Pharmaceutical powder compaction technology

National Research Council Canada - National Science Library

Çelik, Metin

2011-01-01

... through the compaction formulation process and application. Compaction of powder constituents both active ingredient and excipients is examined to ensure consistent and reproducible disintegration and dispersion profiles...

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

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...... on the prediction uncertainty is assessed. Secondly, the paper focuses on the influence of the most sensitive parameters in the model. Finally, a combined analysis (particle level plus most sensitive parameters) is performed and discussed. To propagate the uncertainty originating from the parameter uncertainty...

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

Correlating particle hardness with powder compaction performance.

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Cao, Xiaoping; Morganti, Mikayla; Hancock, Bruno C; Masterson, Victoria M

2010-10-01

Assessing particle mechanical properties of pharmaceutical materials quickly and with little material can be very important to early stages of pharmaceutical research. In this study, a wide range of pharmaceutical materials were studied using atomic force microscopy (AFM) nanoindentation. A significant amount of particle hardness and elastic modulus data were provided. Moreover, powder compact mechanical properties of these materials were investigated in order to build correlation between the particle hardness and powder compaction performance. It was found that the materials with very low or high particle hardness most likely exhibit poor compaction performance while the materials with medium particle hardness usually have good compaction behavior. Additionally, the results from this study enriched Hiestand's special case concept on particle hardness and powder compaction performance. This study suggests that the use of AFM nanoindentation can help to screen mechanical properties of pharmaceutical materials at early development stages of pharmaceutical research.

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,

Study of radial die-wall pressure changes during pharmaceutical powder compaction.

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Abdel-Hamid, Sameh; Betz, Gabriele

2011-04-01

In tablet manufacturing, less attention is paid to the measurement of die-wall pressure than to force-displacement diagrams. Therefore, the aim of this study was to investigate radial stress change during pharmaceutical compaction. The Presster(TM), a tablet-press replicator, was used to characterize compaction behavior of microcrystalline cellulose (viscoelastic), calcium hydrogen phosphate dihydrate (brittle), direct compressible mannitol (plastic), pre-gelatinized starch (plastic/elastic), and spray dried lactose monohydrate (plastic/brittle) by measuring radial die-wall pressure; therefore powders were compacted at different (pre) compaction pressures as well as different speeds. Residual die-wall pressure (RDP) and maximum die-wall pressure (MDP) were measured. Various tablet physical properties were correlated to radial die-wall pressure. With increasing compaction pressure, RDP and MDP (P compaction behavior of materials and detecting friction phenomena in the early stage of development.

Effects of recirculation in a three-tank pilot-scale system for pharmaceutical removal with powdered activated carbon.

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Kårelid, Victor; Larsson, Gen; Björlenius, Berndt

2017-05-15

The removal of pharmaceutically active compounds by powdered activated carbon (PAC) in municipal wastewater is a promising solution to the problem of polluted recipient waters. Today, an efficient design strategy is however lacking with regard to high-level overall, and specific, substance removal in the large scale. The performance of PAC-based removal of pharmaceuticals was studied in pilot-scale with respect to the critical parameters; contact time and PAC dose using one PAC product selected by screening in bench-scale. The goal was a minimum of 95% removal of the pharmaceuticals present in the evaluated municipal wastewater. A set of 21 pharmaceuticals was selected from an initial 100 due to their high occurrence in the effluent water of two selected wastewater treatment plants (WWTPs) in Sweden, whereof candidates discussed for future EU regulation directives were included. By using recirculation of PAC over a treatment system using three sequential contact tanks, a combination of the benefits of powdered and granular carbon performance was achieved. The treatment system was designed so that recirculation could be introduced to any of the three tanks to investigate the effect of recirculation on the adsorption performance. This was compared to use of the setup, but without recirculation. A higher degree of pharmaceutical removal was achieved in all recirculation setups, both overall and with respect to specific substances, as compared to without recirculation. Recirculation was tested with nominal contact times of 30, 60 and 120 min and the goal of 95% removal could be achieved already at the shortest contact times at a PAC dose of 10-15 mg/L. In particular, the overall removal could be increased even to 97% and 99%, at 60 and 120 min, respectively, when the recirculation point was the first tank. Recirculation of PAC to either the first or the second contact tank proved to be comparable, while a slightly lower performance was observed with recirculation to

Weak hydrogen bonding interactions influence slip system activity and compaction behavior of pharmaceutical powders.

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Khomane, Kailas S; Bansal, Arvind K

2013-12-01

Markedly different mechanical behavior of powders of polymorphs, cocrystals, hydrate/anhydrate pairs, or structurally similar molecules has been attributed to the presence of active slip planes system in their crystal structures. Presence of slip planes in the crystal lattice allows easier slip under the applied compaction pressure. This allows greater plastic deformation of the powder and results into increased interparticulate bonding area and greater tensile strength of the compacts. Thus, based on this crystallographic feature, tableting performance of the active pharmaceutical ingredients can be predicted. Recently, we encountered a case where larger numbers of CH···O type interactions across the proposed slip planes hinder the slip and thus resist plastic deformation of the powder under the applied compaction pressure. Hence, attention must be given to these types of interactions while identifying slip planes by visualization method. Generally, slip planes are visualized as flat layers often strengthened by a two-dimensional hydrogen-bonding network within the layers or planes. No hydrogen bonding should exist between these layers to consider them as slip planes. Moreover, one should also check the presence of CH···O type interactions across these planes. Mercury software provides an option for visualization of these weak hydrogen bonding interactions. Hence, caution must be exercised while selecting appropriate solid form based on this crystallographic feature. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Sun drying of residual annatto seed powder

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Dyego da Costa Santos

2015-01-01

Full Text Available Residual annatto seeds are waste from bixin extraction in the food, pharmaceutical and cosmetic industries. Most of this by-product is currently discarded; however, the use of these seeds in human foods through the elaboration of powder added to other commercial powders is seen as a viable option. This study aimed at drying of residual annatto powder, with and without the oil layer derived from the industrial extraction of bixin, fitting different mathematical models to experimental data and calculating the effective moisture diffusivity of the samples. Powder containing oil exhibited the shortest drying time, highest drying rate (≈ 5.0 kg kg-1 min-1 and highest effective diffusivity (6.49 × 10-12 m2 s-1. All mathematical models assessed were a suitable representation of the drying kinetics of powders with and without oil, with R2 above 0.99 and root mean square error values lower than 1.0.

Temperature evolution during compaction of pharmaceutical powders.

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Zavaliangos, Antonios; Galen, Steve; Cunningham, John; Winstead, Denita

2008-08-01

A numerical approach to the prediction of temperature evolution in tablet compaction is presented here. It is based on a coupled thermomechanical finite element analysis and a calibrated Drucker-Prager Cap model. This approach is capable of predicting transient temperatures during compaction, which cannot be assessed by experimental techniques due to inherent test limitations. Model predictions are validated with infrared (IR) temperature measurements of the top tablet surface after ejection and match well with experiments. The dependence of temperature fields on speed and degree of compaction are naturally captured. The estimated transient temperatures are maximum at the end of compaction at the center of the tablet and close to the die wall next to the powder/die interface.

Self-organizing map analysis using multivariate data from theophylline powders predicted by a thin-plate spline interpolation.

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Yasuda, Akihito; Onuki, Yoshinori; Kikuchi, Shingo; Takayama, Kozo

2010-11-01

The quality by design concept in pharmaceutical formulation development requires establishment of a science-based rationale and a design space. We integrated thin-plate spline (TPS) interpolation and Kohonen's self-organizing map (SOM) to visualize the latent structure underlying causal factors and pharmaceutical responses. As a model pharmaceutical product, theophylline powders were prepared based on the standard formulation. The angle of repose, compressibility, cohesion, and dispersibility were measured as the response variables. These responses were predicted quantitatively on the basis of a nonlinear TPS. A large amount of data on these powders was generated and classified into several clusters using an SOM. The experimental values of the responses were predicted with high accuracy, and the data generated for the powders could be classified into several distinctive clusters. The SOM feature map allowed us to analyze the global and local correlations between causal factors and powder characteristics. For instance, the quantities of microcrystalline cellulose (MCC) and magnesium stearate (Mg-St) were classified distinctly into each cluster, indicating that the quantities of MCC and Mg-St were crucial for determining the powder characteristics. This technique provides a better understanding of the relationships between causal factors and pharmaceutical responses in theophylline powder formulations. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association

Nano spray drying for encapsulation of pharmaceuticals.

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Arpagaus, Cordin; Collenberg, Andreas; Rütti, David; Assadpour, Elham; Jafari, Seid Mahdi

2018-05-17

Many pharmaceuticals such as pills, capsules, or tablets are prepared in a dried and powdered form. In this field, spray drying plays a critical role to convert liquid pharmaceutical formulations into powders. In addition, in many cases it is necessary to encapsulate bioactive drugs into wall materials to protect them against harsh process and environmental conditions, as well as to deliver the drug to the right place and at the correct time within the body. Thus, spray drying is a common process used for encapsulation of pharmaceuticals. In view of the rapid progress of nanoencapsulation techniques in pharmaceutics, nano spray drying is used to improve drug formulation and delivery. The nano spray dryer developed in the recent years provides ultrafine powders at nanoscale and high product yields. In this paper, after explaining the concept of nano spray drying and understanding the key elements of the equipment, the influence of the process parameters on the final powders properties, like particle size, morphology, encapsulation efficiency, drug loading and release, will be discussed. Then, numerous application examples are reviewed for nano spray drying and encapsulation of various drugs in the early stages of product development along with a brief overview of the obtained results and characterization techniques. Copyright © 2018 Elsevier B.V. All rights reserved.

Application of powder X-ray diffraction in studying the compaction behavior of bulk pharmaceutical powders.

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Bandyopadhyay, Rebanta; Selbo, Jon; Amidon, Gregory E; Hawley, Michael

2005-11-01

This study investigates the effects of crystal lattice deformation on the powder X-ray diffraction (PXRD) patterns of compressed polycrystalline specimen (compacts/tablets) made from molecular, crystalline powders. The displacement of molecules and the corresponding adjustment of interplanar distances (d-spacings) between diffracting planes of PNU-288034 and PNU-177553, which have crystal habits with a high aspect ratio favoring preferred orientation during tableting, are demonstrated by shifts in the diffracted peak positions. The direction of shift in diffracted peak positions suggests a reduction of interplanar d-spacing in the crystals of PNU-288034 and PNU-177553 following compaction. There is also a general reduction of peak intensities following compression at the different compressive loads. The lattice strain representing the reduction in d-spacing is proportional to the original d-spacing of the uncompressed sample suggesting that, as with systems that obey a simple Hooke's law relationship, the further apart the planes of atoms/molecules within the lattice are, the easier it is for them to approach each other under compressive stresses. For a third model compound comprising more equant-shaped crystals of PNU-141659, the shift in diffracted peak positions are consistent with an expansion of lattice spacing after compression. This apparent anomaly is supported by the PXRD studies of the bulk powder consisting of fractured crystals where also, the shift in peak position suggests expansion of the lattice planes. Thus the crystals of PNU-141659 may be fracturing under the compressive loads used to produce the compacts. Additional studies are underway to relate the PXRD observations with the bulk tableting properties of these model compounds.

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

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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.

Tantalum powder consolidation, modeling and properties

International Nuclear Information System (INIS)

Bingert, S.R.; Vargas, V.D.; Sheinberg, H.C.

1996-01-01

A systematic approach was taken to investigate the consolidation of tantalum powders. The effects of sinter time, temperature and ramp rate; hot isostatic pressing (HIP) temperature and time; and powder oxygen content on consolidation density, kinetics, microstructure, crystallographic texture, and mechanical properties have been evaluated. In general, higher temperatures and longer hold times resulted in higher density compacts with larger grain sizes for both sintering and HIP'ing. HIP'ed compacts were consistently higher in density than sintered products. The higher oxygen content powders resulted in finer grained, higher density HIP'ed products than the low oxygen powders. Texture analysis showed that the isostatically processed powder products demonstrated a near random texture. This resulted in isotropic properties in the final product. Mechanical testing results showed that the HIP'ed powder products had consistently higher flow stresses than conventionally produced plates, and the sintered compacts were comparable to the plate material. A micromechanics model (Ashby HIP model) has been employed to predict the mechanisms active in the consolidation processes of cold isostatic pressing (CIP), HIP and sintering. This model also predicts the density of the end product and whether grain growth should be expected under the applied processing conditions

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

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

2016-04-01

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

A model of the prescription-pharmaceutical sales process

Directory of Open Access Journals (Sweden)

Michael Stros

2018-06-01

Full Text Available The purpose of this paper is to determine the factors in marketing most relevant to achieving pharmaceutical sales success and their interrelations, as well as providing a prescription-pharmaceuticals sales process model. This will enable scholars to obtain a better understanding of the marketing process for prescription pharmaceuticals, as well as enabling marketers to apply more efficient marketing approaches. The study uses a unique data set, combining primary data and secondary data from the Swiss prescription-pharmaceuticals market. The data is analysed using a multiple-regression based model. A multi-level data structure is found, suggesting that factors concerning the specific brand and also the pharmaceutical substance itself are relevant to sales success. It is revealed that the factors most relevant to sales success are: order of market entry, perceived product-quality, average price, and marketing expenditures, leading to practical recommendations for scholars and marketing professionals. The study focuses only on the Swiss prescription-pharmaceuticals market, investigating five medical drug classes. The assumption is made that these results can be generalised to similar markets and drug classes. The study develops a conceptual prescription-pharmaceuticals sales-process model; offers practical guidelines and a good basis for further scholarly research are provided; and identifies several research gaps by giving proposals for future research.

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.

In-line and Real-time Monitoring of Resonant Acoustic Mixing by Near-infrared Spectroscopy Combined with Chemometric Technology for Process Analytical Technology Applications in Pharmaceutical Powder Blending Systems.

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Tanaka, Ryoma; Takahashi, Naoyuki; Nakamura, Yasuaki; Hattori, Yusuke; Ashizawa, Kazuhide; Otsuka, Makoto

2017-01-01

Resonant acoustic ® mixing (RAM) technology is a system that performs high-speed mixing by vibration through the control of acceleration and frequency. In recent years, real-time process monitoring and prediction has become of increasing interest, and process analytical technology (PAT) systems will be increasingly introduced into actual manufacturing processes. This study examined the application of PAT with the combination of RAM, near-infrared spectroscopy, and chemometric technology as a set of PAT tools for introduction into actual pharmaceutical powder blending processes. Content uniformity was based on a robust partial least squares regression (PLSR) model constructed to manage the RAM configuration parameters and the changing concentration of the components. As a result, real-time monitoring may be possible and could be successfully demonstrated for in-line real-time prediction of active pharmaceutical ingredients and other additives using chemometric technology. This system is expected to be applicable to the RAM method for the risk management of quality.

Optimization of Premix Powders for Tableting Use.

Science.gov (United States)

Todo, Hiroaki; Sato, Kazuki; Takayama, Kozo; Sugibayashi, Kenji

2018-05-08

Direct compression is a popular choice as it provides the simplest way to prepare the tablet. It can be easily adopted when the active pharmaceutical ingredient (API) is unstable in water or to thermal drying. An optimal formulation of preliminary mixed powders (premix powders) is beneficial if prepared in advance for tableting use. The aim of this study was to find the optimal formulation of the premix powders composed of lactose (LAC), cornstarch (CS), and microcrystalline cellulose (MCC) by using statistical techniques. Based on the "Quality by Design" concept, a (3,3)-simplex lattice design consisting of three components, LAC, CS, and MCC was employed to prepare the model premix powders. Response surface method incorporating a thin-plate spline interpolation (RSM-S) was applied for estimation of the optimum premix powders for tableting use. The effect of tablet shape identified by the surface curvature on the optimization was investigated. The optimum premix powder was effective when the premix was applied to a small quantity of API, although the function of premix was limited in the case of the formulation of large amount of API. Statistical techniques are valuable to exploit new functions of well-known materials such as LAC, CS, and MCC.

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...... in particle size analysis also enabling the evaluation of the further product quality in the end of the granulation process. The idea of characterization of bulk surface images opens new perspectives for characterization of pharmaceutical solids....

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 mechanistic models of multi‐phase systems which in the end allow process control. This contribution focuses on continuous fluidized bed drying of pharmaceutical wet granules. A stepwise approach is used in model development, starting with the drying behaviour of single granules. Experiments to determine...

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

NARCIS (Netherlands)

Willemsz, T.A.; Hooijmaijers, R.; Rubingh, C.M.; Tran, T.N.; Frijlink, H.W.; Vromans, H.; Maarschalk, K.V.D.V.

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.

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

-time adjustment of critical input variables to ensure that the process stays within the Design Space. Mechanistic models are very useful for this purpose as, once validated, several tools can be applied to gain further process knowledge, for example uncertainty and sensitivity analysis. In addition, several......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...

Modeling of Pharmaceutical Biotransformation by Enriched Nitrifying Culture under Different Metabolic Conditions

DEFF Research Database (Denmark)

Xu, Yifeng; Chen, Xueming; Yuan, Zhiguo

2018-01-01

Pharmaceutical removal could be significantly enhanced through cometabolism during nitrification processes. To date, pharmaceutical biotransformation models have not considered the formation of transformation products associated with the metabolic type of microorganisms. Here we report a comprehe......Pharmaceutical removal could be significantly enhanced through cometabolism during nitrification processes. To date, pharmaceutical biotransformation models have not considered the formation of transformation products associated with the metabolic type of microorganisms. Here we report...... a comprehensive model to describe and evaluate the biodegradation of pharmaceuticals and the formation of their biotransformation products by enriched nitrifying cultures. The biotransformation of parent compounds was linked to the microbial processes via cometabolism induced by ammonium-oxidizing bacteria (AOB......) growth, metabolism by AOB, cometabolism by heterotrophs (HET) growth, and metabolism by HET in the model framework. The model was calibrated and validated using experimental data from pharmaceutical biodegradation experiments at realistic levels, taking two pharmaceuticals as examples, i.e., atenolol...

Study of component distribution in pharmaceutical binary powder mixtures by near infrared chemical imaging

Directory of Open Access Journals (Sweden)

Manel Bautista

2012-12-01

Full Text Available Near infrared chemical imaging (NIR-CI has recently emerged as an effective technique for extracting spatial information from pharmaceutical products in an expeditious, non-destructive and non-invasive manner. These features have turned it into a useful tool for controlling various steps in drug production processes. Imaging techniques provide a vast amount of both spatial and spectral information that can be acquired in a very short time. Such a huge amount of data requires the use of efficient and fast methods to extract the relevant information. Chemometric methods have proved especially useful for this purpose. In this study, we assessed the usefulness of the correlation coefficient (CC between the spectra of samples, the pure spectra of the active pharmaceutical ingredient (API and we assessed the excipients to check for correct ingredient distribution in pharmaceutical binary preparations blended in the laboratory. Visual information about pharmaceutical component distribution can be obtained by using the CC. The performance of this model construction methodology for binary samples was compared with other various common multivariate methods including partial least squares, multivariate curve resolution and classical least squares. Based on the results, correlation coefficients are a powerful tool for the rapid assessment of correct component distribution and for quantitative analysis of pharmaceutical binary formulations. For samples of three or more components it has been shown that if the objective is only to determine uniformity of blending, then the CC image map is very good for this, and easy and fast to compute.

Multiscale mechanistic modeling in pharmaceutical research and development.

Science.gov (United States)

Kuepfer, Lars; Lippert, Jörg; Eissing, Thomas

2012-01-01

Discontinuation of drug development projects due to lack of efficacy or adverse events is one of the main cost drivers in pharmaceutical research and development (R&D). Investments have to be written-off and contribute to the total costs of a successful drug candidate receiving marketing authorization and allowing return on invest. A vital risk for pharmaceutical innovator companies is late stage clinical failure since costs for individual clinical trials may exceed the one billion Euro threshold. To guide investment decisions and to safeguard maximum medical benefit and safety for patients recruited in clinical trials, it is therefore essential to understand the clinical consequences of all information and data generated. The complexity of the physiological and pathophysiological processes and the sheer amount of information available overcharge the mental capacity of any human being and prevent a prediction of the success in clinical development. A rigorous integration of knowledge, assumption, and experimental data into computational models promises a significant improvement of the rationalization of decision making in pharmaceutical industry. We here give an overview of the current status of modeling and simulation in pharmaceutical R&D and outline the perspectives of more recent developments in mechanistic modeling. Specific modeling approaches for different biological scales ranging from intracellular processes to whole organism physiology are introduced and an example for integrative multiscale modeling of therapeutic efficiency in clinical oncology trials is showcased.

Pharmaceutical expenditure forecast model to support health policy decision making

OpenAIRE

R?muzat, C?cile; Urbinati, Duccio; Kornfeld, ?sa; Vataire, Anne-Lise; Cetinsoy, Laurent; Aball?a, Samuel; Mzoughi, Olfa; Toumi, Mondher

2014-01-01

Background and objective: With constant incentives for healthcare payers to contain their pharmaceutical budgets, modelling policy decision impact became critical. The objective of this project was to test the impact of various policy decisions on pharmaceutical budget (developed for the European Commission for the project ‘European Union (EU) Pharmaceutical expenditure forecast’ – http://ec.europa.eu/health/healthcare/key_documents/index_en.htm).Methods: A model was built to assess policy sc...

A drop penetration method to measure powder blend wettability.

Science.gov (United States)

Wang, Yifan; Liu, Zhanjie; Muzzio, Fernando; Drazer, German; Callegari, Gerardo

2018-03-01

Water wettability of pharmaceutical blends affects important quality attributes of final products. We investigate the wetting properties of a pharmaceutical blend lubricated with Magnesium Stearate (MgSt) as a function of the mechanical shear strain applied to the blend. We measure the penetration dynamics of sessile drops deposited on slightly compressed powder beds. We consider a blend composed of 9% Acetaminophen 90% Lactose and 1% MgSt by weight. Comparing the penetration time of water and a reference liquid Polydimethylsiloxane (silicon oil) we obtain an effective cosine of the contact angle with water, based on a recently developed drop penetration method. We repeat the experiments for blends exposed to increasing levels of shear strain and demonstrate a significant decrease in water wettability (decrease in the cosine of the contact angle). The results are consistent with the development of a hydrophobic film coating the powder particles as a result of the increased shear strain. Finally, we show that, as expected dissolution times increase with the level of shear strain. Therefore, the proposed drop penetration method could be used to directly assess the state of lubrication of a pharmaceutical blend and act as a quality control on powder blend attributes before the blend is tableted. Copyright © 2017 Elsevier B.V. All rights reserved.

Pharmaceutical industry and trade liberalization using computable general equilibrium model.

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Barouni, M; Ghaderi, H; Banouei, Aa

2012-01-01

Computable general equilibrium models are known as a powerful instrument in economic analyses and widely have been used in order to evaluate trade liberalization effects. The purpose of this study was to provide the impacts of trade openness on pharmaceutical industry using CGE model. Using a computable general equilibrium model in this study, the effects of decrease in tariffs as a symbol of trade liberalization on key variables of Iranian pharmaceutical products were studied. Simulation was performed via two scenarios in this study. The first scenario was the effect of decrease in tariffs of pharmaceutical products as 10, 30, 50, and 100 on key drug variables, and the second was the effect of decrease in other sectors except pharmaceutical products on vital and economic variables of pharmaceutical products. The required data were obtained and the model parameters were calibrated according to the social accounting matrix of Iran in 2006. The results associated with simulation demonstrated that the first scenario has increased import, export, drug supply to markets and household consumption, while import, export, supply of product to market, and household consumption of pharmaceutical products would averagely decrease in the second scenario. Ultimately, society welfare would improve in all scenarios. We presents and synthesizes the CGE model which could be used to analyze trade liberalization policy issue in developing countries (like Iran), and thus provides information that policymakers can use to improve the pharmacy economics.

Ultrasound-assisted powder-coating technique to improve content uniformity of low-dose solid dosage forms

DEFF Research Database (Denmark)

Genina, Natalja; Räikkönen, Heikki; Antikainen, Osmo

2010-01-01

An ultrasound-assisted powder-coating technique was used to produce a homogeneous powder formulation of a low-dose active pharmaceutical ingredient (API). The powdered particles of microcrystalline cellulose (MCC; Avicel® PH-200) were coated with a 4% m/V aqueous solution of riboflavin sodium...

Numerical modelling of cold compaction of metal powder

DEFF Research Database (Denmark)

Redanz, Pia

1998-01-01

A finite element programme has been developed for the analysis of porosity and stress distributions in a powder compact, based on rate-independent finite strain plasticity theory. The strain hardening versions of the Gurson model (J. Engng. Mater. Technol., 1977, 99, 2-15), the more recent FKM...... 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...... 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...

Modeling of magnetic particle orientation in magnetic powder injection molding

Science.gov (United States)

Doo Jung, Im; Kang, Tae Gon; Seul Shin, Da; Park, Seong Jin

2018-03-01

The magnetic micro powder orientation under viscous shear flow has been analytically understood and characterized into a new analytical orientation model for a powder injection molding process. The effects of hydrodynamic force from the viscous flow, external magnetic force and internal dipole-dipole interaction were considered to predict the orientation under given process conditions. Comparative studies with a finite element method proved the calculation validity with a partial differential form of the model. The angular motion, agglomeration and magnetic chain formation have been simulated, which shows that the effect of dipole-dipole interaction among powders on the orientation state becomes negligible at a high Mason number condition and at a low λ condition (the ratio of external magnetic field strength and internal magnetic moment of powder). Our developed model can be very usefully employed in the process analysis and design of magnetic powder injection molding.

In-line Raman spectroscopic monitoring and feedback control of a continuous twin-screw pharmaceutical powder blending and tableting process.

Science.gov (United States)

Nagy, Brigitta; Farkas, Attila; Gyürkés, Martin; Komaromy-Hiller, Szofia; Démuth, Balázs; Szabó, Bence; Nusser, Dávid; Borbás, Enikő; Marosi, György; Nagy, Zsombor Kristóf

2017-09-15

The integration of Process Analytical Technology (PAT) initiative into the continuous production of pharmaceuticals is indispensable for reliable production. The present paper reports the implementation of in-line Raman spectroscopy in a continuous blending and tableting process of a three-component model pharmaceutical system, containing caffeine as model active pharmaceutical ingredient (API), glucose as model excipient and magnesium stearate as lubricant. The real-time analysis of API content, blend homogeneity, and tablet content uniformity was performed using a Partial Least Squares (PLS) quantitative method. The in-line Raman spectroscopic monitoring showed that the continuous blender was capable of producing blends with high homogeneity, and technological malfunctions can be detected by the proposed PAT method. The Raman spectroscopy-based feedback control of the API feeder was also established, creating a 'Process Analytically Controlled Technology' (PACT), which guarantees the required API content in the produced blend. This is, to the best of the authors' knowledge, the first ever application of Raman-spectroscopy in continuous blending and the first Raman-based feedback control in the formulation technology of solid pharmaceuticals. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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.

Pharmaceutical expenditure forecast model to support health policy decision making.

Science.gov (United States)

Rémuzat, Cécile; Urbinati, Duccio; Kornfeld, Åsa; Vataire, Anne-Lise; Cetinsoy, Laurent; Aballéa, Samuel; Mzoughi, Olfa; Toumi, Mondher

2014-01-01

With constant incentives for healthcare payers to contain their pharmaceutical budgets, modelling policy decision impact became critical. The objective of this project was to test the impact of various policy decisions on pharmaceutical budget (developed for the European Commission for the project 'European Union (EU) Pharmaceutical expenditure forecast' - http://ec.europa.eu/health/healthcare/key_documents/index_en.htm). A model was built to assess policy scenarios' impact on the pharmaceutical budgets of seven member states of the EU, namely France, Germany, Greece, Hungary, Poland, Portugal, and the United Kingdom. The following scenarios were tested: expanding the UK policies to EU, changing time to market access, modifying generic price and penetration, shifting the distribution chain of biosimilars (retail/hospital). Applying the UK policy resulted in dramatic savings for Germany (10 times the base case forecast) and substantial additional savings for France and Portugal (2 and 4 times the base case forecast, respectively). Delaying time to market was found be to a very powerful tool to reduce pharmaceutical expenditure. Applying the EU transparency directive (6-month process for pricing and reimbursement) increased pharmaceutical expenditure for all countries (from 1.1 to 4 times the base case forecast), except in Germany (additional savings). Decreasing the price of generics and boosting the penetration rate, as well as shifting distribution of biosimilars through hospital chain were also key methods to reduce pharmaceutical expenditure. Change in the level of reimbursement rate to 100% in all countries led to an important increase in the pharmaceutical budget. Forecasting pharmaceutical expenditure is a critical exercise to inform policy decision makers. The most important leverages identified by the model on pharmaceutical budget were driven by generic and biosimilar prices, penetration rate, and distribution. Reducing, even slightly, the prices of

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.

Modeling of Powder Bed Manufacturing Defects

Science.gov (United States)

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

2018-01-01

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.

Preconditions of forming of loyalty management model in pharmaceutical institution

Directory of Open Access Journals (Sweden)

O. O. Molodozhonova

2013-04-01

Full Text Available The first stage of the mechanism for implementing of two-level model of efficient management of loyalty was justified. It is based on the fundamental value systems of the formation of consumer commitment and institutional commitment of pharmaceutical professionals. The stage involves recruitment, selection and adaptation period for pharmaceutical professionals and pre-use of axiological questioning of consumers of pharmaceutic goods.

Modelling the mechanical behaviour of metal powder during Die compaction process

Directory of Open Access Journals (Sweden)

G. Cricrì

2016-07-01

Full Text Available In this work, powder compaction process was investigated by using a numerical material model, which involves Mohr-Coulomb theory and an elliptical surface plasticity model. An effective algorithm was developed and implemented in the ANSYS finite element (FEM code by using the subroutine USERMAT. Some simulations were performed to validate the proposed metal powder material model. The interaction between metal powder and die walls was considered by means of contact elements. In addition to the analysis of metal powder behaviour during compaction, the actions transmitted to die were also investigated, by considering different friction coefficients. This information is particularly useful for a correct die design.

Pharmaceutical expenditure forecast model to support health policy decision making

Science.gov (United States)

Rémuzat, Cécile; Urbinati, Duccio; Kornfeld, Åsa; Vataire, Anne-Lise; Cetinsoy, Laurent; Aballéa, Samuel; Mzoughi, Olfa; Toumi, Mondher

2014-01-01

Background and objective With constant incentives for healthcare payers to contain their pharmaceutical budgets, modelling policy decision impact became critical. The objective of this project was to test the impact of various policy decisions on pharmaceutical budget (developed for the European Commission for the project ‘European Union (EU) Pharmaceutical expenditure forecast’ – http://ec.europa.eu/health/healthcare/key_documents/index_en.htm). Methods A model was built to assess policy scenarios’ impact on the pharmaceutical budgets of seven member states of the EU, namely France, Germany, Greece, Hungary, Poland, Portugal, and the United Kingdom. The following scenarios were tested: expanding the UK policies to EU, changing time to market access, modifying generic price and penetration, shifting the distribution chain of biosimilars (retail/hospital). Results Applying the UK policy resulted in dramatic savings for Germany (10 times the base case forecast) and substantial additional savings for France and Portugal (2 and 4 times the base case forecast, respectively). Delaying time to market was found be to a very powerful tool to reduce pharmaceutical expenditure. Applying the EU transparency directive (6-month process for pricing and reimbursement) increased pharmaceutical expenditure for all countries (from 1.1 to 4 times the base case forecast), except in Germany (additional savings). Decreasing the price of generics and boosting the penetration rate, as well as shifting distribution of biosimilars through hospital chain were also key methods to reduce pharmaceutical expenditure. Change in the level of reimbursement rate to 100% in all countries led to an important increase in the pharmaceutical budget. Conclusions Forecasting pharmaceutical expenditure is a critical exercise to inform policy decision makers. The most important leverages identified by the model on pharmaceutical budget were driven by generic and biosimilar prices, penetration rate

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,…

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.

