Sciences for the Future of Medicines

    DEFF Research Database (Denmark)

    Mortier, S.T.F.C.; Vedantam, S.; De Beer, T.;

    Tablets are conventionally produced via consecutive batch process steps. Recent introduction of continuous process equipment is gaining industrial importance in pharmaceutics. Transition to continuous production requires improved understanding of all operations, necessitating the development of m...

  3. Preparation of active proteins, vaccines and pharmaceuticals as fine powders using supercritical or near-critical fluids.

    Science.gov (United States)

    Cape, Stephen P; Villa, Joseph A; Huang, Edward T S; Yang, Tzung-Horng; Carpenter, John F; Sievers, Robert E

    2008-09-01

    Supercritical or near-critical fluid processes for generating microparticles have enjoyed considerable attention in the past decade or so, with good success for substances soluble in supercritical fluids or organic solvents. In this review, we survey their application to the production of protein particles. A recently developed process known as CO2-assisted nebulization with a Bubble Dryer (CAN-BD) has been demonstrated to have broad applicability to small-molecule as well as macromolecule substances (including therapeutic proteins). The principles of CAN-BD are discussed as well as the stabilization, micronization and drying of a wide variety of materials. More detailed case studies are presented for three proteins, two of which are of therapeutic interest: anti-CD4 antibody (rheumatoid arthritis), alpha1-antitrypsin (cystic fibrosis and emphysema), and trypsinogen (a model enzyme). Dry powders were formed in which stability and activity are maintained and which are fine enough to be inhaled and reach the deep lung. Enhancement of apparent activity after CAN-BD processing was also observed in some formulation and processing conditions.

  4. Bioprinting towards Physiologically Relevant Tissue Models for Pharmaceutics.

    Science.gov (United States)

    Peng, Weijie; Unutmaz, Derya; Ozbolat, Ibrahim T

    2016-09-01

    Improving the ability to predict the efficacy and toxicity of drug candidates earlier in the drug discovery process will speed up the introduction of new drugs into clinics. 3D in vitro systems have significantly advanced the drug screening process as 3D tissue models can closely mimic native tissues and, in some cases, the physiological response to drugs. Among various in vitro systems, bioprinting is a highly promising technology possessing several advantages such as tailored microarchitecture, high-throughput capability, coculture ability, and low risk of cross-contamination. In this opinion article, we discuss the currently available tissue models in pharmaceutics along with their limitations and highlight the possibilities of bioprinting physiologically relevant tissue models, which hold great potential in drug testing, high-throughput screening, and disease modeling.

  5. A model for optimizing the production of pharmaceutical products

    Directory of Open Access Journals (Sweden)

    Nevena Gospodinova

    2017-05-01

    Full Text Available The problem associated with the optimal production planning is especially relevant in modern industrial enterprises. The most commonly used optimality criteria in this context are: maximizing the total profit; minimizing the cost per unit of production; maximizing the capacity utilization; minimizing the total production costs. This article aims to explore the possibility for optimizing the production of pharmaceutical products through the construction of a mathematical model that can be viewed in two ways – as a single-product model and a multi-product model. As an optimality criterion it is set the minimization of the cost per unit of production for a given planning period. The author proposes an analytical method for solving the nonlinear optimization problem. An optimal production plan of Tylosin tartrate is found using the single-product model.

  6. Ignition of pyrophoric powders: An entry-level model

    Science.gov (United States)

    Alymov, M. I.; Seplyarskii, B. S.; Gordopolova, I. S.

    2015-11-01

    Chemically prepared metal nanopowders are normally pyrophoric, i.e. are liable to ignite spontaneously on exposure to air because of high reactivity and developed specific surface. On the other side, reliable theoretical models for spontaneous self-ignition of fine dispersed powders at room temperature have not been suggested so far. A deeper insight into the mechanism of the phenomenon would shed new light on the critical conditions for self-inflammation and thus would provide some clues for optimization of the passivation of fine dispersed powders. In this work, we formulated and analyzed an entry-level model for ignition of pyrophoric powders. Analysis of such a model in terms of the ignition theory gave the following results. Depending on the width of the reaction zone, the ignition may get started in either one or two stages. The duration of each stage was evaluated by using the approximate methods of combustion theory. The parametric limits for the model applicability were derived and the influence of sample length on the ignition process was explored as well.

  7. Unification of viscose models for powder suspension system

    Institute of Scientific and Technical Information of China (English)

    梁叔全; 李伟洲; 黄伯云

    2002-01-01

    The viscose models for powder suspension system was reviewed and analysed. It is found that by introducing modification function f(φ) in the differential form of classical Einsteins viscosity law, all of viscose models can be unified if f(φ) takes suitable form . Some rational forms of the function f(φ) were discussed according to functional approximation method, and a new rheological model contained two undetermined parameters was consequently developed, more suitable for high particle concentration dispersing system. The experimental results show that this new model is of better consistence.

  8. Models for financing the regulation of pharmaceutical promotion.

    Science.gov (United States)

    Lexchin, Joel

    2012-07-11

    Pharmaceutical companies spend huge sums promoting their products whereas regulation of promotional activities is typically underfinanced. Any option for financing the monitoring and regulation of promotion should adhere to three basic principles: stability, predictability and lack of (perverse) ties between the level of financing and performance. This paper explores the strengths and weaknesses of six different models. All these six models considered here have positive and negative features and none may necessarily be ideal in any particular country. Different countries may choose to utilize a combination of two or more of these models in order to raise sufficient revenue. Financing of regulation of drug promotion should more than pay for itself through the prevention of unnecessary drug costs and the avoidance of adverse health effects due to inappropriate prescribing. However, it involves an initial outlay of money that is currently not being spent and many national governments, in both rich and poor countries, are unwilling to incur extra costs.

  9. Models for financing the regulation of pharmaceutical promotion

    Directory of Open Access Journals (Sweden)

    Lexchin Joel

    2012-07-01

    Full Text Available Abstract Pharmaceutical companies spend huge sums promoting their products whereas regulation of promotional activities is typically underfinanced. Any option for financing the monitoring and regulation of promotion should adhere to three basic principles: stability, predictability and lack of (perverse ties between the level of financing and performance. This paper explores the strengths and weaknesses of six different models. All these six models considered here have positive and negative features and none may necessarily be ideal in any particular country. Different countries may choose to utilize a combination of two or more of these models in order to raise sufficient revenue. Financing of regulation of drug promotion should more than pay for itself through the prevention of unnecessary drug costs and the avoidance of adverse health effects due to inappropriate prescribing. However, it involves an initial outlay of money that is currently not being spent and many national governments, in both rich and poor countries, are unwilling to incur extra costs.

  10. Modelling and simulation in the pharmaceutical industry--some reflections.

    Science.gov (United States)

    Burman, Carl-Fredrik; Wiklund, Stig Johan

    2011-01-01

    Modelling and simulation (M&S) is increasingly being applied in (clinical) drug development. It provides an opportune area for the community of pharmaceutical statisticians to pursue. In this article, we highlight useful principles behind the application of M&S. We claim that M&S should be focussed on decisions, tailored to its purpose and based in applied sciences, not relying entirely on data-driven statistical analysis. Further, M&S should be a continuous process making use of diverse information sources and applying Bayesian and frequentist methodology, as appropriate. In addition to forming a basis for analysing decision options, M&S provides a framework that can facilitate communication between stakeholders. Besides the discussion on modelling philosophy, we also describe how standard simulation practice can be ineffective and how simulation efficiency can often be greatly improved.

  11. Comparison of high sensitivity micro differential scanning calorimetry with X-ray powder diffractometry and FTIR spectroscopy for the characterization of pharmaceutically relevant non-crystalline materials.

    Science.gov (United States)

    Song, M; Liebenberg, W; De Villiers, M M

    2006-04-01

    In this study, high sensitivity micro differential scanning calorimetry (MDSC) in the scanning of dynamic mode was compared to X-ray powder diffractometry (XRPD) for quantifying amorphous nifedipine in mixtures crystalline nifedipine. This technique was also compared with FTIR for quantifying polymorph A of chloramphenicol palmitate (CAP) and poly DL-lactide-co-glycolide) (PLGA) in pharmaceutical formulations. The limit of determination (LOD) achieved by MDSC were 0.06% compared to 5% for XRPD quantification of amorphous nifedipine and 0.02% compared to 7% for IR quanitfication of polymorph A of CAP. As little as 0.165 mg PLGA could be measured in excipients mixtures. Desirable linearity and repeatability were established in all cases.

  12. A COMPREHENSIVE MODEL OF LASER CLADDING BY POWDER FEEDING

    Institute of Scientific and Technical Information of China (English)

    Y.L. Huang; G.Y. Liang; J.Y. Su

    2004-01-01

    A novel model was presented to predict the evolutionary development of cladding layer,and a method based on Lambert-Beer theorem and Mie's theory was adopted to treat the interaction between powder stream and laser beam. By using the continuum model and enthalpy-porosity method, the fluid flow and heat transfer in solid-liquid phase change system were simulated. The commercial software PHOENICS, to which several modules were appended, was used to accomplish the simulation. Numerical computation was performed for Stellite 6 cladding on steel, the obtained results are coincident with those measured in experiment basically.

  13. Real-time in situ powder X-ray diffraction monitoring of mechanochemical synthesis of pharmaceutical cocrystals.

    Science.gov (United States)

    Halasz, Ivan; Puškarić, Andreas; Kimber, Simon A J; Beldon, Patrick J; Belenguer, Ana M; Adams, Frank; Honkimäki, Veijo; Dinnebier, Robert E; Patel, Bhavnita; Jones, William; Strukil, Vjekoslav; Friščić, Tomislav

    2013-10-25

    Looking in: The penetrating power of high-energy X-rays provides a means to monitor in situ and in real time the course of ball-milling reactions of organic pharmaceutical solids by detecting crystalline phases and assessing the evolution of their particle sizes. Upon switching from neat grinding to liquid-assisted grinding, cocrystal formation is enabled or tremendously accelerated, while the reaction mechanism alters its course.

  14. Multi-residue determination of 115 veterinary drugs and pharmaceutical residues in milk powder, butter, fish tissue and eggs using liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Dasenaki, Marilena E; Thomaidis, Nikolaos S

    2015-06-23

    A simple and sensitive multi-residue method for the determination of 115 veterinary drugs and pharmaceuticals, belonging in more than 20 different classes, in butter, milk powder, egg and fish tissue has been developed. The method involves a simple generic solid-liquid extraction step (solvent extraction, SE) with 0.1% formic acid in aqueous solution of EDTA 0.1% (w/v)-acetonitrile (ACN)-methanol (MeOH) (1:1:1, v/v) with additional ultrasonic-assisted extraction. Precipitation of lipids and proteins was promoted by subjecting the extracts at very low temperature (-23°C) for 12h. Further cleanup with hexane ensures fat removal from the matrix. Analysis was performed by liquid chromatography coupled with electrospray ionization and tandem mass spectrometry (LC-ESI-MS/MS). Two separate runs were performed for positive and negative ionization in multiple reaction monitoring mode (MRM). Particular attention was devoted to extraction optimization: different sample-to-extracting volume ratios, different concentrations of formic acid in the extraction solvent and different ultrasonic extraction temperatures were tested in butter, egg and milk powder samples. The method was also applied in fish tissue samples. It was validated, on the basis of international guidelines, for all four matrices. Quantitative analysis was performed by means of standard addition calibration. For over 80% of the analytes, the recoveries were between 50% and 120% in all matrices studied, with RSD values in the range of 1-18%. Limits of detection (LODs) and quantification (LOQs) ranged from 0.008 μg kg(-1) (oxfendazole in butter) to 3.15 μg kg(-1) (hydrochlorthiazide in egg). The evaluated method provides reliable screening, quantification, and identification of 115 veterinary drug and pharmaceutical residues in foods of animal origin and has been successfully applied in real samples.

  15. Adsorption of selected pharmaceuticals and an endocrine disrupting compound by granular activated carbon. 2. Model prediction

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Z.; Peldszus, S.; Huck, P.M. [University of Waterloo, Waterloo, ON (Canada). NSERC Chair in Water Treatment

    2009-03-01

    The adsorption of two representative pharmaceutically active compounds (PhACs) naproxen and carbamazepine and one endocrine disrupting compound (EDC) nonylphenol was studied in pilot-scale granular activated carbon (GAC) adsorbers using post-sedimentation (PS) water from a full-scale drinking water treatment plant. The GAC adsorbents were coal-based Calgon Filtrasorb 400 and coconut shell-based PICA CTIF TE. Acidic naproxen broke through fastest while nonylphenol was removed best, which was consistent with the degree to which fouling affected compound removals. Model predictions and experimental data were generally in good agreement for all three compounds, which demonstrated the effectiveness and robustness of the pore and surface diffusion model (PSDM) used in combination with the time-variable parameter approach for predicting removals at environmentally relevant concentrations (i.e., ng/L range). Sensitivity analyses suggested that accurate determination of film diffusion coefficients was critical for predicting breakthrough for naproxen and carbamazepine, in particular when high removals are targeted. Model simulations demonstrated that GAC carbon usage rates (CURs) for naproxen were substantially influenced by the empty bed contact time (EBCT) at the investigated conditions. Model-based comparisons between GAC CURs and minimum CURs for powdered activated carbon (PAC) applications suggested that PAC would be most appropriate for achieving 90% removal of naproxen, whereas GAC would be more suitable for nonylphenol. 25 refs., 4 figs., 1 tab.

  16. Analytical method (HPLC, validation used for identification and assay of the pharmaceutical active ingredient, Tylosin tartrate for veterinary use and its finite product Tilodem 50, hydrosoluble powder

    Directory of Open Access Journals (Sweden)

    Maria Neagu

    2010-12-01

    Full Text Available In SC DELOS IMPEX ’96 SRL the quality of the active pharmaceutical ingredient (API for the finite product Tilodem 50 - hydrosoluble powder was acomkplished in the respect of last European Pharmacopoeia.The method for analysis used in this purpose was the compendial method „Tylosin tartrate for veterinary use” in EurPh. in vigour edition and represent a variant developed and validation „in house”.The parameters which was included in the methodology validation for chromatographic method are the followings: Selectivity, Linearity, Linearity range, Detection and Quantification limits, Precision, Repeatability (intra day, Inter-Day Reproductibility, Accuracy, Robustness, Solutions’ stability and System suitability. According to the European Pharmacopoeia, the active pharmaceutical ingredient is consistent, in terms of quality, if it contains Tylosin A - minimum 80% and the amount of Tylosin A, B, C, D, at minimum 95%. Identification and determination of each component separately (Tylosin A, B, C, D is possible by chromatographic separation-HPLC. Validation of analytical methods is presented below.

  17. Pilot-scale removal of pharmaceuticals in municipal wastewater: Comparison of granular and powdered activated carbon treatment at three wastewater treatment plants.

    Science.gov (United States)

    Kårelid, Victor; Larsson, Gen; Björlenius, Berndt

    2017-05-15

    Adsorption with activated carbon is widely suggested as an option for the removal of organic micropollutants including pharmaceutically active compounds (PhACs) in wastewater. In this study adsorption with granular activated carbon (GAC) and powdered activated carbon (PAC) was analyzed and compared in parallel operation at three Swedish wastewater treatment plants with the goal to achieve a 95% PhAC removal. Initially, mapping of the prevalence of over 100 substances was performed at each plant and due to low concentrations a final 22 were selected for further evaluation. These include carbamazepine, clarithromycin and diclofenac, which currently are discussed for regulation internationally. A number of commercially available activated carbon products were initially screened using effluent wastewater. Of these, a reduced set was selected based on adsorption characteristics and cost. Experiments designed with the selected carbons in pilot-scale showed that most products could indeed remove PhACs to the target level, both on total and individual basis. In a setup using internal recirculation the PAC system achieved a 95% removal applying a fresh dose of 15-20 mg/L, while carbon usage rates for the GAC application were much broader and ranged from adsorption for a specific PhAC meaning that knowledge of the target pollutants must be acquired before successful design of a treatment system. In spite of different configurations and operating conditions of the different wastewater treatment plants no considerable differences regarding pharmaceutical removal were observed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Solubility Prediction of Active Pharmaceutical Compounds with the UNIFAC Model

    Science.gov (United States)

    Nouar, Abderrahim; Benmessaoud, Ibtissem; Koutchoukali, Ouahiba; Koutchoukali, Mohamed Salah

    2016-03-01

    The crystallization from solution of an active pharmaceutical ingredient requires the knowledge of the solubility in the entire temperature range investigated during the process. However, during the development of a new active ingredient, these data are missing. Its experimental determination is possible, but tedious. UNIFAC Group contribution method Fredenslund et al. (Vapor-liquid equilibria using UNIFAC: a group contribution method, 1977; AIChE J 21:1086, 1975) can be used to predict this physical property. Several modifications on this model have been proposed since its development in 1977, modified UNIFAC of Dortmund Weidlich et al. (Ind Eng Chem Res 26:1372, 1987), Gmehling et al. (Ind Eng Chem Res 32:178, 1993), Pharma-modified UNIFAC Diedrichs et al. (Evaluation und Erweiterung thermodynamischer Modelle zur Vorhersage von Wirkstofflöslichkeiten, PhD Thesis, 2010), KT-UNIFAC Kang et al. (Ind Eng Chem Res 41:3260, 2002), ldots In this study, we used UNIFAC model by considering the linear temperature dependence of interaction parameters as in Pharma-modified UNIFAC and structural groups as defined by KT-UNIFAC first-order model. More than 100 binary datasets were involved in the estimation of interaction parameters. These new parameters were then used to calculate activity coefficient and solubility of some molecules in various solvents at different temperatures. The model gives better results than those from the original UNIFAC and shows good agreement between the experimental solubility and the calculated one.

  19. Development of an integrated performance measurement (PM) model for pharmaceutical industry.

    Science.gov (United States)

    Shabaninejad, Hosein; Mirsalehian, Mohammad Hossein; Mehralian, Gholamhossein

    2014-01-01

    With respect to special characteristics of pharmaceutical industry and lack of reported performance measure, this study tries to design an integrated PM model for pharmaceutical companies. For generating this model; we first identified the key performance indicators (KPIs) and the key result indicators (KRIs) of a typical pharmaceutical company. Then, based on experts᾽ opinions, the identified indicators were ranked with respect to their importance, and the most important of them were selected to be used in the proposed model; In this model, we identified 25 KPIs and 12 KRIs. Although, this model is mostly appropriate to measure the performances of pharmaceutical companies, it can be also used to measure the performances of other industries with some modifications. We strongly recommend pharmaceutical managers to link these indicators with their payment and reward system, which can dramatically affect the performance of employees, and consequently their organization`s success.

  20. Lactose/beta-lactoglobulin interaction during storage of model whey powders.

    Science.gov (United States)

    Thomas, M E C; Scher, J; Desobry, S

    2004-05-01

    The objective of this study was to evaluate the presence or absence of interaction between lactose and beta-lactoglobulin during storage of model whey powders at different water activities (a(w)). Model whey powders were prepared by colyophilization of lactose with increasing quantities of beta-lactoglobulin. These colyophilized beta-lactoglobulin:lactose powders, assigned as BL powders, were stored from 0.11 to 0.95 a(w). The water sorption behavior of BL powders was studied gravimetrically, and the state of lactose was investigated using differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). Before storage, BL powders were amorphous. After storage, a loss of water was observed on moisture sorption isotherms of BL powders. It was related to the formation of lactose crystals, detected by DSC and SEM analysis, and to the structural collapse of the powders. Water loss due to lactose crystallization was shifted to higher a(w) with increasing beta-lactoglobulin content in BL powders. Moreover, kinetics of moisture sorption demonstrated that beta-lactoglobulin was also responsible for a slower crystallization process in BL powders. Then, the water sorption behavior of BL powders was very different from the behavior of the 2 compounds mixed after separate lyophilization. All these results pointed out interaction between lactose and beta-lactoglobulin, which appeared during lyophilization and still occurred during storage. This lactose/beta-lactoglobulin interaction stabilized model whey powders against lactose crystallization.

  1. Decoupling the contribution of dispersive and acid-base components of surface energy on the cohesion of pharmaceutical powders.

    Science.gov (United States)

    Shah, Umang V; Olusanmi, Dolapo; Narang, Ajit S; Hussain, Munir A; Tobyn, Michael J; Heng, Jerry Y Y

    2014-11-20

    This study reports an experimental approach to determine the contribution from two different components of surface energy on cohesion. A method to tailor the surface chemistry of mefenamic acid via silanization is established and the role of surface energy on cohesion is investigated. Silanization was used as a method to functionalize mefenamic acid surfaces with four different functional end groups resulting in an ascending order of the dispersive component of surface energy. Furthermore, four haloalkane functional end groups were grafted on to the surface of mefenamic acid, resulting in varying levels of acid-base component of surface energy, while maintaining constant dispersive component of surface energy. A proportional increase in cohesion was observed with increases in both dispersive as well as acid-base components of surface energy. Contributions from dispersive and acid-base surface energy on cohesion were determined using an iterative approach. Due to the contribution from acid-base surface energy, cohesion was found to increase ∼11.7× compared to the contribution from dispersive surface energy. Here, we provide an approach to deconvolute the contribution from two different components of surface energy on cohesion, which has the potential of predicting powder flow behavior and ultimately controlling powder cohesion.

  2. Pharmaceutical interventions for mitigating an influenza pandemic : modeling the risks and health-economic impacts

    NARCIS (Netherlands)

    Postma, Maarten J.; Milne, George; Nelson, E. Anthony S.; Pyenson, Bruce; Basili, Marcello; Coker, Richard; Oxford, John; Garrison, Louis P.

    2010-01-01

    Model-based analyses built on burden-of-disease and cost effectiveness theory predict that pharmaceutical interventions may efficiently mitigate both the epidemiologic and economic impact of an influenza pandemic. Pharmaceutical interventions typically encompass the application of (pre)pandemic infl

  3. A Constitutive Model for Uni-axial Compaction of Non-adhesive Corn Stalk Powder

    Institute of Scientific and Technical Information of China (English)

    Zhao Dong; Sun Yanling

    2004-01-01

    In order to study mechanical behaviors of corn stalk powder during the compaction, the yield criterion for corn stalk powder is proposed with a plasticity theory. From the stress-strain curves of uni-axial compaction test for corn stalk powder, the constitutive model, in which the equations are modified by experiments on corn stalk powder, is adopted to describe plastic behaviors of powder, and is discussed based on the incremental theory and deformation theory. The numerical results agree well with the experimental ones.

  4. A Granule Model for Evaluating Adhesion of Pharmaceutical Binders

    Directory of Open Access Journals (Sweden)

    Hossein Orafai

    2003-10-01

    Full Text Available Granule capability is defined in terms of the strength of individual granule and friability of granulation batch to withstand breaking, abrasion and compactibility. Binder(s are added to perform the above properties .The common methods to asses their capability are to test crushing strength of the granules directly and to make statistical analysis and /or testing the friability of bulk granulation. In this work four substrate models including polymethylmetacrylate beads(PMMA,glass powder, acetaminophen, and para-aminobebzoic acid were chosen. The binder models were corn starch, gelatin, methylcellulose (MC and hydroxypropylmethylcellulose (HPMC. After massing the substrates with the binder solutions, discs were produced by the mean of the mold technique. The discs were dried and conditioned and then tested for tensile strength while the failed areas were scanned by SEM. Various granulations were made and the results of friability and crush strength were compared with the discs strength .The bond areas in the SEM showed the trend with the binder concentration .A comparison of the standard deviation shows that discs have much lower level of the strength than granules. The resulting discs showed a higher performance which is related to the stems for the discs shape .In conclusion, this method is a simple and is applicable to differentiate efficacy of binder under studies.

  5. Linear model applied to the evaluation of pharmaceutical stability data

    Directory of Open Access Journals (Sweden)

    Renato Cesar Souza

    2013-09-01

    Full Text Available The expiry date on the packaging of a product gives the consumer the confidence that the product will retain its identity, content, quality and purity throughout the period of validity of the drug. The definition of this term in the pharmaceutical industry is based on stability data obtained during the product registration. By the above, this work aims to apply the linear regression according to the guideline ICH Q1E, 2003, to evaluate some aspects of a product undergoing in a registration phase in Brazil. With this propose, the evaluation was realized with the development center of a multinational company in Brazil, with samples of three different batches composed by two active principal ingredients in two different packages. Based on the preliminary results obtained, it was possible to observe the difference of degradation tendency of the product in two different packages and the relationship between the variables studied, added knowledge so new models of linear equations can be applied and developed for other products.

  6. Modeling the Temperature Fields of Copper Powder Melting in the Process of Selective Laser Melting

    Science.gov (United States)

    Saprykin, A. A.; Ibragimov, E. A.; Babakova, E. V.

    2016-08-01

    Various process variables influence on the quality of the end product when SLM (Selective Laser Melting) synthesizing items of powder materials. The authors of the paper suggest using the model of distributing the temperature fields when forming single tracks and layers of copper powder PMS-1. Relying on the results of modeling it is proposed to reduce melting of powder particles out of the scanning area.

  7. Antisolvent crystallization of pharmaceutical excipients from aqueous solutions and the use of preferred orientation in phase identification by powder X-ray diffraction.

    Science.gov (United States)

    Crisp, J L; Dann, S E; Blatchford, C G

    2011-04-18

    Crystallization of lactose from 10% (w/v) aqueous solutions was investigated with the use of polar antisolvents. Crystal growth was observed at 50-65% antisolvent content and showed a morphological transition from a polyhedral to needle-like habit with increasing antisolvent content, which coincided with a polymorphic transition from alpha lactose monohydrate (Lα·H(2)O) to beta lactose (Lβ). Where dehydrating antisolvents were employed such as methanol and ethanol, evidence of Lα·H(2)O dehydration to form Lα(S) was also observed at 95% antisolvent content. Powder X-ray diffraction (PXRD) analysis of the crystals highlighted the preferred orientation effects exhibited by large crystals of this kind, indicating the difficulties experienced by the non-specialist when performing phase identification of lactose polymorphs. The same studies were applied to raffinose pentahydrate, trehalose dihydrate and mannitol to assess the effects of crystallization conditions on other pharmaceutical excipients. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Ototoxicity of boric acid powder in a rat animal model.

    Science.gov (United States)

    Salihoglu, Murat; Dogru, Salim; Cesmeci, Enver; Caliskan, Halil; Kurt, Onuralp; Kuçukodaci, Zafer; Gungor, Atila

    2017-04-22

    Boric acid, which has antiseptic and acidic properties, is used to treat external and middle ear infections. However, we have not found any literature about the effect of boric acid powder on middle ear mucosa and inner ear. The purpose of this study is to investigate possible ototoxic effects of boric acid powder (BAP) on cochlear outer hair cell function and histological changes in middle ear mucosa in a rat animal model. Twenty healthy, mature Wistar albino rats were used in this study. The rats were divided into two groups, Group A and Group B, each of which consisted of 10 rats. Initially, the animals in each group underwent distortion product otoacoustic emissions (DPOAE) testing of their right and left ears. After the first DPOAE test, a surgical microscope was used to make a small perforation in both ears of the rats in each group, and a second DPOAE test was used to measure both ears in all of the rats. BAP was applied to the right middle ear of the rats using tympanic membrane perforation, and the DPOAEs were measured immediately after the BAP application. The histological changes and DPOAEs were evaluated three days later in Group A and 40 days later in Group B. No significant differences were found at all of the DPOAE frequencies. In Group A, mild inflammation of the middle ear mucosa was found on the third day after BAP application. In Group B, BAP caused mild inflammatory changes on the 40th day, which declined over time. Those changes did not lead to significant fibrosis within the mucosa. In rats, BAP causes mild inflammation in middle ear mucosa and it has no ototoxic effects on cochlear outer hair cell function in the inner ear of rats. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  9. Powdered hide model for vegetable tanning II. hydrolyzable tannin

    Science.gov (United States)

    Vegetable tannages employ both condensed and hydrolyzable tannins. As part of our exploration of tanning mechanisms, we reported last year on interactions of the condensed tannin, quebracho, with powdered hide. In this study, the interactions of chestnut extract, a hydrolyzable tannin, with powdere...

  10. Advances in Thermal Modeling of Selective Laser Sintering of Metal Powders

    CERN Document Server

    Xiao, Bin

    2016-01-01

    Selective laser sintering (SLS) of single component metal powders is a rapid prototyping technology in which a high-energy laser beam scans, melts, shrinks and consolidates metal powders with single component. For better understanding physical mechanisms during laser sintering of single-component metal particles, a temperature transforming model with the consideration of shrinkage and convective flows is introduced to analyze the thermal/fluid behaviors in selective laser sintering of single powder layer. The model is also applied to investigate the sintering of powders on top of existing sintered layers under single- multiple-line scanning manners according to the practical manufacturing processes.

  11. Modelling the effects of promotion expenditures on sales of pharmaceuticals

    NARCIS (Netherlands)

    Wieringa, Jaap E.; Leeflang, Peter S. H.

    2013-01-01

    The successful innovation of pharmaceuticals requires a substantial amount of marketing support, despite concerns about the effects of these marketing efforts. This study considers prior findings that indicate that higher marketing expenditures for a brand reduce its price elasticity of demand, whic

  12. Modelling the effects of promotion expenditures on sales of pharmaceuticals

    NARCIS (Netherlands)

    Wieringa, Jaap E.; Leeflang, Peter S. H.

    2013-01-01

    The successful innovation of pharmaceuticals requires a substantial amount of marketing support, despite concerns about the effects of these marketing efforts. This study considers prior findings that indicate that higher marketing expenditures for a brand reduce its price elasticity of demand,

  13. Physiologically based pharmacokinetic modeling in drug discovery and development: a pharmaceutical industry perspective.

    Science.gov (United States)

    Jones, H M; Chen, Y; Gibson, C; Heimbach, T; Parrott, N; Peters, S A; Snoeys, J; Upreti, V V; Zheng, M; Hall, S D

    2015-03-01

    The application of physiologically based pharmacokinetic (PBPK) modeling has developed rapidly within the pharmaceutical industry and is becoming an integral part of drug discovery and development. In this study, we provide a cross pharmaceutical industry position on "how PBPK modeling can be applied in industry" focusing on the strategies for application of PBPK at different stages, an associated perspective on the confidence and challenges, as well as guidance on interacting with regulatory agencies and internal best practices.

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

    Science.gov (United States)

    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.

  15. An analytical model of beam attenuation and powder heating during coaxial laser direct metal deposition

    Science.gov (United States)

    Pinkerton, Andrew J.

    2007-12-01

    In the laser direct metal deposition process, interaction between the laser beam and powder from a coaxial powder delivery nozzle alters the temperature of powder and the amount and spatial distribution of laser intensity reaching the deposition melt pool. These factors significantly affect the process and are also important input parameters for any finite element or analytical models of the melt pool and deposition tracks. The analytical model in this paper presents a method to calculate laser attenuation and powder temperatures at every point below such a nozzle. It is applicable to laser beams that are approximately parallel over the beam-powder interaction distance of any initial intensity distribution (Top Hat, Gaussian, TEM01ast or other). The volume below the nozzle is divided into the region above the powder consolidation plane, where the powder stream is annular, and below it, where it is a single Gaussian stream, and expressions derived for each region. Modelled and measured results are reasonably matched. Results indicate that attenuation is more severe once the annular powder stream has consolidated into a single stream but is not zero before that point. The temperature of powder reaching any point is not constant but the mean value is a maximum at the centre of the stream.

  16. Effect of decellularized tissue powders on a rat model of acute myocardial infarction.

    Science.gov (United States)

    Tabuchi, Masaki; Negishi, Jun; Yamashita, Akitatsu; Higami, Tetsuya; Kishida, Akio; Funamoto, Seiichi

    2015-11-01

    Many research groups are currently investigating new treatment modalities for myocardial infarction. Numerous aspects need to be considered for the clinical application of these therapies, such as low cell integration and engraftment rates of cell injection techniques. Decellularized tissues are considered good materials for promoting regeneration of traumatic tissues. The properties of the decellularized tissues are sustained after processing to powder form. In this study, we examined the use of decellularized tissue powder in a rat model of acute myocardial infarction. The decellularized tissue powders, especially liver powder, promoted cell integration and neovascularization both in vitro and in vivo. Decellularized liver powder induced neovascularization in the infarct area, resulting in the suppression of myocardial necrosis. The results of this study suggest that decellularized liver powder has good potential for application as a blood supply material for the treatment of myocardial infarction.

  17. Thermal conductivity model for powdered materials under vacuum based on experimental studies

    Directory of Open Access Journals (Sweden)

    N. Sakatani

    2017-01-01

    Full Text Available The thermal conductivity of powdered media is characteristically very low in vacuum, and is effectively dependent on many parameters of their constituent particles and packing structure. Understanding of the heat transfer mechanism within powder layers in vacuum and theoretical modeling of their thermal conductivity are of great importance for several scientific and engineering problems. In this paper, we report the results of systematic thermal conductivity measurements of powdered media of varied particle size, porosity, and temperature under vacuum using glass beads as a model material. Based on the obtained experimental data, we investigated the heat transfer mechanism in powdered media in detail, and constructed a new theoretical thermal conductivity model for the vacuum condition. This model enables an absolute thermal conductivity to be calculated for a powder with the input of a set of powder parameters including particle size, porosity, temperature, and compressional stress or gravity, and vice versa. Our model is expected to be a competent tool for several scientific and engineering fields of study related to powders, such as the thermal infrared observation of air-less planetary bodies, thermal evolution of planetesimals, and performance of thermal insulators and heat storage powders.

  18. Modeling conversion of ammonium diuranate (ADU) into uranium dioxide (UO2) powder

    Science.gov (United States)

    Hung, Nguyen Trong; Thuan, Le Ba; Khoai, Do Van; Lee, Jin-Young; Jyothi, Rajesh Kumar

    2016-10-01

    In the paper, Brandon mathematical model that describes the relationship between the essential fabrication parameters [reduction temperature (TR), calcination temperature (TC), calcination time (tC) and reduction time (tR)] and specific surface area of ammonium diuranate (ADU)-derived UO2 powder products was established. The proposed models can be used to predict and control the specific surface area of UO2 powders prepared through ADU route. Suitable temperatures for conversion of ADU and ammonium uranyl carbonate (AUC) was examined with the proposed model through assessment of the sinterability of UO2 powders.

  19. Monitoring and modelling of a continuous from-powder-to-tablet process line

    DEFF Research Database (Denmark)

    Mortier, Séverine T.F.C.; Nopens, Ingmar; De Beer, Thomas

    2014-01-01

    The intention to shift from batch to continuous production processes within the pharmaceutical industry enhances the need to monitor and control the process in-line and real-time to continuously guarantee the end-product quality. Mass and energy balances have been successfully applied to a drying...... process which is part of a continuous from-powder-to-tablet manufacturing line to calculate the residual moisture content of granules leaving the drying unit on the basis of continuously generated data from univariate sensors. Next to monitoring, the application of continuous processes demands also real...

  20. Modeling of laser radiation transport in powder beds with high-dispersive metal particles

    Energy Technology Data Exchange (ETDEWEB)

    Kharanzhevskiy, Evgeny, E-mail: eh@udsu.ru [Udmurt State University, 426034 Universitetskaya St., 1, Izhevsk (Russian Federation); Kostenkov, Sergey [Udmurt State University, 426034 Universitetskaya St., 1, Izhevsk (Russian Federation)

    2014-02-15

    Highlights: ► Transport of laser energy in dispersive powder beds was numerically simulated. ► The results of simulating are compared with physicals experiments. ► We established the dependence of the extinction coefficient from powder properties. ► A confirmation of a geometric optic approach for monodisperse powders was proposed. -- Abstract: Two-dimensional transfer of laser radiation in a high-dispersive powder heterogeneous media is numerically calculated. The size of particles is comparable with the wave length of laser radiation so the model takes into account all known physical effects that are occurred on the vacuum–metal surface interface. It is shown that in case of small particles size both morphology of powder particles and porosity of beds influence on absorptance by the solid phase and laser radiation penetrate deep into the area of geometric shadow. Intensity of laser radiation may be described as a function corresponded to the Beer–Lambert–Bouguer law.

  1. DEVELOPMENT OF FUZZY MODEL FOR POWDER MIXED ELECTRO DISCHARGE MACHINING USING COPPER AND GRAPHITE TOOL MATERIAL

    Directory of Open Access Journals (Sweden)

    SONI S.S.

    2012-09-01

    Full Text Available This paper describes development of fuzzy logic model for powder mixed electro discharge machining (PMEDM process. The developed fuzzy model implements triangular and trapezoidal membership functionsfor fuzzification and centre-of-area method for defuzzification processes. The process parameters selected as control variables for experimental work were tool material, type of powder, concentration of powder in dielectric medium and peak current. The machining operation was conducted by using copper and graphite as electrode material on mild steel workpiece material. The powder additives used in the experiment were aluminum and silicon because of their significantly different electrical and thermal properties. The dielectric fluid used was kerosene. The response parameters selected are material removal rate and electrode wear rate. Response surfaces are developed from the developed fuzzy system model. Also exemplar plot developed to compare the responses from fuzzy model and experiment.

  2. Analysis of the cold compaction behavior of titanium powders: a comprehensive inter-model comparison study of compaction equations

    CSIR Research Space (South Africa)

    Machaka, R

    2015-05-01

    Full Text Available A brief background to compaction equations and their application to titanium powder is presented. The behavior and mechanisms of densification in selected titanium powders is critically analyzed by means of a comprehensive inter-model comparison...

  3. A user-friendly model for spray drying to aid pharmaceutical product development

    NARCIS (Netherlands)

    Grasmeijer, Niels; de Waard, Hans; Hinrichs, Wouter L J; Frijlink, Henderik W

    2013-01-01

    The aim of this study was to develop a user-friendly model for spray drying that can aid in the development of a pharmaceutical product, by shifting from a trial-and-error towards a quality-by-design approach. To achieve this, a spray dryer model was developed in commercial and open source spreadshe

  4. STOCHASTIC MODELING OF OPTIMIZED CREDIT STRATEGY OF A DISTRIBUTING COMPANY ON THE PHARMACEUTICAL MARKET

    Directory of Open Access Journals (Sweden)

    M. Boychuk

    2015-10-01

    Full Text Available The activity of distribution companies is multifaceted. Ihey establish contacts with producers and consumers, determine the range of prices of medicines, do promotions, hold stocks of pharmaceuticals and take risks in their further selling.Their internal problems are complicated by the political crisis in the country, decreased purchasing power of national currency, and the rise in interest rates on loans. Therefore the usage of stochastic models of dynamic systems for the research into optimizing the management of pharmaceutical products distribution companies taking into account credit payments is of great current interest. A stochastic model of the optimal credit strategy of a pharmaceutical distributor in the market of pharmaceutical products has been constructed in the article considering credit payments and income limitations. From the mathematical point of view the obtained problem is the one of stochastic optimal control where the amount of monetary credit is the control and the amount of pharmaceutical product is the solution curve. The model allows to identify the optimal cash loan and the corresponding optimal quantity of pharmaceutical product that comply with the differential model of the existing quantity of pharmaceutical products in the form of Ito; the condition of the existing initial stock of pharmaceutical products; the limitation on the amount of credit and profit received from the product selling and maximize the average integral income. The research of the stochastic optimal control problem involves the construction of the left process of crediting with determination of the shift point of that control, the choice of the right crediting process and the formation of the optimal credit process. It was found that the optimal control of the credit amount and the shift point of that control are the determined values and don’t depend on the coefficient in the Wiener process and the optimal trajectory of the amount of

  5. An export-marketing model for pharmaceutical firms (the case of iran).

    Science.gov (United States)

    Mohammadzadeh, Mehdi; Aryanpour, Narges

    2013-01-01

    Internationalization is a matter of committed decision-making that starts with export marketing, in which an organization tries to diagnose and use opportunities in target markets based on realistic evaluation of internal strengths and weaknesses with analysis of macro and microenvironments in order to gain presence in other countries. A developed model for export and international marketing of pharmaceutical companies is introduced. The paper reviews common theories of the internationalization process, followed by examining different methods and models for assessing preparation for export activities and examining conceptual model based on a single case study method on a basket of seven leading domestic firms by using mainly questionares as the data gathering tool along with interviews for bias reduction. Finally, in keeping with the study objectives, the special aspects of the pharmaceutical marketing environment have been covered, revealing special dimensions of pharmaceutical marketing that have been embedded within the appropriate base model. The new model for international activities of pharmaceutical companies was refined by expert opinions extracted from result of questionnaires.

  6. Multipole electron-density modelling of synchrotron powder diffraction data: the case of diamond

    DEFF Research Database (Denmark)

    Svendsen, H.; Overgaard, J.; Busselez, R.;

    2010-01-01

    Accurate structure factors are extracted from synchrotron powder diffraction data measured on crystalline diamond based on a novel multipole model division of overlapping reflection intensities. The approach limits the spherical-atom bias in structure factors extracted from overlapping powder data...... parameter. This directly exposes a correlation between electron density and thermal parameters even for a light atom such as carbon, and it also underlines that in organic systems proper deconvolution of thermal motion is important for obtaining correct static electron densities....

  7. Modelling the occurrence, transport and fate of pharmaceuticals in wastewater systems

    DEFF Research Database (Denmark)

    Snip, Laura J.P.; Flores Alsina, Xavier; Plósz, Benedek Gy

    2014-01-01

    This paper demonstrates how occurrence, transport and fate of pharmaceuticals at trace levels can be assessed when modelling wastewater treatment systems using two case studies. Firstly, two approaches based on: 1) phenomenology; and, 2) Markov Chains, are developed to describe the dynamics of ph...

  8. Macro-economic factors influencing the architectural business model shift in the pharmaceutical industry.

    Science.gov (United States)

    Dierks, Raphaela Marie Louisa; Bruyère, Olivier; Reginster, Jean-Yves; Richy, Florent-Frederic

    2016-10-01

    Technological innovations, new regulations, increasing costs of drug productions and new demands are only few key drivers of a projected alternation in the pharmaceutical industry. The purpose of this review is to understand the macro economic factors responsible for the business model revolution to possess a competitive advantage over market players. Areas covered: Existing literature on macro-economic factors changing the pharmaceutical landscape has been reviewed to present a clear image of the current market environment. Expert commentary: Literature shows that pharmaceutical companies are facing an architectural alteration, however the evidence on the rationale driving the transformation is outstanding. Merger & Acquisitions (M&A) deals and collaborations are headlining the papers. Q1 2016 did show a major slowdown in M&A deals by volume since 2013 (with deal cancellations of Pfizer and Allergan, or the downfall of Valeant), but pharmaceutical analysts remain confident that this shortfall was a consequence of the equity market volatility. It seems likely that the shift to an M&A model will become apparent during the remainder of 2016, with deal announcements of Abbott Laboratories, AbbVie and Sanofi worth USD 45billion showing the appetite of big pharma companies to shift from the fully vertical integrated business model to more horizontal business models.

  9. Asynchronous Training in Pharmaceutical Manufacturing: A Model for University and Industrial Collaboration

    Science.gov (United States)

    Elliot, Norbert; Haggerty, Blake; Foster, Mary; Spak, Gale

    2008-01-01

    The present study documents the results of a 17-month program to train Cardinal Health Pharmaceutical Technology Services (PTS) employees in an innovative model that combines investigative and writing techniques. Designed to address the Code of Federal Regulations (CFR) for the United States Food and Drug Administration (FDA), the program is a…

  10. A Model for Evaluating Pharmaceutical R&D Investment Projects under Technical and Economic Uncertainties

    NARCIS (Netherlands)

    H.P.G. Pennings (Enrico); L. Sereno (Luigi)

    2010-01-01

    textabstractThis study sets up a compound option approach for evaluating pharmaceutical R&D investment projects in the presence of technical and economic uncertainties. Technical uncertainty is modeled as a Poisson jump that allows for failure and thus abandonment of the drug development. Economic u

  11. Asynchronous Training in Pharmaceutical Manufacturing: A Model for University and Industrial Collaboration

    Science.gov (United States)

    Elliot, Norbert; Haggerty, Blake; Foster, Mary; Spak, Gale

    2008-01-01

    The present study documents the results of a 17-month program to train Cardinal Health Pharmaceutical Technology Services (PTS) employees in an innovative model that combines investigative and writing techniques. Designed to address the Code of Federal Regulations (CFR) for the United States Food and Drug Administration (FDA), the program is a…

  12. A Model for Evaluating Pharmaceutical R&D Investment Projects under Technical and Economic Uncertainties

    NARCIS (Netherlands)

    H.P.G. Pennings (Enrico); L. Sereno (Luigi)

    2010-01-01

    textabstractThis study sets up a compound option approach for evaluating pharmaceutical R&D investment projects in the presence of technical and economic uncertainties. Technical uncertainty is modeled as a Poisson jump that allows for failure and thus abandonment of the drug development. Economic

  13. Effect of mechanical denaturation on surface free energy of protein powders

    OpenAIRE

    Mohammad, Mohammad Amin; Grimsey, Ian M.; Forbes, Robert T.; Blagbrough, Ian S; Barbara R. Conway

    2016-01-01

    Globular proteins are important both as therapeutic agents and excipients. However, their fragile native\\ud conformations can be denatured during pharmaceutical processing, which leads to modification of\\ud the surface energy of their powders and hence their performance. Lyophilized powders of hen eggwhite\\ud lysozyme and �-galactosidase from Aspergillus oryzae were used as models to study the effects\\ud of mechanical denaturation on the surface energies of basic and acidic protein powders, r...

  14. Kinetic Hydration Heat Modeling for High-Performance Concrete Containing Limestone Powder

    Directory of Open Access Journals (Sweden)

    Xiao-Yong Wang

    2017-01-01

    Full Text Available Limestone powder is increasingly used in producing high-performance concrete in the modern concrete industry. Limestone powder blended concrete has many advantages, such as increasing the early-age strength, reducing the setting time, improving the workability, and reducing the heat of hydration. This study presents a kinetic model for modeling the hydration heat of limestone blended concrete. First, an improved hydration model is proposed which considers the dilution effect and nucleation effect due to limestone powder addition. A degree of hydration is calculated using this improved hydration model. Second, hydration heat is calculated using the degree of hydration. The effects of water to binder ratio and limestone replacement ratio on hydration heat are clarified. Third, the temperature history and temperature distribution of hardening limestone blended concrete are calculated by combining hydration model with finite element method. The analysis results generally agree with experimental results of high-performance concrete with various mixing proportions.

  15. Modeling of mixing processes: Fluids, particulates, and powders

    Energy Technology Data Exchange (ETDEWEB)

    Ottino, J.M.; Hansen, S. [Northwestern Univ., Evanston, IL (United States)

    1995-12-31

    Work under this grant involves two main areas: (1) Mixing of Viscous Liquids, this first area comprising aggregation, fragmentation and dispersion, and (2) Mixing of Powders. In order to produce a coherent self-contained picture, we report primarily on results obtained under (1), and within this area, mostly on computational studies of particle aggregation in regular and chaotic flows. Numerical simulations show that the average cluster size of compact clusters grows algebraically, while the average cluster size of fractal clusters grows exponentially; companion mathematical arguments are used to describe the initial growth of average cluster size and polydispersity. It is found that when the system is well mixed and the capture radius independent of mass, the polydispersity is constant for long-times and the cluster size distribution is self-similar. Furthermore, our simulations indicate that the fractal nature of the clusters is dependent upon the mixing.

  16. Pharmaceutical Metabolism in Fish: Using a 3-D Hepatic In Vitro Model to Assess Clearance

    Science.gov (United States)

    Baron, Matthew G.; Mintram, Kate S.; Owen, Stewart F.; Hetheridge, Malcolm J.; Moody, A. John; Purcell, Wendy M.; Jackson, Simon K.; Jha, Awadhesh N.

    2017-01-01

    At high internal doses, pharmaceuticals have the potential for inducing biological/pharmacological effects in fish. One particular concern for the environment is their potential to bioaccumulate and reach pharmacological levels; the study of these implications for environmental risk assessment has therefore gained increasing attention. To avoid unnecessary testing on animals, in vitro methods for assessment of xenobiotic metabolism could aid in the ecotoxicological evaluation. Here we report the use of a 3-D in vitro liver organoid culture system (spheroids) derived from rainbow trout to measure the metabolism of seven pharmaceuticals using a substrate depletion assay. Of the pharmaceuticals tested, propranolol, diclofenac and phenylbutazone were metabolised by trout liver spheroids; atenolol, metoprolol, diazepam and carbamazepine were not. Substrate depletion kinetics data was used to estimate intrinsic hepatic clearance by this spheroid model, which was similar for diclofenac and approximately 5 fold higher for propranolol when compared to trout liver microsomal fraction (S9) data. These results suggest that liver spheroids could be used as a relevant and metabolically competent in vitro model with which to measure the biotransformation of pharmaceuticals in fish; and propranolol acts as a reproducible positive control. PMID:28045944

  17. Changing R&D models in research-based pharmaceutical companies.

    Science.gov (United States)

    Schuhmacher, Alexander; Gassmann, Oliver; Hinder, Markus

    2016-04-27

    New drugs serving unmet medical needs are one of the key value drivers of research-based pharmaceutical companies. The efficiency of research and development (R&D), defined as the successful approval and launch of new medicines (output) in the rate of the monetary investments required for R&D (input), has declined since decades. We aimed to identify, analyze and describe the factors that impact the R&D efficiency. Based on publicly available information, we reviewed the R&D models of major research-based pharmaceutical companies and analyzed the key challenges and success factors of a sustainable R&D output. We calculated that the R&D efficiencies of major research-based pharmaceutical companies were in the range of USD 3.2-32.3 billion (2006-2014). As these numbers challenge the model of an innovation-driven pharmaceutical industry, we analyzed the concepts that companies are following to increase their R&D efficiencies: (A) Activities to reduce portfolio and project risk, (B) activities to reduce R&D costs, and (C) activities to increase the innovation potential. While category A comprises measures such as portfolio management and licensing, measures grouped in category B are outsourcing and risk-sharing in late-stage development. Companies made diverse steps to increase their innovation potential and open innovation, exemplified by open source, innovation centers, or crowdsourcing, plays a key role in doing so. In conclusion, research-based pharmaceutical companies need to be aware of the key factors, which impact the rate of innovation, R&D cost and probability of success. Depending on their company strategy and their R&D set-up they can opt for one of the following open innovators: knowledge creator, knowledge integrator or knowledge leverager.

  18. CFD modeling of pharmaceutical isolators with experimental verification of airflow.

    Science.gov (United States)

    Nayan, N; Akay, H U; Walsh, M R; Bell, W V; Troyer, G L; Dukes, R E; Mohan, P

    2007-01-01

    Computational fluid dynamics (CFD) models have been developed to predict the airflow in a transfer isolator using a commercial CFD code. In order to assess the ability of the CFD approach in predicting the flow inside an isolator, hot wire anemometry measurements and a novel experimental flow visualization technique consisting of helium-filled glycerin bubbles were used. The results obtained have been shown to agree well with the experiments and show that CFD can be used to model barrier systems and isolators with practical fidelity. This indicates that CFD can and should be used to support the design, testing, and operation of barrier systems and isolators.

  19. A model-based systems approach to pharmaceutical product-process design and analysis

    DEFF Research Database (Denmark)

    Gernaey, Krist; Gani, Rafiqul

    2010-01-01

    This is a perspective paper highlighting the need for systematic model-based design and analysis in pharmaceutical product-process development. A model-based framework is presented and the role, development and use of models of various types are discussed together with the structure of the models...... for the product and the process. The need for a systematic modelling framework is highlighted together with modelling issues related to model identification, adaptation and extension. In the area of product design and analysis, predictive models are needed with a wide application range. In the area of process...... synthesis and design, the use of generic process models from which specific process models can be generated, is highlighted. The use of a multi-scale modelling approach to extend the application range of the property models is highlighted as well. Examples of different types of process models, model...

  20. Modelling ramp-up curves to reflect learning: improving capacity planning in secondary pharmaceutical production

    DEFF Research Database (Denmark)

    Hansen, Klaus Reinholdt Nyhuus; Grunow, Martin

    2015-01-01

    are overestimated. We develop a new method, which captures ramp-up as a function of the cumulative production volume to better reflect the experience gained while producing the new product. The use of the more accurate and computationally effective approach is demonstrated for the case of secondary pharmaceutical...... production. Due to its regulatory framework, this industry cannot fully exploit available capacities during ramp-up. We develop a capacity planning model for a new pharmaceutical drug, which determines the number and location of new production lines and the build-up of inventory such that product...... availability at market launch is ensured. Our MILP model is applied to a real industry case study using three empirically observed ramp-up curves to demonstrate its value as decision support tool. We demonstrate the superiority of our volume-dependent method over the traditional time-dependent ramp...

  1. Towards quality by design in pharmaceutical manufacturing: modelling and control of air jet mills

    Science.gov (United States)

    Bhonsale, Satyajeet; Telen, Dries; Stokbroekx, Bard; Van Impe, Jan

    2017-06-01

    Milling is an important step in pharmaceutical manufacturing as it not only determines the final formulation of the drug product, but also influences the bioavailability and dissolution rate of the active pharmaceutical ingredient (API). In this respect, the air jet mill (AJM) is most commonly used in the pharmaceutical industry as it is a non-contaminating and non-degrading self-classifying process capable of delivering narrow particle size distributions (PSD). Keeping the principles of Quality by Design in mind, the Critical Process Parameters (CPPs) of the AJM have been identified to be the pressures at the grinding nozzles, and the feed rate which affect the PSD, surface charge and the morphology of the product (i.e. the Critical Material Attributes (CMAs)). For the purpose of this research, the PSD is considered to be the only relevant CMA. A population balance based model is proposed to simulate the dynamics milling operation by utilizing the concept of breakage functions. This model agrees qualitatively with experimental observations of the air jet mill unit present at Janssen Pharmaceutica but further steps for model validation need to be carried out.

  2. Towards quality by design in pharmaceutical manufacturing: modelling and control of air jet mills

    Directory of Open Access Journals (Sweden)

    Bhonsale Satyajeet

    2017-01-01

    Full Text Available Milling is an important step in pharmaceutical manufacturing as it not only determines the final formulation of the drug product, but also influences the bioavailability and dissolution rate of the active pharmaceutical ingredient (API. In this respect, the air jet mill (AJM is most commonly used in the pharmaceutical industry as it is a non-contaminating and non-degrading self-classifying process capable of delivering narrow particle size distributions (PSD. Keeping the principles of Quality by Design in mind, the Critical Process Parameters (CPPs of the AJM have been identified to be the pressures at the grinding nozzles, and the feed rate which affect the PSD, surface charge and the morphology of the product (i.e. the Critical Material Attributes (CMAs. For the purpose of this research, the PSD is considered to be the only relevant CMA. A population balance based model is proposed to simulate the dynamics milling operation by utilizing the concept of breakage functions. This model agrees qualitatively with experimental observations of the air jet mill unit present at Janssen Pharmaceutica but further steps for model validation need to be carried out.

  3. Warren-Spring based model for the shear yield locus of cohesive biomass powders

    Science.gov (United States)

    Vanneste-Ibarcq, Clément; Melkior, Thierry; de Ryck, Alain

    2017-06-01

    The objectives of this work are to determine accurately the cohesion of biomass powders from simple measures and to propose a new method for the description of the yield locus of powders with easy to measure parameters. The cohesion of 32 powders (wood, other biomasses and inorganic powders) have been analysed with two methods. The first method is the determination of the yield locus from shear tests at 3 kPa, performed with a powder rheometer, which gives an access to parameters such as cohesion (Y-intercept) and traction (X-intercept). The second method is the measurement of avalanche angles in a rotating drum. A linear relation is found between this angle and the cohesion length, ratio of the cohesion derived from the yield locus and the aerated density. Finally, a model is proposed for the prediction of the cohesion and the yield locus at 3 kPa, using only 2 parameters easy to measure: the avalanche angle and the aerated density.

  4. Molecular Dynamics Simulations of a Powder Model of the Intrinsically Disordered Protein Tau.

    Science.gov (United States)

    Fichou, Yann; Heyden, Matthias; Zaccai, Giuseppe; Weik, Martin; Tobias, Douglas J

    2015-10-01

    The tau protein, whose aggregates are involved in Alzheimer's disease, is an intrinsically disordered protein (IDP) that regulates microtubule activity in neurons. An IDP lacks a single, well-defined structure and, rather, constantly exchanges among multiple conformations. In order to study IDP dynamics, the combination of experimental techniques, such as neutron scattering, and computational techniques, such as molecular dynamics (MD) simulations, is a powerful approach. Amorphous hydrated powder samples have been very useful for studying protein internal dynamics experimentally, e.g., using neutron scattering. Thus, there is demand for realistic in silico models of hydrated protein powders. Here we present an MD simulation analysis of a powder hydrated at 0.4 g water/g protein of the IDP tau in the temperature range 20-300 K. By comparing with neutron scattering data, we identify the protein-water interface as the predominant feature determining IDP dynamics. The so-called protein dynamical transition is shown to be attenuated, but not suppressed, in the parts of the protein that are not exposed to the solvent. In addition, we find similarities in the mean-squared displacements of the core of a globular protein and "dry" clusters formed by the IDP in hydrated powders. Thus, the ps to ns dynamics of proteins in hydrated powders originate mainly from those residues in contact with solvent. We propose that by measuring the dynamics of protein assemblies, such as aggregates, one might assess qualitatively their state of hydration.

  5. Finite Element Modeling and Analysis of Powder Stream in Low Pressure Cold Spray Process

    Science.gov (United States)

    Goyal, Tarun; Walia, Ravinderjit Singh; Sharma, Prince; Sidhu, Tejinder Singh

    2016-07-01

    Low pressure cold gas dynamic spray (LPCGDS) is a coating process that utilize low pressure gas (5-10 bars instead of 25-30 bars) and the radial injection of powder instead of axial injection with the particle range (1-50 μm). In the LPCGDS process, pressurized compressed gas is accelerated to the critical velocity, which depends on length of the divergent section of nozzle, the propellant gas and particle characteristics, and the diameters ratio of the inlet and outer diameters. This paper presents finite element modeling (FEM) of powder stream in supersonic nozzle wherein adiabatic gas flow and expansion of gas occurs in uniform manner and the same is used to evaluate the resultant temperature and velocity contours during coating process. FEM analyses were performed using commercial finite volume package, ANSYS CFD FLUENT. The results are helpful to predict the characteristics of powder stream at the exit of the supersonic nozzle.

  6. Monitoring model drug microencapsulation in PLGA scaffolds using X-ray powder diffraction

    OpenAIRE

    Adeyinka Aina; Manish Gupta; Yamina Boukari; Andrew Morris; Nashiru Billa; Stephen Doughty

    2015-01-01

    The microencapsulation of three model drugs; metronidazole, paracetamol and sulphapyridine into Poly (dl-Lactide-Co-Glycolide) (PLGA) scaffolds were probed using X-ray Powder Diffraction (XRPD). Changes in the diffraction patterns of the PLGA scaffolds after encapsulation was suggestive of a chemical interaction between the pure drugs and the scaffolds and not a physical intermixture.

  7. Monitoring model drug microencapsulation in PLGA scaffolds using X-ray powder d

    Directory of Open Access Journals (Sweden)

    Adeyinka Aina

    2016-03-01

    Full Text Available The microencapsulation of three model drugs; metronidazole, paracetamol and sulphapyridine into Poly (dl-Lactide-Co-Glycolide (PLGA scaffolds were probed using X-ray Powder Diffraction (XRPD. Changes in the diffraction patterns of the PLGA scaffolds after encapsulation was suggestive of a chemical interaction between the pure drugs and the scaffolds and not a physical intermixture.

  8. Monitoring model drug microencapsulation in PLGA scaffolds using X-ray powder diffraction.

    Science.gov (United States)

    Aina, Adeyinka; Gupta, Manish; Boukari, Yamina; Morris, Andrew; Billa, Nashiru; Doughty, Stephen

    2016-03-01

    The microencapsulation of three model drugs; metronidazole, paracetamol and sulphapyridine into Poly (dl-Lactide-Co-Glycolide) (PLGA) scaffolds were probed using X-ray Powder Diffraction (XRPD). Changes in the diffraction patterns of the PLGA scaffolds after encapsulation was suggestive of a chemical interaction between the pure drugs and the scaffolds and not a physical intermixture.

  9. Mechanical characterisation of superconducting BSCCO powder and numerical modelling of the OPIT process

    DEFF Research Database (Denmark)

    Bech, Jakob Ilsted; Eriksen, Morten; Toussaint, F.

    2000-01-01

    Silver/BSCCO composite superconducting tapes are produced using BSCCO-2212 ceramic powder. The manufacturing process implies a large number of forming operations including drawing and rolling. The numerical simulation of the flat rolling process is of a great interest to anticipate the shape....../Prager-Cap plasticity model. Then these data are used to perform the simulation of the wire rolling step....

  10. Industrial application of model predictive control to a milk powder spray drying plant

    DEFF Research Database (Denmark)

    Petersen, Lars Norbert; Poulsen, Niels Kjølstad; Niemann, Hans Henrik

    2016-01-01

    In this paper, we present our first results from an industrial application of model predictive control (MPC) with real-time steady-state target optimization (RTO) for control of an industrial spray dryer that produces enriched milk powder. The MPC algorithm is based on a continuous-time transfer ...

  11. Modeling powder encapsulation in dosator-based machines: II. Experimental evaluation.

    Science.gov (United States)

    Khawam, Ammar; Schultz, Leon

    2011-12-15

    A theoretical model was previously derived to predict powder encapsulation in dosator-based machines. The theoretical basis of the model was discussed earlier. In this part; the model was evaluated experimentally using two powder formulations with substantially different flow behavior. Encapsulation experiments were performed using a Zanasi encapsulation machine under two sets of experimental conditions. Model predicted outcomes such as encapsulation fill weight and plug height were compared to those experimentally obtained. Results showed a high correlation between predicted and actual outcomes demonstrating the model's success in predicting the encapsulation of both formulations. The model is a potentially useful in silico analysis tool that can be used for capsule dosage form development in accordance to quality by design (QbD) principles.

  12. A user-friendly model for spray drying to aid pharmaceutical product development.

    Science.gov (United States)

    Grasmeijer, Niels; de Waard, Hans; Hinrichs, Wouter L J; Frijlink, Henderik W

    2013-01-01

    The aim of this study was to develop a user-friendly model for spray drying that can aid in the development of a pharmaceutical product, by shifting from a trial-and-error towards a quality-by-design approach. To achieve this, a spray dryer model was developed in commercial and open source spreadsheet software. The output of the model was first fitted to the experimental output of a Büchi B-290 spray dryer and subsequently validated. The predicted outlet temperatures of the spray dryer model matched the experimental values very well over the entire range of spray dryer settings that were tested. Finally, the model was applied to produce glassy sugars by spray drying, an often used excipient in formulations of biopharmaceuticals. For the production of glassy sugars, the model was extended to predict the relative humidity at the outlet, which is not measured in the spray dryer by default. This extended model was then successfully used to predict whether specific settings were suitable for producing glassy trehalose and inulin by spray drying. In conclusion, a spray dryer model was developed that is able to predict the output parameters of the spray drying process. The model can aid the development of spray dried pharmaceutical products by shifting from a trial-and-error towards a quality-by-design approach.

  13. Mathematical Model of Hot Metal Desulfurization by Powder Injection

    Directory of Open Access Journals (Sweden)

    Yolanda Cepeda Rodríguez

    2012-01-01

    Full Text Available Although there have been a numerous number of studies on mathematical model of hot metal desulfurization by deep injection of calcium carbide, the research field as a whole is not well integrated. This paper presents a model that takes into account the kinetics, thermodynamics, and transport processes to predict the sulfur levels in the hot metal throughout a blow. The model could be utilized to assess the influence of the treatment temperature, rate of injection, gas flow rate, and initial concentration of sulfur on the desulfurization kinetics. In the second part of this paper an analysis of the industrial data for injection of calcium carbide using this model is described. From a mathematical model that describes the characteristics of a system, it is possible to predict the behavior of the variables involved in the process, resulting in savings of time and money. Discretization is realized through the finite difference method combined with interpolation in the border domain by Taylor series.

  14. Acute toxicities of pharmaceuticals toward green algae. mode of action, biopharmaceutical drug disposition classification system and quantile regression models.

    Science.gov (United States)

    Villain, Jonathan; Minguez, Laetitia; Halm-Lemeille, Marie-Pierre; Durrieu, Gilles; Bureau, Ronan

    2016-02-01

    The acute toxicities of 36 pharmaceuticals towards green algae were estimated from a set of quantile regression models representing the first global quantitative structure-activity relationships. The selection of these pharmaceuticals was based on their predicted environmental concentrations. An agreement between the estimated values and the observed acute toxicity values was found for several families of pharmaceuticals, in particular, for antidepressants. A recent classification (BDDCS) of drugs based on ADME properties (Absorption, Distribution, Metabolism and Excretion) was clearly correlated with the acute ecotoxicities towards algae. Over-estimation of toxicity from our QSAR models was observed for classes 2, 3 and 4 whereas our model results were in agreement for the class 1 pharmaceuticals. Clarithromycin, a class 3 antibiotic characterized by weak metabolism and high solubility, was the most toxic to algae (molecular stability and presence in surface water).

  15. Variation transmission model for setting acceptance criteria in a multi-staged pharmaceutical manufacturing process.

    Science.gov (United States)

    Montes, Richard O

    2012-03-01

    Pharmaceutical manufacturing processes consist of a series of stages (e.g., reaction, workup, isolation) to generate the active pharmaceutical ingredient (API). Outputs at intermediate stages (in-process control) and API need to be controlled within acceptance criteria to assure final drug product quality. In this paper, two methods based on tolerance interval to derive such acceptance criteria will be evaluated. The first method is serial worst case (SWC), an industry risk minimization strategy, wherein input materials and process parameters of a stage are fixed at their worst-case settings to calculate the maximum level expected from the stage. This maximum output then becomes input to the next stage wherein process parameters are again fixed at worst-case setting. The procedure is serially repeated throughout the process until the final stage. The calculated limits using SWC can be artificially high and may not reflect the actual process performance. The second method is the variation transmission (VT) using autoregressive model, wherein variation transmitted up to a stage is estimated by accounting for the recursive structure of the errors at each stage. Computer simulations at varying extent of variation transmission and process stage variability are performed. For the scenarios tested, VT method is demonstrated to better maintain the simulated confidence level and more precisely estimate the true proportion parameter than SWC. Real data examples are also presented that corroborate the findings from the simulation. Overall, VT is recommended for setting acceptance criteria in a multi-staged pharmaceutical manufacturing process.

  16. Modeling of Crystal Orientations in Laser Powder Deposition of Single Crystal Material

    Science.gov (United States)

    Qi, Huan; Liu, Zhaoyang

    This paper presents a numerical model which simulates the dynamic molten pool formation and the crystal orientations of solidified SX alloy in a multi-layer laser powder deposition process. Based on the mathematical model of coaxial laser direct deposition, the effect of parameters (laser power, scanning speed, powder feed rate) on the tendency to form [001] direction expitaxial grains during solidification was evaluated. In the transient three- dimensional model, physical phenomena including heat transfer, melting, grain formation during solidification, mass addition, and fluid flow in the melt pool, were modeled in a self-consistent manner. The temperature fields, fluid flow velocity, clad geometry (width, height and melt pool depth) and grain formation in melting pool of single layer are predicted.

  17. Experiments and modeling of dynamic powder compaction in the scope of deflagration to detonation transition studies

    Science.gov (United States)

    Bodard, S.; Lapébie, E.; Saurel, R.

    2017-01-01

    This paper deals with dynamic compaction of confined powders and associated wave dynamics. An experimental setup has been designed to generate one-dimensional dynamic compaction waves. Quantitative data such as displacement and velocity fields are obtained. A multiphase compaction model is considered as well and its results are compared to experimental data. Grain/wall friction is also modeled as it appeared to have significant effects when considering confined granular beds.

  18. Powder consolidation using cold spray process modeling and emerging applications

    CERN Document Server

    Moridi, Atieh

    2017-01-01

    This book first presents different approaches to modeling of the cold spray process with the aim of extending current understanding of its fundamental principles and then describes emerging applications of cold spray. In the coverage of modeling, careful attention is devoted to the assessment of critical and erosion velocities. In order to reveal the phenomenological characteristics of interface bonding, severe, localized plastic deformation and material jet formation are studied. Detailed consideration is also given to the effect of macroscopic defects such as interparticle boundaries and subsequent splat boundary cracking on the mechanical behavior of cold spray coatings. The discussion of applications focuses in particular on the repair of damaged parts and additive manufacturing in various disciplines from aerospace to biomedical engineering. Key aspects include a systematic study of defect shape and the ability of cold spray to fill the defect, examination of the fatigue behavior of coatings for structur...

  19. A Mathematical Model for the Multiphase Transport and Reaction Kinetics in a Ladle with Bottom Powder Injection

    Science.gov (United States)

    Lou, Wentao; Zhu, Miaoyong

    2017-08-01

    A computation fluid dynamics-population balance model-simultaneous reaction model (CFD-PBM-SRM) coupled model has been proposed to study the multiphase flow behavior and refining reaction kinetics in a ladle with bottom powder injection, and some new and important phenomena and mechanisms are presented. For the multiphase flow behavior, the effects of bubbly plume flow, powder particle motion, particle-particle collision and growth, particle-bubble collision and adhesion, and powder particle removal into top slag are considered. For the reaction kinetics, the mechanisms of multicomponent simultaneous reactions, including Al, S, Si, Mn, Fe, and O, at the multi-interface, including top slag-liquid steel interface, air-liquid steel interface, powder droplet-liquid steel interface, and bubble-liquid steel interface, are presented, and the effect of sulfur solubility in the powder droplet on the desulfurization is also taken into account. Model validation is carried out using hot tests in a 2-t induction furnace with bottom powder injection. The result shows that the powder particles gradually disperse in the entire furnace; in the vicinity of the bottom slot plugs, the desulfurization product CaS is liquid phase, while in the upper region of the furnace, the desulfurization product CaS is solid phase. The predicted sulfur contents by the present model agree well with the measured data in the 2-t furnace with bottom powder injection.

  20. Pharmaceutical interventions for mitigating an influenza pandemic: modeling the risks and health-economic impacts.

    Science.gov (United States)

    Postma, Maarten J; Milne, George; Nelson, E Anthony S; Pyenson, Bruce; Basili, Marcello; Coker, Richard; Oxford, John; Garrison, Louis P

    2010-12-01

    Model-based analyses built on burden-of-disease and cost-effectiveness theory predict that pharmaceutical interventions may efficiently mitigate both the epidemiologic and economic impact of an influenza pandemic. Pharmaceutical interventions typically encompass the application of (pre)pandemic influenza vaccines, other vaccines (notably pneumococcal), antiviral treatments and other drug treatment (e.g., antibiotics to target potential complications of influenza). However, these models may be too limited to capture the full macro-economic impact of pandemic influenza. The aim of this article is to summarize current health-economic modeling approaches to recognize the strengths and weaknesses of these approaches, and to compare these with more recently proposed alternative methods. We conclude that it is useful, particularly for policy and planning purposes, to extend modeling concepts through the application of alternative approaches, including insurers' risk theories, human capital approaches and sectoral and full macro-economic modeling. This article builds on a roundtable meeting of the Pandemic Influenza Economic Impact Group that was held in Boston, MA, USA, in December 2008.

  1. Sonophotolytic degradation of synthetic pharmaceutical wastewater: statistical experimental design and modeling.

    Science.gov (United States)

    Ghafoori, Samira; Mowla, Amir; Jahani, Ramtin; Mehrvar, Mehrab; Chan, Philip K

    2015-03-01

    The merits of the sonophotolysis as a combination of sonolysis (US) and photolysis (UV/H2O2) are investigated in a pilot-scale external loop airlift sonophotoreactor for the treatment of a synthetic pharmaceutical wastewater (SPWW). In the first part of this study, the multivariate experimental design is carried out using Box-Behnken design (BBD). The effluent is characterized by the total organic carbon (TOC) percent removal as a surrogate parameter. The results indicate that the response of the TOC percent removal is significantly affected by the synergistic effects of the linear term of H2O2 dosage and ultrasound power with the antagonistic effect of quadratic term of H2O2 dosage. The statistical analysis of the results indicates a satisfactory prediction of the system behavior by the developed model. In the second part of this study, a novel rigorous mathematical model for the sonophotolytic process is developed to predict the TOC percent removal as a function of time. The mathematical model is based on extensively accepted sonophotochemical reactions and the rate constants in advanced oxidation processes. A good agreement between the model predictions and experimental data indicates that the proposed model could successfully describe the sonophotolysis of the pharmaceutical wastewater.

  2. Critical assessment of inverse gas chromatography as means of assessing surface free energy and acid-base interaction of pharmaceutical powders.

    Science.gov (United States)

    Telko, Martin J; Hickey, Anthony J

    2007-10-01

    Inverse gas chromatography (IGC) has been employed as a research tool for decades. Despite this record of use and proven utility in a variety of applications, the technique is not routinely used in pharmaceutical research. In other fields the technique has flourished. IGC is experimentally relatively straightforward, but analysis requires that certain theoretical assumptions are satisfied. The assumptions made to acquire some of the recently reported data are somewhat modified compared to initial reports. Most publications in the pharmaceutical literature have made use of a simplified equation for the determination of acid/base surface properties resulting in parameter values that are inconsistent with prior methods. In comparing the surface properties of different batches of alpha-lactose monohydrate, new data has been generated and compared with literature to allow critical analysis of the theoretical assumptions and their importance to the interpretation of the data. The commonly used (simplified) approach was compared with the more rigorous approach originally outlined in the surface chemistry literature.

  3. Numerical modeling of sintering of two-component metal powders with laser beams

    Science.gov (United States)

    Niziev, V. G.; Koldoba, A. V.; Mirzade, F. Kh.; Panchenko, V. Ya.; Poveschenko, Yu. A.; Popov, M. V.

    2011-02-01

    Direct laser sintering of a mixture of two metal powders with significantly different melting points is investigated by numerical simulation. The model is based on self-consistent non-linear continuity equations for volume fractions of components and on energy transfer equations for the powder mixture. It includes the movement of the solid particles due to shrinkage because of the density change of the powder mixture and the liquid flow driven by the capillary and gravity forces. The liquid flow is determined by Darcy's law. The effect of surface settlement of the powder is obtained. The width increasing rate of the melting zone depend both on the parameters of the laser radiation (on the power of the beam) and on the physical parameters of the particle's material, and it increases with the increasing of the penetrability or the increasing of the phase-transition heat. The increasing of the laser power under other factors being equal results in the acceleration of the melting front propagation.

  4. Developing a model for agile supply: an empirical study from Iranian pharmaceutical supply chain.

    Science.gov (United States)

    Rajabzadeh Ghatari, Ali; Mehralian, Gholamhossein; Zarenezhad, Forouzandeh; Rasekh, Hamid Reza

    2013-01-01

    Agility is the fundamental characteristic of a supply chain needed for survival in turbulent markets, where environmental forces create additional uncertainty resulting in higher risk in the supply chain management. In addition, agility helps providing the right product, at the right time to the consumer. The main goal of this research is therefore to promote supplier selection in pharmaceutical industry according to the formative basic factors. Moreover, this paper can configure its supply network to achieve the agile supply chain. The present article analyzes the supply part of supply chain based on SCOR model, used to assess agile supply chains by highlighting their specific characteristics and applicability in providing the active pharmaceutical ingredient (API). This methodology provides an analytical modeling; the model enables potential suppliers to be assessed against the multiple criteria using both quantitative and qualitative measures. In addition, for making priority of critical factors, TOPSIS algorithm has been used as a common technique of MADM model. Finally, several factors such as delivery speed, planning and reorder segmentation, trust development and material quantity adjustment are identified and prioritized as critical factors for being agile in supply of API.

  5. Developing a Model for Agile Supply: an Empirical Study from Iranian Pharmaceutical Supply Chain

    Science.gov (United States)

    Rajabzadeh Ghatari, Ali; Mehralian, Gholamhossein; Zarenezhad, Forouzandeh; Rasekh, Hamid Reza

    2013-01-01

    Agility is the fundamental characteristic of a supply chain needed for survival in turbulent markets, where environmental forces create additional uncertainty resulting in higher risk in the supply chain management. In addition, agility helps providing the right product, at the right time to the consumer. The main goal of this research is therefore to promote supplier selection in pharmaceutical industry according to the formative basic factors. Moreover, this paper can configure its supply network to achieve the agile supply chain. The present article analyzes the supply part of supply chain based on SCOR model, used to assess agile supply chains by highlighting their specific characteristics and applicability in providing the active pharmaceutical ingredient (API). This methodology provides an analytical modeling; the model enables potential suppliers to be assessed against the multiple criteria using both quantitative and qualitative measures. In addition, for making priority of critical factors, TOPSIS algorithm has been used as a common technique of MADM model. Finally, several factors such as delivery speed, planning and reorder segmentation, trust development and material quantity adjustment are identified and prioritized as critical factors for being agile in supply of API. PMID:24250689

  6. Phenyl-functionalized magnetic palm-based powdered activated carbon for the effective removal of selected pharmaceutical and endocrine-disruptive compounds.

    Science.gov (United States)

    Wong, Kien Tiek; Yoon, Yeomin; Snyder, Shane A; Jang, Min

    2016-06-01

    Triethoxyphenylsilane (TEPS)-functionalized magnetic palm-based powdered activated carbon (MPPAC-TEPS) was prepared and characterized using various spectroscopic methods, and then tested for the removal of bisphenol A, carbamazepine, ibuprofen and clofibric acid. Magnetite film on MPPAC-TEPS was homogeneously coated on the outer surface of palm-based powdered activated carbon (PPAC) through a hydrothermal co-precipitation technique. Followed by silanization of phenyl-functionalized organosilane on MPPAC's magnetic film. As results, micro/mesopore surface area and volume increased without significant pore clogging and iron (Fe) dissolution under the acidic conditions was greatly decreased. The unique structural and chemical features of MPPAC-TEPS were found to be the main reasons for the enhanced adsorption rates and removal capacities of POPs. The presence of electrolytes and different pH values greatly affected the sorption efficiencies. The dominant sorption mechanism of POPs by MPPAC-TEPS was determined to be π-π interaction (physisorption), based on thermodynamic (ΔG°) and differential scanning calorimetry (DSC). Thermal regeneration at a low temperature (350 °C) was an effective method to desorb the retained POPs and enabled to reactivate MPPAC-TEPS with sustained sorption rates and capacities, whereas PPAC was largely exhausted. As a new type of sorbent for POPs, MPPAC-TEPS has operational advantages, such as magnetic separation and stable regeneration.

  7. Recent analytical developments for powder characterization

    Science.gov (United States)

    Brackx, E.; Pages, S.; Dugne, O.; Podor, R.

    2015-07-01

    Powders and divided solid materials are widely represented as finished or intermediary products in industries as widely varied as foodstuffs, cosmetics, construction, pharmaceuticals, electronic transmission, and energy. Their optimal use requires a mastery of the transformation process based on knowledge of the different phenomena concerned (sintering, chemical reactivity, purity, etc.). Their modelling and understanding need a prior acquisition of sets of data and characteristics which are more or less challenging to obtain. The goal of this study is to present the use of different physico-chemical characterization techniques adapted to uranium-containing powders analyzed either in a raw state or after a specific preparation (ionic polishing). The new developments touched on concern dimensional characterization techniques for grains and pores by image analysis, chemical surface characterization and powder chemical reactivity characterization. The examples discussed are from fabrication process materials used in the nuclear fuel cycle.

  8. Impact of the Skim Milk Powder Manufacturing Process on the Flavor of Model White Chocolate.

    Science.gov (United States)

    Stewart, Ashleigh; Grandison, Alistair S; Ryan, Angela; Festring, Daniel; Methven, Lisa; Parker, Jane K

    2017-02-15

    Milk powder is an important ingredient in the confectionery industry, but its variable nature has consequences for the quality of the final confectionary product. This paper demonstrates that skim milk powders (SMP) produced using different (but typical) manufacturing processes, when used as ingredients in the manufacture of model white chocolates, had a significant impact on the sensory and volatile profiles of the chocolate. SMP was produced from raw bovine milk using either low or high heat treatment, and a model white chocolate was prepared from each SMP. A directional discrimination test with naïve panelists showed that the chocolate prepared from the high heat SMP had more caramel/fudge character (p chocolates showed a concomitant increase in Maillard-derived volatiles which are likely to account for this change in flavor.

  9. INFLUENCE OF THE COMPOSITION OF MILK POWDER ON WATER ACTIVITY APPLYING THE GAB MODEL

    Directory of Open Access Journals (Sweden)

    Julio Gil

    2016-03-01

    Full Text Available The use of sorption isotherms at 25°C, for analyze the influence of water activity (aw of the different compositions of whole milk, skim and low in lactose powder, was study. Precisely the latter incorporating previous work can extend the differential behavior of the various components. The work can establish the relationship between the moisture content of the milk powders studied, with its water activity (aw. The experimental results are evaluated with reference model GAB, noting that the layout of the isotherms and the model parameters were successfully adjusted to the values obtained. The clear influence of the presence of monosaccharides (glucose and galactose in the reduced-lactose milk, which reduce the water activity aw from greater value of 0.4 due to the higher solubility of these, is observed. The fat content in whole milk, not being adsorbent is manifested in higher values for water activity.

  10. On the Influence of Material Parameters in a Complex Material Model for Powder Compaction

    Science.gov (United States)

    Staf, Hjalmar; Lindskog, Per; Andersson, Daniel C.; Larsson, Per-Lennart

    2016-10-01

    Parameters in a complex material model for powder compaction, based on a continuum mechanics approach, are evaluated using real insert geometries. The parameter sensitivity with respect to density and stress after compaction, pertinent to a wide range of geometries, is studied in order to investigate completeness and limitations of the material model. Finite element simulations with varied material parameters are used to build surrogate models for the sensitivity study. The conclusion from this analysis is that a simplification of the material model is relevant, especially for simple insert geometries. Parameters linked to anisotropy and the plastic strain evolution angle have a small impact on the final result.

  11. Developing a Model for Pharmaceutical Palliative Care in Rural Areas—Experience from Scotland

    Directory of Open Access Journals (Sweden)

    Gazala Akram

    2017-02-01

    Full Text Available Palliative care is increasingly delivered in the community but access to medicines, particularly ‘out of hours’ remains problematic. This paper describes the experience of developing a model to deliver pharmaceutical palliative care in rural Scotland via the MacMillan Rural Palliative Care Pharmacist Practitioner (MRPP project. The focus of the service was better integration of the MRPP into different care settings and professional teams, and to develop educational resources for the wider MDT including Care Home and Social Care staff on medicine related issues in palliative care. A variety of integration activities are reported in the paper with advice on how to achieve this. Similarly, many resources were developed, including bespoke training on pharmaceutical matters for Care Home staff. The experience allowed for a three step service and sustainability model for community pharmacy palliative care services to be developed. Moving through the steps, the key roles and responsibilities of the MRPP gradually shift towards the local Community Pharmacist(s, with the MRPP starting from a locality-based hands-on role to a wider supportive facilitating role for local champions. It is acknowledged that successful delivery of the model is dependent on alignment of resources, infrastructure and local community support.

  12. Model investigations 3D of gas-powder two phase flow in descending bed with consideration radial distribution of flow

    Directory of Open Access Journals (Sweden)

    B. Panic

    2013-04-01

    Full Text Available The results of experimental investigations concerning radial distribution of powder accumulation in bed and static pressure were presented in this paper. To realize this research physical model of gas-powder two phase flow with descending bed was projected and constructed. Amounts of “dynamic” and “static” powder accumulated in bed, in dependence on gas velocity and of bed particles were investigated. In 3D model “static” powder (with its radial distribution at the tuyere level and in the higher part of bed was measured. The influence of bed particles, powder and gas radial distribution on values of interaction forces between flow phases in investigated system was defined.

  13. The shielding against radiation produced by powder metallurgy with tungsten copper alloy applied on transport equipment for radio-pharmaceutical products

    Energy Technology Data Exchange (ETDEWEB)

    Cione, Francisco C.; Sene, Frank F.; Souza, Armando C. de; Betini, Evandro G.; Rossi, Jesualdo L., E-mail: fceoni@hotmail.com, E-mail: ffsene@hotmail.com, E-mail: armandocirilo@yahoo.com, E-mail: evandrobetini@gmail.com, E-mail: jelrossi@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Rizzuto, Marcia A., E-mail: marizzutto@if.usp.br [Universidade de Sao Paulo (IF/USP), SP (Brazil). Instituto de Fisica

    2015-07-01

    Safety is mandatory on medicine radiopharmaceutical transportation and dependent on radiation shielding material. The focus of the present work is to minimize the use of harmful materials as lead and depleted uranium usually used in packages transportation. The tungsten-copper composite obtained by powder metallurgy (PM) is non-toxic. In powder metallurgy the density and the porosity of the compacted parts depends basically upon particle size distribution of each component, mixture, compacting pressure and sintering temperature cycle. The tungsten-copper composite, when used for shielding charged particles, X-rays, gamma photons or other photons of lower energy require proper interpretation of the radiation transport phenomena. The radioactive energy reduction varies according to the porosity and density of the materials used as shielding. The main factor for radiation attenuation is the cross section value for tungsten. The motivation research factor is an optimization of the tungsten and cooper composition in order to achieve the best linear absorption coefficient given by equation I{sub (x)} = I{sub 0}e{sup (-ux)}. Experiments were conducted to quantify the effective radiation shielding properties of tungsten-copper composite produced by PM, varying the cooper amount in the composite. The studied compositions were 15%, 20% and 25% copper in mass. The Compaction pressure was 270 MPa and the sintering atmosphere was in 1.1 atm in N{sub 2}+H{sub 2}. The sintering temperature was 980 deg C for 2 h. The linear absorption coefficient factor was similar either for the green and the sintered compacts, due the amount of porosity did not affect the radiation attenuation. Thus the sintered was meant for size reduction and mechanical properties enhancement. (author)

  14. Colistimethate sodium powder and tobramycin powder for inhalation for the treatment of chronic Pseudomonas aeruginosa lung infection in cystic fibrosis: systematic review and economic model.

    Science.gov (United States)

    Tappenden, P; Harnan, S; Uttley, L; Mildred, M; Carroll, C; Cantrell, A

    2013-12-01

    Cystic fibrosis (CF) is an inherited condition characterised by the abnormal transport of chloride ions across transporting epithelia. This leads to the production of thick sticky mucus in the lungs, pancreas, liver, intestine and reproductive tract, and an increase in the salt content in sweat. Among other problems, people with CF experience recurrent respiratory infections and have difficulties digesting food. CF affects over 9000 individuals in the UK. CF shortens life expectancy and adversely affects quality of life. In 2010, CF was recorded as the cause of 103 deaths in England and Wales. To evaluate the clinical effectiveness and cost-effectiveness of colistimethate sodium dry powder for inhalation (DPI) (Colobreathe(®), Forest Laboratories) and tobramycin DPI (TOBI Podhaler(®), Novartis Pharmaceuticals) for the treatment of Pseudomonas aeruginosa lung infection in CF. Electronic databases were searched in February and March 2011 [MEDLINE, MEDLINE In-Process & Other Non-Indexed citations, EMBASE, The Cochrane Library databases, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, Conference Proceedings Citation Index (CPCI) and Bioscience Information Service (BIOSIS) Previews]. Relevant databases were searched for ongoing and unpublished studies, and bibliographies of relevant systematic reviews and the manufacturers' submissions were also hand-searched. A systematic review of the clinical effectiveness and cost-effectiveness of colistimethate sodium DPI and tobramycin DPI for the treatment of chronic P. aeruginosa lung infection in CF was conducted. Existing economic evidence within the literature was reviewed and a de novo health economic model was also developed. Three randomised controlled trials (RCTs) were included in the clinical effectiveness review. Both colistimethate sodium DPI and tobramycin DPI were reported to be non-inferior to nebulised tobramycin for the outcome forced expiratory volume in first second

  15. Modeling & Informatics at Vertex Pharmaceuticals Incorporated: our philosophy for sustained impact

    Science.gov (United States)

    McGaughey, Georgia; Patrick Walters, W.

    2016-11-01

    Molecular modelers and informaticians have the unique opportunity to integrate cross-functional data using a myriad of tools, methods and visuals to generate information. Using their drug discovery expertise, information is transformed to knowledge that impacts drug discovery. These insights are often times formulated locally and then applied more broadly, which influence the discovery of new medicines. This is particularly true in an organization where the members are exposed to projects throughout an organization, such as in the case of the global Modeling & Informatics group at Vertex Pharmaceuticals. From its inception, Vertex has been a leader in the development and use of computational methods for drug discovery. In this paper, we describe the Modeling & Informatics group at Vertex and the underlying philosophy, which has driven this team to sustain impact on the discovery of first-in-class transformative medicines.

  16. Modeling & Informatics at Vertex Pharmaceuticals Incorporated: our philosophy for sustained impact

    Science.gov (United States)

    McGaughey, Georgia; Patrick Walters, W.

    2017-03-01

    Molecular modelers and informaticians have the unique opportunity to integrate cross-functional data using a myriad of tools, methods and visuals to generate information. Using their drug discovery expertise, information is transformed to knowledge that impacts drug discovery. These insights are often times formulated locally and then applied more broadly, which influence the discovery of new medicines. This is particularly true in an organization where the members are exposed to projects throughout an organization, such as in the case of the global Modeling & Informatics group at Vertex Pharmaceuticals. From its inception, Vertex has been a leader in the development and use of computational methods for drug discovery. In this paper, we describe the Modeling & Informatics group at Vertex and the underlying philosophy, which has driven this team to sustain impact on the discovery of first-in-class transformative medicines.

  17. Modeling of wear behavior of Al/B{sub 4}C composites produced by powder metallurgy

    Energy Technology Data Exchange (ETDEWEB)

    Sahin, Ismail; Bektas, Asli [Gazi Univ., Ankara (Turkey). Dept. of Industrial Design Engineering; Guel, Ferhat; Cinci, Hanifi [Gazi Univ., Ankara (Turkey). Dept. of Materials and Metallurgy Engineering

    2017-06-01

    Wear characteristics of composites, Al matrix reinforced with B{sub 4}C particles percentages of 5, 10,15 and 20 produced by the powder metallurgy method were studied in this study. For this purpose, a mixture of Al and B{sub 4}C powders were pressed under 650 MPa pressure and then sintered at 635 C. The analysis of hardness, density and microstructure was performed. The produced samples were worn using a pin-on-disk abrasion device under 10, 20 and 30 N load through 500, 800 and 1200 mesh SiC abrasive papers. The obtained wear values were implemented in an artificial neural network (ANN) model having three inputs and one output using feed forward backpropagation Levenberg-Marquardt algorithm. Thus, the optimum wear conditions and hardness values were determined.

  18. Water modeling of mold powder entrapment in slab continuous casting mold

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The optimal parameters were determined by the water modeling of slab casting. It was found that there are mainly three types of mold powder entrapment in slab continuous casting, i.e., the entrapment caused by the shearing flow near the narrow face of mold, the entrapment caused by vortexes around the submerged entry nozzle (SEN), and the entrapment caused by the Ar bubbling.Both the velocity of the surface flow and the level fluctuation of the liquids are enlarged with increasing the casting speed, reducing the submersion depth of SEN, decreasing the downward angles of the nozzle outlets, and increasing the Ar flowrate, all of which increase the tendency of mold powder entrapment. Among the four above-mentioned factors, casting speed has the largest effect.

  19. Numerical modeling of heat transfer and fluid flow in laser metal deposition by powder injection

    Science.gov (United States)

    Fan, Zhiqiang

    Laser metal deposition is an additive manufacturing technique which allows quick fabrication of fully-dense metallic components directly from Computer Aided Design (CAD) solid models. A self-consistent three-dimensional model was developed for the laser metal deposition process by powder injection, which simulates heat transfer, phase changes, and fluid flow in the melt pool. The governing equations for solid, liquid and gas phases in the calculation domain have been formulated using the continuum model. The free surface in the melt pool has been tracked by the Volume of Fluid (VOF) method, while the VOF transport equation was solved using the Piecewise Linear Interface Calculation (PLIC) method. Surface tension was modeled by taking the Continuum Surface Force (CSF) model combined with a force-balance flow algorithm. Laser-powder interaction was modeled to account for the effects of laser power attenuation and powder temperature rise during the laser metal deposition process. The governing equations were discretized in the physical space using the finite volume method. The advection terms were approximated using the MUSCL flux limiter scheme. The fluid flow and energy equations were solved in a coupled manner. The incompressible flow equations were solved using a two-step projection method, which requires a solution of a Poisson equation for the pressure field. The discretized pressure Poisson equation was solved using the ICCG (Incomplete Cholesky Conjugate Gradient) solution technique. The energy equation was solved by an enthalpy-based method. Temperature-dependent thermal-physical material properties were considered in the numerical implementation. The numerical model was validated by comparing simulations with experimental measurements.

  20. Quality-by-design (QbD): effects of testing parameters and formulation variables on the segregation tendency of pharmaceutical powder measured by the ASTM D 6940-04 segregation tester.

    Science.gov (United States)

    Xie, Lin; Wu, Huiquan; Shen, Meiyu; Augsburger, Larry L; Lyon, Robbe C; Khan, Mansoor A; Hussain, Ajaz S; Hoag, Stephen W

    2008-10-01

    The objective of this study was to examine the effects of testing parameters and formulation variables on the segregation tendency of pharmaceutical powders measured by the ASTM D 6940-04 segregation tester using design of experiments (DOE) approaches. The test blends consisted of 4% aspirin (ASP) and 96% microcrystalline cellulose (MCC) with and without magnesium stearate (MgS). The segregation tendency of a blend was determined by measuring the last/first (L/F) ratio, the ratio of aspirin concentrations between the first and last samples discharged from the tester. A 2(2) factorial design was used to determine the effects of measurement parameters [amount of material loaded (W), number of segregation cycles] with number of replicates 6. ANOVA showed that W was a critical parameter for segregation testing. The L/F value deviated further from 1 (greater segregation tendency) with increasing W. A 2(3) full factorial design was used to assess the effects of formulation variables: grade of ASP (unmilled, milled), grade of MCC, and amount of lubricant, MgS. MLR and ANOVA showed that the grade of ASP was the main effect contributing to segregation tendency. Principal Component Regression Analysis established a correlation between L/F and the physical properties of the blend related to ASP and MCC, the ASP/MCC particle size ratio (PSR) and powder cohesion. The physical properties of the blend related to density and flow were not influenced by the grade of ASP and were not related to the segregation tendency of the blend. The direct relationship between L/F and PSR was determined by univariate analysis. Segregation tendency increased as the ASP to MCC particle size increased. This study highlighted critical test parameters for segregation testing and identified critical physical properties of the blends that influence segregation tendency.

  1. Flow injection spectrophotometric determination of vitamin E in Pharmaceuticals, milk powder and blood serum using potassium ferricyanide-Fe(Ⅲ) detection system

    Institute of Scientific and Technical Information of China (English)

    Saima

    2010-01-01

    A simple and sensitive flow injection spectrophotometric method is reported for the determination of vitamin E using potassium ferricyanide-Fe(Ⅲ detection system. In the presence of vitamin E, Fe(Ⅲ/ferricyanide reduces. The in situ reduced ions are then reacted with unreduced portion of ferricyanide/Fe(Ⅲ to make soluble Prussian blue, which is monitored at absorption wavelength of 735 nm. Linear calibration graph was obtained in the concentration range of 0.1-40 μg mL-1. The relative standard deviations (n = 4) were in the range of 1.1-3.6%, with limits of detection (3 s blank) of 0.04 μg mL-1. The proposed method allowed 12 injections h-1. The method is applied to determine vitamin E in Pharmaceuticals, infant milk and blood serum samples using hexane extraction with the recoveries in the range of 93 ± 3 to 97.5 ± 4%. The method is validated using certified reference materials SRM 968c for blood serum samples.

  2. Design, Modeling and Optimization of a Piezoelectric Pressure Sensor based on a Thin-Film PZT Membrane Containing Nanocrystalline Powders

    National Research Council Canada - National Science Library

    Vahid Mohammadi; Mohammad Hossein Sheikhi

    2009-01-01

    ...^ thin film has been presented and then a pressure sensor based on multilayer thin-film PZT diaphragm contain of Lead Zirconate Titanate nanocrystalline powders was designed, modeled and optimized...

  3. PHARMACEUTICAL AEROSOLS FOR THE TREATMENT AND PREVENTION OF TUBERCULOSIS

    Directory of Open Access Journals (Sweden)

    Shumaila N Muhammad Hanif

    2012-09-01

    Full Text Available Historically, pharmaceutical aerosols have been employed for the treatment of obstructive airway diseases, such as asthma and chronic obstructive pulmonary disease, but in the past decades their use has been expanded to treat lung infections associated with cystic fibrosis and other respiratory diseases. Tuberculosis (TB is acquired after inhalation of aerosol droplets containing the bacilli from the cough of infected individuals. Even though TB affects other organs, the lungs are the primary site of infection, which makes the pulmonary route an ideal alternative route to administer vaccines or drug treatments. Optimization of formulations and delivery systems for anti-TB vaccines and drugs, as well as the proper selection of the animal model to evaluate those is of paramount importance if novel vaccines or drug treatments are to be successful. Pharmaceutical aerosols for patient use are generated from metered dose inhalers, nebulizers and dry powder inhalers. In addition to the advantages of providing more efficient delivery of the drug, low cost and portability, pharmaceutical dry powder aerosols are more stable than inhalable liquid dosage forms and do not require refrigeration. Methods to manufacture dry powders in respirable sizes include micronization, spray drying and other proprietary technologies. Inhalable dry powders are characterized in terms of their drug content, particle size and dispersibility to ensure deposition in the appropriate lung region and effective aerosolization from the device. These methods will be illustrated as they were applied for the manufacture and characterization of powders containing anti-tubercular agents and vaccines for pulmonary administration. The influence of formulation, selection of animal model, method of aerosol generation and administration on the efficacy demonstrated in a given study will be illustrated by the evaluation of pharmaceutical aerosols of anti-TB drugs and vaccines in guinea pigs by

  4. Effect of mechanical denaturation on surface free energy of protein powders.

    Science.gov (United States)

    Mohammad, Mohammad Amin; Grimsey, Ian M; Forbes, Robert T; Blagbrough, Ian S; Conway, Barbara R

    2016-10-01

    Globular proteins are important both as therapeutic agents and excipients. However, their fragile native conformations can be denatured during pharmaceutical processing, which leads to modification of the surface energy of their powders and hence their performance. Lyophilized powders of hen egg-white lysozyme and β-galactosidase from Aspergillus oryzae were used as models to study the effects of mechanical denaturation on the surface energies of basic and acidic protein powders, respectively. Their mechanical denaturation upon milling was confirmed by the absence of their thermal unfolding transition phases and by the changes in their secondary and tertiary structures. Inverse gas chromatography detected differences between both unprocessed protein powders and the changes induced by their mechanical denaturation. The surfaces of the acidic and basic protein powders were relatively basic, however the surface acidity of β-galactosidase was higher than that of lysozyme. Also, the surface of β-galactosidase powder had a higher dispersive energy compared to lysozyme. The mechanical denaturation decreased the dispersive energy and the basicity of the surfaces of both protein powders. The amino acid composition and molecular conformation of the proteins explained the surface energy data measured by inverse gas chromatography. The biological activity of mechanically denatured protein powders can either be reversible (lysozyme) or irreversible (β-galactosidase) upon hydration. Our surface data can be exploited to understand and predict the performance of protein powders within pharmaceutical dosage forms. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Quality Assessment of Persian Translation of English Pharmaceutical Leaflets Based on House’s Model

    Directory of Open Access Journals (Sweden)

    Atefeh Zekri

    2016-11-01

    Full Text Available This research attempted to evaluate the quality of Persian translation of drug leaflets. The researchers randomly selected a set of 30 pharmaceutical leaflets collected between March-August, 2015. The leaflets were analyzed based on House’s functional-pragmatic model of translation quality assessment. At first, the profiles of both source texts and target texts were collected. Then, their overtly and covertly erroneous errors and the kinds of strategies used by the translators in translating the pharmaceutical leaflets into Persian were identified. The results indicate that out of 90 selected sentences of English leaflets, 47 were overtly erroneous and 43 were error-free. These overtly erroneous translations had 27 instances of “mistranslation”, 15 instances of “grammatical mistakes”, six instances of “addition”, six instances of “omission” and four instances of “substitution”. The only covert error was “tenor mismatch” in all sample sentences. The study findings can help teachers in translation studies to improve the quality of students’ translation. Moreover, awareness of the errors in the current leaflet translations can assist students in performing their future jobs as translators. The findings may directly and indirectly affect the health of patients in an efficient and effective way.

  6. One- and two-stage Arrhenius models for pharmaceutical shelf life prediction.

    Science.gov (United States)

    Fan, Zhewen; Zhang, Lanju

    2015-01-01

    One of the most challenging aspects of the pharmaceutical development is the demonstration and estimation of chemical stability. It is imperative that pharmaceutical products be stable for two or more years. Long-term stability studies are required to support such shelf life claim at registration. However, during drug development to facilitate formulation and dosage form selection, an accelerated stability study with stressed storage condition is preferred to quickly obtain a good prediction of shelf life under ambient storage conditions. Such a prediction typically uses Arrhenius equation that describes relationship between degradation rate and temperature (and humidity). Existing methods usually rely on the assumption of normality of the errors. In addition, shelf life projection is usually based on confidence band of a regression line. However, the coverage probability of a method is often overlooked or under-reported. In this paper, we introduce two nonparametric bootstrap procedures for shelf life estimation based on accelerated stability testing, and compare them with a one-stage nonlinear Arrhenius prediction model. Our simulation results demonstrate that one-stage nonlinear Arrhenius method has significant lower coverage than nominal levels. Our bootstrap method gave better coverage and led to a shelf life prediction closer to that based on long-term stability data.

  7. Determination of 5,7-dichloroquinolin-8-ol and 5-chloroquinolin-8-ol in bulk drug powder and pharmaceutical preparation by TLC

    Directory of Open Access Journals (Sweden)

    B H Pavithra

    2011-01-01

    Full Text Available Aim: The study aims to develop a simple, rapid and economical normal phase thin layer chromatography (TLC method for identification and quantification of 5,7-dichloroquinolin-8-ol and 5-chloroquinolin-8-ol, two active ingredients of halquinol, an antimicrobial agent. Materials and Methods: The analysis was performed on silica gel 60 TLC plates pre-washed with disodium ethylenedinitrilotetraacetic acid disodium salt (Na 2 EDTA solution with methanol-ethyl acetate-iso-propyl alcohol-ammonia solution [8:20:1:0.6 (v/v] as the mobile phase. Detection and quantification was performed densitometrically at 247 nm. Results: Responses of both 5,7-dichloroquinolin-8-ol and 5-chloroquinolin-8-ol were linear functions of concentration in the range of 300-800 ng. The intraday precision and intermediate precision of the method for 5,7-dichloroquinolin-8-ol and 5-chloroquinolin-8-ol was determined and it was found to be precise. Conclusion: The TLC method developed for simultaneous quantitative determination of 5,7-dichloroquinolin-8-ol and 5-chloroquinolin-8-ol was found to be simple and economical. Therefore, it can be used in routine quality control analysis of halquinol in bulk drug powder and halquinol bolus.

  8. Modelling of the mechanical behaviour of two pure PTFE powders during their compaction at room temperature

    Science.gov (United States)

    Frédy, Carole; Canto, Rodrigo B.; Schmitt, Nicolas; Roux, Stéphane; Billardon, René

    2013-06-01

    Since PolyTetraFluoroEthylene (PTFE) is not melt processible because of its very high melt viscosity, parts made of this material are generally manufactured by cold compaction of powder material followed by sintering of the green compact. The aim of this study is to identify 3-D constitutive equations suitable for the finite element analysis of PTFE powder compaction. To exhibit the influence of their geometrical aspect on their mechanical behaviour, two pure PTFE resins were tested, viz. a free flowing pelletized resin and a granular fine cut resin. To study the behaviour of these powders during their compaction along different loading paths, a novel triaxial device has been designed and installed on a six-actuator triaxial testing machine. The results obtained for hydrostatic loading were favourably compared with results obtained by isostatic pressing. Various complex loading paths were also investigated. Full 3D elasto-viscoplastic non-associated constitutive equations, viz. a non-linear Drucker-Prager/cap type model, could be identified.

  9. Comparison of rheological analytic model with numerical simulation in powder injection molding filling process

    Institute of Scientific and Technical Information of China (English)

    刘跃军; 李祥刚; 黄宇刚; 魏珊珊; 曾广胜

    2008-01-01

    Mathematical model of filling disk-shaped mold cavity in steady state was studied.And the mathematical model under vibration field was developed from the model in steady state.According to the model of filling disk-shaped mold cavity in steady state,the filling time,the distribution of velocity field and the pressure field were obtained.The analysis results from rheological analytic model were compared with the numerical simulation results using Moldflow software in the powder injection molding filling process.Through the comparison,it is found that it is unreasonable to neglect the influence of temperature when calculated the pressure changing with the time at the cavity gate,while it can be neglected in other situations such as calculating the distribution of the velocity fields.This provides a theoretical reference for the establishment of correct model both in steady state and under vibration force field in the future.

  10. Forming limit prediction of powder forging process by the energy-based elastoplastic damage model

    Science.gov (United States)

    Yeh, Hung-Yang; Cheng, Jung-Ho; Huang, Cheng-Chao

    2004-06-01

    An energy-based elastoplastic damage model is developed and then applied to predict the deformation and fracture initiation in powder forging processes. The fracture mechanism is investigated by the newly proposed damage model, which is based on the plastic energy dissipation. The developed formulations are implemented into finite element program ABAQUS in order to simulate the complex loading conditions. The forming limits of sintered porous metals under various operational conditions are explored by comparing the relevant experiments with the finite element analyses. The sintered iron-powder preforms of various initial relative densities (RDs) and aspect ratios are compressed until crack initiates. The deformation level of the bulged billets at fracture stroke obtained from compressive fracture tests is utilized to validate the finite element model and then the forming limit diagrams are constructed with the validated model. This model is further verified by the gear blank forging. The fracture site and corresponding deformation level are predicted by the finite element simulations. Meanwhile, the gear forging experiment is performed on the sintered preforms. The predicted results agree well with the experimental observations.

  11. Modeling high adsorption capacity and kinetics of organic macromolecules on super-powdered activated carbon.

    Science.gov (United States)

    Matsui, Yoshihiko; Ando, Naoya; Yoshida, Tomoaki; Kurotobi, Ryuji; Matsushita, Taku; Ohno, Koichi

    2011-02-01

    The capacity to adsorb natural organic matter (NOM) and polystyrene sulfonates (PSSs) on small particle-size activated carbon (super-powdered activated carbon, SPAC) is higher than that on larger particle-size activated carbon (powdered-activated carbon, PAC). Increased adsorption capacity is likely attributable to the larger external surface area because the NOM and PSS molecules do not completely penetrate the adsorbent particle; they preferentially adsorb near the outer surface of the particle. In this study, we propose a new isotherm equation, the Shell Adsorption Model (SAM), to explain the higher adsorption capacity on smaller adsorbent particles and to describe quantitatively adsorption isotherms of activated carbons of different particle sizes: PAC and SPAC. The SAM was verified with the experimental data of PSS adsorption kinetics as well as equilibrium. SAM successfully characterized PSS adsorption isotherm data for SPACs and PAC simultaneously with the same model parameters. When SAM was incorporated into an adsorption kinetic model, kinetic decay curves for PSSs adsorbing onto activated carbons of different particle sizes could be simultaneously described with a single kinetics parameter value. On the other hand, when SAM was not incorporated into such an adsorption kinetic model and instead isotherms were described by the Freundlich model, the kinetic decay curves were not well described. The success of the SAM further supports the adsorption mechanism of PSSs preferentially adsorbing near the outer surface of activated carbon particles.

  12. Minipig and beagle animal model genomes aid species selection in pharmaceutical discovery and development

    Energy Technology Data Exchange (ETDEWEB)

    Vamathevan, Jessica J., E-mail: jessica.j.vamathevan@gsk.com [Computational Biology, Quantitative Sciences, GlaxoSmithKline, Stevenage (United Kingdom); Hall, Matthew D.; Hasan, Samiul; Woollard, Peter M. [Computational Biology, Quantitative Sciences, GlaxoSmithKline, Stevenage (United Kingdom); Xu, Meng; Yang, Yulan; Li, Xin; Wang, Xiaoli [BGI-Shenzen, Shenzhen (China); Kenny, Steve [Safety Assessment, PTS, GlaxoSmithKline, Ware (United Kingdom); Brown, James R. [Computational Biology, Quantitative Sciences, GlaxoSmithKline, Collegeville, PA (United States); Huxley-Jones, Julie [UK Platform Technology Sciences (PTS) Operations and Planning, PTS, GlaxoSmithKline, Stevenage (United Kingdom); Lyon, Jon; Haselden, John [Safety Assessment, PTS, GlaxoSmithKline, Ware (United Kingdom); Min, Jiumeng [BGI-Shenzen, Shenzhen (China); Sanseau, Philippe [Computational Biology, Quantitative Sciences, GlaxoSmithKline, Stevenage (United Kingdom)

    2013-07-15

    Improving drug attrition remains a challenge in pharmaceutical discovery and development. A major cause of early attrition is the demonstration of safety signals which can negate any therapeutic index previously established. Safety attrition needs to be put in context of clinical translation (i.e. human relevance) and is negatively impacted by differences between animal models and human. In order to minimize such an impact, an earlier assessment of pharmacological target homology across animal model species will enhance understanding of the context of animal safety signals and aid species selection during later regulatory toxicology studies. Here we sequenced the genomes of the Sus scrofa Göttingen minipig and the Canis familiaris beagle, two widely used animal species in regulatory safety studies. Comparative analyses of these new genomes with other key model organisms, namely mouse, rat, cynomolgus macaque, rhesus macaque, two related breeds (S. scrofa Duroc and C. familiaris boxer) and human reveal considerable variation in gene content. Key genes in toxicology and metabolism studies, such as the UGT2 family, CYP2D6, and SLCO1A2, displayed unique duplication patterns. Comparisons of 317 known human drug targets revealed surprising variation such as species-specific positive selection, duplication and higher occurrences of pseudogenized targets in beagle (41 genes) relative to minipig (19 genes). These data will facilitate the more effective use of animals in biomedical research. - Highlights: • Genomes of the minipig and beagle dog, two species used in pharmaceutical studies. • First systematic comparative genome analysis of human and six experimental animals. • Key drug toxicology genes display unique duplication patterns across species. • Comparison of 317 drug targets show species-specific evolutionary patterns.

  13. Applying mixture toxicity modelling to predict bacterial bioluminescence inhibition by non-specifically acting pharmaceuticals and specifically acting antibiotics.

    Science.gov (United States)

    Neale, Peta A; Leusch, Frederic D L; Escher, Beate I

    2017-04-01

    Pharmaceuticals and antibiotics co-occur in the aquatic environment but mixture studies to date have mainly focused on pharmaceuticals alone or antibiotics alone, although differences in mode of action may lead to different effects in mixtures. In this study we used the Bacterial Luminescence Toxicity Screen (BLT-Screen) after acute (0.5 h) and chronic (16 h) exposure to evaluate how non-specifically acting pharmaceuticals and specifically acting antibiotics act together in mixtures. Three models were applied to predict mixture toxicity including concentration addition, independent action and the two-step prediction (TSP) model, which groups similarly acting chemicals together using concentration addition, followed by independent action to combine the two groups. All non-antibiotic pharmaceuticals had similar EC50 values at both 0.5 and 16 h, indicating together with a QSAR (Quantitative Structure-Activity Relationship) analysis that they act as baseline toxicants. In contrast, the antibiotics' EC50 values decreased by up to three orders of magnitude after 16 h, which can be explained by their specific effect on bacteria. Equipotent mixtures of non-antibiotic pharmaceuticals only, antibiotics only and both non-antibiotic pharmaceuticals and antibiotics were prepared based on the single chemical results. The mixture toxicity models were all in close agreement with the experimental results, with predicted EC50 values within a factor of two of the experimental results. This suggests that concentration addition can be applied to bacterial assays to model the mixture effects of environmental samples containing both specifically and non-specifically acting chemicals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Prioritization of diseases for the development of a pharmaceutical care service model in South Korea using the analytic hierarchy process
.

    Science.gov (United States)

    Rhew, Kiyon; Han, Nayoung; Cho, Keun-Tae; Yoon, Jeong-Hyun; Oh, Jung Mi

    2017-08-30

    Drug therapy plays a critical role in most chronic diseases. Effectiveness of pharmaceutical care services in the improvement of clinical, social, or economic outcomes has been scientifically proven through numerous studies. In South Korea, to optimize and standardize pharmaceutical care for patients with chronic metabolic diseases, the development of a pharmaceutical care service model is needed. To determine the priority of diseases in developing pharmaceutical care service models, analytic hierarchny process (AHP)analysis was used. A survey questionnaire standardized with detailed evaluation areas and an index, to ensure sufficient understanding and identical standards of evaluators, was designed. It was prepared for pair-wise comparisons of individual criteria of candidate diseases. Medical specialists and pharmacists who have clinical experience and expertise in chronic metabolic diseases or at least 10 years of experience in pharmacy practice were recruited. They responded to a survey consisting of nine sections by using the pair-wise comparison method. A total of seven candidate diseases were selected for prioritization. Diabetes mellitus was given the highest score of 0.2695, cardiovascular disease (0.2598) being the next, followed by chronic kidney disease (0.2000), and cerebrovascular diseases (0.1087). The criteria were weighted as follows: disease characteristics (0.4964), patient-oriented care (0.3649), and improvement in services (0.1386). Diabetes, cardiovascular diseases, and chronic kidney disease were found to have high priority in developing a pharmaceutical care service model in South Korea. In the future, further research for the development and application of pharmaceutical care services models for different types of diseases is required.
.

  15. A decade of innovation in pharmaceutical R&D: the Chorus model.

    Science.gov (United States)

    Owens, Paul K; Raddad, Eyas; Miller, Jeffrey W; Stille, John R; Olovich, Kenneth G; Smith, Neil V; Jones, Rosie S; Scherer, Joel C

    2015-01-01

    Chorus is a small, operationally independent clinical development organization within Eli Lilly and Company that specializes in drug development from candidate selection to clinical proof of concept. The mission of Chorus is to achieve proof of concept rapidly and at a low cost while positioning successful projects for 'pharma-quality' late-stage development. Chorus uses a small internal staff of experienced drug developers and a network of external vendors to design and implement chemistry, manufacturing and control processes, preclinical toxicology and biology, and Phase I/II clinical trials. In the decade since it was established, Chorus has demonstrated substantial productivity improvements in both time and cost compared to traditional pharmaceutical research and development. Here, we describe its development philosophy, organizational structure, operational model and results to date.

  16. Understanding and Modeling the Liquid Uptake in Porous Compacted Powder Preparations.

    Science.gov (United States)

    Esteban, Jesús; Moxon, Thomas E; Simons, Tom A H; Bakalis, Serafim; Fryer, Peter J

    2017-07-18

    Porous solid materials commonly undergo coating processes during their manufacture, where liquids are put in contact with solids for different purposes. The study of liquid penetration in porous substrates is a process of high relevance in activities in several industries. In particular, powder detergents are subject to coating with surfactants that will boost their performance, although this may affect the flowability and even cause caking of the particulate material, which can be detrimental to consumer acceptance. Here we present a methodology to make compacted preparations of powders relevant to detergent making and evaluate the internal structure of such porous substrates by means of X-ray microcomputed tomography. Liquid penetration in the preparation and the total mass uptake of fluid were monitored by a gravimetric technique based on a modified Wilhelmy plate method consisting of consecutive cycles. Taking into account the geometry of the system, two models were proposed to describe the liquid uptake based on the process being driven by mass (model 1) or pressure (model 2) gradients. A comparison between both from statistical and physical points of view led to the conclusion that the latter was more appropriate for describing the process and retrieving values of the permeability of the solid between 0.03 × 10(-12) and 0.95 × 10(-12) m(2). Finally, with the parameters retrieved from model 2, the force balance observed throughout the experiment was simulated satisfactorily.