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. PMID:24250597

Evaluation of Pharmaceutical and Microbial Qualities of Some ...

African Journals Online (AJOL)

The tablet formulation (Product A) showed acceptable crushing strength and friability but failed the test for disintegration time. The angle of repose of the powder dosage ... Keywords: Herbal medicinal products, microbial quality, pharmaceutical quality. > Tropical Journal of ... Featuring journals from 32 Countries: Algeria (5) ...

Modelling and Simulation of Tensile Fracture in High Velocity Compacted Metal Powder

International Nuclear Information System (INIS)

Jonsen, P.; Haeggblad, H.-A.

2007-01-01

In cold uniaxial powder compaction, powder is formed into a desired shape with rigid tools and a die. After pressing, but before sintering, the compacted powder is called green body. A critical property in the metal powder pressing process is the mechanical properties of the green body. Beyond a green body free from defects, desired properties are high strength and uniform density. High velocity compaction (HVC) using a hydraulic operated hammer is a production method to form powder utilizing a shock wave. Pre-alloyed water atomised iron powder has been HVC-formed into circular discs with high densities. The diametral compression test also called the Brazilian disc test is an established method to measure tensile strength in low strength material like e.g. rock, concrete, polymers and ceramics. During the test a thin disc is compressed across the diameter to failure. The compression induces a tensile stress perpendicular to the compressed diameter. In this study the test have been used to study crack initiation and the tensile fracture process of HVC-formed metal powder discs with a relative density of 99%. A fictitious crack model controlled by a stress versus crack-width relationship is utilized to model green body cracking. Tensile strength is used as a failure condition and limits the stress in the fracture interface. The softening rate of the model is obtained from the corresponding rate of the dissipated energy. The deformation of the powder material is modelled with an elastic-plastic Cap model. The characteristics of the tensile fracture development of the central crack in a diametrically loaded specimen is numerically studied with a three dimensional finite element simulation. Results from the finite element simulation of the diametral compression test shows that it is possible to simulate fracturing of HVC-formed powder. Results from the simulation agree reasonably with experiments

A review of the terms agglomerate and aggregate with a recommendation for nomenclature used in powder and particle characterization.

Science.gov (United States)

Nichols, Gary; Byard, Stephen; Bloxham, Mark J; Botterill, Joanne; Dawson, Neil J; Dennis, Andrew; Diart, Valerie; North, Nigel C; Sherwood, John D

2002-10-01

The terms "agglomerate" and "aggregate" are widely used by powder technologists to describe assemblages of particles that are found in dry powders and powders in liquid suspensions. Each term has a specific meaning but, unfortunately, they are frequently interchanged at will and this has resulted in universal confusion. This confusion is perpetuated by conflicting definitions in national and international standards and this presents problems when describing powder properties or communicating results in reports and research papers. This paper reviews the current status of the definitions, with particular emphasis on their use in the pharmaceutical industry. It is proposed that just one term, agglomerate, should be used to describe an assemblage of particles in a powder and that the term aggregate should be confined to pre-nucleation structures. Copyright 2002 Wiley-Liss Inc. and the American Pharmaceutical Association

Methylprednisolone and its related substances in freeze-dried powders for injections

OpenAIRE

LJILJANA SOLOMUN; SVETLANA IBRIĆ; VLATKA VAJS; IVAN VUČKOVIĆ; ZORICA VUJIĆ

2010-01-01

In this work, the behavior of the active pharmaceutical substances methylprednisolone (in a form of methylprednisolone sodium succinate) in finished pharmaceutical dosage form, i.e., freeze-dried powder for injections was examined. The goal was to evaluate the chemical stabilities of methyl-prednisolone sodium succinate packaged in a dual chamber vial, as a specific container closure system. The effect of different parameters: temperature, moisture and light were monitored. The method propose...

In-line monitoring and optimization of powder flow in a simulated continuous process using transmission near infrared spectroscopy.

Science.gov (United States)

Alam, Md Anik; Shi, Zhenqi; Drennen, James K; Anderson, Carl A

2017-06-30

In-line monitoring of continuous powder flow is an integral part of the continuous manufacturing process of solid oral dosage forms in the pharmaceutical industry. Specifically, monitoring downstream from loss-in-weight (LIW) feeders and/or continuous mixers provides important data about the state of the process. Such measurements support control of the process and thereby enhance product quality. Near Infrared Spectroscopy (NIRS) is a potential PAT tool to monitor the homogeneity of a continuous powder flow stream in pharmaceutical manufacturing. However, the association of analytical results from NIR sampling of the powder stream and the homogeneity (content uniformity) of the resulting tablets provides several challenges; appropriate sampling strategies, adequately robust modeling techniques and poor sensitivities (for low dose APIs) are amongst them. Information from reflectance-based NIRS sampling is limited. The region of the powder bed that is interrogated is confined to the surface where the measurement is made. This potential bias in sampling may, in turn, limit the ability to predict the homogeneity of the finished dosage form. Further, changes to the processing parameters (e.g., rate of powder flow) often have a significant effect on the resulting data. Sample representation, interdependence between process parameters and their effects on powder flow behavior are critical factors for NIRS monitoring of continuous powder flow system. A transmission NIR method was developed as an alternative technique to monitor continuous powder flow and quantify API in the powder stream. Transmission NIRS was used to determine the thickness of the powder stream flowing from a loss-in-weight feeder. The thickness measurement of the powder stream provided an in-depth understanding about the effects of process parameters such as tube angles and powder flow rates on powder flow behaviors. This knowledge based approach helped to define an analytical design space that was

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. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

Prospective of Transformation of Current Models of the Global Pharmaceutical Market

Directory of Open Access Journals (Sweden)

Yuriy Solodkovskyy

2012-02-01

Full Text Available This article thoroughly analyzes the current state of the global pharmaceutical market, defines the key factors for its development and outlines the promising areas of transformation of existing business models of top companies. The forecasted data relating to the market development until 2015 have been investigated. The global, market, technological and organizational factors of transformation of modern model of the global pharmaceutical market have been identified.

The relationship between the particle properties, mechanical behavior, and surface roughness of some pharmaceutical excipient compacts

International Nuclear Information System (INIS)

Narayan, Padma; Hancock, Bruno C.

2003-01-01

Several common pharmaceutical excipient powders were compacted at a constant solid fraction (SF) in order to study the relationship between powder properties, compact surface roughness, and compact mechanical properties such as hardness, elasticity, and brittleness. The materials used in this study included microcrystalline cellulose (MCC), fumaric acid, mannitol, lactose monohydrate, spray dried lactose, sucrose, and dibasic calcium phosphate dihydrate. A slow consolidation process was used to make compacts at a SF of 0.85 (typical for most pharmaceutical tablets) from single excipient components. A model was proposed to describe the surface roughness of compacts based on the brittle or ductile deformation tendencies of the powder materials. The roughness profile would also be dependent upon the magnitude of the compression stress in relation to the yield stress (onset of irreversible deformation) values of the excipients. It was hypothesized that brittle materials would produce smooth compacts with high surface variability due to particle fracture, and the converse would apply for ductile materials. Compact surfaces should be smoother if the materials were compressed above their yield pressure values. Non-contact optical profilometry was used along with scanning electron microscopy to quantify and characterize the surface morphology of the excipient compacts. The roughness parameters R a (average roughness), R q (RMS roughness), R q /R a (ratio describing surface variability), and R sk (skewness) were found to correlate with the deformation properties of the excipients. Brittle materials such as lactose, sucrose, and calcium phosphate produced compacts with low values of R a and R q , high variability, and negative R sk . The opposite was found with plastic materials such as MCC, mannitol, and fumaric acid. The highly negative skewness values for brittle material compacts may indicate their propensity to be vulnerable to cracks or surface defects. These findings

The relationship between the particle properties, mechanical behavior, and surface roughness of some pharmaceutical excipient compacts

Energy Technology Data Exchange (ETDEWEB)

Narayan, Padma; Hancock, Bruno C

2003-08-25

Several common pharmaceutical excipient powders were compacted at a constant solid fraction (SF) in order to study the relationship between powder properties, compact surface roughness, and compact mechanical properties such as hardness, elasticity, and brittleness. The materials used in this study included microcrystalline cellulose (MCC), fumaric acid, mannitol, lactose monohydrate, spray dried lactose, sucrose, and dibasic calcium phosphate dihydrate. A slow consolidation process was used to make compacts at a SF of 0.85 (typical for most pharmaceutical tablets) from single excipient components. A model was proposed to describe the surface roughness of compacts based on the brittle or ductile deformation tendencies of the powder materials. The roughness profile would also be dependent upon the magnitude of the compression stress in relation to the yield stress (onset of irreversible deformation) values of the excipients. It was hypothesized that brittle materials would produce smooth compacts with high surface variability due to particle fracture, and the converse would apply for ductile materials. Compact surfaces should be smoother if the materials were compressed above their yield pressure values. Non-contact optical profilometry was used along with scanning electron microscopy to quantify and characterize the surface morphology of the excipient compacts. The roughness parameters R{sub a} (average roughness), R{sub q} (RMS roughness), R{sub q}/R{sub a} (ratio describing surface variability), and R{sub sk} (skewness) were found to correlate with the deformation properties of the excipients. Brittle materials such as lactose, sucrose, and calcium phosphate produced compacts with low values of R{sub a} and R{sub q}, high variability, and negative R{sub sk}. The opposite was found with plastic materials such as MCC, mannitol, and fumaric acid. The highly negative skewness values for brittle material compacts may indicate their propensity to be vulnerable to

Powder X-ray diffraction studies of structural and kinetic aspects of polymorphism

International Nuclear Information System (INIS)

Chan, F.C.

1999-01-01

Polymorphism is a poorly understood phenomenon that is of considerable technological interest to the pharmaceutical industry. The polymorph selected can influence the bioavailability, processing and stability of the pharmaceutical dosage form. In this study structural, kinetic and thermodynamics aspects of polymorphism and polymorphic phase transformations have been examined using powder X-ray diffraction (PXRD). The compound sulphathiazole is a well-studied model in the investigation of polymorphism and crystal growth. There are five known polymorphic forms and the structure of form V was unknown until this study. The difficulty has been that it has not been possibly to prepare crystals of appropriate size and quality for single crystal diffraction. Furthermore, structure solution from powder data for organic molecules is almost impossible. Despite the challenge the structure of sulphathiazole form V have been solved ab initio from powder data using direct methods. With 16 non-hydrogen atoms in the molecule and two molecules in the asymmetric unit, this structure represents a significant advance in terms of the complexity of an organic structure solved from PXRD data. The structural data should be invaluable for rationalizing experimental observations and the development of theoretical ideas regarding polymorphism and crystal growth. The second part of the study, has examined kinetics of polymorphic phase transformations as a function of pressure combined with temperature using real-time synchrotron PXRD. The significance of pressure arises from the fact that phase transitions can be induced in pharmaceuticals during tabletting. The phase transformation behaviour of rubidium iodide (chosen as a simple test model) has been investigated as a function of isobaric pressure at ambient and elevated temperatures. The kinetics have been characterized by using the Johnson-Melil-Avrami equation. The effect of successive cycling across the transition pressure was also

Journal of Pharmaceutical and Allied Sciences - Vol 14, No 1 (2017)

African Journals Online (AJOL)

Physico-chemical properties of a modified biomaterial from Tympanotonus fuscata (periwinkle) shell powder considered as pharmaceutical excipient · EMAIL FULL TEXT EMAIL FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. K.C Ugoeze, A Chukwu, 2417-2429 ...

Tricalcium phosphate powder: Preparation, characterization and compaction abilities

Directory of Open Access Journals (Sweden)

Abida Fatima

2017-02-01

Full Text Available In this work, we characterize tricalcium phosphate powders Ca9(HPO4(PO45(OH resulting from a reaction between calcium hydroxide and orthophosphoric acid at room temperature, without pH adjustment and in absence of ionic impurities. The prepared powder has an atomic ratio Ca/P of 1.512 ± 0.005. The real density is 2.68 ± 0.02 g/cm3 and the specific surface area is 80 ± 02 m2/g. During compression, the microstructure of Ca-deficient apatite powder with the presence of HPO4 groups seems to support the cohesion between particles. The transmission ratio is 90%, the transfer ratio is 41.8 and the ratio of the die-wall friction is 0.22. These results show that apatitic tricalcium powder gives a good aptitude to the compaction which leads to a good tensile strength (0.79 MPa. The heat treatment of the prepared powder shows the precise temperature for the formation of pyrophosphate, β-TCP and α-TCPa phases.  The purity and aptitude to compaction of the prepared powders are very promising for pharmaceutical and medical applications.

3D Model Studies on the Effect of Bed and Powder Type Upon Radial Static Pressure and Powder Distribution in Metallurgical Shaft Furnaces

Directory of Open Access Journals (Sweden)

Panic B.

2017-09-01

Full Text Available The flow of gases in metallurgical shaft furnaces has a decisive influence on the course and process efficiency. Radial changes in porosity of the bed cause uneven flow of gas along the radius of the reactor, which sometimes is deliberate and intentional. However, holdup of solid particles in descending packed beds of metallurgical shaft furnaces can lead to unintentional changes in porosity of the bed along the radial reactor. Unintentional changes in porosity often disrupt the flow of gas causing poor performance of the furnace. Such disruptions of flow may occur in the blast furnace due to high level of powder content in gas caused by large amount of coal dust/powder insufflated as fuel substitute. The paper describes the model test results of radial distribution of static pressure and powder hold up within metallurgical reactor. The measurements were carried out with the use of 3D physical model of two-phase flow gas-powder in the moving (descending packed bed. Sinter or blast furnace pellets were used as packed bed while carbon powder or iron powder were used as the powder. Wide diversity within both static pressure distribution and powder distribution along the radius of the reactor were observed once the change in the type of powder occurred.

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

Directory of Open Access Journals (Sweden)

Akiko Tanaka

Full Text Available 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.

Thin-coating as an alternative approach to improve flow properties of ibuprofen powder

DEFF Research Database (Denmark)

Genina, Natalja; Räikkönen, Heikki; Ehlers, Henrik

2010-01-01

In the present study, thin-coating as a potential method for improving flow properties of cohesive ibuprofen powder was introduced. Briefly, the technique was based on the successive deposition of ultrasound-assisted fine polymer mist onto the surface of the powdered active pharmaceutical...... ingredient (API), producing individual particles with a hydrophilic thin-coat. A 0.15% m/V aqueous solution of hydroxypropyl methylcellulose (HPMC) was used. Particle size and surface analysis revealed a decrease in the cohesiveness of ibuprofen powder and an increase in the homogeneity of particle surfaces...

MODELING MERCURY CONTROL WITH POWDERED ACTIVATED CARBON

Science.gov (United States)

The paper presents a mathematical model of total mercury removed from the flue gas at coal-fired plants equipped with powdered activated carbon (PAC) injection for Mercury control. The developed algorithms account for mercury removal by both existing equipment and an added PAC in...

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.

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.

[Study on moisture sorption process model and application traditional Chinese medicine extract powder].

Science.gov (United States)

Lin, Tingting; He, Yan; Xiao, Xiong; Yuan, Liang; Rao, Xiaoyong; Luo, Xiaojian

2010-04-01

Study on the moisture sorption process characteristics of traditional Chinese medicine extract powder, to establish a mathematical model, provide a new method for in-depth study for moisture sorption behavior of traditional Chinese medicine extract powder and a reference for determine the production cycle, and predict product stability. Analyzed moisture absorption process of traditional Chinese medicine extract powder by utilized the law of conservation of mass and Fick's first law to establish the double exponential absorption model, fitted the moisture absorption data and compared with other commonly used five kinds of model to estimate the double-exponential absorption model. The statistical analysis showed that the coefficient of determination (R2) of double exponential model, Weibull distribution model and first order kinetics model were large, but the residues sum of squares (RSS) and AIC values were small. Synthesized the practical application meaning, we consided that the double exponential model was more suitable for simulating the process of Chinese medicine extract powder moisture absorption. The double exponential is suitable for characterization the process of traditional Chinese medicine extract moisture absorption.

THz spectroscopy: An emerging technology for pharmaceutical development and pharmaceutical Process Analytical Technology (PAT) applications

Science.gov (United States)

Wu, Huiquan; Khan, Mansoor

2012-08-01

As an emerging technology, THz spectroscopy has gained increasing attention in the pharmaceutical area during the last decade. This attention is due to the fact that (1) it provides a promising alternative approach for in-depth understanding of both intermolecular interaction among pharmaceutical molecules and pharmaceutical product quality attributes; (2) it provides a promising alternative approach for enhanced process understanding of certain pharmaceutical manufacturing processes; and (3) the FDA pharmaceutical quality initiatives, most noticeably, the Process Analytical Technology (PAT) initiative. In this work, the current status and progress made so far on using THz spectroscopy for pharmaceutical development and pharmaceutical PAT applications are reviewed. In the spirit of demonstrating the utility of first principles modeling approach for addressing model validation challenge and reducing unnecessary model validation "burden" for facilitating THz pharmaceutical PAT applications, two scientific case studies based on published THz spectroscopy measurement results are created and discussed. Furthermore, other technical challenges and opportunities associated with adapting THz spectroscopy as a pharmaceutical PAT tool are highlighted.

Low-field vortex pinning model for undoped sintered MgB2 powders

International Nuclear Information System (INIS)

Agassi, Y D

2011-01-01

Sintered MgB 2 powders constitute a porous ensemble of irregularly shaped agglomerates of tightly packed grains. The low-field critical current density in such powders was experimentally observed to scale with the inverse of the average agglomerate size. Motivated by this observation we consider a flux pinning model which accounts for the MgB 2 powder porosity by focusing on a single finite-size agglomerate size. According to the model the observed critical current density dependence on the agglomerate size reflects the outward pull exerted on a vortex that is pinned in proximity to the agglomerate edges. The calculated critical current density replicates the observed scaling within agglomerate-size bounds. Implications of the model are discussed.

Analysis of solid-state transformations of pharmaceutical compounds using vibrational spectroscopy

DEFF Research Database (Denmark)

Heinz, Andrea; Strachan, Clare J; Gordon, Keith C

2009-01-01

OBJECTIVES: Solid-state transformations may occur during any stage of pharmaceutical processing and upon storage of a solid dosage form. Early detection and quantification of these transformations during the manufacture of solid dosage forms is important since the physical form of an active...... pharmaceutical ingredient can significantly influence its processing behaviour, including powder flow and compressibility, and biopharmaceutical properties such as solubility, dissolution rate and bioavailability. KEY FINDINGS: Vibrational spectroscopic techniques such as infrared, near-infrared, Raman and, most...... multivariate approaches where even overlapping spectral bands can be analysed. SUMMARY: This review discusses the applications of different vibrational spectroscopic techniques to detect and monitor solid-state transformations possible for crystalline polymorphs, hydrates and amorphous forms of pharmaceutical...

Modeling conversion of ammonium diuranate (ADU) into uranium dioxide (UO{sub 2}) powder

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); Khoai, Do Van [Institute for Technology of Radioactive and Rare Elements (ITRRE), 48 Lang Ha, Dong Da, Ha Noi (Viet Nam); Current Postdoctoral Fellow at Tokai Reprocessing Technology Development Center, Japan Atomic Energy Agency (JAEA), 4-33 Tokaimura, Nakagun, Ibaraki, 319-1194 (Japan); Lee, Jin-Young, E-mail: jylee@kigam.re.kr [Convergence Research Center for Development of Mineral Resources (DMR), Korea Institute of Geoscience and Mineral Resources (KIGAM), Daejeon, 34132 (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, 34132 (Korea, Republic of)

2016-10-15

In the paper, Brandon mathematical model that describes 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 specific surface area of ammonium diuranate (ADU)-derived UO{sub 2} powder products was established. The proposed models can be used to predict and control the specific surface area of UO{sub 2} 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 UO{sub 2} powders.

Effect of Shear Applied During a Pharmaceutical Process on Near Infrared Spectra.

Science.gov (United States)

Hernández, Eduardo; Pawar, Pallavi; Rodriguez, Sandra; Lysenko, Sergiy; Muzzio, Fernando J; Romañach, Rodolfo J

2016-03-01

This study describes changes observed in the near-infrared (NIR) diffuse reflectance (DR) spectra of pharmaceutical tablets after these tablets were subjected to different levels of strain (exposure to shear) during the mixing process. Powder shearing is important in the mixing of powders that are cohesive. Shear stress is created in a system by moving one surface over another causing displacements in the direction of the moving surface and is part of the mixing dynamics of particulates in many industries including the pharmaceutical industry. In continuous mixing, shear strain is developed within the process when powder particles are in constant movement and can affect the quality attributes of the final product such as dissolution. These changes in the NIR spectra could affect results obtained from NIR calibration models. The aim of the study was to understand changes in the NIR diffuse reflectance spectra that can be associated with different levels of strain developed during blend shearing of laboratory samples. Shear was applied using a Couette cell and tablets were produced using a tablet press emulator. Tablets with different shear levels were measured using NIR spectroscopy in the diffuse reflectance mode. The NIR spectra were baseline corrected to maintain the scattering effect associated with the physical properties of the tablet surface. Principal component analysis was used to establish the principal sources of variation within the samples. The angular dependence of elastic light scattering shows that the shear treatment reduces the size of particles and produces their uniform and highly isotropic distribution. Tablet compaction further reduces the diffuse component of scattering due to realignment of particles. © The Author(s) 2016.

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

Science.gov (United States)

Sun, Changquan Calvin

2017-05-01

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

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.

A survivability model for ejection of green compacts in powder metallurgy technology

Directory of Open Access Journals (Sweden)

Payman Ahi

2012-01-01

Full Text Available Reliability and quality assurance have become major considerations in the design and manufacture of today’s parts and products. Survivability of green compact using powder metallurgy technology is considered as one of the major quality attributes in manufacturing systems today. During powder metallurgy (PM production, the compaction conditions and behavior of the metal powder dictate the stress and density distribution in the green compact prior to sintering. These parameters greatly influence the mechanical properties and overall strength of the final component. In order to improve these properties, higher compaction pressures are usually employed, which make unloading and ejection of green compacts more challenging, especially for the powder-compacted parts with relatively complicated shapes. This study looked at a mathematical survivability model concerning green compact characteristics in PM technology and the stress-strength failure model in reliability engineering. This model depicts the relationship between mechanical loads (stress during ejection, experimentally determined green strength and survivability of green compact. The resulting survivability is the probability that a green compact survives during and after ejection. This survivability model can be used as an efficient tool for selecting the appropriate parameters for the process planning stage in PM technology. A case study is presented here in order to demonstrate the application of the proposed survivability model.

Quantitative modelling to estimate the transfer of pharmaceuticals through the food production system

NARCIS (Netherlands)

Chitescu, C.L.; Nicolau, A.I.; Romkens, P.F.A.M.; Fels-Klerx, van der H.J.

2014-01-01

Use of pharmaceuticals in animal production may cause an indirect route of contamination of food products of animal origin. This study aimed to assess, through mathematical modelling, the transfer of pharmaceuticals from contaminated soil, through plant uptake, into the dairy food production chain.

Modeling the geometric formation and powder deposition mass in laser induction hybrid cladding

International Nuclear Information System (INIS)

Huang, Yong Jun; Yuan, Sheng Fa

2012-01-01

A new laser induction hybrid cladding technique on cylinder work piece is presented. Based on a series of laser induction hybrid experiments by off axial powder feeding, the predicting models of individual clad geometric formation and powder catchment were developed in terms of powder feeding rate, laser special energy and induction energy density using multiple regression analysis. In addition, confirmation tests were performed to make a comparison between the predicting results and measured ones. Via the experiments and analysis, the conclusions can be lead to that the process parameters have crucial influence on the clad geometric formation and powder catchment, and that the predicting model reflects well the relationship between the clad geometric formation and process parameters in laser induction hybrid cladding

Precipitation in Powder Metallurgy, Nickel Base Superalloys: Review of Modeling Approach and Formulation of Engineering (Postprint)

Science.gov (United States)

2016-12-01

AFRL-RX-WP-JA-2016-0333 PRECIPITATION IN POWDER- METALLURGY , NICKEL-BASE SUPERALLOYS: REVIEW OF MODELING APPROACH AND FORMULATION OF...PRECIPITATION IN POWDER- METALLURGY , NICKEL- BASE SUPERALLOYS: REVIEW OF MODELING APPROACH AND FORMULATION OF ENGINEERING (POSTPRINT) 5a...and kinetic parameters required for the modeling of γ′ precipitation in powder- metallurgy (PM), nickel-base superalloys are summarized. These

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...... phase (submodel 2), the water inside the granule evaporates. The second submodel contains an empirical power coefficient, b. A sensitivity analysis was performed to study the influence of parameters on the moisture content of single pharmaceutical granules, which clearly points towards the importance...

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

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...

An analysis of un-dissolved powders of instant powdered soup by using ultrasonographic image

Science.gov (United States)

Kawaai, Yukinori; Kato, Kunihito; Yamamoto, Kazuhiko; Kasamatsu, Chinatsu

2008-11-01

Nowadays, there are many instant powdered soups around us. When we make instant powdered soup, sometimes we cannot dissolve powders perfectly. Food manufacturers want to improve this problem in order to make better products. Therefore, they have to measure the state and volume of un-dissolved powders. Earlier methods for analyzing removed the un-dissolved powders from the container, the state of the un-dissolved power was changed. Our research using ultrasonographic image can measure the state of un-dissolved powders with no change by taking cross sections of the soup. We then make 3D soup model from these cross sections of soup. Therefore we can observe the inside of soup that we do not have ever seen. We construct accurate 3D model. We can visualize the state and volume of un-dissolved powders with analyzing the 3D soup models.

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.

Investigation of a new mathematical model for compression of pharmaceutical powders

DEFF Research Database (Denmark)

Sonnergaard, Jørn

2001-01-01

A new compaction equation, the log-exp model: V=V-w log(P)+V exp(P/P) is presented. The model presumes that two compaction processes: a logarithmic and an exponential decline may be active simultaneously. Using non-linear regression techniques the model gives an excellent fit to a number of model...... substances with wide differences in compaction behaviour. Compared to the Kawakita equation the model covers a broader range of the compaction profile. The new model and the Cooper and Eaton equation fit the data on the same level, but the parameters derived from the log-exp model seems to have more...

Validating CFD Predictions of Pharmaceutical Aerosol Deposition with In Vivo Data.

Science.gov (United States)

Tian, Geng; Hindle, Michael; Lee, Sau; Longest, P Worth

2015-10-01

CFD provides a powerful approach to evaluate the deposition of pharmaceutical aerosols; however, previous studies have not compared CFD results of deposition throughout the lungs with in vivo data. The in vivo datasets selected for comparison with CFD predictions included fast and slow clearance of monodisperse aerosols as well as 2D gamma scintigraphy measurements for a dry powder inhaler (DPI) and softmist inhaler (SMI). The CFD model included the inhaler, a characteristic model of the mouth-throat (MT) and upper tracheobronchial (TB) airways, stochastic individual pathways (SIPs) representing the remaining TB region, and recent CFD-based correlations to predict pharmaceutical aerosol deposition in the alveolar airways. For the monodisperse aerosol, CFD predictions of total lung deposition agreed with in vivo data providing a percent relative error of 6% averaged across aerosol sizes of 1-7 μm. With the DPI and SMI, deposition was evaluated in the MT, central airways (bifurcations B1-B7), and intermediate plus peripheral airways (B8 through alveoli). Across these regions, CFD predictions produced an average relative error <10% for each inhaler. CFD simulations with the SIP modeling approach were shown to accurately predict regional deposition throughout the lungs for multiple aerosol types and different in vivo assessment methods.

Actor modelling and its contribution to the development of integrative strategies for management of pharmaceuticals in drinking water.

Science.gov (United States)

Titz, Alexandra; Döll, Petra

2009-02-01

Widespread presence of human pharmaceuticals in water resources across the globe is documented. While some, but certainly not enough, research on the occurrence, fate and effect of pharmaceuticals in water resources has been carried out, a holistic risk management strategy is missing. The transdisciplinary research project "start" aimed to develop an integrative strategy by the participation of experts representing key actors in the problem field "pharmaceuticals in drinking water". In this paper, we describe a novel modelling method, actor modelling with the semi-quantitative software DANA (Dynamic Actor Network Analysis), and its application in support of identifying an integrative risk management strategy. Based on the individual perceptions of different actors, the approach allows the identification of optimal strategies. Actors' perceptions were elicited by participatory model building and interviews, and were then modelled in perception graphs. Actor modelling indicated that an integrative strategy that targets environmentally-responsible prescription, therapy, and disposal of pharmaceuticals on one hand, and the development of environmentally-friendly pharmaceuticals on the other hand, will likely be most effective for reducing the occurrence of pharmaceuticals in drinking water (at least in Germany where the study was performed). However, unlike most other actors, the pharmaceutical industry itself does not perceive that the production of environmentally-friendly pharmaceuticals is an action that helps to achieve its goals, but contends that continued development of highly active pharmaceutical ingredients will help to reduce the occurrence of pharmaceuticals in the water cycle. Investment in advanced waste or drinking water treatment is opposed by both the wastewater treatment company and the drinking water supplier, and is not mentioned as appropriate by the other actors. According to our experience, actor modelling is a useful method to suggest effective

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.

Densification behavior of aluminum alloy powder mixed with zirconia powder inclusion under cold compaction

International Nuclear Information System (INIS)

Ryu, Hyun Seok; Lee, Sung Chul; Kim, Ki Tae

2002-01-01

Densification behavior of composite powders was investigated during cold compaction. Experimental data were obtained for aluminum alloy powder mixed with zirconia powder inclusion under triaxial compression. The cap model with constraint factors was implemented into a finite element program(ABAQUS) to simulate compaction responses of composite powders during cold compaction. Finite element results were compared with experimental data for densification behavior of composite powders under cold isostatic pressing and die compaction. The agreements between experimental data and finite element calculations from the cap model with constraint factors were good

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 carbon product. The performance of the PAC products generally gave better results for individual PhACs in regards to carbon availability. All carbon products showed a specific 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.

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

2017-12-01

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.

Development of materials science by Ab initio powder diffraction analysis

International Nuclear Information System (INIS)

Fujii, Kotaro

2015-01-01

Crystal structure is most important information to understand properties and behavior of target materials. Technique to analyze unknown crystal structures from powder diffraction data (ab initio powder diffraction analysis) enables us to reveal crystal structures of target materials even we cannot obtain a single crystal. In the present article, three examples are introduced to show the power of this technique in the field of materials sciences. The first example is dehydration/hydration of the pharmaceutically relevant material erythrocycin A. In this example, crystal structures of two anhydrous phases were determined from synchrotron X-ray powder diffraction data and their different dehydration/hydration properties were understood from the crystal structures. In the second example, a crystal structure of a three dimensional metal-organic-framework prepared by a mechanochemical reaction was determined from laboratory X-ray powder diffraction data and the reaction scheme has been revealed. In the third example, a crystal structure of a novel oxide-ion conductor of a new structure family was determined from synchrotron X-ray and neutron powder diffraction data which gave an important information to understand the mechanism of the oxide-ion conduction. (author)

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.

[Pharmaceutical logistic in turnover of pharmaceutical products of Azerbaijan].

Science.gov (United States)

Dzhalilova, K I

2009-11-01

Development of pharmaceutical logistic system model promotes optimal strategy for pharmaceutical functioning. The goal of such systems is organization of pharmaceutical product's turnover in required quantity and assortment, at preset time and place, at a highest possible degree of consumption readiness with minimal expenses and qualitative service. Organization of the optimal turnover chain in the region is offered to start from approximate classification of medicaments by logistic characteristics. Supplier selection was performed by evaluation of timeliness of delivery, quality of delivered products (according to the minimum acceptable level of quality) and time-keeping of time spending for orders delivery.

Experiment Analysis and Modelling of Compaction Behaviour of Ag60Cu30Sn10 Mixed Metal Powders

Science.gov (United States)

Zhou, Mengcheng; Huang, Shangyu; Liu, Wei; Lei, Yu; Yan, Shiwei

2018-03-01

A novel process method combines powder compaction and sintering was employed to fabricate thin sheets of cadmium-free silver based filler metals, the compaction densification behaviour of Ag60Cu30Sn10 mixed metal powders was investigated experimentally. Based on the equivalent density method, the density-dependent Drucker-Prager Cap (DPC) model was introduced to model the powder compaction behaviour. Various experiment procedures were completed to determine the model parameters. The friction coefficients in lubricated and unlubricated die were experimentally determined. The determined material parameters were validated by experiments and numerical simulation of powder compaction process using a user subroutine (USDFLD) in ABAQUS/Standard. The good agreement between the simulated and experimental results indicates that the determined model parameters are able to describe the compaction behaviour of the multicomponent mixed metal powders, which can be further used for process optimization simulations.

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...

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

between experiment and theory, and the study therefore demonstrates that synchrotron powder diffraction can indeed provide accurate structure-factor values based on data measured in minutes with limited sample preparation. Thus, potential systematic errors such as extinction and twinning commonly......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...

Pharmaceutical spray drying: solid-dose process technology platform for the 21st century.

Science.gov (United States)

Snyder, Herman E

2012-07-01

Requirement for precise control of solid-dosage particle properties created with a scalable process technology are continuing to expand in the pharmaceutical industry. Alternate methods of drug delivery, limited active drug substance solubility and the need to improve drug product stability under room-temperature conditions are some of the pharmaceutical applications that can benefit from spray-drying technology. Used widely for decades in other industries with production rates up to several tons per hour, pharmaceutical uses for spray drying are expanding beyond excipient production and solvent removal from crystalline material. Creation of active pharmaceutical-ingredient particles with combinations of unique target properties are now more common. This review of spray-drying technology fundamentals provides a brief perspective on the internal process 'mechanics', which combine with both the liquid and solid properties of a formulation to enable high-throughput, continuous manufacturing of precision powder properties.

[Glass transition of Chinese medicine extract powder and its application].

Science.gov (United States)

Luo, Xiao-Jian; Liu, Hui; Liang, Hong-Bo; Xiong, Lei; Rao, Xiao-Yong; Xie, Yin; He, Yan

2017-01-01

Glass transition theory is an important theory in polymer science, which is used to characterize the physical properties. It refers to the transition of amorphous polymer from the glassy state to the rubber state due to heating or the transition from rubber state to glassy state due to cooling. In this paper, the glassy state and glass transition of food and the similar relationship between the composition of Chinese medicine extract powder and food ingredients were described; the determination method for glass transition temperature (Tg) of Chinese medicine extract powder was established and its main influencing factors were analyzed. Meanwhile, the problems in drying process, granulation process and Chinese medicine extract powder and solid preparation storage were analyzed and investigated based on Tg, and then the control strategy was put forward to provide guidance for the research and production of Chinese medicine solid preparation. Copyright© by the Chinese Pharmaceutical Association.

Modeling of quantitative relationships between physicochemical properties of active pharmaceutical ingredients and tensile strength of tablets using a boosted tree.

Science.gov (United States)

Hayashi, Yoshihiro; Oishi, Takuya; Shirotori, Kaede; Marumo, Yuki; Kosugi, Atsushi; Kumada, Shungo; Hirai, Daijiro; Takayama, Kozo; Onuki, Yoshinori

2018-07-01

The aim of this study was to explore the potential of boosted tree (BT) to develop a correlation model between active pharmaceutical ingredient (API) characteristics and a tensile strength (TS) of tablets as critical quality attributes. First, we evaluated 81 kinds of API characteristics, such as particle size distribution, bulk density, tapped density, Hausner ratio, moisture content, elastic recovery, molecular weight, and partition coefficient. Next, we prepared tablets containing 50% API, 49% microcrystalline cellulose, and 1% magnesium stearate using direct compression at 6, 8, and 10 kN, and measured TS. Then, we applied BT to our dataset to develop a correlation model. Finally, the constructed BT model was validated using k-fold cross-validation. Results showed that the BT model achieved high-performance statistics, whereas multiple regression analysis resulted in poor estimations. Sensitivity analysis of the BT model revealed that diameter of powder particles at the 10th percentile of the cumulative percentage size distribution was the most crucial factor for TS. In addition, the influences of moisture content, partition coefficients, and modal diameter were appreciably meaningful factors. This study demonstrates that BT model could provide comprehensive understanding of the latent structure underlying APIs and TS of tablets.

Development and evaluation of mathematical model to predict disintegration time of fast disintegrating tablets using powder characteristics.

Science.gov (United States)

Goel, H; Arora, A; Tiwary, A K; Rana, V

2011-02-01

The objective of the study was to develop a mathematical model for predicting the disintegration time of fast disintegrating tablets (FDTs) by estimating the powder characteristics of powder blend prior to compression. A combination of chitosan-alginate complex and glycine in the ratio of 50:50 was used for preparing FDTs. The developed mathematical model allowed water sorption time (WST), effective pore radius (R(eff.p)) and swelling Index (SI) of powder mixture as well as tablet crushing strength to be successfully correlated with disintegration time (DT) of FDTs. The predicted model showed that disintegration time of FDTs to be directly correlated with powder characteristics and inversely correlated with tablet crushing strength. Furthermore, a correlation of 0.97 was obtained when DT of FDTs was compared with SI/(WST * R(eff.p)). This correlation was not affected by inclusion of water soluble (ondansetron hydrochloride or metaclopramide hydrochloride) or water insoluble (domperidone) drugs in the powder blend or FDTs. These observations indicated the versatility of the mathematical model in predicting the disintegration time of FDTs by evaluating the selected characteristics of the powder blends without actually preparing the FDTs.

Investigation of the Sensitivity of Transmission Raman Spectroscopy for Polymorph Detection in Pharmaceutical Tablets.

Science.gov (United States)

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

2017-08-01

Polymorph detection is critical for ensuring pharmaceutical product quality in drug substances exhibiting polymorphism. Conventional analytical techniques such as X-ray powder diffraction and solid-state nuclear magnetic resonance are utilized primarily for characterizing the presence and identity of specific polymorphs in a sample. These techniques have encountered challenges in analyzing the constitution of polymorphs in the presence of other components commonly found in pharmaceutical dosage forms. Laborious sample preparation procedures are usually required to achieve satisfactory data interpretability. There is a need for alternative techniques capable of probing pharmaceutical dosage forms rapidly and nondestructively, which is dictated by the practical requirements of applications such as quality monitoring on production lines or when quantifying product shelf lifetime. The sensitivity of transmission Raman spectroscopy for detecting polymorphs in final tablet cores was investigated in this work. Carbamazepine was chosen as a model drug, polymorph form III is the commercial form, whereas form I is an undesired polymorph that requires effective detection. The concentration of form I in a direct compression tablet formulation containing 20% w/w of carbamazepine, 74.00% w/w of fillers (mannitol and microcrystalline cellulose), and 6% w/w of croscarmellose sodium, silicon dioxide, and magnesium stearate was estimated using transmission Raman spectroscopy. Quantitative models were generated and optimized using multivariate regression and data preprocessing. Prediction uncertainty was estimated for each validation sample by accounting for all the main variables contributing to the prediction. Multivariate detection limits were calculated based on statistical hypothesis testing. The transmission Raman spectroscopic model had an absolute prediction error of 0.241% w/w for the independent validation set. The method detection limit was estimated at 1.31% w/w. The

Modelling and computer simulation for the manufacture by powder HIPing of Blanket Shield components for ITER

International Nuclear Information System (INIS)

Gillia, O.; Bucci, Ph.; Vidotto, F.; Leibold, J.-M.; Boireau, B.; Boudot, C.; Cottin, A.; Lorenzetto, P.; Jacquinot, F.

2006-01-01

In components of blanket modules for ITER, intricate cooling networks are needed in order to evacuate all heat coming from the plasma. Hot Isostatic Pressing (HIPing) technology is a very convenient method to produce near net shape components with complex cooling network through massive stainless steel parts by bonding together tubes inserted in grooves machined in bulk stainless steel. Powder is often included in the process so as to release difficulties arising with gaps closure between tube and solid part or between several solid parts. In the mean time, it releases the machining precision needed on the parts to assemble before HIP. However, inserting powder in the assembly means densification, i.e. volume change of powder during the HIP cycle. This leads to global and local shape changes of HIPed parts. In order to control the deformations, modelling and computer simulation are used. This modelling and computer simulation work has been done in support to the fabrication of a shield prototype for the ITER blanket. Problems such as global bending of the whole part and deformations of tubes in their powder bed are addressed. It is important that the part does not bend too much. It is important as well to have circular tube shape after HIP, firstly in order to avoid their rupture during HIP but also because non destructive ultrasonic examination is needed to check the quality of the densification and bonding between tube and powder or solid parts; the insertions of a probe in the tubes requires a minimal circular tube shape. For simulation purposes, the behaviour of the different materials has to be modelled. Although the modelling of the massive stainless steel behaviour is not neglected, the most critical modelling is about power. For this study, a thorough investigation on the powder behaviour has been performed with some in-situ HIP dilatometry experiments and some interrupted HIP cycles on trial parts. These experiments have allowed the identification of a

Modelling of the elastic behaviour of metallic powders

International Nuclear Information System (INIS)

Riera, M.D.; Prado, J.M.

1998-01-01

In this work the elastic behaviour of metal powders compacted to different densities is studied. The authors apply a model based on the experimental observation that the elastic volumetric strain and the hydrostatic component of the applied stress are exponentially related. While a complete analysis should include both the volumetric and deviatoric components of the elastic strain, we only present here the first one. (Author) 9 refs

To Study Capping or Lamination Tendency of Tablets Through Evaluation of Powder Rheological Properties and Tablet Mechanical Properties of Directly Compressible Blends.

Science.gov (United States)

Dudhat, Siddhi M; Kettler, Charles N; Dave, Rutesh H

2017-05-01

Air entrapment efficiency of the powders is one of the main factors leading to occurrence of capping or lamination tendency of tablets manufactured from the directly compressible powder blends. The purpose of the current research was to study this underlying cause leading to occurrence of capping or lamination of tablets through evaluation of powder rheological properties. Powder blends were prepared by addition of 0% w/w to 100% w/w of individual active pharmaceutical ingredient (API) [two model API: acetaminophen (APAP) and ibuprofen (IBU)] with microcrystalline cellulose without and with 0.5% w/w Magnesium Stearate as lubricant. Powder rheological properties were analyzed using FT4 Powder Rheometer for dynamic, bulk, and shear properties. Tablet mechanical properties of the respective blends were studied by determining the ability of the material to form tablet of specific strength under applied compaction pressure through tabletability profile. The results showed that powder rheometer distinguished the powder blends based on their ability to relieve entrapped air along with the distinctive flow characteristics. Powder blend prepared with increasing addition of APAP displayed low powder permeability as compared to IBU blends with better powder permeability, compressibility and flow characteristics. Also, lubrication of the APAP blends did not ease their ability to relieve air. Tabletability profiles revealed the potential occurrence of capping or lamination in tablets prepared from the powder blends with high APAP content. This study can help scientist to understand tableting performance at the early-developmental stages and can avoid occurrence capping and lamination of tablets.

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...... approach; and, iii) future pathways to improve the overall modelling of micropollutants...

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.

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

International Nuclear Information System (INIS)

Kharanzhevskiy, Evgeny; Kostenkov, Sergey

2014-01-01

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

Two-dimensional model of laser alloying of binary alloy powder with interval of melting temperature

Science.gov (United States)

Knyzeva, A. G.; Sharkeev, Yu. P.

2017-10-01

The paper contains two-dimensional model of laser beam melting of powders from binary alloy. The model takes into consideration the melting of alloy in some temperature interval between solidus and liquidus temperatures. The external source corresponds to laser beam with energy density distributed by Gauss law. The source moves along the treated surface according to given trajectory. The model allows investigating the temperature distribution and thickness of powder layer depending on technological parameters.

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...

Modelling of powder die compaction for press cycle optimization

Directory of Open Access Journals (Sweden)

Bayle Jean-Philippe

2016-01-01

Full Text Available A new electromechanical press for fuel pellet manufacturing was built last year in partnership between CEA-Marcoule and ChampalleAlcen. This press was developed to shape pellets in a hot cell via remote handling. It has been qualified to show its robustness and to optimize the compaction cycle, thus obtaining a better sintered pellet profile and limiting damage. We will show you how 400 annular pellets have been produced with good geometry's parameters, based on press settings management. These results are according to a good phenomenological pressing knowledge with Finite Element Modeling calculation. Therefore, during die pressing, a modification in the punch displacement sequence induces fluctuation in the axial distribution of frictional forces. The green pellet stress and density gradients are based on these frictional forces between powder and tool, and between grains in the powder, influencing the shape of the pellet after sintering. The pellet shape and diameter tolerances must be minimized to avoid the need for grinding operations. To find the best parameters for the press settings, which enable optimization, FEM calculations were used and different compaction models compared to give the best calculation/physical trial comparisons. These simulations were then used to predict the impact of different parameters when there is a change in the type of powder and the pellet size, or when the behavior of the press changes during the compaction time. In 2016, it is planned to set up the press in a glove box for UO2 manufacturing qualification based on our simulation methodology, before actual hot cell trials in the future.

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....

Grid computing in large pharmaceutical molecular modeling.

Science.gov (United States)

Claus, Brian L; Johnson, Stephen R

2008-07-01

Most major pharmaceutical companies have employed grid computing to expand their compute resources with the intention of minimizing additional financial expenditure. Historically, one of the issues restricting widespread utilization of the grid resources in molecular modeling is the limited set of suitable applications amenable to coarse-grained parallelization. Recent advances in grid infrastructure technology coupled with advances in application research and redesign will enable fine-grained parallel problems, such as quantum mechanics and molecular dynamics, which were previously inaccessible to the grid environment. This will enable new science as well as increase resource flexibility to load balance and schedule existing workloads.

Modeling of microwave heating of metallic powders

International Nuclear Information System (INIS)

Buchelnikov, V.D.; Louzguine-Luzgin, D.V.; Anzulevich, A.P.; Bychkov, I.V.; Yoshikawa, N.; Sato, M.; Inoue, A.

2008-01-01

As it is known from the experiment that bulk metallic samples reflect microwaves while powdered samples can absorb such a radiation and be heated efficiently. In the present paper we investigate theoretically the mechanisms of penetration of a layer of metallic powder by microwave radiation and microwave heating of such a system

Introducing a novel gravitation-based high-velocity compaction analysis method for pharmaceutical powders.

Science.gov (United States)

Tanner, Timo; Antikainen, Osmo; Ehlers, Henrik; Yliruusi, Jouko

2017-06-30

With modern tableting machines large amounts of tablets are produced with high output. Consequently, methods to examine powder compression in a high-velocity setting are in demand. In the present study, a novel gravitation-based method was developed to examine powder compression. A steel bar is dropped on a punch to compress microcrystalline cellulose and starch samples inside the die. The distance of the bar is being read by a high-accuracy laser displacement sensor which provides a reliable distance-time plot for the bar movement. In-die height and density of the compact can be seen directly from this data, which can be examined further to obtain information on velocity, acceleration and energy distribution during compression. The energy consumed in compact formation could also be seen. Despite the high vertical compression speed, the method was proven to be cost-efficient, accurate and reproducible. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Effect of pulverization of the bulk powder on the hydration of creatine anhydrate tablets and their pharmaceutical properties.

Science.gov (United States)

Sakata, Yukoh; Shiraishi, Sumihiro; Otsuka, Makoto

2005-12-10

The hydration behavior and expansion properties of untreated and pulverized creatine anhydrate (CRA) tablets were studied under 60 and 75%RH at 25 degrees C by using differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD). The tablet hardness of untreated and pulverized CRA tablets was significantly decreased after hydration. There was a linear relationship between the degree of hydration and the tablet hardness of untreated CRA tablets compressed at 1000 kg/cm2. In contrast, the relationship between the degree of hydration and the tablet hardness of pulverized CRA tablets was nonlinear. These results suggest that the reduction in hardness of pulverized CRA tablets does not depend solely on the hydration level of crystal water. PXRD analysis indicated that the diffraction pattern of the pulverized CRA powder was similar to that of the untreated CRA powder. However, the diffraction intensity of the pulverized CRA powder was slightly lower than that of the untreated CRA powder at high angle. The micropore radius of both untreated and pulverized CRA tablets was significantly increased after hydration, but analysis of the relationship between micropore radius and fractional hydration of crystal water showed that untreated CRA tablets were more affected than pulverized CRA tablets. Therefore, the reduction in tablet hardness depends not only on the hydration behavior but also on the crystal orientation of the CRA powder.

Diffusion and Swelling Measurements in Pharmaceutical Powder Compacts Using Terahertz Pulsed Imaging

Science.gov (United States)

Yassin, Samy; Su, Ke; Lin, Hungyen; Gladden, Lynn F; Zeitler, J Axel

2015-01-01

Tablet dissolution is strongly affected by swelling and solvent penetration into its matrix. A terahertz-pulsed imaging (TPI) technique, in reflection mode, is introduced as a new tool to measure one-dimensional swelling and solvent ingress in flat-faced pharmaceutical compacts exposed to dissolution medium from one face of the tablet. The technique was demonstrated on three tableting excipients: hydroxypropylmethyl cellulose (HPMC), Eudragit RSPO, and lactose. Upon contact with water, HPMC initially shrinks to up to 13% of its original thickness before undergoing expansion. HPMC and lactose were shown to expand to up to 20% and 47% of their original size in 24 h and 13 min, respectively, whereas Eudragit does not undergo dimensional change. The TPI technique was used to measure the ingress of water into HPMC tablets over a period of 24 h and it was observed that water penetrates into the tablet by anomalous diffusion. X-ray microtomography was used to measure tablet porosity alongside helium pycnometry and was linked to the results obtained by TPI. Our results highlight a new application area of TPI in the pharmaceutical sciences that could be of interest in the development and quality testing of advanced drug delivery systems as well as immediate release formulations. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:1658–1667, 2015 PMID:25645509

Pharmaceuticals as emerging contaminants and their removal from water. A review.

Science.gov (United States)

Rivera-Utrilla, José; Sánchez-Polo, Manuel; Ferro-García, María Ángeles; Prados-Joya, Gonzalo; Ocampo-Pérez, Raúl

2013-10-01

The main objective of this study was to conduct an exhaustive review of the literature on the presence of pharmaceutical-derived compounds in water and on their removal. The most representative pharmaceutical families found in water were described and related water pollution issues were analyzed. The performances of different water treatment systems in the removal of pharmaceuticals were also summarized. The water treatment technologies were those based on conventional systems (chlorine, chlorine dioxide, wastewater treatment plants), adsorption/bioadsorption on activated carbon (from lotus stalks, olive-waste cake, coal, wood, plastic waste, cork powder waste, peach stones, coconut shell, rice husk), and advanced oxidation processes by means of ozonation (O₃, O₃/H₂O₂, O₃/activated carbon, O₃/biological treatment), photooxidation (UV, UV/H₂O₂, UV/K₂S₂O₈, UV/TiO₂, UV/H₂O₂/TiO₂, UV/TiO₂/activated carbon, photo-Fenton), radiolysis (e-Beam, ⁶⁰Co, ¹³⁷Cs. Additives used: H₂O₂, SO₃²⁻, HCO₃⁻, CH₃₋OH, CO₃²⁻, or NO₃⁻), and electrochemical processes (Electrooxidation without and with active chlorine generation). The effect of these treatments on pharmaceutical compounds and the advantages and disadvantages of different methodologies used were described. The most important parameters of the above water treatment systems (experimental conditions, removal yield, pharmaceutical compound mineralization, TOC removal, toxicity evolution) were indicated. The key publications on pharmaceutical removal from water were summarized. Copyright © 2013 Elsevier Ltd. All rights reserved.

A Simple Model of Pharmaceutical Price Dynamics

OpenAIRE

Bhattacharya, Jayanta; Vogt, William B

2003-01-01

Branded pharmaceutical firms use price and promotional strategy to manage public knowledge about their drugs. We propose a dynamic theory of pharmaceutical pricing and conduct an exploratory empirical analysis inspired by the theory. Our theory predicts a pattern of increasing prices and decreasing promotional activities over a drug's life cycle. Prices are kept low and advertising levels high early in the life cycle in order to build public knowledge about the drug. As knowledge grows, price...

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. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

EU pharmaceutical expenditure forecast.

Science.gov (United States)

Urbinati, Duccio; Rémuzat, Cécile; Kornfeld, Åsa; Vataire, Anne-Lise; Cetinsoy, Laurent; Aballéa, Samuel; Mzoughi, Olfa; Toumi, Mondher

2014-01-01

With constant incentives for healthcare payers to contain their pharmaceutical budgets, forecasting has become critically important. Some countries have, for instance, developed pharmaceutical horizon scanning units. The objective of this project was to build a model to assess the net effect of the entrance of new patented medicinal products versus medicinal products going off-patent, with a defined forecast horizon, on selected European Union (EU) Member States' pharmaceutical budgets. This model took into account population ageing, as well as current and future country-specific pricing, reimbursement, and market access policies (the project was performed for the European Commission; see http://ec.europa.eu/health/healthcare/key_documents/index_en.htm). In order to have a representative heterogeneity of EU Member States, the following countries were selected for the analysis: France, Germany, Greece, Hungary, Poland, Portugal, and the United Kingdom. A forecasting period of 5 years (2012-2016) was chosen to assess the net pharmaceutical budget impact. A model for generics and biosimilars was developed for each country. The model estimated a separate and combined effect of the direct and indirect impacts of the patent cliff. A second model, estimating the sales development and the risk of development failure, was developed for new drugs. New drugs were reviewed individually to assess their clinical potential and translate it into commercial potential. The forecast was carried out according to three perspectives (healthcare public payer, society, and manufacturer), and several types of distribution chains (retail, hospital, and combined retail and hospital). Probabilistic and deterministic sensitivity analyses were carried out. According to the model, all countries experienced drug budget reductions except Poland (+€41 million). Savings were expected to be the highest in the United Kingdom (-€9,367 million), France (-€5,589 million), and, far behind them

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.

Rapid quantitation of atorvastatin in process pharmaceutical powder sample using Raman spectroscopy and evaluation of parameters related to accuracy of analysis

Science.gov (United States)

Lim, Young-Il; Han, Janghee; Woo, Young-Ah; Kim, Jaejin; Kang, Myung Joo

2018-07-01

The purpose of this study was to determine the atorvastatin (ATV) content in process pharmaceutical powder sample using Raman spectroscopy. To establish the analysis method, the influence of the type of Raman measurements (back-scattering or transmission mode), preparation of calibration sample (simple admixing or granulation), sample pre-treatment (pelletization), and spectral pretreatment on the Raman spectra was investigated. The characteristic peak of the active compound was more distinctively detected in transmission Raman mode with a laser spot size of 4 mm than in the back-scattering method. Preparation of calibration samples by wet granulation, identical to the actual manufacturing process, provided unchanged spectral patterns for the in process sample, with no changes and/or shifts in the spectrum. Pelletization before Raman analysis remarkably improved spectral reproducibility by decreasing the difference in density between the samples. Probabilistic quotient normalization led to accurate and consistent quantification of the ATV content in the calibration samples (standard error of cross validation: 1.21%). Moreover, the drug content in the granules obtained from five commercial batches were reliably quantified, with no statistical difference (p = 0.09) with that obtained by HPLC assay. From these findings, we suggest that transmission Raman analysis may be a fast and non-invasive method for the quantification of ATV in actual manufacturing processes.

Electrical conductivity of metal powders under pressure

Science.gov (United States)

Montes, J. M.; Cuevas, F. G.; Cintas, J.; Urban, P.

2011-12-01

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.

Analysis of Pharmaceutical Excipient MCC Avicel PH102 Using Compaction Equations

Directory of Open Access Journals (Sweden)

Peciar Peter

2016-07-01

Full Text Available This paper focuses on the characterization of the tabletting process and analysis one of the most common pharmaceutical excipients MCC Avicel PH102 by Heckel, Kawakita, Cooper-Eaton and Adams compaction equations. Experimental material was determined by measuring its parameters as particle size distribution, angle of wall friction and flow properties and for more detailed characteristics of the material particles, microscopy images of the powder before and after compressing were created.

Evaluation of drug-carrier interactions in quaternary powder mixtures containing perindopril tert-butylamine and indapamide.

Science.gov (United States)

Voelkel, Adam; Milczewska, Kasylda; Teżyk, Michał; Milanowski, Bartłomiej; Lulek, Janina

2016-04-30

Interactions occurring between components in the quaternary powder mixtures consisting of perindopril tert-butylamine, indapamide (active pharmaceutical ingredients), carrier substance and hydrophobic colloidal silica were examined. Two grades of lactose monohydrate: Spherolac(®) 100 and Granulac(®) 200 and two types of microcrystalline cellulose: M101D+ and Vivapur(®) 102 were used as carriers. We determined the size distribution (laser diffraction method), morphology (scanning electron microscopy) and a specific surface area of the powder particles (by nitrogen adsorption-desorption). For the determination of the surface energy of powder mixtures the method of inverse gas chromatography was applied. Investigated mixtures were characterized by surface parameters (dispersive component of surface energy, specific interactions parameters, specific surface area), work of adhesion and cohesion as well as Flory-Huggins parameter χ23('). Results obtained for all quaternary powder mixtures indicate existence of interactions between components. The strongest interactions occur for both blends with different types of microcrystalline cellulose (PM-1 and PM-4) while much weaker ones for powder mixtures with various types of lactose (PM-2 and PM-3). Published by Elsevier B.V.

Nonlinear Optical Imaging for Sensitive Detection of Crystals in Bulk Amorphous Powders

OpenAIRE

KESTUR, UMESH S.; WANAPUN, DUANGPORN; TOTH, SCOTT J.; WEGIEL, LINDSAY A.; SIMPSON, GARTH J.; TAYLOR, LYNNE S.

2012-01-01

The primary aim of this study was to evaluate the utility of second-order nonlinear imaging of chiral crystals (SONICC) to quantify crystallinity in drug–polymer blends, including solid dispersions. Second harmonic generation (SHG) can potentially exhibit scaling with crystallinity between linear and quadratic depending on the nature of the source, and thus, it is important to determine the response of pharmaceutical powders. Physical mixtures containing different proportions of crystalline n...

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.

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.

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.

Advances in beryllium powder consolidation simulations

International Nuclear Information System (INIS)

Reardon, B.J.

1998-01-01

A fuzzy logic based multiobjective genetic algorithm (GA) is introduced and the algorithm is used to optimize micromechanical densification modeling parameters for warm isopressed beryllium powder, HIPed copper powder and CIPed/sintered and HIPed tantalum powder. In addition to optimizing the main model parameters using the experimental data points as objective functions, the GA provides a quantitative measure of the sensitivity of the model to each parameter, estimates the mean particle size of the powder, and determines the smoothing factors for the transition between stage 1 and stage 2 densification. While the GA does not provide a sensitivity analysis in the strictest sense, and is highly stochastic in nature, this method is reliable and reproducible in optimizing parameters given any size data set and determining the impact on the model of slight variations in each parameter

Performance of Dry Powder Inhalers with Single Dosed Capsules in Preschool Children and Adults Using Improved Upper Airway Models

Directory of Open Access Journals (Sweden)

Sandra Lindert

2014-02-01

Full Text Available The pulmonary administration of pharmaceutical aerosols to patients is affected by age-dependent variations in the anatomy of the upper airways and the inhalation pattern. Considering this aspect, different upper airway models, representing the geometries of adults and preschool children, and a conventional induction port according to the European Pharmacopeia were used for in vitro testing of dry powder inhalers with single dosed capsules (Cyclohaler®, Handihaler® and Spinhaler®. Deposition measurements were performed using steady flow rates of 30 and 60 L/min for the Handihaler®/Spinhaler® and 30, 60 and 75 L/min for the Cyclohaler®. The inhalation volume was set at 1 L. For the Cyclohaler®, the in vitro testing was supplemented by a pediatric inhalation profile. Slight differences of pulmonary deposition between the idealized adult (11%–15% and pediatric (9%–11% upper airway model were observed for the Cyclohaler®. The applied pediatric inhalation profile resulted in a reduction of pulmonary deposition by 5% compared to steady conditions and indicated the influence of the inhalation pattern on the amount of pulmonary deposited particles. The comparison of two pediatric upper airway models showed no differences. The performance of the Handihaler® was similar to the Cyclohaler®. The Spinhaler® showed an insufficient performance and limited reproducibility in our investigations.

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.

An experimental evaluation of powder flow predictions in small-scale process equipment based on Jenike's hopper design methodology

DEFF Research Database (Denmark)

Søgaard, Søren Vinter; Olesen, Niels Erik; Hirschberg, Cosima

2017-01-01

. The comparison of the observed and predicted critical outlet diameters showed good agreement for the powder with the best flowability when linear extrapolation of the flow function was applied. In contrast, the predicted critical outlet diameter was slightly overestimated compared to the experimentally observed...... diameter for the two more cohesive powders. A likely reason for this overestimation is that the flow function probably has a non-linear convex upward shape for these two powders at very small consolidation stresses. These findings illustrate the relevance of measuring shear and wall shear stresses at very...... small consolidation stresses to improve the flow behavior predictions for small-scale process equipment typically used during production of solid state pharmaceuticals....

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.

Shock compaction of molybdenum powder

Science.gov (United States)

Ahrens, T. J.; Kostka, D.; Vreeland, T., Jr.; Schwarz, R. B.; Kasiraj, P.

1983-01-01

Shock recovery experiments which were carried out in the 9 to 12 GPa range on 1.4 distension Mo and appear adequate to compact to full density ( 45 (SIGMA)m) powders were examined. The stress levels, however, are below those calculated to be from 100 to approx. 22 GPa which a frictional heating model predicts are required to consolidate approx. 10 to 50 (SIGMA)m particles. The model predicts that powders that have a distension of m=1.6 shock pressures of 14 to 72 GPa are required to consolidate Mo powders in the 50 to 10 (SIGMA)m range.

The validation of the analytical method (HPLC, use for identification and assay of the pharmaceutical active ingredient, colistine sulphate and the finished product Colidem 50 – hydrosoluble powder, in SC DELOS impex ‘96 SRL

Directory of Open Access Journals (Sweden)

Maria Neagu,

2011-06-01

Full Text Available In SC DELOS IMPEX ’96 SRL the quality of the active pharmaceutical ingredient (API for the finished product Colidem 50 - hydrosoluble powder is make according to European Pharmacopoeia, curent edition. The method for analysis use in this purpose is the compendial method „Colistine sulphate” in E.P. in current edition and represent a optimized variant, developed and validated „in house”.The parameters which was included in the methodology validation for chromatographic method are the follow: Selectivity/Specificity, Linearity, Range of Linearity, Limit of Detection and Limit of Quantification, Precision (Repeatability - intra day, inter-Day Reproducibility, Accuracy, Robustness, Stability Solutions and System Suitability.

Changing R&D models in research-based pharmaceutical companies

OpenAIRE

Schuhmacher, Alexander; Gassmann, Oliver; Hinder, Markus

2016-01-01

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 re...