  17. Effect of garlic powder on acrylamide formation in a low-moisture model system and bread baking.

    Science.gov (United States)

    Li, Jinwang; Zuo, Jie; Qiao, Xuguang; Zhang, Yongju; Xu, Zhixiang

    2016-02-01

    Acrylamide (AA) is of concern worldwide because of its neurotoxicity, genotoxicity and reproductive/developmental toxicity. Consequently, methods for minimizing AA formation during food processing are vital. In this study, the formation and elimination of AA in an asparagine/glucose low-moisture model system were investigated by response surface methodology. The effect of garlic powder on the kinetics of AA formation/elimination was also evaluated. The AA content reached a maximum level (674.0 nmol) with 1.2 mmol of glucose and 1.2 mmol of asparagine after heating at 200 °C for 6 min. The AA content was greatly reduced with the addition of garlic powder. Compared to without garlic powder, an AA reduction rate of 43% was obtained with addition of garlic powder at a mass fraction of 0.05 g. Garlic powder inhibited AA formation during the generation-predominant kinetic stage and had no effect on the degradation-predominant kinetic stage. The effect of garlic powder on AA formation in bread and bread quality was also investigated. Adding a garlic powder mass fraction of 15 g to 500 g of dough significantly (P < 0.05) reduced the formation of AA (reduction rate of 46%) and had no obvious effect on the sensory qualities of the bread. This study provides a possible method for reducing the AA content in bread and other heat-treated starch-rich foods. © 2015 Society of Chemical Industry.

  18. At-line determination of pharmaceuticals small molecule's blending end point using chemometric modeling combined with Fourier transform near infrared spectroscopy

    Science.gov (United States)

    Tewari, Jagdish; Strong, Richard; Boulas, Pierre

    2017-02-01

    This article summarizes the development and validation of a Fourier transform near infrared spectroscopy (FT-NIR) method for the rapid at-line prediction of active pharmaceutical ingredient (API) in a powder blend to optimize small molecule formulations. The method was used to determine the blend uniformity end-point for a pharmaceutical solid dosage formulation containing a range of API concentrations. A set of calibration spectra from samples with concentrations ranging from 1% to 15% of API (w/w) were collected at-line from 4000 to 12,500 cm- 1. The ability of the FT-NIR method to predict API concentration in the blend samples was validated against a reference high performance liquid chromatography (HPLC) method. The prediction efficiency of four different types of multivariate data modeling methods such as partial least-squares 1 (PLS1), partial least-squares 2 (PLS2), principal component regression (PCR) and artificial neural network (ANN), were compared using relevant multivariate figures of merit. The prediction ability of the regression models were cross validated against results generated with the reference HPLC method. PLS1 and ANN showed excellent and superior prediction abilities when compared to PLS2 and PCR. Based upon these results and because of its decreased complexity compared to ANN, PLS1 was selected as the best chemometric method to predict blend uniformity at-line. The FT-NIR measurement and the associated chemometric analysis were implemented in the production environment for rapid at-line determination of the end-point of the small molecule blending operation.

  19. Ecotoxicity interspecies QAAR models from Daphnia toxicity of pharmaceuticals and personal care products.

    Science.gov (United States)

    Sangion, A; Gramatica, P

    2016-10-01

    Pharmaceutical and Personal Care Products (PPCPs) became a class of contaminants of emerging concern because are ubiquitously detected in surface water and soil, where they can affect wildlife. Ecotoxicological data are only available for a few PPCPs, thus modelling approaches are essential tools to maximize the information contained in the existing data. In silico methods may be helpful in filling data gaps for the toxicity of PPCPs towards various ecological indicator organisms. The good correlation between toxicity toward Daphnia magna and those on two fish species (Pimephales promelas and Oncorhynchus mykiss), improved by the addition of one theoretical molecular descriptor, allowed us to develop predictive models to investigate the relationship between toxicities in different species. The aim of this work is to propose quantitative activity-activity relationship (QAAR) models, developed in QSARINS and validated for their external predictivity. Such models can be used to predict the toxicity of PPCPs to a particular species using available experimental toxicity data from a different species, thus reducing the tests on organisms of higher trophic level. Similarly, good QAAR models, implemented by molecular descriptors to improve the quality, are proposed here for fish interspecies. We also comment on the relevance of autocorrelation descriptors in improving all studied interspecies correlations.

  20. Consolidation of nanostructured metal powders by rapid forging: Processing, modeling, and subsequent mechanical behavior

    Science.gov (United States)

    Shaik, G. R.; Milligan, W. W.

    1997-03-01

    Fe-10Cu powders containing 20-nm grains were produced by attritor milling of elemental powders in argon. A rapid powder forging technique was developed to consolidate the powders into fully dense compacts while maintaining nanoscale grain sizes. Grain growth during the consolidation was controlled by reducing the time of exposure at elevated temperature to a few minutes or less, a technique which is applicable to all materials and does not necessitate the addition of dispersoids. This was achieved by heating green compacts quickly using an induction heater, and then forging and rapidly cooling them back to room temperature. Forging was conducted in a protective argon atmosphere to limit contamination. Fully dense compacts were produced at relatively low temperatures, mainly due to the accelerated creep rates exhibited by the nanostructures. Transmission electron microscopy and X-ray diffraction analysis found an average grain size of 45 nm in the fully dense samples forged at 530°C. Indications are that finer grain sizes should be attainable by using slightly lower temperatures and higher pressures. The success of the technique (compared to hot-isostatic pressing (“hipping”)) is due to both reducing time at elevated temperatures and applying relatively high pressures. Microhardness tests revealed a significant strengthening effect due to grain size refinement, following a Hall-Petch relation. Compression testing at room temperature showed no strain hardening during plastic deformation, which occurred by shear banding. High strengths, up to 1800 MPa, were obtained at room temperature. Compression testing at 575°C revealed a significant strain rate dependence of mechanical behavior and also the possibility of superplastic behavior. Power-law creep was observed at 575°C, with very high steady-state creep rates on the order of 50 pct/s at 230 MPa. The consolidation process was successfully modeled by slightly modifying and applying the Arzt, Ashby, and

  1. Does brand differentiate pharmaceuticals?

    Science.gov (United States)

    Bednarik, Josef

    2005-12-01

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

  2. Intellectual property and pharmaceutical innovation : a model for managing the creation of knowledge under proprietary conditions

    NARCIS (Netherlands)

    Reekum, Antonie Henric van

    1999-01-01

    This study focused on IP management in the context of pharmaceutical innovation. The pharmaceutical industry was chosen because, in an early stage of the project, several indications were found that intellectual property is of particular concern to management in this industry. The theoretical contri

  3. Modeling the Phase Behavior in Mixtures of Pharmaceuticals with Liquid or Supercritical Solvents

    DEFF Research Database (Denmark)

    Tsivintzelis, Ioannis; Economou, Ioannis; Kontogeorgis, Georgios

    2009-01-01

    the phase behavior of mixtures of six pharmaceuticals (i.e., ibuprofen, ketoprofen, naproxen, benzoic acid, methyl paraben, and ethyl paraben). The pure fluid parameters of the studied pharmaceuticals were estimated using limited available experimental (or predicted) data on sublimation pressures, liquid...

  4. Modeling the effects of promotional efforts on aggregate pharmaceutical demand : What we know and challenges for the future

    NARCIS (Netherlands)

    Wieringa, J.E.; Osinga, E.C.; Conde, E.R.; Leeflang, P.S.H.; Stern, P.; Ding, M.; Eliashberg, J.; Stremersch, S.

    2014-01-01

    Pharmaceutical marketing is becoming an important area of research in its own right, as evidenced by the steady increase in relevant papers published in the major marketing journals in recent years. These papers utilize different modeling techniques and types of data. In this chapter we focus on

  5. Radiation chemistry of salicylic and methyl substituted salicylic acids: Models for the radiation chemistry of pharmaceutical compounds

    Science.gov (United States)

    Ayatollahi, Shakiba; Kalnina, Daina; Song, Weihua; Turks, Maris; Cooper, William J.

    2013-11-01

    Salicylic acid and its derivatives are components of many medications and moieties found in numerous pharmaceutical compounds. They have been used as models for various pharmaceutical compounds in pharmacological studies, for the treatment of pharmaceuticals and personal care products (PPCPs), and, reactions with natural organic matter (NOM). In this study, the radiation chemistry of benzoic acid, salicylic acid and four methyl substituted salicylic acids (MSA) is reported. The absolute bimolecular reaction rate constants for hydroxyl radical reaction with benzoic and salicylic acids as well as 3-methyl-, 4-methyl-, 5-methyl-, and 6-methyl-salicylic acid were determined (5.86±0.54)×109, (1.07±0.07)×1010, (7.48±0.17)×109, (7.31±0.29)×109, (5.47±0.25)×109, (6.94±0.10)×109 (M-1 s-1), respectively. The hydrated electron reaction rate constants were measured (3.02±0.10)×109, (8.98±0.27)×109, (5.39±0.21)×109, (4.33±0.17)×109, (4.72±0.15)×109, (1.42±0.02)×109 (M-1 s-1), respectively. The transient absorption spectra for the six model compounds were examined and their role as model compounds for the radiation chemistry of pharmaceuticals investigated.

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

    Science.gov (United States)

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

    2012-01-01

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

  7. De-risking pharmaceutical tablet manufacture through process understanding, latent variable modeling, and optimization technologies.

    Science.gov (United States)

    Muteki, Koji; Swaminathan, Vidya; Sekulic, Sonja S; Reid, George L

    2011-12-01

    In pharmaceutical tablet manufacturing processes, a major source of disturbance affecting drug product quality is the (lot-to-lot) variability of the incoming raw materials. A novel modeling and process optimization strategy that compensates for raw material variability is presented. The approach involves building partial least squares models that combine raw material attributes and tablet process parameters and relate these to final tablet attributes. The resulting models are used in an optimization framework to then find optimal process parameters which can satisfy all the desired requirements for the final tablet attributes, subject to the incoming raw material lots. In order to de-risk the potential (lot-to-lot) variability of raw materials on the drug product quality, the effect of raw material lot variability on the final tablet attributes was investigated using a raw material database containing a large number of lots. In this way, the raw material variability, optimal process parameter space and tablet attributes are correlated with each other and offer the opportunity of simulating a variety of changes in silico without actually performing experiments. The connectivity obtained between the three sources of variability (materials, parameters, attributes) can be considered a design space consistent with Quality by Design principles, which is defined by the ICH-Q8 guidance (USDA 2006). The effectiveness of the methodologies is illustrated through a common industrial tablet manufacturing case study.

  8. Modelling On Photogeneration Of Hydroxyl Radical In Surface Waters And Its Reactivity Towards Pharmaceutical Wastes

    Science.gov (United States)

    Das, Radha; Vione, Davide; Rubertelli, Francesca; Maurino, Valter; Minero, Claudio; Barbati, Stéphane; Chiron, Serge

    2010-10-01

    This paper reports a simple model to describe the formation and reactivity of hydroxyl radicals in the whole column of freshwater lakes. It is based on empirical irradiation data and is a function of the water chemical composition (the photochemically significant parameters NPOC, nitrate, nitrite, carbonate and bicarbonate), the lake conformation best expressed as the average depth, and the water absorption spectrum in a simplified Lambert-Beer approach. The purpose is to derive the lifetime of dissolved molecules, due to reaction with •OH, on the basis of their second-order rate constants with the hydroxyl radical. The model was applied to two compounds of pharmaceutical wastes ibuprofen and carbamazepine, for which the second-order rate constants for reaction with the hydroxyl radical were measured by means of the competition kinetics with 2-propanol. The measured values of the rate constants are 1.0×1010 and 1.6×1010M-1 s-1 for ibuprofen and carbamazepine, respectively. The model suggests that the lifetime of a given compound can be very variable in different lakes, even more than the lifetime of different compounds in the same lake. It can be concluded that as far as the reaction with •OH, is concerned the concepts of photolability and photostability, traditionally attached to definite compounds, are ecosystem-dependent at least as much as they depend on the molecule under consideration.

  9. Fatigue-crack-initiation numerical modelling of a Ni-base powder metallurgy alloy

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    A simplified three-dimensional numerical model was presented to simulate the micro-crack nucleation and growth to some predefined dimension(approximately 0.38 mm) on the throat surface of a Ni-base powder metallurgy(PM) specimen.The numerical simulation of micro-crack initiation was based on the Tanaka-Mura micro-crack initiation models,where individual grains of the mesoscopic model were simulated using the Voronoi tessellation.Four improvements were made in the model.(1) Considering crack initiation along with 12 principal slip systems on octahedral slip planes of face centered cubic(FCC) crystal in three-dimensional(3-D) models.(2) Considering the effect of secondary phase precipitate due to impinging slip and dislocation pileup.(3) The Tanaka-Mura theory of fatigue-crack-initiation from notches was applied to simulate the crack initiation from another crack tip.(4) The coalescence of random initiated micro-cracks was simulated once they intersected with each other and a macro-crack was finally formed.The calculated results were in good agreement with the experimental data which verified the rationality of the simulation model.The applicability of the proposed model for treating fatigue-crack-initiation life in engineering structures was preliminarily achieved.%A simplified three-dimensional numerical model was presented to simulate the micro-crack nucleation and growth to some predefined dimension(approximately 0.38 mm) on the throat surface of a Ni-base powder metallurgy(PM) specimen.The numerical simulation of micro-crack initiation was based on the Tanaka-Mura micro-crack initiation models,where individual grains of the mesoscopic model were simulated using the Voronoi tessellation.Four improvements were made in the model.(1) Considering crack initiation along with 12 principal slip systems on octahedral slip planes of face centered cubic(FCC) crystal in three-dimensional(3-D) models.(2) Considering the effect of secondary phase

  10. Numerical Modelling of Agglomeration and Deagglomeration in Dry Powder Inhalers: A Review.

    Science.gov (United States)

    Yang, Jiecheng; Wu, Chuan-Yu; Adams, Michael

    2015-01-01

    Numerical modelling using computational fluid mechanics (CFD) and discrete element method (DEM) becomes increasingly prevalent for the exploration of agglomeration and deagglomeration in dry powder inhalers (DPIs). These techniques provide detailed information on air flow and particle-particle/wall interaction, respectively. Coupling of CFD and DEM enables an in-depth investigation of the mechanisms at the microscopic level. This paper reviews the applications of CFD and DEM in DPI development and optimisation. The recent progress in modelling of two key processes in DPIs, i.e. agglomeration and deagglomeration, is presented. It has been demonstrated that DEM-CFD is a promising numerical approach to investigate the underlying agglomeration and deagglomeration mechanisms for DPIs. With further advances in computing capacity, it is expected that DEM-CFD will be capable of addressing more realistic and complicated issues in DPI improvement.

  11. Application of powder densification models to the consolidation processing of composites

    Science.gov (United States)

    Wadley, H. N. G.; Elzey, D. M.

    1991-01-01

    Unidirectional fiber reinforced metal matrix composite tapes (containing a single layer of parallel fibers) can now be produced by plasma deposition. These tapes can be stacked and subjected to a thermomechanical treatment that results in a fully dense near net shape component. The mechanisms by which this consolidation step occurs are explored, and models to predict the effect of different thermomechanical conditions (during consolidation) upon the kinetics of densification are developed. The approach is based upon a methodology developed by Ashby and others for the simpler problem of HIP of spherical powders. The complex problem is devided into six, much simpler, subproblems, and then their predicted contributions are added to densification. The initial problem decomposition is to treat the two extreme geometries encountered (contact deformation occurring between foils and shrinkage of isolated, internal pores). Deformation of these two geometries is modelled for plastic, power law creep and diffusional flow. The results are reported in the form of a densification map.

  12. Rapid Characterization of Tanshinone Extract Powder by Near Infrared Spectroscopy

    Directory of Open Access Journals (Sweden)

    Gan Luo

    2015-01-01

    Full Text Available Chemical and physical quality attributes of herbal extract powders play an important role in the research and development of Chinese medicine preparations. The active pharmaceutical ingredients have a direct impact on the herbal extract’s efficacy, while the physical properties of raw material affect the pharmaceutical manufacturing process and the final products’ quality. In this study, tanshinone extract powders from Salvia miltiorrhiza which are widely used for the treatment of cardiovascular diseases in the clinic are taken as the research object. Both the chemical information and physical information of tanshinone extract powders are analyzed by near infrared (NIR spectroscopy. The partial least squares (PLS and least square support vector machine (LS-SVM models are investigated to build the relationship between NIR spectra and reference values. PLS models performed well for the content of crytotanshinone, tanshinone IIA, the moisture, and average median particle size, while, for specific surface area and tapped density, the LS-SVM models performed better than the PLS models. Results demonstrated NIR to be a valid and fast process analytical technology tool to simultaneously determine multiple quality attributes of herbal extract powders and indicated that there existed some nonlinear relationship between NIR spectra and physical quality attributes.

  13. Branched pore kinetic model analysis of geosmin adsorption on super-powdered activated carbon.

    Science.gov (United States)

    Matsui, Yoshihiko; Ando, Naoya; Sasaki, Hiroshi; Matsushita, Taku; Ohno, Koichi

    2009-07-01

    Super-powdered activated carbon (S-PAC) is activated carbon of much finer particle size than powdered activated carbon (PAC). Geosmin is a naturally occurring taste and odor compound that impairs aesthetic quality in drinking water. Experiments on geosmin adsorption on S-PAC and PAC were conducted, and the results using adsorption kinetic models were analyzed. PAC pulverization, which produced the S-PAC, did not change geosmin adsorption capacity, and geosmin adsorption capacities did not differ between S-PAC and PAC. Geosmin adsorption kinetics, however, were much higher on S-PAC than on PAC. A solution to the branched pore kinetic model (BPKM) was developed, and experimental adsorption kinetic data were analyzed by BPKM and by a homogeneous surface diffusion model (HSDM). The HSDM describing the adsorption behavior of geosmin required different surface diffusivity values for S-PAC and PAC, which indicated a decrease in surface diffusivity apparently associated with activated carbon particle size. The BPKM, consisting of macropore diffusion followed by mass transfer from macropore to micropore, successfully described the batch adsorption kinetics on S-PAC and PAC with the same set of model parameter values, including surface diffusivity. The BPKM simulation clearly showed geosmin removal was improved as activated carbon particle size decreased. The simulation also implied that the rate-determining step in overall mass transfer shifted from intraparticle radial diffusion in macropores to local mass transfer from macropore to micropore. Sensitivity analysis showed that adsorptive removal of geosmin improved with decrease in activated carbon particle size down to 1microm, but further particle size reduction produced little improvement.

  14. Finite Element Method (FEM) Modeling of Freeze-drying: Monitoring Pharmaceutical Product Robustness During Lyophilization.

    Science.gov (United States)

    Chen, Xiaodong; Sadineni, Vikram; Maity, Mita; Quan, Yong; Enterline, Matthew; Mantri, Rao V

    2015-12-01

    Lyophilization is an approach commonly undertaken to formulate drugs that are unstable to be commercialized as ready to use (RTU) solutions. One of the important aspects of commercializing a lyophilized product is to transfer the process parameters that are developed in lab scale lyophilizer to commercial scale without a loss in product quality. This process is often accomplished by costly engineering runs or through an iterative process at the commercial scale. Here, we are highlighting a combination of computational and experimental approach to predict commercial process parameters for the primary drying phase of lyophilization. Heat and mass transfer coefficients are determined experimentally either by manometric temperature measurement (MTM) or sublimation tests and used as inputs for the finite element model (FEM)-based software called PASSAGE, which computes various primary drying parameters such as primary drying time and product temperature. The heat and mass transfer coefficients will vary at different lyophilization scales; hence, we present an approach to use appropriate factors while scaling-up from lab scale to commercial scale. As a result, one can predict commercial scale primary drying time based on these parameters. Additionally, the model-based approach presented in this study provides a process to monitor pharmaceutical product robustness and accidental process deviations during Lyophilization to support commercial supply chain continuity. The approach presented here provides a robust lyophilization scale-up strategy; and because of the simple and minimalistic approach, it will also be less capital intensive path with minimal use of expensive drug substance/active material.

  15. Using pharmacoeconomic modelling to determine value-based pricing for new pharmaceuticals in malaysia.

    Science.gov (United States)

    Dranitsaris, George; Truter, Ilse; Lubbe, Martie S; Sriramanakoppa, Nitin N; Mendonca, Vivian M; Mahagaonkar, Sangameshwar B

    2011-10-01

    Decision analysis (DA) is commonly used to perform economic evaluations of new pharmaceuticals. Using multiples of Malaysia's per capita 2010 gross domestic product (GDP) as the threshold for economic value as suggested by the World Health Organization (WHO), DA was used to estimate a price per dose for bevacizumab, a drug that provides a 1.4-month survival benefit in patients with metastatic colorectal cancer (mCRC). A decision model was developed to simulate progression-free and overall survival in mCRC patients receiving chemotherapy with and without bevacizumab. Costs for chemotherapy and management of side effects were obtained from public and private hospitals in Malaysia. Utility estimates, measured as quality-adjusted life years (QALYs), were determined by interviewing 24 oncology nurses using the time trade-off technique. The price per dose was then estimated using a target threshold of US$44 400 per QALY gained, which is 3 times the Malaysian per capita GDP. A cost-effective price for bevacizumab could not be determined because the survival benefit provided was insufficient According to the WHO criteria, if the drug was able to improve survival from 1.4 to 3 or 6 months, the price per dose would be $567 and $1258, respectively. The use of decision modelling for estimating drug pricing is a powerful technique to ensure value for money. Such information is of value to drug manufacturers and formulary committees because it facilitates negotiations for value-based pricing in a given jurisdiction.

  16. Model-Based PAT for Quality Management in Pharmaceuticals Freeze-Drying: State of the Art

    Science.gov (United States)

    Fissore, Davide

    2017-01-01

    Model-based process analytical technologies can be used for the in-line control and optimization of a pharmaceuticals freeze-drying process, as well as for the off-line design of the process, i.e., the identification of the optimal operating conditions. This paper aims at presenting the state of the art in this field, focusing, particularly, on three groups of systems, namely, those based on the temperature measurement (i.e., the soft sensor), on the chamber pressure measurement (i.e., the systems based on the test of pressure rise and of pressure decrease), and on the sublimation flux estimate (i.e., the tunable diode laser absorption spectroscopy and the valveless monitoring system). The application of these systems for in-line process optimization (e.g., using a model predictive control algorithm) and to get a true quality by design (e.g., through the off-line calculation of the design space of the process) is presented and discussed. PMID:28224123

  17. A QSAR model for predicting rejection of emerging contaminants (pharmaceuticals, endocrine disruptors) by nanofiltration membranes.

    Science.gov (United States)

    Yangali-Quintanilla, Victor; Sadmani, Anwar; McConville, Megan; Kennedy, Maria; Amy, Gary

    2010-01-01

    A quantitative structure activity relationship (QSAR) model has been produced for predicting rejection of emerging contaminants (pharmaceuticals, endocrine disruptors, pesticides and other organic compounds) by polyamide nanofiltration (NF) membranes. Principal component analysis, partial least square regression and multiple linear regressions were used to find a general QSAR equation that combines interactions between membrane characteristics, filtration operating conditions and compound properties for predicting rejection. Membrane characteristics related to hydrophobicity (contact angle), salt rejection, and surface charge (zeta potential); compound properties describing hydrophobicity (log K(ow), log D), polarity (dipole moment), and size (molar volume, molecular length, molecular depth, equivalent width, molecular weight); and operating conditions namely flux, pressure, cross flow velocity, back diffusion mass transfer coefficient, hydrodynamic ratio (J(o)/k), and recovery were identified as candidate variables for rejection prediction. An experimental database produced by the authors that accounts for 106 rejection cases of emerging contaminants by NF membranes as result of eight experiments with clean and fouled membranes (NF-90, NF-200) was used to produce the QSAR model. Subsequently, using the QSAR model, rejection predictions were made for external experimental databases. Actual rejections were compared against predicted rejections and acceptable R(2) correlation coefficients were found (0.75 and 0.84) for the best models. Additionally, leave-one-out cross-validation of the models achieved a Q(2) of 0.72 for internal validation. In conclusion, a unified general QSAR equation was able to predict rejections of emerging contaminants during nanofiltration; moreover the present approach is a basis to continue investigation using multivariate analysis techniques for understanding membrane rejection of organic compounds.

  18. Preparation and properties of dough-modeling compound/fly ash/reclaim powder composites

    Energy Technology Data Exchange (ETDEWEB)

    Wu, W.L. [Qiqihar University, Qiqihar (China)

    2007-12-15

    A novel composite was prepared with reclaim powder (RP) matrix, dough-modeling compound (DMC) reinforcement and fly ash (FA) filler in this article. The compatibility and crosslinking construction of the FA/RP composites were respectively, studied by the polarizing microscope and IR, the optimal formulation and experimental process were determined by measuring the mechanical properties such as shore A hardness, tensile strength, elongation at break, wear resistance and the thermal stability. The results showed that DMC/FA/RP composites exhibited extremely high mechanical and thermal properties when the mass ratio of the DMC/FA/RP composites was 45/25/100, and the cure condition is at 145 {sup o}C for 30 min under 9 MPa.

  19. Evaluating the environmental fate of pharmaceuticals using a level III model based on poly-parameter linear free energy relationships.

    Science.gov (United States)

    Zukowska, Barbara; Breivik, Knut; Wania, Frank

    2006-04-15

    We recently proposed how to expand the applicability of multimedia models towards polar organic chemicals by expressing environmental phase partitioning with the help of poly-parameter linear free energy relationships (PP-LFERs). Here we elaborate on this approach by applying it to three pharmaceutical substances. A PP-LFER-based version of a Level III fugacity model calculates overall persistence, concentrations and intermedia fluxes of polar and non-polar organic chemicals between air, water, soil and sediments at steady-state. Illustrative modeling results for the pharmaceuticals within a defined coastal region are presented and discussed. The model results are highly sensitive to the degradation rate in water and the equilibrium partitioning between organic carbon and water, suggesting that an accurate description of this particular partitioning equilibrium is essential in order to obtain reliable predictions of environmental fate. The PP-LFER based modeling approach furthermore illustrates that the greatest mobility in aqueous phases may be experienced by pharmaceuticals that combines a small molecular size with strong H-acceptor properties.

  20. Evaluating the environmental fate of pharmaceuticals using a level III model based on poly-parameter linear free energy relationships

    Energy Technology Data Exchange (ETDEWEB)

    Zukowska, Barbara [Department of Analytical Chemistry, Chemical Faculty, Gdansk University of Technology, 11/12 G. Narutowicza St., 80-952 Gdansk (Poland); Breivik, Knut [NILU- Norwegian Institute for Air Research, P.O. Box 100, NO-2027 Kjeller (Norway)]. E-mail: knut.breivik@nilu.no; Wania, Frank [Department of Physical and Environmental Sciences, University of Toronto at Scarborough, 1265 Military Trail, Scarborough, Ontario, M1C 1A4 (Canada)

    2006-04-15

    We recently proposed how to expand the applicability of multimedia models towards polar organic chemicals by expressing environmental phase partitioning with the help of poly-parameter linear free energy relationships (PP-LFERs). Here we elaborate on this approach by applying it to three pharmaceutical substances. A PP-LFER-based version of a Level III fugacity model calculates overall persistence, concentrations and intermedia fluxes of polar and non-polar organic chemicals between air, water, soil and sediments at steady-state. Illustrative modeling results for the pharmaceuticals within a defined coastal region are presented and discussed. The model results are highly sensitive to the degradation rate in water and the equilibrium partitioning between organic carbon and water, suggesting that an accurate description of this particular partitioning equilibrium is essential in order to obtain reliable predictions of environmental fate. The PP-LFER based modeling approach furthermore illustrates that the greatest mobility in aqueous phases may be experienced by pharmaceuticals that combines a small molecular size with strong H-acceptor properties.

  1. Oral administration of red ginseng powder fermented with probiotic alleviates the severity of dextran-sulfate sodium-induced colitis in a mouse model.

    Science.gov (United States)

    Jang, Sun-Hee; Park, Jisang; Kim, Sae-Hae; Choi, Kyung-Min; Ko, Eun-Sil; Cha, Jeong-Dan; Lee, Young-Ran; Jang, Hyonseok; Jang, Yong-Suk

    2017-03-01

    Red ginseng is a well-known alternative medicine with anti-inflammatory activity. It exerts pharmacological effects through the transformation of saponin into metabolites by intestinal microbiota. Given that intestinal microflora vary among individuals, the pharmacological effects of red ginseng likely vary among individuals. In order to produce homogeneously effective red ginseng, we prepared probiotic-fermented red ginseng and evaluated its activity using a dextran sulfate sodium (DSS)-induced colitis model in mice. Initial analysis of intestinal damage indicated that the administration of probiotic-fermented red ginseng significantly decreased the severity of colitis, compared with the control and the activity was higher than that induced by oral administration of ginseng powder or probiotics only. Subsequent analysis of the levels of serum IL-6 and TNF-α, inflammatory biomarkers that are increased at the initiation stage of colitis, were significantly decreased in probiotic-fermented red ginseng-treated groups in comparison to the control group. The levels of inflammatory cytokines and mRNAs for inflammatory factors in colorectal tissues were also significantly decreased in probiotic-fermented red ginseng-treated groups. Collectively, oral administration of probiotic-fermented red ginseng reduced the severity of colitis in a mouse model, suggesting that it can be used as a uniformly effective red ginseng product. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  2. Confined wetting of FoCa clay powder/pellet mixtures: Experimentation and numerical modeling

    Science.gov (United States)

    Maugis, Pascal; Imbert, Christophe

    Potential geological nuclear waste disposals must be properly sealed to prevent contamination of the biosphere by radionuclides. In the framework of the RESEAL project, the performance of a bentonite shaft seal is currently studied at Mol (Belgium). This paper focuses on the hydro-mechanical physical behavior of centimetric, unsaturated samples of the backfilling material - a mixture of FoCa-clay powder and pellets - during oedometer tests. The hydro-mechanical response of the samples is observed experimentally, and then compared to numerical simulations performed by our Cast3M Finite Element code. The generalized Darcy’s law and the Barcelona Basic Model mechanical model formed the physical basis of the numerical model and the interpretation. They are widely used in engineered barriers modeling. Vertical swelling pressure and water intake were measured throughout the test. Although water income presents a monotonous increase, the swelling pressure evolution is marked by a peak, and then a local minimum before increasing again to an asymptotic value. This unexpected behavior is explained by yielding rather than by heterogeneity. It is satisfactorily reproduced by the model after parameter calibration. Several samples with different heights ranging from 5 to 12 cm show the same hydro-mechanical response, apart from a dilatation of the time scale. The interest of the characterization of centimetric samples to predicting the efficiency of a metric sealing is discussed.

  3. Finite element modeling of the powder-in- tube process for manufacture of BSCCO-2212 superconducting wires

    Science.gov (United States)

    Shah, R.; Tangrila, S.; Rachakonda, S.; Thirukkonda, M.

    1995-12-01

    High-temperature superconductors have recently attracted a great deal of attention owing to their potential use in a variety of applications including power generators, superconducting magnets for mine sweepers or ship propulsion motors, and magnetic levitation transportation systems. The powder-in-tube (PIT) process has emerged as one of the most promising and economically feasible techniques to produce long lengths high-Tc oxide based superconducting wires. The PIT method involves multi-pass wire drawing followed by rolling and heat treatment. This work focuses on the development of finite element models to simulate the PIT drawing process for fabrication of silver sheathed Bi-2212 superconducting wires. The numerical models were used to predict the density of the oxide powder, the wire drawing forces, and the silver-oxide ratio during drawing. A cap-type pressure dependent constitutive equation was implemented in the model to simulate the powder behavior. The model incorporated experimentally obtained material data for the silver and powder. Data from wire drawing experiments were used to verify model predictions.

  4. Grape powder treatment prevents anxiety-like behavior in a rat model of aging.

    Science.gov (United States)

    Patki, Gaurav; Ali, Quaisar; Pokkunuri, Indira; Asghar, Mohammad; Salim, Samina

    2015-06-01

    Earlier, we have reported that grape powder (GP) treatment prevented pharmacologic and psychological stress-induced anxiety-like behavior and memory impairment in rats. Protective effects of GP were attributed to its antioxidant effects. In this study, we tested the hypothesis that age-associated behavioral and cognitive deficits such as anxiety and memory impairment will be ameliorated with GP treatment. Using a National Institute of Aging recommended rodent model of aging, we examined a potentially protective role of antioxidant-rich GP in age-associated anxiety-like behavior and memory impairment. Male Fischer 344 rats were randomly assigned into 4 groups: young rats (3 months old) provided with tap water or with 15 g/L GP dissolved in tap water for 3 weeks, aged rats (21 months old) provided with tap water or with GP-treated tap water for 3 weeks (AG-GP). Anxiety-like behavior was significantly greater in aged rats compared with young rats, GP-treated young rats, or aged control rats (P treatment prevented age-induced anxiety-like behavior in AG-GP rats (P treatment in AG-GP rats. Furthermore, aged rats showed increased level of physiological stress (corticosterone) and increased oxidative stress in the plasma (8-isoprostane) as well as in selected brain areas (protein carbonylation). Grape powder treatment prevented age-induced increase in corticosterone levels and plasma 8-isoprostane levels in aged rats (P anxiety-like behavior in rats, whereas age-associated memory deficits seem unaffected with GP treatment.

  5. Conference report: reviving pharmaceutical R&D with translational science, regulatory efficiency and innovative models.

    Science.gov (United States)

    Zhang, Tianyi Tee; Weng, Naidong; Lee, Mike

    2013-10-01

    The 4th Annual Shanghai Symposium on Clinical & Pharmaceutical Solutions through Analysis (CPSA Shanghai 2013) was held on 24-27 April 2013 in Shanghai, China. The meeting provided an educational forum for scientists from pharmaceutical industry, academia, CROs and instrument vendors to share experience and ideas, and discuss current challenges, issues and innovative solutions associated with pharmaceutical R&D. The meeting featured highly interactive events, including diversified symposia, roundtable discussions, workshops, poster sessions and conference awards. Education and specialized training are the foundation of CPSA events. The CPSA Shanghai 2013 meeting also featured an inaugural satellite workshop event in Beijing, as well as joint sessions traditionally held with local bioanalytical and drug metabolism discussion groups.

  6. The CTSA Pharmaceutical Assets Portal – a public–private partnership model for drug repositioning

    Science.gov (United States)

    Marusina, Kate; Welsch, Dean J.; Rose, Lynn; Brock, Doug; Bahr, Nathan

    2011-01-01

    The Pharmaceutical Assets Portal aims to facilitate industry-academic collaborations for discovery of new indications for compounds no longer being developed by pharmaceutical companies, through eliminating barriers to access such compounds. The Portal’s enabling infrastructure includes a national investigator database; a Foci-of-Expertise browser; a material transfer agreement template; and a funding partner. Whereas the goal of creating a shared compound repository remains to be achieved, the Portal has established a mechanism to facilitate future drug repositioning opportunities. PMID:22768020

  7. Pulmonary drug delivery by powder aerosols.

    Science.gov (United States)

    Yang, Michael Yifei; Chan, John Gar Yan; Chan, Hak-Kim

    2014-11-10

    The efficacy of pharmaceutical aerosols relates to its deposition in the clinically relevant regions of the lungs, which can be assessed by in vivo lung deposition studies. Dry powder formulations are popular as devices are portable and aerosolisation does not require a propellant. Over the years, key advancements in dry powder formulation, device design and our understanding on the mechanics of inhaled pharmaceutical aerosol have opened up new opportunities in treatment of diseases through pulmonary drug delivery. This review covers these advancements and future directions for inhaled dry powder aerosols.

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

    Science.gov (United States)

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

    2014-09-15

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

  9. Evaluation of a model for the removal of pharmaceuticals, personal care products, and hormones from wastewater

    Energy Technology Data Exchange (ETDEWEB)

    Blair, Benjamin D. [School of Freshwater Sciences, University of Wisconsin-Milwaukee, 600 E. Greenfield Ave, Milwaukee, WI 53204 (United States); Crago, Jordan P. [Department of Biology, University of Wisconsin-Milwaukee, 600 E. Greenfield Ave, Milwaukee, WI 53204 (United States); Hedman, Curtis J. [State Laboratory of Hygiene, University of Wisconsin-Madison, 2601 Agriculture Drive, Madison, WI 53718 (United States); Treguer, Ronan J.F. [Veolia Water North America, 101 West Washington St., Ste. 1400 East, Indianapolis, IN 46204 (United States); Magruder, Christopher [Milwaukee Metropolitan Sewer District, 260 W. Seeboth St, Milwaukee, WI 53204 (United States); Royer, L. Scott [Veolia Water Milwaukee, 700 E. Jones St., Milwaukee, WI 53207 (United States); Klaper, Rebecca D., E-mail: rklaper@uwm.edu [School of Freshwater Sciences, University of Wisconsin-Milwaukee, 600 E. Greenfield Ave, Milwaukee, WI 53204 (United States)

    2013-02-01

    Current wastewater treatment processes are insufficient at removing many pharmaceutical and personal care products (PPCPs) from wastewater and it is necessary to identify the chemical characteristics that determine their fate. Models that predict the fate of various chemicals lack verification using in situ data, particularly for PPCPs. BIOWIN4 is a quantitative structure–activity relationship (QSAR) model that has been proposed to estimate the removal of PPCPs from wastewater, but data verifying the accuracy of its predictions is limited. In this study, the in situ soluble and suspended solid concentrations were assessed from raw influent, primary effluent, secondary effluent, and final effluent for 54 PPCPs and hormones over six dates. When assessing the removal efficiency across the different stages of the WWTP, the majority of the removal occurred across the secondary treatment process for the majority of the compounds. The primary treatment and disinfection process had limited impacts on the removal of most PPCPs. Sorption to solids was found to influence the removal for compounds with a log octanol–water partitioning coefficient greater than 4.5 across the secondary treatment process. For other compounds, the removal of PPCPs across the secondary treatment process was significantly correlated with the biodegradation predicted by BIOWIN4. Removal efficiencies across the aerobic secondary treatment process were predicted by integrating BIOWIN4 into pseudo-first order kinetics of PPCPs and these predicted values were compared to the in situ data. This study determines that under a certain set of operating conditions, two chemical characteristics — the expected hydrophobic interaction and the modeled biological degradation from BIOWIN4 — were found to predict the removal of highly degradable and recalcitrant PPCPs from a wastewater secondary treatment process. - Highlights: ► Fifty-six PPCPs were assessed across the stages of a wastewater treatment

  10. Nasal Absorption of Macromolecules from Powder Formulations and Effects of Sodium Carboxymethyl Cellulose on Their Absorption.

    Science.gov (United States)

    Tanaka, Akiko; Furubayashi, Tomoyuki; Matsushita, Akifumi; Inoue, Daisuke; Kimura, Shunsuke; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

    2016-01-01

    The nasal absorption of macromolecules from powder formulations and the effect of sodium carboxymethyl cellulose (CMC-Na) as a pharmaceutical excipient on their absorption were studied. Model macromolecules were fluorescein isothiocyanate-labeled dextran (average molecular weight of 4.4kDa, FD4) and insulin. The plasma concentration of FD4 after application of the powder containing 50% starch (control) was higher than that after application of the solution, and the absorption from 50% starch powder was enhanced by the substitution of starch with CMC-Na. The fractional absorption of FD4 after administration of the CMC-Na powder formulation was 30% and 40% higher than that after administration from the solution and the starch powder, respectively. The nasal absorption of insulin from the powder and the effect of CMC-Na were similar with those of FD4. The effective absorption of FD4 and insulin after application of powder with CMC-Na could be due to the increase in the nasal residence of FD4 and insulin. No damage in the nasal mucosa or dysfunction of the mucociliary clearance was observed after application of the drug powder and CMC-Na. The present findings indicate that nasal delivery of powder formulations with the addition of CMC-Na as an excipient is a promising approach for improving the nasal absorption of macromolecules.

  11. Nasal Absorption of Macromolecules from Powder Formulations and Effects of Sodium Carboxymethyl Cellulose on Their Absorption

    Science.gov (United States)

    Tanaka, Akiko; Furubayashi, Tomoyuki; Matsushita, Akifumi; Inoue, Daisuke; Kimura, Shunsuke; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

    2016-01-01

    The nasal absorption of macromolecules from powder formulations and the effect of sodium carboxymethyl cellulose (CMC-Na) as a pharmaceutical excipient on their absorption were studied. Model macromolecules were fluorescein isothiocyanate-labeled dextran (average molecular weight of 4.4kDa, FD4) and insulin. The plasma concentration of FD4 after application of the powder containing 50% starch (control) was higher than that after application of the solution, and the absorption from 50% starch powder was enhanced by the substitution of starch with CMC-Na. The fractional absorption of FD4 after administration of the CMC-Na powder formulation was 30% and 40% higher than that after administration from the solution and the starch powder, respectively. The nasal absorption of insulin from the powder and the effect of CMC-Na were similar with those of FD4. The effective absorption of FD4 and insulin after application of powder with CMC-Na could be due to the increase in the nasal residence of FD4 and insulin. No damage in the nasal mucosa or dysfunction of the mucociliary clearance was observed after application of the drug powder and CMC-Na. The present findings indicate that nasal delivery of powder formulations with the addition of CMC-Na as an excipient is a promising approach for improving the nasal absorption of macromolecules. PMID:27598527

  12. In silico modelling of drug-polymer interactions for pharmaceutical formulations

    NARCIS (Netherlands)

    Ahmad, Samina; Johnston, Blair F.; Mackay, Simon P.; Schatzlein, Andreas G.; Gellert, Paul; Sengupta, Durba; Uchegbu, Ijeoma F.

    2010-01-01

    Selecting polymers for drug encapsulation in pharmaceutical formulations is usually made after extensive trial and error experiments. To speed up excipient choice procedures, we have explored coarse-grained computer simulations (dissipative particle dynamics (DPD) and coarse-grained molecular dynami

  13. Pharmaceutical Frenzy

    Institute of Scientific and Technical Information of China (English)

    LAN XINZHEN

    2010-01-01

    @@ When shares of Shanghai Pharmaceutical(Group)Co.Ltd.(Shanghai Pharma)resumed normal transactions on March9,2010,the biggest listed pharmaceutical company on China's stock market was born.By the time the closing bell rang at the end of the trading day,the market value of Shanghai Pharma had reached 32.28 billion yuan($4.73 billion).

  14. Storage stability of hen egg white powders in three protein/water dough model systems.

    Science.gov (United States)

    Rao, Qinchun; Rocca-Smith, Jeancarlo R; Labuza, Theodore P

    2013-06-01

    In recent years, due to the specific health benefits associated with bioactive peptides and the reduction of protein allergenicity by enzymatic hydrolysis, the utilisation of protein hydrolysates in the intermediate-moisture food (IMF) market, such as high protein nutrition bars (HPNB), has significantly increased. Currently, no reported study is related to the storage stability of dried hen egg white (DEW) and its hydrolysates (HEW) in an IMF matrix. Therefore, three DEW/HEW dough model systems (100%HEW+0%DEW, 75%HEW+25%DEW and 50%HEW+50%DEW) were established using two commercial spray-dried egg white powders to study the effect of temperature and fraction of HEW on these IMF models (water activity (a(w)): ∼0.8). During storage at three different temperatures (23, 35 and 45°C) for 70 days, the selected physicochemical properties of the dough systems were compared. Overall, kinetic analysis showed an apparent zero-order model fit for the change in the colour (L(∗)), fluorescence intensity (FI) and hardness, as a function of time, for different dough model systems. As expected, the L(∗), FI and hardness increased as a function of time mainly due to the Maillard reaction. The amount of free amino groups decreased, with an increase in rate of loss, as temperature increased in the 100%HEW+0%DEW model. When DEW was substituted for some HEW, the regeneration of the free amino groups after loss was observed as a function of time. Furthermore, when the percentage of HEW was decreased, the incidence of mouldy samples occurred sooner, which indicates that HEW has some antimicrobial ability, especially in the 100%HEW+0%DEW system where mould growth did not occur. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Influences of "spasmolytic powder" on pgp expression of Coriaria Lactone-kindling drug-resistant epileptic rat model.

    Science.gov (United States)

    Chen, Lei; Feng, Peimin; Li, Yaohua; Zhou, Dong

    2013-09-01

    The earliest records of traditional Chinese medicine (TCM) prevention and treatment of epilepsy dated back to famous "Huang Di Nei Jing." TCM "spasmolytic powder" (equal-ratio compatibility of scorpion and centipede) is a famous prescription which was recognized as a useful add-on drug for refractory epilepsy in clinical observations. Multidrug resistance gene (mdr1) product Pgp overexpression in blood-brain barrier and blood-cerebrospinal fluid barrier is well recognized as the drug resistance mechanism of refractory epilepsy. Here, we established the drug-resistant epilepsy Sprague-Dawley rat model induced by Coriaria Lactone and treated these rats with topiramate and verapamil and low dose, middle dose, and high dose of spasmolytic powder by intragastric administration for 1 week. Electroencephalogram, real-time PCR, and immunohistochemistry were respectively used to detect epileptic discharge frequencies and amplitudes and expression of mdrl mRNA and Pgp on hippocampus and temporal lobe of rats. The results showed that the seizure decreases significantly in the high- and middle-dose groups of spasmolytic powder and topiramate group; in addition, mdr1 mRNA and Pgp expressions on hippocampus and temporal lobe of these drug intervention groups were significantly less than the model group (P < 0.05). These findings indicate that inhibition of intracephalic Pgp expression is possibly one of mechanisms of spasmolytic powder treating refractory epilepsy.

  16. Hot-melt extruded filaments based on pharmaceutical grade polymers for 3D printing by fused deposition modeling.

    Science.gov (United States)

    Melocchi, Alice; Parietti, Federico; Maroni, Alessandra; Foppoli, Anastasia; Gazzaniga, Andrea; Zema, Lucia

    2016-07-25

    Fused deposition modeling (FDM) is a 3D printing technique based on the deposition of successive layers of thermoplastic materials following their softening/melting. Such a technique holds huge potential for the manufacturing of pharmaceutical products and is currently under extensive investigation. Challenges in this field are mainly related to the paucity of adequate filaments composed of pharmaceutical grade materials, which are needed for feeding the FDM equipment. Accordingly, a number of polymers of common use in pharmaceutical formulation were evaluated as starting materials for fabrication via hot melt extrusion of filaments suitable for FDM processes. By using a twin-screw extruder, filaments based on insoluble (ethylcellulose, Eudragit(®) RL), promptly soluble (polyethylene oxide, Kollicoat(®) IR), enteric soluble (Eudragit(®) L, hydroxypropyl methylcellulose acetate succinate) and swellable/erodible (hydrophilic cellulose derivatives, polyvinyl alcohol, Soluplus(®)) polymers were successfully produced, and the possibility of employing them for printing 600μm thick disks was demonstrated. The behavior of disks as barriers when in contact with aqueous fluids was shown consistent with the functional application of the relevant polymeric components. The produced filaments were thus considered potentially suitable for printing capsules and coating layers for immediate or modified release, and, when loaded with active ingredients, any type of dosage forms.

  17. Modeling of pharmaceuticals mixtures toxicity with deviation ratio and best-fit functions models.

    Science.gov (United States)

    Wieczerzak, Monika; Kudłak, Błażej; Yotova, Galina; Nedyalkova, Miroslava; Tsakovski, Stefan; Simeonov, Vasil; Namieśnik, Jacek

    2016-11-15

    The present study deals with assessment of ecotoxicological parameters of 9 drugs (diclofenac (sodium salt), oxytetracycline hydrochloride, fluoxetine hydrochloride, chloramphenicol, ketoprofen, progesterone, estrone, androstenedione and gemfibrozil), present in the environmental compartments at specific concentration levels, and their mutual combinations by couples against Microtox® and XenoScreen YES/YAS® bioassays. As the quantitative assessment of ecotoxicity of drug mixtures is an complex and sophisticated topic in the present study we have used two major approaches to gain specific information on the mutual impact of two separate drugs present in a mixture. The first approach is well documented in many toxicological studies and follows the procedure for assessing three types of models, namely concentration addition (CA), independent action (IA) and simple interaction (SI) by calculation of a model deviation ratio (MDR) for each one of the experiments carried out. The second approach used was based on the assumption that the mutual impact in each mixture of two drugs could be described by a best-fit model function with calculation of weight (regression coefficient or other model parameter) for each of the participants in the mixture or by correlation analysis. It was shown that the sign and the absolute value of the weight or the correlation coefficient could be a reliable measure for the impact of either drug A on drug B or, vice versa, of B on A. Results of studies justify the statement, that both of the approaches show similar assessment of the mode of mutual interaction of the drugs studied. It was found that most of the drug mixtures exhibit independent action and quite few of the mixtures show synergic or dependent action. Copyright © 2016. Published by Elsevier B.V.

  18. Modelling of laser cladding of magnesium alloys with pre-placed powders

    Science.gov (United States)

    Guo, Li-Feng

    As a surface engineering technique, high-power laser cladding, has shown great potential for improving the corrosion resistance of magnesium alloys. Its main advantage over other processes, is its ability to form relatively thick protective coatings on selected areas where improved properties are desired. It is also a 'clean' process. However, previous research studies have found that in laser cladding of magnesium alloys, the problem of a high degree of dilution cannot be easily overcome. Moreover, in-depth studies using analytical or numerical modelling can rarely be found in the literature for addressing laser cladding with pre-placed powders with the aim of predicting the level of dilution. In the first phase of this study, a simplified thermal model based on the finite element method (FEM) was developed to study the phenomenon of dilution in laser cladding of a magnesium alloy. In the model, the powder bed was treated as a continuum, and a high power continuous wave (CW) laser was employed. The results of the simulations of the FEM model together with those of the statistical analyses showed that although, under normal cladding conditions, a process window can be established for achieving good interfacial bonding between the substrate and the clad coating, a low dilution level was extremely difficult to achieve. This was primarily attributed to the low melting point and the high thermal diffusivity of magnesium as well as the relatively long laser-material interaction time. To overcome the dilution problem, the double-layer cladding technique was explored, and was found to be able to produce low dilution clads with improved corrosion resistance. In considering the improvement of corrosion resistance that can be caused by laser surface modification to magnesium alloys, a comparison was made between the techniques of laser surface melting and laser cladding. The results of the potentiodynamic polarisation tests showed that the improvement obtained from laser

  19. Semi-synthetic artemisinin: a model for the use of synthetic biology in pharmaceutical development.

    Science.gov (United States)

    Paddon, Chris J; Keasling, Jay D

    2014-05-01

    Recent developments in synthetic biology, combined with continued progress in systems biology and metabolic engineering, have enabled the engineering of microorganisms to produce heterologous molecules in a manner that was previously unfeasible. The successful synthesis and recent entry of semi-synthetic artemisinin into commercial production is the first demonstration of the potential of synthetic biology for the development and production of pharmaceutical agents. In this Review, we describe the metabolic engineering and synthetic biology approaches that were used to develop this important antimalarial drug precursor. This not only demonstrates the incredible potential of the available technologies but also illuminates how lessons learned from this work could be applied to the production of other pharmaceutical agents.

  20. Non-destructive and rapid prediction of moisture content in red pepper (Capsicum annuum L.) powder using near-infrared spectroscopy and a partial least squares regression model

    Science.gov (United States)

    Purpose: The aim of this study was to develop a technique for the non-destructive and rapid prediction of the moisture content in red pepper powder using near-infrared (NIR) spectroscopy and a partial least squares regression (PLSR) model. Methods: Three red pepper powder products were separated in...

  1. Sustainable use of veterinary pharmaceuticals on the territory (Sust-PHarm): Linking available database of manure management and environmental fate models.

    Science.gov (United States)

    Di Guardo, Andrea; Finizio, Antonio

    2017-01-01

    Analogously to the evolution of the EU legislation on pesticides, there is an increasing need of strategies aiming to reach a "sustainable use of veterinary pharmaceuticals". To this end, it is essential to develop tools, such as supporting information systems (SIS), for managing the environmental risks of veterinary pharmaceuticals on a territorial scale. In this context, we propose Sust-PHarm (SUSTainable use of veterinary Pharmaceuticals), a SIS useful to identify groundwater vulnerable areas to veterinary pharmaceuticals at both local and regional scale. As background, Sust-PHarm follows the schemes of SIS for pesticides. The latter are based on the integration of predictive models in GIS. The proposed approach goes a step forward by integrating also data on the typologies of livestock farm, their spatial distribution and manure management techniques. This information allows to identify the potential environmental loads of veterinary pharmaceuticals. In this paper, we discuss the innovative elements characterizing Sust-PHarm through a comparison with the SIS currently used for pesticides. The advantages of Sust-PHarm are discussed using Lombardia Region (Northern Italy) as a case study. Simulations were made on 12 veterinary pharmaceuticals characterized by different physical-chemical properties. Results are compared with the current guidelines for the evaluation of veterinary pharmaceuticals leaching highlighting some substantial differences when realistic data are utilized making our approach more accurate than guidelines one.

  2. Adsorption of Remazol Brilliant Blue R using ZnO fine powder: Equilibrium, kinetic and thermodynamic modeling studies

    Energy Technology Data Exchange (ETDEWEB)

    Ada, Kezban [Department of Chemistry, Faculty of Arts and Sciences, Kirikkale University, 71450 Yahsihan-Kirikkale (Turkey); Ergene, Aysun, E-mail: ayergene@yahoo.com [Department of Biology, Faculty of Arts and Sciences, Kirikkale University, 71450 Yahsihan-Kirikkale (Turkey); Tan, Sema; Yalcin, Emine [Department of Biology, Faculty of Arts and Sciences, Kirikkale University, 71450 Yahsihan-Kirikkale (Turkey)

    2009-06-15

    Zinc oxide powders with six-sided flake-like particles were prepared by homogeneous precipitation from boiling aqueous solutions that contained excess urea and 0.075 (Z075) and 0.300 (Z300) M Zn{sup 2+}. The average sizes of the particles are 37 and 46 {mu}m, while the average sizes of the crystals are {approx}45 for Z075 and Z300 at 1000 deg. C. Equilibrium, kinetic and thermodynamic studies were carried out for the adsorption of RBBR dye from aqueous solution using both types of ZnO in the form of fine powders. The effects of pH, initial dye concentration, contact time and temperature of solution on the adsorption were studied. Langmuir, Temkin and Dubinin-Radushkevich (D-R) isotherm models were used to describe the adsorption of RBBR onto ZnO powders. The Langmuir and D-R isotherm models fit the equilibrium data better than the Temkin isotherm model. The monomolecular adsorption capacity of Z075 and Z300 was determined to be 190 and 345 mg g{sup -1} for RBBR, respectively. The Lagergren first-order, Ritchie second-order kinetic and intra-particle diffusion models were used for the adsorption of the dye onto ZnO powders. The Ritchie second-order model was suitable for describing the adsorption kinetics for the removal of RBBR from aqueous solution onto Z075 and Z300. Thermodynamic parameters, such as the Gibbs free energy ({Delta}G{sup numbersign}), enthalpy ({Delta}H{sup numbersign}), entropy ({Delta}S{sup numbersign}) and equilibrium constant of activation (K{sup numbersign}) were calculated. These parameters showed that the adsorption process of RBBR onto Z075 and Z300 was an endothermic process of a chemical nature under the studied conditions.

  3. Adsorption of Remazol Brilliant Blue R using ZnO fine powder: equilibrium, kinetic and thermodynamic modeling studies.

    Science.gov (United States)

    Ada, Kezban; Ergene, Aysun; Tan, Sema; Yalçin, Emine

    2009-06-15

    Zinc oxide powders with six-sided flake-like particles were prepared by homogeneous precipitation from boiling aqueous solutions that contained excess urea and 0.075 (Z075) and 0.300 (Z300)M Zn(2+). The average sizes of the particles are 37 and 46 microm, while the average sizes of the crystals are approximately 45 for Z075 and Z300 at 1000 degrees C. Equilibrium, kinetic and thermodynamic studies were carried out for the adsorption of RBBR dye from aqueous solution using both types of ZnO in the form of fine powders. The effects of pH, initial dye concentration, contact time and temperature of solution on the adsorption were studied. Langmuir, Temkin and Dubinin-Radushkevich (D-R) isotherm models were used to describe the adsorption of RBBR onto ZnO powders. The Langmuir and D-R isotherm models fit the equilibrium data better than the Temkin isotherm model. The monomolecular adsorption capacity of Z075 and Z300 was determined to be 190 and 345 mg g(-1) for RBBR, respectively. The Lagergren first-order, Ritchie second-order kinetic and intra-particle diffusion models were used for the adsorption of the dye onto ZnO powders. The Ritchie second-order model was suitable for describing the adsorption kinetics for the removal of RBBR from aqueous solution onto Z075 and Z300. Thermodynamic parameters, such as the Gibbs free energy (DeltaG(#)), enthalpy (DeltaH(#)), entropy (DeltaS(#)) and equilibrium constant of activation (K(#)) were calculated. These parameters showed that the adsorption process of RBBR onto Z075 and Z300 was an endothermic process of a chemical nature under the studied conditions.