Analysis of the domestic pharmaceutical market drugs for the treatment of urolithiasis

Directory of Open Access Journals (Sweden)

V. L. Shevina

2014-12-01

was to identify the value of drugs. In the market of Ukraine manufacturers mainly offer the medicines of natural origin, which is 66.66%. For further study of this segment, the products were subject to analysis regarding their pharmaceutical form. The studies have revealed that in the pharmaceutical market of Ukraine the drugs are presented in the following pharmaceutical forms: tablets - 32%, capsules - 11 %, syrups - 16 %, drops - 17 %, gel, powders, granules and teas - 6 % of each. Thus, the most common dosage form is tablets. It is worth mentioning that to date, in the pharmaceutical market of Ukraine the main portfolio of the medicinal products in tablets is compiled by the medicinal products of foreign origin. The share of registered medicinal products in tablets manufactured by Ukrainian manufacturers versus imported medicines is 33.33 % to 66.66 %. However, only one domestic manufacturer present in the market produces the tablets of plant crude: knotweed extract powder, St. John's wort extract powder, horsetail extract dry, avisan. Conclusions The study of the market of medicinal products used for treatment of urolithiasis approved in Ukraine has been performed. It has been established that the pharmaceutical market of Ukraine presents 21 trade names of drugs used to treat urolithiasis. Preparations are analyzed depending on the origin and content of active components, presentation, type of dosage form. Based on the marketing analysis, it has been established that regardless of the general quantity of medicines of plant origin, in the study group the share of herbal medicines in tablets is insignificant (1 manufacturer. The feasibility of study regarding the development of products of plant origin in tablets for treatment of urolithiasis has been confirmed.

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. FIGURE 1: Correlation coefficient vs Rank plot FIGURE 2: FT-NIR spectra of different steps of Blend and final blend FIGURE 3: Predictions ability of PCR FIGURE 4: Blend uniformity predication ability of PLS2 FIGURE 5: Prediction efficiency of blend uniformity using ANN FIGURE 6: Comparison of prediction efficiency of chemometric models TABLE 1: Order of Addition for Blending Steps

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

International Nuclear Information System (INIS)

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

2013-01-01

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)×10 9 , (1.07±0.07)×10 10 , (7.48±0.17)×10 9 , (7.31±0.29)×10 9 , (5.47±0.25)×10 9 , (6.94±0.10)×10 9 (M −1 s −1 ), respectively. The hydrated electron reaction rate constants were measured (3.02±0.10)×10 9 , (8.98±0.27)×10 9 , (5.39±0.21)×10 9 , (4.33±0.17)×10 9 , (4.72±0.15)×10 9 , (1.42±0.02)×10 9 (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. - Highlights: • Free radical chemistry of salicylic and 4 methyl salicylic acids is investigated. • The transient absorptions spectra for model compounds are measured. • Absolute bimolecular reaction rate constants for hydroxyl radical are determined. • Solvated electron reaction rate constants are calculated. • The use of salicylic acids as models for pharmaceuticals is explored

Thermodynamic model of the compaction of powder materials by shock waves

NARCIS (Netherlands)

Dijken, Durandus; Hosson, J.Th.M. De

1994-01-01

For powder materials a model is proposed to predict the mean temperature behind the shock wave, the ratio between the increase of thermal energy and increase of total internal energy, as well as the mean final temperature after release of adiabatic pressure. Further, the change of pressure, specific

Rapid quantitation of atorvastatin in process pharmaceutical powder sample using Raman spectroscopy and evaluation of parameters related to accuracy of analysis.

Science.gov (United States)

Lim, Young-Il; Han, Janghee; Woo, Young-Ah; Kim, Jaejin; Kang, Myung Joo

2018-07-05

The purpose of this study was to determine the atorvastatin (ATV) content in process pharmaceutical powder sample using Raman spectroscopy. To establish the analysis method, the influence of the type of Raman measurements (back-scattering or transmission mode), preparation of calibration sample (simple admixing or granulation), sample pre-treatment (pelletization), and spectral pretreatment on the Raman spectra was investigated. The characteristic peak of the active compound was more distinctively detected in transmission Raman mode with a laser spot size of 4mm than in the back-scattering method. Preparation of calibration samples by wet granulation, identical to the actual manufacturing process, provided unchanged spectral patterns for the in process sample, with no changes and/or shifts in the spectrum. Pelletization before Raman analysis remarkably improved spectral reproducibility by decreasing the difference in density between the samples. Probabilistic quotient normalization led to accurate and consistent quantification of the ATV content in the calibration samples (standard error of cross validation: 1.21%). Moreover, the drug content in the granules obtained from five commercial batches were reliably quantified, with no statistical difference (p=0.09) with that obtained by HPLC assay. From these findings, we suggest that transmission Raman analysis may be a fast and non-invasive method for the quantification of ATV in actual manufacturing processes. Copyright © 2018 Elsevier B.V. All rights reserved.

EU pharmaceutical expenditure forecast

OpenAIRE

Urbinati, Duccio; Rémuzat, Cécile; Kornfeld, Åsa; Vataire, Anne-Lise; Cetinsoy, Laurent; Aballéa, Samuel; Mzoughi, Olfa; Toumi, Mondher

2014-01-01

Background and Objectives: With constant incentives for healthcare payers to contain their pharmaceutical budgets, forecasting has become critically important. Some countries have, for instance, developed pharmaceutical horizon scanning units. The objective of this project was to build a model to assess the net effect of the entrance of new patented medicinal products versus medicinal products going off-patent, with a defined forecast horizon, on selected European Union (EU) Member States’ ph...

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...... provides significantly better control of the residual moisture content, increases the throughput and decreases the energy consumption compared to conventional PI-control. The MPC operates the spray dryer closer to the residual moisture constraint of the powder product. Thus, the same amount of feed...

Integrated DEM-CFD modeling of the contact charging of pneumatically conveyed powders

NARCIS (Netherlands)

Korevaar, M.W.; Padding, J.T.; Hoef, van der M.A.; Kuipers, J.A.M.

2014-01-01

A model is proposed that incorporates contact charging (also known as triboelectric charging) of pneumatically conveyed powders in a DEM–CFD framework, which accounts for the electrostatic interactions, both between particles and between the particles and conducting walls. The simulation results

Integrated DEM–CFD modeling of the contact charging of pneumatically conveyed powders

NARCIS (Netherlands)

Korevaar, M.W.; Padding, J.T.; van der Hoef, Martin Anton; Kuipers, J.A.M.

2014-01-01

A model is proposed that incorporates contact charging (also known as triboelectric charging) of pneumatically conveyed powders in a DEM–CFD framework, which accounts for the electrostatic interactions, both between particles and between the particles and conducting walls. The simulation results

Dry and coating of powders

International Nuclear Information System (INIS)

Alonso, M.; Alguacil, F. J.

1999-01-01

This paper presents a review on the mixing and coating of powders by dry processes. The reviews surveys fundamental works on mixture characterization (mixing index definitions and sampling techniques), mixing mechanisms and models, segregation with especial emphasis on free-surface segregation, mixing of cohesive powders and interparticle forces, ordered mixing (dry coating) including mechanism, model and applications and mixing equipment selection. (Author) 180 refs

Nanotechnology tools in pharmaceutical R&D

OpenAIRE

Challa S.S.R. Kumar

2010-01-01

Nanotechnology is a new approach to problem solving and can be considered as a collection of tools and ideas which can be applied in pharmaceutical industry. Application of nanotechnology tools in pharmaceutical R&D is likely to result in moving the industry from ‘blockbuster drug’ model to ‘personalized medicine’. There are compelling applications in pharmaceutical industry where inexpensive nanotechnology tools can be utilized. The review explores the possibility of categorizing various nan...

Understanding deformation mechanisms during powder compaction using principal component analysis of compression data.

Science.gov (United States)

Roopwani, Rahul; Buckner, Ira S

2011-10-14

Principal component analysis (PCA) was applied to pharmaceutical powder compaction. A solid fraction parameter (SF(c/d)) and a mechanical work parameter (W(c/d)) representing irreversible compression behavior were determined as functions of applied load. Multivariate analysis of the compression data was carried out using PCA. The first principal component (PC1) showed loadings for the solid fraction and work values that agreed with changes in the relative significance of plastic deformation to consolidation at different pressures. The PC1 scores showed the same rank order as the relative plasticity ranking derived from the literature for common pharmaceutical materials. The utility of PC1 in understanding deformation was extended to binary mixtures using a subset of the original materials. Combinations of brittle and plastic materials were characterized using the PCA method. The relationships between PC1 scores and the weight fractions of the mixtures were typically linear showing ideal mixing in their deformation behaviors. The mixture consisting of two plastic materials was the only combination to show a consistent positive deviation from ideality. The application of PCA to solid fraction and mechanical work data appears to be an effective means of predicting deformation behavior during compaction of simple powder mixtures. Copyright © 2011 Elsevier B.V. All rights reserved.

Characterization of polymorphic solid-state changes using variable temperature X-ray powder diffraction

DEFF Research Database (Denmark)

Karjalainen, Milja; Airaksinen, Sari; Rantanen, Jukka

2005-01-01

The aim of this study was to use variable temperature X-ray powder diffraction (VT-XRPD) to understand the solid-state changes in the pharmaceutical materials during heating. The model compounds studied were sulfathiazole, theophylline and nitrofurantoin. This study showed that the polymorph form...... of sulfathiazole SUTHAZ01 was very stable and SUTHAZ02 changed as a function of temperature to SUTHAZ01. Theophylline monohydrate changed via its metastable form to its anhydrous form during heating and nitrofurantoin monohydrate changed via amorphous form to its anhydrous form during heating. The crystallinity...... to the anhydrous form. The average crystallite size of sulfathiazole samples varied only a little during heating. The average crystallite size of both theophylline and nitrofurantoin monohydrate decreased during heating. However, the average crystallite size of nitrofurantoin monohydrate returned back to starting...

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

Real-time measurement of dust in the workplace using video exposure monitoring: Farming to pharmaceuticals

International Nuclear Information System (INIS)

Walsh, P T; Forth, A R; Clark, R D R; Dowker, K P; Thorpe, A

2009-01-01

Real-time, photometric, portable dust monitors have been employed for video exposure monitoring (VEM) to measure and highlight dust levels generated by work activities, illustrate dust control techniques, and demonstrate good practice. Two workplaces, presenting different challenges for measurement, were used to illustrate the capabilities of VEM: (a) poultry farming activities and (b) powder transfer operations in a pharmaceutical company. For the poultry farm work, the real-time monitors were calibrated with respect to the respirable and inhalable dust concentrations using cyclone and IOM reference samplers respectively. Different rankings of exposure for typical activities were found on the small farm studied here compared to previous exposure measurements at larger poultry farms: these were mainly attributed to the different scales of operation. Large variations in the ratios of respirable, inhalable and real-time monitor TWA concentrations of poultry farm dust for various activities were found. This has implications for the calibration of light-scattering dust monitors with respect to inhalable dust concentration. In the pharmaceutical application, the effectiveness of a curtain barrier for dust control when dispensing powder in a downflow booth was rapidly demonstrated.

Deflagration to Detonation Transition (DDT) Simulations of HMX Powder Using the HERMES Model

Science.gov (United States)

White, Bradley; Reaugh, John; Tringe, Joseph

2017-06-01

We performed computer simulations of DDT experiments with Class I HMX powder using the HERMES model (High Explosive Response to MEchanical Stimulus) in ALE3D. Parameters for the model were fitted to the limited available mechanical property data of the low-density powder, and to the Shock to Detonation Transition (SDT) test results. The DDT tests were carried out in steel-capped polycarbonate tubes. This arrangement permits direct observation of the event using both flash X-ray radiography and high speed camera imaging, and provides a stringent test of the model. We found the calculated detonation transition to be qualitatively similar to experiment. Through simulation we also explored the effects of confinement strength, the HMX particle size distribution and porosity on the computed detonation transition location. This work was performed under the auspices of the US DOE by LLNL under Contract DE-AC52-07NA27344.

Inverse mathematical modelling and identification in metal powder compaction process

International Nuclear Information System (INIS)

Gakwaya, A.; Hrairi, M.; Guillot, M.

2000-01-01

An online assessment of the quality of advanced integrated computer aided manufacturing systems require the knowledge of accurate and reliable non-linear constitutive material behavior. This paper is concerned with material parameter identification based on experimental data for which non uniform distribution of stresses and deformation within the volume of the specimen is considered. Both geometric and material non linearities as well interfacial frictional contact are taken into account during the simulation. Within the framework of finite deformation theory, a multisurface multiplicative plasticity model for metal powder compaction process is presented. The model is seen to involve several parameters which are not always activated by a single state variable even though it may be technologically important in assessing the final product quality and manufacturing performance. The resulting expressions are presented in spatial setting and gradient based descent method utilizing the modified Levenberg-Marquardt scheme is used for the minimization of least square functional so as to obtain the best agreement between relevant experimental data and simulated data in a specified energy norm. The identification of a subset of material parameters of the cap model for stainless steel powder compaction is performed. The obtained parameters are validated through a simulation of an industrial part manufacturing case. A very good agreement between simulated final density and measured density is obtained thus demonstrating the practical usefulness of the proposed approach. (author)

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.

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...

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

International Nuclear Information System (INIS)

Zukowska, Barbara; Breivik, Knut; Wania, Frank

2006-01-01

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

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.

Predictive modeling capabilities from incident powder and laser to mechanical properties for laser directed energy deposition

Science.gov (United States)

Shin, Yung C.; Bailey, Neil; Katinas, Christopher; Tan, Wenda

2018-01-01

This paper presents an overview of vertically integrated comprehensive predictive modeling capabilities for directed energy deposition processes, which have been developed at Purdue University. The overall predictive models consist of vertically integrated several modules, including powder flow model, molten pool model, microstructure prediction model and residual stress model, which can be used for predicting mechanical properties of additively manufactured parts by directed energy deposition processes with blown powder as well as other additive manufacturing processes. Critical governing equations of each model and how various modules are connected are illustrated. Various illustrative results along with corresponding experimental validation results are presented to illustrate the capabilities and fidelity of the models. The good correlations with experimental results prove the integrated models can be used to design the metal additive manufacturing processes and predict the resultant microstructure and mechanical properties.

Predictive modeling capabilities from incident powder and laser to mechanical properties for laser directed energy deposition

Science.gov (United States)

Shin, Yung C.; Bailey, Neil; Katinas, Christopher; Tan, Wenda

2018-05-01

This paper presents an overview of vertically integrated comprehensive predictive modeling capabilities for directed energy deposition processes, which have been developed at Purdue University. The overall predictive models consist of vertically integrated several modules, including powder flow model, molten pool model, microstructure prediction model and residual stress model, which can be used for predicting mechanical properties of additively manufactured parts by directed energy deposition processes with blown powder as well as other additive manufacturing processes. Critical governing equations of each model and how various modules are connected are illustrated. Various illustrative results along with corresponding experimental validation results are presented to illustrate the capabilities and fidelity of the models. The good correlations with experimental results prove the integrated models can be used to design the metal additive manufacturing processes and predict the resultant microstructure and mechanical properties.

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

Science.gov (United States)

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

2012-01-23

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. Achieving sufficient blend uniformity requires that the blending conditions are able to break up agglomerates, which is often an abrasion process. This study was based on the assumption that the abrasion rate of agglomerates determines the required blending time. It is shown that the kinetic energy density of the moving powder bed is a relevant parameter which correlates with the abrasion rate of agglomerates. However, aspects related to the strength of agglomerates should also be considered. For this reason the Stokes abrasion number (St(Abr)) has been defined. This parameter describes the ratio between the kinetic energy density of the moving powder bed and the work of fracture of the agglomerate. The St(Abr) number is shown to predict the abrasion potential of agglomerates in the dry-mixing process. It appeared possible to include effects of filler particle size and impeller rotational rate into this concept. A clear relationship between abrasion rate of agglomerates and the value of St(Abr) was demonstrated. Copyright © 2011 Elsevier B.V. All rights reserved.

Specificity of HPLC to assess the chemical stability based on partenine from Parthenium hysterophorus L. powdered dry foliage (escoba amarga)

International Nuclear Information System (INIS)

Saucedo Hernandez, Yanelis; Mohamad Safa, Bassam; Gonzalez Bedia, Mirtha Mayra

2010-01-01

It is required a specific analysis technique allowing the follow-up to stability study intrinsic of Parthenium hysterophorus L. (escoba amarga) powdered dry foliage to achieve in a pharmaceutical way a antiparasitic usefulness with the quality, safety and effectiveness demanded requirements. High performance liquid chromatography was applied to P. hysterophorus degraded samples under degradation conditions in an oxidative, basic and acid medium. The analysis technique specificity was assessed to detect the interest component without interferences of its degradation products and its possible usefulness in studies on solid stability in the plant powder

A material-sparing method for simultaneous determination of true density and powder compaction properties--aspartame as an example.

Science.gov (United States)

Sun, Changquan Calvin

2006-12-01

True density results for a batch of commercial aspartame are highly variable when helium pycnometry is used. Alternatively, the true density of the problematic aspartame lot was obtained by fitting tablet density versus pressure data. The fitted true density was in excellent agreement with that predicted from single crystal structure. Tablet porosity was calculated from the true density and tablet apparent density. After making the necessary measurements for calculating tablet apparent density, the breaking force of each intact tablet was measured and tensile strength was calculated. With the knowledge of compaction pressure, tablet porosity and tensile strength, powder compaction properties were characterized using tabletability (tensile strength versus pressure), compactibility (tensile strength versus porosity), compressibility (porosity versus pressure) and Heckel analysis. Thus, a wealth of additional information on the compaction properties of the powder was obtained through little added work. A total of approximately 4 g of powder was used in this study. Depending on the size of tablet tooling, tablet thickness and true density, 2-10 g of powder would be sufficient for characterizing most pharmaceutical powders.

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

Science.gov (United States)

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

2014-12-30

The purpose of this work was to develop stable xylitol particles with modified physical properties, improved compactibility and enhanced pharmaceutical performance without altering polymorphic form of xylitol. Xylitol was crystallized using antisolvent crystallization technique in the presence of various hydrophilic polymer additives, i.e., polyethylene glycol (PEG), polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA) at a range of concentrations. The crystallization process did not influence the stable polymorphic form or true density of xylitol. However, botryoidal-shaped crystallized xylitols demonstrated different particle morphologies and lower powder bulk and tap densities in comparison to subangular-shaped commercial xylitol. Xylitol crystallized without additive and xylitol crystallized in the presence of PVP or PVA demonstrated significant improvement in hardness of directly compressed tablets; however, such improvement was observed to lesser extent for xylitol crystallized in the presence of PEG. Crystallized xylitols produced enhanced dissolution profiles for indomethacin in comparison to original xylitol. The influence of additive concentration on tablet hardness was dependent on the type of additive, whereas an increased concentration of all additives provided an improvement in the dissolution behavior of indomethacin. Antisolvent crystallization using judiciously selected type and concentration of additive can be a potential approach to prepare xylitol powders with promising physicomechanical and pharmaceutical properties. Copyright © 2014 Elsevier B.V. All rights reserved.

Photoluminescence of crystalline and disordered BTO:Mn powder: Experimental and theoretical modeling

International Nuclear Information System (INIS)

Gurgel, M.F.C.; Espinosa, J.W.M.; Campos, A.B.; Rosa, I.L.V.; Joya, M.R.; Souza, A.G.; Zaghete, M.A.; Pizani, P.S.; Leite, E.R.; Varela, J.A.; Longo, E.

2007-01-01

Disordered and crystalline Mn-doped BaTiO 3 (BTO:Mn) powders were synthesized by the polymeric precursor method. After heat treatment, the nature of visible photoluminescence (PL) at room temperature in amorphous BTO:Mn was discussed, considering results of experimental and theoretical studies. X-ray diffraction (XRD), PL, and UV-vis were used to characterize this material. Rietveld refinement of the BTO:Mn from XRD data was used to built two models, which represent the crystalline BTO:Mn (BTO:Mn c ) and disordered BTO:Mn (BTO:Mn d ) structures. Theses models were analyzed by the periodic ab initio quantum mechanical calculations using the CRYSTAL98 package within the framework of density functional theory at the B3LYP level. The experimental and theoretical results indicated that PL is related with the degree of disorder in the BTO:Mn powders and also suggests the presence of localized states in the disordered structure

Integrating systems Approaches into Pharmaceutical Sciences

DEFF Research Database (Denmark)

Westerhoff, H.V.; Mosekilde, Erik; Noe, C. R.

2008-01-01

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...... 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...... 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...

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.

Characteristics of Inconel Powders for Powder-Bed Additive Manufacturing

Directory of Open Access Journals (Sweden)

Quy Bau Nguyen

2017-10-01

Full Text Available In this study, the flow characteristics and behaviors of virgin and recycled Inconel powder for powder-bed additive manufacturing (AM were studied using different powder characterization techniques. The results revealed that the particle size distribution (PSD for the selective laser melting (SLM process is typically in the range from 15 μm to 63 μm. The flow rate of virgin Inconel powder is around 28 s·(50 g−1. In addition, the packing density was found to be 60%. The rheological test results indicate that the virgin powder has reasonably good flowability compared with the recycled powder. The inter-relation between the powder characteristics is discussed herein. A propeller was successfully printed using the powder. The results suggest that Inconel powder is suitable for AM and can be a good reference for researchers who attempt to produce AM powders.

Numerical algorithm for laser treatment of powder layer with variable thickness

Science.gov (United States)

Soboleva, Polina; Knyazeva, Anna

2017-12-01

Two-dimensional model of laser treatment of powder layer on the substrate is proposed in this paper. The model takes into account the shrinkage of powder layer due to the laser treatment. Three simplified variants of the model were studied. Firstly, the influence of optical properties of powder layer on the maximal temperature was researched. Secondly, two-dimensional model for given thickness of powder layer was studied where practically uniform temperature distribution across thin powder layer was demonstrated. Then, the numerical algorithm was developed to calculate the temperature field for the area of variable size. The impact of the optical properties of powder material on the character of the temperature distribution was researched numerically.

An Export-Marketing Model for Pharmaceutical Firms (The Case of Iran)

OpenAIRE

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 internationalizati...

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.

Modeling Li-ion conductivity in LiLa(PO3)4 powder

International Nuclear Information System (INIS)

Mounir, Ferhi; Karima, Horchani-Naifer; Khaled, Ben Saad; Mokhtar, Férid

2012-01-01

Polycrystalline powder and single-crystal of LiLa(PO 3 ) 4 are synthesized by solid state reaction and flux technique, respectively. A morphological description of the obtained product was made based on scanning electron microscopy micrographs. The obtained powder was characterized by X-ray powder diffraction, FTIR and Raman spectroscopies. Ionic conductivity of the LiLa(PO 3 ) 4 powder was measured and evaluated over a temperature range from 553 to 913 K. Single crystals of LiLa(PO 3 ) 4 are characterized by single-crystal X-ray diffraction. The LiLa(PO 3 ) 4 structure was found to be isotypic with LiNd(PO 3 ) 4 . It crystallizes in the monoclinic system with space group C2/c and cell parameters: a=16.635(6) Å, b=7.130(3) Å, c=9.913(3) Å, β=126.37(4)°, V=946.72(6) Å 3 and Z=4. The LiLa(PO 3 ) 4 structure was described as an alternation between spiraling chains (PO 3 ) n and (La 3+ , Li + ) cations along the b direction. The small Li + ions, coordinated to four oxygen atoms, were located in the large connected cavities created between the LaO 8 polyhedra and the polyphosphate chains. The jumping of Li + through tunnels of the crystalline network was investigated using complex impedance spectroscopy. The close value of the activation energies calculated through the analysis of conductivity data and loss spectra indicate that the transport in the investigated system is through hopping mechanism. The correlation between ionic conductivity of LiLa(PO 3 ) 4 and its crystallographic structure was investigated and the most probably transport pathway model was determined.

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,

Dry powder segregation and flowability: Experimental and numerical studies

Science.gov (United States)

Ely, David R.

Dry powder blending is a very important industrial and physical process used in the production of numerous pharmaceutical dosage forms such as tablets, capsules, and dry powder aerosols. Key aspects of this unit operation are process monitoring and control. Process control is particularly difficult due to the complexity of particle-particle interactions, which arise from the adhesion/cohesion characteristics of interfaces and morphological characteristics such as particle size, shape, and dispersity. The effects of such characteristics need to be understood in detail in order to correlate individual particle properties to bulk powder properties. The present dissertation numerically and experimentally quantifies the mixing process to rationalize particle-particle interactions. In particular, near infrared spectroscopy (NIRS) was used to non-invasively characterize in real-time the blending processes and thus investigate the dynamics of blending under different operating conditions. A novel image analysis technique was developed to quantify the scale of segregation from images obtained non-destructively via near infrared chemical imaging (NIR-CI). Although NIR-CI data acquisition times are too long for real-time data collection, NIR-CI has an advantage, in that it provides the spatial distribution of the drug. Therefore, NIRS and NIR-CI are complementary techniques for investigating the complex process of blending dry powders and assessing end-product quality. Additionally, the discrete element method was used to investigate the effect of powder cohesion on the packing fraction. Simulations indicated an exponential relationship between the random loose packing fraction and cohesive forces. Specifically, the packing fraction decreased asymptotically with increased ratio of cohesive force to particle weight. Thus, increasing this force ratio above a critical value has negligible impact on the packing fraction. Such result directly impacts the Hausner ratio flowability

Wuling powder prevents the depression-like behavior in learned helplessness mice model through improving the TSPO mediated-mitophagy.

Science.gov (United States)

Li, Dongmei; Zheng, Ji; Wang, Mingyang; Feng, Lu; Liu, Yanyong; Yang, Nan; Zuo, Pingping

2016-06-20

Wuling powder (trade name: Wuling capsule), a traditional Chinese medicine (TCM), was extracted from mycelia of precious Xylaria Nigripes (Kl.) Sacc by modern fermentation technology, and has been claimed to be fully potent in improving the signs of insomnia and cognitive deficits. Moreover, Wuling capsule was effective in treating post-stroke and orther co-cormbid depression both in clinical and in basic research. In order to clarify the molecular mechanisms of the antidepressant effect of Wuling powder, we established learned helplessness (LH) depression animal model and focused on 18kDa translocator protein (TSPO) mediated-mitophagy pathway. Mice were exposed to the inescapable e-shock (IS) once a day for three consecutive days to establish the LH model. Then mice were orally administered Wuling powder for 2 weeks. For the behavioral assessment, Shuttle box test, novelty suppressed feeding test (NSF) and forced swimming test (FST) were performed. Following the behavioral assessment, we assessed the protein expression level that were related to TSPO-mediated mitophagy signaling pathway by Western blotting analysis. Finally, immunohistochemistry method was used to assess the neuroprotective effects of Wuling powder. Compared with mice that were subjected to inescapable e-shock, Wuling powder exhibited antidepressant effect in the multiple behavioral tests. In addition, Wuling powder altered the expression level of multiple proteins related to TSPO-mediated mitophagy signaling pathway. Our results suggested that Wuling powder exhibited an obvious antidepressant effect, which could be due to the improvement of TSPO-mediated mitophagy signaling pathway. Copyright © 2016. Published by Elsevier Ireland Ltd.

The Pharmaceutical Industry Beamline of Pharmaceutical Consortium for Protein Structure Analysis

International Nuclear Information System (INIS)

Nishijima, Kazumi; Katsuya, Yoshio

2002-01-01

The Pharmaceutical Industry Beamline was constructed by the Pharmaceutical Consortium for Protein Structure Analysis which was established in April 2001. The consortium is composed of 22 pharmaceutical companies affiliating with the Japan Pharmaceutical Manufacturers Association. The beamline is the first exclusive on that is owned by pharmaceutical enterprises at SPring-8. The specification and equipments of the Pharmaceutical Industry Beamline is almost same as that of RIKEN Structural Genomics Beamline I and II. (author)

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

Science.gov (United States)

Candan, Gökçe; Yazgan, Harun Reşit

2016-02-24

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

A validated high performance thin layer chromatography method for determination of yohimbine hydrochloride in pharmaceutical preparations.

Science.gov (United States)

Badr, Jihan M

2013-01-01

Yohimbine is an indole alkaloid used as a promising therapy for erectile dysfunction. A number of methods were reported for the analysis of yohimbine in the bark or in pharmaceutical preparations. In the present work, a simple and sensitive high performance thin layer chromatographic method is developed for determination of yohimbine (occurring as yohimbine hydrochloride) in pharmaceutical preparations and validated according to International Conference of Harmonization (ICH) guidelines. The method employed thin layer chromatography aluminum sheets precoated with silica gel as the stationary phase and the mobile phase consisted of chloroform:methanol:ammonia (97:3:0.2), which gave compact bands of yohimbine hydrochloride. Linear regression data for the calibration curves of standard yohimbine hydrochloride showed a good linear relationship over a concentration range of 80-1000 ng/spot with respect to the area and correlation coefficient (R(2)) was 0.9965. The method was evaluated regarding accuracy, precision, selectivity, and robustness. Limits of detection and quantitation were recorded as 5 and 40 ng/spot, respectively. The proposed method efficiently separated yohimbine hydrochloride from other components even in complex mixture containing powdered plants. The amount of yohimbine hydrochloride ranged from 2.3 to 5.2 mg/tablet or capsule in preparations containing the pure alkaloid, while it varied from zero (0) to 1.5-1.8 mg/capsule in dietary supplements containing powdered yohimbe bark. We concluded that this method employing high performance thin layer chromatography (HPTLC) in quantitative determination of yohimbine hydrochloride in pharmaceutical preparations is efficient, simple, accurate, and validated.

Synthesis of Uranium nitride powders using metal uranium powders

International Nuclear Information System (INIS)

Yang, Jae Ho; Kim, Dong Joo; Oh, Jang Soo; Rhee, Young Woo; Kim, Jong Hun; Kim, Keon Sik

2012-01-01

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 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

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.

New Polymorphic Forms of Pemetrexed Diacid and Their Use for the Preparation of Pharmaceutically Pure Amorphous and Hemipentahydrate Forms of Pemetrexed Disodium

Directory of Open Access Journals (Sweden)

Olga Michalak

2015-07-01

Full Text Available The preparation of stable amorphous pemetrexed disodium of pharmaceutical purity as well as the process optimization for the preparation of the hemipentahydrate form of pemetrexed disodium are described. Analytical methods for the polymorphic and chemical purity studies of pemetrexed disodium and pemetrexed diacid forms were developed. The physicochemical properties of the amorphous and hydrate forms of pemetrexed disodium, as well as new forms of pemetrexed diacid (a key synthetic intermediate were studied by thermal analysis and powder X-ray diffraction. High-performance liquid chromatography and gas chromatography methods were used for the chemical purity and residual solvents determination. In order to study the polymorphic and chemical stability of the amorphous and hemipentahydrate forms, a hygroscopicity test (25 °C, 80% RH was performed. Powder diffraction and high-performance liquid chromatography analyses revealed that the amorphous character and high chemical purity were preserved after the hygroscopicity test. The hemipentahydrate form transformed completely to the heptahydrate form of pemetrexed disodium. Both pemetrexed disodium forms were produced with high efficiency and pharmaceutical purity in a small commercial scale. Amorphous pemetrexed disodium was selected for further pharmaceutical development. Two new polymorphs (forms 1 and 2 of pemetrexed diacid were used for the preparation of high purity amorphous pemetrexed disodium.

Comparison of preference and safety of powder and liquid lactulose in adult patients with chronic constipation

Directory of Open Access Journals (Sweden)

Charles F Barish

2010-10-01

Full Text Available Charles F Barish1, Bryan Voss2, Byron Kaelin21Wake Research Associates, Raleigh, North Carolina, USA; 2Cumberland Pharmaceuticals Inc., Nashville, Tennessee, USABackground: Chronic constipation is an important clinical condition which can result in serious discomfort and even require hospitalization. Powder and liquid lactulose are designated as clinically equivalent for the treatment of constipation, but there are significant differences in the taste, consistency, and portability of the products, which may affect patient compliance and therefore clinical outcome.Aim: To evaluate patient preference between powder and liquid lactulose in terms of overall preference, taste, consistency, and portability, and safety in terms of adverse events.Methods: Three sites randomized patients (total n = 50 to powder or liquid lactulose for seven days with crossover. Patient preference was assessed by a questionnaire, and the occurrence of adverse events was monitored.Results: Of those expressing a preference, 44% and 57% more patients preferred the taste and consistency, respectively, of powder over liquid lactulose. More than six times as many patients preferred the portability of powder compared with liquid lactulose and, overall, 77% more patients preferred powder over liquid lactulose. There was no difference between treatment groups in terms of adverse events (P = 0.635.Conclusions: More patients preferred powder compared with liquid lactulose and the products were equally safe. These findings may impact patient compliance, and therefore may affect clinical outcome.Keywords: constipation, lactulose, laxative

Preclinical Pharmacokinetic/Pharmacodynamic Modeling and Simulation in the Pharmaceutical Industry: An IQ Consortium Survey Examining the Current Landscape

OpenAIRE

Schuck, Edgar; Bohnert, Tonika; Chakravarty, Arijit; Damian-Iordache, Valeriu; Gibson, Christopher; Hsu, Cheng-Pang; Heimbach, Tycho; Krishnatry, Anu Shilpa; Liederer, Bianca M; Lin, Jing; Maurer, Tristan; Mettetal, Jerome T; Mudra, Daniel R; Nijsen, Marjoleen JMA; Raybon, Joseph

2015-01-01

The application of modeling and simulation techniques is increasingly common in preclinical stages of the drug discovery and development process. A survey focusing on preclinical pharmacokinetic/pharmacodynamics (PK/PD) analysis was conducted across pharmaceutical companies that are members of the International Consortium for Quality and Innovation in Pharmaceutical Development. Based on survey responses, ~68% of companies use preclinical PK/PD analysis in all therapeutic areas indicating its...

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

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.

Using peer teaching to introduce the Pharmaceutical Care Model to incoming pharmacy students.

Science.gov (United States)

Kolar, Claire; Hager, Keri; Janke, Kristin K

2018-02-01

The aim of this initiative was to design and evaluate a peer teaching activity where pairs of second-year pharmacy students introduced the Pharmaceutical Care Model and discussed success in the broader first-year pharmacy curriculum with pairs of first year students. Second-year pharmacy students individually created concept maps illustrating the main components of pharmaceutical care to be used as teaching tools with first-year students. First-year students were given a brief introduction to pharmaceutical care by faculty and prepared questions to ask their second-year colleagues. Two second-year students were then matched with two first-year students for a two-part peer teaching event. Each student completed documentation of the peer experience, which included questions about the effectiveness of the teaching, changes to be made in the future, and the usefulness of the exercise. The documentation was analyzed via content analysis and instructors evaluated the concept maps based on their effectiveness as a teaching tool for novices. A rubric was used to evaluate 166 concept maps of which 145 were rated good, 18 were rated as better, and 3 as best. Themes emerging from the content analysis included: positive impact of teaching and learning pharmaceutical care, value of broader curriculum discussion, and beneficial first- and second-year connections. A structured peer teaching event outside the traditional classroom setting can create a space for: teaching and learning to occur, student-student connections to be made, and advice on the curriculum to be shared. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of preference and safety of powder and liquid lactulose in adult patients with chronic constipation

OpenAIRE

Barish, Charles F; Voss, Bryan; Kaelin, Byron

2010-01-01

Charles F Barish1, Bryan Voss2, Byron Kaelin21Wake Research Associates, Raleigh, North Carolina, USA; 2Cumberland Pharmaceuticals Inc., Nashville, Tennessee, USABackground: Chronic constipation is an important clinical condition which can result in serious discomfort and even require hospitalization. Powder and liquid lactulose are designated as clinically equivalent for the treatment of constipation, but there are significant differences in the taste, consistency, and portability of the prod...

Three-dimensional printing in pharmaceutics: promises and problems.

Science.gov (United States)

Yu, Deng Guang; Zhu, Li-Min; Branford-White, Christopher J; Yang, Xiang Liang

2008-09-01

Three-dimensional printing (3DP) is a rapid prototyping (RP) technology. Prototyping involves constructing specific layers that uses powder processing and liquid binding materials. Reports in the literature have highlighted the many advantages of the 3DP system over other processes in enhancing pharmaceutical applications, these include new methods in design, development, manufacture, and commercialization of various types of solid dosage forms. For example, 3DP technology is flexible in that it can be used in applications linked to linear drug delivery systems (DDS), colon-targeted DDS, oral fast disintegrating DDS, floating DDS, time controlled, and pulse release DDS as well as dosage form with multiphase release properties and implantable DDS. In addition 3DP can also provide solutions for resolving difficulties relating to the delivery of poorly water-soluble drugs, peptides and proteins, preparation of DDS for high toxic and potent drugs and controlled-release of multidrugs in a single dosage forms. Due to its flexible and highly reproducible manufacturing process, 3DP has some advantages over conventional compressing and other RP technologies in fabricating solid DDS. This enables 3DP to be further developed for use in pharmaceutics applications. However, there are some problems that limit the further applications of the system, such as the selections of suitable excipients and the pharmacotechnical properties of 3DP products. Further developments are therefore needed to overcome these issues where 3DP systems can be successfully combined with conventional pharmaceutics. Here we present an overview and the potential 3DP in the development of new drug delivery systems.

Effect of process variables on the Drucker-Prager cap model and residual stress distribution of tablets estimated by the finite element method.

Science.gov (United States)

Hayashi, Yoshihiro; Otoguro, Saori; Miura, Takahiro; Onuki, Yoshinori; Obata, Yasuko; Takayama, Kozo

2014-01-01

A multivariate statistical technique was applied to clarify the causal correlation between variables in the manufacturing process and the residual stress distribution of tablets. Theophylline tablets were prepared according to a Box-Behnken design using the wet granulation method. Water amounts (X1), kneading time (X2), lubricant-mixing time (X3), and compression force (X4) were selected as design variables. The Drucker-Prager cap (DPC) model was selected as the method for modeling the mechanical behavior of pharmaceutical powders. Simulation parameters, such as Young's modulus, Poisson rate, internal friction angle, plastic deformation parameters, and initial density of the powder, were measured. Multiple regression analysis demonstrated that the simulation parameters were significantly affected by process variables. The constructed DPC models were fed into the analysis using the finite element method (FEM), and the mechanical behavior of pharmaceutical powders during the tableting process was analyzed using the FEM. The results of this analysis revealed that the residual stress distribution of tablets increased with increasing X4. Moreover, an interaction between X2 and X3 also had an effect on shear and the x-axial residual stress of tablets. Bayesian network analysis revealed causal relationships between the process variables, simulation parameters, residual stress distribution, and pharmaceutical responses of tablets. These results demonstrated the potential of the FEM as a tool to help improve our understanding of the residual stress of tablets and to optimize process variables, which not only affect tablet characteristics, but also are risks of causing tableting problems.

Study of nuclear fuel powders forming by axial compaction

International Nuclear Information System (INIS)

Fourcade, J.

2002-12-01

Nuclear fuel powders forming, although perfectly dominated, fail to make compacts without density gradients. Density heterogeneities induce diametric deformations during firing which force manufacturers to adjust shape with a high cost machining stage. Manufacturing process improvement is a major project to obtain perfectly shaped pellets and reduce their cost. One way of investigation of this project is the study of powders compaction mechanisms to understand and improve their behaviour. The goal of this study is to identify the main mechanisms linked with powder properties that act on pressing. An empirical model is developed to predict pellet deformations from a single compaction test. This model has to link powder properties with their compaction behaviour. Then, compaction tests identify the main mechanisms whereas a contact dynamic program is used to explain them. These works, done to improve the understanding in powders behaviour, focus on powders agglomeration state and macroscopic particles arrangement during the die filling stage. Actually, for granulated powders, granules cohesion act on the powder bed behaviour under pressure. The first particles arrangement is responsible for the first transfer directions into the powder and so for its transfer homogeneity and isotropy. As a consequence, the knowledge of all the macroscopic powder properties is essential to understand and improve the manufacturing process. Moreover, tests on UO 2 powders have shown that it is better to use granulated powders with spherical granules, short size distribution and granules cohesion according with compaction pressure to improve compact homogeneity of densification. (author)

A new model for predicting moisture uptake by packaged solid pharmaceuticals.

Science.gov (United States)

Chen, Y; Li, Y

2003-04-14

A novel mathematical model has been developed for predicting moisture uptake by packaged solid pharmaceutical products during storage. High density polyethylene (HDPE) bottles containing the tablet products of two new chemical entities and desiccants are investigated. Permeability of the bottles is determined at different temperatures using steady-state data. Moisture sorption isotherms of the two model drug products and desiccants at the same temperatures are determined and expressed in polynomial equations. The isotherms are used for modeling the time-humidity profile in the container, which enables the prediction of the moisture content of individual component during storage. Predicted moisture contents agree well with real time stability data. The current model could serve as a guide during packaging selection for moisture protection, so as to reduce the cost and cycle time of screening study.

Metal powder production by gas atomization

Science.gov (United States)

Ting, E. Y.; Grant, N. J.

1986-01-01

The confined liquid, gas-atomization process was investigated. Results from a two-dimensional water model showed the importance of atomization pressure, as well as delivery tube and atomizer design. The atomization process at the tip of the delivery tube was photographed. Results from the atomization of a modified 7075 aluminum alloy yielded up to 60 wt pct. powders that were finer than 45 microns in diameter. Two different atomizer designs were evaluated. The amount of fine powders produced was correlated to a calculated gas-power term. An optimal gas-power value existed for maximized fine powder production. Atomization at gas-power greater than or less than this optimal value produced coarser powders.

Clarification of Pharmaceutical Wastewater with Moringa Oleifera: Optimization Through Response Surface Methodology

Directory of Open Access Journals (Sweden)

Iva Rustanti Eri

2018-05-01

Full Text Available Herbal pharmaceutical industrial wastewater contains a high amount of suspended solids and alkaline (pH > 8; therefore it requires approprite coagulant and flocculant compounds for its wastewater treatment. The most widely used flocculant is a synthetic that has certain problems such as non-biodegradability and releases of toxic residual monomers. The use of eco-friendly flocculants as alternative materials for conventional flocculant in water and wastewater treatments is increasing. Numerous factors influence the performance of coagulation-flocculation process, such as coagulant dosage, flocculant dosage, initial potential of hydrogen (pH and velocity gradient of coagulation-flocculation. The main aim of this research is to evaluate the capability and effectiveness of Moringa oleifera extract for removal of suspended solid in herbal pharmaceutical industry. A coagulation-flocculation test was done by performing jar test at various speeds, according to the variation of the conducted treatment research. In this study, response surface methodology (RSM approach was used to optimize the concentration of coagulant dosage, flocculant dosage and flocculation velocity gradient (G, and the results were measured as maximum percentage of suspended solid removal. The wastewater used in this research originally came from the inlet of herbal pharmaceutical industry wastewater treatment plant, which was collected over 3 days. The wastewater has a total suspended solids of more than 1250 mg/L, and was alkaline (pH 9-10. The moringa extract was made from the extraction of a fat free moringa powder with a salt solution in a certain ratio. The percentage removal of suspended solid was 93.42-99.54%. The final results of the analysis of response surface showed that the variables of flocculant dosage and the flocculation velocity gradient (G have a huge impact on the amount of suspended solid removal, compared with the coagulant dosage. The model generated from the

Basic pharmaceutical technology

OpenAIRE

Angelovska, Bistra; Drakalska, Elena

2017-01-01

The lecture deals with basics of pharmaceutical technology as applied discipline of pharmaceutical science, whose main subject of study is formulation and manufacture of drugs. In a broad sense, pharmaceutical technology is science of formulation, preparation, stabilization and determination of the quality of medicines prepared in the pharmacy or in pharmaceutical industry

Pharmaceutical care in Kuwait: hospital pharmacists' perspectives.

Science.gov (United States)

Katoue, Maram G; Awad, Abdelmoneim I; Schwinghammer, Terry L; Kombian, Samuel B

2014-12-01

Pharmaceutical care practice has been championed as the primary mission of the pharmacy profession, but its implementation has been suboptimal in many developing countries including Kuwait. Pharmacists must have sufficient knowledge, skills, and positive attitudes to practise pharmaceutical care, and barriers in the pharmacy practice model must be overcome before pharmaceutical care can be broadly implemented in a given healthcare system. To investigate hospital pharmacists' attitudes towards pharmaceutical care, perceptions of their preparedness to provide pharmaceutical care, and the barriers to its implementation in Kuwait. Six general hospitals, eight specialized hospitals and seven specialized health centers in Kuwait. A descriptive, cross-sectional survey was distributed to all pharmacists working in the governmental hospitals in Kuwait (385 pharmacists). Data were collected via a pre-tested self-administered questionnaire. Descriptive statistics including percentages, medians and means Likert scale rating (standard deviations) were calculated and compared using statistical package for social sciences, version 20. Statistical significance was accepted at a p value of Kuwait. Completed surveys were received from 250 (64.9%) of the 385 pharmacists. Pharmacists expressed overall positive attitudes towards pharmaceutical care. They felt well prepared to implement the various aspects of pharmaceutical care, with the least preparedness in the administrative/management aspects. Pharmacists with more practice experience expressed significantly more positive attitudes towards pharmaceutical care (p = 0.001) and they felt better prepared to provide pharmaceutical care competencies (p Kuwait advocate implementation of pharmaceutical care while also appreciating the organizational, technical and professional barriers to its widespread adoption. Collaborative efforts between health authorities and educational institutions, and the integration of innovative approaches in

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.

The influence of high shear mixing on ternary dry powder inhaler formulations.

Science.gov (United States)

Hertel, Mats; Schwarz, Eugen; Kobler, Mirjam; Hauptstein, Sabine; Steckel, Hartwig; Scherließ, Regina

2017-12-20

The blending process is a key step in the production of dry powder inhaler formulations, but only little is known about the influence of process parameters. This is especially true for high shear blending of ternary formulations. For this reason, this study aims to investigate the influence of high shear mixing process parameters (mixing time and rotation speed) on the fine particle fraction (FPF) of ternary mixtures when using budesonide as model drug, two different carrier materials and two different mixing orders. Prolonged mixing time and higher rotation speeds led to lower FPFs, possibly due to higher press-on forces acting on the active pharmaceutical ingredients (API). In addition, a clear correlation between the energy consumption of the blender (the energy input into the blend) and the reduction of the FPF could be shown. Furthermore blending the carrier and the fines before adding the API was also found to be favorable. Copyright © 2017 Elsevier B.V. All rights reserved.

Model evaluation for the prediction of solubility of active pharmaceutical ingredients (APIs to guide solid–liquid separator design

Directory of Open Access Journals (Sweden)

Kuveneshan Moodley

2018-05-01

Full Text Available The assumptions and models for solubility modelling or prediction in systems using non-polar solvents, or water and complex triterpene and other active pharmaceutical ingredients as solutes aren't well studied. Furthermore, the assumptions concerning heat capacity effects (negligibility, experimental values or approximations are explored, using non-polar solvents (benzene, or water as reference solvents, for systems with solute melting points in the range of 306–528 K and molecular weights in the range of 90–442 g/mol. New empirical estimation methods for the ΔfusCpi of APIs are presented which correlate the solute molecular masses and van der Waals surface areas with ΔfusCpi. Separate empirical parameters were required for oxygenated and non-oxygenated solutes. Subsequently, the predictive capabilities of the various approaches to solubility modelling for complex pharmaceuticals, for which data is limited, are analysed. The solute selection is based on a principal component analysis, considering molecular weights, fusion temperatures, and solubilities in a non-polar solvent, alcohol, and water, where data was available. New NRTL-SAC parameters were determined for selected steroids, by regression. The original UNIFAC, modified UNIFAC (Dortmund, COSMO-RS (OL, and COSMO-SAC activity coefficient predictions are then conducted, based on the availability of group constants and sigma profiles. These are undertaken to assess the predictive capabilities of these models when each assumption concerning heat capacity is employed. The predictive qualities of the models are assessed, based on the mean square deviation and provide guidelines for model selection, and assumptions concerning phase equilibrium, when designing solid–liquid separators for the pharmaceutical industry on process simulation software. The most suitable assumption regarding ΔfusCpi was found to be system specific, with modified UNIFAC (Dortmund performing well in benzene as

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.

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. PMID:24250442

Modelling continuous pharmaceutical and bio-based processes at plant-wide level: A roadmap towards efficient decision-making

DEFF Research Database (Denmark)

Ramin, Pedram; Mansouri, Seyed Soheil; Udugama, Isuru A.

2018-01-01

The importance of developing simulation models for decision making in pharmaceutical and bio-based production processes is elaborated in this article. The advantages of modelling continuous processes are outlined and certain barriers in this regard are identified. Although there have been some...

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

simpler molecules of similar chemical structure and/or are fitted to Hansen's partial solubility parameters. The methodology is applied to modeling the solubility of three pharmaceuticals, namely acetanilide, phenacetin, and paracetamol, using the nonrandom hydrogen bonding (NRHB) EoS. In all cases...

Effect of hydrophobicity of pharmaceuticals and personal care products for adsorption on activated carbon: Adsorption isotherms, kinetics and mechanism.

Science.gov (United States)

Kaur, Harkirat; Bansiwal, Amit; Hippargi, Girivyankatesh; Pophali, Girish R

2017-09-11

Adsorption of three pharmaceuticals and personal care products (PPCPs), namely caffeine, ibuprofen and triclosan on commercial powdered activated carbon was examined in aqueous medium. The contaminants were chosen based on their diverse log K ow (octanol-water partition coefficient) viz. - 0.07 for caffeine, 3.97 for ibuprofen and 4.76 for triclosan to examine the role of hydrophobicity on adsorption process. The adsorbent characterisation was achieved using BET surface area, SEM, pore size distribution studies and FTIR. Influence of mass of PAC, contact time, solution pH and initial concentration on adsorption capacity of PAC was studied. Adsorption isotherms and kinetics were applied to establish the mechanism of adsorption. The kinetics followed pseudo-second order with physisorption occurring through particle diffusion. The Freundlich model fitted best among the isotherm models. The adsorption capacity increased in the order CFN activated carbon.

Organically functionalized mesoporous SBA-15 as sorbents for removal of selected pharmaceuticals from water

Energy Technology Data Exchange (ETDEWEB)

Bui, Tung Xuan [School of Environmental Science and Engineering, Gwangju Institute of Science and Technology (GIST), 261 Cheomdan-gwagiro, Buk-gu, Gwangju 500-712 (Korea, Republic of); Kang, Seo-Young [International Environmental Research Center (IERC), Gwangju Institute of Science and Technology (GIST), 261 Cheomdan-gwagiro, Buk-gu, Gwangju 500-712 (Korea, Republic of); Lee, Sang-Hyup [Water Environment Center, Korea Institute of Science and Technology, Cheongryang, Seoul 130-650 (Korea, Republic of); Choi, Heechul, E-mail: hcchoi@gist.ac.kr [School of Environmental Science and Engineering, Gwangju Institute of Science and Technology (GIST), 261 Cheomdan-gwagiro, Buk-gu, Gwangju 500-712 (Korea, Republic of)

2011-10-15

Highlights: {yields} SBA-15 grafted with aminopropyl, hydroxymethyl, and trimethylsilyl groups as sorbents. {yields} Sorbents for removal of a mixture of 12 pharmaceuticals from water. {yields} Hydroxymethyl-SBA-15 shows similar adsorption efficiency like SBA-15. {yields} Aminopropyl-SBA-15 makes increase for clofibric acid, diclofenac, decrease for atenolol, estrone, trimethoprim. {yields} Trimethylsilyl-SBA-15 makes increase for 9 compounds; 7 compounds from 70.6% to 98.9%. - Abstract: Mesoporous silica SBA-15 and its postfunctionalized counterparts with hydroxymethyl (HM-SBA-15), aminopropyl (AP-SBA-15), and trimethylsilyl (TMS-SBA-15) were prepared and characterized by powder X-ray diffraction, N{sub 2} adsorption-desorption measurement, Fourier-transform infrared spectroscopy, and elemental analysis. The removal of a mixture of 12 selected pharmaceuticals was investigated by batch adsorption experiments onto SBA-15 and the grafted materials. SBA-15 showed to have moderate adsorption affinity with amino-containing (atenolol, trimethoprim) and hydrophobic pharmaceuticals, but it displayed minimal adsorption affinity toward hydrophilic compounds. HM-SBA-15 was analogous with SBA-15 in terms of the adsorption efficiency toward all pharmaceuticals. AP-SBA-15 exhibited an increase in the adsorption of two acidic compounds (clofibric acid, diclofenac) but a decrease in the adsorption of estrone and the two amino-containing compounds. Among the grafted materials, TMS-SBA-15 had the highest adsorption affinity toward most pharmaceuticals. Moreover, the adsorption of nine pharmaceuticals to TMS-SBA-15 was significantly higher than that to SBA-15; seven of which showed the removal percentages from 70.6% to 98.9% onto TMS-SBA-15. The number of pharmaceuticals showing high adsorption efficiency onto TMS-SBA-15 did not alter significantly as the pH changed in the range of 5.5-7.6. The results suggest that TMS-SBA-15 is a promising material for the removal of pharmaceuticals

Organically functionalized mesoporous SBA-15 as sorbents for removal of selected pharmaceuticals from water

International Nuclear Information System (INIS)

Bui, Tung Xuan; Kang, Seo-Young; Lee, Sang-Hyup; Choi, Heechul

2011-01-01

Highlights: → SBA-15 grafted with aminopropyl, hydroxymethyl, and trimethylsilyl groups as sorbents. → Sorbents for removal of a mixture of 12 pharmaceuticals from water. → Hydroxymethyl-SBA-15 shows similar adsorption efficiency like SBA-15. → Aminopropyl-SBA-15 makes increase for clofibric acid, diclofenac, decrease for atenolol, estrone, trimethoprim. → Trimethylsilyl-SBA-15 makes increase for 9 compounds; 7 compounds from 70.6% to 98.9%. - Abstract: Mesoporous silica SBA-15 and its postfunctionalized counterparts with hydroxymethyl (HM-SBA-15), aminopropyl (AP-SBA-15), and trimethylsilyl (TMS-SBA-15) were prepared and characterized by powder X-ray diffraction, N 2 adsorption-desorption measurement, Fourier-transform infrared spectroscopy, and elemental analysis. The removal of a mixture of 12 selected pharmaceuticals was investigated by batch adsorption experiments onto SBA-15 and the grafted materials. SBA-15 showed to have moderate adsorption affinity with amino-containing (atenolol, trimethoprim) and hydrophobic pharmaceuticals, but it displayed minimal adsorption affinity toward hydrophilic compounds. HM-SBA-15 was analogous with SBA-15 in terms of the adsorption efficiency toward all pharmaceuticals. AP-SBA-15 exhibited an increase in the adsorption of two acidic compounds (clofibric acid, diclofenac) but a decrease in the adsorption of estrone and the two amino-containing compounds. Among the grafted materials, TMS-SBA-15 had the highest adsorption affinity toward most pharmaceuticals. Moreover, the adsorption of nine pharmaceuticals to TMS-SBA-15 was significantly higher than that to SBA-15; seven of which showed the removal percentages from 70.6% to 98.9% onto TMS-SBA-15. The number of pharmaceuticals showing high adsorption efficiency onto TMS-SBA-15 did not alter significantly as the pH changed in the range of 5.5-7.6. The results suggest that TMS-SBA-15 is a promising material for the removal of pharmaceuticals from aqueous phase

Drug-disease modeling in the pharmaceutical industry - where mechanistic systems pharmacology and statistical pharmacometrics meet.

Science.gov (United States)

Helmlinger, Gabriel; Al-Huniti, Nidal; Aksenov, Sergey; Peskov, Kirill; Hallow, Karen M; Chu, Lulu; Boulton, David; Eriksson, Ulf; Hamrén, Bengt; Lambert, Craig; Masson, Eric; Tomkinson, Helen; Stanski, Donald

2017-11-15

Modeling & simulation (M&S) methodologies are established quantitative tools, which have proven to be useful in supporting the research, development (R&D), regulatory approval, and marketing of novel therapeutics. Applications of M&S help design efficient studies and interpret their results in context of all available data and knowledge to enable effective decision-making during the R&D process. In this mini-review, we focus on two sets of modeling approaches: population-based models, which are well-established within the pharmaceutical industry today, and fall under the discipline of clinical pharmacometrics (PMX); and systems dynamics models, which encompass a range of models of (patho-)physiology amenable to pharmacological intervention, of signaling pathways in biology, and of substance distribution in the body (today known as physiologically-based pharmacokinetic models) - which today may be collectively referred to as quantitative systems pharmacology models (QSP). We next describe the convergence - or rather selected integration - of PMX and QSP approaches into 'middle-out' drug-disease models, which retain selected mechanistic aspects, while remaining parsimonious, fit-for-purpose, and able to address variability and the testing of covariates. We further propose development opportunities for drug-disease systems models, to increase their utility and applicability throughout the preclinical and clinical spectrum of pharmaceutical R&D. Copyright © 2017 Elsevier B.V. All rights reserved.

Spray drying of beryllium oxide powder

International Nuclear Information System (INIS)

Sepulveda, J.L.; Kahler, D.A.

1991-01-01

Forming of beryllia ceramics through dry pressing requires the agglomeration of the powder through spray drying. To produce high quality fired ceramics it is necessary to disperse/grind the primary powder prior to binder addition. Size reduction of the powder is accomplished using an aqueous system in Vibro-Energy mills (VEM) charged with beryllia media to minimize contamination. Two VEM mills of different size were used to characterize the grinding operation. Details of the grinding kinetics are described within the context of the Macroscopic Population Balance Model approach. Spray drying of the ceramic slurry was accomplished with both a centrifugal atomizer and a two fluid nozzle atomizer. Two different spray dryers were used. Important operating parameters affecting the size distribution of the spray dried powder are discussed

Pharmaceutical supply chain models: A synthesis from a systems view of operations research

Directory of Open Access Journals (Sweden)

Ettore Settanni

Full Text Available This research evaluates reconfiguration opportunities in Pharmaceutical Supply Chains (PSC resulting from technology interventions in manufacturing, and new, more patient-centric delivery models. A critical synthesis of the academic and practice literature is used to identify, conceptualise, analyse and categorise PSC models. From a theoretical perspective, a systems view of operations research is adopted to provide insights on a broader range of OR activities, from conceptual to mathematical modelling and model solving, up to implementation.The research demonstrates that: 1 current definitions of the PSC are largely production-centric and fail to capture patient consumption, and hence healthcare outcomes; 2 most PSC mathematical models lack adequate conceptualisation of the structure and behaviour of the supply chain, and the boundary conditions that need to be considered for a given problem; 3 models do not adequately specify current unit operations or future production technology options, and are therefore unable to address the critical questions around alternative product or process technologies; 4 economic evaluations are limited to direct costing, rather than systemic approaches such as supply chain costing and total cost of ownership.While current models of the PSC may help with the optimisation of specific unit operations, their theoretical benefits could be offset by the dynamics of complex upstream (supply and downstream (distribution and healthcare delivery systems. To overcome these limitations, this research provides initial directions towards an integrated systems approach to PSC modelling. This perspective involves problem conceptualisation and boundary definition; design, formulation and solution of mathematical models, through to practical implementation of identified solutions. For both academics and practitioners, research findings suggest a systems approach to PSC modelling can provide improved conceptualisation and

Effect of surface coating with magnesium stearate via mechanical dry powder coating approach on the aerosol performance of micronized drug powders from dry powder inhalers.

Science.gov (United States)

Zhou, Qi Tony; Qu, Li; Gengenbach, Thomas; Larson, Ian; Stewart, Peter J; Morton, David A V

2013-03-01

The objective of this study was to investigate the effect of particle surface coating with magnesium stearate on the aerosolization of dry powder inhaler formulations. Micronized salbutamol sulphate as a model drug was dry coated with magnesium stearate using a mechanofusion technique. The coating quality was characterized by X-ray photoelectron spectroscopy. Powder bulk and flow properties were assessed by bulk densities and shear cell measurements. The aerosol performance was studied by laser diffraction and supported by a twin-stage impinger. High degrees of coating coverage were achieved after mechanofusion, as measured by X-ray photoelectron spectroscopy. Concomitant significant increases occurred in powder bulk densities and in aerosol performance after coating. The apparent optimum performance corresponded with using 2% w/w magnesium stearate. In contrast, traditional blending resulted in no significant changes in either bulk or aerosolization behaviour compared to the untreated sample. It is believed that conventional low-shear blending provides insufficient energy levels to expose host micronized particle surfaces from agglomerates and to distribute guest coating material effectively for coating. A simple ultra-high-shear mechanical dry powder coating step was shown as highly effective in producing ultra-thin coatings on micronized powders and to substantially improve the powder aerosolization efficiency.

MODEL OF HYDRODYNAMIC MIXING OF CARBONIC POWDERS IN VACUUMATOR, USED IN STEEL-MAKING OF RUP “BMZ”

Directory of Open Access Journals (Sweden)

A. N. Chichko

2005-01-01

Full Text Available The mathematical model of the mixing and dissolving process of carbonic powder in a system '"vacuumator-bowl” under influence of circulating argon is offered. The spatial distribution of hydrodynamic currents at mixing of carbonic powder, received on the basis of computer calculations is presented. The character of distribution of hydrodynamic speeds of melt (circulating currents in industrial bowl and vacuumator for different time slots of mixing is determined. 

Controlling in situ crystallization of pharmaceutical particles within the spray dryer.

Science.gov (United States)

Woo, Meng Wai; Lee, May Ginn; Shakiba, Soroush; Mansouri, Shahnaz

2017-11-01

Simultaneous solidification and in situ crystallization (or partial crystallization) of droplets within the drying chamber are commonly encountered in the spray drying of pharmaceuticals. The crystallinity developed will determine the functionality of the powder and its stability during storage. This review discusses strategies that can be used to control the in situ crystallization process. Areas covered: The premise of the strategies discussed focuses on the manipulation of the droplet drying rate relative to the timescale of crystallization. This can be undertaken by the control of the spray drying operation, by the use of volatile materials and by the inclusion of additives. Several predictive approaches for in situ crystallization control and new spray dryer configuration strategies are further discussed. Expert opinion: Most reports, hitherto, have focused on the crystallinity of the spray dried material or the development of crystallinity during storage. More mechanistic understanding of the in situ crystallization process during spray drying is required to guide product formulation trials. The key challenge will be in adapting the mechanistic approach to the myriad possible formulations in the pharmaceutical industry.

Preclinical QSP Modeling in the Pharmaceutical Industry: An IQ Consortium Survey Examining the Current Landscape

Science.gov (United States)

Wu, Fan; Bansal, Loveleena; Bradshaw‐Pierce, Erica; Chan, Jason R.; Liederer, Bianca M.; Mettetal, Jerome T.; Schroeder, Patricia; Schuck, Edgar; Tsai, Alice; Xu, Christine; Chimalakonda, Anjaneya; Le, Kha; Penney, Mark; Topp, Brian; Yamada, Akihiro

2018-01-01

A cross‐industry survey was conducted to assess the landscape of preclinical quantitative systems pharmacology (QSP) modeling within pharmaceutical companies. This article presents the survey results, which provide insights on the current state of preclinical QSP modeling in addition to future opportunities. Our results call attention to the need for an aligned definition and consistent terminology around QSP, yet highlight the broad applicability and benefits preclinical QSP modeling is currently delivering. PMID:29349875

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. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association

Regularities of formation of granules at granulation of powdered materials in drum devices

International Nuclear Information System (INIS)

Kelbaliyev, G.I; Samedli, V.M.