  4. Studying and Modeling the Effect of Graphite Powder Mixing Electrical Discharge Machining on the Main Process Characteristics

    Directory of Open Access Journals (Sweden)

    Ahmed N. Al-Khazraji

    2015-09-01

    Full Text Available This paper concerned with study the effect of a graphite micro powder mixed in the kerosene dielectric fluid during powder mixing electric discharge machining (PMEDM of high carbon high chromium AISI D2 steel. The type of electrode (copper and graphite, the pulse current and the pulse-on time and mixing powder in kerosene dielectric fluid are taken as the process main input parameters. The material removal rate MRR, the tool wear ratio TWR and the work piece surface roughness (SR are taken as output parameters to measure the process performance. The experiments are planned using response surface methodology (RSM design procedure. Empirical models are developed for MRR, TWR and SR, using the analysis of variance (ANOVA.The best results for the productivity of the process (MRR obtained when using the graphite electrodes, the pulse current (22 A, the pulse on duration (120 µs and using the graphite powder mixing in kerosene dielectric reaches (82.84mm³/min. The result gives an improvement in material removal rate of (274% with respect to the corresponding value obtained when copper electrodes with kerosene dielectric alone. The best results for the tool wear ratio (TWR of the process obtained when using the copper electrodes, the pulse current (8 A, the pulse on duration (120 µs and using the kerosene dielectric alone reaches (0.31 %. The use of graphite electrodes, the kerosene dielectric with 5g/l graphite powder mixing, the pulse current (8 A, the pulse on duration (40 µs give the best surface roughness of a value (2.77 µm.This result yields an improvement in SR by (141% with respect to the corresponding value obtained when using copper electrodes and the kerosene dielectric alone with the same other parameters and machining conditions.

  5. Pt-modified molybdenum carbide for the hydrogen evolution reaction: From model surfaces to powder electrocatalysts

    Science.gov (United States)

    Kelly, Thomas G.; Lee, Kevin X.; Chen, Jingguang G.

    2014-12-01

    This work explores the opportunity to substantially reduce the cost of hydrogen evolution reaction (HER) electrocatalysts by supporting one monolayer (ML) of platinum (Pt) on low-cost molybdenum carbide (Mo2C) substrate. These efforts were primarily directed towards scaling a thin-film catalyst to high surface area particles. Electrochemical experiments investigated single-phase Mo2C thin films modified by different coverages of Pt for the HER. The ML Pt-Mo2C thin film showed Pt-like HER activity while displaying excellent stability under HER conditions. The promising results on thin films were then extended to more practical powder catalysts. Samples of various Pt loadings on Mo2C powders were synthesized using the co-impregnation method and were evaluated for HER activity. The ability to successfully link electrochemical activity on thin films and powder catalysts was thus demonstrated.

  6. Baseline toxicity and ion-trapping models to describe the pH-dependence of bacterial toxicity of pharmaceuticals.

    Science.gov (United States)

    Baumer, Andreas; Bittermann, Kai; Klüver, Nils; Escher, Beate I

    2017-07-19

    In numerous studies on the toxicity of ionisable organic chemicals, it has been shown that the toxicity was typically higher, when larger fractions of the neutral species were present. This observation was explained in some cases by slower uptake of charged species. In other cases it was suggested that the neutral species has intrinsically higher toxicity than the charged species or is alone responsible for the toxicity. However, even permanently charged and organic chemicals with multiple acid and base functional groups and zwitterions are toxic. We set out to reconcile the divergent views and to compare the various existing models for describing the pH-dependence of toxicity with the goal to derive one model that is valid independent of the type and number of charges on the molecule. To achieve this goal we measured the cytotoxicity of 18 acidic, 15 basic and 9 multiprotic/zwitterionic pharmaceuticals at pH 5.5 to pH 9 with the bioluminescence inhibition test using Aliivibrio fischeri (Microtox assay). This assay is useful for an evaluation of various models to describe pH-dependent toxicity because the majority of chemicals act as baseline toxicants in this 30 min cytotoxicity assay. Therefore baseline toxicity with constant membrane concentrations of the sum of all chemical species of approximately 200 mmol kglip(-1) served for the validation of the suitability of the various tested models. We confirmed that most tested pharmaceuticals acted as baseline toxicants in this assay at all examined pH values, when toxicity was modeled with a mixture model of concentration addition between the neutral species and all charged species. An ion trapping model, that assumes that the membrane permeability of charged species is kinetically limited, improved model predictions for some pharmaceuticals and pH values. However, neither unhindered uptake nor no uptake of the charged species were ideal models; the reality lies presumably between the two limiting cases with a slower

  7. Conceptualizing Pharmaceutical Plants

    DEFF Research Database (Denmark)

    Larsen, Bent Dalgaard; Jensen, Klaes Ladeby; Gjøl, Mikkel

    2006-01-01

    In the conceptual design phase of pharmaceutical plants as much as 80%-90% of the total cost of a project is committed. It is therefore essential that the chosen concept is viable. In this design process configuration and 3D models can help validate the decisions made. Designing 3D models...... is a complex task and requires skilled users. We demonstrate that a simple 2D/3D configuration tool can support conceptualizing of pharmaceutical plants. Present paper reports on preliminary results from a full scale implementation project at a Danish engineering company....

  8. Capsaicinoids content prediction model development for Korean red-pepper powder using a visible and near-infrared spectroscopy

    Science.gov (United States)

    Lim, Jongguk; Mo, Changyeun; Noh, Sang Ha; Kang, Sukwon; Lee, Kangjin; Kim, Moon S.

    2012-05-01

    A nondestructive, real-time pungency measuring system with visible and near-infrared spectroscopy has been recently developed to measure capsaicinoids content in Korean red-pepper powder. One hundred twenty-five red-pepper powder samples produced from 11 regions in Republic of Korea were used for this investigation. The visible and near-infrared absorption spectra in the range from 450 to 950 nm were acquired and used for the development of prediction models of capsaicinoids contents in red-pepper powders without any chemical pretreatment to the samples. Partial Least Squares Regression (PLSR) models were developed to predict the regional capsaicinoids contents using the acquired absorption spectra. The chemical analysis of the total capsaicinoids (capsaicin and dihydrocapsaicin) was performed by a high performance liquid chromatographic (HPLC) method. The determination coefficient of validation (RV 2) and the standard error of prediction (SEP) for the capsaicinoids content prediction model, for a representative region in this study, were 0.9585 and +/-10.147 mg/100g, respectively.

  9. Mesoscale modeling of irreversible volume growth in powders of anisotropic crystals

    Energy Technology Data Exchange (ETDEWEB)

    Gee, R; Maiti, A; Fried, L

    2006-05-05

    Careful thermometric analysis (TMA) on powders of micron-sized triamino-trinitrobenzene (TATB) crystallites are shown to display irreversible growth in volume when subjected to repeated cycles of heating and cooling. Such behavior is counter-intuitive to typical materials response to simulated annealing cycles in atomic-scale molecular dynamics. However, through coarse-grained simulations using a mesoscale Hamiltonian we quantitatively reproduce irreversible growth behavior in such powdered material. We demonstrate that irreversible growth happens only in the presence of intrinsic crystalline anisotropy, and is mediated by particles much smaller than the average crystallite size.

  10. Compaction of Titanium Powders

    Energy Technology Data Exchange (ETDEWEB)

    Gerdemann, Stephen,J; Jablonski, Paul, J

    2011-05-01

    Accurate modeling of powder densification has been an area of active research for more than 60 years. The earliest efforts were focused on linearization of the data because computers were not readily available to assist with curve-fitting methods. In this work, eight different titanium powders (three different sizes of sponge fines<150 {micro}m,<75 {micro}m, and<45 {micro}m; two different sizes of a hydride-dehydride [HDH]<75 {micro}m and<45 {micro}m; an atomized powder; a commercially pure [CP] Ti powder from International Titanium Powder [ITP]; and a Ti 6 4 alloy powder) were cold pressed in a single-acting die instrumented to collect stress and deformation data during compaction. From these data, the density of each compact was calculated and then plotted as a function of pressure. The results show that densification of all the powders, regardless of particle size, shape, or chemistry, can be modeled accurately as the sum of an initial density plus the sum of a rearrangement term and a work-hardening term. These last two terms are found to be a function of applied pressure and take the form of an exponential rise.

  11. Mechanical characterisation of superconducting BSCCO powder and numerical modelling of the OPIT process

    DEFF Research Database (Denmark)

    Bech, Jakob Ilsted; Eriksen, Morten; Toussaint, F.;

    2000-01-01

    Silver/BSCCO composite superconducting tapes are produced using BSCCO-2212 ceramic powder. The manufacturing process implies a large number of forming operations including drawing and rolling. The numerical simulation of the flat rolling process is of a great interest to anticipate the shape of t...

  12. Modelling the X-ray powder diffraction of nitrogen-expanded austenite using the Debye formula

    DEFF Research Database (Denmark)

    Oddershede, Jette; Christiansen, Thomas; Ståhl, Kenny

    2008-01-01

    Stress-free and homogeneous samples of nitrogen-expanded austenite, a defect-rich f.c.c. structure with a high interstitial nitrogen occupancy (between 0.36 and 0.61), have been studied using X-ray powder diffraction and Debye simulations. The simulations confirm the presence of deformation stack...

  13. An empirical-statistical model for coaxial laser cladding of NiCrAlY powder on Inconel 738 superalloy

    Science.gov (United States)

    Ansari, M.; Shoja Razavi, R.; Barekat, M.

    2016-12-01

    In this study, coaxial laser cladding of NiCrAlY powder on a nickel-based superalloy is investigated from an experimental point of view so as to propose an empirical-statistical model for the process. The correlations between main processing parameters (i.e. scanning speed, powder feeding rate, and laser power) and geometrical characteristics (i.e. width, height, penetration depth, dilution and wetting angle) of single clad tracks have been predicted and are discussed using regression analysis (RA). The validity of the predictions is confirmed by providing correlation coefficient and analysis of the residuals. The correlations are established as a combined parameter (PαVβFγ) for each studied characteristic of single clad tracks. These correlations finally lead to the design of a processing map that can be practically used to select proper processing parameters for laser cladding of the particular material.

  14. Occurrence and modeling of pharmaceuticals on a sewage-impacted Mediterranean river and their dynamics under different hydrological conditions.

    Science.gov (United States)

    Osorio, Victoria; Marcé, Rafael; Pérez, Sandra; Ginebreda, Antoni; Cortina, Jose Luís; Barceló, Damià

    2012-12-01

    The occurrence of 73 representative pharmacologically active compounds (PhACs) was assessed in a sewage-impacted section of the Llobregat River (NE Catalonia, Spain). This Mediterranean river is characterized by flow rate fluctuations strongly influenced by seasonal rainfall. River flow variations increase the potential environmental risk posed by organic micro-pollutants as their concentrations may increase substantially under low flow conditions. Little is known about the transport behavior of emerging contaminants in surface waters once they are discharged from waste water treatment plants (WWTP) into rivers. This research aimed to study the presence and fate of emerging contaminants under different hydrological conditions by sampling two different sites along the river in different seasons. The highest levels of pharmaceuticals were determined during cold and dry periods. The impact of the flow changes on the concentration of the pharmaceuticals in the river was assessed with the relative sensitive coefficients. Due to expected dilution effects, the response of pharmaceuticals to river flow was negative. Only in a few cases, positive relationships between drug concentrations and flow were detected, suggesting an important role of other hydrological phenomena like sediment re-suspension as well as the source of pollutants. To evaluate the role of other factors influencing PhAC concentrations, a plug-flow model was applied to obtain disappearance constants "k" for a set of selected compounds. Erythromycin presented k values of -0.15 h(-1) in both sites being the compound more efficiently removed from the water column. The k values for ibuprofen, furosemide, enrofloxacin, enalapril, acetaminophen, diclofenac and Ketoprofen were between -0.04 and -0.10 h(-1) showing less disappearance than erythromycin in the water column. However, other compounds presented k values<0.06, which suggested conservative behavior of these compounds in the water column. This study

  15. Modeling Uptake of Selected Pharmaceuticals and Personal Care Products into Food Crops from Biosolids-Amended Soil

    DEFF Research Database (Denmark)

    Prosser, Ryan S.; Trapp, Stefan; Sibley, Paul K.

    2014-01-01

    Biosolids contain a variety of pharmaceuticals and personal care products (PPCPs). Studies have observed the uptake of PPCPs into plants grown in biosolids-amended soils. This study examined the ability of Dynamic Plant Uptake (DPU) model and Biosolids-amended Soil Level IV (BASL4) model to predict...... the concentration of eight PPCPs in the tissue of plants grown in biosolids-amended soil under a number of exposure scenarios. Concentrations in edible tissue predicted by the models were compared to concentrations reported in the literature by calculating estimated human daily intake values for both sets of data...... and comparing them to an acceptable daily intake value. The equilibrium partitioning (EqP) portion of BASL4 overpredicted the concentrations of triclosan, triclocarban, and miconazole in root and shoot tissue by two to three orders of magnitude, while the dynamic carrot root (DCR) portion overpredicted...

  16. Characterizing dense suspensions: two case studies from the pharmaceutical industry

    Science.gov (United States)

    Goldfarb, David J.; Khawaja, Nazia; Kazakevich, Irina; Bhattacharjee, Himanshu; Heslinga, Michael; Dalton, Chad

    2015-11-01

    Liquid suspensions of Active Pharmaceutical Ingredient powders are present as pharmaceutical dosage forms in the form of oral suspensions and injectables. We present two case studies, both dense (~ 30-40%) suspensions, in which the physical characterization of the product, specifically, particle size & shape and rheology were key to understanding the key product attributes as pertaining to the manufacturing process and to patient administration. For the one case study, an oral suspension, identifying variations in particle morphology during the wet milling of the product was key to the product understanding necessary to modify the milling process. Rheological measurements were applied as well. For the second case study, an injectable, results from different particle size measurement techniques and rheological measurements indicated the possibility of flocculation in a formulation. Additionally, measurements were obtained to assess the ``injectability'' of the product via rheometer and texture analyzer measurements and Poiseuille flow modeling. As a result, the relevant shear rate regime for this drug product administration was identified.

  17. Computer simulation of model cohesive powders: Plastic consolidation, structural changes, and elasticity under isotropic loads

    Science.gov (United States)

    Gilabert, F. A.; Roux, J.-N.; Castellanos, A.

    2008-09-01

    The quasistatic behavior of a simple two-dimensional model of a cohesive powder under isotropic loads is investigated by discrete element simulations. We ignore contact plasticity and focus on the effect of geometry and collective rearrangements on the material behavior. The loose packing states, as assembled and characterized in a previous numerical study [Gilabert, Roux, and Castellanos, Phys. Rev. E 75, 011303 (2007)], are observed, under growing confining pressure P , to undergo important structural changes, while solid fraction Φ irreversibly increases (typically, from 0.4-0.5 to 0.75-0.8). The system state goes through three stages, with different forms of the plastic consolidation curve, i.e., Φ as a function of the growing reduced pressure P*=Pa/F0 , defined with adhesion force F0 and grain diameter a . In the low-confinement regime (I), the system undergoes negligible plastic compaction, and its structure is influenced by the assembling process. In regime II the material state is independent of initial conditions, and the void ratio varies linearly with lnP [i.e., Δ(1/Φ)=λΔ(lnP*) ], as described in the engineering literature. Plasticity index λ is reduced in the presence of a small rolling resistance (RR). In the last stage of compaction (III), Φ approaches an asymptotic, maximum solid fraction Φmax , as a power law Φmax-Φ∝(P*)-α , with α≃1 , and properties of cohesionless granular packs are gradually retrieved. Under consolidation, while the range ξ of fractal density correlations decreases, force patterns reorganize from self-balanced clusters to force chains, with correlative evolutions of force distributions, and elastic moduli increase by a large amount. Plastic deformation events correspond to very small changes in the network topology, while the denser regions tend to move like rigid bodies. Elastic properties are dominated by the bending of thin junctions in loose systems. For growing RR those tend to form particle chains, the

  18. Pharmaceutical virtue.

    Science.gov (United States)

    Martin, Emily

    2006-06-01

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

  19. Modelling and synthesis of pharmaceutical processes: moving from batch to continuous

    DEFF Research Database (Denmark)

    Papadakis, Emmanouil

    understanding of the pharmaceutical process has resulted in major improvements in the field. Process systems engineering (PSE) approaches, which have been successfully applied in the design, analysis and optimization of chemical and petrochemical processes, might be also important for the improvement...... scenarios. The developed framework is divided into four main sections: the reaction pathway, reaction analysis, separation synthesis and process evaluation-operation based on evaluation. In the first section, the selection of the reaction pathway to produce a desired active ingredient is examined...... optimization studies are performed by defining optimization target based on the process analysis. The application of the developed integrated framework is highlighted through four case studies. In the first case study, the overall use of the framework is highlighted using the synthesis of ibuprofen...

  20. Application of the ellipsoid modeling of the average shape of nanosized crystallites in powder diffraction

    DEFF Research Database (Denmark)

    Katerinopoulou, Anna; Balic Zunic, Tonci; Lundegaard, Lars Fahl

    2012-01-01

    Anisotropic broadening correction in X-ray powder diffraction by an ellipsoidal formula is applied on samples with nanosized crystals. Two cases of minerals with largely anisotropic crystallite shapes are presented. The properly applied formalism not only improves the fitting of the theoretical a...... and observed diffraction diagrams but also gives direct information about realistic crystallite shapes and sizes. The approach is demonstrated using the Rietveld refinement program TOPAS and it is easily adaptable to other similar software....

  1. Determination of amoxicillin content in powdered pharmaceutical formulations using DRIFTS and PLS Determinação de amoxicilina em formulações farmacêuticas em pó empregando DRIFTS-PLS

    Directory of Open Access Journals (Sweden)

    Graciele Parisotto

    2007-03-01

    Full Text Available The amount of amoxicillin in pharmaceutical formulations was determined using spectra of diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS, in association with partial least squares (PLS regression. The spectra of 24 different samples (17 for the calibration set and 7 for the validation set, which had been registered using a Nicolet Magna 550 spectrophotometer, contained 76.7-94.3% of amoxicillin in starch. The PLS models were constructed with auto-scaled or variance-scaled data, and multiplicative scatter correction (MSC. The best model presented R²=0.9936, RMSEC=0.441 and RMSEV=0.790. The analytical method proposed is non-destructive and the cost and time of analysis are very much reduced, allowing for the fast and direct determination of amoxicillin content.Neste trabalho propõe-se a quantificação de amoxicilina em formulações farmacêuticas empregando espectroscopia por refletância difusa no infravermelho com transformada de Fourier (DRIFTS e regressão por mínimos quadrados parciais (PLS. Foram coletados em um espectrômetro Nicolet Magna 550 os espectros de 24 amostras (17 para o conjunto de calibração e 7 para o conjunto de validação contendo de 76,7-94,3 % de amoxicilina em amido. Para a construção dos modelos PLS foi empregada a correção do espalhamento de luz (MSC e os dados foram autoescalados ou escalados pela variância. Foi obtido um excelente modelo para a previsão da amoxicilina o qual apresentou R²=0,9936, RMSEC=0,441 e RMSEV=0,790. O método proposto além de não destrutivo apresenta baixo tempo de análise e baixo custo podendo ser facilmente empregado no controle de qualidade das indústrias farmacêuticas.

  2. Regulatory acceptance and use of 3R models for pharmaceuticals and chemicals: Expert opinions on the state of affairs and the way forward

    NARCIS (Netherlands)

    Schiffelers, M.J.W.A.; Blaauboer, B.J.; Bakker, W.E.; Beken, S.; Hendriksen, C.F.M.; Koeter, H.; Krul, C.A.M.

    2014-01-01

    Pharmaceuticals and chemicals are subjected to regulatory safety testing accounting for approximately 25% of laboratory animal use in Europe. This testing meets various objections and has led to the development of a range of 3R models to Replace, Reduce or Refine the animal models. However, these

  3. Regulatory acceptance and use of 3R models for pharmaceuticals and chemicals: Expert opinions on the state of affairs and the way forward

    NARCIS (Netherlands)

    Schiffelers, M.J.W.A.; Blaauboer, B.J.; Bakker, W.E.; Beken, S.; Hendriksen, C.F.M.; Koeter, H.; Krul, C.A.M.

    2014-01-01

    Pharmaceuticals and chemicals are subjected to regulatory safety testing accounting for approximately 25% of laboratory animal use in Europe. This testing meets various objections and has led to the development of a range of 3R models to Replace, Reduce or Refine the animal models. However, these mo

  4. Modeling the Impact of Simulated Educational Interventions on the Use and Abuse of Pharmaceutical Opioids in the United States: A Report on Initial Efforts

    Science.gov (United States)

    Wakeland, Wayne; Nielsen, Alexandra; Schmidt, Teresa D.; McCarty, Dennis; Webster, Lynn R.; Fitzgerald, John; Haddox, J. David

    2013-01-01

    Three educational interventions were simulated in a system dynamics model of the medical use, trafficking, and nonmedical use of pharmaceutical opioids. The study relied on secondary data obtained in the literature for the period of 1995 to 2008 as well as expert panel recommendations regarding model parameters and structure. The behavior of the…

  5. Effect of experimental design on the prediction performance of calibration models based on near-infrared spectroscopy for pharmaceutical applications.

    Science.gov (United States)

    Bondi, Robert W; Igne, Benoît; Drennen, James K; Anderson, Carl A

    2012-12-01

    Near-infrared spectroscopy (NIRS) is a valuable tool in the pharmaceutical industry, presenting opportunities for online analyses to achieve real-time assessment of intermediates and finished dosage forms. The purpose of this work was to investigate the effect of experimental designs on prediction performance of quantitative models based on NIRS using a five-component formulation as a model system. The following experimental designs were evaluated: five-level, full factorial (5-L FF); three-level, full factorial (3-L FF); central composite; I-optimal; and D-optimal. The factors for all designs were acetaminophen content and the ratio of microcrystalline cellulose to lactose monohydrate. Other constituents included croscarmellose sodium and magnesium stearate (content remained constant). Partial least squares-based models were generated using data from individual experimental designs that related acetaminophen content to spectral data. The effect of each experimental design was evaluated by determining the statistical significance of the difference in bias and standard error of the prediction for that model's prediction performance. The calibration model derived from the I-optimal design had similar prediction performance as did the model derived from the 5-L FF design, despite containing 16 fewer design points. It also outperformed all other models estimated from designs with similar or fewer numbers of samples. This suggested that experimental-design selection for calibration-model development is critical, and optimum performance can be achieved with efficient experimental designs (i.e., optimal designs).

  6. Occurrence and modeling of pharmaceuticals on a sewage-impacted Mediterranean river and their dynamics under different hydrological conditions

    Energy Technology Data Exchange (ETDEWEB)

    Osorio, Victoria [IDAEA-CSIC, Jordi Girona 18-26, Barcelona (Spain); Marce, Rafael [Catalan Institute for Water Research (ICRA), Scientific and Technological Park of the University of Girona, Emili Grahit 101, Girona (Spain); Perez, Sandra [IDAEA-CSIC, Jordi Girona 18-26, Barcelona (Spain); Ginebreda, Antoni, E-mail: agmqam@idaea.csic.es [IDAEA-CSIC, Jordi Girona 18-26, Barcelona (Spain); Cortina, Jose Luis [Cetaqua, Water Technology Centre, UPC North Campus, Paseo de los Tilos, 3, Barcelona (Spain); Barcelo, Damia [IDAEA-CSIC, Jordi Girona 18-26, Barcelona (Spain); Catalan Institute for Water Research (ICRA), Scientific and Technological Park of the University of Girona, Emili Grahit 101, Girona (Spain)

    2012-12-01

    The occurrence of 73 representative pharmacologically active compounds (PhACs) was assessed in a sewage-impacted section of the Llobregat River (NE Catalonia, Spain). This Mediterranean river is characterized by flow rate fluctuations strongly influenced by seasonal rainfall. River flow variations increase the potential environmental risk posed by organic micro-pollutants as their concentrations may increase substantially under low flow conditions. Little is known about the transport behavior of emerging contaminants in surface waters once they are discharged from waste water treatment plants (WWTP) into rivers. This research aimed to study the presence and fate of emerging contaminants under different hydrological conditions by sampling two different sites along the river in different seasons. The highest levels of pharmaceuticals were determined during cold and dry periods. The impact of the flow changes on the concentration of the pharmaceuticals in the river was assessed with the relative sensitive coefficients. Due to expected dilution effects, the response of pharmaceuticals to river flow was negative. Only in a few cases, positive relationships between drug concentrations and flow were detected, suggesting an important role of other hydrological phenomena like sediment re-suspension as well as the source of pollutants. To evaluate the role of other factors influencing PhAC concentrations, a plug-flow model was applied to obtain disappearance constants 'k' for a set of selected compounds. Erythromycin presented k values of - 0.15 h{sup -1} in both sites being the compound more efficiently removed from the water column. The k values for ibuprofen, furosemide, enrofloxacin, enalapril, acetaminophen, diclofenac and Ketoprofen were between - 0.04 and - 0.10 h{sup -1} showing less disappearance than erythromycin in the water column. However, other compounds presented k values < 0.06, which suggested conservative behavior of these compounds in the water

  7. Cracking the Egg: Potential of the Developing Chicken as a Model System for Nonclinical Safety Studies of Pharmaceuticals.

    Science.gov (United States)

    Bjørnstad, Sigrid; Austdal, Lars Peter Engeset; Roald, Borghild; Glover, Joel Clinton; Paulsen, Ragnhild Elisabeth

    2015-12-01

    The advance of perinatal medicine has improved the survival of extremely premature babies, thereby creating a new and heterogeneous patient group with limited information on appropriate treatment regimens. The developing fetus and neonate have traditionally been ignored populations with regard to safety studies of drugs, making medication during pregnancy and in newborns a significant safety concern. Recent initiatives of the Food and Drug Administration and European Medicines Agency have been passed with the objective of expanding the safe pharmacological treatment options in these patients. There is a consensus that neonates should be included in clinical trials. Prior to these trials, drug leads are tested in toxicity and pharmacology studies, as governed by several guidelines summarized in the multidisciplinary International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use M3 (R2). Pharmacology studies must be performed in the major organ systems: cardiovascular, respiratory, and central nervous system. The chicken embryo and fetus have features that make the chicken a convenient animal model for nonclinical safety studies in which effects on all of these organ systems can be tested. The developing chicken is inexpensive, accessible, and nutritionally self-sufficient with a short incubation time and is ideal for drug-screening purposes. Other high-throughput models have been implemented. However, many of these have limitations, including difficulty in mimicking natural tissue architecture and function (human stem cells) and obvious differences from mammals regarding the respiratory organ system and certain aspects of central nervous system development (Caenorhabditis elegans, zebrafish).This minireview outlines the potential and limitations of the developing chicken as an additional model for the early exploratory phase of development of new pharmaceuticals.

  8. Modelling of growth of aflatoxigenic A. flavus isolates from red chilli powder as a function of water availability.

    Science.gov (United States)

    Marín, Sonia; Colom, Carmen; Sanchis, Vicente; Ramos, Antonio J

    2009-01-15

    The aim of the present work was to apply mathematical models for the prediction of growth of aflatoxigenic moulds in powdered Capsicum fruits as a function of its water availability. As prevention of fungal growth effectively conduces to prevention of mycotoxin accumulation, the development of models for prediction of growth of mycotoxigenic fungi becomes a key step in risk management. Two aflatoxigenic A. flavus from chilli powder were grown on 3% chilli powder extract agar at different water activity levels and their growth was evaluated over time in terms of colony sizes and ergosterol accumulation. Both variables were modelled over time, and the resulting parameters (growth rates and lag phases) were modelled as a function of water availability using the Rosso cardinal model. Linear logistic regression was also applied to predict the probability of growth over storage time. Both isolates showed a similar pattern of behaviour, with decreasing growth rates and increasing lag phases with decreasing water activity level. While estimation of optimum a(w) for growth was consistently around 0.97-0.99, the minimum estimated a(w) varied from 0.82 to 0.88 depending on the isolate and on the parameters used for predictions. Comparing growth rates obtained for colony size and ergosterol accumulation, a linear relationship between them could be observed. The rate of root square ergosterol/colony diameter/unit of time was 0.25-0.27. Probabilities of growth before 10 days over 90% were estimated at a(w) 0.91, while the safe period could be extended to more than 20 days (22-29 days) if water activity was decreased to an a(w)=0.87. Finally, the probability of growth is always under 50% when water availability is under a(w) 0.85, and almost null for A. flavus UdLTA 3.147. It was concluded that for safe production, storage and transport, chillies and chilli powder must be kept under 31% mc (db) (probability of growth control point (HACCP) techniques during raw material production

  9. Analysis of the laser powder bed fusion additive manufacturing process through experimental measurement and finite element modeling

    Science.gov (United States)

    Dunbar, Alexander Jay

    The objective in this work is to provide rigourous experimental measurements to aid in the development of laser powder bed fusion (LPBF) additive manufacturing (AM). A specialized enclosed instrumented measurement system is designed to provide in situ experimental measurements of temperature and distortion. Experiments include comparisons of process parameters, materials and LPBF machines. In situ measurements of distortion and temperature made throughout the build process highlight inter-layer distortion effects previously undocumented for laser powder bed fusion. Results from these experiments are also be implemented in the development and validation of finite element models of the powder bed build process. Experimental analysis is extended from small-scale to larger part-scale builds where experimental post-build measurements are used in analysis of distortion profiles. Experimental results provided from this study are utilized in the validation of a finite element model capable of simulating production scale parts. The validated finite element model is then implemented in the analysis of the part to provide information regarding the distortion evolution process. A combination of experimental measurements and simulation results are used to identify the mechanism that results in the measured distortion profile for this geometry. Optimization of support structure primarily focuses on the minimization of material use and scan time, but no information regarding failure criteria for support structure is available. Tensile test samples of LPBF built support structure are designed, built, and tested to provide measurements of mechanical properties of the support structure. Experimental tests show that LPBF built support structure has only 30-40% of the ultimate tensile strength of solid material built in the same machine. Experimental measurement of LPBF built support structure provides clear failure criteria to be utilized in the future design and implementation of

  10. Brandon mathematical model describing the effect of calcination and reduction parameters on specific surface area of UO{sub 2} powders

    Energy Technology Data Exchange (ETDEWEB)

    Hung, Nguyen Trong; Thuan, Le Ba [Institute for Technology of Radioactive and Rare Elements (ITRRE), 48 Lang Ha, Dong Da, Ha Noi (Viet Nam); Van Khoai, Do [Micro-Emission Ltd., 1-1 Asahidai, Nomi, Ishikawa, 923-1211 (Japan); Lee, Jin-Young, E-mail: jinlee@kigam.re.kr [Convergence Research Center for Development of Mineral Resources (DMR), Korea Institute of Geoscience and Mineral Resources (KIGAM), Daejeon, 305-350 (Korea, Republic of); Jyothi, Rajesh Kumar, E-mail: rkumarphd@kigam.re.kr [Convergence Research Center for Development of Mineral Resources (DMR), Korea Institute of Geoscience and Mineral Resources (KIGAM), Daejeon, 305-350 (Korea, Republic of)

    2016-06-15

    Uranium dioxide (UO{sub 2}) powder has been widely used to prepare fuel pellets for commercial light water nuclear reactors. Among typical characteristics of the powder, specific surface area (SSA) is one of the most important parameter that determines the sintering ability of UO{sub 2} powder. This paper built up a mathematical model describing the effect of the fabrication parameters on SSA of UO{sub 2} powders. To the best of our knowledge, the Brandon model is used for the first time to describe the relationship between the essential fabrication parameters [reduction temperature (T{sub R}), calcination temperature (T{sub C}), calcination time (t{sub C}) and reduction time (t{sub R})] and SSA of the obtained UO{sub 2} powder product. The proposed model was tested with Wilcoxon's rank sum test, showing a good agreement with the experimental parameters. The proposed model can be used to predict and control the SSA of UO{sub 2} powder.

  11. Spark Plasma Sintering of Aluminum-Magnesium-Matrix Composites with Boron Carbide and Tungsten Nano-powder Inclusions: Modeling and Experimentation

    Science.gov (United States)

    Dvilis, E. S.; Khasanov, O. L.; Gulbin, V. N.; Petyukevich, M. S.; Khasanov, A. O.; Olevsky, E. A.

    2016-03-01

    Spark-plasma sintering (SPS) is used to fabricate fully-dense metal-matrix (Al/Mg) composites containing hard ceramic (boron carbide) and refractory metal (tungsten) inclusions. The study objectives include the modeling (and its experimental verification) of the process of the consolidation of the composites consisted of aluminum-magnesium alloy AMg6 (65 wt.%), B4C powder (15 wt.%), and W nano-powder (20 wt.%), as well as the optimization of the composite content and of the SPS conditions to achieve higher density. Discrete element modeling of the composite particles packing based on the particle size distribution functions of real powders is utilized for the determination of the powder compositions rendering maximum mixture packing densities. Two models: a power-law creep model of the high temperature deformation of powder materials, and an empirical logarithmic pressure-temperature-relative density relationship are successfully applied for the description of the densification of the aluminum-magnesium metal matrix powder composite subjected to spark-plasma sintering. The elastoplastic properties of the sintered composite samples are assessed by nanoindentation.

  12. In silico predictions of gastrointestinal drug absorption in pharmaceutical product development: application of the mechanistic absorption model GI-Sim.

    Science.gov (United States)

    Sjögren, Erik; Westergren, Jan; Grant, Iain; Hanisch, Gunilla; Lindfors, Lennart; Lennernäs, Hans; Abrahamsson, Bertil; Tannergren, Christer

    2013-07-16

    Oral drug delivery is the predominant administration route for a major part of the pharmaceutical products used worldwide. Further understanding and improvement of gastrointestinal drug absorption predictions is currently a highly prioritized area of research within the pharmaceutical industry. The fraction absorbed (fabs) of an oral dose after administration of a solid dosage form is a key parameter in the estimation of the in vivo performance of an orally administrated drug formulation. This study discloses an evaluation of the predictive performance of the mechanistic physiologically based absorption model GI-Sim. GI-Sim deploys a compartmental gastrointestinal absorption and transit model as well as algorithms describing permeability, dissolution rate, salt effects, partitioning into micelles, particle and micelle drifting in the aqueous boundary layer, particle growth and amorphous or crystalline precipitation. Twelve APIs with reported or expected absorption limitations in humans, due to permeability, dissolution and/or solubility, were investigated. Predictions of the intestinal absorption for different doses and formulations were performed based on physicochemical and biopharmaceutical properties, such as solubility in buffer and simulated intestinal fluid, molecular weight, pK(a), diffusivity and molecule density, measured or estimated human effective permeability and particle size distribution. The performance of GI-Sim was evaluated by comparing predicted plasma concentration-time profiles along with oral pharmacokinetic parameters originating from clinical studies in healthy individuals. The capability of GI-Sim to correctly predict impact of dose and particle size as well as the in vivo performance of nanoformulations was also investigated. The overall predictive performance of GI-Sim was good as >95% of the predicted pharmacokinetic parameters (C(max) and AUC) were within a 2-fold deviation from the clinical observations and the predicted plasma AUC

  13. Integrating X-ray fluorescence and infrared imaging microspectroscopies for comprehensive characterization of an acetaminophen model pharmaceutical.

    Science.gov (United States)

    Patterson, Brian M; Havrilla, George J

    2006-05-01

    The integration of full spectral images using the complementary microspectroscopic imaging techniques X-ray fluorescence and Fourier transform infrared is demonstrated. This effort surpasses previous work in that a single chemometric software package is used to elicit chemical information from the integrated spectroscopic images. Integrating these two complementary spectroscopic methods provides both elemental and molecular spatial distribution within a specimen. The critical aspect in this work is using full spectral maps from each pixel within the image and subsequent processing with chemometric tools to provide integrated chemical information. This integration enables a powerful approach to more comprehensive materials characterization. Issues addressed include sample registration and beam penetration depth and how each affects post-processing. An inorganic salt and an acetaminophen pharmaceutical model mixture demonstrate the power of integrating these techniques with chemometric software.

  14. The Consultancy Activity on In Silico Models for Genotoxic Prediction of Pharmaceutical Impurities.

    Science.gov (United States)

    Pavan, Manuela; Kovarich, Simona; Bassan, Arianna; Broccardo, Lorenza; Yang, Chihae; Fioravanzo, Elena

    2016-01-01

    The toxicological assessment of DNA-reactive/mutagenic or clastogenic impurities plays an important role in the regulatory process for pharmaceuticals; in this context, in silico structure-based approaches are applied as primary tools for the evaluation of the mutagenic potential of the drug impurities. The general recommendations regarding such use of in silico methods are provided in the recent ICH M7 guideline stating that computational (in silico) toxicology assessment should be performed using two (Q)SAR prediction methodologies complementing each other: a statistical-based method and an expert rule-based method.Based on our consultant experience, we describe here a framework for in silico assessment of mutagenic potential of drug impurities. Two main applications of in silico methods are presented: (1) support and optimization of drug synthesis processes by providing early indication of potential genotoxic impurities and (2) regulatory evaluation of genotoxic potential of impurities in compliance with the ICH M7 guideline. Some critical case studies are also discussed.

  15. Extending the reach of powder diffraction modelling by user defined macros

    CERN Document Server

    Scardi, Paolo

    2010-01-01

    The main focus of this special topic volume is the development and possibilities of the MACRO language within TOPAS, with a specific session dedicated to WPPM. The collection is presented here in the form of a ""macro tutorial"" for the benefit of the entire powder diffraction community. More than a collection of standard scientific papers, the contributions to this special issue provide methods, tutorials and practical suggestions and solutions for the proper use of TOPAS and WPPM in a number of applications; ranging from the most common to the most refined and specific cases.Readers will fin

  16. Tuning the Morphology of Pharmaceutical Compounds via Model Based Solvent Selection%通过模型为基础的溶液选择来调控药品化合物的形貌

    Institute of Scientific and Technical Information of China (English)

    A.T.Karunanithi; C.Acquah; L.E.K.Achenie

    2008-01-01

    In this paper we present a strategy for tuning the crystal morphology of pharmaceutical compounds by the appropriate choice of solvent via an optimization model. A three-stage approach involving a pre-design stage, a product design stage and a post-design experimental verification stage is presented. The pre-design stage addresses the formulation of the property constraint for crystal morphology. This involves crystallization experiments and development of property models and constraints for morphology. In the design stage various property requirements for the solvent along with crystal morphology are considered and the product design problem is formulated as a mixed integer nonlinear programming model. The design stage provides an optimal solvent/list of candidate solvents. Similar to the pre-design stage, in the post design experimental verification stage, the morphology of the crystals (precipitated from the designed solvent) is verified through crystallization experiments followed by productcharacterization via scanning electron microscopy, powder X-ray diffraction imaging and Fourier transform spectra analysis.

  17. PENENTUAN WAKTU KADALUARSA DAN MODEL SORPSI ISOTERMIS BIJI DAN BUBUK LADA HITAM (Piper ningrum L. [Shelf Life Prediction and Isotherm Sorption Model of Dried Grain and Powdered Black Pepper (Piper ningrum L.

    Directory of Open Access Journals (Sweden)

    Erika Diah2

    2005-04-01

    Full Text Available Black pepper is one of the most popular spice traded around the globe, either in dried grain form or in bulky powder. However, for retailing purpose both are usually packaged in plastic film. This research was conducted to predict the shelf life of packaged black pepper (both dried grain and powder by applying isotherm sorption and Labuza models. Initial moisture content of dried grain was 12.17 % d.b and for the powder was 10.27 % d.b. The shelf life of black pepper calculated for the dried grain was longer than the powder. When stored at 90 % RH, the dried grain black pepper packaged in HDPE demonstrated the longest shelf life which was equal to 2187 days and for the powder equal to 2037 days. The volatile oil loss for dried grain black pepper after 30 days of preservation was 1.36 % and for the powder was 40.82%.

  18. The effect of vancomycin powder on bone healing in a rat spinal rhBMP-2 model.

    Science.gov (United States)

    Mendoza, Marco C; Sonn, Kevin A; Kannan, Abhishek S; Bellary, Sharath S; Mitchell, Sean M; Singh, Gurmit; Park, Christian; Yun, Chawon; Stock, Stuart R; Hsu, Erin L; Hsu, Wellington K

    2016-08-01

    OBJECTIVE This study aims to quantify the impact of vancomycin powder application on new bone formation and spine fusion rates in a rat posterolateral arthrodesis model. METHODS Thirty-six female Sprague-Dawley rats underwent a posterolateral lumbar spinal fusion (PLF) at the L-4 and L-5 vertebrae. Fusion was elicited via implantation of an absorbable collagen sponge containing 3 µg rhBMP-2. Rats were divided into 3 groups: no vancomycin (control), standard-dose vancomycin, and high-dose vancomycin, based on what was applied to the fusion bed. Clinical studies typically describe the application of 1 g vancomycin into the surgical wound. Presuming an average individual patient weight of 70 kg, a weight-based equivalent dose of vancomycin powder was applied subfascially in the PLF model constituting a "standard-dose" treatment group (14.3 mg/kg, n = 12). To determine whether there is a critical threshold beyond which vancomycin increases the risk of pseudarthrosis, a 10-fold higher dose was administered to a "high-dose" treatment group (143 mg/kg, n = 12). No vancomycin powder was applied to the surgical site in the control group (n = 12). Fusion was evaluated with plain radiographs at 4 and 8 weeks after surgery. The spines were harvested after the 8-week radiographs were obtained and evaluated using manual palpation, microCT analysis, and histological analysis. RESULTS Radiographs demonstrated equivalent bridging bone formation in all groups. No significant differences in fusion scores were seen in the standard-dose (mean 2.25) or high-dose (2.13) treatment groups relative to untreated control animals (1.78). Similarly, fusion rates did not differ significantly different between vancomycin-treated animals (100% for both groups) and control animals (92%). Quantification of new bone formation via microCT imaging revealed no significant between-groups differences in the volume of newly regenerated bone (control vs standard-dose vancomycin, p = 0.57; control vs high

  19. Observed and modeled effects of pH on bioconcentration of diphenhydramine, a weakly basic pharmaceutical, by fathead minnows

    Science.gov (United States)

    Understanding the influence of pH on uptake and accumulation of ionizable pharmaceuticals by fish was recently identified as a major research need. In the present study, fathead minnows were exposed to diphenhydramine (DPH), a weakly basic pharmaceutical (pKa = 9.1). Fish were ...

  20. "Partners in Science": A Model Cooperative Program Introducing High School Teachers and Students to Leading-Edge Pharmaceutical Science

    Science.gov (United States)

    Woska, Joseph R., Jr.; Collins, Danielle M.; Canney, Brian J.; Arcario, Erin L.; Reilly, Patricia L.

    2005-01-01

    "Partners in Science" is a cooperative program between Boehringer Ingelheim Pharmaceuticals, Inc. and area high schools in the community surrounding our Connecticut campus. It is a two-phase program that introduces high school students and teachers to the world of drug discovery and leading-edge pharmaceutical research. Phase 1 involves…

  1. Observed and modeled effects of pH on bioconcentration of diphenhydramine, a weakly basic pharmaceutical, by fathead minnows

    Science.gov (United States)

    Understanding the influence of pH on uptake and accumulation of ionizable pharmaceuticals by fish was recently identified as a major research need. In the present study, fathead minnows were exposed to diphenhydramine (DPH), a weakly basic pharmaceutical (pKa = 9.1). Fish were ...

  2. Aquivalence revisited--new model formulation and application to assess environmental fate of ionic pharmaceuticals in Hamilton Harbour, Lake Ontario.

    Science.gov (United States)

    Csiszar, Susan A; Gandhi, Nilima; Alexy, Radka; Benny, Donald T; Struger, John; Marvin, Chris; Diamond, Miriam L

    2011-07-01

    A model formulation based on "aquivalence", as defined in terms of activity is presented to estimate the multimedia fate of ionizing chemicals. The aquivalence approach is analogous to fugacity but aquivalence is applicable to neutral and ionizing compounds, and has been applied previously to speciating chemicals, notably metals. The new aquivalence-based mass-balance model treats ionizing organic compounds that exist as interconverting neutral and ionic species which are subject to fate processes at differing rates. The model is illustrated by application to four ionizing pharmaceuticals in Hamilton Harbour, Lake Ontario. At the system pH of 7.9-8.5, ibuprofen, gemfibrozil, and naproxen are expected to be almost entirely ionic and triclosan split between ionic and neutral forms. Measured seasonal surface water concentrations, which were 2-10 times lower in the late summer and fall than during spring, were used to solve for unknown values of chemical half-life in the water column due to degradation (photo- and bio-) of the ionizing and neutral forms and secondarily, ionic sorption coefficients of the ionizing forms. Model estimates of half-lives in the habour's water ranged from 11 to 77, 11 to 147 and 10 to 37 for ionic ibuprofen, gemfibrozil, and naproxen, respectively; and 4-22 days and 2-9 days for ionic and neutral triclosan, respectively, with the shortest half-lives in spring and the longest in summer.

  3. Adsorption of pharmaceuticals onto activated carbon fiber cloths - Modeling and extrapolation of adsorption isotherms at very low concentrations.

    Science.gov (United States)

    Fallou, Hélène; Cimetière, Nicolas; Giraudet, Sylvain; Wolbert, Dominique; Le Cloirec, Pierre

    2016-01-15

    Activated carbon fiber cloths (ACFC) have shown promising results when applied to water treatment, especially for removing organic micropollutants such as pharmaceutical compounds. Nevertheless, further investigations are required, especially considering trace concentrations, which are found in current water treatment. Until now, most studies have been carried out at relatively high concentrations (mg L(-1)), since the experimental and analytical methodologies are more difficult and more expensive when dealing with lower concentrations (ng L(-1)). Therefore, the objective of this study was to validate an extrapolation procedure from high to low concentrations, for four compounds (Carbamazepine, Diclofenac, Caffeine and Acetaminophen). For this purpose, the reliability of the usual adsorption isotherm models, when extrapolated from high (mg L(-1)) to low concentrations (ng L(-1)), was assessed as well as the influence of numerous error functions. Some isotherm models (Freundlich, Toth) and error functions (RSS, ARE) show weaknesses to be used as an adsorption isotherms at low concentrations. However, from these results, the pairing of the Langmuir-Freundlich isotherm model with Marquardt's percent standard of deviation was evidenced as the best combination model, enabling the extrapolation of adsorption capacities by orders of magnitude.

  4. Midbrain enkephalin expression in a rat migraine model following intragastric scorpion powder administration

    Institute of Scientific and Technical Information of China (English)

    Gang Yao; Xiangdan Luo; Dihui Ma; Tingmin Yu

    2011-01-01

    Scorpion has strong analgesic effects, but its analgesic mechanisms remain unclear. This study investigated the effects of scorpion powder on enkephalin expression in the midbrain of rats with nitroglycerin-induced migraine at mRNA and protein levels. Results confirmed that migraine rat abnormal behavior was significantly improved, and proenkephalin mRNA expression was significantly increased following treatment with scorpion. The number of methionine-enkephalin- positive cells in the migraine rats following treatment with scorpion was significantly increased, but no significant difference in the number of leucine-enkephalin-positive cells was detectable compared with migraine and normal rats. Taken together, these results show that scorpion exerts potentially beneficial effects by promoting enkephalin expression in nitroglycerin-induced migraine rats.

  5. Path dependence and strength anisotropy of mechanical behavior in cold-compacted powders

    Science.gov (United States)

    Galen, Steven A.

    2005-12-01

    The problem of compaction of powders at low homologous temperatures has been studied over the last twenty years in many fields including powder metallurgy, ceramics, pharmaceutical, agricultural, and mining. Recent emphasis of research efforts has been on the use of phenomenological models that are capable of predicting compaction loads and density distributions in the final product. However, the mechanical properties of the compact cannot be predicted from current models since they consider strength as a function of density alone. A number of studies have shown that strength is dependent on other variables besides density, including the stress path used for consolidation. In prior work, path dependence in ductile powders has been shown experimentally. In this thesis, a ceramic, dibasic calcium phosphate, was consolidated using a variety of stress paths, ranging from nearly isostatic to nearly closed-die. Yield loci were shown to be dependent on stress path as well as compact density. Strength anisotropy in ductile and brittle powders was shown to exist after closed-die compaction and is dependent on compact density. Ductile powders become increasingly anisotropic with density. Brittle powders exhibit anisotropy during the early stages of compaction, but this diminishes as densification continues. Separate mechanisms to explain these behaviors are proposed and supported with experimental data from tensile strength testing, SEM fracture surface analysis and surface area testing. Finally, path dependence and strength anisotropy are shown to have a common origin, namely, directionality of microstructure resulting from initial particle morphology and particle deformation during compaction.

  6. Effect of detergent on powder triboelectrification.

    Science.gov (United States)

    Murtomaa, Matti; Ojanen, Kalle; Laine, Ensio; Poutanen, Jutta

    2002-12-01

    Triboelectrification of pharmaceutical powders during processing and manufacture may cause adhesion/cohesion effects, reduce fill and dose uniformity, affect powder flow and packing behaviour and even obstruct the manufacturing of the product. This paper presents the results of an experimental study on the triboelectrification of microcrystalline cellulose in contact with stainless steel pipes washed with several different detergents. Detergents and their concentrations were chosen to be similar to typical industrial manufacturing stages. The adhesion of powder to the surface had a considerable effect on the triboelectrification process. Therefore, polystyrene spheres were also charged in a similar way and the results were compared with the powder charging results. The results clearly indicate that detergent contamination on the pipe surface has a considerable effect on the generated charge. The detergents and powders used could be arranged in a triboelectric series with only one exception.

  7. Influence of Turmeric Rhizome Powder diets on decreasing oxidative stress caused by heat stress inbroiler model

    Directory of Open Access Journals (Sweden)

    Seyyed Javad Hosseini-Vashan

    2012-08-01

    Full Text Available Background and Aim: Production of reactive oxygen species (ROS increases during oxidative stress conditions, which stimulates diabetes, inflammatory reactions, rheumatism and anemia. Some antioxidant properties of turmeric rhizome powder (TRP were revealed by previous researchers. The present study was conducted to evaluate the influence of TRP on decreasing effects of oxidative stress resulted from heat stress in broiler chickens.   Materials and Methods: In this experimental study, two-hundred-sixty-four 1-day-old broilers were divided into 3 dietary treatments. The dietary treatments involved 0(control, 0.4 and 0.8% turmeric rhizome powder (cases. In order to create oxidative stress, the ambient temperature was daily raised from 21 to 33oc for 5 hours (11a.m-4p.m throughout the 28th-42nd days. Blood lipids, Glutathione peroxidase (GPx ,superoxide dismutase (SOD, and Tiobarbituric acid reaction score (TBARS were determined at the end of the experiment.   Results: The results revealed that total cholesterol and triglyceride were not affected. The 0.4 TRP diet decreased blood LDL (46.7±3.01 compared to basal group (52.0±2.17. HDL increased in broilers fed 0.8% TRP (74.0 ± 3.87 compared to chickens with basal diet (63.7± 2.98. Enzyme activity of GPx improved in broilers fed TRP diets (225.9± 11.52 as compared to chickens with basal diet(183.1± 8.52 however, the TRP diet did not affect enzyme activity of SOD (P > 0.05. The TBARS index decreased in broilers fed TRP (0.76 ± 0.0052 in basal vs.0.49 ± 0.0032 in 0.8% TRP.   Conclusion: The major bioactive component of TRP is Curcumin that can improve the antioxidant properties under oxidative stress and high ambient temperature.

  8. Degradation of pharmaceuticals in UV (LP)/H₂O₂ reactors simulated by means of kinetic modeling and computational fluid dynamics (CFD).

    Science.gov (United States)

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

    2015-05-15

    UV/H2O2 treatment is a well-established technique to degrade organic micropollutants. A CFD model in combination with an advanced kinetic model is presented to predict the degradation of organic micropollutants in UV (LP)/H2O2 reactors, accounting for the hydraulics, fluence rate, complex (photo)chemical reactions in the water matrix and the interactions between these processes. The model incorporates compound degradation by means of direct UV photolysis, OH radical and carbonate radical reactions. Measurements of pharmaceutical degradations in pilot-scale UV/H2O2 reactors are presented under different operating conditions. A comparison between measured and modeled degradation for a group of 35 pharmaceuticals resulted in good model predictions for most of the compounds. The research also shows that the degradation of organic micropollutants can be dependent on temperature, which is relevant for full-scale installations that are operated at different temperatures over the year.

  9. Densification and volumetric change during supersolidus liquid phase sintering of prealloyed brass Cu28Zn powder: Modeling and optimization

    Directory of Open Access Journals (Sweden)

    Mohammadzadeh A.

    2014-01-01

    Full Text Available An investigation has been made to use response surface methodology and central composite rotatable design for modeling and optimizing the effect of sintering variables on densification of prealloyed Cu28Zn brass powder during supersolidus liquid phase sintering. The mathematical equations were derived to predict sintered density, densification parameter, porosity percentage and volumetric change of samples using second order regression analysis. As well as the adequacy of models was evaluated by analysis of variance technique at 95% confidence level. Finally, the influence and interaction of sintering variables, on achieving any desired properties was demonstrated graphically in contour and three dimensional plots. In order to better analyze the samples, microstructure evaluation was carried out. It was concluded that response surface methodology based on central composite rotatable design, is an economical way to obtain arbitrary information with performing the fewest number of experiments in a short period of time.

  10. Modeling and multi-objective optimization of powder mixed electric discharge machining process of aluminum/alumina metal matrix composite

    Directory of Open Access Journals (Sweden)

    Gangadharudu Talla

    2015-09-01

    Full Text Available Low material removal rate (MRR and high surface roughness values hinder large-scale application of electro discharge machining (EDM in the fields like automobile, aerospace and medical industry. In recent years, however, EDM has gained more significance in these industries as the usage of difficult-to-machine materials including metal matrix composites (MMCs increased. In the present work, an attempt has been made to fabricate and machine aluminum/alumina MMC using EDM by adding aluminum powder in kerosene dielectric. Results showed an increase in MRR and decrease in surface roughness (Ra compared to those for conventional EDM. Semi empirical models for MRR and Ra based on machining parameters and important thermo physical properties were established using a hybrid approach of dimensional and regression analysis. A multi response optimization was also performed using principal component analysis-based grey technique (Grey-PCA to determine optimum settings of process parameters for maximum MRR and minimum Ra within the experimental range. The recommended setting of process parameters for the proposed process has been found to be powder concentration (Cp = 4 g/l, peak current (Ip = 3 A, pulse on time (Ton = 150 μs and duty cycle (Tau = 85%.

  11. Detection of melamine in milk powders using near-infrared hyperspectral imaging combined with regression coefficient of partial least square regression model.

    Science.gov (United States)

    Lim, Jongguk; Kim, Giyoung; Mo, Changyeun; Kim, Moon S; Chao, Kuanglin; Qin, Jianwei; Fu, Xiaping; Baek, Insuck; Cho, Byoung-Kwan

    2016-05-01

    Illegal use of nitrogen-rich melamine (C3H6N6) to boost perceived protein content of food products such as milk, infant formula, frozen yogurt, pet food, biscuits, and coffee drinks has caused serious food safety problems. Conventional methods to detect melamine in foods, such as Enzyme-linked immunosorbent assay (ELISA), High-performance liquid chromatography (HPLC), and Gas chromatography-mass spectrometry (GC-MS), are sensitive but they are time-consuming, expensive, and labor-intensive. In this research, near-infrared (NIR) hyperspectral imaging technique combined with regression coefficient of partial least squares regression (PLSR) model was used to detect melamine particles in milk powders easily and quickly. NIR hyperspectral reflectance imaging data in the spectral range of 990-1700nm were acquired from melamine-milk powder mixture samples prepared at various concentrations ranging from 0.02% to 1%. PLSR models were developed to correlate the spectral data (independent variables) with melamine concentration (dependent variables) in melamine-milk powder mixture samples. PLSR models applying various pretreatment methods were used to reconstruct the two-dimensional PLS images. PLS images were converted to the binary images to detect the suspected melamine pixels in milk powder. As the melamine concentration was increased, the numbers of suspected melamine pixels of binary images were also increased. These results suggested that NIR hyperspectral imaging technique and the PLSR model can be regarded as an effective tool to detect melamine particles in milk powders.

  12. The Pharmaceutical Commons

    OpenAIRE

    Lezaun, Javier; Catherine M Montgomery

    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 p...

  13. Investigation of active pharmaceutical ingredient loss in pharmaceutical compounding of capsules.

    Science.gov (United States)

    D'Hondt, Matthias; Wynendaele, Evelien; Vandercruyssen, Kirsten; Bauters, Tiene; Vandenbroucke, Johan; Mullens, Steven; Vervaet, Chris; Remon, Jean Paul; De Spiegeleer, Bart

    2014-08-05

    Pharmaceutical compounding of capsules is still an important corner stone in today's health care. It allows for a more patient specific treatment plan as opposed to the "one size fits all"-approach, used by the pharmaceutical industry when producing fixed dose finished drug products. However, loss of active pharmaceutical ingredient (API) powder during pharmaceutical capsule compounding can lead to under-dosed finished drug products and annul the beneficiary therapeutic effects for the patient. The amount and location of API loss was experimentally determined during capsule compounding of five different preparations: 10 and 20mg hydrocortisone capsules, 4mg triamcinolone capsules and 0.25mg dexamethasone capsules, using a 10% m/m self-made or commercial trituration. The total API amount present in the five capsule preparations varied between 90.8% and 96.6%, demonstrating that for certain preparations, significant API mass loss occurred during the pharmaceutical compounding of capsules. Swabbing results of the different compounding equipment and working areas indicated the mortar surface as the largest API loss location. An agate mortar accounted for the least amount of API loss, whereas an extensively used porcelain mortar accounted for the highest amount of API loss. Optical microscopy and roughness (Ra) determination by profilometry of the different mortar surfaces revealed a significant influence of the mortar surface wear and tear on the observed API loss. This observation can be explained by physical deformation, or scratch formation, of the relatively soft porcelain mortar surface, in which the API particles can become adsorbed. Furthermore, a small effect of the capsulation device material on the API loss was also observed. The presence of a chemical molecule effect on the API loss was demonstrated through data mining using a set of assay results containing 17 different molecules and 1922 assay values. The 17 median assay values were modeled in function of

  14. Effects of a pharmaceutical care model on medication adherence and glycemic control of people with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Chung WW

    2014-09-01

    Full Text Available Wen Wei Chung,1,2 Siew Siang Chua,1 Pauline Siew Mei Lai,3 Siew Pheng Chan4 1Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 2Pharmacy Department, University Malaya Medical Centre, Kuala Lumpur, Malaysia; 3Department of Primary Care Medicine, University Malaya Primary Care Research Group, 4Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia Background: Diabetes mellitus is a lifelong chronic condition that requires self-management. Lifestyle modification and adherence to antidiabetes medications are the major determinants of therapeutic success in the management of diabetes.Purpose: To assess the effects of a pharmaceutical care (PC model on medication adherence and glycemic levels of people with type 2 diabetes mellitus. Patients and methods: A total of 241 people with type 2 diabetes were recruited from a major teaching hospital in Malaysia and allocated at random to the control (n=121 or intervention (n=120 groups. Participants in the intervention group received PC from an experienced pharmacist, whereas those in the control group were provided the standard pharmacy service. Medication adherence was assessed using the Malaysian Medication Adherence Scale, and glycemic levels (glycated hemoglobin values and fasting blood glucose [FBG] of participants were obtained at baseline and after 4, 8, and 12 months. Results: At baseline, there were no significant differences in demographic data, medication adherence, and glycemic levels between participants in the control and intervention groups. However, statistically significant differences in FBG and glycated hemoglobin values were observed between the control and intervention groups at months 4, 8, and 12 after the provision of PC (median FBG, 9.0 versus 7.2 mmol/L [P<0.001]; median glycated hemoglobin level, 9.1% versus 8.0% [P<0.001] at 12 months. Medication adherence was also significantly associated with the

  15. Kinetic energy density and agglomerate abrasion rate during blending of agglomerates into powders

    NARCIS (Netherlands)

    Willemsz, Tofan A; Hooijmaijers, Ricardo; Rubingh, Carina M; Tran, Thanh N; Frijlink, Henderik W; Vromans, Herman; van der Voort Maarschalk, Kees

    2012-01-01

    Problems related to the blending of a cohesive powder with a free flowing bulk powder are frequently encountered in the pharmaceutical industry. The cohesive powder often forms lumps or agglomerates which are not dispersed during the mixing process and are therefore detrimental to blend uniformity.

  16. A Spatially Offset Raman Spectroscopy Method for Non-Destructive Detection of Gelatin-Encapsulated Powders

    Science.gov (United States)

    Chao, Kuanglin; Dhakal, Sagar; Qin, Jianwei; Peng, Yankun; Schmidt, Walter F.; Kim, Moon S.; Chan, Diane E.

    2017-01-01

    Non-destructive subsurface detection of encapsulated, coated, or seal-packaged foods and pharmaceuticals can help prevent distribution and consumption of counterfeit or hazardous products. This study used a Spatially Offset Raman Spectroscopy (SORS) method to detect and identify urea, ibuprofen, and acetaminophen powders contained within one or more (up to eight) layers of gelatin capsules to demonstrate subsurface chemical detection and identification. A 785-nm point-scan Raman spectroscopy system was used to acquire spatially offset Raman spectra for an offset range of 0 to 10 mm from the surfaces of 24 encapsulated samples, using a step size of 0.1 mm to obtain 101 spectral measurements per sample. As the offset distance was increased, the spectral contribution from the subsurface powder gradually outweighed that of the surface capsule layers, allowing for detection of the encapsulated powders. Containing mixed contributions from the powder and capsule, the SORS spectra for each sample were resolved into pure component spectra using self-modeling mixture analysis (SMA) and the corresponding components were identified using spectral information divergence values. As demonstrated here for detecting chemicals contained inside thick capsule layers, this SORS measurement technique coupled with SMA has the potential to be a reliable non-destructive method for subsurface inspection and authentication of foods, health supplements, and pharmaceutical products that are prepared or packaged with semi-transparent materials. PMID:28335453

  17. A Spatially Offset Raman Spectroscopy Method for Non-Destructive Detection of Gelatin-Encapsulated Powders

    Directory of Open Access Journals (Sweden)

    Kuanglin Chao

    2017-03-01

    Full Text Available Non-destructive subsurface detection of encapsulated, coated, or seal-packaged foods and pharmaceuticals can help prevent distribution and consumption of counterfeit or hazardous products. This study used a Spatially Offset Raman Spectroscopy (SORS method to detect and identify urea, ibuprofen, and acetaminophen powders contained within one or more (up to eight layers of gelatin capsules to demonstrate subsurface chemical detection and identification. A 785-nm point-scan Raman spectroscopy system was used to acquire spatially offset Raman spectra for an offset range of 0 to 10 mm from the surfaces of 24 encapsulated samples, using a step size of 0.1 mm to obtain 101 spectral measurements per sample. As the offset distance was increased, the spectral contribution from the subsurface powder gradually outweighed that of the surface capsule layers, allowing for detection of the encapsulated powders. Containing mixed contributions from the powder and capsule, the SORS spectra for each sample were resolved into pure component spectra using self-modeling mixture analysis (SMA and the corresponding components were identified using spectral information divergence values. As demonstrated here for detecting chemicals contained inside thick capsule layers, this SORS measurement technique coupled with SMA has the potential to be a reliable non-destructive method for subsurface inspection and authentication of foods, health supplements, and pharmaceutical products that are prepared or packaged with semi-transparent materials.

  18. A Spatially Offset Raman Spectroscopy Method for Non-Destructive Detection of Gelatin-Encapsulated Powders.

    Science.gov (United States)

    Chao, Kuanglin; Dhakal, Sagar; Qin, Jianwei; Peng, Yankun; Schmidt, Walter F; Kim, Moon S; Chan, Diane E

    2017-03-18

    Non-destructive subsurface detection of encapsulated, coated, or seal-packaged foods and pharmaceuticals can help prevent distribution and consumption of counterfeit or hazardous products. This study used a Spatially Offset Raman Spectroscopy (SORS) method to detect and identify urea, ibuprofen, and acetaminophen powders contained within one or more (up to eight) layers of gelatin capsules to demonstrate subsurface chemical detection and identification. A 785-nm point-scan Raman spectroscopy system was used to acquire spatially offset Raman spectra for an offset range of 0 to 10 mm from the surfaces of 24 encapsulated samples, using a step size of 0.1 mm to obtain 101 spectral measurements per sample. As the offset distance was increased, the spectral contribution from the subsurface powder gradually outweighed that of the surface capsule layers, allowing for detection of the encapsulated powders. Containing mixed contributions from the powder and capsule, the SORS spectra for each sample were resolved into pure component spectra using self-modeling mixture analysis (SMA) and the corresponding components were identified using spectral information divergence values. As demonstrated here for detecting chemicals contained inside thick capsule layers, this SORS measurement technique coupled with SMA has the potential to be a reliable non-destructive method for subsurface inspection and authentication of foods, health supplements, and pharmaceutical products that are prepared or packaged with semi-transparent materials.

  19. COMPUTER MODELING AS ONE OF CONTEMPORARY METHODS OF FORECASTING IN PHARMACEUTICAL TECHNOLOGY

    Directory of Open Access Journals (Sweden)

    S. O. Losenkova

    2014-01-01

    Full Text Available The work presents researches devoted to the forecasting of compatibility of additive and drug substances with a method of computer modeling for its use in composition elaboration and technology of transdermal therapeutic systems.

  20. A comprehensive adsorption study and modeling of antibiotics as a pharmaceutical waste by graphene oxide nanosheets.

    Science.gov (United States)

    Rostamian, Rahele; Behnejad, Hassan

    2017-08-22

    The adsorption behavior of tetracycline (TCN), doxycycline (DCN) as the most common antibiotics in veterinary and ciprofloxacin (CPN) onto graphene oxide nanosheets (GOS) in aqueous solution was evaluated. The four factors influencing the adsorption of antibiotics (initial concentration, pH, temperature and contact time) were studied. The results showed that initial pH ∼ 6 to 7 and contact time ∼ 100 - 200min are optimum for each drug. The monolayer adsorption capacity was reduced with the increasing temperature from 25°C to 45°C. Non-linear regressions were carried out in order to define the best fit model for every system. To do this, eight error functions were applied to predict the optimum model. Among various models, Hill and Toth isotherm models represented the equilibrium adsorption data of antibiotics while the kinetic data were well fitted by pseudo second-order (PSO) kinetic model (DCN and TCN) and Elovich (CPN) models. The maximum adsorption capacity (qmax) is found to be in the following order: CPN > DCN > TCN, obtained from sips equation at the same temperature. The GOS shows highest adsorption capacity towards CPN up to 173.4mgg(-1). The study showed that GOS can be removed more efficiently from water solution. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Effects of halogenated aromatics/aliphatics and nitrogen(N)-heterocyclic aromatics on estimating the persistence of future pharmaceutical compounds using a modified QSAR model.

    Science.gov (United States)

    Lim, Seung Joo; Fox, Peter

    2014-02-01

    The effects of halogenated aromatics/aliphatics and nitrogen(N)-heterocyclic aromatics on estimating the persistence of future pharmaceutical compounds were investigated using a modified half life equation. The potential future pharmaceutical compounds investigated were approximately 2000 pharmaceutical drugs currently undergoing the United States Food and Drug Administration (US FDA) testing. EPI Suite (BIOWIN) model estimates the fates of compounds based on the biodegradability under aerobic conditions. While BIOWIN considered the biodegradability of a compound only, the half life equation used in this study was modified by biodegradability, sorption and cometabolic oxidation. It was possible that the potential future pharmaceutical compounds were more accurately estimated using the modified half life equation. The modified half life equation considered sorption and cometabolic oxidation of halogenated aromatic/aliphatics and nitrogen(N)-heterocyclic aromatics in the sub-surface, while EPI Suite (BIOWIN) did not. Halogenated aliphatics in chemicals were more persistent than halogenated aromatics in the sub-surface. In addition, in the sub-surface environment, the fates of organic chemicals were much more affected by halogenation in chemicals than by nitrogen(N)-heterocyclic aromatics.

  2. Testing strategies for embryo-fetal toxicity of human pharmaceuticals. Animal models vs. in vitro approaches: a workshop report.

    Science.gov (United States)

    van der Laan, Jan Willem; Chapin, Robert E; Haenen, Bert; Jacobs, Abigail C; Piersma, Aldert

    2012-06-01

    Reproductive toxicity testing is characterized by high animal use. For registration of pharmaceutical compounds, developmental toxicity studies are usually conducted in both rat and rabbits. Efforts have been underway for a long time to design alternatives to animal use. Implementation has lagged, partly because of uncertainties about the applicability domain of the alternatives. The reproductive cycle is complex and not all mechanisms of development can be mimicked in vitro. Therefore, efforts are underway to characterize the available alternative tests with regard to the mechanism of action they include. One alternative test is the mouse embryonic stem cell test (EST), which has been studied since the late 1990s. It is a genuine 3R "alternative" assay as it is essentially animal-free. A meeting was held to review the state-of-the-art of various in vitro models for prediction of developmental toxicity. Although the predictivity of individual assays is improving, a battery of several assays is likely to have even higher predictivity, which is necessary for regulatory acceptance. The workshop concluded that an important first step is a thorough survey of the existing rat and rabbit studies, to fully characterize the frequency of responses and the types of effects seen. At the same time, it is important to continue the optimization of in vitro assays. As more experience accumulates, the optimal conditions, assay structure, and applicability of the alternative assays are expected to emerge. Copyright © 2012 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2014-09-10

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

  4. The future of preclinical animal models in pharmaceutical discovery and development: a need to bring in cerebro to the in vivo discussions.

    Science.gov (United States)

    Everitt, Jeffrey I

    2015-01-01

    Animal models have provided an important tool to help make the decision to take potential therapies from preclinical studies to humans. In the past several years, the strong reliance of the pharmaceutical discovery and development process on the use of animal models has come under increasing scrutiny for ethical and scientific reasons. Several prominent and widely publicized articles have reported limited concordance of animal experiments with subsequent human clinical trials. Recent assessments of the quality of animal studies have suggested that this translational failure may be due in part to shortcomings in the planning, conduct, and reporting of in vivo studies. This article will emphasize methods to assure best practice rigor in animal study methods and reporting. It will introduce the so-called scientific 3Rs of relevance, robustness, and reproducibility to the in vivo study approach and will review important new trends in the animal research and pharmaceutical discovery and development communities.

  5. Multi-scale flowsheet simulation of an integrated continuous purification-downstream pharmaceutical manufacturing process.

    Science.gov (United States)

    Sen, Maitraye; Chaudhury, Anwesha; Singh, Ravendra; John, Joyce; Ramachandran, Rohit

    2013-03-10

    Properties of active pharmaceutical ingredients influence the critical quality attributes (CQAs) of final solid dosage forms (e.g. tablets). In the last decade, continuous manufacturing has been shown to be a promising alternative to batch processing in the pharmaceutical industry. Therefore, a quantitative model-based analysis of the influence of upstream API properties on downstream processing quality metrics will lead to enhanced QbD in pharmaceutical drug product manufacturing (Benyahia et al., 2012). In this study, a dynamic flowsheet simulation of an integrated API purification step (crystallization), followed by filtration and drying, with a downstream process (powder mixing) is presented. Results show that the temperature profile of a cooling crystallization process influences the crystal size distribution which in turn impacts the RSD and API concentration of the powder mixing process, which in turn has a direct effect on tablet properties (Boukouvala et al., 2012). A hybrid PBM-DEM model is also presented to demonstrate the coupling of particle-scale information with process-scale information leading to enhanced elucidation of the dynamics of the overall flowsheet simulation. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Effects of a pharmaceutical care model on medication adherence and glycemic control of people with type 2 diabetes

    Science.gov (United States)

    Chung, Wen Wei; Chua, Siew Siang; Lai, Pauline Siew Mei; Chan, Siew Pheng

    2014-01-01

    Background Diabetes mellitus is a lifelong chronic condition that requires self-management. Lifestyle modification and adherence to antidiabetes medications are the major determinants of therapeutic success in the management of diabetes. Purpose To assess the effects of a pharmaceutical care (PC) model on medication adherence and glycemic levels of people with type 2 diabetes mellitus. Patients and methods A total of 241 people with type 2 diabetes were recruited from a major teaching hospital in Malaysia and allocated at random to the control (n=121) or intervention (n=120) groups. Participants in the intervention group received PC from an experienced pharmacist, whereas those in the control group were provided the standard pharmacy service. Medication adherence was assessed using the Malaysian Medication Adherence Scale, and glycemic levels (glycated hemoglobin values and fasting blood glucose [FBG]) of participants were obtained at baseline and after 4, 8, and 12 months. Results At baseline, there were no significant differences in demographic data, medication adherence, and glycemic levels between participants in the control and intervention groups. However, statistically significant differences in FBG and glycated hemoglobin values were observed between the control and intervention groups at months 4, 8, and 12 after the provision of PC (median FBG, 9.0 versus 7.2 mmol/L [P<0.001]; median glycated hemoglobin level, 9.1% versus 8.0% [P<0.001] at 12 months). Medication adherence was also significantly associated with the provision of PC, with a higher proportion in the intervention group than in the control group achieving it (75.0% versus 58.7%; P=0.007). Conclusion The provision of PC has positive effects on medication adherence as well as the glycemic control of people with type 2 diabetes. Therefore, the PC model used in this study should be duplicated in other health care settings for the benefit of more patients with type 2 diabetes. PMID:25214772

  7. Measurements and semi-empirical model describing the onset of powder formation as a function of process parameters in an RF silane hydrogen discharge

    Science.gov (United States)

    van den Donker, M. N.; Hamers, E. A. G.; Kroesen, G. M. W.

    2005-07-01

    The transition pressure above which powder formation takes place was experimentally determined in a parallel plate RF silane-hydrogen plasma as a function of the process parameters—power, temperature, gas flow and hydrogen dilution—using the dc-bias voltage as powder formation indicator. The resulting empirical scaling law describes in what conditions powders are formed and in what conditions the plasma is powder-free. Second, a semi-empirical model was developed that treats the nano-particle density in the plasma. This model was applied to analytically describe the transition pressure above which nano-particle coagulation takes place as a function of process parameters. The resulting modelled scaling law shows good correspondence with the experimentally found scaling law. Finally, a series of amorphous silicon films was deposited. The reflection-transmission spectra of the films were measured and modelled through Tauc-Lorentz formalism. The optical analysis shows that at around the plasma transition pressure there occurs also a transition in the properties of the deposited material.

  8. Modeling nonequilibrium adsorption of MIB and sulfamethoxazole by powdered activated carbon and the role of dissolved organic matter competition.

    Science.gov (United States)

    Shimabuku, Kyle K; Cho, Hyukjin; Townsend, Eli B; Rosario-Ortiz, Fernando L; Summers, R Scott

    2014-12-02

    This study demonstrates that the ideal adsorbed solution theory-equivalent background compound (IAST-EBC) as a stand-alone model can simulate and predict the powdered activated carbon (PAC) adsorption of organic micropollutants found in drinking water sources in the presence of background dissolved organic matter (DOM) under nonequilibrium conditions. The IAST-EBC represents the DOM competitive effect as an equivalent background compound (EBC). When adsorbing 2-methylisoborneol (MIB) with PAC, the EBC initial concentration was a similar percentage, on average 0.51%, of the dissolved organic carbon in eight nonwastewater impacted surface waters. Using this average percentage in the IAST-EBC model yielded good predictions for MIB removal in two nonwastewater impacted waters. The percentage of competitive DOM was significantly greater in wastewater impacted surface waters, and varied markedly in DOM size fractions. Fluorescence parameters exhibited a strong correlation with the percentage of competitive DOM in these waters. Utilizing such correlations in the IAST-EBC successfully modeled MIB and sulfamethoxazole adsorption by three different PACs in the presence of DOM that varied in competitive effect. The influence of simultaneous coagulant addition on PAC adsorption of micropollutants was also investigated. Coagulation caused the DOM competitive effect to increase and decrease with MIB and sulfamethoxazole, respectively.

  9. The pH-dependent toxicity of basic pharmaceuticals in the green algae Scenedesmus vacuolatus can be explained with a toxicokinetic ion-trapping model

    Energy Technology Data Exchange (ETDEWEB)

    Neuwoehner, Judith [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Uberlandstr. 133, 8600 Duebendorf (Switzerland); Institute of Biogeochemistry and Pollutant Dynamics (IBP), ETH Zuerich, 8092 Zuerich (Switzerland); Escher, Beate I., E-mail: b.escher@uq.edu.au [The University of Queensland, National Research Centre for Environmental Toxicology (Entox), 39 Kessels Road, Brisbane, QLD 4108 (Australia); Eawag, Swiss Federal Institute of Aquatic Science and Technology, Uberlandstr. 133, 8600 Duebendorf (Switzerland)

    2011-01-17

    Several previous studies revealed that pharmaceuticals with aliphatic amine function exhibit a higher toxicity toward algae than toward other aquatic organisms. Here we investigated the pH-dependent toxicity of the five basic pharmaceuticals fluoxetine, its metabolite norfluoxetine, propranolol, lidocaine, and trimipramine. For all of them, the toxicity increased with increasing pH when aqueous effect concentrations were considered. Since these pharmaceuticals contain a basic amine group that is protonated and thus positively charged at physiological pH and because algae are capable of biological homeostasis, i.e., pH inside the algal cell remains virtually independent of variable external pH, the speciation of aliphatic amines can be different inside the algal cell compared to the external medium. Therefore, we hypothesized that the high toxicity of aliphatic amines in algae is a toxicokinetic effect caused by speciation and not a toxicodynamic effect caused by a specific mode of toxic action. This hypothesis also implies that internal effect concentrations are independent on external pH. On this basis we developed a simple toxicokinetic model, which assumes that only the neutral molecule is bioavailable and can pass the plasma membrane. This assumption is likely to be valid at pH values down to two units below the acidity constant (pK{sub a}). For lower pH values a more complex model would have to be evoked that includes, an, albeit smaller, permeability of the charged species. For pH > pK{sub a} - 2, we can safely assume that the outer membrane serves as insulator and that the charged species is formed inside the cell according to the pH in the cytoplasm. Thus this toxicokinetic model is an ion-trapping model. The input parameters of this model are the measured aqueous effect concentrations determined as a function of pH and the membrane-water partitioning, which was modelled by the liposome-water partition coefficients of the neutral and cationic species. They

  10. Visualisation of the velocity field in a scaled water model for validation of numerical calculations for a powder fuelled boiler

    Energy Technology Data Exchange (ETDEWEB)

    Dumortier, Laurent [Luleaa Univ. of Technology (Sweden)

    2001-01-01

    Validation of numerical predictions of the flow field in a powder fired industry boiler by flow visualisation in a water model has been studied. The bark powder fired boiler at AssiDomaen Kraftliner in Piteaa has been used as a case study. A literature study covering modelling of combusting flows by water models and different flow visualisation techniques has been carried out. The main conclusion as regards the use of water models is that only qualitative information can be expected. As far as turbulent flow is assured in the model as well as the real furnace, the same Reynolds number is not required. Geometrical similarity is important but modelling of burner jets requires adaptation of the jet diameters in the model. Guidelines for this are available and are presented in the report. The review of visualisation techniques shows that a number of methods have been used successfully for validation of flow field predictions. The conclusion is that the Particle Image Velocimetry and Particle Tracking Velocimetry methods could be very suitable for validation purposes provided that optical access is possible. The numerical predictions include flow fields in a 1130 scale model of the AssiDomaen furnace with water flow as well as flow and temperature fields in the actual furnace. Two burner arrangements were considered both for the model and the actual furnace, namely the present configuration with four front burners and a proposed modification where an additional burner is positioned at a side wall below the other burners. There are many similarities between the predicted flow fields in the model and the full scale furnace but there are also some differences, in particular in the region above the burners and the effects of the low region re-circulation on the lower burner jets. The experiments with the water model have only included the arrangement with four front burners. There were problems determining the velocities in the jets and the comparisons with predictions are

  11. Assessing the cost-effectiveness of new pharmaceuticals in epilepsy in adults: the results of a probabilistic decision model.

    Science.gov (United States)

    Hawkins, Neil; Epstein, David; Drummond, Michael; Wilby, Jennifer; Kainth, Anita; Chadwick, David; Sculpher, Mark

    2005-01-01

    Epilepsy currently affects more than 400,000 people in the United Kingdom and 2.3 million in the United States. Drug therapy is the mainstay of treatment for patients with epilepsy, but therapies vary widely in their mechanism of action and acquisition cost. This article describes a decision model developed for the National Institute for Clinical Excellence in the United Kingdom. It compares the long-term cost-effectiveness of drugs licensed in adults for use in 3 situations: monotherapy for newly diagnosed patients, monotherapy for refractory patients, and combination therapy for refractory patients. The analysis separately considers the treatment of partial and generalized seizures. The full range of pharmaceutical therapies feasibly used in the UK health system was included in the analysis. The analysis showed that, on the basis of existing evidence, for newly diagnosed patients with partial seizures, carbamazepine and valproate are likely to be the most cost-effective mono-therapies. Carbamazepine is likely to be the most cost-effective 2nd-line monotherapy for refractory patients, and oxcarbazepine would probably be the most cost-effective adjunctive therapy for refractory patients if the willingness to pay for additional health benefits is greater than 18,000 pounds per quality-adjusted life year (QALY). For patients with generalized seizures, valproate is most likely to be cost-effective for newly diagnosed patients. For refractory patients, adjunctive topiramate is more cost-effective than monotherapy alone if the willingness to pay for additional health benefits is greater than 35,000 pounds per QALY. There is, however, considerable uncertainty regarding these results. Some of the methodological features of the study will be of value in designing cost-effectiveness analyses of other therapies for chronic conditions. These include the methods used to deal with the absence of head-to-head trial data and the need to reflect time dependency in Markov

  12. A simple model of gas flow in a porous powder compact.

    Energy Technology Data Exchange (ETDEWEB)

    Shugard, Andrew D.; Robinson, David B.

    2014-04-01

    This report describes a simple model for ideal gas flow from a vessel through a bed of porous material into another vessel. It assumes constant temperature and uniform porosity. Transport is treated as a combination of viscous and molecular flow, with no inertial contribution (low Reynolds number). This model can be used to fit data to obtain permeability values, determine flow rates, understand the relative contributions of viscous and molecular flow, and verify volume calibrations. It draws upon the Dusty Gas Model and other detailed studies of gas flow through porous media.

  13. A Simple Model of Gas Flow in a Porous Powder Compact

    Energy Technology Data Exchange (ETDEWEB)

    Shugard, Andrew D. [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Robinson, David [Sandia National Lab. (SNL-CA), Livermore, CA (United States)

    2012-07-01

    This report describes a simple model for ideal gas flow from a vessel through a bed of porous material into another vessel. It assumes constant temperature and uniform porosity. Transport is treated as a combination of viscous and molecular flow, with no inertial contribution (low Reynolds number). This model can be used to fit data to obtain permeability values, determine flow rates, understand the relative contributions of viscous and molecular flow, and verify volume calibrations. It draws upon the Dusty Gas Model and other detailed studies of gas flow through porous media.

  14. Mechanistic Models for Ignition and Combustion of Metallic Powders in Different Environments

    Science.gov (United States)

    2010-09-17

    contradicting the expected higher oxidation rate that would be caused a non-continuous Al2O3 layer. A new model of heterogeneous oxidation of Al...accelerated Al oxidation during melting, contradicting the expected higher oxidation rate that would be caused by a non-continuous Al2O3 layer. A model of...particle, respectively, and the constant c accounts for the differences in molar weight and in density between the metal core and the oxide shell

  15. Performance and model of a full-scale up-flow anaerobic sludge blanket (UASB) to treat the pharmaceutical wastewater containing 6-APA and amoxicillin.

    Science.gov (United States)

    Chen, Zhiqiang; Wang, Hongcheng; Chen, Zhaobo; Ren, Nanqi; Wang, Aijie; Shi, Yue; Li, Xiaoming

    2011-01-30

    A full-scale test was conducted with an up-flow anaerobic sludge blanket (UASB) pre-treating pharmaceutical wastewater containing 6-aminopenicillanic acid (6-APA) and amoxicillin. The aim of the study is to investigate the performance of UASB in the condition of a high chemical oxygen demand (COD) loading rate from 12.57 to 21.02 kgm(-3)d(-1) and a wide pH from 5.57 to 8.26, in order to provide a reference for treating the similar chemical synthetic pharmaceutical wastewater containing 6-APA and amoxicillin. The results demonstrated that the UASB average percentage reduction in COD, 6-APA and amoxicillin were 52.2%, 26.3% and 21.6%, respectively. In addition, three models, built on the back propagation neural network (BPNN) theory and linear regression techniques were developed for the simulation of the UASB system performance in the biodegradation of pharmaceutical wastewater containing 6-APA and amoxicillin. The average error of COD, 6-APA and amoxicillin were -0.63%, 2.19% and 5.40%, respectively. The results indicated that these models built on the BPNN theory were well-fitted to the detected data, and were able to simulate and predict the removal of COD, 6-APA and amoxicillin by UASB. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

  16. Model to predict inhomogeneous protein-sugar distribution in powders prepared by spray drying

    NARCIS (Netherlands)

    Grasmeijer, Niels; Frijlink, Henderik W.; Hinrichs, Wouter L. J.

    2016-01-01

    A protein can be stabilized by spray drying an aqueous solution of the protein and a sugar, thereby incorporating the protein into a glassy sugar matrix. For optimal stability, the protein should be homogeneously distributed inside the sugar matrix. The aim of this study was to develop a model that

  17. Heisenberg Model Analysis on Inelastic Powder Neutron Scattering Data Using Pure and K doped BaMn2 As2 samples

    Science.gov (United States)

    Ramazanoglu, Mehmet; Sapkota, A.; Pandey, A.; Johnston, D.; Goldman, Alan; Kreyssig, A.; Abernathy, D.; Niedziela, J.; Stone, M.; McQueeney, R. J.

    Low temperature powder inelastic neutron scattering measurements (INS) were performed on powders of Ba(1-x)KxMn2As2 with x=0(BMA),0.125 and 0.25. BMA is a G type antiferromagnet (AFM) which has local magnetic modulations bridging between the pnictide and cuprate superconductors. Hole doping (K) introduces more metallic behavior. The magnetic contribution to the intensities were retrieved by subtracting the estimated phonon background obtained at high momentum transfers from the raw. The resultant estimated magnetic intensities were analyzed by using damped harmonic oscillator model. The K doping effects create a broadening in the magnetic peak profiles consistent with expected weak FM fluctuations. We also analyzed the INS data using a powder integration routine which is based on J1-J2-Jz Heisenberg Model. The Monte Carlo integration technique is used to obtain the powder-averaged S(Q,E) for a series of Js. The representative values (with lowest chi-squared) obtained for BMA are in agreement with previous results. The values obtained for K doped samples were found in the close proximity to the parent ones. Overall we conclude that the original AFM structure seen in BMA retained its character even in the K doped samples with minimal differences. Work at Ames Laboratory is supported by USDOE under Contract No. DE-AC02-07CH11358 and Work at ITU is supported by TUBITAK 2232.

  18. Protective effects of Purendan superfine powder on retinal neuron apoptosis in a rat model of type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    Zhijun Dong; Xiangyi Tao; Xiaoxiao Fu; Haibin Wang; Donghua Wang; Tiemin Zhang

    2012-01-01

    This study sought to investigate the effects of Purendan superfine powder comprised of Momordica charantia, Radix Ginseng, and Radix Salviae Miltiorrhiae on neuronal apoptosis and expression of bcl-2, bax, and caspase-3, which are retinal apoptosis-associated factors in rats with diabetes mellitus induced by continuous intraperitoneal injection of streptozotocin. The results showed that Purendan superfine powder could upregulate the expression of bcl-2 protein and mRNA, and downregulate the expression of bax and caspase-3 in the retina of diabetes mellitus rats. In addition, Purendan superfine powder was shown to reduce the number of apoptotic neurons. Our experimental findings indicate that Purendan superfine powder can inhibit neuronal apoptosis in the retina of diabetes mellitus rats and has protective effects on diabetic retinopathy.

  19. Modeling of evaporation and oxidation phenomena in plasma spraying of metal powders

    Science.gov (United States)

    Zhang, Hanwei

    Plasma spraying of metals in air is usually accompanied by evaporation and oxidation of the sprayed material. Optimization of the spraying process must ensure that the particles are fully molten during their short residence time in the plasma jet and prior to hitting the substrate, but not overheated to minimize evaporation losses. In atmospheric plasma spraying (ASP), it is also clearly desirable to be able to control the extent of oxide formation. The objective of this work to develop an overall mathematical model of the oxidization and volatilization phenomena involved in the plasma-spraying of metallic particles in air atmosphere. Four models were developed to simulate the following aspects of the atmospheric plasma spraying (APS) process: (a) the particle trajectories and the velocity and temperature profiles in an Ar-H 2 plasma jet, (b) the heat and mass transfer between particles and plasma jet, (c) the interaction between the evaporation and oxidation phenomena, and (d) the oxidation of liquid metal droplets. The resulting overall model was generated by adapting the computational fluid dynamics code FIDAP and was validated by experimental measurements carried out at the collaborating plasma laboratory of the University of Limoges. The thesis also examined the environmental implications of the oxidization and volatilization phenomena in the plasma spraying of metals. The modeling results showed that the combination of the standard k-s model of turbulence and the Boussinesq eddy-viscosity model provided a more accurate prediction of plasma gas behavior. The estimated NOx generation levels from APS were lower than the U.S.E.P.A. emission standard. Either enhanced evaporation or oxidation can occur on the surface of the metal particles and the relative extent is determined by the process parameters. Comparatively, the particle size has the greatest impact on both evaporation and oxidation. The extent of particle oxidation depends principally on gas

  20. On modeling the CNC end milling characteristics of Al-7075/WC powder metallurgy composites

    Science.gov (United States)

    Hanuman, N. S. V. N.; Rao, P. Gangadhara; Kumar, B. Sudheer; Karthik, N.

    2017-07-01

    Surface finish and material removal rate are two important factors in the manufacturing which affect acceptability of the product which in turn reflects on the profitability of the organization. The worth of the production setup to produce the components with high material removal rate (MRR) without sacrificing the surface requirements can play vital role in sustainability and profitability of the organization. In this paper, the effect of process parameters on metal removal rate and surface roughness has been investigated in milling of Al7075-MMC with WC as reinforcement element. Cutting speed, feed and depth of cut have been taken as input factors in three level response surface methodologies used for experimentation. Mathematical models have been developed using response surface methodology to predict surface finish, and metal removal rate in term of machining parameters. Depth of cut and feed rate are found to be a dominant parameter for surface roughness; whereas feed rate mainly affects the metal removal rate. The results of mathematical models have been compared with the experimental and found to be in good agreement. The results of predicted model can be used in selection of process parameters to insure desired quality and improved productivity.

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

    Science.gov (United States)

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

    2015-01-01

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

  2. Comparing and modeling organic micro-pollutant adsorption onto powdered activated carbon in different drinking waters and WWTP effluents.

    Science.gov (United States)

    Zietzschmann, Frederik; Aschermann, Geert; Jekel, Martin

    2016-10-01

    The adsorption of organic micro-pollutants (OMP) onto powdered activated carbon (PAC) was compared between regionally different waters within two groups, namely five drinking waters and seven wastewater treatment plant (WWTP) effluents. In all waters, OMP were spiked to adjust similar ratios of the initial OMP and DOC concentrations (c0,OMP/c0,DOC). PAC was dosed specific to the respective DOC (e.g. 2 mg PAC/per mg DOC). Liquid chromatography with online carbon detection shows differences of the background organic matter (BOM) compositions. The OMP removals at given DOC-specific PAC doses vary by ±15% (drinking waters) and ±10% (WWTP effluents). Similar BOM-induced adsorption competition in the waters of the respective group results in overall relationships between the PAC loadings and the liquid phase concentrations of each OMP (in the case of strong adsorbates). Weaker adsorbates show no overall relationships because of the strong BOM-induced adsorption competition near the initial OMP concentration. Correlations between OMP removals and UV254 removals were independent of the water (within the respective group). The equivalent background compound (EBC) model was applied to the experimental data. Using global EBC Freundlich coefficients, the initial EBC concentration correlates with the DOC (both water groups separately) and the low molecular weight (LMW) organics concentrations (all waters combined). With these correlations, the EBC could be initialized by using the DOC or the LMW organics concentration of additional drinking water, WWTP effluent, and surface water samples.

  3. Computational modeling of electrically-driven deposition of ionized polydisperse particulate powder mixtures in advanced manufacturing processes

    Science.gov (United States)

    Zohdi, T. I.

    2017-07-01

    A key part of emerging advanced additive manufacturing methods is the deposition of specialized particulate mixtures of materials on substrates. For example, in many cases these materials are polydisperse powder mixtures whereby one set of particles is chosen with the objective to electrically, thermally or mechanically functionalize the overall mixture material and another set of finer-scale particles serves as an interstitial filler/binder. Often, achieving controllable, precise, deposition is difficult or impossible using mechanical means alone. It is for this reason that electromagnetically-driven methods are being pursued in industry, whereby the particles are ionized and an electromagnetic field is used to guide them into place. The goal of this work is to develop a model and simulation framework to investigate the behavior of a deposition as a function of an applied electric field. The approach develops a modular discrete-element type method for the simulation of the particle dynamics, which provides researchers with a framework to construct computational tools for this growing industry.

  4. Importance of surface diffusivities in pesticide adsorption kinetics onto granular versus powdered activated carbon: experimental determination and modeling.

    Science.gov (United States)

    Baup, S; Wolbert, D; Laplanche, A

    2002-10-01

    Three pesticides (atrazine, bromoxynil and diuron) and two granular activated carbons are involved in equilibrium and kinetic adsorption experiments. Equilibrium is represented by Freundlich isotherm law and kinetic is described by the Homogeneous Surface Diffusion Model, based on external mass transfer and intraparticle surface diffusion. Equilibrium and long-term experiments are conducted to compare Powdered Activated Carbon and Granular Activated Carbon. These first investigations show that crushing GAC into PAC improves the accessibility of the adsorption sites without increasing the number of these sites. In a second part, kinetics experiments are carried out using a Differential Column Batch Reactor. Thanks to this experimental device, the external mass transfer coefficient k(f) is calculated from empirical correlation and the effect of external mass transfer on adsorption is likely to be minimized. In order to obtain the intraparticle surface diffusion coefficient D. for these pesticides, comparisons between experimental kinetic data and simulations are conducted and the best agreement leads to the Ds coefficient. This procedure appears to be an efficient way to acquire surface diffusion coefficients for the adsorption of pesticides onto GAC. Finally it points out the role of surface diffusivity in the adsorption rate. As a matter of fact, even if the amount of the target-compound that could be potentially adsorbed is really important, its surface diffusion coefficient may be small, so that its adsorption may not have enough contact time to be totally achieved.

  5. Virtual pharmaceutical companies: collaborating flexibly in pharmaceutical development.

    Science.gov (United States)

    Forster, Simon P; Stegmaier, Julia; Spycher, Rene; Seeger, Stefan

    2014-03-01

    Research and development (R&D) collaborations represent one approach chosen by the pharmaceutical industry to tackle current challenges posed by declining internal R&D success rates and fading of the blockbuster model. In recent years, a flexible concept to collaborate in R&D has emerged: virtual pharmaceutical companies (VPCs). These differ from other R&D companies, such as biotech start-ups, collaborating with big pharmaceutical companies, because they solely comprise experienced teams of managers. VPCs have only been described anecdotally in literature. Thus, we present here the characteristics of a VPC and suggest how big pharma can leverage the concept of VPCs by introducing five possible modes of collaboration. We find that one mode, investing, is particularly promising for big pharma.

  6. Regulatory acceptance and use of 3R models for pharmaceuticals and chemicals: expert opinions on the state of affairs and the way forward.

    Science.gov (United States)

    Schiffelers, Marie-Jeanne W A; Blaauboer, Bas J; Bakker, Wieger E; Beken, Sonja; Hendriksen, Coenraad F M; Koëter, Herman B W M; Krul, Cyrille

    2014-06-01

    Pharmaceuticals and chemicals are subjected to regulatory safety testing accounting for approximately 25% of laboratory animal use in Europe. This testing meets various objections and has led to the development of a range of 3R models to Replace, Reduce or Refine the animal models. However, these models must overcome many barriers before being accepted for regulatory risk management purposes. This paper describes the barriers and drivers and options to optimize this acceptance process as identified by two expert panels, one on pharmaceuticals and one on chemicals. To untangle the complex acceptance process, the multilevel perspective on technology transitions is applied. This perspective defines influences at the micro-, meso- and macro level which need alignment to induce regulatory acceptance of a 3R model. This paper displays that there are many similar mechanisms within both sectors that prevent 3R models from becoming accepted for regulatory risk assessment and management. Shared barriers include the uncertainty about the value of the new 3R models (micro level), the lack of harmonization of regulatory requirements and acceptance criteria (meso level) and the high levels of risk aversion (macro level). In optimizing the process commitment, communication, cooperation and coordination are identified as critical drivers.

  7. Pharmaceutical counterfeiting and the RFID technology intervention.

    Science.gov (United States)

    Coustasse, Alberto; Arvidson, Cody; Rutsohn, Phil

    2010-07-01

    Both nationally and internationally, pharmaceutical counterfeiting has become a problem that is threatening economic stability and public health. The purpose of the present research study review was to analyze the scope and severity of pharmaceutical counterfeiting and to establish if the implantation of the Radio Frequency Identification Device (RFID) model can more efficiently be used within the pharmaceutical supply chain to reduce the problem counterfeit drugs impose on public health and international economic stability. Results indicated that implementing the RFID model for tracking drugs at the item level in the pharmaceutical supply chain has potential to alleviate the scope of the counterfeit drug problem. Recommendations for how the pharmaceutical industry may sooner adopt the RFID model are made.

  8. The Pharmaceutical Commons

    Science.gov (United States)

    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

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

    Science.gov (United States)

    Dickenson, E R V; Drewes, J E

    2010-01-01

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

  10. The Sustained Delivery of Resveratrol or a Defined Grape Powder Inhibits New Blood Vessel Formation in a Mouse Model of Choroidal Neovascularization

    Science.gov (United States)

    Kanavi, Mozhgan Rezaie; Darjatmoko, Soesiawati; Wang, Shoujian; Azari, Amir A.; Farnoodian, Mitra; Kenealey, Jason D.; van Ginkel, Paul R.; Albert, Daniel M.; Sheibani, Nader; Polans, Arthur S.

    2015-01-01

    The objective of this study was to determine whether resveratrol or a defined, reconstituted grape powder can attenuate the formation of new blood vessels in a mouse model of choroidal neovascularization (CNV). To accomplish this objective, C57BL/6J mice were randomized into control or treatment groups which received either resveratrol or grape powder by daily oral gavage, resveratrol or grape powder delivered ad libitum through the drinking water, or resveratrol by slow release via implanted osmotic pumps. A laser was used to rupture Bruch’s membrane to induce CNV which was then detected in sclerochoroidal eyecups stained with antibodies against intercellular adhesion molecule-2. CNV area was measured using fluorescence microscopy and Image J software. Ad libitum delivery of both resveratrol and grape powder was shown to significantly reduce the extent of CNV by 68% and 57%, respectively. Parallel experiments conducted in vitro demonstrated that resveratrol activates p53 and inactivates Akt/protein kinase B in choroidal endothelial cells, contributing to its anti-proliferative and anti-migratory properties. In addition resveratrol was shown to inhibit the formation of endothelial cell networks, augmenting its overall anti-angiogenic effects. The non-toxic nature of resveratrol makes it an especially attractive candidate for the prevention and/or treatment of CNV. PMID:25361423

  11. The Sustained Delivery of Resveratrol or a Defined Grape Powder Inhibits New Blood Vessel Formation in a Mouse Model of Choroidal Neovascularization

    Directory of Open Access Journals (Sweden)

    Mozhgan Rezaie Kanavi

    2014-10-01

    Full Text Available The objective of this study was to determine whether resveratrol or a defined, reconstituted grape powder can attenuate the formation of new blood vessels in a mouse model of choroidal neovascularization (CNV. To accomplish this objective, C57BL/6J mice were randomized into control or treatment groups which received either resveratrol or grape powder by daily oral gavage, resveratrol or grape powder delivered ad libitum through the drinking water, or resveratrol by slow release via implanted osmotic pumps. A laser was used to rupture Bruch’s membrane to induce CNV which was then detected in sclerochoroidal eyecups stained with antibodies against intercellular adhesion molecule-2. CNV area was measured using fluorescence microscopy and Image J software. Ad libitum delivery of both resveratrol and grape powder was shown to significantly reduce the extent of CNV by 68% and 57%, respectively. Parallel experiments conducted in vitro demonstrated that resveratrol activates p53 and inactivates Akt/protein kinase B in choroidal endothelial cells, contributing to its anti-proliferative and anti-migratory properties. In addition resveratrol was shown to inhibit the formation of endothelial cell networks, augmenting its overall anti-angiogenic effects. The non-toxic nature of resveratrol makes it an especially attractive candidate for the prevention and/or treatment of CNV.

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

    Science.gov (United States)

    Yamamoto, Keiji; Limwikrant, Waree; Moribe, Kunikazu

    2011-01-01

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

  13. Model approach to estimate the probability of accepting a lot of heterogeneously contaminated powdered food using different sampling strategies.

    Science.gov (United States)

    Valero, Antonio; Pasquali, Frédérique; De Cesare, Alessandra; Manfreda, Gerardo

    2014-08-01

    Current sampling plans assume a random distribution of microorganisms in food. However, food-borne pathogens are estimated to be heterogeneously distributed in powdered foods. This spatial distribution together with very low level of contaminations raises concern of the efficiency of current sampling plans for the detection of food-borne pathogens like Cronobacter and Salmonella in powdered foods such as powdered infant formula or powdered eggs. An alternative approach based on a Poisson distribution of the contaminated part of the lot (Habraken approach) was used in order to evaluate the probability of falsely accepting a contaminated lot of powdered food when different sampling strategies were simulated considering variables such as lot size, sample size, microbial concentration in the contaminated part of the lot and proportion of contaminated lot. The simulated results suggest that a sample size of 100g or more corresponds to the lower number of samples to be tested in comparison with sample sizes of 10 or 1g. Moreover, the number of samples to be tested greatly decrease if the microbial concentration is 1CFU/g instead of 0.1CFU/g or if the proportion of contamination is 0.05 instead of 0.01. Mean contaminations higher than 1CFU/g or proportions higher than 0.05 did not impact on the number of samples. The Habraken approach represents a useful tool for risk management in order to design a fit-for-purpose sampling plan for the detection of low levels of food-borne pathogens in heterogeneously contaminated powdered food. However, it must be outlined that although effective in detecting pathogens, these sampling plans are difficult to be applied since the huge number of samples that needs to be tested. Sampling does not seem an effective measure to control pathogens in powdered food.

  14. Near infra red spectroscopy as a multivariate process analytical tool for predicting pharmaceutical co-crystal concentration.

    Science.gov (United States)

    Wood, Clive; Alwati, Abdolati; Halsey, Sheelagh; Gough, Tim; Brown, Elaine; Kelly, Adrian; Paradkar, Anant

    2016-09-10

    The use of near infra red spectroscopy to predict the concentration of two pharmaceutical co-crystals; 1:1 ibuprofen-nicotinamide (IBU-NIC) and 1:1 carbamazepine-nicotinamide (CBZ-NIC) has been evaluated. A partial least squares (PLS) regression model was developed for both co-crystal pairs using sets of standard samples to create calibration and validation data sets with which to build and validate the models. Parameters such as the root mean square error of calibration (RMSEC), root mean square error of prediction (RMSEP) and correlation coefficient were used to assess the accuracy and linearity of the models. Accurate PLS regression models were created for both co-crystal pairs which can be used to predict the co-crystal concentration in a powder mixture of the co-crystal and the active pharmaceutical ingredient (API). The IBU-NIC model had smaller errors than the CBZ-NIC model, possibly due to the complex CBZ-NIC spectra which could reflect the different arrangement of hydrogen bonding associated with the co-crystal compared to the IBU-NIC co-crystal. These results suggest that NIR spectroscopy can be used as a PAT tool during a variety of pharmaceutical co-crystal manufacturing methods and the presented data will facilitate future offline and in-line NIR studies involving pharmaceutical co-crystals. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  15. Lubricants in Pharmaceutical Solid Dosage Forms

    Directory of Open Access Journals (Sweden)

    Jinjiang Li

    2014-02-01

    Full Text Available Lubrication plays a key role in successful manufacturing of pharmaceutical solid dosage forms; lubricants are essential ingredients in robust formulations to achieve this. Although many failures in pharmaceutical manufacturing operations are caused by issues related to lubrication, in general, lubricants do not gain adequate attention in the development of pharmaceutical formulations. In this paper, the fundamental background on lubrication is introduced, in which the relationships between lubrication and friction/adhesion forces are discussed. Then, the application of lubrication in the development of pharmaceutical products and manufacturing processes is discussed with an emphasis on magnesium stearate. In particular, the effect of its hydration state (anhydrate, monohydrate, dihydrate, and trihydrate and its powder characteristics on lubrication efficiency, as well as product and process performance is summarized. In addition, the impact of lubrication on the dynamics of compaction/compression processes and on the mechanical properties of compacts/tablets is presented. Furthermore, the online monitoring of magnesium stearate in a blending process is briefly mentioned. Finally, the chemical compatibility of active pharmaceutical ingredient (API with magnesium stearate and its reactive impurities is reviewed with examples from the literature illustrating the various reaction mechanisms involved.

  16. Macrophytes may not contribute significantly to removal of nutrients, pharmaceuticals, and antibiotic resistance in model surface constructed wetlands.

    Science.gov (United States)

    Cardinal, Pascal; Anderson, Julie C; Carlson, Jules C; Low, Jennifer E; Challis, Jonathan K; Beattie, Sarah A; Bartel, Caitlin N; Elliott, Ashley D; Montero, Oscar F; Lokesh, Sheetal; Favreau, Alex; Kozlova, Tatiana A; Knapp, Charles W; Hanson, Mark L; Wong, Charles S

    2014-06-01

    Outdoor shallow wetland mesocosms, designed to simulate surface constructed wetlands to improve lagoon wastewater treatment, were used to assess the role of macrophytes in the dissipation of wastewater nutrients, selected pharmaceuticals, and antibiotic resistance genes (ARGs). Specifically, mesocosms were established with or without populations of Typha spp. (cattails), Myriophyllum sibiricum (northern water milfoil), and Utricularia vulgaris (bladderwort). Following macrophyte establishment, mesocosms were seeded with ARG-bearing organisms from a local wastewater lagoon, and treated with a single pulse of artificial municipal wastewater with or without carbamazepine, clofibric acid, fluoxetine, and naproxen (each at 7.6μg/L), as well as sulfamethoxazole and sulfapyridine (each at 150μg/L). Rates of pharmaceutical dissipation over 28d ranged from 0.073 to 3.0d(-1), corresponding to half-lives of 0.23 to 9.4d. Based on calculated rate constants, observed dissipation rates were consistent with photodegradation driving clofibric acid, naproxen, sulfamethoxazole, and sulfapyridine removal, and with sorption also contributing to carbamazepine and fluoxetine loss. Of the seven gene determinants assayed, only two genes for both beta-lactam resistance (blaCTX and blaTEM) and sulfonamide resistance (sulI and sulII) were found in sufficient quantity for monitoring. Genes disappeared relatively rapidly from the water column, with half-lives ranging from 2.1 to 99d. In contrast, detected gene levels did not change in the sediment, with the exception of sulI, which increased after 28d in pharmaceutical-treated systems. These shallow wetland mesocosms were able to dissipate wastewater contaminants rapidly. However, no significant enhancement in removal of nutrients or pharmaceuticals was observed in mesocosms with extensive aquatic plant communities. This was likely due to three factors: first, use of naïve systems with an unchallenged capacity for nutrient assimilation and

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

    Science.gov (United States)

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

    2010-01-01

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

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

    Science.gov (United States)

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

    2010-01-01

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

  19. Qualitative and Quantitative Analysis of 11 Sulfonamides in Veterinary Pharmaceutical Powder by HPLC -Diode Array Detector%高效液相色谱-二极管阵列检测法同时分析兽药粉剂中11种磺胺类药物

    Institute of Scientific and Technical Information of China (English)

    沈祥广; 李维铖; 刘戎; 古小燕; 余静贤; 张嘉慧; 苏贻娟

    2012-01-01

    A novel method was developed for the simultaneous determination of 11 sulfonamides in veterinary pharmaceutical powder by high performance liquid chromatography - diode array detection. The sample was extracted with 95% acetonitrile solution and then purified by an Alumina - B solid phase extraction cartridge. The extraction residue was redissolved in 15% acetonitrile solution and separated on a TC - C18 chromatographic column. The mobile phase was composed of 0.017 mol/L phosphoric acid and acetonitrile and a gradient elution program was carried out. The diode assay detection was used for the qualitative and quantitative analysis. The results indicated that the chromatographic peaks of 11 sulfonamides drugs and their corresponding spectra were ideal under the optimal conditions. The calibration curves of 11 ana-lyte were linear in the range of 0.25 -10.0 mg/L. The average recoveries of 11 sulfonamides at three spiked levels of 0.5, 1.0, 5.0 mg/kg were between 67% and 97% , with relative standard deviations ranged from 1.5% to 9.9% . Based on signal to noise ratio(S/N =3) and the corresponding spectra, the limits of detection of 11 analytes in veterinary pharmaceutical powder were all 0. 25 mg/kg.%建立了高效液相色谱-二极管阵列检测法同时测定兽药粉剂中11种磺胺类药物的分析方法.试样采用95%乙腈提取,经碱性氧化铝固相萃取小柱净化,15%乙腈复溶残渣后用Agilent TC - C18色谱柱分离,0.017 mol/L磷酸溶液和乙腈为流动相进行梯度洗脱,二极管阵列检测器进行检测.结果表明,在优化实验条件下,11种磺胺类药物的色谱分离和相应光谱图匹配理想;在0.25~ 10.0 mg/L范围内线性关系良好;兽药粉剂中添加0.5~ 5.0 mg/kg水平的11种磺胺类药物的回收率在67%~ 97%之间,相对标准偏差为1.5%~9.9%;以3倍信噪比(S/N=3)结合相应光谱图计算得11种磺胺类药物的检出限均为0.25 mg/kg.

  20. 社区药学服务实践及模式创建%Practice and the model establishment of community pharmaceutical care

    Institute of Scientific and Technical Information of China (English)

    王忠壮

    2011-01-01

    Practice experience, establishment of the model, the evaluation index system and the beneficial results in respect of community pharmaceutical care are introduced in this paper. Meanwhile, the main problems are discussed and the way to resolve the problems are also pointed out.%介绍从事社区药学服务的工作实践、模式创建、评价指标及该模式产生的各种良好结果等,并就存在的问题进行讨论,指出解决方法.

  1. Design, Modeling and Optimization of a Piezoelectric Pressure Sensor based on a Thin-Film PZT Membrane Containing Nanocrystalline Powders

    Directory of Open Access Journals (Sweden)

    Vahid MOHAMMADI

    2009-11-01

    Full Text Available In this paper fabrication of a 0-3 ceramic/ceramic composite lead zirconate titanate, Pb(Zr0.52Ti0.48O3 thin film has been presented and then a pressure sensor based on multilayer thin-film PZT diaphragm contain of Lead Zirconate Titanate nanocrystalline powders was designed, modeled and optimized. Dynamics characteristics of this multilayer diaphragm have been investigated by ANSYS® FE software. By this simulation the effective parameters of the multilayer PZT diaphragm for improving the performance of a pressure sensor in different ranges of pressure are optimized. The optimized thickness ratio of PZT layer to SiO2 was given in the paper to obtain the maximum deflection of the multilayer thin-film PZT diaphragm. A 0-3 ceramic/ceramic composite lead zirconate titanate, Pb(Zr0.52Ti0.48O3 film has been developed to fabricate the pressure sensor by a hybrid sol gel process. PZT nanopowders fabricated via conventional sol gel method and uniformly dispersed in PZT precursor solution by an attrition mill. XRD analysis shows that perovskite structure would be formed due to the presence of a significant amount of ceramic nanopowders. This texture has a good effect on piezoelectric properties of perovskite structure. The film forms a strongly bonded network and less shrinkage occurs, so the films do not crack during process. Also the aspect ratio through this process would be increased. SEM micrographs indicated that PZT films were uniform, crack free and have a composite microstructure and a piezoelectric coefficient d31 of -40 pC.N-1 and d33 ranged from 50pm.N-1 to 60pm.N-1.

  2. Dispensação farmacêutica: uma análise de diferentes conceitos e modelos Pharmaceutical dispensing: an analysis of different concepts and models

    Directory of Open Access Journals (Sweden)

    Daniela Angonesi

    2008-04-01

    Full Text Available Apresenta-se uma revisão das definições e metodologias de dispensação elaboradas pelos órgãos públicos reguladores, organizações profissionais e de saúde no Brasil e em outros países e alguns autores brasileiros, sob a perspectiva da contemplação de aspectos técnicos relativos aos medicamentos e a influência da filosofia da atenção farmacêutica. Vários modelos de dispensação consideram os aspectos técnicos relativos aos medicamentos e alguns acrescentam a necessidade de orientação para o uso correto dos medicamentos ou ainda elementos da filosofia da atenção farmacêutica. Mas é necessário rever a definição da dispensação no Brasil para que possam ser criados procedimentos possíveis de serem realizados na prática em uma farmácia comunitária e que cumpram com os objetivos desta atividade farmacêutica.The present article presents a review of the definitions and methodologies of pharmaceutical dispensing elaborated by the regulating authorities, professional and health organizations in Brazil and abroad and also by some Brazilian authors from the perspective of the technical and philosophical aspects involved. Several dispensing models consider the technical aspects related to the medicines and some add the need for orientation with regard to correct use or even elements of the philosophy underlying the pharmacist care model. However, for creating procedures that can be put into practice in a community pharmacy and that meet the purpose of this pharmaceutical activity it is necessary to rethink the concept of pharmaceutical dispensing in Brazil.

  3. Support vector regression and artificial neural network models for stability indicating analysis of mebeverine hydrochloride and sulpiride mixtures in pharmaceutical preparation: a comparative study.

    Science.gov (United States)

    Naguib, Ibrahim A; Darwish, Hany W

    2012-02-01

    A comparison between support vector regression (SVR) and Artificial Neural Networks (ANNs) multivariate regression methods is established showing the underlying algorithm for each and making a comparison between them to indicate the inherent advantages and limitations. In this paper we compare SVR to ANN with and without variable selection procedure (genetic algorithm (GA)). To project the comparison in a sensible way, the methods are used for the stability indicating quantitative analysis of mixtures of mebeverine hydrochloride and sulpiride in binary mixtures as a case study in presence of their reported impurities and degradation products (summing up to 6 components) in raw materials and pharmaceutical dosage form via handling the UV spectral data. For proper analysis, a 6 factor 5 level experimental design was established resulting in a training set of 25 mixtures containing different ratios of the interfering species. An independent test set consisting of 5 mixtures was used to validate the prediction ability of the suggested models. The proposed methods (linear SVR (without GA) and linear GA-ANN) were successfully applied to the analysis of pharmaceutical tablets containing mebeverine hydrochloride and sulpiride mixtures. The results manifest the problem of nonlinearity and how models like the SVR and ANN can handle it. The methods indicate the ability of the mentioned multivariate calibration models to deconvolute the highly overlapped UV spectra of the 6 components' mixtures, yet using cheap and easy to handle instruments like the UV spectrophotometer.

  4. Integrating systems Approaches into Pharmaceutical Sciences

    DEFF Research Database (Denmark)

    Westerhoff, H.V.; Mosekilde, Erik; Noe, C. R.

    2008-01-01

    of the conference was to promote the ‘Integration of Systems Approaches into Pharmaceutical Sciences’ in view of optimising the development of new effective drugs. And a challenge this is, considering both the high attrition rates in the pharmaceutical industry and the failure of finding definitive drug solutions......During the first week of December 2007, the European Federation for Pharmaceutical Sciences (EUFEPS) and BioSim, the major European Network of Excellence on Systems Biology, held a challenging conference on the use of mathematical models in the drug development process. More precisely, the purpose...... for many of the diseases that plague mankind today. The conference was co-sponsored by the American College of Clinical Pharmacology, the European Center for Pharmaceutical Medicine, and the Swiss Society of Pharmaceutical Sciences and, besides representatives from the European Regulatory Agencies and FDA...