2008-01-01

Full text:Granulation of powdered materials in the presence of binding agent is widely used in the most multi-tankage productions of chemical, food, pharmaceutical, metallurgical and agrarian technology. Granulation of powdered materials with participation of liquid phase is carried out in screw, disk, plase-shaped and drum devices and also in devices with mixers. In all cases a formation and growth of granules takes place owing to wetting of separate particles of powder leading to agglomeration and coagulation of particles in their contact with each other. It is apparent that in early stage of granule formation a growth and formation of granules takes place owing to adherence of small particles and agglomerates to larger granules. The content of liquid phase owing to which are appeared adhesive, capillary and surface forces, keeping particles on surface of granule exerts an essential influence on process of granule formation. Besides composition of mixture, its moisture and physical-chemical properties of initial components a mixing frequency degree of filling and angle of inclination of the device, ratio of liquid and hard phases which defines finally qualitative characteristics of the process exert an essential influence on formation of granules as a result of agglomeration of particles of powder. Powder lamination on granule surface is as consequence of its consolidation whereas as a result of consolidation and compression, a binding agent containing in pores squeezed out to a surface, which increases a possibility and probability of further sticking of dry particles of powder. In all cases the further growth and completeness of form of granule is determined by distribution of concentration of binding agent in volume of granule, i.e. moisture content or moisture of granule surface

The coefficient of rolling resistance (CoRR) of some pharmaceutical tablets.

Science.gov (United States)

Ketterhagen, William R; Bharadwaj, Rahul; Hancock, Bruno C

2010-06-15

Experiments have been conducted to measure the coefficient of rolling resistance (CoRR) of some pharmaceutical tablets and several common materials, such as glass beads and steel ball bearings. CoRR values are required as inputs for discrete element method (DEM) models which can be used to model particulate flows and solid dosage form manufacturing processes. Until now there have been no CoRR data reported for pharmaceutical materials, and thus these new data will help to facilitate more accurate modeling of pharmaceutical systems. Copyright 2010 Elsevier B.V. All rights reserved.

New Product Introduction in the Pharmaceutical Industry

DEFF Research Database (Denmark)

Hansen, Klaus Reinholdt Nyhuus

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...... 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...... uncertainty and several important industry characteristics. The model is used to gain several insights on the use of risk packaging and on keeping time-to-market short. As capacity in secondary pharmaceutical production is critical for product availability, a capacity planning model for a new drug delivery...

Thermokinetic Modeling of Phase Transformation in the Laser Powder Deposition Process

Science.gov (United States)

Foroozmehr, Ehsan; Kovacevic, Radovan

2009-08-01

A finite element model coupled with a thermokinetic model is developed to predict the phase transformation of the laser deposition of AISI 4140 on a substrate with the same material. Four different deposition patterns, long-bead, short-bead, spiral-in, and spiral-out, are used to cover a similar area. Using a finite element model, the temperature history of the laser powder deposition (LPD) process is determined. The martensite transformation as well as martensite tempering is considered to calculate the final fraction of martensite, ferrite, cementite, ɛ-carbide, and retained austenite. Comparing the surface hardness topography of different patterns reveals that path planning is a critical parameter in laser surface modification. The predicted results are in a close agreement with the experimental results.

New Strategies for Powder Compaction in Powder-based Rapid Prototyping Techniques

OpenAIRE

Budding, A.; Vaneker, T.H.J.

2013-01-01

In powder-based rapid prototyping techniques, powder compaction is used to create thin layers of fine powder that are locally bonded. By stacking these layers of locally bonded material, an object is made. The compaction of thin layers of powder mater ials is of interest for a wide range of applications, but this study solely focuses on the application for powder -based three-dimensional printing (e.g. SLS, 3DP). This research is primarily interested in powder compaction for creating membrane...

Anticonvulsant activity of Aloe vera leaf extract in acute and chronic models of epilepsy in mice.

Science.gov (United States)

Rathor, Naveen; Arora, Tarun; Manocha, Sachin; Patil, Amol N; Mediratta, Pramod K; Sharma, Krishna K

2014-03-01

The effect of Aloe vera in epilepsy has not yet been explored. This study was done to explore the effect of aqueous extract of Aloe vera leaf powder on three acute and one chronic model of epilepsy. In acute study, aqueous extract of Aloe vera leaf (extract) powder was administered in doses 100, 200 and 400 mg/kg p.o. Dose of 400 mg/kg of Aloe vera leaf extract was chosen for chronic administration. Oxidative stress parameters viz. malondialdehyde (MDA) and reduced glutathione (GSH) were also estimated in brain of kindled animals. In acute study, Aloe vera leaf (extract) powder in a dose-dependent manner significantly decreased duration of tonic hind limb extension in maximal electroshock seizure model, increased seizure threshold current in increasing current electroshock seizure model, and increased latency to onset and decreased duration of clonic convulsion in pentylenetetrazole (PTZ) model as compared with control group. In chronic study, Aloe vera leaf (extract) powder prevented progression of kindling in PTZ-kindled mice. Aloe vera leaf (extract) powder 400 mg/kg p.o. also reduced brain levels of MDA and increased GSH levels as compared to the PTZ-kindled non-treated group. The results of study showed that Aloe vera leaf (extract) powder possessed significant anticonvulsant and anti-oxidant activity. © 2013 Royal Pharmaceutical Society.

Solventless dry powder coating for sustained drug release using mechanochemical treatment based on the tri-component system of acetaminophen, carnauba wax and glidant.

Science.gov (United States)

Hoashi, Yohei; Tozuka, Yuichi; Takeuchi, Hirofumi

2013-02-01

Solventless dry powder coating methods have many advantages compared to solvent-based methods: they are more economical, simpler, safer, more environmentally friendly and easier to scale up. The purpose of this study was to investigate a highly effective dry powder coating method using the mechanofusion system, a mechanochemical treatment equipped with high compressive and shearing force. Acetaminophen (AAP) and carnauba wax (CW) were selected as core particles of the model drug and coating material, respectively. Mixtures of AAP and CW with and without talc were processed using the mechanofusion system. Sustained AAP release was observed by selecting appropriate processing conditions for the rotation speed and the slit size. The dissolution rate of AAP processed with CW substantially decreased with an increase in talc content up to 40% of the amount of CW loaded. Increasing the coating amount by two-step addition of CW led to more effective coating and extended drug release. Scanning electron micrographs indicated that CW adhered and showed satisfactory coverage of the surface of AAP particles. Effective CW coating onto the AAP surface was successfully achieved by strictly controlling the processing conditions and the composition of core particles, coating material and glidant. Our mechanochemical dry powder coating method using the mechanofusion system is a simple and promising means of solventless pharmaceutical coating.

Corrosion-resistant powder-metallurgy stainless steel powders and compacts therefrom

International Nuclear Information System (INIS)

Klar, E.; Ro, D.H.; Whitman, C.I.

1980-01-01

Disclosed is a process for improving the corrosion resistance of a stainless steel powder or compact thereof wherein the powder is produced by atomizing a melt of metals in an oxidizing environment whereby the resulting stainless steel powder is surface-enriched in silicon oxides. The process comprises adding an effective proportion of modifier metal to the melt prior to the atomization, the modifier metal selected from the group consisting of tin, aluminum, lead, zinc, magnesium, rare earth metals and like metals capable of enrichment about the surface of the resulting atomized stainless steel powder and effective under reductive sintering conditions in the depletion of the silicon oxides about the surface; and sintering the resulting atomized powder or a compact thereof under reducing conditions, the sintered powder or compact thereof being depleted in the silicon oxides and the corrosion resistance of the powder or compact thereof being improved thereby

Effects of pressure on thermal transport in plutonium oxide powder

International Nuclear Information System (INIS)

Bielenberg, Patricia; Prenger, F. Coyne; Veirs, Douglas Kirk; Jones, Jerry

2004-01-01

Radial temperature profiles in plutonium oxide (PuO 2 ) powder were measured in a cylindrical vessel over a pressure range of 0.055 to 334.4 kPa with two different fill gases, helium and argon. The fine PuO 2 powder provides a very uniform self-heating medium amenable to relatively simple mathematical descriptions. At low pressures ( 2 powder has small particle sizes (on the order of 1 to 10 μm), random particle shapes, and high porosity so a more general model was required for this system. The model correctly predicts the temperature profiles of the powder over the wide pressure range for both argon and helium as fill gases. The effective thermal conductivity of the powder bed exhibits a pressure dependence at higher pressures because the pore sizes in the interparticle contact area are relatively small (less than 1 μm) and the Knudsen number remains above the continuum limit at these conditions for both fill gases. Also, the effective thermal conductivity with argon as a fill gas is higher than expected at higher pressures because the solid pathways account for over 80% of the effective powder conductivity. The results obtained from this model help to bring insight to the thermal conductivity of very fine ceramic powders with different fill gases.

Effective High-Frequency Permeability of Compacted Metal Powders

Science.gov (United States)

Volkovskaya, I. I.; Semenov, V. E.; Rybakov, K. I.

2018-03-01

We propose a model for determination of the effective complex permeability of compacted metal-powder media. It is based on the equality of the magnetic moment in a given volume of the media with the desired effective permeability to the total magnetic moment of metal particles in the external high-frequency magnetic field, which arises due to excitation of electric eddy currents in the particles. Calculations within the framework of the proposed model allow us to refine the values of the real and imaginary components of the permeability of metal powder compacts in the microwave band. The conditions of applicability of the proposed model are formulated, and their fulfillment is verified for metal powder compacts in the microwave and millimeter wavelength bands.

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.

Pharmaceutical new product development: the increasing role of in-licensing.

Science.gov (United States)

Edwards, Nancy V

2008-12-01

Many pharmaceutical companies are facing a pipeline gap because of the increasing economic burden and uncertainty associated with internal research and development programs designed to develop new pharmaceutical products. To fill this pipeline gap, pharmaceutical companies are increasingly relying on in-licensing opportunities. New business development identifies new pharmaceuticals that satisfy unmet needs and are a good strategic fit for the company, completes valuation models and forecasts, evaluates the ability of the company to develop and launch products, and pursues in-licensing agreements for pharmaceuticals that cannot be developed internally on a timely basis. These agreements involve the transfer of access rights for patents, trademarks, or similar intellectual property from an outside company in exchange for payments. Despite the risks, in-licensing is increasingly becoming the preferred method for pharmaceutical companies with pipeline gaps to bring new pharmaceuticals to the clinician.

A novel strategy for pharmaceutical cocrystal generation without knowledge of stoichiometric ratio: myricetin cocrystals and a ternary phase diagram.

Science.gov (United States)

Hong, Chao; Xie, Yan; Yao, Yashu; Li, Guowen; Yuan, Xiurong; Shen, Hongyi

2015-01-01

To develop a streamlined strategy for pharmaceutical cocrystal preparation without knowledge of the stoichiometric ratio by preparing and characterizing the cocrystals of myricetin (MYR) with four cocrystal coformers (CCF). An approach based on the phase solubility diagram (PSD) was used for MYR cocrystals preparation and the solid-state properties were characterized by differential scanning calorimetry (DSC), fourier transform-infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The ternary phase diagram (TPD) was constructed by combining the PSD and nuclear magnetic resonance (NMR) data. After that, the TPD was verified by traditional methods. The dissolution of MYR in the four cocrystals and pure MYR within three different media were also evaluated. A simple research method for MYR cocrystal preparation was obtained as follows: first, the PSD of MYR and CCF was constructed and analyzed; second, by transforming the curve in the PSD to a TPD, a region of pure cocrystals formation was exhibited, and then MYR cocrystals were prepared and identified by DSC, FT-IR, PXRD, and SEM; third, with the composition of the prepared cocrystal from NMR, the TPD of the MYR-CCF-Solvent system was constructed. The powder dissolution data showed that the solubility and dissolution rate of MYR was significantly enhanced by the cocrystals. A novel strategy for pharmaceutical cocrystals preparation without knowledge of the stoichiometric ratio based on the TPD was established and MYR cocrystals were successfully prepared. The present study provides a systematic approach for pharmaceutical cocrystal generation, which benefits the development and application of cocrystal technology in drug delivery.

Determining the degree of powder homogeneity using PC-based program

Directory of Open Access Journals (Sweden)

Đuragić Olivera M.

2010-01-01

Full Text Available The mixing of powders and the quality control of the obtained mixtures are critical operations involved in the processing of granular materials in chemical, metallurgical, food and pharmaceutical industries. Studies on mixing efficiency and the time needed for achieving homogeneity in the powder mashes production have significant importance. Depending on the characteristic of the materials, a number of methods have been used for the homogeneity tests. Very often, the degree of mixing has been determined by analyzing images of particle arrays in the sample using microscopy, photography and/or video tools. In this paper, a new PC-based method for determining the number of particles in the powder homogeneity tests has been developed. Microtracers®, red iron particles, were used as external tracer added before mixing. Iron particles in the samples of the mixtures were separated by rotary magnet and spread onto a filter paper. The filter paper was sprayed with 50% solution of ethanol for color development and the particles counted where the number of spots presented the concentration of added tracer. The number of spots was counted manually, as well as by the developed PC program. The program which analyzes scanned filter papers with spots is based on digital image analyses, where red spots were converted through few filters into a black and white, and counted. Results obtained by manual and PC counting were compared. A high correlation was established between the two counting methods.

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.

Light extinction in metallic powder beds: Correlation with powder structure

International Nuclear Information System (INIS)

Rombouts, M.; Froyen, L.; Gusarov, A.V.; Bentefour, E.H.; Glorieux, C.

2005-01-01

A theoretical correlation between the effective extinction coefficient, the specific surface area, and the chord length distribution of powder beds is verified experimentally. The investigated powder beds consist of metallic particles of several tens of microns. The effective extinction coefficients are measured by a light-transmission technique at a wavelength of 540 nm. The powder structure is characterized by a quantitative image analysis of powder bed cross sections resulting in two-point correlation functions and chord length distributions. The specific surface area of the powders is estimated by laser-diffraction particle-size analysis and by the two-point correlation function. The theoretically predicted tendency of increasing extinction coefficient with specific surface area per unit void volume is confirmed by the experiments. However, a significant quantitative discrepancy is found for several powders. No clear correlation of the extinction coefficient with the powder material and particle size, and morphology is revealed, which is in line with the assumption of geometrical optics

Zein as a Pharmaceutical Excipient in Oral Solid Dosage Forms: State of the Art and Future Perspectives.

Science.gov (United States)

Berardi, Alberto; Bisharat, Lorina; AlKhatib, Hatim S; Cespi, Marco

2018-05-07

Zein is the main storage protein of corn and it has several industrial applications. Mainly in the last 10-15 years, zein has emerged as a potential pharmaceutical excipient with unique features. Zein is a natural, biocompatible and biodegradable material produced from renewable sources. It is insoluble, yet due to its amphiphilic nature, it has self-assembling properties, which have been exploited for the formation of micromicroparticle and nanoparticle and films. Moreover, zein can hydrate so it has been used in swellable matrices for controlled drug release. Other pharmaceutical applications of zein in oral drug delivery include its incorporation in solid dispersions of poorly soluble drugs and in colonic drug delivery systems. This review describes the features of zein significant for its use as a pharmaceutical excipient for oral drug delivery, and it summaries the literature relevant to macroscopic zein-based oral dosage forms, i.e. tablets, capsules, beads and powders. Particular attention is paid to the most novel formulations and applications of zein. Moreover, gaps of knowledge as well as possible venues for future investigations on zein are highlighted.

AMOC studies of positronium in fine MgO powder

International Nuclear Information System (INIS)

Waeyenberge, B. van; Dauwe, C.

2001-01-01

A first set of AMOC spectra on fine powdered MgO were measured at the Stuttgart relativistic positron beam facility. A special AMOC spectrometer was set up in order to determine the long lifetimes of ortho-positronium in the powder cavities. The spectra were taken on pellets of pressed powder in air and in an oxygen atmosphere to ensure ortho- to para-positronium conversion. An analysis of the data is made in the light of previous lifetime measurements on MgO. Here the lifetime spectrum was fitted with an age dependent lifetime describing the slow thermalisation of epithermal ortho-positronium between the powder grains. Based on the lifetime spectrum of the integrated AMOC spectra the data could not discriminate between a 5-component model and a model including slow positronium thermalisation. On the other hand, analysis of the age dependent line shape parameter shows better variances for a thermalisation model. (orig.)

AMOC studies of positronium in fine MgO powder

Energy Technology Data Exchange (ETDEWEB)

Waeyenberge, B. van; Dauwe, C. [Ghent Univ. (Belgium). Dept. of Subatomic and Radiation Physics; Stoll, H. [Max-Planck-Institut fuer Metallforschung, Stuttgart (Germany)

2001-07-01

A first set of AMOC spectra on fine powdered MgO were measured at the Stuttgart relativistic positron beam facility. A special AMOC spectrometer was set up in order to determine the long lifetimes of ortho-positronium in the powder cavities. The spectra were taken on pellets of pressed powder in air and in an oxygen atmosphere to ensure ortho- to para-positronium conversion. An analysis of the data is made in the light of previous lifetime measurements on MgO. Here the lifetime spectrum was fitted with an age dependent lifetime describing the slow thermalisation of epithermal ortho-positronium between the powder grains. Based on the lifetime spectrum of the integrated AMOC spectra the data could not discriminate between a 5-component model and a model including slow positronium thermalisation. On the other hand, analysis of the age dependent line shape parameter shows better variances for a thermalisation model. (orig.)

Treatment of micropollutants in municipal wastewater: Ozone or powdered activated carbon?

International Nuclear Information System (INIS)

Margot, Jonas; Kienle, Cornelia; Magnet, Anoÿs; Weil, Mirco; Rossi, Luca; Alencastro, Luiz Felippe de; Abegglen, Christian; Thonney, Denis; Chèvre, Nathalie; Schärer, Michael

2013-01-01

Many organic micropollutants present in wastewater, such as pharmaceuticals and pesticides, are poorly removed in conventional wastewater treatment plants (WWTPs). To reduce the release of these substances into the aquatic environment, advanced wastewater treatments are necessary. In this context, two large-scale pilot advanced treatments were tested in parallel over more than one year at the municipal WWTP of Lausanne, Switzerland. The treatments were: i) oxidation by ozone followed by sand filtration (SF) and ii) powdered activated carbon (PAC) adsorption followed by either ultrafiltration (UF) or sand filtration. More than 70 potentially problematic substances (pharmaceuticals, pesticides, endocrine disruptors, drug metabolites and other common chemicals) were regularly measured at different stages of treatment. Additionally, several ecotoxicological tests such as the Yeast Estrogen Screen, a combined algae bioassay and a fish early life stage test were performed to evaluate effluent toxicity. Both treatments significantly improved the effluent quality. Micropollutants were removed on average over 80% compared with raw wastewater, with an average ozone dose of 5.7 mg O 3 l −1 or a PAC dose between 10 and 20 mg l −1 . Depending on the chemical properties of the substances (presence of electron-rich moieties, charge and hydrophobicity), either ozone or PAC performed better. Both advanced treatments led to a clear reduction in toxicity of the effluents, with PAC-UF performing slightly better overall. As both treatments had, on average, relatively similar efficiency, further criteria relevant to their implementation were considered, including local constraints (e.g., safety, sludge disposal, disinfection), operational feasibility and cost. For sensitive receiving waters (drinking water resources or recreational waters), the PAC-UF treatment, despite its current higher cost, was considered to be the most suitable option, enabling good removal of most

[Studies on the brand traceability of milk powder based on NIR spectroscopy technology].

Science.gov (United States)

Guan, Xiao; Gu, Fang-Qing; Liu, Jing; Yang, Yong-Jian

2013-10-01

Brand traceability of several different kinds of milk powder was studied by combining near infrared spectroscopy diffuse reflectance mode with soft independent modeling of class analogy (SIMCA) in the present paper. The near infrared spectrum of 138 samples, including 54 Guangming milk powder samples, 43 Netherlands samples, and 33 Nestle samples and 8 Yili samples, were collected. After pretreatment of full spectrum data variables in training set, principal component analysis was performed, and the contribution rate of the cumulative variance of the first three principal components was about 99.07%. Milk powder principal component regression model based on SIMCA was established, and used to classify the milk powder samples in prediction sets. The results showed that the recognition rate of Guangming milk powder, Netherlands milk powder and Nestle milk powder was 78%, 75% and 100%, the rejection rate was 100%, 87%, and 88%, respectively. Therefore, the near infrared spectroscopy combined with SIMCA model can classify milk powder with high accuracy, and is a promising identification method of milk powder variety.

Characterization of herbal powder blends homogeneity using near-infrared spectroscopy

Directory of Open Access Journals (Sweden)

Wenlong Li

2014-11-01

Full Text Available Homogeneity of powder blend is essential to obtain uniform contents for the tablets and capsules. Near-infrared (NIR spectroscopy with fiber-optic probe was used as an on-line technique for monitoring the homogeneity of pharmaceutical blend during the blending process instead of the traditional techniques, such as high performance liquid chromatograph (HPLC method. In this paper NIRS with a SabIR diffuse reflectance fiber-optic probe was used to monitor the blending process of coptis powder and lactose (excipient with different contents, and further qualitative methods, like similarity, moving block of standard deviation and mean square were used for calculation purposes with the collected spectra after the pretreatment of multiplicative signal correction (MSC and second derivative. Correlation spectrum was used for the wavelength selection. Four different coptis were blended with lactose separately to validate the proposed method, and the blending process of "liu wei di huang" pill was also simulated in bottles to verify this method on multiple herbal blends. The overall results suggest that NIRS is a simple, effective and noninvasive technique can be successfully applied to the determination of homogeneity in the herbal blend.

Halogen bonding and pharmaceutical cocrystals: the case of a widely used preservative.

Science.gov (United States)

Baldrighi, Michele; Cavallo, Gabriella; Chierotti, Michele R; Gobetto, Roberto; Metrangolo, Pierangelo; Pilati, Tullio; Resnati, Giuseppe; Terraneo, Giancarlo

2013-05-06

3-Iodo-2-propynyl-N-butylcarbamate (IPBC) is an iodinated antimicrobial product used globally as a preservative, fungicide, and algaecide. IPBC is difficult to obtain in pure form as well as to handle in industrial products because it tends to be sticky and clumpy. Here, we describe the preparation of four pharmaceutical cocrystals involving IPBC. The obtained cocrystals have been characterized by X-ray diffraction, solution and solid-state NMR, IR, and DSC analyses. In all the described cases the halogen bond (XB) is the key interaction responsible for the self-assembly of the pharmaceutical cocrystals thanks to the involvement of the 1-iodoalkyne moiety of IPBC, which functions as a very reliable XB-donor, with both neutral and anionic XB-acceptors. Most of the obtained cocrystals have improved properties with respect to the source API, in terms, e.g., of thermal stability. The cocrystal involving the GRAS excipient CaCl2 has superior powder flow characteristics compared to the pure IPBC, representing a promising solution to the handling issues related to the manufacturing of products containing IPBC.

Pharmaceutical Logistics at the 121st General Hospital, Seoul, Korea

National Research Council Canada - National Science Library

Giraud, Roger S

2004-01-01

...). The sample consists of 122 days of pharmaceutical requisitions. Pharmaceutical logistics data are used to estimate a multiple regression model of OST for demand satisfaction and accommodation, requisition cost and volume and source of supply...

New Strategies for Powder Compaction in Powder-based Rapid Prototyping Techniques

NARCIS (Netherlands)

Budding, A.; Vaneker, Thomas H.J.

2013-01-01

In powder-based rapid prototyping techniques, powder compaction is used to create thin layers of fine powder that are locally bonded. By stacking these layers of locally bonded material, an object is made. The compaction of thin layers of powder mater ials is of interest for a wide range of

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.

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. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Moisture sorption of Thai red curry powder

Directory of Open Access Journals (Sweden)

Sudathip Inchuen

2009-12-01

Full Text Available Moisture sorption study was conducted on Thai red curry powder prepared by two different drying methods, viz. microwave and hot-air drying. Moisture sorption isotherms of the red curry powder at 30 C and water activity in the range of 0.113-0.970 were determined by a static gravimetric method. The isotherms exhibited Type III behaviour. The moisture sorption data were fitted to several sorption models and a non-linear regression analysis method was used to evaluate the constants of the sorption equations. The fit was evaluated using the coefficient of determination (R2, the reduced chi-square (2 and the root mean square error (RMSE. The GAB model followed by the Lewiski-3 model gave the best fit to the experimental data. The monolayer moisture content, taken as the safe minimum moisture level in the red curry powder, was determined using the BET equation and was found to range between 0.080 - 0.085 gram water per gram dry matter.

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.

Integration of pharmaceuticals with higher plants as a model of phytoremediation

OpenAIRE

Pomeislová, Alice

2015-01-01

The presence of pharmaceuticals in wastewater, which are not eliminated in sewage treatment plant process and thus get easily into rivers and aquatic environment in general, constitutes a severe problem to the whole society. The research into the removal of pharmaceuticals from the environment began about twenty years ago. Phytoremediation represents one of the most promising wastewater treatment methods. It is based on the ability of plants to remove xenobiotics from their environment and se...

Modeling of wear behavior of Al/B_4C composites produced by powder metallurgy

International Nuclear Information System (INIS)

Sahin, Ismail; Bektas, Asli; Guel, Ferhat; Cinci, Hanifi

2017-01-01

Wear characteristics of composites, Al matrix reinforced with B_4C 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_4C 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.

A novel nasal powder formulation of glucagon: toxicology studies in animal models

OpenAIRE

Reno, Frederick E.; Normand, Patrick; McInally, Kevin; Silo, Sherwin; Stotland, Patricia; Triest, Myriam; Carballo, Dolores; Pich?, Claude

2015-01-01

Background Glucagon nasal powder (GNP), a novel intranasal formulation of glucagon being developed to treat insulin-induced severe hypoglycemia, contains synthetic glucagon (10?% w/w), beta-cyclodextrin, and dodecylphosphocholine. The safety of this formulation was evaluated in four studies in animal models. Methods The first study evaluated 28-day sub-chronic toxicology in rats treated intranasally with 1 and 2?mg of GNP/day (0.1 and 0.2?mg glucagon/rat/day). The second study evaluated 28-da...

Dry coating of micronized API powders for improved dissolution of directly compacted tablets with high drug loading.

Science.gov (United States)

Han, Xi; Ghoroi, Chinmay; Davé, Rajesh

2013-02-14

Motivated by our recent study showing improved flow and dissolution rate of the active pharmaceutical ingredient (API) powders (20 μm) produced via simultaneous micronization and surface modification through continuous fluid energy milling (FEM) process, the performance of blends and direct compacted tablets with high drug loading is examined. Performance of 50 μm API powders dry coated without micronization is also considered for comparison. Blends of micronized, non-micronized, dry coated or uncoated API powders at 30, 60 and 70% drug loading, are examined. The results show that the blends containing dry coated API powders, even micronized ones, have excellent flowability and high bulk density compared to the blends containing uncoated API, which are required for direct compaction. As the drug loading increases, the difference between dry coated and uncoated blends is more pronounced, as seen in the proposed bulk density-FFC phase map. Dry coating led to improved tablet compactibility profiles, corresponding with the improvements in blend compressibility. The most significant advantage is in tablet dissolution where for all drug loadings, the t(80) for the tablets with dry coated APIs was well under 5 min, indicating that this approach can produce nearly instant release direct compacted tablets at high drug loadings. Copyright © 2012 Elsevier B.V. All rights reserved.

effect of chronic consumption of powdered tobacco (snuff)

African Journals Online (AJOL)

Uwaifoh

2012-12-31

Dec 31, 2012 ... The effect of chronic consumption of tobacco powder on anxiety, fear and social ... only, while the test group received mixed feed of 1gram powdered tobacco per ..... alkaloid, nicotine decrease tension and depressive feelings and promote the ... Ethnologically based animal models of anxiety disorders.

Powder bed charging during electron-beam additive manufacturing

International Nuclear Information System (INIS)

Cordero, Zachary C.; Meyer, Harry M.; Nandwana, Peeyush; Dehoff, Ryan R.

2017-01-01

Electrons injected into the build envelope during powder bed electron-beam additive manufacturing can accumulate on the irradiated particles and cause them to repel each other. Under certain conditions, these electrostatic forces can grow so large that they drive the particles out of the build envelope in a process known as “smoking”. In the present work, we investigate the causes of powder bed charging and smoking during electron-beam additive manufacturing. In the first part of the paper, we characterize the surface chemistry of a common feedstock material—gas-atomized Ti-6Al-4V powder—and find that a thick, electrically insulating oxide overlayer encapsulates the particles. Based on these experimental results, we then formulate an analytical model of powder bed charging in which each particle is approximated as a capacitor, where the particle and its substrate are the electrodes and the oxide overlayer is the dielectric. Using this model, we estimate the charge distribution in the powder bed, the electrostatic forces acting on the particles, and the conditions under which the powder bed will smoke. It is found that the electrical resistivity of the oxide overlayer strongly influences the charging behavior of the powder bed and that a high resistivity promotes charge accumulation and consequent smoking. This analysis suggests new quality control and process design measures that can help suppress smoking.

Fabrication of nuclear fuel by powder injection moulding: Study of the binders systems and the de-binding of feedstock containing actinide powder

International Nuclear Information System (INIS)

Bricout, J.

2012-01-01

Powder Injection Moulding (PIM) is identified as an innovative process for the nuclear fuel fabrication. Technological breakthrough compared to the current process of powder metallurgy, the impact of actinide powder's specificities on the different steps of PIM is performed. Alumina powders simulating actinide powder have been implemented with a reference binders system. Thermal and rheological studies show the injectability and the de-binding of feedstocks with adequate solid loading (≥50 %vol), thanks to the de-agglomeration during the mixing step, which allow to obtain net shape fuel pellet. Specific surface area of powders, acting as a key role in behaviour's feedstocks, has been integrated in analysis models of viscosity prediction according to the shear rate. Also conducted studies on uranium oxide powder show that the selected binders systems, which have a compatible rheological behaviour with PIM process, impact the de-agglomeration of powder and final microstructure of the fuel pellet, consistent with the results obtained on alumina powders. Independent behaviour of binders and uranium oxide powder, showing no adverse chemical reaction against the PIM process, show a residual mass of carbon of about 150 ppm after sintering. Binders system using polystyrene, resistant to radiolysis phenomena and loadable more than 50 %(vol) of actinide powder, shows the promising potential of PIM process for the fuel fabrication. (author) [fr

Modeling Li-ion conductivity in LiLa(PO{sub 3}){sub 4} powder

Energy Technology Data Exchange (ETDEWEB)

Mounir, Ferhi, E-mail: ferhi.mounir@gmail.com [Laboratoire de Physicochimie des Materiaux Mineraux et leurs Applications, Centre National des Recherches en Sciences des Materiaux, BP No. 73, 8027 Soliman (Tunisia); Karima, Horchani-Naifer [Laboratoire de Physicochimie des Materiaux Mineraux et leurs Applications, Centre National des Recherches en Sciences des Materiaux, BP No. 73, 8027 Soliman (Tunisia); Khaled, Ben Saad [Laboratoire de Photovoltaieque, Centre des Recherches et des Technologies de l' Energie, Technopole Borj Cedria, BP No. 95, 2050 Hammam Lif (Tunisia); Mokhtar, Ferid [Laboratoire de Physicochimie des Materiaux Mineraux et leurs Applications, Centre National des Recherches en Sciences des Materiaux, BP No. 73, 8027 Soliman (Tunisia)

2012-07-01

Polycrystalline powder and single-crystal of LiLa(PO{sub 3}){sub 4} are synthesized by solid state reaction and flux technique, respectively. A morphological description of the obtained product was made based on scanning electron microscopy micrographs. The obtained powder was characterized by X-ray powder diffraction, FTIR and Raman spectroscopies. Ionic conductivity of the LiLa(PO{sub 3}){sub 4} powder was measured and evaluated over a temperature range from 553 to 913 K. Single crystals of LiLa(PO{sub 3}){sub 4} are characterized by single-crystal X-ray diffraction. The LiLa(PO{sub 3}){sub 4} structure was found to be isotypic with LiNd(PO{sub 3}){sub 4}. It crystallizes in the monoclinic system with space group C2/c and cell parameters: a=16.635(6) A, b=7.130(3) A, c=9.913(3) A, {beta}=126.37(4) Degree-Sign , V=946.72(6) A{sup 3} and Z=4. The LiLa(PO{sub 3}){sub 4} structure was described as an alternation between spiraling chains (PO{sub 3}){sub n} and (La{sup 3+}, Li{sup +}) cations along the b direction. The small Li{sup +} ions, coordinated to four oxygen atoms, were located in the large connected cavities created between the LaO{sub 8} polyhedra and the polyphosphate chains. The jumping of Li{sup +} through tunnels of the crystalline network was investigated using complex impedance spectroscopy. The close value of the activation energies calculated through the analysis of conductivity data and loss spectra indicate that the transport in the investigated system is through hopping mechanism. The correlation between ionic conductivity of LiLa(PO{sub 3}){sub 4} and its crystallographic structure was investigated and the most probably transport pathway model was determined.