  5. Biological and Pharmaceutical Nanomaterials

    Science.gov (United States)

    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.

  6. Analytical method development for powder characterization: Visualization of the critical drug loading affecting the processability of a formulation for direct compression

    DEFF Research Database (Denmark)

    Hirschberg, Cosima; Sun, Calvin Changquan; Rantanen, Jukka

    2016-01-01

    Characterization of particulate systems (powders) is one of the remaining scientific challenges. Evaluation of powder behaviour is often empirical and the decision-making processes are experience-based. There is a need for development of analytical instrumentation enabling more fundamental...... understanding of powder behaviour. Flowability and tabletability, two key factors in commercial scale manufacturing of tablets with direct compression (DC) approach, were analysed for formulations containing increasing amounts of several model active pharmaceutical ingredients (APIs). Flowability......H 102) was used as a threshold for adequate flowability of model formulations. The threshold for tablet tensile strength was set to 2 MPa. Simultaneous visual presentation of both- flowability and tabletability were used for a fast evaluation of manufacturability of a given formulation. The results...

  7. Powdered Hexagonal Boron Nitride Reducing Nanoscale Wear

    Science.gov (United States)

    Chkhartishvili, L.; Matcharashvili, T.; Esiava, R.; Tsagareishvili, O.; Gabunia, D.; Margiev, B.; Gachechiladze, A.

    2013-05-01

    A morphology model is suggested for nano-powdered hexagonal boron nitride that can serve as an effective solid additive to liquid lubricants. It allows to estimate the specific surface, that is a hard-to-measure parameter, based on average size of powder particles. The model can be used also to control nanoscale wear processes.

  8. Artificial neural network modelling of pharmaceutical residue retention times in wastewater extracts using gradient liquid chromatography-high resolution mass spectrometry data.

    Science.gov (United States)

    Munro, Kelly; Miller, Thomas H; Martins, Claudia P B; Edge, Anthony M; Cowan, David A; Barron, Leon P

    2015-05-29

    The modelling and prediction of reversed-phase chromatographic retention time (tR) under gradient elution conditions for 166 pharmaceuticals in wastewater extracts is presented using artificial neural networks for the first time. Radial basis function, multilayer perceptron and generalised regression neural networks were investigated and a comparison of their predictive ability for model solutions discussed. For real world application, the effect of matrix complexity on tR measurements is presented. Measured tR for some compounds in influent wastewater varied by >1min in comparison to tR in model solutions. Similarly, matrix impact on artificial neural network predictive ability was addressed towards developing a more robust approach for routine screening applications. Overall, the best neural network had a predictive accuracy of <1.3min at the 75th percentile of all measured tR data in wastewater samples (<10% of the total runtime). Coefficients of determination for 30 blind test compounds in wastewater matrices lay at or above R(2)=0.92. Finally, the model was evaluated for application to the semi-targeted identification of pharmaceutical residues during a weeklong wastewater sampling campaign. The model successfully identified native compounds at a rate of 83±4% and 73±5% in influent and effluent extracts, respectively. The use of an HRMS database and the optimised ANN model was also applied to shortlisting of 37 additional compounds in wastewater. Ultimately, this research will potentially enable faster identification of emerging contaminants in the environment through more efficient post-acquisition data mining. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Spray-dried powders enhance vaginal siRNA delivery by potentially modulating the mucus molecular sieve structure

    Directory of Open Access Journals (Sweden)

    Wu N

    2015-08-01

    Full Text Available Na Wu,1,2,* Xinxin Zhang,2,* Feifei Li,2 Tao Zhang,2 Yong Gan,2 Juan Li1 1School of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China; 2Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Vaginal small interfering RNA (siRNA delivery provides a promising strategy for the prevention and treatment of vaginal diseases. However, the densely cross-linked mucus layer on the vaginal wall severely restricts nanoparticle-mediated siRNA delivery to the vaginal epithelium. In order to overcome this barrier and enhance vaginal mucus penetration, we prepared spray-dried powders containing siRNA-loaded nanoparticles. Powders with Pluronic F127 (F127, hydroxypropyl methyl cellulose (HPMC, and mannitol as carriers were obtained using an ultrasound-assisted spray-drying technique. Highly dispersed dry powders with diameters of 5–15 µm were produced. These powders showed effective siRNA protection and sustained release. The mucus-penetrating properties of the powders differed depending on their compositions. They exhibited different potential of opening mesh size of molecular sieve in simulated vaginal mucus system. A powder formulation with 0.6% F127 and 0.1% HPMC produced the maximum increase in the pore size of the model gel used to simulate vaginal mucus by rapidly extracting water from the gel and interacting with the gel; the resulting modulation of the molecular sieve effect achieved a 17.8-fold improvement of siRNA delivery in vaginal tract and effective siRNA delivery to the epithelium. This study suggests that powder formulations with optimized compositions have the potential to alter the steric barrier posed by mucus and hold promise for effective vaginal siRNA delivery. Keywords: siRNA delivery, vaginal administration, spray-dried powders, mucus penetration, molecular sieve effect

  10. Fusion strategies for selecting multiple tuning parameters for multivariate calibration and other penalty based processes: A model updating application for pharmaceutical analysis

    Energy Technology Data Exchange (ETDEWEB)

    Tencate, Alister J. [Department of Chemistry, Idaho State University, Pocatello, ID 83209 (United States); Kalivas, John H., E-mail: kalijohn@isu.edu [Department of Chemistry, Idaho State University, Pocatello, ID 83209 (United States); White, Alexander J. [Department of Physics and Optical Engineering, Rose-Hulman Institute of Technology, Terre Huate, IN 47803 (United States)

    2016-05-19

    New multivariate calibration methods and other processes are being developed that require selection of multiple tuning parameter (penalty) values to form the final model. With one or more tuning parameters, using only one measure of model quality to select final tuning parameter values is not sufficient. Optimization of several model quality measures is challenging. Thus, three fusion ranking methods are investigated for simultaneous assessment of multiple measures of model quality for selecting tuning parameter values. One is a supervised learning fusion rule named sum of ranking differences (SRD). The other two are non-supervised learning processes based on the sum and median operations. The effect of the number of models evaluated on the three fusion rules are also evaluated using three procedures. One procedure uses all models from all possible combinations of the tuning parameters. To reduce the number of models evaluated, an iterative process (only applicable to SRD) is applied and thresholding a model quality measure before applying the fusion rules is also used. A near infrared pharmaceutical data set requiring model updating is used to evaluate the three fusion rules. In this case, calibration of the primary conditions is for the active pharmaceutical ingredient (API) of tablets produced in a laboratory. The secondary conditions for calibration updating is for tablets produced in the full batch setting. Two model updating processes requiring selection of two unique tuning parameter values are studied. One is based on Tikhonov regularization (TR) and the other is a variation of partial least squares (PLS). The three fusion methods are shown to provide equivalent and acceptable results allowing automatic selection of the tuning parameter values. Best tuning parameter values are selected when model quality measures used with the fusion rules are for the small secondary sample set used to form the updated models. In this model updating situation, evaluation of

  11. Validation of DEM modeling of sintering using an in situ X-ray microtomography analysis of the sintering of NaCl powder

    Science.gov (United States)

    Martin, Sylvain; Navarro, Sebastián; Palancher, Hervé; Bonnin, Anne; Léchelle, Jacques; Guessasma, Mohamed; Fortin, Jérôme; Saleh, Khashayar

    2016-11-01

    This paper aims to validate the discrete element method (DEM) model of sintering. In situ X-ray microtomography experiments have been carried out at the ESRF to follow the sintering of NaCl powder, the properties of which are close to the DEM model assumptions. DEM simulations are then run using an improved implicit method. The comparison between experiment and simulation shows the capability of DEM to predict the behavior of the sample on both particle and packing scale. The main advantages and limits of this approach are finally discussed based on these results and those of previous studies.

  12. Predictive modeling, simulation, and optimization of laser processing techniques: UV nanosecond-pulsed laser micromachining of polymers and selective laser melting of powder metals

    Science.gov (United States)

    Criales Escobar, Luis Ernesto

    One of the most frequently evolving areas of research is the utilization of lasers for micro-manufacturing and additive manufacturing purposes. The use of laser beam as a tool for manufacturing arises from the need for flexible and rapid manufacturing at a low-to-mid cost. Laser micro-machining provides an advantage over mechanical micro-machining due to the faster production times of large batch sizes and the high costs associated with specific tools. Laser based additive manufacturing enables processing of powder metals for direct and rapid fabrication of products. Therefore, laser processing can be viewed as a fast, flexible, and cost-effective approach compared to traditional manufacturing processes. Two types of laser processing techniques are studied: laser ablation of polymers for micro-channel fabrication and selective laser melting of metal powders. Initially, a feasibility study for laser-based micro-channel fabrication of poly(dimethylsiloxane) (PDMS) via experimentation is presented. In particular, the effectiveness of utilizing a nanosecond-pulsed laser as the energy source for laser ablation is studied. The results are analyzed statistically and a relationship between process parameters and micro-channel dimensions is established. Additionally, a process model is introduced for predicting channel depth. Model outputs are compared and analyzed to experimental results. The second part of this research focuses on a physics-based FEM approach for predicting the temperature profile and melt pool geometry in selective laser melting (SLM) of metal powders. Temperature profiles are calculated for a moving laser heat source to understand the temperature rise due to heating during SLM. Based on the predicted temperature distributions, melt pool geometry, i.e. the locations at which melting of the powder material occurs, is determined. Simulation results are compared against data obtained from experimental Inconel 625 test coupons fabricated at the National

  13. A review of factors affecting electrostatic charging of pharmaceuticals and adhesive mixtures for inhalation.

    Science.gov (United States)

    Kaialy, Waseem

    2016-04-30

    Pharmaceutical powders are typically insulators consisting of relatively small particles and thus they usually exhibit significant electrostatic charging behaviours. In the inhalation field, the measurement of electrostatic charge is an imperative stage during pharmaceutical formulation development. The electrostatic charge is affected by the interplay of many factors. This article reviews the factors affecting the electrostatic charging of pharmaceutical powders with a focus on dry powder inhalations. The influences of particle resistivity, size distribution, shape distribution, surface roughness, polymorphic form and hygroscopicity, as well as the effects of moisture uptake, environmental conditions, pharmaceutical processing (i.e., milling, sieving, spray drying and blending), and storage on the electrostatic charge behaviours of pharmaceuticals, with focus on inhalation powders, were reviewed. The influence of electrostatic charge on the performance of dry powder inhaler formulations in terms of drug content homogeneity, the passage of drug through the inhaler device, drug-carrier adhesion/detachment, and drug deposition on the respiratory airways were discussed. The understanding gained is crucial to improving the safety, quality, and efficiency of the pharmaceutical inhalation products.

  14. In vivo-in vitro correlations: predicting pulmonary drug deposition from pharmaceutical aerosols.

    Science.gov (United States)

    Byron, Peter R; Hindle, Michael; Lange, Carlos F; Longest, P Worth; McRobbie, Donald; Oldham, Michael J; Olsson, Bo; Thiel, Charles G; Wachtel, Herbert; Finlay, Warren H

    2010-12-01

    In order to answer the question "what research remains to be done?" we review the current state of the art in pharmaceutical aerosol deposition modeling and explore possible in vivo- in vitro correlations (IVIVC) linking drug deposition in the human lung to predictions made using in vitro physical airway models and in silico computer models. The use of physical replicas of portions of the respiratory tract is considered, alongside the advantages and disadvantages of the different imaging methods used to obtain their dimensions. The use of airway replicas to determine drug deposition in vitro is discussed and compared with the predictions from different empirical curve fits to long-standing in vivo deposition data for monodisperse aerosols. The use of improved computational models and three-dimensional computational fluid dynamics (CFD) to predict aerosol deposition within the respiratory tract is examined. CFD's ability to predict both drug deposition from pharmaceutical aerosol sprays and powder behavior in dry powder inhalers is examined; both were highlighted as important areas for future research. Although the authors note the abilities of current in vitro and in silico methods to predict in vivo data, a number of limitations remain. These include our present inability to either image or replicate all but the most proximal airways in sufficient spatial and temporal detail to allow full capture of the fluid and aerosol mechanics in these regions. In addition, the highly complex microscale behavior of aerosols within inhalers and the respiratory tract places extreme computational demands on in silico methods. When the complexity of variations in respiratory tract geometry is associated with additional factors such as breathing pattern, age, disease state, postural position, and patient-device interaction are all considered, it is clear that further research is required before the prediction of all aspects of inhaled pharmaceutical aerosol deposition is possible.

  15. Fusion strategies for selecting multiple tuning parameters for multivariate calibration and other penalty based processes: A model updating application for pharmaceutical analysis.

    Science.gov (United States)

    Tencate, Alister J; Kalivas, John H; White, Alexander J

    2016-05-19

    New multivariate calibration methods and other processes are being developed that require selection of multiple tuning parameter (penalty) values to form the final model. With one or more tuning parameters, using only one measure of model quality to select final tuning parameter values is not sufficient. Optimization of several model quality measures is challenging. Thus, three fusion ranking methods are investigated for simultaneous assessment of multiple measures of model quality for selecting tuning parameter values. One is a supervised learning fusion rule named sum of ranking differences (SRD). The other two are non-supervised learning processes based on the sum and median operations. The effect of the number of models evaluated on the three fusion rules are also evaluated using three procedures. One procedure uses all models from all possible combinations of the tuning parameters. To reduce the number of models evaluated, an iterative process (only applicable to SRD) is applied and thresholding a model quality measure before applying the fusion rules is also used. A near infrared pharmaceutical data set requiring model updating is used to evaluate the three fusion rules. In this case, calibration of the primary conditions is for the active pharmaceutical ingredient (API) of tablets produced in a laboratory. The secondary conditions for calibration updating is for tablets produced in the full batch setting. Two model updating processes requiring selection of two unique tuning parameter values are studied. One is based on Tikhonov regularization (TR) and the other is a variation of partial least squares (PLS). The three fusion methods are shown to provide equivalent and acceptable results allowing automatic selection of the tuning parameter values. Best tuning parameter values are selected when model quality measures used with the fusion rules are for the small secondary sample set used to form the updated models. In this model updating situation, evaluation of

  16. DEM analysis of particle adhesion during powder mixing for dry powder inhaler formulation development

    OpenAIRE

    Yang, J; Wu, C-Y; Adams, M.

    2013-01-01

    Understanding the adhesive interactions between active pharmaceutical ingredient (API) particles and carrier particles in dry powder inhalers (DPIs) is critical for the development of formulations and process design. In the current study, a discrete element method, which accounts for particle adhesion, is employed to investigate the attachment processes in DPIs. A critical velocity criterion is proposed to determine the lowest impact velocity at which two elastic autoadhesive spherical partic...

  17. Wisdom Pharmaceutical Co., Ltd.

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    @@ Wisdom Pharmaceutical Co., Ltd. (Wisdom) headquartered in Haimen, Nantong, Jiangsu Province, China, is specialized in providing highly efficient production processes of active pharmaceutical ingredients (API) and intermediates. Currently, Wisdom is in the process of expanding GMP (Good Manufacturing Practice) capabilities, which is expected to be approved by the authorities before the end of September 2003.

  18. Development of a quantitative approach using surface-enhanced Raman chemical imaging: first step for the determination of an impurity in a pharmaceutical model.

    Science.gov (United States)

    De Bleye, C; Sacré, P-Y; Dumont, E; Netchacovitch, L; Chavez, P-F; Piel, G; Lebrun, P; Hubert, Ph; Ziemons, E

    2014-03-01

    This publication reports, for the first time, the development of a quantitative approach using surface-enhanced Raman chemical imaging (SER-CI). A pharmaceutical model presented as tablets based on paracetamol, which is the most sold drug around the world, was used to develop this approach. 4-Aminophenol is the main impurity of paracetamol and is actively researched in pharmaceutical formulations because of its toxicity. As its concentration is generally very low (<0.1%, w/w), conventional Raman chemical imaging cannot be used. In this context, a SER-CI method was developed to quantify 4-aminophenol assessing a limit of quantification below its limit of specification of 1000 ppm. Citrate-reduced silver nanoparticles were used as SERS substrate and these nanoparticles were functionalized using 1-butanethiol. Different ways to cover the tablets surface by butanethiol-functionalized silver nanoparticles were tested and a homogeneity study of the silver nanoparticles covering was realized. This homogeneity study was performed in order to choose the best way to cover the surface of tablets by silver colloid. Afterwards, the optimization of the SER-CI approach was necessary and different spectral intensity normalizations were tested. Finally, a quantitative approach using SER-CI was developed enabling to quantify 4-aminophenol from 0.025% to 0.2% in paracetamol tablets. This quantitative approach was tested on two different series of tablets using different batches of silver nanoparticles.

  19. Aluminum powder metallurgy processing

    Energy Technology Data Exchange (ETDEWEB)

    Flumerfelt, J.F.

    1999-02-12

    The objective of this dissertation is to explore the hypothesis that there is a strong linkage between gas atomization processing conditions, as-atomized aluminum powder characteristics, and the consolidation methodology required to make components from aluminum powder. The hypothesis was tested with pure aluminum powders produced by commercial air atomization, commercial inert gas atomization, and gas atomization reaction synthesis (GARS). A comparison of the GARS aluminum powders with the commercial aluminum powders showed the former to exhibit superior powder characteristics. The powders were compared in terms of size and shape, bulk chemistry, surface oxide chemistry and structure, and oxide film thickness. Minimum explosive concentration measurements assessed the dependence of explosibility hazard on surface area, oxide film thickness, and gas atomization processing conditions. The GARS aluminum powders were exposed to different relative humidity levels, demonstrating the effect of atmospheric conditions on post-atomization processing conditions. The GARS aluminum powders were exposed to different relative humidity levels, demonstrating the effect of atmospheric conditions on post-atomization oxidation of aluminum powder. An Al-Ti-Y GARS alloy exposed in ambient air at different temperatures revealed the effect of reactive alloy elements on post-atomization powder oxidation. The pure aluminum powders were consolidated by two different routes, a conventional consolidation process for fabricating aerospace components with aluminum powder and a proposed alternative. The consolidation procedures were compared by evaluating the consolidated microstructures and the corresponding mechanical properties. A low temperature solid state sintering experiment demonstrated that tap densified GARS aluminum powders can form sintering necks between contacting powder particles, unlike the total resistance to sintering of commercial air atomization aluminum powder.

  20. Practical approach for measuring heat capacity of pharmaceutical crystals/glasses by modulated-temperature differential scanning calorimetry.

    Science.gov (United States)

    Harada, Takuji; Kawakami, Kohsaku; Yoshihashi, Yasuo; Yonemochi, Etsuo; Terada, Katsuhide; Moriyama, Hiroshi

    2013-01-01

    A practical protocol to obtain accurate heat capacity values of pharmaceutical compounds using modulated-temperature differential scanning calorimetry was established. Three pharmaceutical compounds, acetaminophen, indomethacin, and tri-O-methyl-β-cyclodextrin were used as model compounds. Powder samples did not produce reproducible results, presumably due to inclusion of gas in gap of powders that influenced the measured heat capacity and thermal homogeneity in the sample. Thus, the amorphous characteristics were evaluated using quench-cooled samples. Crystalline samples were obtained by partially melting the sample to allow recrystallization using the residual crystal as a template. Optimum sample mass was about 10 mg. Use of too small sample size resulted in poor reproducibility due to localization of the sample in the pan, while too large size resulted in low heat capacity values probably because of heterogeneity of the sample temperature. The optimum modulation period was in the range of 60 s and 90 s, to which the ramp rates of 2°C/min and 1°C/min, respectively, were applied. The ramp amplitude was less significant in the evaluation. This information should help in comprehending basic characteristics of pharmaceutical compounds.

  1. Strategic Management of Innovations at Pharmaceutical Enterprises

    Directory of Open Access Journals (Sweden)

    Honcharova Svіtlana Yu.

    2014-01-01

    Full Text Available The article is devoted to theoretical and practical issues of the use of the concept of strategic management of innovations at pharmaceutical enterprises. It studies main barriers, which restrict development of Ukrainian pharmaceutical enterprises. It analyses the state and tendencies of development of innovation activity of pharmaceutical enterprises and studies foreign experience of innovation activity. It marks out specific features of strategic management of innovation development in pharmaceutical industry. It specifies the role and advantages of methods of strategic analysis in the system of management of a pharmaceutical enterprise. It considers the essence of “innovation development” and “innovation model of development” notions and analyses their organisational and legal provision. It justifies strategic tasks of the pharmaceutical filed to focus on in order to achieve a breakthrough when building an innovation model of economic development. The article proves that the most important factors that ensure growth of efficiency of pharmaceutical production are: wide application of the concept of strategic management and creation of innovations.

  2. Electrostatics of Pharmaceutical Aerosols for Pulmonary Delivery.

    Science.gov (United States)

    Lip Kwok, Philip Chi

    2015-01-01

    This paper provides a review on key research findings in the rapidly developing area of pharmaceutical aerosol electrostatics. Solids and liquids can become charged without electric fields, the former by contact or friction and the latter by flowing or spraying. Therefore, charged particles and droplets carrying net charges are produced from pharmaceutical inhalers (e.g. dry powder inhalers, metered dose inhalers, and nebulisers) due to the mechanical processes involved in aerosolisation. The charging depends on many physicochemical factors, such as formulation composition, solid state properties, inhaler material and design, and relative humidity. In silico, in vitro, and limited in vivo studies have shown that electrostatic charges may potentially influence particle deposition in the airways. However, the evidence is not yet conclusive. Furthermore, there are currently no regulatory requirements on the characterisation and control of the electrostatic properties of inhaled formulations. Besides the need for further investigations on the relationship between physicochemical factors and charging characteristics of the aerosols, controlled and detailed in vivo studies are also required to confirm whether charges can affect particle deposition in the airways. Since pharmaceutical aerosol electrostatics is a relatively new research area, much remains to be explored. Thus there is certainly potential for development. New findings in the future may contribute to the advancement of pharmaceutical aerosol formulations and respiratory drug delivery.

  3. Adsorption of lignosulfonate compounds using powdered eggshell

    Directory of Open Access Journals (Sweden)

    Muhammad Ali Zulfikar

    2012-07-01

    Full Text Available Batch adsorption of lignosulfonates using untreated powdered eggshell under the influences of mixing time, pH,particle size and dose of powdered eggshell was investigated. Adsorption isotherms of lignosulfonates onto powder eggshellwere also studied. Eggshells were collected from the Balubur traditional market in Bandung, Indonesia, washed with distilledwater, air dried, and then ground into powder of different particle sizes. Kinetic studies found that equilibrium time was ashigh as 90 minutes. From experiments carried out at different pH, it was observed that pH plays an important role in theadsorption of lignosulfonate compounds. It was also observed that particles size has no significant effect on the adsorptionof lignosulfonate compounds. The optimum dosage of powdered eggshell was 30 g/100 mL of 500 mg/L lignosulfonatesolution. Adsorption isotherms studied through the use of graphical methods revealed that the adsorption of lignosulfonatesonto powdered eggshell follows the Langmuir model.

  4. Processing Methods and Storage Conditions on Chocolate and Coffee Powder Flow Properties

    OpenAIRE

    Gong, Sunland L; Della Bella, Andrea; Carvajal, Teresa M.

    2015-01-01

    Powders are widely used in a countless number of industries, and are crucial to the quality control of products in areas such as pharmaceuticals and food. Particle physicochemical properties (morphology, solid state – crystalline, amorphous or both) are important factors for powder flow, which in turn can have significant impact on the stability, performance, and presentation of powders. Different processing methods as well as storage conditions such as relative humidity (RH) can drastically ...

  5. Effect of particle shape of active pharmaceutical ingredients prepared by fluidized-bed jet-milling on cohesiveness.

    Science.gov (United States)

    Fukunaka, Tadashi; Sawaguchi, Kohta; Golman, Boris; Shinohara, Kunio

    2005-05-01

    Milling is a common procedure to improve bioavailability of many active pharmaceutical ingredients (APIs), which typically have low solubility in water. But such micronization can yield an increase in the cohesiveness of particles. Although particle cohesiveness is desirable for tablet strength in the subsequent formulation process, increased particle cohesiveness can lead to operational difficulties in a milling equipment due to compaction of particles inside. In this article, the impact of milling via a fluidized-bed jet-mill on the cohesive strength and interparticle force was studied using Ethenzamide as a pharmaceutical model compound. As a result, the particle shape was found to affect both the tensile strength of powder bed and the interparticle cohesive force. A powder bed, having relatively high void fraction by direct tensile test, shows a positive correlation between the cohesive force and the particle sphericity, while powders with low void fraction by diametral compression test show a positive correlation between the cohesive force and the angularity of the particle.

  6. Analytical Modeling for Mechanical Strength Prediction with Raman Spectroscopy and Fractured Surface Morphology of Novel Coconut Shell Powder Reinforced: Epoxy Composites

    Science.gov (United States)

    Singh, Savita; Singh, Alok; Sharma, Sudhir Kumar

    2016-06-01

    In this paper, an analytical modeling and prediction of tensile and flexural strength of three dimensional micro-scaled novel coconut shell powder (CSP) reinforced epoxy polymer composites have been reported. The novel CSP has a specific mixing ratio of different coconut shell particle size. A comparison is made between obtained experimental strength and modified Guth model. The result shows a strong evidence for non-validation of modified Guth model for strength prediction. Consequently, a constitutive modeled equation named Singh model has been developed to predict the tensile and flexural strength of this novel CSP reinforced epoxy composite. Moreover, high resolution Raman spectrum shows that 40 % CSP reinforced epoxy composite has high dielectric constant to become an alternative material for capacitance whereas fractured surface morphology revealed that a strong bonding between novel CSP and epoxy polymer for the application as light weight composite materials in engineering.

  7. 干粉吸入剂空气动力学分散模型的建立和验证%Development and Validation of a Dry Powder Inhalation Aerodynamic Dispersion Model

    Institute of Scientific and Technical Information of China (English)

    姜力群; 汤玥; 鲁锡峰; 陈西敬; 朱家壁

    2011-01-01

    在Weiler干粉粒子聚集体全分散理论模型基础上,以硫酸沙丁胺醇为模型药物,建立了一种更加深入的千粉吸入剂空气动力学分散模型.硫酸沙丁胺醇干粉吸入剂体外沉积试验表明,该模型可预测干粉粒子的空气动力学分散行为,并可结合计算流体动力学,估算干粉吸入剂在吸入装置中的分散及微细粒子分数.%An improved dry powder inhalation aerodynamic dispersion model was developed based on the model introduced by Weiler for describing the complete disintegration of dry powder clusters with salbutamol sulfate as the model drug. The results of in vitro deposition experiments of salbutamol sulfate dry powder inhalation showed that the model could predict the dry powder aerodynamic dispersion behavior and estimate the dispersion behavior of a dry powder inhalation in a dry powder inhaler device and the fine particle fraction of the inhalation combined with computational fluid dynamics.

  8. Numerical Simulation of Upsetting a Cubic Sintered Iron Powder Compact

    Institute of Scientific and Technical Information of China (English)

    Wei XIA; Puqing CHEN; Zhaoyao ZHOU; Weibin ZHAO; Yuanyuan LI

    2003-01-01

    This paper establishes a mechanical model for sintered powder metal material and simulates the material behavior.Powder metal specimens were compacted, sintered and upset. Relative density and contour of the specimen were measured. The force displacement

  9. Modeling the photochemical attenuation of down-the-drain chemicals during river transport by stochastic methods and field measurements of pharmaceuticals and personal care products.

    Science.gov (United States)

    Hanamoto, Seiya; Nakada, Norihide; Yamashita, Naoyuki; Tanaka, Hiroaki

    2013-01-01

    Existing stochastic models for predicting concentrations of down-the-drain chemicals in aquatic environments do not account for the diurnal variation of direct photolysis by sunlight, despite its being an important factor in natural attenuation. To overcome this limitation, we developed a stochastic model incorporating temporal variations in direct photolysis. To verify the model, we measured 57 pharmaceuticals and personal care products (PPCPs) in a 7.6-km stretch of an urban river, and determined their physical and biological properties in laboratory experiments. During transport along the river, 8 PPCPs, including ketoprofen and azithromycin, were attenuated by >20%, mainly owing to direct photolysis and adsorption to sediments. The photolabile PPCPs attenuated significantly in the daytime but persisted in the nighttime. The observations were similar to the values predicted by the photolysis model for the photolabile PPCPs (i.e., ketoprofen, diclofenac and furosemide) but not by the existing model. The stochastic model developed in this study was suggested to be a novel and useful stochastic model for evaluating direct photolysis of down-the-drain chemicals, which occurs during the river transport.

  10. Aerated bunker discharge of fine dilating powders

    NARCIS (Netherlands)

    Ouwerkerk, C.E.D.; Molenaar, H.J.; Frank, M.J.W.

    1992-01-01

    The discharge rate of coarse powders (mean particle size 500 ¿m) from bunkers without aeration can be described by both empirical relations and theoretical models. In the case of small particles the discharge rate is largely overestimated. As the powder dilates during flow a negative pressure gradie

  11. Study of Velocity and Materials on Tribocharging of Polymer Powders for Powder Coating Applications

    Science.gov (United States)

    Biris, Alex S.; Trigwell, Steve; Sims, Robert A.; Mazumder, Malay K.

    2005-01-01

    Electrostatic powder deposition is widely used in a plethora of industrial-applications ranging from the pharmaceutical and food.industries, to farm equipment and automotive applications. The disadvantages of this technique are possible back corona (pin-like formations) onset and the Faraday penetration limitation (when the powder does not penetrate in some recessed areas). A possible solution to overcome these problems is to use tribochargers to electrostatically charge the powder. Tribocharging, or contact charging while two materials are in contact, is related to the work function difference between the contacting materials and generates bipolarly charged particles. The generation of an ion-free powder cloud by tribocharging with high bipolar charge and an overall charge density of almost zero, provides a better coverage of the recessed areas. In this study, acrylic and epoxy powders were fluidized and charged by passing through stainless steel, copper, aluminum, and polycarbonate static mixers, respectively. The particle velocity was varied to determine its effect on the net charge-to-mass ratio (QIM) acquired by the powders. In general, the Q/M increases rapidly when the velocity was increased from 1.5 to 2.5 m/s, remaining almost constant for higher velocities. Charge separation experiments showed bipolar charging for all chargers.

  12. Analysis of powder phenomena inside a Fette 3090 feed frame using in-line NIR spectroscopy.

    Science.gov (United States)

    Mateo-Ortiz, Daniel; Colon, Yleana; Romañach, Rodolfo J; Méndez, Rafael

    2014-11-01

    New analytical methods are needed to understand and optimize the processes by which tablets are produced. Fette 3090 tablet presses are commonly used in the pharmaceutical industry. A near-infrared (NIR) probe was installed into a Fette 3090 feed frame to understand and monitor the die filling process. The second objective was to analyze in detail the different factors that could affect the prediction of the developed NIR calibration models. Two monitoring positions for NIR spectrometers were evaluated; one at each side of the feed frame. A powder wave behavior caused by the paddle motion was observed inside the feed frame. The study also revealed that NIR spectra can help in the understanding of powder flow inside the feed frame. It was demonstrated that NIR spectra baselines can also be used to determine changes in mass inside the feed frame. The new NIR method showed that the paddle wheel speed has a significant impact in the powder dynamics inside the feed frame. The baselines of the NIR spectra depended on the mass hold-up inside the feed frame and paddle wheel speed. Studies using blends were performed to develop a NIR calibration model based on the feed frame system dynamics to determine acetaminophen drug concentration variability during the die filling process. The study found that variation in the distance from the powder to the probe due to paddle wheel speed has a significant effect on the NIR prediction. This study found that with NIR spectroscopy, blend uniformity can be assessed with high accuracy during the die filling process using the corresponding paddle wheel speed in-line calibration model. NIR was demonstrated to be a good development tool for the in-line monitoring of powder during the die filling process.

  13. Pharmaceutical policy in China.

    Science.gov (United States)

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

    2008-01-01

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

  14. Powder lubrication of faults by powder rolls in gouge zones

    Science.gov (United States)

    Chen, X.; Madden, A. S.; Reches, Z.

    2013-12-01

    increased development of rolls (= increasing surface coverage) enhanced fault weakening. We applied the Eldredge and Tabor (1955) model for rolling friction to the AFM observed morphology of the rolls and PSZs, and found good agreement between measured and modeled friction coefficients. We conclude that the measured friction reduction reflects a transition from sliding-dominated slip to rolling-dominated slip due to the presence and density of powder rolls. We further argue that powder rolling is an effective mechanism of powder lubrication, and that spontaneous growth of such rolls along crustal faults is likely to control earthquake weakening.

  15. Pharmaceutical pricing and reimbursement reforms in Greece.

    Science.gov (United States)

    Yfantopoulos, John

    2008-02-01

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

  16. Fundamental Study on Applicability of Powder-Based 3D Printer for Physical Modeling in Rock Mechanics

    Science.gov (United States)

    Fereshtenejad, Sayedalireza; Song, Jae-Joon

    2016-06-01

    Applications of 3D printing technology become more widespread in many research fields because of its rapid development and valuable capabilities. In rock mechanics and mining engineering, this technology has the potential to become a useful tool that might help implement a number of research studies previously considered impractical. Most commercial 3D printers cannot print prototypes with mechanical properties that match precisely those of natural rock samples. Therefore, some additional enhancements are required for 3D printers to be effectively utilized for rock mechanics applications. In this study, we printed and studied specimens using a powder-based commercial ZPrinter® 450 with ZP® 150 powder and Zb® 63 binder used as raw materials. The specimens printed by this 3D printer exhibited relatively low strength and ductile behavior, implying that it needs further improvements. Hence, we focused on several ways to determine the best combination of printing options and post-processing including the effects of the printing direction, printing layer thickness, binder saturation level, and heating process on the uniaxial compressive strength (UCS) and stress-strain behavior of the printed samples. The suggested procedures have demonstrated their effectiveness by obtaining the printed samples that behave similarly to the natural rocks with low UCS. Although our optimization methods were particularly successful, further improvements are required to expand 3D printer application in the area of rock mechanics.

  17. Pharmaceutical Industry Develops Steadily

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ With the development of the economy, the growth of the total population, the growing proportion of older citizens, and the increasing awareness of people's health care,the pharmaceutical market in China has seen a sustained and rapid expansion.

  18. Ethiopian Pharmaceutical Journal: Submissions

    African Journals Online (AJOL)

    Ethiopian Pharmaceutical Journal (EPJ) is a bian-nual Journal, which ... Acknowledgements, References, Illustrations (Tables, Figures and chemistry ... Nomenclature and spelling should conform to the directions given by IUPAC and IUB.

  19. Amorphous pharmaceutical solids.

    Science.gov (United States)

    Vranić, Edina

    2004-07-01

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

  20. A systematic review of cost-effectiveness modeling of pharmaceutical therapies in neuropathic pain: variation in practice, key challenges, and recommendations for the future.

    Science.gov (United States)

    Critchlow, Simone; Hirst, Matthew; Akehurst, Ron; Phillips, Ceri; Philips, Zoe; Sullivan, Will; Dunlop, Will C N

    2017-02-01

    Complexities in the neuropathic-pain care pathway make the condition difficult to manage and difficult to capture in cost-effectiveness models. The aim of this study is to understand, through a systematic review of previous cost-effectiveness studies, some of the key strengths and limitations in data and modeling practices in neuropathic pain. Thus, the aim is to guide future research and practice to improve resource allocation decisions and encourage continued investment to find novel and effective treatments for patients with neuropathic pain. The search strategy was designed to identify peer-reviewed cost-effectiveness evaluations of non-surgical, pharmaceutical therapies for neuropathic pain published since January 2000, accessing five key databases. All identified publications were reviewed and screened according to pre-defined eligibility criteria. Data extraction was designed to reflect key data challenges and approaches to modeling in neuropathic pain and based on published guidelines. The search strategy identified 20 cost-effectiveness analyses meeting the inclusion criteria, of which 14 had original model structures. Cost-effectiveness modeling in neuropathic pain is established and increasing across multiple jurisdictions; however, amongst these studies, there is substantial variation in modeling approach, and there are common limitations. Capturing the effect of treatments upon health outcomes, particularly health-related quality-of-life, is challenging, and the health effects of multiple lines of ineffective treatment, common for patients with neuropathic pain, have not been consistently or robustly modeled. To improve future economic modeling in neuropathic pain, further research is suggested into the effect of multiple lines of treatment and treatment failure upon patient outcomes and subsequent treatment effectiveness; the impact of treatment-emergent adverse events upon patient outcomes; and consistent and appropriate pain measures to inform

  1. Applying a novel electrostatic dry powder coating technology to pellets.

    Science.gov (United States)

    Yang, Qingliang; Ma, Yingliang; Zhu, Jesse

    2015-11-01

    The present study aimed to apply a novel dry powder technology to coat pellets with different coating materials grounded into fine powders. Piroxicam, a non-steroidal anti-inflammatory drug, was used as the active pharmaceutical ingredient (API). Eudragit® EPO, Eudragit® RS/RL and Acryl EZE were used as the coating materials to achieve immediate release, sustained release and delayed release, respectively. Three steps including preheating, powder adhesion and curing were carried out to form the coating film while liquid plasticizers were used to decrease the glass transition temperature of coating powders and also served to reduce the electrical resistance of pellets. Results of SEM indicated coating film could be better formed by increasing curing temperature or extending curing time. Dissolution tests showed that three different drug release profiles, including immediate release, sustained release and delayed release, were achieved by this coating technology with different coating formulations. And the dry powder coated pellets using this developed technology exhibited an excellent stability with 1 month at 40 °C/75% RH. The coating procedure could be shortened to within 120 min and the use of fluidized hot air was minimized, both cutting down the overall cost dramatically compared to organic solvent coating and aqueous coating. All results demonstrated that the novel electrostatic dry powder coating method is a promising technology in the pharmaceutical coating industry.

  2. Using the computerized glow curve deconvolution method and the R package tgcd to determination of thermoluminescence kinetic parameters of chilli powder samples by GOK model and OTOR one

    Science.gov (United States)

    Sang, Nguyen Duy; Van Hung, Nguyen; Van Hung, Tran; Hien, Nguyen Quoc

    2017-03-01

    The kinetic parameters of thermoluminescence (TL) glow peaks of chilli powder irradiated by gamma rays with the different doses of 0, 4 and 8 kGy have been calculated and estimate by computerized glow curve deconvolution (CGCD) method and the R package tgcd by using the TL glow curve data. The kinetic parameters of TL glow peaks (i.e. activation energies (E), order of kinetics (b), trapping and recombination probability coefficients (R) and frequency factors (s)) are fitted by modeled general-orders of kinetics (GOK) and one trap-one recombination (OTOR). The kinetic parameters of the chilli powder are different toward the difference of the sample time-storage, radiation doses, GOK model and OTOR one. The samples spending the shorter period of storage time have the smaller the kinetic parameters values than the samples spending the longer period of storage. The results obtained as comparing the kinetic parameters values of the three samples show that the value of non-irradiated samples are lowest whereas the 4 kGy irradiated-samples' value are greater than the 8 kGy irradiated-samples' one time.

  3. Evaluation of two dynamic in vitro models simulating fasted and fed state conditions in the upper gastrointestinal tract (TIM-1 and tiny-TIM) for investigating the bioaccessibility of pharmaceutical compounds from oral dosage forms

    NARCIS (Netherlands)

    Verwei, M.; Minekus, M.; Zeijdner, E.; Schilderink, R.; Havenaar, R.

    2016-01-01

    Pharmaceutical research needs predictive in vitro tools for API bioavailability in humans. We evaluated two dynamic in vitro gastrointestinal models: TIM-1 and tiny-TIM. Four low-soluble APIs in various formulations were investigated in the TIM systems under fasted and fed conditions. API small-inte

  4. Granulation of fine powder

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ching-Fong

    2016-08-09

    A mixture of fine powder including thorium oxide was converted to granulated powder by forming a first-green-body and heat treating the first-green-body at a high temperature to strengthen the first-green-body followed by granulation by crushing or milling the heat-treated first-green-body. The granulated powder was achieved by screening through a combination of sieves to achieve the desired granule size distribution. The granulated powder relies on the thermal bonding to maintain its shape and structure. The granulated powder contains no organic binder and can be stored in a radioactive or other extreme environment. The granulated powder was pressed and sintered to form a dense compact with a higher density and more uniform pore size distribution.

  5. New perspectives for visual characterization of pharmaceutical solids

    DEFF Research Database (Denmark)

    Laitinen, Niklas; Antikainen, Osmo; Rantanen, Jukka

    2004-01-01

    The utilization of descriptive image information in pharmaceutical powder technology is rather limited. Consequently, the development of this discipline is a challenge within physical characterization of pharmaceutical solids. The aim of this study was to develop and evaluate an inventive visual...... the GSDM and sieve analysis measurements. The image information of the end-point samples was also evaluated with respect to tabletting behavior of the granules produced. Principal component analysis (PCA) was used for data visualization. The introduced approach was suitable in particle size measurements...

  6. Uniting Electron Crystallography and Powder Diffraction

    CERN Document Server

    Shankland, Kenneth; Meshi, Louisa; Avilov, Anatoly; David, William

    2012-01-01

    The polycrystalline and nanocrystalline states play an increasingly important role in exploiting the properties of materials, encompassing applications as diverse as pharmaceuticals, catalysts, solar cells and energy storage. A knowledge of the three-dimensional atomic and molecular structure of materials is essential for understanding and controlling their properties, yet traditional single-crystal X-ray diffraction methods lose their power when only polycrystalline and nanocrystalline samples are available. It is here that powder diffraction and single-crystal electron diffraction techniques take over, substantially extending the range of applicability of the crystallographic principles of structure determination.  This volume, a collection of teaching contributions presented at the Crystallographic Course in Erice in 2011, clearly describes the fundamentals and the state-of-the-art of powder diffraction and electron diffraction methods in materials characterisation, encompassing a diverse range of discipl...

  7. Model-based analysis of high shear wet granulation from batch to continuous processes in pharmaceutical production--a critical review.

    Science.gov (United States)

    Kumar, Ashish; Gernaey, Krist V; De Beer, Thomas; Nopens, Ingmar

    2013-11-01

    The manufacturing of pharmaceutical dosage forms, which has traditionally been a batch-wise process, is now also transformed into a series of continuous operations. Some operations such as tabletting and milling are already performed in continuous mode, while the adaptation towards a complete continuous production line is still hampered by complex steps such as granulation and drying which are considered to be too inflexible to handle potential product change-overs. Granulation is necessary in order to achieve good flowability properties and better control of drug content uniformity. This paper reviews modelling and supporting measurement tools for the high shear wet granulation (HSWG) process, which is an important granulation technique due to the inherent benefits and the suitability of this unit operation for the desired switch to continuous mode. For gaining improved insight into the complete system, particle-level mechanisms are required to be better understood, and linked with an appropriate meso- or macro-scale model. A brief review has been provided to understand the mechanisms of the granulation process at micro- or particle-level such as those involving wetting and nucleation, aggregation, breakage and consolidation. Further, population balance modelling (PBM) and the discrete element method (DEM), which are the current state-of-the-art methods for granulation modelling at micro- to meso-scale, are discussed. The DEM approach has a major role to play in future research as it bridges the gap between micro- and meso-scales. Furthermore, interesting developments in the measurement technologies are discussed with a focus towards inline measurements of the granulation process to obtain experimental data which are required for developing good models. Based on the current state of the developments, the review focuses on the twin-screw granulator as a device for continuous HSWG and attempts to critically evaluate the current process. As a result, a set of open

  8. Cow dung powder poisoning

    Directory of Open Access Journals (Sweden)

    Khaja Mohideen Sherfudeen

    2015-01-01

    Full Text Available Cow dung, which has germicidal property, was used in ancient days to clean living premises in South India. Nowadays, people are using commercially available synthetic cow dung powder. It is locally known as "saani powder" in Tamil Nadu. It is freely available in homes and is sometimes accidentally consumed by children. It is available in two colors - yellow and green. Cow dung powder poisoning is common in districts of Tamil Nadu such as Coimbatore, Tirupur, and Erode. We report two cases of yellow cow dung powder poisoning from our hospital.

  9. Cow dung powder poisoning.

    Science.gov (United States)

    Sherfudeen, Khaja Mohideen; Kaliannan, Senthil Kumar; Dammalapati, Pavan Kumar

    2015-11-01

    Cow dung, which has germicidal property, was used in ancient days to clean living premises in South India. Nowadays, people are using commercially available synthetic cow dung powder. It is locally known as "saani powder" in Tamil Nadu. It is freely available in homes and is sometimes accidentally consumed by children. It is available in two colors - yellow and green. Cow dung powder poisoning is common in districts of Tamil Nadu such as Coimbatore, Tirupur, and Erode. We report two cases of yellow cow dung powder poisoning from our hospital.

  10. Determination of model parameters for zinc (II) ion biosorption onto powdered waste sludge (PWS) in a fed-batch system.

    Science.gov (United States)

    Kargi, Fikret; Cikla, Sinem

    2007-12-01

    Biosorption of zinc (II) ions onto pre-treated powdered waste sludge (PWS) was investigated using a completely mixed tank operating in fed-batch mode instead of an adsorption column. Experiments with variable feed flow rate (0.05-0.5 L h(-1)), feed Zn(II) ion concentrations (37.5-275 mg L(-1)) and amount of adsorbent (1-6 g PWS) were performed using fed-batch operation at pH 5 and room temperature (20-25 degrees C). Break-through curves describing variations of aqueous (effluent) zinc ion concentrations with time were determined for different operating conditions. Percent zinc removal from the aqueous phase decreased, but the biosorbed (solid phase) zinc ion concentration increased with increasing feed flow rate and zinc concentration. A modified Bohart-Adams equation was used to determine the biosorption capacity of PWS (q'(s)) and the rate constant (K) for zinc ion biosorption. Biosorption capacity (q'(s)=57.7 g Zn kg(-1) PWS) of PWS in fed-batch operation was found to be comparable with powdered activated carbon (PAC) in column operations. However, the adsorption rate constant (K=9.17 m(3) kg(-1) h(-1)) in fed-batch operation was an order of magnitude larger than those obtained in adsorption columns because of elimination of mass transfer limitations encountered in the column operations. Therefore, a completely mixed tank operated in fed-batch mode was proven to be more advantageous as compared to adsorption columns due to better contact between the phases yielding faster adsorption rates.

  11. Understanding pharmaceutical quality by design.

    Science.gov (United States)

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

    2014-07-01

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

  12. Improved partial least squares models for stability-indicating analysis of mebeverine and sulpiride mixtures in pharmaceutical preparation: a comparative study.

    Science.gov (United States)

    Darwish, Hany W; Naguib, Ibrahim A

    2013-05-01

    Performance of partial least squares regression (PLSR) is enhanced in the presented work by three multivariate models, including weighted regression PLSR (Weighted-PLSR), genetic algorithm PLSR (GA-PLSR), and wavelet transform PLSR (WT-PLSR). The proposed models were applied for the stability-indicating analysis of mixtures of mebeverine hydrochloride (meb) and sulpiride (sul) in the presence of their reported impurities and degradation products. The work introduced in this paper aims to compare these different chemometric methods, showing the underlying algorithm for each and making a comparison of analysis results. For proper analysis, a 6-factor, 5-level experimental design was established resulting in a training set of 25 mixtures containing different ratios of the interfering species. A test set consisting of 5 mixtures was used to validate the prediction ability of the suggested models. Leave one out (LOO) and bootstrap were applied to predict number of PLS components. The GA-PLSR proposed method was successfully applied for the analysis of raw material (test set 101.03% ± 1.068, 101.47% ± 2.721 for meb and sul, respectively) and pharmaceutical tablets containing meb and sul mixtures (10.10% ± 0.566, 98.16% ± 1.081 for meb and sul).

  13. Equivalência farmacêutica da formulação combinada de budesonida e formoterol em cápsula única com dispositivo inalador de pó Pharmaceutical equivalence of the combination formulation of budesonide and formoterol in a single capsule with a dry powder inhaler

    Directory of Open Access Journals (Sweden)

    Marina Andrade-Lima

    2012-12-01

    Full Text Available OBJETIVO: Avaliar a equivalência farmacêutica da formulação teste (associação fixa de budesonida e fumarato de formoterol em cápsula única dispensada com o dispositivo Aerocaps® em relação a uma formulação referência (budesonida e fumarato de formoterol em duas cápsulas distintas dispensadas com o dispositivo Aerolizer®. MÉTODOS: Estudo in vitro no qual foram realizadas identificação/quantificação dos ingredientes ativos por HPCL e determinação da uniformidade da dose liberada e da distribuição aerodinâmica das partículas das formulações teste e referência. RESULTADOS: Na formulação teste, o teor de budesonida e de formoterol foi de 111,0% e 103,8%, respectivamente, enquanto esse foi de 110,5% e 104,5% na formulação referência. Na formulação teste, a uniformidade das doses de budesonida e de formoterol foi de 293,2 µg e 10,2 µg, respectivamente, enquanto essa foi de 353,0 µg e 11,1 µg na formulação referência. Esses resultados estão dentro da faixa recomendada para esse tipo de formulação (75-125% da dose rotulada. A fração de partículas finas (OBJECTIVE: To evaluate the pharmaceutical equivalence of a test formulation (fixed-dose combination of budesonide and formoterol fumarate in a single capsule dispensed in an Aerocaps® inhaler in relation to a reference formulation (budesonide and formoterol fumarate in two separate capsules dispensed in an Aerolizer® inhaler. METHODS: This was an in vitro study in which we performed the identification/quantification of the active ingredients by HPLC and determined dose uniformity and aerodynamic particle size distribution in the test and reference formulations. RESULTS: In the test formulation, the content of budesonide and formoterol was 111.0% and 103.8%, respectively, compared with 110.5% and 104.5%, respectively, in the reference formulation. In the test formulation, dose uniformity regarding budesonide and formoterol was 293.2 µg and 10.2 µg

  14. Measurement of low amounts of amorphous content in hydrophobic active pharmaceutical ingredients with dynamic organic vapor sorption.

    Science.gov (United States)

    Müller, Thorsten; Schiewe, Jörg; Smal, Rüdiger; Weiler, Claudius; Wolkenhauer, Markus; Steckel, Hartwig

    2015-05-01

    Today, a variety of devices for dry powder inhalers (DPIs) is available and many different formulations for optimized deposition in the lung are developed. However, during the production of powder inhalers, processing steps may induce changes to both, the carrier and active pharmaceutical ingredients (APIs). It is well known that standard pharmaceutical operations may lead to structural changes, crystal defects and amorphous regions. Especially operations such as milling, blending and even sieving generate these effects. These disorders may induce re-crystallization and particle size changes post-production which have a huge influence on drug delivery and product stability. In this study, pilot tests with a polar solvent (water) and hydrophilic drug (Salbutamol sulfate) were performed to receive a first impression on further possible implementation of hydrophobic samples with organic solvents. Thereafter, a reliable method for the accurate detection of low amounts of amorphous content is described up to a limit of quantification (LOQ) of 0.5% for a hydrophobic model API (Ciclesonide). The organic vapor sorption method which is a gravimetric method quantifies exactly these low amounts of amorphous content in the hydrophobic powder once the suitable solvent (isopropanol), the correct p/p0 value (0.1) and the exact temperature (25°C) have been found. Afterward it was possible to quantitate low amorphous amounts in jet-milled powders (0.5-17.0%). In summary, the data of the study led to a clearer understanding in what quantity amorphous parts were generated in single production steps and how variable these parts behave to fully crystalline material. Nevertheless it showed how difficult it was to re-crystallize hydrophobic material with water vapor over a short period. For the individual samples it was possible to determine the single humidity at which the material starts to re-crystallize, the behavior against different nonpolar solvents and the calculation of the

  15. [Fourcroy and pharmaceutical journals].

    Science.gov (United States)

    Bonnemain, Bruno

    2011-04-01

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

  16. Omeprazole/Antacid-powder suspension-Santarus: omeprazole/sodium bicarbonate powder-Santarus, SAN 05.

    Science.gov (United States)

    2004-01-01

    Santarus Inc. is developing an immediate-release formulation of omeprazole in combination with an antacid (sodium bicarbonate) as a powder for suspension, known as Acitreltrade mark [SAN 05] and also as Rapinex powder for oral suspension. This omeprazole powder suspension will be used to treat gastrointestinal haemorrhage, gastro-oesophageal reflux disease, heartburn and peptic ulcers. Acitreltrade mark is based on technology licensed from the University of Missouri. Santarus have also licensed technology from Tulane and North Carolina Universities relating to potential treatments for gastrointestinal (GI) diseases. Santarus has licensed exclusive, worldwide rights to patent applications covering specific combination formulations of proton pump inhibitors (PPIs) and antacids for treating various upper GI diseases and disorders. Santarus plans to license the development, distribution and marketing rights of omeprazole powder for oral suspension 20 mg outside the US, to one or more well established pharmaceutical companies. The US FDA has requested that Santarus pursue a name other than Rapinex for the product. Santarus is currently discussing potential alternative names for the product with the FDA. Santarus announced positive results in August 2003 from a phase III trial comparing oral Acitrel (Rapinex 40 mg) with intravenous cimetidine in preventing upper GI bleeding in 359 critically ill adult patients. Santarus has also completed an open-label clinical trial in 243 patients, including 97 patients with gastric ulcers, evaluating the safety of this omeprazole 40 mg powder suspension for an 8-week period. In connection with the NDA for omeprazole powder suspension 40 mg, Santarus provided notice to the NDA holder for Prilosec delayed-release capsules and related patent owners that omeprazole powder suspension 40 mg does not infringe currently listed patents for Prilosec or that those patents are invalid.

  17. In vivo pretreatment of Eudrilus eugeniae powder attenuates β-adrenoceptor toxicity mediated by isoproterenol in rat model

    Directory of Open Access Journals (Sweden)

    Jaganathan Anitha

    2016-08-01

    Full Text Available The present study was designed to discover the potential cardioprotective function of earthworm powder (EWP extracted from Eudrilus eugeniae on isoproterenol (ISO-induced myocardial infarction in male Wistar rats. The rats were divided into four groups, with six rats in each group. Certain rats were pretreated with EWP (200 mg/kg bwt (Group III, and a myocardial infarction was then induced by subcutaneous injection of ISO (85 mg/kg bwt (Group II. Oral pretreatment of 200 mg/kg bwt of EWP for 28 days significantly (p > 0.05 improved the blood profile levels, including (a the lipid profile of total cholesterol (TC, free fatty acids (FFA, and triglycerides (TG; (b low-density lipoprotein (LDL, very low-density lipoprotein (VLDL, high-density lipoprotein (HDL, and protein; and (c A/G ratio, glucose and uric acid levels. The electrophoretic pattern of elevated lactose dehydrogenase (LDH levels was recovered by EWP treatment as evidenced by comparison with ISO-induced rats with cardiac damage. The above results indicate that EWP (200 mg/kg bwt provides a cardioprotective effect by attenuating the blood profile, lipid profile, biochemical levels, and LDH patterns in rats that experienced an ISO-induced myocardial infarction.

  18. Spray drying technique: II. Current applications in pharmaceutical technology.

    Science.gov (United States)

    Sollohub, Krzysztof; Cal, Krzysztof

    2010-02-01

    This review presents current applications of spray drying in pharmaceutical technology. The topics discussed include the obtention of excipients and cospray dried composites, methods for increasing the aqueous solubility and bioavailability of active substances, and modified release profiles from spray-dried particles. This review also describes the use of the spray drying technique in the context of biological therapies, such as the spray drying of proteins, inhalable powders, and viable organisms, and the modification of the physical properties of dry plant extracts.

  19. Rheology in Pharmaceutical Sciences

    DEFF Research Database (Denmark)

    Aho, Johanna; Hvidt, Søren; Baldursdottir, Stefania

    2016-01-01

    Rheology is the science of flow and deformation of matter. Particularly gels and non-Newtonian fluids, which exhibit complex flow behavior, are frequently encountered in pharmaceutical engineering and manufacturing, or when dealing with various in vivo fluids. Therefore understanding rheology...... is important, and the ability to use rheological characterization tools is of great importance for any pharmaceutical scientist involved in the field. Flow can be generated by shear or extensional deformations, or a combination of both. This chapter introduces the basics of both shear and extensional rheology...

  20. Subtask 6: Recommended practices for powder characterization. IEA Programme on Advanced Fuel Cells, Annex 2: Modelling and evaluation of Solid Oxide Fuel Cells

    Energy Technology Data Exchange (ETDEWEB)

    Van Heuveln, F.H.; Huijsmans, J.P.P. [eds.

    1992-08-01

    Powders, or precursors of powders, for the fabrication of Solid Oxide Fuel Cell (SOFC) anode-, cathode-, electrolyte- and ceramic interconnect structures are the relevant products to be evaluated. The aim is to provide a standard set of powder properties which have to be measured according to recommended methods and measurement conditions. The set is based on the results of a round robin test for electrolyte powder between five laboratories. The selected powder properties to be measured are chemical composition, phase composition, specific surface, particle size distribution, particle shape, sinterability, powder density, and flowability. The laboratories involved are Cookson Group (United Kingdom), Eniricerche (Italy), Senter for Industriforskning (Norway), Alusuisse/Lonza (Switzerland), and the Netherlands Energy Research Foundation. 2 app., 8 refs.