Pharmaceutical manufacturing facility discharges can substantially increase the pharmaceutical load to U.S. wastewaters

Science.gov (United States)

Scott, Tia-Marie; Phillips, Patrick J.; Kolpin, Dana W.; Colella, Kaitlyn M.; Furlong, Edward T.; Foreman, William T.; Gray, James L.

2018-01-01

Discharges from pharmaceutical manufacturing facilities (PMFs) previously have been identified as important sources of pharmaceuticals to the environment. Yet few studies are available to establish the influence of PMFs on the pharmaceutical source contribution to wastewater treatment plants (WWTPs) and waterways at the national scale. Consequently, a national network of 13 WWTPs receiving PMF discharges, six WWTPs with no PMF input, and one WWTP that transitioned through a PMF closure were selected from across the United States to assess the influence of PMF inputs on pharmaceutical loading to WWTPs. Effluent samples were analyzed for 120 pharmaceuticals and pharmaceutical degradates. Of these, 33 pharmaceuticals had concentrations substantially higher in PMF-influenced effluent (maximum 555,000 ng/L) compared to effluent from control sites (maximum 175 ng/L). Concentrations in WWTP receiving PMF input are variable, as discharges from PMFs are episodic, indicating that production activities can vary substantially over relatively short (several months) periods and have the potential to rapidly transition to other pharmaceutical products. Results show that PMFs are an important, national-scale source of pharmaceuticals to the environment.

Development and validation of a RP–HPLC method for the quantization studies of metronidazole in tablets and powders dosage forms

Directory of Open Access Journals (Sweden)

Elena Gabriela Oltean,

2011-12-01

Full Text Available An isocratic high-performance liquid chromatography (HPLC procedure was developed for the quantitative determination of metronidazole in tablets and powders. HPLC separation was carried out by reversed phasechromatography on Kromasil C18 (250 mm x 4.6 mm i.e.; 5 ìm particle size, held in thermostat at 25°C. The mobile phase consisted of methanol/ 0.1% phosphoric acid aq. (20/80v/v, with a flow rate of 1 ml/min and with UV detection at 317 nm. In order to validate the method, the following parameters have been investigated: linearity (r2=0.9999, range, precision, accuracy, specificity, limit of detection and limit of quantification. The described method can be successfully applied for the analysis of the active pharmaceuticalcompound in tablets and powders. This paper aimed to develop and validate an HPLC sensitive applicable method to determine the quantity of metronidazole in tablets and powders, contributing to the quality and safety control of these types of pharmaceutical preparations.

Conceptual Configuration of Pharmaceutical Plants in 3D

DEFF Research Database (Denmark)

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

2007-01-01

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. Configuration and 3D models can help validate the decisions made in the conceptual design process. 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....

Standardized reporting for rapid relative effectiveness assessments of pharmaceuticals.

Science.gov (United States)

Kleijnen, Sarah; Pasternack, Iris; Van de Casteele, Marc; Rossi, Bernardette; Cangini, Agnese; Di Bidino, Rossella; Jelenc, Marjetka; Abrishami, Payam; Autti-Rämö, Ilona; Seyfried, Hans; Wildbacher, Ingrid; Goettsch, Wim G

2014-11-01

Many European countries perform rapid assessments of the relative effectiveness (RE) of pharmaceuticals as part of the reimbursement decision making process. Increased sharing of information on RE across countries may save costs and reduce duplication of work. The objective of this article is to describe the development of a tool for rapid assessment of RE of new pharmaceuticals that enter the market, the HTA Core Model® for Rapid Relative Effectiveness Assessment (REA) of Pharmaceuticals. Eighteen member organisations of the European Network of Health Technology Assessment (EUnetHTA) participated in the development of the model. Different versions of the model were developed and piloted in this collaboration and adjusted accordingly based on feedback on the content and feasibility of the model. The final model deviates from the traditional HTA Core Model® used for assessing other types of technologies. This is due to the limited scope (strong focus on RE), the timing of the assessment (just after market authorisation), and strict timelines (e.g. 90 days) required for performing the assessment. The number of domains and assessment elements was limited and it was decided that the primary information sources should preferably be a submission file provided by the marketing authorisation holder and the European Public Assessment Report. The HTA Core Model® for Rapid REA (version 3.0) was developed to produce standardised transparent RE information of pharmaceuticals. Further piloting can provide input for possible improvements, such as further refining the assessment elements and new methodological guidance on relevant areas.

A novel analytical method for pharmaceutical polymorphs by terahertz spectroscopy and the optimization of crystal form at the discovery stage.

Science.gov (United States)

Ikeda, Yukihiro; Ishihara, Yoko; Moriwaki, Toshiya; Kato, Eiji; Terada, Katsuhide

2010-01-01

A novel analytical method for the determination of pharmaceutical polymorphs was developed using terahertz spectroscopy. It was found out that each polymorph of a substance showed a specific terahertz absorption spectrum. In particular, analysis of the second derivative spectrum was enormously beneficial in the discrimination of closely related polymorphs that were difficult to discern by powder X-ray diffractometry. Crystal forms that were obtained by crystallization from various solvents and stored under various conditions were specifically characterized by the second derivative of each terahertz spectrum. Fractional polymorphic transformation for substances stored under stressed conditions was also identified by terahertz spectroscopy during solid-state stability test, but could not be detected by powder X-ray diffractometry. Since polymorphs could be characterized clearly by terahertz spectroscopy, further physicochemical studies could be conducted in a timely manner. The development form of compound examined was determined by the results of comprehensive physicochemical studies that included thermodynamic relationships, as well as chemical and physicochemical stability. In conclusion, terahertz spectroscopy, which has unique power in the elucidation of molecular interaction within a crystal lattice, can play more important role in physicochemical research. Terahertz spectroscopy has a great potential as a tool for polymorphic determination, particularly since the second derivative of the terahertz spectrum possesses high sensitivity for pharmaceutical polymorphs.

Optimization of the pharmaceutical care system for diabetes patients using modern pharmaceutical informatics methodology

Directory of Open Access Journals (Sweden)

Андрій Ігорович Бойко

2016-04-01

Full Text Available Aim. Implementation of pharmaceutical informatics methods in the system of pharmaceutical care for diabetes patients in Ukraine.Methods. System method was used for the analysis of status and reforming the pharmaceutical care for patients with diabetes; program-oriented management at informatization project realization; pharmaceutical informatics in the creation of computer pharmaceutical knowledge bases; methods of data synthesis and summarizing.Results. System analysis of the basic directions of reforming the pharmaceutical care for patients with diabetes in Ukraine was carried out. Ways of it’s of optimization were processed: establishment of specialized pharmacies with implementation of modern information technologies and special postgraduate education for pharmacists. Structure and information providing of computer knowledge base “Pharmaceutical care for patients with diabetes” was substantiated.Conclusion. Based on the regional project “Informatization of prescription antidiabetic drugs circulation in Ukraine” realization, the necessity of establishment of specialized pharmacies providing pharmaceutical care for patients with diabetes was substantiated. Ways for optimization of postgraduate education for pharmacists of the specialized pharmacies by implementation of special thematic improvement cycles were proceed. Computer knowledge base as an effective tool for optimization of pharmaceutical care for patients with diabetes was realized

Probabilistic environmental risk characterization of pharmaceuticals in sewage treatment plant discharges.

Science.gov (United States)

Christensen, Anne Munch; Markussen, Bo; Baun, Anders; Halling-Sørensen, Bent

2009-10-01

The occurrence of pharmaceuticals in different water bodies and the findings of effects on aquatic organisms in ecotoxicity tests have raised concerns about environmental risks of pharmaceuticals in receiving waters. Due to the fact that the amount of ecotoxicological studies has increased significantly during the last decade, probabilistic approaches for risk characterization of these compounds may be feasible. This approach was evaluated by applying it to 22 human-used pharmaceuticals covering both pharmaceuticals with a high volume and high ecotoxicity, using ecotoxicological effect data from laboratory studies and comparing these to monitoring data on the effluents from sewage treatment plants in Europe and pharmaceutical sales quantities. We found that for 19 of the 22 selected pharmaceuticals the existing data were sufficient for probabilistic risk characterizations. The subsequently modeled ratios between monitored concentrations and low-effect concentrations were mostly above a factor of 100. Compared to the current paradigm for EU environmental risk assessment where a safety factor of 10 or 100 might have been used it seems that for the modeled compounds there's a low environmental risk. However, similarly calculated ratios for five pharmaceuticals (propranolol, ibuprofen, furosemide, ofloxacin, and ciprofloxacin) were below 100, while ibuprofen and ciprofloxacin are considered to be of high concern due to lack of ecotoxicity studies. This paper shows that by applying probabilistic approaches, existing data can be used to execute a comprehensive study on probability of impacts, thereby contributing to a more comprehensive environmental risk assessment of pharmaceuticals.

Mathematical modelling of powder material motion and transportation in high-temperature flow core during plasma coatings application

Science.gov (United States)

Bogdanovich, V. I.; Giorbelidze, M. G.

2018-03-01

A problem of mathematical modelling of powder material motion and transportation in gas thermal flow core has been addressed. Undertaken studies indicate significant impact on dynamics of motion of sprayed particles of phenomenological law for drag coefficient and accounting momentum loss of a plasma jet upon acceleration of these particles and their diameter. It is determined that at great dispersion of spraying particles, they reach detail surface at different velocity and significant particles separation takes place at spraying spot. According to the results of mathematical modelling, requirements for admissible dispersion of diameters of particles used for spraying have been formulated. Research has also allowed reducing separation of particles at the spraying spot due to the selection of the method of powder feed to the anode channel of the plasma torch.

Powder and compaction characteristics of pregelatinized starches.

Science.gov (United States)

Rojas, J; Uribe, Y; Zuluaga, A

2012-06-01

Pregelatinized starch is widely used as a pharmaceutical aid, especially as a filler-binder. It is known that the tableting performance of excipients could be affected by their source. The aim of this study was to evaluate the powder and tableting properties of pregelatinized starches obtained from yucca, corn and rice and compare those properties with those of Starch 1500. This material had the lowest particle size, and porosity and largest density and best flow. However, yucca starch and corn starch showed an irregular granule morphology, better compactibility and compressibility than Starch 1500. Their onset of plastic deformation and their strain rate sensitivity was comparable to that of Starch 1500. These two materials showed compact disintegration slower that Starch 1500. Conversely, rice starch showed a high elasticity, and friability, low compactibility, which are undesirable for direct compression. This study demonstrated the potential use of pregelatinized starches, especially those obtained from yucca and corn as direct compression filler-binders.

Development of a Population Balance Model of a pharmaceutical drying process and testing of solution methods

DEFF Research Database (Denmark)

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

2013-01-01

Drying is frequently used in the production of pharmaceutical tablets. Simulation-based control strategy development for such a drying process requires a detailed model. First, the drying of wet granules is modelled using a Population Balance Model. A growth term based on a reduced model was used......, which describes the decrease of the moisture content, to follow the moisture content distribution for a batch of granules. Secondly, different solution methods for solving the PBM are compared. The effect of grid size (discretization methods) is analyzed in terms of accuracy and calculation time. All...

Thermophysical characterization of the powder resulting from the ...

African Journals Online (AJOL)

This paper presents the results of thermophysical characterization of the powder resulting from the solar drying of Moringa oleifera leaves. The desorption isotherms of the powder, are determined by the gravimetric static method. The models of B.E.T, Smith, Henderson, Iglesias and GAB are used for the smoothing of the ...

Transport of Powders through Rotary Kilns: Experimental Study and Modelling

OpenAIRE

Debacq , Marie; Hartmann , Didier; Houzelot , Jean-Leon; Ablitzer , Denis

1999-01-01

International audience; During the nuclear fuel cycle, uranium as hexafluoride is enriched by means of gaseous-diffusion process. The depleted UF6 resulting from the isotope separation stage is converted into U3O8 to enable its safe storage (conversion carried out by COGEMA). The UF6 -> UO2 conversion is performed in four identical plants : UF6 is hydrolysed in the gaseous phase through a vertical reactor, then the UO2F2 powder formed is pyrohydrolysed into U3O8 powder through a lightly incli...

FEM modeling on the compaction of Fe and Al composite powders

Directory of Open Access Journals (Sweden)

Han P.

2015-01-01

Full Text Available The compaction process of Fe and Al composite powders subjected to single action die compaction was numerically modeled by FEM method. The relationship between the overall relative density and compaction pressure of the compacts with various Al contents was firstly identified, and the influences of Al content on the local relative density, stress, and their distributions were studied. Then the compaction pressure effects on the above properties with fixed Al content were discussed. Furthermore, detailed flow behaviors of the composite powders during compaction and the relationship between the compaction pressure and the ejection force/spring back of the compact were analyzed. The results show that: (1 With each compaction pressure, higher relative density can be realized with the increase of Al content and the relative density distribution tends to be uniform; (2 When the Al content is fixed, higher compaction pressure can lead to composite compact with higher relative density, and the equivalent Von Mises stress in the central part of the compact increases gradually; (3 Convective flow occurs at the top and bottom parts of the compact close to the die wall, each indicates a different flow behavior; (4 The larger the compaction pressure for each case, the higher the residual elasticity, and the larger the ejection force needed.

Spherical rhenium metal powder

International Nuclear Information System (INIS)

Leonhardt, T.; Moore, N.; Hamister, M.

2001-01-01

The development of a high-density, spherical rhenium powder (SReP) possessing excellent flow characteristics has enabled the use of advanced processing techniques for the manufacture of rhenium components. The techniques that were investigated were vacuum plasma spraying (VPS), direct-hot isostatic pressing (D-HIP), and various other traditional powder metallurgy processing methods of forming rhenium powder into near-net shaped components. The principal disadvantages of standard rhenium metal powder (RMP) for advanced consolidation applications include: poor flow characteristics; high oxygen content; and low and varying packing densities. SReP will lower costs, reduce processing times, and improve yields when manufacturing powder metallurgy rhenium components. The results of the powder characterization of spherical rhenium powder and the consolidation of the SReP are further discussed. (author)

Measurement of loose powder density

International Nuclear Information System (INIS)

Akhtar, S.; Ali, A.; Haider, A.; Farooque, M.

2011-01-01

Powder metallurgy is a conventional technique for making engineering articles from powders. Main objective is to produce final products with the highest possible uniform density, which depends on the initial loose powder characteristics. Producing, handling, characterizing and compacting materials in loose powder form are part of the manufacturing processes. Density of loose metallic or ceramic powder is an important parameter for die design. Loose powder density is required for calculating the exact mass of powder to fill the die cavity for producing intended green density of the powder compact. To fulfill this requirement of powder metallurgical processing, a loose powder density meter as per ASTM standards is designed and fabricated for measurement of density. The density of free flowing metallic powders can be determined using Hall flow meter funnel and density cup of 25 cm/sup 3/ volume. Density of metal powders like cobalt, manganese, spherical bronze and pure iron is measured and results are obtained with 99.9% accuracy. (author)

Evaluation of P-Listed Pharmaceutical Residues in Empty Pharmaceutical Containers

Science.gov (United States)

Under the Resource Conservation and Recovery Act (RCRA), some pharmaceuticals are considered acute hazardous wastes because their sole active pharmaceutical ingredients are P-listed commercial chemical products (40 CFR 261.33). Hospitals and other healthcare facilities have stru...

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

Design of Continuous Crystallizers for Production of Active Pharmaceutical Ingredients

DEFF Research Database (Denmark)

Capellades Mendez, Gerard; Christensen, Troels V.

The production of Active Pharmaceutical Ingredients (APIs) is conducted primarily in batch processes. This manufacturing approach is reinforced by a patent-driven business model and the need to minimize the process development times for newly patented drugs. However, the regulatory and business...... environments are now changing. The increasing costs of drug development, combined with the strict regulations and the competition from generic manufacturers, have pushed pharmaceutical companies to seek cheaper and more sustainable production methods. Transition from batch to Continuous Pharmaceutical...

The influence of direct compression powder blend transfer method from the container to the tablet press on product critical quality attributes: a case study.

Science.gov (United States)

Teżyk, Michał; Jakubowska, Emilia; Milczewska, Kasylda; Milanowski, Bartłomiej; Voelkel, Adam; Lulek, Janina

2017-06-01

The aim of this article is to compare the gravitational powder blend loading method to the tablet press and manual loading in terms of their influence on tablets' critical quality attributes (CQA). The results of the study can be of practical relevance to the pharmaceutical industry in the area of direct compression of low-dose formulations, which could be prone to content uniformity (CU) issues. In the preliminary study, particle size distribution (PSD) and surface energy of raw materials were determined using laser diffraction method and inverse gas chromatography, respectively. For trials purpose, a formulation containing two pharmaceutical ingredients (APIs) was used. Tablet samples were collected during the compression progress to analyze their CQAs, namely assay and CU. Results obtained during trials indicate that tested direct compression powder blend is sensitive to applied powder handling method. Mild increase in both APIs content was observed during manual scooping. Gravitational approach (based on discharge into the drum) resulted in a decrease in CU, which is connected to a more pronounced assay increase at the end of tableting than in the case of manual loading. The correct design of blend transfer over single unit processes is an important issue and should be investigated during the development phase since it may influence the final product CQAs. The manual scooping method, although simplistic, can be a temporary solution to improve the results of API's content and uniformity when compared to industrial gravitational transfer.

A review of monitoring methods for pharmaceutical wet granulation.

Science.gov (United States)

Hansuld, E M; Briens, L

2014-09-10

High-shear wet granulation is commonly used in the pharmaceutical industry to improve powder properties for downstream processes such as tabletting. Granule growth, however, is difficult to predict because the process is sensitive to raw material properties and operating conditions. Development of process analytical technologies is encouraged by regulatory bodies to improve process understanding and monitor quality online. The primary technologies investigated for high-shear wet granulation monitoring include power consumption, near-infrared spectroscopy, Raman spectroscopy, capacitance measurements, microwave measurements, imaging, focused beam reflectance measurements, spatial filter velocimetry, stress and vibration measurements, as well as acoustic emissions. This review summarizes relevant research related to each of these technologies and discusses the challenges associated with each approach as a possible process analytical technology tool for high-shear wet granulation. Copyright © 2014 Elsevier B.V. All rights reserved.

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. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fundamentals of powder metallurgy

International Nuclear Information System (INIS)

Khan, I.H.; Qureshi, K.A.; Minhas, J.I.

1988-01-01

This book is being presented to introduce the fundamentals of technology of powder metallurgy. An attempt has been made to present an overall view of powder metallurgy technology in the first chapter, whereas chapter 2 to 8 deal with the production of metal powders. The basic commercial methods of powder production are briefly described with illustrations. Chapter 9 to 12 describes briefly metal powder characteristics and principles of testing, mixing, blending, conditioning, compaction and sintering. (orig./A.B.)

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.

An investigation into the impact of magnesium stearate on powder feeding during roller compaction.

Science.gov (United States)

Dawes, Jason; Gamble, John F; Greenwood, Richard; Robbins, Phil; Tobyn, Mike

2012-01-01

A systematic evaluation on the effect of magnesium stearate on the transmission of a placebo formulation from the hopper to the rolls during screw fed roller compaction has been carried out. It is demonstrated that, for a system with two 'knurled' rollers, addition of 0.5% w/w magnesium stearate can lead to a significant increase in ribbon mass throughput, with a consequential increase in roll gap, compared to an unlubricated formulation (manufactured at equivalent process conditions). However, this effect is reduced if one of the rollers is smooth. Roller compaction of a lubricated formulation using two smooth rollers was found to be ineffective due to a reduction in friction at the powder/roll interface, i.e. powder was not drawn through the rollers leading to a blockage in the feeding system. An increase in ribbon mass throughput could also be achieved if the equipment surfaces were pre-lubricated. However this increase was found to be temporary suggesting that the residual magnesium stearate layer was removed from the equipment surfaces. Powder sticking to the equipment surfaces, which is common during pharmaceutical manufacturing, was prevented if magnesium stearate was present either in the blend, or at the roll surface. It is further demonstrated that the influence of the hopper stirrer, which is primarily used to prevent bridge formation in the hopper and help draw powder more evenly into the auger chamber, can lead to further mixing of the formulation, and could therefore affect a change in the lubricity of the carefully blended input material.

Modelling the Peak Elongation of Nylon6 and Fe Powder Based Composite Wire for FDM Feedstock Filament

Science.gov (United States)

Garg, Harish Kumar; Singh, Rupinder

2017-10-01

In the present work, to increase the application domain of fused deposition modelling (FDM) process, Nylon6-Fe powder based composite wire has been prepared as feed stock filament. Further for smooth functioning of feed stock filament without any change in the hardware and software of the commercial FDM setup, the mechanical properties of the newly prepared composite wire must be comparable/at par to the existing material i.e. ABS, P-430. So, keeping this in consideration; an effort has been made to model the peak elongation of in house developed feedstock filament comprising of Nylon6 and Fe powder (prepared on single screw extrusion process) for commercial FDM setup. The input parameters of single screw extruder (namely: barrel temperature, temperature of the die, speed of the screw, speed of the winding machine) and rheological property of material (melt flow index) has been modelled with peak elongation as the output by using response surface methodology. For validation of model the result of peak elongation obtained from the model equation the comparison was made with the results of actual experimentation which shows the variation of ±1 % only.

The evolution of hot-stage microscopy to aid solid-state characterizations of pharmaceutical solids

International Nuclear Information System (INIS)

Vitez, I.M.; Davidovich, M.; Newman, A.W.; Kiesnowski, C.

1998-01-01

A variety of techniques can be used to characterize the physical properties of pharmaceutical solids, including thermal analysis, hot-stage microscopy, X-ray powder diffraction, spectroscopic and micromeritic analysis. Comprehensive characterizations of the physical properties of pharmaceutical solids require a multi-disciplinary approach, since no single technique is capable of characterizing the materials completely.The combination of traditional hot-stage microscopy with new technologies such as high-resolution micrography, image capture, storage manipulation, and presentation, have permitted more comprehensive physical property characterizations to be conducted. As a result of these technological advances, it is possible to present the results of these microscopic analyses, as they were initially collected by the microscopist, outside of the laboratory.An evolutionary trail detailing the use of hot-stage microscopy in the Materials Science Group, from a simple melting point apparatus to the current hot-stage DSC microscopy instrument, will be presented. Examples of materials characterized using the hot-stage microscopy system will also be presented. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

MODERN METHODS OF PRICING IN THE STRATEGIC ACTIVITIES PLANNING OF PHARMACEUTICAL COMPANIES IN UKRAINE

Directory of Open Access Journals (Sweden)

N. Slushaenko

2015-04-01

Full Text Available This article investigated the role of pricing for strategic activities of pharmaceutical companies. It has been modified Bass diffusion model for new products, and it has been conducted empirical testing of the model on the sample of the products of the Ukrainian pharmaceutical market. Among the analyzed pricing models for new product allocated to one that meets the needs of the pharmaceutical industry and is based on available statistics. Formed a clear selection algorithm pricing policy of the company to the new product.

Novel methodology for pharmaceutical expenditure forecast.

Science.gov (United States)

Vataire, Anne-Lise; Cetinsoy, Laurent; Aballéa, Samuel; Rémuzat, Cécile; Urbinati, Duccio; Kornfeld, Åsa; Mzoughi, Olfa; Toumi, Mondher

2014-01-01

The value appreciation of new drugs across countries today features a disruption that is making the historical data that are used for forecasting pharmaceutical expenditure poorly reliable. Forecasting methods rarely addressed uncertainty. The objective of this project was to propose a methodology to perform pharmaceutical expenditure forecasting that integrates expected policy changes and uncertainty (developed for the European Commission as the 'EU Pharmaceutical expenditure forecast'; see http://ec.europa.eu/health/healthcare/key_documents/index_en.htm). 1) Identification of all pharmaceuticals going off-patent and new branded medicinal products over a 5-year forecasting period in seven European Union (EU) Member States. 2) Development of a model to estimate direct and indirect impacts (based on health policies and clinical experts) on savings of generics and biosimilars. Inputs were originator sales value, patent expiry date, time to launch after marketing authorization, price discount, penetration rate, time to peak sales, and impact on brand price. 3) Development of a model for new drugs, which estimated sales progression in a competitive environment. Clinical expected benefits as well as commercial potential were assessed for each product by clinical experts. Inputs were development phase, marketing authorization dates, orphan condition, market size, and competitors. 4) Separate analysis of the budget impact of products going off-patent and new drugs according to several perspectives, distribution chains, and outcomes. 5) Addressing uncertainty surrounding estimations via deterministic and probabilistic sensitivity analysis. This methodology has proven to be effective by 1) identifying the main parameters impacting the variations in pharmaceutical expenditure forecasting across countries: generics discounts and penetration, brand price after patent loss, reimbursement rate, the penetration of biosimilars and discount price, distribution chains, and the time

[The species traceability of the ultrafine powder and the cell wall-broken powder of herbal medicine based on DNA barcoding].

Science.gov (United States)

Xiang, Li; Tang, Huan; Cheng, Jin-le; Chen, Yi-long; Deng, Wen; Zheng, Xia-sheng; Lai, Zhi-tian; Chen, Shi-lin

2015-12-01

Ultrafine powder and cell wall-broken powder of herbal medicine lack of the morphological characters and microscopic identification features. This makes it hard to identify herb's authenticity with traditional methods. We tested ITS2 sequence as DNA barcode in identification of herbal medicine in ultrafine powder and cell wall-broken powder in this study. We extracted genomic DNAs of 93 samples of 31 representative herbal medicines (28 species), which include whole plant, roots and bulbs, stems, leaves, flowers, fruits and seeds. The ITS2 sequences were amplified and sequenced bidirectionally. The ITS2 sequences were identified using Basic Local Alignment Search Tool (BLAST) method in the GenBank database and DNA barcoding system to identify the herbal medicine. The genetic distance was analyzed using the Kimura 2-parameter (K2P) model and the Neighbor-joining (NJ) phylogenetic tree was constructed using MEGA 6.0. The results showed that DNA can be extracted successfully from 93 samples and high quality ITS2 sequences can be amplified. All 31 herbal medicines can get correct identification via BLAST method. The ITS2 sequences of raw material medicines, ultrafine powder and cell wall-broken powder have same sequence in 26 herbal medicines, while the ITS2 sequences in other 5 herbal medicines exhibited variation. The maximum intraspecific genetic-distances of each species were all less than the minimum interspecific genetic distances. ITS2 sequences of each species are all converged to their standard DNA barcodes using NJ method. Therefore, using ITS2 barcode can accurately and effectively distinguish ultrafine powder and cell wall-broken powder of herbal medicine. It provides a new molecular method to identify ultrafine powder and cell wall-broken powder of herbal medicine in the quality control and market supervision.

Laser cladding with powder

NARCIS (Netherlands)

Schneider, M.F.; Schneider, Marcel Fredrik

1998-01-01

This thesis is directed to laser cladding with powder and a CO2 laser as heat source. The laser beam intensity profile turned out to be an important pa6 Summary rameter in laser cladding. A numerical model was developed that allows the prediction of the surface temperature distribution that is

Tungsten and tungsten alloys by powder metallurgy

International Nuclear Information System (INIS)

Belhadjhamida, A.; German, R.M.

1991-01-01

Tungsten has a historical link with powder metallurgy and there is continued progress in expanding the available compositions and processing options. This paper starts with an introduction to the history of tungsten powder metallurgy and use this as a basis for analyzing some of the current trends. The literature base in tungsten processing is expanding and includes new alloys, microstructures, and processing routes. A few examples will be emphasize here to produce a frame work for this program, including description of sintering mechanisms for tungsten, liquid phase sintering advances, hot consolidation fundamentals, and options for complex shaping using powder injection modeling. For this base, subsequent presentations will expand on these fundamental advances

Acemetacin cocrystal structures by powder X-ray diffraction

Science.gov (United States)

Bolla, Geetha

2017-01-01

Cocrystals of acemetacin drug (ACM) with nicotinamide (NAM), p-aminobenzoic acid (PABA), valerolactam (VLM) and 2-pyridone (2HP) were prepared by melt crystallization and their X-ray crystal structures determined by high-resolution powder X-ray diffraction. The powerful technique of structure determination from powder data (SDPD) provided details of molecular packing and hydrogen bonding in pharmaceutical cocrystals of acemetacin. ACM–NAM occurs in anhydrate and hydrate forms, whereas the other structures crystallized in a single crystalline form. The carboxylic acid group of ACM forms theacid–amide dimer three-point synthon R 3 2(9)R 2 2(8)R 3 2(9) with three different syn amides (VLM, 2HP and caprolactam). The conformations of the ACM molecule observed in the crystal structures differ mainly in the mutual orientation of chlorobenzene fragment and the neighboring methyl group, being anti (type I) or syn (type II). ACM hydrate, ACM—NAM, ACM–NAM-hydrate and the piperazine salt of ACM exhibit the type I conformation, whereas ACM polymorphs and other cocrystals adopt the ACM type II conformation. Hydrogen-bond interactions in all the crystal structures were quantified by calculating their molecular electrostatic potential (MEP) surfaces. Hirshfeld surface analysis of the cocrystal surfaces shows that about 50% of the contribution is due to a combination of strong and weak O⋯H, N⋯H, Cl⋯H and C⋯H interactions. The physicochemical properties of these cocrystals are under study. PMID:28512568

Acemetacin cocrystal structures by powder X-ray diffraction

Directory of Open Access Journals (Sweden)

Geetha Bolla

2017-05-01

Full Text Available Cocrystals of acemetacin drug (ACM with nicotinamide (NAM, p-aminobenzoic acid (PABA, valerolactam (VLM and 2-pyridone (2HP were prepared by melt crystallization and their X-ray crystal structures determined by high-resolution powder X-ray diffraction. The powerful technique of structure determination from powder data (SDPD provided details of molecular packing and hydrogen bonding in pharmaceutical cocrystals of acemetacin. ACM–NAM occurs in anhydrate and hydrate forms, whereas the other structures crystallized in a single crystalline form. The carboxylic acid group of ACM forms theacid–amide dimer three-point synthon R32(9R22(8R32(9 with three different syn amides (VLM, 2HP and caprolactam. The conformations of the ACM molecule observed in the crystal structures differ mainly in the mutual orientation of chlorobenzene fragment and the neighboring methyl group, being anti (type I or syn (type II. ACM hydrate, ACM—NAM, ACM–NAM-hydrate and the piperazine salt of ACM exhibit the type I conformation, whereas ACM polymorphs and other cocrystals adopt the ACM type II conformation. Hydrogen-bond interactions in all the crystal structures were quantified by calculating their molecular electrostatic potential (MEP surfaces. Hirshfeld surface analysis of the cocrystal surfaces shows that about 50% of the contribution is due to a combination of strong and weak O...H, N...H, Cl...H and C...H interactions. The physicochemical properties of these cocrystals are under study.