  1. Aripiprazole (Otsuka Pharmaceutical Co).

    Science.gov (United States)

    Ozdemir, Vural; Fourie, Jeanne; Ozdener, Fatih

    2002-01-01

    Otsuka Pharmaceuticals in collaboration with Bristol-Myers Squibb is developing aripiprazole, a dual dopamine autoreceptor agonist and postsynaptic D2 receptor antagonist, for the potential treatment of psychoses including schizophrenia [281327], [340364]. A regulatory filing for schizophrenia in the US was submitted at the end of 2001 [340364]. The compound entered phase III trials in Japan in 1995 [192966]. Although presynaptic dopamine autoreceptor agonists may be efficacious in the treatment of schizophrenia, they may also potentially increase the risk for exacerbation of psychosis through stimulation of postsynaptic dopaminergic receptors [245791], [350478], [350479]. However, earlier neuropharmacology studies have shown that aripiprazole can act as a presynaptic D2 agonist while displaying an antagonistic effect at the postsynaptic D2 receptors [281327], [337126], [350479], [424587], [424588]. In animal models, aripiprazole inhibits the apomorphine-induced stereotypy, without causing catalepsy [281327], [337126]. Moreover, in contrast to classical antipsychotics that produce disabling movement disorders, aripiprazole does not cause an upregulation of D2 receptors or an increase in expression of the c-fos mRNA in the striatum, in agreement with the low risk for extrapyramidal side effects (EPS) during aripiprazole treatment [245781], [262096], [350481], [350483]. Collectively, aripiprazole is an important atypical antipsychotic candidate with a favorable safety profile. Moreover, the mechanism of action of aripiprazole differentiates it from both typical and atypical antipsychotics and hence, may provide important leads for pharmacotherapy of schizophrenia and other psychotic disorders. In January 2000, Lehman Brothers predicted peak sales of aripiprazole could reach US $500 million [357788]. In February 2001, Credit Suisse First Boston predicted sales of US $403 million in 2005 [399484].

  2. Towards an improved understanding of strength and anisotropy of cold compacted powder

    Science.gov (United States)

    Wang, Wenhai

    The strength of powder compacts after cold compaction is known to be anisotropic, which comes from the directionality of microstructure resulting from initial particle morphology and/or from particle deformation during compaction. Current work focuses on multi-scale numerical analysis of powder compaction with emphasis on the role of interparticle cohesion on post-compaction mechanical properties. At macroscopic level, we applied phenomenological model to describe the mechanical behavior of powder, in which the material is considered to be continuum medium. A user subroutine (VUMAT) was successfully developed for ABAQUS/Explicit analysis, in which one of the popular phenomenological models for powder compaction---Drucker Prager/Cap model---is implemented. By studying of pharmaceutical powder die compaction and subsequent diametrical compression test via finite element analysis, the capabilities and limitations of current constitutive models are evaluated on predicting such as density, stress and tool force evolution, as well as the strength and fracture tendency. Our results illustrate that current model has good predictive capability of powder densification (e.g. density evolution) but can not predict post-compaction strength well. The following studies focus on evaluating the physics and mechanics occurring at particle level. The compaction of granular media was explored by using MPFEM approach. In the new model, individual particles discretized with a finite element mesh allow for a full description of contact mechanics and local and global particle kinematics. The introduction of a layer of degrading material on the surface of each particle provides the means of introducing variable cohesion and its effect on the final strength of compacts. The simulations show that the unloading creates tensile stresses at the root of the contact necks, which may cause partial or full separation of contact interface when the cohesion developed during loading is not strong

  3. Modeling the Solid-Liquid Equilibrium in Pharmaceutical-Solvent Mixtures: Systems with Complex Hydrogen Bonding Behvaior

    DEFF Research Database (Denmark)

    Tsivintzelis, Ioannis; Economou, Ioannis; Kontogeorgis, Georgios

    2009-01-01

    A methodology is suggested for modeling the phase equilibria of complex chemical mixtures with an equation of state (EoS) for the case where only limited experimental data exist. The complex hydrogen bonding behavior is explicitly accounted for and the corresponding parameters are adopted from......, accurate correlations were obtained. The prediction ability of the approach was evaluated against predictions from the COSMO-RS model. A thorough discussion is made for the appropriate modeling of solid solubility considering the effect of the difference of the heat capacities of the solute in liquid...

  4. Hygroscopic behavior of lyophilized acerola pulp powder

    Directory of Open Access Journals (Sweden)

    Luciana C. Ribeiro

    2016-03-01

    Full Text Available ABSTRACT Powder products are characterized by their practicality and long life. However, fruit powders have high hygroscopicity and tend to agglomerate due to its hydrophilic nature. The isotherms of equilibrium moisture content apply to the study of dehydrated food preservation potential. Acerola is a nutritionally rich fruit, with great economic and industrial potential. The objective of this study was to analyse acerola powder adsorption isotherms obtained by lyophilization and characterize the powder obtained from lyophilized acerola pulp. Analysis of hygroscopicity, solubility and degree of caking were performed. Isotherms were represented by the mathematical models of GAB, BET, Henderson and Oswin, at temperatures of 25, 35 and 45 °C. According to the results, the obtained powder showed hygroscopicity of 5.96 g of absorbed water 100g-1 of solids, solubility of 95.08% and caking of 14.12%. The BET model showed the best fit to the adsorption isotherms of the acerola pulp powder obtained by lyophilization. The obtained isotherm was of type III, with a "J" shape. There was an inversion of the effect of temperature on the isotherms of acerola powders.

  5. Identification Technology Research for Powder Model of Artillery%火炮发射药装药自动识别方法

    Institute of Scientific and Technical Information of China (English)

    崔凯波; 秦俊奇; 狄长春; 原瑞宏; 祝天宇

    2013-01-01

    发射装药号是影响火炮身管寿命的重要因素,为自动识别火炮发射药的装药号,避免人工记录失误和完善火炮射弹履历,分析了装药号自动识别原理,运用火炮动力学分析理论和ADAMS虚拟样机技术,建立火炮发射动力学虚拟样机.通过仿真试验获取样本数据,应用BP神经网络进行学习和训练,从而建立装药号和测试数据之间的非线性映射关系,实现对火炮发射装药号的精确预测.%In order to identify the powder model of artillery,which is the important factor to affect the life of cannon barrel,avoiding the manually record mistake and supplementing the firing record,the thesis focusing this theme includes the following work:analyzsis of the identify theory of charge,establish ment of the virtual prototype of a type of howitzer based on the dynamics analysis technology and ADAMS software.The sample couple is obtained by simulation.The back propagation algorithm is used to study and train the sample couple based on artificial neural network,and then the nonlinearity relation is achieved between the powder model and the influencing parameters.Therefore,it can provide the accurate measure to forecast the cannon charge.

  6. Structure-Property Relationships of Solids in Pharmaceutical Processing

    Science.gov (United States)

    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.

  7. Rapid Screening for Exposure to "Non-Target" Pharmaceuticals from Wastewater Effluents by Combining HRMS-Based Suspect Screening and Exposure Modeling.

    Science.gov (United States)

    Singer, Heinz P; Wössner, Annika E; McArdell, Christa S; Fenner, Kathrin

    2016-07-01

    Active pharmaceutical ingredients (APIs) have raised considerable concern over the past decade due to their widespread detection in water resources and their potential to affect ecosystem health. This triggered many attempts to prioritize the large number of known APIs to target monitoring efforts and testing of fate and effects. However, so far, a comprehensive approach to screen for their presence in surface waters has been missing. Here, we explore a combination of an automated suspect screening approach based on liquid chromatography coupled to high-resolution mass spectrometry and a model-based prioritization using consumption data, readily predictable fate properties and a generic mass balance model for activated sludge treatment to comprehensively detect APIs with relevant exposure in wastewater treatment plant effluents. The procedure afforded the detection of 27 APIs that had not been covered in our previous target method, which included 119 parent APIs. The newly detected APIs included seven compounds with a high potential for bioaccumulation and persistence, and also three compounds that were suspected to stem from point sources rather than from consumption as medicines. Analytical suspect screening proved to be more selective than model-based prioritization, making it the method of choice for focusing analytical method development or fate and effect testing on those APIs most relevant to the aquatic environment. However, we found that state-of-the-practice exposure modeling used to predict potential high-exposure substances can be a useful complement to point toward oversights and known or suspected detection gaps in the analytical method, most of which were related to insufficient ionization.

  8. Electrical conductivity of metal powders under pressure

    Energy Technology Data Exchange (ETDEWEB)

    Montes, J.M.; Cintas, J.; Urban, P. [Universidad de Sevilla, Department of Mechanical and Materials Engineering Escuela Tecnica Superior de Ingenieria, Sevilla (Spain); Cuevas, F.G. [Universidad de Huelva, Department of Chemistry and Materials Science Escuela Tecnica Superior de Ingenieria, Palos de la Frontera (Spain)

    2011-12-15

    A model for calculating the electrical conductivity of a compressed powder mass consisting of oxide-coated metal particles has been derived. A theoretical tool previously developed by the authors, the so-called 'equivalent simple cubic system', was used in the model deduction. This tool is based on relating the actual powder system to an equivalent one consisting of deforming spheres packed in a simple cubic lattice, which is much easier to examine. The proposed model relates the effective electrical conductivity of the powder mass under compression to its level of porosity. Other physically measurable parameters in the model are the conductivities of the metal and oxide constituting the powder particles, their radii, the mean thickness of the oxide layer and the tap porosity of the powder. Two additional parameters controlling the effect of the descaling of the particle oxide layer were empirically introduced. The proposed model was experimentally verified by measurements of the electrical conductivity of aluminium, bronze, iron, nickel and titanium powders under pressure. The consistency between theoretical predictions and experimental results was reasonably good in all cases. (orig.)

  9. A Study of Comparative Advantage and Intra-Industry Trade in the Pharmaceutical Industry of Iran.

    Science.gov (United States)

    Yusefzadeh, Hassan; Rezapour, Aziz; Lotfi, Farhad; Ebadifard Azar, Farbod; Nabilo, Bahram; Abolghasem Gorji, Hassan; Hadian, Mohammad; Shahidisadeghi, Niusha; Karami, Atiyeh

    2015-04-23

    Drug costs in Iran accounts for about 30% of the total health care expenditure. Moreover, pharmaceutical business lies among the world's greatest businesses. The aim of this study was to analyze Iran's comparative advantage and intra-industry trade in pharmaceuticals so that suitable policies can be developed and implemented in order to boost Iran's trade in this field. To identify Iran's comparative advantage in pharmaceuticals, trade specialization, export propensity, import penetration and Balassa and Vollrath indexes were calculated and the results were compared with other pharmaceutical exporting countries. The extent and growth of Iran's intra-industry trade in pharmaceuticals were measured and evaluated using the Grubel-Lloyd and Menon-Dixon indexes. The required data was obtained from Iran's Customs Administration, Iran's pharmaceutical Statistics, World Bank and International Trade Center. The results showed that among pharmaceutical exporting countries, Iran has a high level of comparative disadvantage in pharmaceutical products because it holds a small share in world's total pharmaceutical exports. Also, the low extent of bilateral intra-industry trade between Iran and its trading partners in pharmaceuticals shows the trading model of Iran's pharmaceutical industry is mostly inter-industry trade rather than intra-industry trade. In addition, the growth of Iran's intra-industry trade in pharmaceuticals is due to its shares of imports from pharmaceutical exporting countries to Iran and exports from Iran to its neighboring countries. The results of the analysis can play a valuable role in helping pharmaceutical companies and policy makers to boost pharmaceutical trade.

  10. Multivariate modelling of the tablet manufacturing process with wet granulation for tablet optimization and in-process control

    NARCIS (Netherlands)

    Westerhuis, J.A; Coenegracht, P.M J; Lerk, C.F

    1997-01-01

    The process of tablet manufacturing with granulation is described as a two-step process. The first step comprises wet granulation of the powder mixture, and in the second step the granules are compressed into tablets. For the modelling of the pharmaceutical process of wet granulation and tableting,

  11. The Effectiveness of Pharmaceutical Marketing

    NARCIS (Netherlands)

    E.R. Kappe

    2011-01-01

    textabstractPharmaceutical marketing effectiveness comprises the measurement of marketing efforts of pharmaceutical firms towards doctors and patients. These firms spend billions of dollars yearly to promote their prescription drugs. This dissertation provides empirical analyses and methods to contr

  12. The Effectiveness of Pharmaceutical Marketing

    NARCIS (Netherlands)

    E.R. Kappe

    2011-01-01

    textabstractPharmaceutical marketing effectiveness comprises the measurement of marketing efforts of pharmaceutical firms towards doctors and patients. These firms spend billions of dollars yearly to promote their prescription drugs. This dissertation provides empirical analyses and methods to

  13. Free trade in pharmaceuticals.

    Science.gov (United States)

    Outterson, M Kevin

    2004-09-06

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

  14. Doctors and pharmaceutical industry.

    Science.gov (United States)

    Beran, Roy G

    2009-09-01

    The pharmaceutical industry is seen as seducing doctors by providing expensive gifts, subsidising travel and underwriting practice expenses in return for those doctors prescribing products that otherwise they would not use. This paints doctors in a very negative light; suggests doctors are available to the highest bidder; implies doctors do not adequately act as independent agents; and that doctors are driven more by self-interest than by patient needs. Similar practices, in other industries, are accepted as normal business behaviour but it is automatically assumed to be improper if the pharmaceutical industry supports doctors. Should the pharmaceutical industry withdraw educational grants then there would be: fewer scientific meetings; reduced attendance at conferences; limited post graduate education; and a depreciated level of maintenance of professional standards. To suggest that doctors prescribe inappropriately in return for largesse maligns their integrity but where there is no scientific reason to choose between different treatments then there can be little argument against selecting the product manufactured by a company that has invested in the doctor and the question arises as to whether this represents bad medicine? This paper will examine what constitutes non-professional conduct in response to inducements by the pharmaceutical industry. It will review: conflict of interest; relationships between doctors and pharma and the consequences for patients; and the need for critical appraisal before automatically decrying this relationship while accepting that there remain those who do not practice ethical medicine.

  15. The extended pharmaceutical enterprise.

    Science.gov (United States)

    Cavalla, David

    2003-03-15

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

  16. Model-based analysis of high shear wet granulation from batch to continuous processes in pharmaceutical production - A critical review

    DEFF Research Database (Denmark)

    Kumar, Ashish; Gernaey, Krist; De Beer, Thomas

    2013-01-01

    , aggregation, breakage and consolidation. Further, population balance modelling (PBM) and the discrete element method (DEM), which are the current state-of-the-art methods for granulation modelling at micro- to meso-scale, are discussed. The DEM approach has a major role to play in future research...... of the developments, the review focuses on the twin-screw granulator as a device for continuous HSWG and attempts to critically evaluate the current process. As a result, a set of open research questions are identified. These questions need to be answered in the future in order to fill the knowledge gap...

  17. Active Gold-Ceria and Gold-Ceria/titania Catalysts for CO Oxidation. From Single-Crystal Model Catalysts to Powder Catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez, Jose A. [Brookhaven National Lab. (BNL), Upton, NY (United States); Si, Rui [Brookhaven National Lab. (BNL), Upton, NY (United States); Evans, Jaime [Central Univ. of Venezuela, Caracas (Venezuela); Xu, Wenqian [Brookhaven National Lab. (BNL), Upton, NY (United States); Hanson, Jonathan C. [Brookhaven National Lab. (BNL), Upton, NY (United States); Tao, Jing [Brookhaven National Lab. (BNL), Upton, NY (United States); Zhu, Yimei [Brookhaven National Lab. (BNL), Upton, NY (United States)

    2014-07-23

    We studied CO oxidation on model and powder catalysts of Au-CeO2 and Au-CeOx/TiO2. Phenomena observed in Au-CeO2(1 1 1) and Au-CeO2/TiO2(1 1 0) provided useful concepts for designing and preparing highly active and stable Au-CeOx/TiO2 powder catalysts for CO oxidation. Small particles of Au dispersed on CeO2(1 1 1) displayed high catalytic activity, making Au-CeO2(1 1 1) a better CO oxidation catalyst than Au-TiO2(1 1 0) or Au-MgO(1 0 0). An excellent support for gold was found after depositing nanoparticles of ceria on TiO2(1 1 0). The CeOx nanoparticles act as nucleation centers for gold, improving dispersion of the supported metal and helping in the creation of reaction sites efficient for the adsorption of CO and the dissociation of the O2 molecule. High-surface area catalysts were prepared by depositing gold on ceria nanorods and CeOx/TiO2 powders. The samples were tested for the low-temperature (10–70 °C) oxygen-rich (1%CO/4%O2/He) CO oxidation reaction after pre-oxidation (20%O2/He, 300 °C) and pre-reduction (5%H2/He, 300 °C) treatments. Moreover, synchrotron-based operando X-ray diffraction (XRD) and X-ray absorption (XAS) spectroscopy were used to study the Au-CeO2 and Au-CeOx/TiO2 catalysts under reaction conditions. Our operando findings indicate that the most active phase of these catalysts for low-temperature CO oxidation consist of small particles of metallic Au dispersed on CeO2 or CeOx/TiO2.

  18. Pharmaceuticals Exposed to the Space Environment: Problems and Prospects

    Science.gov (United States)

    Jaworske, Donald A.; Myers, Jerry G.

    2016-01-01

    The NASA Human Research Program (HRP) Health Countermeasures Element maintains ongoing efforts to inform detailed risks, gaps, and further questions associated with the use of pharmaceuticals in space. Most recently, the Pharmacology Risk Report, released in 2010, illustrates the problems associated with maintaining pharmaceutical efficacy. Since the report, one key publication includes evaluation of pharmaceutical products stored on the International Space Station (ISS). This study shows that selected pharmaceuticals on ISS have a shorter shelf-life in space than corresponding terrestrial controls. The HRP Human Research Roadmap for planetary exploration identifies the risk of ineffective or toxic medications due to long-term storage during missions to Mars. The roadmap also identifies the need to understand and predict how pharmaceuticals will behave when exposed to radiation for long durations. Terrestrial studies of returned samples offer a start for predictive modeling. This paper shows that pharmaceuticals returned to Earth for post-flight analyses are amenable to a Weibull distribution analysis in order to support probabilistic risk assessment modeling. The paper also considers the prospect of passive payloads of key pharmaceuticals on sample return missions outside of Earth's magnetic field to gather additional statistics. Ongoing work in radiation chemistry suggests possible mitigation strategies where future work could be done at cryogenic temperatures to explore methods for preserving the strength of pharmaceuticals in the space radiation environment, perhaps one day leading to an architecture where pharmaceuticals are cached on the Martian surface and preserved cryogenically.

  19. Adsorption of geosmin and 2-methylisoborneol onto powdered activated carbon at non-equilibrium conditions: influence of NOM and process modelling.

    Science.gov (United States)

    Zoschke, Kristin; Engel, Christina; Börnick, Hilmar; Worch, Eckhard

    2011-10-01

    The adsorption of the taste and odour (T&O) compounds geosmin and 2-methylisoborneol (2-MIB) onto powdered activated carbon (PAC) has been studied under conditions which are typical for a drinking water treatment plant that uses reservoir water for drinking water production. The reservoir water as well as the pre-treated water (after flocculation) contains NOM that competes with the trace compounds for the adsorption sites on the carbon surface. Although the DOC concentrations in the reservoir water and in the pre-treated water were different, no differences in the competitive adsorption could be seen. By using two special characterisation methods for NOM (adsorption analysis, LC/OCD) it could be proved that flocculation removes only NOM fractions which are irrelevant for competitive adsorption. Different model approaches were applied to describe the competitive adsorption of the T&O compounds and NOM, the tracer model, the equivalent background compound model, and the simplified equivalent background compound model. All these models are equilibrium models but in practice the contact time in flow-through reactors is typically shorter than the time needed to establish the adsorption equilibrium. In this paper it is demonstrated that the established model approaches can be used to describe competitive adsorption of T&O compounds and NOM also under non-equilibrium conditions. The results of the model applications showed that in particular the simplified equivalent background compound model is a useful tool to determine the PAC dosage required to reduce the T&O compounds below the threshold concentration.

  20. Pharmaceutical Public-Private Partnerships

    DEFF Research Database (Denmark)

    Bagley, Constance; Tvarnø, Christina D.

    2014-01-01

    This article provides a game theory and law-and-management analysis of for- profit pharmaceutical public-private partnerships, a complex type of legal arrangement in the highly regulated pharmaceutical industry. A pharmaceutical public-private partnership (PPPP) agreement is a legally binding con...

  1. Experimental study of tensile strength of pharmaceutical tablets: effect of the diluent nature and compression pressure

    Science.gov (United States)

    Juban, Audrey; Briançon, Stéphanie; Puel, François; Hoc, Thierry; Nouguier-Lehon, Cécile

    2017-06-01

    In the pharmaceutical field, tablets are the most common dosage form for oral administration in the world. Among different manufacturing processes, direct compression is widely used because of its economics interest and it is a process which avoids the steps of wet granulation and drying processes. Tablets are composed of at least two ingredients: an active pharmaceutical ingredient (API) which is mixed with a diluent. The nature of the powders and the processing conditions are crucial for the properties of the blend and, consequently, strongly influence the mechanical characteristics of tablets. Moreover, tablets have to present a suitable mechanical strength to avoid crumbling or breaking when handling, while ensuring an appropriate disintegration after administration. Accordingly, this mechanical property is an essential parameter to consider. Experimental results showed that proportion of the diluent, fragmentary (DCPA) or plastic (MCC), had a large influence on the tensile strength evolution with API content as well as the compression load applied during tableting process. From these results a model was developed in order to predict the tensile strength of binary tablets by knowing the compression pressure. The validity of this model was demonstrated for the two studied systems and a comparison was made with two existing models.

  2. Experimental study of tensile strength of pharmaceutical tablets: effect of the diluent nature and compression pressure

    Directory of Open Access Journals (Sweden)

    Juban Audrey

    2017-01-01

    Full Text Available In the pharmaceutical field, tablets are the most common dosage form for oral administration in the world. Among different manufacturing processes, direct compression is widely used because of its economics interest and it is a process which avoids the steps of wet granulation and drying processes. Tablets are composed of at least two ingredients: an active pharmaceutical ingredient (API which is mixed with a diluent. The nature of the powders and the processing conditions are crucial for the properties of the blend and, consequently, strongly influence the mechanical characteristics of tablets. Moreover, tablets have to present a suitable mechanical strength to avoid crumbling or breaking when handling, while ensuring an appropriate disintegration after administration. Accordingly, this mechanical property is an essential parameter to consider. Experimental results showed that proportion of the diluent, fragmentary (DCPA or plastic (MCC, had a large influence on the tensile strength evolution with API content as well as the compression load applied during tableting process. From these results a model was developed in order to predict the tensile strength of binary tablets by knowing the compression pressure. The validity of this model was demonstrated for the two studied systems and a comparison was made with two existing models.

  3. Transverse flow of cohesive powders in rotating kilns: experimental study and modeling; Ecoulement transversal de poudres cohesives en four tournant: etude experimentale et modelisation

    Energy Technology Data Exchange (ETDEWEB)

    Debacq, M.; Patisson, F.; Ablitzer, D. [Ecoles des Mines de Nancy, Lab. de Science et Genie des Materiaux Metalliques, UMR 7584, 54 - Nancy (France); Houzelot, J.L. [Ecole Nationale Superieure des Industries Chimiques (ENSIC), Lab. des Sciences du Genie Chimique, UPR 6811, 54 - Villers-les-Nancy (France); Feugier, A. [Societe Franco-Belge de Fabrication Combustibles, F.B.F.C., Dir. Technique, 26 - Romans (France); Hartmann, D. [Cogema, 26 - Pierrelatte (France)

    2001-07-01

    The transverse flow of cohesive powders of uranium in a rotating kiln equipped with raising levers has been studied experimentally at ambient temperature and at the temperatures of the process. The simple laws obtained have permitted to calculate the average distribution of the powder in a straight section of the kiln. (J.S.)

  4. Comparison of performance of partial prestressed beam-column subassemblages made of reactive powder concrete and normal concrete materials using finite element models

    Science.gov (United States)

    Nurjannah, S. A.; Budiono, B.; Imran, I.; Sugiri, S.

    2016-04-01

    Research on concrete material continues in several countries and had produced a concrete type of Ultra High Performance Concrete (UHPC) which has a better compressive strength, tensile strength, flexural strength, modulus of elasticity, and durability than normal concrete (NC) namely Reactive Powder Concrete (RPC). Researches on structures using RPC material showed that the RPC structures had a better performance than the NC structures in resisting gravity and lateral cyclic loads. In this study, an experiment was conducted to apply combination of constant axial and lateral cyclic loads to a prototype of RPC interior partial prestressed beam-column subassemblage (prototype of BCS-RPC) with a value of Partial Prestressed Ratio (PPR) of 31.72% on the beam. The test results were compared with finite element model of beam-column subassemblage made of RPC by PPR of 31.72% (BCS-RPC-31.72). Furthermore, there was BCS-RPC modeling with PPR of 21.39% (BCS-RPC-21.39) and beam-column subassemblages made of NC materials modeling with a value of PPR at 21.09% (BCS-NC-21.09) and 32.02% (BCS-NC-32.02). The purpose of this study was to determine the performance of the BCS-RPC models compared to the performance of the BCS-NC models with PPR values below and above 25%, which is the maximum limit of permitted PPR. The results showed that all models of BCS-RPC had a better performance than all models of BCS-NC and the BCS-RPC model with PPR above 25% still behaved ductile and was able to dissipate energy well.

  5. An in vitro method for detecting chemical sensitization using human reconstructed skin models and its applicability to cosmetic, pharmaceutical, and medical device safety testing.

    Science.gov (United States)

    McKim, James M; Keller, Donald J; Gorski, Joel R

    2012-12-01

    Chemical sensitization is a serious condition caused by small reactive molecules and is characterized by a delayed type hypersensitivity known as allergic contact dermatitis (ACD). Contact with these molecules via dermal exposure represent a significant concern for chemical manufacturers. Recent legislation in the EU has created the need to develop non-animal alternative methods for many routine safety studies including sensitization. Although most of the alternative research has focused on pure chemicals that possess reasonable solubility properties, it is important for any successful in vitro method to have the ability to test compounds with low aqueous solubility. This is especially true for the medical device industry where device extracts must be prepared in both polar and non-polar vehicles in order to evaluate chemical sensitization. The aim of this research was to demonstrate the functionality and applicability of the human reconstituted skin models (MatTek Epiderm(®) and SkinEthic RHE) as a test system for the evaluation of chemical sensitization and its potential use for medical device testing. In addition, the development of the human 3D skin model should allow the in vitro sensitization assay to be used for finished product testing in the personal care, cosmetics, and pharmaceutical industries. This approach combines solubility, chemical reactivity, cytotoxicity, and activation of the Nrf2/ARE expression pathway to identify and categorize chemical sensitizers. Known chemical sensitizers representing extreme/strong-, moderate-, weak-, and non-sensitizing potency categories were first evaluated in the skin models at six exposure concentrations ranging from 0.1 to 2500 µM for 24 h. The expression of eight Nrf2/ARE, one AhR/XRE and two Nrf1/MRE controlled gene were measured by qRT-PCR. The fold-induction at each exposure concentration was combined with reactivity and cytotoxicity data to determine the sensitization potential. The results demonstrated that

  6. Powder detergents production plant

    OpenAIRE

    Stanković Mirjana S.; Pezo Lato L.

    2003-01-01

    The IGPC Engineering Department designed basic projects for powder detergent production plant, using technology developed in the IGPC laboratories, in 1998. - 2000. Several projects were completed: technological, machine, electrical, automation. On the basis of these projects, a production plant with a capacity of 25,000 t/y was manufactured, at "Delta In", Zrenjanin, in 2000.This technology was an innovation, because new approach in mixing a powder materials was used, as well as introducing ...

  7. Volumetric properties of some pharmaceutical binary mixtures at low temperatures and correlation with the jouyban-acree model

    OpenAIRE

    Rodriguez, Gerson

    2011-01-01

    Excess molar volumes and partial molar volumes were investigated from density values for a) ethanol (1) + water (2), b) 1,2-propanediol (1) + water (2), and c) ethanol (1) + 1,2-propanediol (2) mixtures, at temperatures from (278.15 to 288.15) K. Excess molar volumes were fitted by Redlich-Kister equation. The systems exhibit negative excess volumes probably due to increased interactions like hydrogen bonding and/ or large differences in molar volumes of components. The Jouyban-Acree model wa...

  8. Magnetically responsive enzyme powders

    Energy Technology Data Exchange (ETDEWEB)

    Pospiskova, Kristyna, E-mail: kristyna.pospiskova@upol.cz [Regional Centre of Advanced Technologies and Materials, Palacky University, Slechtitelu 11, 783 71 Olomouc (Czech Republic); Safarik, Ivo, E-mail: ivosaf@yahoo.com [Regional Centre of Advanced Technologies and Materials, Palacky University, Slechtitelu 11, 783 71 Olomouc (Czech Republic); Department of Nanobiotechnology, Institute of Nanobiology and Structural Biology of GCRC, Na Sadkach 7, 370 05 Ceske Budejovice (Czech Republic)

    2015-04-15

    Powdered enzymes were transformed into their insoluble magnetic derivatives retaining their catalytic activity. Enzyme powders (e.g., trypsin and lipase) were suspended in various liquid media not allowing their solubilization (e.g., saturated ammonium sulfate and highly concentrated polyethylene glycol solutions, ethanol, methanol, 2-propanol) and subsequently cross-linked with glutaraldehyde. Magnetic modification was successfully performed at low temperature in a freezer (−20 °C) using magnetic iron oxides nano- and microparticles prepared by microwave-assisted synthesis from ferrous sulfate. Magnetized cross-linked enzyme powders were stable at least for two months in water suspension without leakage of fixed magnetic particles. Operational stability of magnetically responsive enzymes during eight repeated reaction cycles was generally without loss of enzyme activity. Separation of magnetically modified cross-linked powdered enzymes from reaction mixtures was significantly simplified due to their magnetic properties. - Highlights: • Cross-linked enzyme powders were prepared in various liquid media. • Insoluble enzymes were magnetized using iron oxides particles. • Magnetic iron oxides particles were prepared by microwave-assisted synthesis. • Magnetic modification was performed under low (freezing) temperature. • Cross-linked powdered trypsin and lipase can be used repeatedly for reaction.

  9. (TECTONA GRANDIS LEAF POWDER

    Directory of Open Access Journals (Sweden)

    Yash Mishra

    2015-01-01

    Full Text Available In this study, the adsorption potential of Teak (Tectona grandis leaf powder (TLP toremove Methylene blue (MB and Malachite Green (MG dye molecules from aqueoussolution was investigated. Batch experiments were conducted to evaluate the influenceof operational parameters such as, pH (2−9, adsorbent dosage (1−7 g/L, contact time(15−150 minutes and initial dye concentration (20−120 mg/L at stirring speed of 150rpm for the adsorption of MB and MG on TLP. Maximum removal efficiency of 98.4%and 95.1% was achieved for MB and MG dye, respectively. The experimentalequilibrium data were analysed using Langmuir, Freundlich and Temkin isothermmodels and it was found that, it fitted well to the Freundlich isotherm model. Thesurface structure and morphology of the adsorbent was characterized using scanningelectron microscopy (SEM and the presence of functional groups and its interactionwith the dye molecules were analysed using Fourier transform infrared spectroscopy(FTIR. Based on the investigation, it has been demonstrated that the teak leaf powderhas good potential for effective adsorption of methylene blue and malachite green dye.

  10. Determining potential adverse effects in marine fish exposed to pharmaceuticals and personal care products with the fish plasma model and whole-body tissue concentrations.

    Science.gov (United States)

    Meador, James P; Yeh, Andrew; Gallagher, Evan P

    2017-07-26

    The Fish Plasma Model (FPM) was applied to water exposure and tissue concentrations in fish collected from two wastewater treatment plant impacted estuarine sites. In this study we compared predicted fish plasma concentrations to Cmax values for humans, which represents the maximum plasma concentration for the minimum therapeutic dose. The results of this study show that predictions of plasma concentrations for a variety of pharmaceutical and personal care products (PPCPs) from effluent concentrations resulted in 37 compounds (54%) exceeding the response ratio (RR = Fish [Plasma]/1%Cmaxtotal) of 1 compared to 3 compounds (14%) detected with values generated with estuarine receiving water concentrations. When plasma concentrations were modeled from observed whole-body tissue residues, 16 compounds out of 24 detected for Chinook (67%) and 7 of 14 (50%) for sculpin resulted in an RRtissue value greater than 1, which highlights the importance of this dose metric over that using estuarine water. Because the tissue residue approach resulted in a high percentage of compounds with calculated response ratios exceeding a value of unity, we believe this is a more accurate representation for exposure in the field. Predicting plasma concentrations from tissue residues improves our ability to assess the potential for adverse effects in fish because exposure from all sources is captured. Tissue residues are also more likely to represent steady-state conditions compared to those from water exposure because of the inherent reduction in variability usually observed for field data and the time course for bioaccumulation. We also examined the RR in a toxic unit approach to highlight the importance of considering multiple compounds exhibiting a similar mechanism of action. Published by Elsevier Ltd.

  11. International Conference on Harmonisation; guidance on Q10 Pharmaceutical Quality System; availability. Notice.

    Science.gov (United States)

    2009-04-08

    The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "Q10 Pharmaceutical Quality System." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance describes a model for an effective quality management system for the pharmaceutical industry, referred to as the Pharmaceutical Quality System. The guidance is intended to provide a comprehensive approach to an effective pharmaceutical quality system that is based on International Organization for Standardization (ISO) concepts, includes applicable good manufacturing practice (GMP) regulations and complements ICH guidances on "Q8 Pharmaceutical Development" and "Q9 Quality Risk Management."

  12. Characterisation of flowability of cohesive powders by testing small quantities of weak compacts

    Institute of Scientific and Technical Information of China (English)

    Chuan Wang; Ali Hassanpour; Mojtaba Ghadiri

    2008-01-01

    Characterisation of flowability of small quantifies of cohesive powders is of great industrial interest, particularly for the pharmaceutical sec tors, where a limited amount of material is available or the material is not easily accessible. In this paper, ball indentation on a powder bed is evaluated for flow charaeterisation of small quantifies of cohesive powders at low levels of consolidation pressures. In parallel, the bulk powder is subjected to the common test method of unconfined direct compression. Analogous to indentation hardness testing, for which the indentation pressure is related to the flow stress, a constraint factor (C) is defined relating the unconfined yield stress and indentation pres sure. The constraint factors for the test powders have been evaluated, enabling an easy method to characterize the flow behaviour of cohesive powders.

  13. Biaxially textured articles formed by powder metallurgy

    Science.gov (United States)

    Goyal, Amit; Williams, Robert K.; Kroeger, Donald M.

    2003-07-29

    A biaxially textured alloy article having a magnetism less than pure Ni includes a rolled and annealed compacted and sintered powder-metallurgy preform article, the preform article having been formed from a powder mixture selected from the group of mixtures consisting of: at least 60 at % Ni powder and at least one of Cr powder, W powder, V powder, Mo powder, Cu powder, Al powder, Ce powder, YSZ powder, Y powder, Mg powder, and RE powder; the article having a fine and homogeneous grain structure; and having a dominant cube oriented {100} orientation texture; and further having a Curie temperature less than that of pure Ni.

  14. Physical model and simulation system of powder packing%粉末材料堆积的物理模型与仿真系统

    Institute of Scientific and Technical Information of China (English)

    钟文镇; 何克晶; 周照耀; 夏伟; 李元元

    2009-01-01

    The physical model and the computational system for powder packing process simulation are presented, and the high performance computing methods of simulating the random packing of mixed particles with different sizes are studied. In the simulation system the effects of gravity, contact forces, damping, friction, van der Waals force etc are take into account, therby forming several kinds of mechanical models and damping models. The system is very suitable for the three-dimensional simulation of large scale powder packing process. Finally, to demonstrate the usefulness of the simulation system, two typical applications are presented in the paper. One is to simulate the random packing of binary mixture with size ratio 10, and when the number of small particles is 300 times as large as that of big particles, the maximal packing density (volume fraction) is achieved to be 0.824, and the other is to simulate the random mixed packing dynamics of particles with two different densities. The segregation phenomenon and clustering phenomenon take place obviously after the packing process has come to an end. The physical model and the simulation system presented in this paper are not only suitable for the study of powder packing process, but also applicable to the packing process simulation of spherical objects.%研究了粉末材料堆积过程仿真的物理模型和系统,并探讨了适合多种不同粒径颗粒混合堆积过程仿真的高性能计算方法.在该仿真系统中,考虑了重力、接触力、阻尼力、摩擦力和范德瓦耳斯力等多种作用力的影响,集成了多种接触力模型和阻尼模型,使其适用于三维大规模粉末材料堆积过程的计算机仿真.利用该系统对粉末材料领域中的两个典型应用进行了模拟研究.模拟了两种相同密度不同粒径颗粒(粒径比为10)的混合堆积过程.当小颗粒数为大颗粒数的300倍时,得到最大的堆积密度(体积分数)为0.82.另外,还模拟了两

  15. Analysis of the cold compaction behaviour of TiH2-316L nanocomposite powder blend using compaction models

    CSIR Research Space (South Africa)

    Machio, Christopher N

    2015-07-01

    Full Text Available equations. Among the models, the Kawakita-Lüdde and Cooper-Eaton models fitted the experimental data very well with a good correlation (the correlation coefficient greater than 0.99) throughout the entire pressure range under investigation. The nature...

  16. Pharmaceutical market in Serbia

    Directory of Open Access Journals (Sweden)

    Veselin Tima Dickov

    2012-02-01

    Full Text Available Marketing concept formed around the focus on the consumers, their needs, wants and demands, evolves in the case of pharmaceutical into a care of the complex interest of constituents generating demand on this market and #8211; pres scribers whose role is to select therapies, pharmacists who dispense drugs within a specialized distribution channel to the final consumer -patient, alongside the payers and #8211; the state and or insurance companies refund a part of or total costs of the pharmaceutical product. A special challenge that the subject raises is the existence of controversy generated from two sources. Marketing controversy stems from criticism leveled at the effectiveness and efficiency of marketing activities and the debatable ethical code of conduct. [J Intercult Ethnopharmacol 2012; 1(1.000: 44-51

  17. Trade, TRIPS, and pharmaceuticals.

    Science.gov (United States)

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

    2009-02-21

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

  18. The pharmaceutical quality revolution

    Directory of Open Access Journals (Sweden)

    Jordi Botet

    2016-01-01

    Full Text Available Pharmaceutical products are patient-oriented. If they had a deficient quality they might put live at risk. Ensuring their quality is not, however, a straightforward task and this is why different approaches have been used along the way. This article analyzes them and shows how our present approach, if well implemented, is very effective in ensuring quality.Methods. This article analyzes the current pharmaceutical quality system as described by international guidances in the light of practical experience gathered by the author as an international GMP-consultant.Result. Nowadays we have come to understand that as quality is a global concept in terms of time and of requirements, it has to be assured in a global way too. This is why quality assurance is a permanent process that starts during the development of a product and goes on during its manufacturing life. Manufacturing should be performed within a pharmaceutical quality system which ensures GMP compliance. Decisions should be science and risk-based. Products and processes are monitored by means of critical variables.Conclusions. The approach followed in the 21st century for ensuring quality is very effective and allows for a progressive reduction of the level of quality risk. However, this quality system is either comprehensive or there is no quality

  19. RISK MANAGEMENT IN PHARMACEUTICALS

    Directory of Open Access Journals (Sweden)

    V. SIVA RAMA KRISHNA

    2014-04-01

    Full Text Available Objective: To review the risk in pharmaceutical industries and the risk management process and tools. There is risk always in anything we do. All the industries on this globe perform actions that involve risks; risk is only dangerous when there is no anticipation to manage it. Risks if assessed and controlled properly will benefit the industries against the fall and makes stronger. Risk should not be assessed as bad, but should assess as an opportunity for making things resilient by proper management. Risk management can benefit industries from disasters either natural or human. The impact of the risk should be assessed in order to plan alternatives and minimize the effect of the impact. Risk in pharmaceutical industry is very high because it involves research, money and health. The impact is severe and the probability of the risk is more often in pharmaceutical industry. A risk management plans and control measures will help the companies to do better at the time of uncertainties and create positive opportunities to turn those risks into benefits which maximize quality. Materials and Methods: The information was collected and compiled from scientific literature present in different databases and articles, books. Results: The risk management process and tools helps to minimize the risk and its effects. Conclusion: The risk management is at the core of any organization. Risk management should be part of organization culture. The risk management is a wise investment if properly processed.

  20. 新型ARIMA-BP组合模型在医药企业销售管理中的应用%Application of ARIMA-BP model in the sales management of the listed pharmaceutical companies

    Institute of Scientific and Technical Information of China (English)

    吴磊; 徐怀伏

    2016-01-01

    The importance of sales management in pharmaceutical enterprises has become increasingly prominent with the intensiifcation of market competition among them. Since the forecast of pharmaceutical sales is a complex nonlinear system, the data of historical sales for sodium aescinate, a prescription drug from the listed pharmaceutical companies were selected, and an ARIMA linear model and a BP network nonlinear model were established and veriifed based on the theory of linear and nonlinear prediction in order to improve the accuracy of sales forecast. It is proved that adoption of a combination of two models can effectively reduce errors and bring in some new ideas for the sales management and policy decision of pharmaceutical enterprises.%随着医药企业间的市场竞争加剧,企业销售管理的重要性逐渐凸显。医药销售预测是个复杂的非线性系统,为提高企业销售预测的准确性,本文选取医药上市企业处方药七叶皂苷钠历史销售数据,分别建立ARIMA线性模型和BP神经网络非线性模型并加以验证。证明了在销售预测上采用ARIMA-BP组合模型可以有效降低误差,为医药企业的销售管理和企业决策带来新的思路。

  1. Phase diagram of crushed powders

    Science.gov (United States)

    Bodard, Sébastien; Jalbaud, Olivier; Saurel, Richard; Burtschell, Yves; Lapebie, Emmanuel

    2016-12-01

    Compression of monodisperse powder samples in quasistatic conditions is addressed in a pressure range such that particles fragmentation occurs while the solid remains incompressible (typical pressure range of 1-300 MPa for glass powders). For a granular bed made of particles of given size, the existence of three stages is observed during compression and crush up. First, classical compression occurs and the pressure of the granular bed increases along a characteristic curve as the volume decreases. Then, a critical pressure is reached for which fragmentation begins. During the fragmentation process, the granular pressure stays constant in a given volume range. At the end of this second stage, 20%-50% of initial grains are reduced to finer particles, depending on the initial size. Then the compression undergoes the third stage and the pressure increases along another characteristic curve, in the absence of extra fragmentation. The present paper analyses the analogies between the phase transition in liquid-vapour systems and powder compression with crush-up. Fragmentation diagram for a soda lime glass is determined by experimental means. The analogues of the saturation pressure and latent heat of phase change are determined. Two thermodynamic models are then examined to represent the crush-up diagram. The first one uses piecewise functions while the second one is of van der Waals type. Both equations of state relate granular pressure, solid volume fraction, and initial particle diameter. The piecewise functions approach provides reasonable representations of the phase diagram while the van der Waals one fails.

  2. Advances in powder diffraction analysis

    Energy Technology Data Exchange (ETDEWEB)

    Louer, D. [Lab. de Chimie du Solide et Inorganique Moleculaire, Rennes (France). Groupe de Cristallochimie

    1998-11-01

    Powder diffraction offers a wide spectrum of applications to solid-state scientists. The method traditionally used for phase analysis and the study of structural imperfections has benefited, in the last twenty years, from great advances in the instrumentation and computer-based approaches for pattern indexing and modelling. The factors at the origin of the metamorphosis of the method are presented. The major modern applications reported include quantitative analysis and the extraction of three-dimensional structural and microstructural properties. The use of pattern-fitting techniques for the characterization of the microstructure is discussed through applications to nanocrystalline materials. Remarkable results achieved in the solution of crystal structures are presented, as well as the impact in solid-state chemistry of powder crystallography, particularly for elucidating the crystal chemistry of families of compounds for which only powders are available. New strategies for solving the phase problem have been introduced and new classes of solids are being studied, such as drugs, coordination and organic compounds. (orig.) 100 refs.

  3. 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".

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2015-09-30

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

  5. Launch Decisions of Pharmaceutical Companies

    Directory of Open Access Journals (Sweden)

    Abdülkadir Civan

    2016-04-01

    Full Text Available This paper models the launch decision of pharmaceutical companies in regard to new drugs and country markets. New drugs are launched with a delay or not launched at all in many countries. Considering that many of these new drugs would have created health benefits to the patients, there seems to be welfare loss. We use market characteristics to explain this phenomenon. We show that most of the estimated launch with a delay and no-launch decision is due to observable market characteristics. The model has an accuracy of 70 percent in explaining the no-launch decision. Intellectual property rights protection is especially important. The policy implication is that stronger property rights increase the likelihood and speed of new drug launch.

  6. Model of temperature field for the preparation process of melt-spun NdFeB powders

    Institute of Scientific and Technical Information of China (English)

    赖彬; 李岩峰; 王会杰; 李安华; 朱明刚; 李卫; 张跃

    2014-01-01

    Melt-spun ribbons which are the important raw material for hot-deformed magnets can be prepared by single-roller melt-spinning. In order to prepare well-structured ribbons, the model of temperature field for single-roller melt-spinning process was constructed in this work. The heat conduction in this process was simplified as one dimensional heat conduction problem. It was shown by modeling that, the temperature field in the melt-spinning before solidification in this model could be described as this equa-tionT(x,t)=Tmoexp[-k(x-x0)-k2αt]+T0. The temperatureT(x,t) of the alloy melts decreased with increased positionx and cooling timet exponentially from the wheel-free surface to the wheel-side surface. The constantk determined the decrease speed of alloy tempera-tureT(x,t), which was proportional to the interfacial heat transfer coefficienth and the interfacial area of heat conductionA0, but in-versely proportional to the thermal conductivityK.x0 was the thickness of the alloy melt. With increasedx0, the temperature differ-ence between wheel-free surface and the wheel-side surface became larger, which would lead to larger difference in grain size. In ex-periments, the influence of melt-spinning process parameters on the temperature field model was discussed, such as cooling roller materials, wheel speed, and so on. Melt-spun ribbons prepared by single-roller melt spinning at different wheel speed were investi-gated and magnetic properties of die-upset magnets from melt-spun ribbons on different cooling roller were analyzed. The variation of grain size in the depth direction consisted with temperature field model. This model provided directions for the preparation of melt-spun ribbons with uniformly distributed fine grains, which were very necessary for producing hot-deformed magnets with high magnetic performance.

  7. [Pharmaceutical technology and pharmaceutical care in the dispensary].

    Science.gov (United States)

    Remon, J P

    2007-01-01

    In this lecture the science 'Pharmaceutical Technology' was briefly elucidated, but the main part was about the concept of 'Pharmaceutical Care' in the community pharmacy. Pharmaceutical Care aims at ensuring a safe, efficacious, and cost-effective pharmacotherapy. Thus the pharmacist tries--in collaboration with other healthcare professionals --to improve the clinical and humanistic outcomes of the therapy. Moreover, an efficacious and rational drug therapy is cost-saving, for the patient as well as for the health insurer. A pharmacist delivering Pharmaceutical Care not only dispenses medication, but also takes responsibility about the outcome of the drug therapy. Pharmaceutical Care in community pharmacies encompasses the following activities: Advice about prescribed drugs, to ensure that patients take their medication as correct, as safe and as compliant as possible. Advice about self-care: counselling about OTC-medication. Prevention of medication errors, for example drug interactions. Pay attention to prevention of diseases: for example stimulation of vaccination. Collaboration with physicians, especially general practitioners, both aiming at an optimal drug therapy for the patient Pharmaceutical Care in the hospital setting ('Clinical Pharmacy'): clinical pharmacists participate in drawing up, evaluating and following up the pharmacotherapy of every individual patient, in close collaboration with physicians, nurses and other healthcare professionals on the ward. In Belgium Pharmaceutical Care is in the making. Scientific research on this topic is carried out by the Pharmaceutical Care Unit of Ghent University. An overview of their ongoing research projects was given. Finally, the problems encountered with the implementation of Pharmaceutical Care were highlighted.

  8. Application of Ring Shear Testing to Optimize Pharmaceutical Formulation and Process Development of Solid Dosage Forms

    DEFF Research Database (Denmark)

    Søgaard, Søren Vinter; Pedersen, Troels; Allesø, Morten

    This study investigates how shear and wall friction tests performed at small stresses can be applied to predict critical flow properties of powders, such as flow patterns and arching tendencies, in pharmaceutical manufacturing operations. The study showed that this approach is a promising method...

  9. Cow dung powder poisoning

    OpenAIRE

    Khaja Mohideen Sherfudeen; Senthil Kumar Kaliannan; Pavan Kumar Dammalapati

    2015-01-01

    Cow dung, which has germicidal property, was used in ancient days to clean living premises in South India. Nowadays, people are using commercially available synthetic cow dung powder. It is locally known as “saani powder” in Tamil Nadu. It is freely available in homes and is sometimes accidentally consumed by children. It is available in two colors - yellow and green. Cow dung powder poisoning is common in districts of Tamil Nadu such as Coimbatore, Tirupur, and Erode. We report two cases of ...

  10. Impact of Electrostatics on Processing and Product Performance of Pharmaceutical Solids.

    Science.gov (United States)

    Desai, Parind Mahendrakumar; Tan, Bernice Mei Jin; Liew, Celine Valeria; Chan, Lai Wah; Heng, Paul Wan Sia

    2015-01-01

    Manufacturing of pharmaceutical solids involves different unit operations and processing steps such as powder blending, fluidization, sieving, powder coating, pneumatic conveying and spray drying. During these operations, particles come in contact with other particles, different metallic, glass or polymer surfaces and can become electrically charged. Electrostatic charging often gives a negative connotation as it creates sticking, jamming, segregation or other issues during tablet manufacturing, capsule filling, film packaging and other pharmaceutical operations. A thorough and fundamental appreciation of the current knowledge of mechanisms and the potential outcomes is essential in order to minimize potential risks resulting from this phenomenon. The intent of this review is to discuss the electrostatic properties of pharmaceutical powders, equipment surfaces and devices affecting pharmaceutical processing and product performance. Furthermore, the underlying mechanisms responsible for the electrostatic charging are described and factors affecting electrostatic charging have been reviewed in detail. Feasibility of different methods used in the laboratory and pharmaceutical industry to measure charge propensity and decay has been summarized. Different computational and experimental methods studied have proven that the particle charging is a very complex phenomenon and control of particle charging is extremely important to achieve reliable manufacturing and reproducible product performance.

  11. Experimental Study and Finite Element Polycrystal Model Simulation of the Cold Rolling Textures in a Powder Metallurgy Processed Pure Aluminum Plate

    Institute of Scientific and Technical Information of China (English)

    Liqing CHEN; Naoyuki Kanetake

    2005-01-01

    Ingot metallurgy (IM) aluminum has long been the subject and attracted the attention of many metallurgists and textural researchers of materials. Due to the introduction of large amounts of ex situ interfaces, however, the textures in powder metallurgy (PM) processed aluminum has been rarely reported. In this article, a pure aluminum plate was prepared via PM route. The starting billet was first produced with uni-axially cold compaction and flat hot-extrusion and then followed by cold rolling processes. The hot-extruded and cold rolling deformation textures of the pure PM aluminum at 50%, 80% and 90% cold rolling reductions were studied by orientation distribution functions (ODFs) analysis. The finite element polycrystal model (FEPM) was finally utilized to simulate the cold rolling textural evolution at various stages of cold rolling. In FEPM simulation, the initial hot-extruded textures were taken into account as inputs. The results showed that typical β-fiber texture formed in pure PM aluminum with the cold rolling reduction increased till 80%, and there was not much change after excessive cold rolling deformation.Homogeneous slip is not the only deformation mode in PM processed pure aluminum plate at over 80% cold rolling reduction. The experimental results were qualitatively in good agreement with the simulated ones.

  12. New aspects of developing a dry powder inhalation formulation applying the quality-by-design approach.

    Science.gov (United States)

    Pallagi, Edina; Karimi, Keyhaneh; Ambrus, Rita; Szabó-Révész, Piroska; Csóka, Ildikó

    2016-09-10

    The current work outlines the application of an up-to-date and regulatory-based pharmaceutical quality management method, applied as a new development concept in the process of formulating dry powder inhalation systems (DPIs). According to the Quality by Design (QbD) methodology and Risk Assessment (RA) thinking, a mannitol based co-spray dried formula was produced as a model dosage form with meloxicam as the model active agent. The concept and the elements of the QbD approach (regarding its systemic, scientific, risk-based, holistic, and proactive nature with defined steps for pharmaceutical development), as well as the experimental drug formulation (including the technological parameters assessed and the methods and processes applied) are described in the current paper. Findings of the QbD based theoretical prediction and the results of the experimental development are compared and presented. Characteristics of the developed end-product were in correlation with the predictions, and all data were confirmed by the relevant results of the in vitro investigations. These results support the importance of using the QbD approach in new drug formulation, and prove its good usability in the early development process of DPIs. This innovative formulation technology and product appear to have a great potential in pulmonary drug delivery.

  13. China's Chemical Pharmaceutical Industry Rebounding

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ After reorganization in 2006, China's chemical pharmaceutical industry began to pick up in 2007. According to the China Pharmaceutical Industry Association,China's chemical pharmaceutical industry achieved sales revenues of RMB202.5 billion in the first eight months this year, a growth of 24.6% - 5.6 percentage points faster than January to May this year. The net profit was RMB17.4 billion, an increase of 50.8% over the same period of 2006.

  14. [Adhesive cutaneous pharmaceutical forms].

    Science.gov (United States)

    Gafiţanu, E; Matei, I; Mungiu, O C; Pavelescu, M; Mîndreci, I; Apostol, I; Ionescu, G

    1989-01-01

    The adhesive cutaneous pharmaceutical forms aimed to local action release the drug substance in view of a dermatological, traumatological, antirheumatic, cosmetic action. Two such preparations were obtained and their stability, consistency and pH were determined. The "in vitro" tests of their bioavailability revealed the dynamics of calcium ions release according to the associations of each preparation. The bioavailability determined by evaluating the pharmacological response demonstrated the antiinflammatory action obtained by the association of calcium ions with the components extracted from poplar muds. The therapeutical efficiency of the studied preparations has proved in the treatment of some sport injuries.

  15. [Amorphization in pharmaceutical technology].

    Science.gov (United States)

    Révész, Piroska; Laczkovich, Orsolya; Eros, István

    2004-01-01

    The amorphization of crystalline active ingredients may be necessary because of the polymorphism of the active substance, the poor water-solubility of the drug material, difficult processing in the crystalline form and the taking out of a patent for a new (amorphous) form. This article introduces protocols for amorphization, which use methods traditionally applied in pharmaceutical technology. The protocols involve three possible routes: solvent methods, hot-melt technologies and milling procedures. With this presentation, the authors suggest help for practising experts to find the correct amorphization method.

  16. Bolaamphiphiles: A Pharmaceutical Review

    Directory of Open Access Journals (Sweden)

    Mayur Fariya

    2014-12-01

    Full Text Available 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.

  17. Thermal Decomposition Behaviour of Zn3N2 Powder

    Institute of Scientific and Technical Information of China (English)

    ZONG Fu-Jian; ZHUANG Hui-Zhao; MA Hong-Lei; LIANG Wei; DU Wei; ZHANG Xi-Jian; XIAO Hong-Di; MA Jin; JI Feng; XUE Cheng-Shan

    2005-01-01

    @@ Thermal gravimetric analysis (TGA) and differential thermal analysis (DTA) are employed to investigate the thermal decomposition behaviour of zinc nitride powder, which indicated that the thermal oxidation of zinc nitride powder in air follows the two-step reaction model.When the temperature is between 200 and 500℃,compact ZnO or ZnxOyNz layers in the surface of zinc nitride powder will begin to form, and prevent the interior of zinc nitride powder from the thermal oxidation.When the temperature is higher than 500 ℃, fast thermal oxidation occurs in the interior of zinc nitride powder.Over 750 ℃, all the zinc nitride will turn into zinc oxide.The x-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) of the zinc nitride powder annealed at different temperature in air are consistent with the two-step reaction model.

  18. Adsorptive removal of selected pharmaceuticals by mesoporous silica SBA-15

    Energy Technology Data Exchange (ETDEWEB)

    Bui, Tung Xuan, E-mail: bxtung@gist.ac.kr [Department of Environmental Science and Engineering, Gwangju Institute of Science and Technology (GIST), 261 Cheomdan-gwagiro, Buk-gu, Gwangju 500-712 (Korea, Republic of); Choi, Heechul, E-mail: hcchoi@gist.ac.kr [Department of Environmental Science and Engineering, Gwangju Institute of Science and Technology (GIST), 261 Cheomdan-gwagiro, Buk-gu, Gwangju 500-712 (Korea, Republic of)

    2009-09-15

    The removal of five selected pharmaceuticals, viz., carbamazepine, clofibric acid, diclofenac, ibuprofen, and ketoprofen was examined by batch sorption experiments onto a synthesized mesoporous silica SBA-15. SBA-15 was synthesized and characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), N{sub 2} adsorption-desorption measurement, and point of zero charge (PZC) measurement. Pharmaceutical adsorption kinetics was rapid and occurred on a scale of minutes, following a pseudo-second-order rate expression. Adsorption isotherms were best fitted by the Freundlich isotherm model. High removal rates of individual pharmaceuticals were achieved in acidic media (pH 3-5) and reached 85.2% for carbamazepine, 88.3% for diclofenac, 93.0% for ibuprofen, 94.3% for ketoprofen, and 49.0% for clofibric acid at pH 3 but decreased with increase in pH. SBA-15 also showed high efficiency for removal of a mixture of 5 pharmaceuticals. Except for clofibric acid (35.6%), the removal of pharmaceuticals in the mixture ranged from 75.2 to 89.3%. Based on adsorption and desorption results, the mechanism of the selected pharmaceuticals was found to be a hydrophilic interaction, providing valuable information for further studies to design materials for the purpose. The results of this study suggest that mesoporous-silica-based materials are promising adsorbents for removing pharmaceuticals from not only surface water but also wastewater of pharmaceutical industrial manufactures.

  19. Application of mathematical models for the prediction of adsorption isotherms in solid mixture for mango powder refreshment

    Directory of Open Access Journals (Sweden)

    Edmar Clemente

    2011-09-01

    Full Text Available Solid mixtures for refreshment are already totally integrated to the Brazilian consumers' daily routine, because of their quick preparation method, yield and reasonable price - quite lower if compared to 'ready-to-drink' products or products for prompt consumption, what makes them economically more accessible to low-income populations. Within such a context, the aim of this work was to evaluate the physicochemical and mineral composition, as well as the hygroscopic behavior of four different brands of solid mixture for mango refreshment. The BET, GAB, Oswim and Henderson mathematical models were built through the adjustment of experimental data to the isotherms of adsorption. Results from the physiochemical evaluation showed that the solid mixtures for refreshments are considerable sources of ascorbic acid and reductor sugar; and regarding mineral compounds, they are significant sources of calcium, sodium and potassium. It was also verified that the solid mixtures for refreshments of the four studied brands are considered highly hygroscopic.

  20. Red ginseng powder fermented with probiotics exerts antidiabetic effects in the streptozotocin-induced mouse diabetes model.

    Science.gov (United States)

    Jang, Sun-Hee; Park, Jisang; Kim, Sae-Hae; Choi, Kyung-Min; Ko, Eun-Sil; Cha, Jeong-Dan; Lee, Young-Ran; Jang, Hyonseok; Jang, Yong-Suk

    2017-12-01

    Red ginseng (heat-processed Panax ginseng) is a well-known alternative medicine with pharmacological antidiabetic activity. It exerts pharmacological effects through the transformation of saponin into metabolites by the intestinal microbiota. Given that intestinal conditions and intestinal microflora vary among individuals, the pharmacological effects of orally administered red ginseng likely may vary among individuals. To overcome this variation and produce homogeneously effective red ginseng, we evaluated the antidiabetic effects of probiotic-fermented red ginseng in a mouse model. The antidiabetic efficacy of orally administered probiotic-fermented red ginseng was assessed in ICR mice after induction of diabetes using streptozotocin (170 mg/kg body weight). Samples were given orally for 8 weeks, and indicators involved in diabetic disorders such as body weight change, water intake, blood glucose, glucose tolerance and various biochemical parameters were determined. Oral administration of probiotic-fermented red ginseng significantly decreased the level of blood glucose of about 62.5% in the fasting state and induced a significant increase in glucose tolerance of about 10.2% compared to the control diabetic mice. Additionally, various indicators of diabetes and biochemical data (e.g., blood glycosylated haemoglobin level, serum concentrations of insulin, and α-amylase activity) showed a significant improvement in the diabetic conditions of the mice treated with probiotic-fermented red ginseng in comparison with those of control diabetic mice. Our results demonstrate the antidiabetic effects of probiotic-fermented red ginseng in the streptozotocin-induced mouse diabetes model and suggest that probiotic-fermented red ginseng may be a uniformly effective red ginseng product.

  1. Anti-inflammatory and Analgesic Activities of Topical Formulations of Pterocarpus Santalinus Powder in Rat Model of Chronic Inflammation.

    Science.gov (United States)

    Dhande, Priti Pravin; Gupta, Amit O; Jain, Sourav; Dawane, Jayshree Shriram

    2017-07-01

    The incidence of arthritis is quite high and there is a need for the search of natural products to halt the progression of disease or provide symptomatic relief without significant adverse effects. This study aimed at evaluating the anti-inflammatory and analgesic activities of topical Pterocarpus santalinus in an animal model of chronic inflammation. Albino rats of either sex were divided into five groups of six rats each (Group I - Control, Group II -Gel base, Group III -P. santalinus paste, Group IV -P. santalinus gel, Group V- Diclofenac gel). Chronic inflammation was induced on day 0 by injecting 0.1 ml Complete Freund's Adjuvant (CFA) in sub-plantar tissue of left hind paw of the rats. Topical treatment was started from day 12 till day 28. Body weight and paw volume (Plethysmometer) were assessed on day 0, 12 and 28. Pain assessment was done using Randall and Selitto paw withdrawal method. Data was analysed using GraphPad Prism version 5. Unpaired students t-test and ANOVA followed by Tukey's test was used for comparison among groups. Only topical P.santalinus gel significantly reduced the body weight (p=0.02) due to reduction in inflammatory oedema of the left limb. P. santalinus gel also showed significant reduction (p=0.03) in paw volume of rats compared to the other groups. There was significant reduction in pain threshold (gm/sec) due to chronic inflammation, with all the study drugs (p<0.05) but with P. santalinus gel, this reduction was less (p<0.001). Gel showed significant anti-inflammatory and mild analgesic activity on topical application in rat model of chronic inflammation.

  2. Removal of pharmaceuticals in WWTP effluents by ozone and ...

    African Journals Online (AJOL)

    2013-02-12

    Feb 12, 2013 ... Keywords: ozone; pharmaceuticals; hydrogen peroxide; wastewater effluents ... discharge of effluents by wastewater treatment plants (WWTPs) that are ...... assessment and modeling of an ozonation step for full-scale munic-.

  3. Pharmaceutical Education and the Translation of Pharmaceutical Care into Practice.

    Science.gov (United States)

    Newton, Gail D.

    1991-01-01

    A systematic approach to reform of pharmaceutical education is seen as necessary to link intended outcomes of reform to a progressive and generally accepted mission of professional practice. Cooperation between pharmaceutical education, professional organizations, and regulatory agencies is viewed as necessary and refinement of professional…

  4. Geosmin and 2-methylisoborneol removal using superfine powdered activated carbon: shell adsorption and branched-pore kinetic model analysis and optimal particle size.

    Science.gov (United States)

    Matsui, Yoshihiko; Nakao, Soichi; Taniguchi, Takuma; Matsushita, Taku

    2013-05-15

    2-Methylisoborneol (MIB) and geosmin are naturally occurring compounds responsible for musty-earthy taste and odor in public drinking-water supplies, a severe problem faced by many utilities throughout the world. In this study, we investigated adsorptive removal of these compounds by superfine powdered activation carbon (SPAC, particle size geosmin adsorbed more in the exterior of a carbon particle than in the center. The extremely high uptake rates of MIB and geosmin by SPAC were simulated well by a combination of the branched-pore kinetic model and the shell adsorption model, in which intraparticle diffusion through macropores was followed by diffusion from macropore to micropore. Simulations suggested that D40 was on the whole the best characteristic diameter to represent a size-disperse group of adsorbent particles; D40 is the diameter through which 40% of the particles by volume pass. Therefore, D40 can be used as an index for evaluating the improvement of adsorptive removal that resulted from pulverization. The dose required for a certain percentage removal of MIB or geosmin decreased linearly with carbon particle size (D40), but the dose reduction became less effective as the activated carbon was ground down to smaller sizes around a critical value of D40. For a 60-min contact time, critical D40 was 2-2.5 μm for MIB and 0.4-0.5 μm for geosmin. The smaller critical D40 was when the shorter the carbon-water contact time was or the slower the intraparticle mass transfer rate of an adsorbate was.

  5. Pharmaceutical Receivables, the Source of the Pharmaceutical Units Solvency

    Directory of Open Access Journals (Sweden)

    Doina Margaritti

    2016-07-01

    Full Text Available The objective of this work is to analyze the current assets recorded by the pharmaceutical units, namely the role of the pharmaceutical receivables to improve the financial performances carried out by the pharmaceutical entities. The study was carried out through the analysis of the financial statements drawn up by a community pharmaceutical entity from Bucharest. In order to achieve the proposed objective, we analyzed the current assets in their structure, namely the pharmaceutical receivables which are to be recovered by the Bucharest Health Insurance House and the Insurance House OPSNAJ, resulting from the issuance of the compensated drugs prescriptions. Thus, it was determined the total receivables, but also differentiated release programs, how they are created, the term of settlement and the manner in which they have influenced the level of financial performance indicators.

  6. Capillary Drop Penetration Method to Characterize the Liquid Wetting of Powders.

    Science.gov (United States)

    Liu, Zhanjie; Wang, Yifan; Muzzio, Fernando J; Callegari, Gerardo; Drazer, German

    2017-01-10

    We present a method to characterize the wettability of powders, based on the penetration dynamics of a sessile drop deposited on a slightly compressed powder bed. First, we show that a direct comparison of the wetting properties of different liquids is possible without having to solve the three-dimensional liquid penetration problem, by considering the appropriate dimensionless variables. We show that the contact area between the sessile drop and the powder bed remains constant during most of the penetration process and demonstrate that as a result, the evolution of the dimensionless penetration volume is given by a universal function of the dimensionless time, with no dimensionless parameters. Then, using a reference liquid that completely wets the powder, it is possible to obtain an effective contact angle for a test liquid of interest, independent of other properties of the powder bed, such as permeability and a characteristic pore size. We apply the proposed method to estimate the contact angle of water with different powder blends, by using silicone oil as the reference liquid. Finally, to highlight the potential of the proposed method to characterize pharmaceutical powders, we consider a blend of lactose, acetaminophen, and a small amount of lubricant (magnesium stearate). The proposed method adequately captures a significant decrease in hydrophilicity that results from exposing the blend to excessive mixing, a well-known effect in the pharmaceutical industry.

  7. The Application of Modern Powder Characterisation Methods in Product and Process Development of Solid Dosage Forms.

    Science.gov (United States)

    Freeman, Tim; Brockbank, Katrina; Armstrong, Brian

    2015-01-01

    The pharmaceutical industry still produces the vast majority of their products, from powdered ingredients, in the form of solid doses. Despite their ubiquity, powders are difficult materials to characterise and understand, as evidenced by the frequent problems encountered during manufacture. The reason for this is their complex rheological behaviour coupled with numerous environmental variations, such as humidity. Equally, the range of processes used to manipulate powders subject them to extremes of stress from high compaction loads seen in compactors to the dispersed state seen in fluidised bed dryers. Thus, it is evident that ensuring that the powders characteristics are compatible with the way they are to be processed is a clear prerequisite for today's Quality by Design driven manufacturing. Modern, computer controlled instrumental techniques, including the dynamic, bulk and shear property measurements have enabled direct measurements of a powders response to aeration, consolidation and flow rate - all at low stresses - as well as quantifying shear and bulk properties (such as density, compressibility and permeability). In order to demonstrate how fully characterising a powder can be used in the design, operation and troubleshooting of processes, this paper will present examples of common pharmaceutical unit operations and the different powder characteristics that most influence the performance of each.

  8. Whey protein/polysaccharide-stabilized oil powders for topical application-release and transdermal delivery of salicylic acid from oil powders compared to redispersed powders.

    Science.gov (United States)

    Kotzé, Magdalena; Otto, Anja; Jordaan, Anine; du Plessis, Jeanetta

    2015-08-01

    Oil-in-water (o/w) emulsions are commonly converted into solid-like powders in order to improve their physical and chemical stabilities. The aim of this study was to investigate whether whey protein/polysaccharide-stabilized o/w emulsions could be converted into stable oil powders by means of freeze-drying. Moreover, during this study, the effects of pH and polymer type on release and trans(dermal) delivery of salicylic acid, a model drug, from these oil powders were investigated and compared to those of the respective template emulsions and redispersed oil powders. Physical characterization of the various formulations was performed, such as droplet size analysis and oil leakage, and relationships drawn with regards to release and trans(dermal) delivery. The experimental outcomes revealed that the oil powders could be redispersed in water without changing the release characteristics of salicylic acid. pH and polymer type affected the release of salicylic acid from the oil powders, template emulsions, and redispersed powders similarly. Contrary, the transdermal delivery from the oil powders and from their respective redispersed oil powders was differently affected by pH and polymer type. It was hypothesized that the release had been influenced by the electrostatic interactions between salicylic acid and emulsifiers, whereas the transdermal performance could have been determined by the particle or aggregate sizes of the formulations.

  9. Platelet-containing tantalum powders

    Energy Technology Data Exchange (ETDEWEB)

    Schiele, E.K.

    1988-04-26

    A method of forming platelet tantalum powders is described comprising the steps of: (a) providing an ingot-derived precursor tantalum powder, and (b) ball-milling the precursor powder for a time sufficient to form a platelet powder having an average FSSS of less than about 2 micrometers, a Scott density not greater than about 30 g/in/sup 3/ and a BET surface area of at least about 0.7 in/sup 2//g.

  10. Measuring Apparatus for Coal Powder

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The measuring apparatus for coal powder, equipped with radioactive source, is a set of device andcan be used to measure the density in the pipes and cumulative consumed amount of coal powder in apower plant, and to examine and display the status of the coal powder input system. It is sketched asFig. 1.

  11. PSE in Pharmaceutical Process Development

    DEFF Research Database (Denmark)

    Gernaey, Krist; Cervera Padrell, Albert Emili; Woodley, John

    2011-01-01

    The pharmaceutical industry is under growing pressure to increase efficiency, both in production and in process development. This paper will discuss the use of Process Systems Engineering (PSE) methods in pharmaceutical process development, and searches for answers to questions such as: Which PSE...

  12. Designing a Pharmaceutical Care Curriculum.

    Science.gov (United States)

    Perrier, Donald G.; And Others

    1995-01-01

    Guidelines for developing a pharmacy school curriculum based on the principle of pharmaceutical care and professional responsibility are offered, beginning with mission statements for profession, practice, and pharmaceutical education in general. The University of Toronto experience in designing such a curriculum is chronicled as an illustration…

  13. Patents in the pharmaceutical industry

    Directory of Open Access Journals (Sweden)

    Jovanović Slobodanka

    2003-01-01

    Full Text Available The pharmaceutical industry is characterized by dynamic development, the existence of big multinational companies and a global market. Such development of the pharmaceutical industry was highly influenced by the introduction of patent protection and compliance with intellectual property regulations. One of the most important international obligations is the TRIPS Agreement.

  14. Patents in the pharmaceutical industry

    OpenAIRE

    Jovanović Slobodanka

    2003-01-01

    The pharmaceutical industry is characterized by dynamic development, the existence of big multinational companies and a global market. Such development of the pharmaceutical industry was highly influenced by the introduction of patent protection and compliance with intellectual property regulations. One of the most important international obligations is the TRIPS Agreement.

  15. Effect of superfine grinding on the physico-chemical, morphological and thermogravimetric properties of Lentinus edodes mushroom powders.

    Science.gov (United States)

    Ming, Jian; Chen, Long; Hong, Hui; Li, Jinlong

    2015-09-01

    Lentinus edodes is an edible mushroom commonly known as shiitake, which is the second most produced and consumed edible mushroom in the world and is an important nutrient source in the human diet. To fully use L. edodes, the mushrooms are occasionally ground into powder as a flavourful and functional food additive. This study produces powders from the cap and stipe of Lentinus edodes mushrooms through superfine grinding. These powders are composed of sub-micron range particles with various size distributions. The superfine grinding process is then compared with shear pulverisation to determine the different effects on both the cap and stipe powders in terms of particle size and physico-chemical, morphological and thermogravimetric properties. When average particle size was reduced to 0.54 and 0.46 µm, respectively, the moisture and protein content, angles of repose and slide, and water holding capacity of the powders decreased to varied extents. However, soluble dietary fibre, water solubility index, and swelling capacity increased. Scanning electron microscope images suggested that the superfine grinding process effectively changed the original surface structure of the L. edodes powders. The curves of thermogravimetric analysis and those of the derivatives of thermogravimetry indicated that superfine grinding can improve the thermostability of L. edodes powders. Furthermore, superfinely ground L. edodes powders may be used as pharmaceutical or food additives in various fields. The present study suggests that superfinely ground L. edodes powders may be applied in various fields as pharmaceutical or food additives. © 2014 Society of Chemical Industry.

  16. Synthesis of Uranium nitride powders using metal uranium powders

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Jae Ho; Kim, Dong Joo; Oh, Jang Soo; Rhee, Young Woo; Kim, Jong Hun; Kim, Keon Sik [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2012-10-15

    Uranium nitride (UN) is a potential fuel material for advanced nuclear reactors because of their high fuel density, high thermal conductivity, high melting temperature, and considerable breeding capability in LWRs. Uranium nitride powders can be fabricated by a carbothermic reduction of the oxide powders, or the nitriding of metal uranium. The carbothermic reduction has an advantage in the production of fine powders. However it has many drawbacks such as an inevitable engagement of impurities, process burden, and difficulties in reusing of expensive N{sup 15} gas. Manufacturing concerns issued in the carbothermic reduction process can be solved by changing the starting materials from oxide powder to metals. However, in nitriding process of metal, it is difficult to obtain fine nitride powders because metal uranium is usually fabricated in the form of bulk ingots. In this study, a simple reaction method was tested to fabricate uranium nitride powders directly from uranium metal powders. We fabricated uranium metal spherical powder and flake using a centrifugal atomization method. The nitride powders were obtained by thermal treating those metal particles under nitrogen containing gas. We investigated the phase and morphology evolutions of powders during the nitriding process. A phase analysis of nitride powders was also a part of the present work.

  17. Anti-inflammatory and carbonic anhydrase restoring actions of yam powder (Dioscorea spp) contribute to the prevention of cysteamine-induced duodenal ulcer in a rat model.

    Science.gov (United States)

    Park, Jong-Min; Kim, Yoon-Jae; Kim, Ju-Seung; Han, Young-Min; Kangwan, Napapan; Hahm, Ki Baik; Kim, Tae-Sok; Kwon, Oran; Kim, Eun-Hee

    2013-08-01

    Increased acid output, accompanied with a defective defense system, is considered a fundamental pathogenesis of duodenal ulcer (DU). However, relapse of DU occurs despite proton pump inhibitors and H2 receptor antagonists, hence imposing the enforcement of the defense system. Dried powder of the yam tuber (Dioscorea spp) has been used in traditional folk medicine as a nutritional fortification. We hypothesized that dried-yam powder would prevent DU through improvement of anti-inflammatory actions and carbonic anhydrase (CA) activity. Therefore, we investigated the preventive effects of dried-yam powder against the cysteamine-induced DU and elucidated the underlying mechanisms. Duodenal ulcers were induced in Sprague-Dawley rats by intragastric administration of 500 mg/kg cysteamine-HCl. The dried-yam powder was used as a pretreatment before the cysteamine-HCl. The number and size of DU were measured. The expressions of inflammation mediators were checked in duodenal tissues, and the expressions of CAs and malondialdehyde levels were also examined. Cysteamine provoked perforated DU, whereas dried-yam powder significantly prevented DU as much as pantoprazole and significantly reduced the incidence of perforation. The messenger RNA expressions of cyclooxygenase-2 and inducible nitric oxide synthase were remarkably decreased in the yam group compared with the cysteamine group, and the serum levels of proinflammatory cytokines including interleukin-1β, interleukin-6, and tumor necrosis factor were significantly attenuated in the yam group. Cysteamine significantly decreased the expression of CAs, whereas yam treatment significantly preserved the expressions of CA IX, XII, and XIV. In conclusion, dried-yam powder exerts a significant protective effect against cysteamine-induced DU by lowering the activity of inflammatory cytokines and free radicals and restoring the activity of CAs, except in CA IV. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Horizon Scanning for Pharmaceuticals

    DEFF Research Database (Denmark)

    Lepage-Nefkens, Isabelle; Douw, Karla; Mantjes, GertJan

    will collect country-specific information, liaise between the central HS unit and country-specific clinical and other experts, coordinate the national prioritization process (to select products for early assessment), and communicate the output of the HSS to national decision makers.  The outputs of the joint...... for a joint horizon scanning system (HSS).  We propose to create a central “horizon scanning unit” to perform the joint HS activities (a newly established unit, an existing HS unit, or a third party commissioned and financed by the collaborating countries). The unit will be responsible for the identification...... and filtration of new and emerging pharmaceutical products. It will maintain and update the HS database, organise company pipeline meetings, and disseminate the HSS’s outputs.  The HS unit works closely together with the designated national HS experts in each collaborating country. The national HS experts...

  19. Bioremediation Kinetics of Pharmaceutical Industrial Effluent

    Directory of Open Access Journals (Sweden)

    M. Šabić

    2015-05-01

    results of changes in concentrations of substrate γS0 = 5.01 g dm–3 for different initial concentrations of activated sludge in comparison to Endo-Haldane model. Changes in concentrations of activated sludge during four days of experiments P1 and P2 are presented in Figs. 4 and 5, respectively. These results suggest that the bioremediation process is well described by the selected model. Process efficiency of pharmaceutical wastewater treatment was approximately 64.8 % (Fig. 3, while in experiment P2 with bioaugmented activated sludge (Fig. 2, the same efficiency was obtained 24 hours earlier than in experiment P1 (Fig.1. Microscopic examination of the activated sludge (Fig. 6 showed that bioaugmentation has no effect on formation of the flocs, but increases efficiency of the bioremediation in a way that the pharmaceutical wastewater treatment is faster and more efficient with bioaugmented activated sludge (Table 3, Fig. 2.

  20. Advanced powder processing

    Energy Technology Data Exchange (ETDEWEB)

    Janney, M.A. [Oak Ridge National Lab., TN (United States)

    1997-04-01

    Gelcasting is an advanced powder forming process. It is most commonly used to form ceramic or metal powders into complex, near-net shapes. Turbine rotors, gears, nozzles, and crucibles have been successfully gelcast in silicon nitride, alumina, nickel-based superalloy, and several steels. Gelcasting can also be used to make blanks that can be green machined to near-net shape and then high fired. Green machining has been successfully applied to both ceramic and metal gelcast blanks. Recently, the authors have used gelcasting to make tooling for metal casting applications. Most of the work has centered on H13 tool steel. They have demonstrated an ability to gelcast and sinter H13 to near net shape for metal casting tooling. Also, blanks of H13 have been cast, green machined into complex shape, and fired. Issues associated with forming, binder burnout, and sintering are addressed.

  1. Powder detergents production plant

    Directory of Open Access Journals (Sweden)

    Stanković Mirjana S.

    2003-01-01

    Full Text Available The IGPC Engineering Department designed basic projects for powder detergent production plant, using technology developed in the IGPC laboratories, in 1998. - 2000. Several projects were completed: technological, machine, electrical, automation. On the basis of these projects, a production plant with a capacity of 25,000 t/y was manufactured, at "Delta In", Zrenjanin, in 2000.This technology was an innovation, because new approach in mixing a powder materials was used, as well as introducing a new type of dryer in detergent production. The product meets all quality demands for detergents with high specific weight (1000 g/l, as well as environmental regulations. The detergent production process is fully automatized, and the product has uniform quality. There is no waste material in detergent zeolite production, because all products with unsatisfactory quality are returned to the process. The production process can be controlled manually, which is necessary during start-up, and repairs.

  2. Dispersing powders in liquids

    CERN Document Server

    Nelson, RD

    1988-01-01

    This book provides powder technologists with laboratory procedures for selecting dispersing agents and preparing stable dispersions that can then be used in particle size characterization instruments. Its broader goal is to introduce industrial chemists and engineers to the phenomena, terminology, physical principles, and chemical considerations involved in preparing and handling dispersions on a commercial scale. The book introduces novices to: - industrial problems due to improper degree of dispersion; - the nomenclature used in describing particles; - the basic physica

  3. Predicting the Fine Particle Fraction of Dry Powder Inhalers Using Artificial Neural Networks.

    Science.gov (United States)

    Muddle, Joanna; Kirton, Stewart B; Parisini, Irene; Muddle, Andrew; Murnane, Darragh; Ali, Jogoth; Brown, Marc; Page, Clive; Forbes, Ben

    2017-01-01

    Dry powder inhalers are increasingly popular for delivering drugs to the lungs for the treatment of respiratory diseases, but are complex products with multivariate performance determinants. Heuristic product development guided by in vitro aerosol performance testing is a costly and time-consuming process. This study investigated the feasibility of using artificial neural networks (ANNs) to predict fine particle fraction (FPF) based on formulation device variables. Thirty-one ANN architectures were evaluated for their ability to predict experimentally determined FPF for a self-consistent dataset containing salmeterol xinafoate and salbutamol sulfate dry powder inhalers (237 experimental observations). Principal component analysis was used to identify inputs that significantly affected FPF. Orthogonal arrays (OAs) were used to design ANN architectures, optimized using the Taguchi method. The primary OA ANN r(2) values ranged between 0.46 and 0.90 and the secondary OA increased the r(2) values (0.53-0.93). The optimum ANN (9-4-1 architecture, average r(2) 0.92 ± 0.02) included active pharmaceutical ingredient, formulation, and device inputs identified by principal component analysis, which reflected the recognized importance and interdependency of these factors for orally inhaled product performance. The Taguchi method was effective at identifying successful architecture with the potential for development as a useful generic inhaler ANN model, although this would require much larger datasets and more variable inputs.

  4. Macromolecular Powder Diffraction: Ready for genuine biological problems.

    Science.gov (United States)

    Karavassili, Fotini; Margiolaki, Irene

    2016-01-01

    Knowledge of 3D structures of biological molecules plays a major role in both understanding important processes of life and developing pharmaceuticals. Among several methods available for structure determination, macromolecular X-ray powder diffraction (XRPD) has transformed over the past decade from an impossible dream to a respectable method. XRPD can be employed in biosciences for various purposes such as observing phase transitions, characterizing bulk pharmaceuticals, determining structures via the molecular replacement method, detecting ligands in protein-ligand complexes, as well as combining micro-sized single crystal crystallographic data and powder diffraction data. Studies using synchrotron and laboratory sources in some standard configuration setups are reported in this review, including their respective advantages and disadvantages. Methods presented here provide an alternative, complementary set of tools to resolve structural problems. A variety of already existing software packages for powder diffraction data processing and analysis, some of which have been adapted to large unit cell studies, are briefly described. This review aims to provide necessary elements of theory and current methods, along with practical explanations, available software packages and highlighted case studies.

  5. Matrix-assisted cocrystallization (MAC) simultaneous production and formulation of pharmaceutical cocrystals by hot-melt extrusion.

    Science.gov (United States)

    Boksa, Kevin; Otte, Andrew; Pinal, Rodolfo

    2014-09-01

    A novel method for the simultaneous production and formulation of pharmaceutical cocrystals, matrix-assisted cocrystallization (MAC), is presented. Hot-melt extrusion (HME) is used to create cocrystals by coprocessing the drug and coformer in the presence of a matrix material. Carbamazepine (CBZ), nicotinamide (NCT), and Soluplus were used as a model drug, coformer, and matrix, respectively. The MAC product containing 80:20 (w/w) cocrystal:matrix was characterized by differential scanning calorimetry, Fourier transform infrared spectroscopy, and powder X-ray diffraction. A partial least squares (PLS) regression model was developed for quantifying the efficiency of cocrystal formation. The MAC product was estimated to be 78% (w/w) cocrystal (theoretical 80%), with approximately 0.3% mixture of free (unreacted) CBZ and NCT, and 21.6% Soluplus (theoretical 20%) with the PLS model. A physical mixture (PM) of a reference cocrystal (RCC), prepared by precipitation from solution, and Soluplus resulted in faster dissolution relative to the pure RCC. However, the MAC product with the exact same composition resulted in considerably faster dissolution and higher maximum concentration (∼five-fold) than those of the PM. The MAC product consists of high-quality cocrystals embedded in a matrix. The processing aspect of MAC plays a major role on the faster dissolution observed. The MAC approach offers a scalable process, suitable for the continuous manufacturing and formulation of pharmaceutical cocrystals. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  6. WHO Expert Committee on Specifications for Pharmaceutical Preparations.

    Science.gov (United States)

    2014-01-01

    The Expert Committee on Specifications for Pharmaceutical Preparations works towards clear, independent and practical standards and guidelines for the quality assurance of medicines. Standards are developed by the Committee through worldwide consultation and an international consensus-building process. The following new guidelines were adopted and recommended for use, in addition to 20 monographs and general texts for inclusion in The International Pharmacopoeia and 11 new International Chemical Reference Substances. The International Pharmacopoeia--updating mechanism for the section on radiopharmaceuticals; WHO good manufacturing practices for pharmaceutical products: main principles; Model quality assurance system for procurement agencies; Assessment tool based on the model quality assurance system for procurement agencies: aide-memoire for inspection; Guidelines on submission of documentation for prequalification of finished pharmaceutical products approved by stringent regulatory authorities; and Guidelines on submission of documentation for a multisource (generic) finished pharmaceutical product: quality part.

  7. 制药工程人才培养模式改革与实践%Reform and Practice of Talents Training Model for Pharmaceutical Engineering

    Institute of Scientific and Technical Information of China (English)

    高志刚; 王世盛; 宋其玲; 赵伟杰

    2016-01-01

    Pharmaceutical Engineering is a new speciality involving pharmacy,chemistry,biology,chemis-try engineering,management science and other subjects.Considering the development of this speciality in china,schools from different backgrounds define the core connotation of this speciality differently,their patterns of talents training have their own characteristics.This paper learned from achievements of famous domestic universities on pharmaceutical training mode, course construction and pedagogical practice, based on engineering education accreditation constructed a pattern of pharmaceutical engineering talents training which features comprehensive university school characteristics, and finally achieved remarkable results.%制药工程专业是涉及药学、化学、生物学、化学工程学和管理学等多门学科的新兴专业,从国内该专业的发展来看,不同背景的院校对制药工程专业核心内涵界定不同,人才培养模式也各具特色。该文借鉴国内高校制药工程专业人才培养、课程建设、教学实践方面的实践成果,以工程教育认证为依托,结合专业实际,构建具有综合性大学办学特色的工程人才培养模式,在人才培养方面取得显著成效。

  8. [Pharmaceutical technology: development and research].

    Science.gov (United States)

    Traisnel, M

    1994-06-01

    Production of pharmaceutics cannot be compared to the manufacture of consumer goods: pharmaceutical manufacturing is the study and bulk manufacture of the ingredients from which medicines are made, and is concerned with the mixing, preparing, packing, of the ingredients into a dosage form for the patient, in according to the good manufacturing practices (GMP). Development and manufacture are not discrete activities but links in a single chain of activity. Research and development, pharmaceutical training, regulatory requirements: these concepts are present with three ways: bioavailability, targeting and compliance.

  9. GMK (Progenics Pharmaceuticals).

    Science.gov (United States)

    Knutson, Keith L

    2002-01-01

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

  10. PHARMACEUTICAL COMPANIES BETWEEN CRISIS AND COMPETITIVENESS - SECTORAL DIAGNOSIS

    Directory of Open Access Journals (Sweden)

    Mihaela\tBÎRSAN

    2015-06-01

    Full Text Available The evolution of the pharmaceutical industry was a positive constant with the indicators of industrial production even in years of crisis. Although the economic crisis in Romania decreased average growth rate of pharmaceutical companies, market value is expected to increase. The explanation comes from the fact that in order to boost productivity, pharmaceutical companies are turning to emerging countries with aging populations such as open new markets for future development. Add to this the recent health policies implemented by newly industrialized countries that are aimed at ensuring increased access to care. Analysts see the field phenomenon called "Farma-merger" a good chance for European pharmaceutical companies oriented to developing countries where drug sales should record a double-digit annual growth until 2017. In Erste Group reports stated that the impact of the crisis on the pharmaceutical industry should be limited markets for EU only their economic slowdown. This will be possible because the external indebtedness of pharmaceutical companies in the EU remains at a minimum, they are able to finance their investment plans without tapping financial markets, are not adversely affected by the current limited availability of credit resources. Therefore major pharmaceutical companies in the EU will remain a solid investment on the long term, the negative developments are limited due to high resistance to the crisis their business model segment "generic". The consequence of these developments is reflected in the recognition for the first time, the pharmaceutical sector as a strategic sector for the Romanian economy. In the context of public debate launching the National Strategy for Competitiveness 2014-2020, Generic Medicines Industry Association of Romania (APMGR local pharmaceutical industry reminds the Government proposals on correcting the current fiscal and operational regulatory framework, to allow unlocking investments in facilities

  11. A Study of Comparative Advantage and Intra-Industry Trade in the Pharmaceutical Industry of Iran

    Science.gov (United States)

    Yusefzadeh, Hassan; Rezapour, Aziz; Lotfi, Farhad; Azar, Farbod Ebadifard; Nabilo, Bahram; Gorji, Hassan Abolghasem; Hadian, Mohammad; Shahidisadeghi, Niusha; Karami, Atiyeh

    2015-01-01

    Background: Drug costs in Iran accounts for about 30% of the total health care expenditure. Moreover, pharmaceutical business lies among the world’s greatest businesses. The aim of this study was to analyze Iran’s comparative advantage and intra-industry trade in pharmaceuticals so that suitable policies can be developed and implemented in order to boost Iran’s trade in this field. Methods: To identify Iran’s comparative advantage in pharmaceuticals, trade specialization, export propensity, import penetration and Balassa and Vollrath indexes were calculated and the results were compared with other pharmaceutical exporting countries. The extent and growth of Iran’s intra-industry trade in pharmaceuticals were measured and evaluated using the Grubel-Lloyd and Menon-Dixon indexes. The required data was obtained from Iran’s Customs Administration, Iran’s pharmaceutical Statistics, World Bank and International Trade Center. Results: The results showed that among pharmaceutical exporting countries, Iran has a high level of comparative disadvantage in pharmaceutical products because it holds a small share in world’s total pharmaceutical exports. Also, the low extent of bilateral intra-industry trade between Iran and its trading partners in pharmaceuticals shows the trading model of Iran’s pharmaceutical industry is mostly inter-industry trade rather than intra-industry trade. In addition, the growth of Iran’s intra-industry trade in pharmaceuticals is due to its shares of imports from pharmaceutical exporting countries to Iran and exports from Iran to its neighboring countries. Conclusions: The results of the analysis can play a valuable role in helping pharmaceutical companies and policy makers to boost pharmaceutical trade. PMID:26153184

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

    Science.gov (United States)

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

    2015-08-01

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

  13. Powder wettability at a static air-water interface.

    Science.gov (United States)

    Dupas, Julien; Forny, Laurent; Ramaioli, Marco

    2015-06-15

    The reconstitution of a beverage from a dehydrated powder involves several physical mechanisms that determine the practical difficulty to obtain a homogeneous drink in a convenient way and within an acceptable time for the preparation of a beverage. When pouring powder onto static water, the first hurdle to overcome is the air-water interface. We propose a model to predict the percentage of powder crossing the interface in 45 s, namely the duration relevant for this application. We highlight theoretically the determinant role of the contact angle and of the particle size distribution. We validate experimentally the model for single spheres and use it to predict the wettability performance of commercial food powders for different contact angles and particles sizes. A good agreement is obtained when comparing the predictions and the wettability of the tested powders.

  14. PHARMACEUTICALS AS UBIQUITOUS POLLUTANTS ...

    Science.gov (United States)

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

  15. OSI-774 OSI Pharmaceuticals.

    Science.gov (United States)

    Norman, P

    2001-02-01

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

  16. Parts per Million Powder X-ray Diffraction.

    Science.gov (United States)

    Newman, Justin A; Schmitt, Paul D; Toth, Scott J; Deng, Fengyuan; Zhang, Shijie; Simpson, Garth J

    2015-11-01

    Here we demonstrate the use of second harmonic generation (SHG) microscopy-guided synchrotron powder X-ray diffraction (PXRD) for the detection of trace crystalline active pharmaceutical ingredients in a common polymer blend. The combined instrument is capable of detecting 100 ppm crystalline ritonavir in an amorphous hydroxypropyl methylcellulose matrix with a high signal-to-noise ratio (>5000). The high spatial resolution afforded by SHG microscopy allows for the use of a minibeam collimator to reduce the total volume of material probed by synchrotron PXRD. The reduction in probed volume results in reduced background from amorphous material. The ability to detect low crystalline loading has the potential to improve measurements in the formulation pipeline for pharmaceutical solid dispersions, for which even trace quantities of crystalline active ingredients can negatively impact the stability and bioavailability of the final drug product.

  17. 基于结构-行为-绩效范式的我国医药产业分析%Analysis of the Pharmaceutical Industry in China Based on Structure-conduct-performance Model

    Institute of Scientific and Technical Information of China (English)

    李树祥

    2015-01-01

    目的:了解我国医药产业的现状,为其进一步发展提出建议。方法:应用产业组织理论中的结构-行为-绩效(SCP)范式,对我国2004-2012年的医药产业数据进行分析。结果与结论:我国医药产业市场结构的特点是医药企业数量众多,但行业集中度较低;市场进入壁垒较低;企业产品差异化程度有增大的趋势;新产品产值率近年基本呈逐年增长趋势。行业市场行为的特点是企业定价能力较弱,2400多种药品定价受到政府监控;企业药品广告投放增加,仅2013年通过网络平台投放的广告就达6.3亿元;医药行业并购活跃,2013年公开的医药行业并购达43宗;企业研发支出逐年增加,专利申请数和有效发明专利数在2012年分别达9580件和10073件。市场绩效的特点表现为销售利润率逐年增长,2012年达11%;新产品产值率也连续几年增长,到2011新产品产值率达到16.68%,但是与国外相比仍然存在着较大差距。建议未来我国医药产业的发展需通过战略并购提升产业结构;加大研发投入;注重创新研发平台的建设,提高协同创新能力;加强对医药企业的监管,推行规范化管理。%OBJECTIVE:To know the current situation of pharmaceutical industry in China and provide suggestion for its fur-ther development. MATHODS:The structure-conduct-performance model in industrial organization theory was adopted to analyze the pharmaceutical industry statistics data in China from 2004 to 2012. RESULTS&CONCLUSIONS:The characteristic of pharma-ceutical industry market structure was numerous pharmaceutical industries,but with low industry concentration;market entry barri-ers were low;the degree of product differentiation was increasing;new product output rate was basically increased year by year in recent years. The characteristic of pharmaceutical industry market conduct was weak pricing power,more than 2

  18. Low Temperature Powder Coating

    Science.gov (United States)

    2011-02-09

    of volatile organic compounds (VOCs) and hazardous air pollutants (HAPs) • Legacy primers contain hexavalent chrome • Conventional powder coatings...panels • Third panel exhibited a single filament extending slightly beyond allowable tolerance Filiform Corrosion Resistance LTCPC on 2024 T-3 Clad ...LTCPC on 2024 T-3 Clad O G D E N A I R L O G I S T I C S C E N T E R BE AMERICA’S BEST JTP Results • LTCPC performance similar or better than wet

  19. LEARNING ORGANISATION CHALLENGE FOR ROMANIAN PHARMACEUTICAL SMEs

    Directory of Open Access Journals (Sweden)

    Otilia-Maria BORDEIANU

    2014-04-01

    Full Text Available The concept of the learning organization has gone through many changes both theoretically and also as practical implementation. Learning organizations do not appear automatically, they require a strong commitment for developing the skills needed in the workplace, and this commitment should start from the top of the organization. The learning process should be managed at different levels within the organization. Learning, therefore, is made up of several different components and requires a special management. Successful companies are the result of carefully cultivated attitudes, commitments and management processes. This paper investigates the learning organization dimensions analysed in case of pharmaceutical SMEs from Romania. The results obtained in this study allow us to draw relevant conclusions, constituting a practical starting point for businesses. The paper highlights the fact that SMEs pharmaceutical companies have taken important steps toward learning organization model, but reaching different levels from one key dimension to another.

  20. New Product Introduction in the Pharmaceutical Industry

    DEFF Research Database (Denmark)

    Hansen, Klaus Reinholdt Nyhuus

    is unknown and negotiations with authorities have become harder, making market introduction more difficult. This dissertation treats the new product introduction process in the pharmaceutical industry from an operations perspective. The overarching aim of this dissertation is to improve the planning......Due to the limited time of the monopoly provided by patent protection that is used for recouping the R&D investment, pharmaceutical companies focus on keeping time-to-market for new products as short as possible. This process is however getting more uncertain, as the outcome of clinical trials...... methodology in this critical process. In an empirical study, the process is first analyzed in detail, leading to the identification of several gaps in the industry’s current planning approaches. To support a set of key operational decisions towards market launch, a model is subsequently developed, considering...

  1. LEARNING ORGANISATION CHALLENGE FOR ROMANIAN PHARMACEUTICAL SMEs

    Directory of Open Access Journals (Sweden)

    Otilia-Maria BORDEIANU

    2014-04-01

    Full Text Available The concept of the learning organization has gone through many changes both theoretically and also as practical implementation. Learning organizations do not appear automatically, they require a strong commitment for developing the skills needed in the workplace, and this commitment should start from the top of the organization. The learning process should be managed at different levels within the organization. Learning, therefore, is made up of several different components and requires a special management. Successful companies are the result of carefully cultivated attitudes, commitments and management processes. This paper investigates the learning organization dimensions analysed in case of pharmaceutical SMEs from Romania. The results obtained in this study allow us to draw relevant conclusions, constituting a practical starting point for businesses. The paper highlights the fact that SMEs pharmaceutical companies have taken important steps toward learning organization model, but reaching different levels from one key dimension to another.

  2. The argument for pharmaceutical policy

    DEFF Research Database (Denmark)

    Traulsen, Janine Morgall; Almarsdóttir, Anna Birna

    2005-01-01

    Pharmaceutical policy is a global concern. It has become a hot political topic in most countries--developed as well as developing--and can be found on the agenda of international organizations such as WHO, OECD, EU, WTO and even the World Bank. Pharmaceutical policy affects everyone in the world...... of pharmacy and it is therefore imperative that it be understood, discussed and debated within the pharmacy profession and included in the curriculum of schools of pharmacy. This, the first article in a series, argues for the importance of the academic discipline of pharmaceutical policy analysis...... and the involvement of pharmacists in this endeavour. The aim of the authors is to stimulate an informed and critical appreciation of this field. The authors begin with an introduction to the field of pharmaceutical policy, introducing several important concepts and current trends including: medicines regulation; how...

  3. PARTICULARITIES OF MODERN PHARMACEUTICAL PROMOTION

    Directory of Open Access Journals (Sweden)

    Юрий Владимирович Тарасов

    2014-02-01

    Full Text Available Pharmaceutical products market is one of the most saturated consumers’ markets. Characteristic features of it are: high competition, fierce struggle for the customer, specific technologies of promotion. In conditions of globalization and increase in competition both in world pharmaceutical market and in the market of medicines and goods of medical purpose in Russia modern marketing techniques of promotion of the products to the end consumers are the key tools for strengthening market positions – both of producers of pharmaceutical goods and their suppliers, distributors, big whole-sale companies. Among main tools of promotion are: advertising, public relations, stimulation of sales on the market of medicines, personal sales, computer technologies. The article describes different technologies of promotion of medicines: indoor-advertising, hot lines, pharmaceutical exhibitions, packing. DOI: http://dx.doi.org/10.12731/2218-7405-2013-12-1

  4. Recognizing misleading pharmaceutical marketing online.

    Science.gov (United States)

    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.

  5. Marketing orientation in pharmaceutical industry

    Directory of Open Access Journals (Sweden)

    Prošić Danica

    2006-01-01

    Full Text Available Pharmaceutical companies are major stakeholders in the global health agenda Virtually all drugs used by patients in Europe reach markets through the promotion tactics of a small number of corporations with a tremendous impact on global health. The sector is both fast growing and highly profitable. Effective marketing strategies are a crucial ingredient in making sure pharmaceutical products and profits flow in a virtuous cycle. At first glance, the relationship between doctors and drug companies, as well as advertising practices for over-the-counter medication, appears tightly regulated. According to many consumer organizations, drug promotion in Europe today can be characterized as nice and friendly marketing. This refers to the creation of a false sense of trust that consumers associate with branded pharmaceutical products, as a result of pharmaceutical marketing efforts disguised as genuine corporate responsibility.

  6. The argument for pharmaceutical policy

    DEFF Research Database (Denmark)

    Traulsen, Janine Morgall; Almarsdóttir, Anna Birna

    2005-01-01

    of pharmacy and it is therefore imperative that it be understood, discussed and debated within the pharmacy profession and included in the curriculum of schools of pharmacy. This, the first article in a series, argues for the importance of the academic discipline of pharmaceutical policy analysis......Pharmaceutical policy is a global concern. It has become a hot political topic in most countries--developed as well as developing--and can be found on the agenda of international organizations such as WHO, OECD, EU, WTO and even the World Bank. Pharmaceutical policy affects everyone in the world...... and the involvement of pharmacists in this endeavour. The aim of the authors is to stimulate an informed and critical appreciation of this field. The authors begin with an introduction to the field of pharmaceutical policy, introducing several important concepts and current trends including: medicines regulation; how...

  7. PARTICULARITIES OF MODERN PHARMACEUTICAL PROMOTION

    OpenAIRE

    Юрий Владимирович Тарасов

    2014-01-01

    Pharmaceutical products market is one of the most saturated consumers’ markets. Characteristic features of it are: high competition, fierce struggle for the customer, specific technologies of promotion. In conditions of globalization and increase in competition both in world pharmaceutical market and in the market of medicines and goods of medical purpose in Russia modern marketing techniques of promotion of the products to the end consumers are the key tools for strengthening market position...

  8. [Pharmaceutical chemistry of general anaesthetics].

    Science.gov (United States)

    Szász, György; Takácsné, Novák Krisztina

    2004-01-01

    The paper represents the first part of a planned series of reviews about pharmaceutical chemistry of drugs acting on the central nervous system. The authorial aim and editorial concepts are the same were followed in a former series of papers about pharmaceutical chemistry of agents effecting the heart, blood circulation and vegetative nervous system. Consequently, general anaesthetics are discussed in the present paper through the chapters "history, preparation; structure-properties-activity; application; analysis".

  9. Pharmaceutical compounds in drinking water

    Directory of Open Access Journals (Sweden)

    Vikas Chander

    2016-06-01

    Full Text Available Pharmaceutical products and their wastes play a major role in the degradation of environment. These drugs have positive as well as negative consequences on different environmental components including biota in different ways. Many types of pharmaceutical substances have been detected with significant concentrations through various advanced instrumental techniques in surface water, subsurface water, ground water, domestic waste water, municipal waste water and industrial effluents. The central as well as state governments in India are providing supports by creating excise duty free zones to promote the pharmaceutical manufacturers for their production. As a result, pharmaceutical companies are producing different types of pharmaceutical products at large scale and also producing complex non-biodegradable toxic wastes byproducts and releasing untreated or partially treated wastes in the environment in absence of strong regulations. These waste pollutants are contaminating all types of drinking water sources. The present paper focuses on water quality pollution by pharmaceutical pollutants, their occurrences, nature, metabolites and their fate in the environment.

  10. Dispersion of powders in liquids and stabilization of suspensions

    CERN Document Server

    Tadros, Tharwat F

    2012-01-01

    Teaching the fundamental knowledge required for successful dispersion of powders in a liquid, this book covers a host of topics -- from recent advances to industrial applications.In 15 chapters it supports formulation chemists in preparing a suspension in a more rational way, by applying the principles of colloid and interface science, while at the same time enabling the research scientist to discover new methods for preparing stable suspensions.Essential reading for those working in the pharmaceutical, cosmetic, food, paint, ceramic and agricultural industries.

  11. Scientific misconduct, the pharmaceutical industry, and the tragedy of institutions.

    Science.gov (United States)

    Cohen-Kohler, Jillian Clare; Esmail, Laura C

    2007-09-01

    This paper examines how current legislative and regulatory models do not adequately govern the pharmaceutical industry towards ethical scientific conduct. In the context of a highly profit-driven industry, governments need to ensure ethical and legal standards are not only in place for companies but that they are enforceable. We demonstrate with examples from both industrialized and developing countries how without sufficient controls, there is a risk that corporate behaviour will transgress ethical boundaries. We submit that there is a critical need for urgent drug regulatory reform. There must be robust regulatory structures in place which enforce corporate governance mechanisms to ensure that pharmaceutical companies maintain ethical standards in drug research and development and the marketing of pharmaceuticals. What is also needed is for the pharmaceutical industry to adopt authentic "corporate social responsibility" policies as current policies and practices are insufficient.

  12. NDMA formation kinetics from three pharmaceuticals in four water matrices.

    Science.gov (United States)

    Shen, Ruqiao; Andrews, Susan A

    2011-11-01

    N, N-nitrosodimethylamine (NDMA) is an emerging disinfection by-product (DBP) that has been widely detected in many drinking water systems and commonly associated with the chloramine disinfection process. Some amine-based pharmaceuticals have been demonstrated to form NDMA during chloramination, but studies regarding the reaction kinetics are largely lacking. This study investigates the NDMA formation kinetics from ranitidine, chlorphenamine, and doxylamine under practical chloramine disinfection conditions. The formation profile was monitored in both lab-grade water and real water matrices, and a statistical model is proposed to describe and predict the NDMA formation from selected pharmaceuticals in various water matrices. The results indicate the significant impact of water matrix components and reaction time on the NDMA formation from selected pharmaceuticals, and provide fresh insights on the estimation of ultimate NDMA formation potential from pharmaceutical precursors.

  13. An update on pharmaceutical film coating for drug delivery.

    Science.gov (United States)

    Felton, Linda A; Porter, Stuart C

    2013-04-01

    Pharmaceutical coating processes have generally been transformed from what was essentially an art form in the mid-twentieth century to a much more technology-driven process. This review article provides a basic overview of current film coating processes, including a discussion on polymer selection, coating formulation additives and processing equipment. Substrate considerations for pharmaceutical coating processes are also presented. While polymeric coating operations are commonplace in the pharmaceutical industry, film coating processes are still not fully understood, which presents serious challenges with current regulatory requirements. Novel analytical technologies and various modeling techniques that are being used to better understand film coating processes are discussed. This review article also examines the challenges of implementing process analytical technologies in coating operations, active pharmaceutical ingredients in polymer film coatings, the use of high-solids coating systems and continuous coating and other novel coating application methods.

  14. NIR Analysis of Powder Mixing Quality in a Ribbon Blender

    Science.gov (United States)

    Goodridge, Chris; Duong, Nhat-Hang; Muzzio, Fernando

    2001-11-01

    We present experimental results on powder mixing performed in a common industrial mixer, the batch ribbon blender. Our experiments explore the effectiveness of this device on mixture quality as a function of fill level, loading pattern, ribbon speed, mixing time, and ribbon angle. We study two powder formulations consisting of common compounds used in food and pharmaceutical processing. Mixture quality is evaluated by core sampling throughout the blender and determining the composition of small samples using NIR spectroscopy. We use the spectra from NIR to calculate the intensity and scale of segregation for the three-dimensional mixing region. The mixing rates in the axial and radial directions are obtained from plots of composition variance vs. mixing time. We examine the effects of ribbon speed and fill level as the main parameters affecting mixing rate. Dead regions that remain isolated from the remainder of the flow are identified.

  15. Assessment of powder blend uniformity: Comparison of real-time NIR blend monitoring with stratified sampling in combination with HPLC and at-line NIR Chemical Imaging.

    Science.gov (United States)

    Bakri, Barbara; Weimer, Marco; Hauck, Gerrit; Reich, Gabriele

    2015-11-01

    Scope of the study was (1) to develop a lean quantitative calibration for real-time near-infrared (NIR) blend monitoring, which meets the requirements in early development of pharmaceutical products and (2) to compare the prediction performance of this approach with the results obtained from stratified sampling using a sample thief in combination with off-line high pressure liquid chromatography (HPLC) and at-line near-infrared chemical imaging (NIRCI). Tablets were manufactured from powder blends and analyzed with NIRCI and HPLC to verify the real-time results. The model formulation contained 25% w/w naproxen as a cohesive active pharmaceutical ingredient (API), microcrystalline cellulose and croscarmellose sodium as cohesive excipients and free-flowing mannitol. Five in-line NIR calibration approaches, all using the spectra from the end of the blending process as reference for PLS modeling, were compared in terms of selectivity, precision, prediction accuracy and robustness. High selectivity could be achieved with a "reduced" approach i.e. API and time saving approach (35% reduction of API amount) based on six concentration levels of the API with three levels realized by three independent powder blends and the additional levels obtained by simply increasing the API concentration in these blends. Accuracy and robustness were further improved by combining this calibration set with a second independent data set comprising different excipient concentrations and reflecting different environmental conditions. The combined calibration model was used to monitor the blending process of independent batches. For this model formulation the target concentration of the API could be achieved within 3 min indicating a short blending time. The in-line NIR approach was verified by stratified sampling HPLC and NIRCI results. All three methods revealed comparable results regarding blend end point determination. Differences in both mean API concentration and RSD values could be

  16. Green synthesis of silver nanoparticles using cranberry powder aqueous extract: characterization and antimicrobial properties

    Directory of Open Access Journals (Sweden)

    Ashour AA

    2015-12-01

    Full Text Available Asmaa A Ashour,1 Dina Raafat,2 Hanan M El-Gowelli,3 Amal H El-Kamel1 1Department of Pharmaceutics, 2Department of Pharmaceutical Microbiology, 3Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt Background: The growing threat of microbial resistance against traditional antibiotics has prompted the development of several antimicrobial nanoparticles (NPs, including silver NPs (AgNPs. In this article, a simple and eco-friendly method for the synthesis of AgNPs using the cranberry powder aqueous extract is reported.Materials and methods: Cranberry powder aqueous extracts (0.2%, 0.5%, and 0.8% w/v were allowed to interact for 24 hours with a silver nitrate solution (10 mM at 30°C at a ratio of 1:10. The formation of AgNPs was confirmed by ultraviolet-visible spectroscopy and their concentrations were determined using atomic absorption spectroscopy. The prepared NPs were evaluated by transmission electron microscopy, measurement of ζ-potential, and Fourier-transform infrared spectroscopy. The in vitro antimicrobial properties of AgNPs were then investigated against several microbial strains. Finally, in vivo appraisal of both wound-healing and antimicrobial properties of either plain AgNPs (prepared using 0.2% extract or AgNP-Pluronic F-127 gel was conducted in a rat model after induction of a Staphylococcus aureus ATCC 6538P wound infection.Results: The formation of AgNPs was confirmed by ultraviolet-visible spectroscopy, where a surface-plasmon resonance absorption peak was observed between 432 and 438 nm. Both size and concentration of the formed AgNPs increased with increasing concentration of the extracts. The developed NPs were stable, almost spherical, and polydisperse, with a size range of 1.4–8.6 nm. The negative ζ-potential values, as well as Fourier-transform infrared spectroscopy analysis, indicated the presence of a capping agent adsorbed onto the surface of the particles. In

  17. Particles and powders: tools of innovation for non-invasive drug administration.

    Science.gov (United States)

    Buttini, Francesca; Colombo, Paolo; Rossi, Alessandra; Sonvico, Fabio; Colombo, Gaia

    2012-07-20

    The paper briefly illustrates several approaches applied in delivering particulate drugs as powders. Microparticulate drug powders are difficult to manipulate with respect to dosage form preparation, particularly when they have very small size as this leads to poor flow and packing properties. When the dosage form performance resides in the presence of individual intact drug particles, the particle characteristics have to be retained in their original state, i.e., not altered during manufacturing and/or within the dosage form. There are several examples of dry powder dosage forms intended for different administration routes whose performance is strictly dependent on particle characteristics. In addition, the preparation of the finished dosage form is dependent on powder properties. The paper addresses dry powder formulations with special focus on oral powders mainly for elderly people or children, nasal powders and inhalation dry powders. These dosage forms are very attractive for both researchers and companies. Their formulation requires deep investigation, mainly in order to define particle structure and performance. Indeed, this makes for a new breakthrough in pharmaceutics and may lead to innovative products. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Inkjet printing for pharmaceutics - A review of research and manufacturing.

    Science.gov (United States)

    Daly, Ronan; Harrington, Tomás S; Martin, Graham D; Hutchings, Ian M

    2015-10-30

    Global regulatory, manufacturing and consumer trends are driving a need for change in current pharmaceutical sector business models, with a specific focus on the inherently expensive research costs, high-risk capital-intensive scale-up and the traditional centralised batch manufacturing paradigm. New technologies, such as inkjet printing, are being explored to radically transform pharmaceutical production processing and the end-to-end supply chain. This review provides a brief summary of inkjet printing technologies and their current applications in manufacturing before examining the business context driving the exploration of inkjet printing in the pharmaceutical sector. We then examine the trends reported in the literature for pharmaceutical printing, followed by the scientific considerations and challenges facing the adoption of this technology. We demonstrate that research activities are highly diverse, targeting a broad range of pharmaceutical types and printing systems. To mitigate this complexity we show that by categorising findings in terms of targeted business models and Active Pharmaceutical Ingredient (API) chemistry we have a more coherent approach to comparing research findings and can drive efficient translation of a chosen drug to inkjet manufacturing.

  19. Animal-derived pharmaceutical proteins.

    Science.gov (United States)

    Redwan, el-Rashdy M

    2009-01-01

    Livestock animals have made a significant contribution to human health and well-being throughout humankind's history. A significant contribution of farm animals to human health are the longstanding use of bovine and porcine for production of insulin (for treatment of diabetes), gelatin (for pharmaceutical and other purposes), as well as horse and sheep antibody against natural venoms, toxins, drugs and microbial peptides. Gelatin being the biggest animal protein consumed in human health, follows with antibodies fragments. The chronic problem of animal-derived therapeutics, especially those of high molecular weight, is the immunogenicity induction in addition to their biosafety. However, the invertebrates and lower vertebrates donate the human being a several crucial emergency saving life small-peptides or their analogs such as Refludan, Prialt, Exendin. Not only, but the farm animals are enormously using as models for novel surgical strategies, testing of biodegradable implants and sources of tissue replacements, such as skin and heart valves. Recently, they are being harnessing as bioreactor for production of biopharmaceutical related products through gene farming with efficiency far greater than any conventional microbial or cell-culture production systems. Only 16 transgenic cows would be covering the worldwide needs from human growth hormone. The transgenic, especially animal, technology would be solving a several biopharmaceutical products disadvantages, such as cost, biosafety, immunogenicity and the availability dimensions.

  20. Planets, Powders, and Piledrivers

    Science.gov (United States)

    Peak, David

    1996-05-01

    Granular materials have enormous economic importance -- in, for example, agriculture, the pharmaceutical, paint, and cosmetic industries, lubrication applications, and the prediction and control of landslides and avalanches. Moreover, our very existence may have been made possible only because of the properties of the granular state. Despite the centrality of granular phenomena, this state of matter -- intermediate between solid and fluid -- is still poorly characterized. I will describe some simple mechanical experiments -- done, in part, on loosely packed dusts by my students and me in the laboratory, and, in part, on dense soils by others in the field -- that present a strong challenge to the development of a general theory of granular matter. These experiments show that granular systems behave like "soft solids" under impact and that the form of their response is universal, independent of chemical composition, packing fraction, or impact energy.