Low pressure powder injection moulding of stainless steel powders

Energy Technology Data Exchange (ETDEWEB)

Zampieron, J.V.; Soares, J.P.; Mathias, F.; Rossi, J.L. [Powder Processing Center CCP, Inst. de Pesquisas Energeticas e Nucleares, Sao Paulo, SP (Brazil); Filho, F.A. [IPEN, Inst. de Pesquisas Energeticas e Nucleares, Cidade Univ., Sao Paulo, SP (Brazil)

2001-07-01

Low-pressure powder injection moulding was used to obtain AISI 316L stainless steel parts. A rheological study was undertaken using gas-atomised powders and binders. The binders used were based on carnauba wax, paraffin, low density polyethylene and microcrystalline wax. The metal powders were characterised in terms of morphology, particle size distribution and specific surface area. These results were correlated to the rheological behaviour. The mixture was injected in the shape of square bar specimens to evaluate the performance of the injection process in the green state, and after sintering. The parameters such as injection pressure, viscosity and temperature were analysed for process optimisation. The binders were thermally removed in low vacuum with the assistance of alumina powders. Debinding and sintering were performed in a single step. This procedure shortened considerably the debinding and sintering time. (orig.)

The argument for pharmaceutical policy.

Science.gov (United States)

Traulsen, Janine Morgall; Almarsdóttir, Anna Birna

2005-02-01

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 pharmaceutical policy is made; pharmaceutical policy as a dynamic process; and the new public health as a global issue. The article ends with a short description of the remaining five articles in the series which will deal with important aspects of pharmaceutical policy. The topics include: economic pressures on health care systems; drug utilization from the clinical viewpoint (rational use of medicines); the impact of pharmaceutical policy on patients and the patient impact on pharmaceutical policy; the professional perspective; and finally the last article which deals with studying and evaluating pharmaceutical policy.

Atlas of hot isostatic beryllium powder pressing diagrams

International Nuclear Information System (INIS)

Stoev, P.I.; Papirov, I.I.; Tikhinskij, G.F.; Vasil'ev, A.A.

1995-01-01

Diagrams of hot isotopic pressing (HIP) of beryllium powder with different grain size in a wide range of pressing parameters are built by mathematical modeling methods. The HIP diagrams presented are divided into 3 groups: parametric dependencies D=f(P,T); technological HIP diagrams; compacting mechanisms. The created data bank permits to optimise beryllium powder HIP with changing parameters. 4 refs., 23 figs

Modelling continuous pharmaceutical and bio-based processes at plant-wide level: A roadmap towards efficient decision-making

DEFF Research Database (Denmark)

Ramin, Pedram; Mansouri, Seyed Soheil; Udugama, Isuru A.

2018-01-01

The importance of developing simulation models for decision making in pharmaceutical and bio-based production processes is elaborated in this article. The advantages of modelling continuous processes are outlined and certain barriers in this regard are identified. Although there have been some...... advancements in the field, there needs to be a larger international collaboration in this regard for providing reliable data for model validation, for development of generic modelbased frameworks and implementing them in computer-aided platforms in the form of software tools....

Foundations of powder metallurgy

International Nuclear Information System (INIS)

Libenson, G.A.

1987-01-01

Consideration is being given to physicochemical foundations and technology of metal powders, moulding and sintering of bars, made of them or their mixtures with nonmetal powders. Data on he design of basic equipment used in the processes of powder metallurgy and its servicing are presented. General requirements of safety engineering when fabricating metal powders and products of them are mentioned

Shock wave equation of state of powder material

OpenAIRE

Dijken, D.K.; Hosson, J.Th.M. De

1994-01-01

A model is proposed to predict the following quantities for powder materials compacted by shock waves: the pressure, the specific volume, the internal energy behind the shock wave, and the shock-wave velocity U-s. They are calculated as a function of flyerplate velocity u(p) and initial powder specific volume V-00. The model is tested on Cu, Al2024, and Fe. Calculated U-s vs u(p) curves agree well with experiments provided V-00 is smaller than about two times the solid specific volume. The mo...

Preparation and utilization of metal oxide fine powder

Energy Technology Data Exchange (ETDEWEB)

Kim, Joon Soo; Jang, Hee Dong; Lim, Young Woong; Kim, Sung Don; Lee, Hi Sun; Lee, Hoo In; Kim, Chul Joo; Shim, Gun Joo; Jang, Dae Kyu [Korea Inst. of Geology Mining and Materials, Taejon (Korea, Republic of)

1995-12-01

Metal oxide fine powders finds many applications in industry as new materials. It is very much necessary for the development of such powders to improve the domestic industry. The purpose of present research is to develop a process for the preparation and utilization of metal oxide fine powder. This project is consisted of two main subjects. (1) Production of ultrafine metal oxide powder: Ultrafine metal oxide powder is defined as a metal oxide powder of less than 100 nanometer in particle size. Experiments for the control of particle size and distributions in the various reaction system and compared with results of (2 nd year research). Various reaction systems were adopted for the development of feasible process. Ultrafine particles could be prepared even higher concentration of TiCl{sub 4} and lower gas flowrate compared to TiCl{sub 4}-O{sub 2} system in the TiCl{sub 4}-Air-H{sub 2}O system. Ultrafine Al{sub 2}O{sub 3} powders also prepared with the change of concentration and gas flowrate. Experiments on the treatment of surface characteristics of ultrafine TiO{sub 2} powders were investigated using esterification and surface treating agents. A mathematical model that can predict the particle size and distribution was also developed. (2) Preparation of cerium oxide for high-grade polishing powder: Used cerium polishing powder was recycled for preparation of high grade cerium oxide polishing powder. Also, cerium hydroxide which was generated as by-product in processing of monazite ore was used as another material. These two materials were leached respectively by using acid, and the precipitate was gained in each leached solution by adjusting pH of the solution, and by selective crystallization. These precipitates were calcined to make high grade cerium oxide polishing powder. The effect of several experimental variables were investigated, and the optimum conditions were obtained through the experiments. (author). 81 refs., 49 figs., 27 tabs.

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."

Formation and mechanism of nanocrystalline AZ91 powders during HDDR processing

Energy Technology Data Exchange (ETDEWEB)

Liu, Yafen; Fan, Jianfeng, E-mail: fanjianfeng@tyut.edu.cn; Zhang, Hua; Zhang, Qiang; Gao, Jing; Dong, Hongbiao, E-mail: hd38@leicester.ac.uk; Xu, Bingshe

2017-03-15

Grain sizes of AZ91 alloy powders were markedly refined to about 15 nm from 100 to 160 μm by an optimized hydrogenation-disproportionation-desorption-recombination (HDDR) process. The effect of temperature, hydrogen pressure and processing time on phase and microstructure evolution of AZ91 alloy powders during HDDR process was investigated systematically by X-ray diffraction, optical microscopy, scanning electron microscopy and transmission electron microscopy, respectively. The optimal HDDR process for preparing nanocrystalline Mg alloy powders is hydriding at temperature of 350 °C under 4 MPa hydrogen pressure for 12 h and dehydriding at 350 °C for 3 h in vacuum. A modified unreacted core model was introduced to describe the mechanism of grain refinement of during HDDR process. - Highlights: • Grain size of the AZ91 alloy powders was significantly refined from 100 μm to 15 nm. • The optimal HDDR technology for nano Mg alloy powders is obtained. • A modified unreacted core model of grain refinement mechanism was proposed.

Pharmaceutical Residues Affecting the UNESCO Biosphere Reserve Kristianstads Vattenrike Wetlands

DEFF Research Database (Denmark)

Björklund, Erland; Svahn, Ola; Bak, Søren Alex

2016-01-01

This study is the first to investigate the pharmaceutical burden from point sources affecting the UNESCO Biosphere Reserve Kristianstads Vattenrike, Sweden. The investigated Biosphere Reserve is a >1000 km(2) wetland system with inflows from lakes, rivers, leachate from landfill, and wastewater......-treatment plants (WWTPs). We analysed influent and treated wastewater, leachate water, lake, river, and wetland water alongside sediment for six model pharmaceuticals. The two WWTPs investigated released pharmaceutical residues at levels close to those previously observed in Swedish monitoring exercises. Compound......-dependent WWTP removal efficiencies ranging from 12 to 100 % for bendroflumethiazide, oxazepam, atenolol, carbamazepine, and diclofenac were observed. Surface-water concentrations in the most affected lake were ≥100 ng/L for the various pharmaceuticals with atenolol showing the highest levels (>300 ng...

[Logistics in the pharmaceutical service].

Science.gov (United States)

Stanko, P; Fulmeková, M

2005-11-01

The conception of the field of pharmaceutical service defines pharmaceutical service as the basic part of pharmacy, the principal task of which is to provide pharmaceutical care as an inseparable part of providing health care. It represents a set of professional activities of the pharmacist oriented to securing human and veterinary pharmaceutical products and health care products and to optimising effective, safe and quality pharmacotherapy. Technically, pharmaceutical service is an applied discipline, as it makes use of knowledge gained in other pharmaceutical, medical, psychological, social, and economic sciences. Because of its interdisciplinary character it is necessary to extend the theory of pharmaceutical service in such a way so that it may reflect all aspects of its sphere of activity. One of the possibilities is to define the pharmacy premises as an independent functional unit which operates on the basis of valid legal standards in such a way that on the one hand it secures the provision of health (pharmaceutical) care, and on the other hand it maintains its cost-effectiveness. To keep the quality of care of the patient and the economic aspect in balance, it is necessary to define the term pharmaceutical logistics also under the conditions of Slovak (Czech) pharmacy as early satisfaction of the requirements of the patient (client) in the pharmacy premises, which means that the appropriate pharmaceutical product or health care product and the appropriate information must be at the right time in the required amount and required quality in the right place.

Adsorptive removal of selected pharmaceuticals by mesoporous silica SBA-15

International Nuclear Information System (INIS)

Bui, Tung Xuan; Choi, Heechul

2009-01-01

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 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.

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.

An Instructional Design Model for Developing a Computer Curriculum To Increase Employee Productivity in a Pharmaceutical Company.

Science.gov (United States)

Stumpf, Mark R.

This report presents an instructional design model that was developed for use by the End-Users Computing department of a large pharmaceutical company in developing effective--but not lengthy--microcomputer training seminars to train office workers and executives in the proper use of computers and thus increase their productivity. The 14 steps of…

Fabrication of metal matrix composite by semi-solid powder processing

Energy Technology Data Exchange (ETDEWEB)

Wu, Yufeng [Iowa State Univ., Ames, IA (United States)

2011-01-01

Various metal matrix composites (MMCs) are widely used in the automotive, aerospace and electrical industries due to their capability and flexibility in improving the mechanical, thermal and electrical properties of a component. However, current manufacturing technologies may suffer from insufficient process stability and reliability and inadequate economic efficiency and may not be able to satisfy the increasing demands placed on MMCs. Semi-solid powder processing (SPP), a technology that combines traditional powder metallurgy and semi-solid forming methods, has potential to produce MMCs with low cost and high efficiency. In this work, the analytical study and experimental investigation of SPP on the fabrication of MMCs were explored. An analytical model was developed to understand the deformation mechanism of the powder compact in the semi-solid state. The densification behavior of the Al6061 and SiC powder mixtures was investigated with different liquid fractions and SiC volume fractions. The limits of SPP were analyzed in terms of reinforcement phase loading and its impact on the composite microstructure. To explore adoption of new materials, carbon nanotube (CNT) was investigated as a reinforcing material in aluminum matrix using SPP. The process was successfully modeled for the mono-phase powder (Al6061) compaction and the density and density distribution were predicted. The deformation mechanism at low and high liquid fractions was discussed. In addition, the compaction behavior of the ceramic-metal powder mixture was understood, and the SiC loading limit was identified by parametric study. For the fabrication of CNT reinforced Al6061 composite, the mechanical alloying of Al6061-CNT powders was first investigated. A mathematical model was developed to predict the CNT length change during the mechanical alloying process. The effects of mechanical alloying time and processing temperature during SPP were studied on the mechanical, microstructural and

Use of whey powder and skim milk powder for the production of fermented cream

Directory of Open Access Journals (Sweden)

Ceren AKAL

2016-01-01

Full Text Available Abstract This study is about the production of fermented cream samples having 18% fat by addition of starter cultures. In order to partialy increase non-fat solid content of fermented cream samples, skim milk powder and demineralized whey powder in two different rates (50% and 70% were used. Samples were analyzed for changes in their biochemical and physicochemical properties (total solid, ash, fat, titratable acidity, pH value, total nitrogen, viscosity, tyrosine, acid number, peroxide and diacetyl values during 29-day of storage period. Samples tested consisted of 7 different groups; control group (without adding any powder, skim milk powder, 50% demineralized whey powder and 70% demineralized whey powder samples were in two different addition rate (2% and 4%. Also samples were analyzed for sensory properties. According to the results obtained, the addition of milk powder products affected titratable acidity and tyrosine values of fermented cream samples. Although powder addition and/or storage period didn’t cause significant variations in total solid, ash, fat, pH value, viscosity, acid number, peroxide, tyrosine and diacetyl values; sensory properties of fermented cream samples were influenced by both powder addition and storage period. Fermented cream containing 2% skim milk powder gets the top score of sensory evaluation among the samples.

Development of a microparticle-based dry powder inhalation formulation of ciprofloxacin hydrochloride applying the quality by design approach

Directory of Open Access Journals (Sweden)

Karimi K

2016-10-01

Full Text Available Keyhaneh Karimi, Edina Pallagi, Piroska Szabó-Révész, Ildikó Csóka, Rita Ambrus Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Szeged, Hungary Abstract: Pulmonary drug delivery of ciprofloxacin hydrochloride offers effective local antibacterial activity and convenience of easy application. Spray drying is a trustworthy technique for the production of ciprofloxacin hydrochloride microparticles. Quality by design (QbD, an up-to-date regulatory-based quality management method, was used to predict the final quality of the product. According to the QbD-based theoretical preliminary parameter ranking and priority classification, dry powder inhalation formulation tests were successfully performed in practice. When focusing on the critical parameters, the practical development was more effective and was in correlation with our previous findings. Spray drying produced spherical microparticles. The dry powder formulations prepared were examined by particle size analysis, scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray powder diffraction, differential scanning calorimetry, and in vitro drug release and aerodynamic particle size analyses were also performed. These formulations showed an appropriate particle size ranging between 2 and 4 µm and displayed an enhanced aerosol performance with fine particle fraction up to 80%. Keywords: antibiotic, carrier-free formulation, quality by design, aerodynamic evaluation, dry powder for inhalation

A comparison between two powder compaction parameters of plasticity: the effective medium A parameter and the Heckel 1/K parameter.

Science.gov (United States)

Mahmoodi, Foad; Klevan, Ingvild; Nordström, Josefina; Alderborn, Göran; Frenning, Göran

2013-09-10

The purpose of the research was to introduce a procedure to derive a powder compression parameter (EM A) representing particle yield stress using an effective medium equation and to compare the EM A parameter with the Heckel compression parameter (1/K). 16 pharmaceutical powders, including drugs and excipients, were compressed in a materials testing instrument and powder compression profiles were derived using the EM and Heckel equations. The compression profiles thus obtained could be sub-divided into regions among which one region was approximately linear and from this region, the compression parameters EM A and 1/K were calculated. A linear relationship between the EM A parameter and the 1/K parameter was obtained with a strong correlation. The slope of the plot was close to 1 (0.84) and the intercept of the plot was small in comparison to the range of parameter values obtained. The relationship between the theoretical EM A parameter and the 1/K parameter supports the interpretation of the empirical Heckel parameter as being a measure of yield stress. It is concluded that the combination of Heckel and EM equations represents a suitable procedure to derive a value of particle plasticity from powder compression data. Copyright © 2013 Elsevier B.V. All rights reserved.

Computational fluid dynamics (CFD) assisted performance evaluation of the Twincer™ disposable high-dose dry powder inhaler.

Science.gov (United States)

de Boer, Anne H; Hagedoorn, Paul; Woolhouse, Robert; Wynn, Ed

2012-09-01

To use computational fluid dynamics (CFD) for evaluating and understanding the performance of the high-dose disposable Twincer™ dry powder inhaler, as well as to learn the effect of design modifications on dose entrainment, powder dispersion and retention behaviour. Comparison of predicted flow and particle behaviour from CFD computations with experimental data obtained with cascade impactor and laser diffraction analysis. Inhaler resistance, flow split, particle trajectories and particle residence times can well be predicted with CFD for a multiple classifier based inhaler like the Twincer™. CFD computations showed that the flow split of the Twincer™ is independent of the pressure drop across the inhaler and that the total flow rate can be decreased without affecting the dispersion efficacy or retention behaviour. They also showed that classifier symmetry can be improved by reducing the resistance of one of the classifier bypass channels, which for the current concept does not contribute to the swirl in the classifier chamber. CFD is a highly valuable tool for development and optimisation of dry powder inhalers. CFD can assist adapting the inhaler design to specific physico-chemical properties of the drug formulation with respect to dispersion and retention behaviour. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

21 CFR 520.1696a - Buffered penicillin powder, penicillin powder with buffered aqueous diluent.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Buffered penicillin powder, penicillin powder with... FORM NEW ANIMAL DRUGS § 520.1696a Buffered penicillin powder, penicillin powder with buffered aqueous diluent. (a) Specifications. When reconstituted, each milliliter contains penicillin G procaine equivalent...

Biaxially textured articles formed by powder metallurgy

Science.gov (United States)

Goyal, Amit; Williams, Robert K.; Kroeger, Donald M.

2003-08-05

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 ternary mixtures consisting of: Ni powder, Cu powder, and Al powder, Ni powder, Cr powder, and Al powder; Ni powder, W powder and Al powder; Ni powder, V powder, and Al powder; Ni powder, Mo powder, and Al 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.

Analysis of tablet compaction. I. Characterization of mechanical behavior of powder and powder/tooling friction.

Science.gov (United States)

Cunningham, J C; Sinka, I C; Zavaliangos, A

2004-08-01

In this first of two articles on the modeling of tablet compaction, the experimental inputs related to the constitutive model of the powder and the powder/tooling friction are determined. The continuum-based analysis of tableting makes use of an elasto-plastic model, which incorporates the elements of yield, plastic flow potential, and hardening, to describe the mechanical behavior of microcrystalline cellulose over the range of densities experienced during tableting. Specifically, a modified Drucker-Prager/cap plasticity model, which includes material parameters such as cohesion, internal friction, and hydrostatic yield pressure that evolve with the internal state variable relative density, was applied. Linear elasticity is assumed with the elastic parameters, Young's modulus, and Poisson's ratio dependent on the relative density. The calibration techniques were developed based on a series of simple mechanical tests including diametrical compression, simple compression, and die compaction using an instrumented die. The friction behavior is measured using an instrumented die and the experimental data are analyzed using the method of differential slices. The constitutive model and frictional properties are essential experimental inputs to the finite element-based model described in the companion article. Copyright 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:2022-2039, 2004

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

Medical Representatives' Intention to Use Information Technology in Pharmaceutical Marketing.

Science.gov (United States)

Kwak, Eun-Seon; Chang, Hyejung

2016-10-01

Electronic detailing (e-detailing), the use of electronic devices to facilitate sales presentations to physicians, has been adopted and expanded in the pharmaceutical industry. To maximize the potential outcome of e-detailing, it is important to understand medical representatives (MRs)' behavior and attitude to e-detailing. This study investigates how information technology devices such as laptop computers and tablet PCs are utilized in pharmaceutical marketing, and it analyzes the factors influencing MRs' intention to use devices. This study has adopted and modified the theory of Roger's diffusion of innovation model and the technology acceptance model. To test the model empirically, a questionnaire survey was conducted with 221 MRs who were working in three multinational or eleven domestic pharmaceutical companies in Korea. Overall, 28% and 35% of MRs experienced using laptop computers and tablet PCs in pharmaceutical marketing, respectively. However, the rates were different across different groups of MRs, categorized by age, education level, position, and career. The results showed that MRs' intention to use information technology devices was significantly influenced by perceived usefulness in general. Perceived ease of use, organizational and individual innovativeness, and several MR characteristics were also found to have significant impacts. This study provides timely information about e-detailing devices to marketing managers and policy makers in the pharmaceutical industry for successful marketing strategy development by understanding the needs of MRs' intention to use information technology. Further in-depth study should be conducted to understand obstacles and limitations and to improve the strategies for better marketing tools.

Pharmaceutical advertising in emergency departments.

Science.gov (United States)

Marco, Catherine A

2004-04-01

Promotion of prescription drugs represents a growing source of pharmaceutical marketing expenditures. This study was undertaken to identify the frequency of items containing pharmaceutical advertising in clinical emergency departments (EDs). In this observational study, emergency physician on-site investigators quantified a variety of items containing pharmaceutical advertising present at specified representative times and days, in clinical EDs. Measurements were obtained by 65 on-site investigators, representing 22 states. Most EDs in this study were community EDs (87% community and 14% university or university affiliate), and most were in urban settings (50% urban, 38% suburban, and 13% rural). Investigators measured 42 items per ED (mean = 42; median = 31; interquartile range of 14-55) containing pharmaceutical advertising in the clinical area. The most commonly observed items included pens (mean 15 per ED; median 10), product brochures (mean 5; median 3), stethoscope labels (mean 4; median 2), drug samples (mean 3; median 0), books (mean 3.4), mugs (mean 2.4), and published literature (mean 3.1). EDs with a policy restricting pharmaceutical representatives in the ED had significantly fewer items containing pharmaceutical advertising (median 7.5; 95% CI = 0 to 27) than EDs without such a policy (median 35; 95% CI = 27 to 47, p = 0.005, nonparametric Wilcoxon two-sample test). There were no differences in quantities of pharmaceutical advertising for EDs in community compared with university settings (p = 0.5), rural compared with urban settings (p = 0.3), or annual ED volumes (p = 0.9). Numerous items containing pharmaceutical advertising are frequently observed in EDs. Policies restricting pharmaceutical representatives in the ED are associated with reduced pharmaceutical advertising.

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%.

Improved understanding of factors contributing to quantification of anhydrate/hydrate powder mixtures

DEFF Research Database (Denmark)

Rantanen, Jukka; Wikström, Håkan; Rhea, Francis E

2005-01-01

Different spectroscopic approaches have proved to be excellent analytical tools for monitoring process-induced transformations of active pharmaceutical ingredients during pharmaceutical unit operations. In order to use these tools effectively, it is necessary to build calibration models that desc...

Mathematical modelling of liquid transport in swelling pharmaceutical immediate release tablets.

Science.gov (United States)

Markl, Daniel; Yassin, Samy; Wilson, D Ian; Goodwin, Daniel J; Anderson, Andrew; Zeitler, J Axel

2017-06-30

Oral dosage forms are an integral part of modern health care and account for the majority of drug delivery systems. Traditionally the analysis of the dissolution behaviour of a dosage form is used as the key parameter to assess the performance of a drug product. However, understanding the mechanisms of disintegration is of critical importance to improve the quality of drug delivery systems. The disintegration performance is primarily impacted by the hydration and subsequent swelling of the powder compact. Here we compare liquid ingress and swelling data obtained using terahertz pulsed imaging (TPI) to a set of mathematical models. The interlink between hydration kinetics and swelling is described by a model based on Darcy's law and a modified swelling model based on that of Schott. Our new model includes the evolution of porosity, pore size and permeability as a function of hydration time. Results obtained from two sets of samples prepared from pure micro-crystalline cellulose (MCC) indicate a clear difference in hydration and swelling for samples of different porosities and particle sizes, which are captured by the model. Coupling a novel imaging technique, such as TPI, and mathematical models allows better understanding of hydration and swelling and eventually tablet disintegration. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Tropical Journal of Pharmaceutical Research

African Journals Online (AJOL)

Journal Homepage Image. We seek to encourage pharmaceutical and allied research of tropical and international relevance and to foster multidisciplinary research and collaboration among scientists, the pharmaceutical industry and the healthcare professionals. We publish articles in pharmaceutical sciences and related ...

Pharmaceutical Raw Material Identification Using Miniature Near-Infrared (MicroNIR) Spectroscopy and Supervised Pattern Recognition Using Support Vector Machine.

Science.gov (United States)

Sun, Lan; Hsiung, Chang; Pederson, Christopher G; Zou, Peng; Smith, Valton; von Gunten, Marc; O'Brien, Nada A

2016-05-01

Near-infrared spectroscopy as a rapid and non-destructive analytical technique offers great advantages for pharmaceutical raw material identification (RMID) to fulfill the quality and safety requirements in pharmaceutical industry. In this study, we demonstrated the use of portable miniature near-infrared (MicroNIR) spectrometers for NIR-based pharmaceutical RMID and solved two challenges in this area, model transferability and large-scale classification, with the aid of support vector machine (SVM) modeling. We used a set of 19 pharmaceutical compounds including various active pharmaceutical ingredients (APIs) and excipients and six MicroNIR spectrometers to test model transferability. For the test of large-scale classification, we used another set of 253 pharmaceutical compounds comprised of both chemically and physically different APIs and excipients. We compared SVM with conventional chemometric modeling techniques, including soft independent modeling of class analogy, partial least squares discriminant analysis, linear discriminant analysis, and quadratic discriminant analysis. Support vector machine modeling using a linear kernel, especially when combined with a hierarchical scheme, exhibited excellent performance in both model transferability and large-scale classification. Hence, ultra-compact, portable and robust MicroNIR spectrometers coupled with SVM modeling can make on-site and in situ pharmaceutical RMID for large-volume applications highly achievable. © The Author(s) 2016.

The Korean Pharmaceutical Industry and the Expansion of the General Pharmaceuticals Market in the 1950-1960s

Directory of Open Access Journals (Sweden)

Kyu-Hwan SIHN

2015-12-01

Full Text Available After the Liberation, the Korean economy was dependent on relief supplies and aid after the ruin of the colonial regime and war. The pharmaceutical business also searched for their share in the delivery of military supplies and the distribution of relief supplies. The supply-side pharmaceutical policy made the pharmaceutical market a wholesale business. The gravity of the situation led to an increased importation of medical supplies, and wholesalers took the lead in establishing the distribution structure, whereas consumers and pharmaceutical business were relatively intimidated. The aid provided by the International Cooperation Administration (ICA marked a turning point in the Korean pharmaceutical industry after the middle of the 1950s. ICA supplied raw materials and equipment funds, while the pharmaceutical business imported advanced technology and capital. The government invited the local production of medical substances, whereas pharmaceutical businesses replaced imported medical substances with locally produced antibiotics. After the 1960s, the production of antibiotics reached saturation. Pharmaceutical businesses needed new markets to break through the stalemate, so they turned their attention to vitamins and health tonics as general pharmaceuticals, as these were suitable for mass production and mass consumption. The modernized patent medicine market after the Opening of Korea was transformed into the contemporized general pharmaceuticals market equipped with the up-to-date facilities and technology in 1960s. Pharmaceutical businesses had to advertise these new products extensively and reform the distribution structure to achieve high profits. With the introduction of TV broadcasting, these businesses invested in TV advertising and generated sizable sales figures. They also established retail pharmacy and chain stores to reform the distribution structure. The end result was a dramatic expansion of the general pharmaceuticals market. The

[The Korean Pharmaceutical Industry and the Expansion of the General Pharmaceuticals Market in the 1950-1960s].

Science.gov (United States)

Sihn, Kyu-Hwan

2015-12-01

After the Liberation, the Korean economy was dependent on relief supplies and aid after the ruin of the colonial regime and war. The pharmaceutical business also searched for their share in the delivery of military supplies and the distribution of relief supplies. The supply-side pharmaceutical policy made the pharmaceutical market a wholesale business. The gravity of the situation led to an increased importation of medical supplies, and wholesalers took the lead in establishing the distribution structure, whereas consumers and pharmaceutical business were relatively intimidated. The aid provided by the International Cooperation Administration (ICA) marked a turning point in the Korean pharmaceutical industry after the middle of the 1950s. ICA supplied raw materials and equipment funds, while the pharmaceutical business imported advanced technology and capital. The government invited the local production of medical substances, whereas pharmaceutical businesses replaced imported medical substances with locally produced antibiotics. After the 1960s, the production of antibiotics reached saturation. Pharmaceutical businesses needed new markets to break through the stalemate, so they turned their attention to vitamins and health tonics as general pharmaceuticals, as these were suitable for mass production and mass consumption. The modernized patent medicine market after the Opening of Korea was transformed into the contemporized general pharmaceuticals market equipped with the up-to-date facilities and technology in 1960s. Pharmaceutical businesses had to advertise these new products extensively and reform the distribution structure to achieve high profits. With the introduction of TV broadcasting, these businesses invested in TV advertising and generated sizable sales figures. They also established retail pharmacy and chain stores to reform the distribution structure. The end result was a dramatic expansion of the general pharmaceuticals market. The market for

Pharmaceutical Formulation Facilities as Sources of Opioids and Other Pharmaceuticals to Wastewater Treatment Plant Effluents

Science.gov (United States)

2010-01-01

Facilities involved in the manufacture of pharmaceutical products are an under-investigated source of pharmaceuticals to the environment. Between 2004 and 2009, 35 to 38 effluent samples were collected from each of three wastewater treatment plants (WWTPs) in New York and analyzed for seven pharmaceuticals including opioids and muscle relaxants. Two WWTPs (NY2 and NY3) receive substantial flows (>20% of plant flow) from pharmaceutical formulation facilities (PFF) and one (NY1) receives no PFF flow. Samples of effluents from 23 WWTPs across the United States were analyzed once for these pharmaceuticals as part of a national survey. Maximum pharmaceutical effluent concentrations for the national survey and NY1 effluent samples were generally effluent had median concentrations ranging from 3.4 to >400 μg/L. Maximum concentrations of oxycodone (1700 μg/L) and metaxalone (3800 μg/L) in samples from NY3 effluent exceeded 1000 μg/L. Three pharmaceuticals (butalbital, carisoprodol, and oxycodone) in samples of NY2 effluent had median concentrations ranging from 2 to 11 μg/L. These findings suggest that current manufacturing practices at these PFFs can result in pharmaceuticals concentrations from 10 to 1000 times higher than those typically found in WWTP effluents. PMID:20521847

Synthesis of Gold Nanoparticles Stabilized in Dextran Solution by Gamma Co-60 Ray Irradiation and Preparation of Gold Nanoparticles/Dextran Powder

Directory of Open Access Journals (Sweden)

Phan Ha Nu Diem

2017-01-01

Full Text Available Gold nanoparticles (AuNPs in spherical shape with diameter of 6–35 nm stabilized by dextran were synthesized by γ-irradiation method. The AuNPs were characterized by UV-Vis spectroscopy and transmission electron microscopy. The influence of pH, Au3+ concentration, and dextran concentration on the size of AuNPs was investigated. Results indicated that the smallest AuNPs size (6 nm and the largest AuNPs size (35 nm were obtained for pH of 1 mM Au3+/1% dextran solution of 5.5 and 7.5, respectively. The smaller Au3+ concentration favored smaller size and conversely the smaller dextran concentration favored bigger size of AuNPs. AuNPs powders were prepared by spay drying, coagulation, and centrifugation and their sizes were also evaluated. The purity of prepared AuNPs powders was also examined by energy dispersive X-ray (EDX analysis. Thus, the as-prepared AuNPs stabilized by biocompatible dextran in solution and/or in powder form can be potentially applied in biomedicine and pharmaceutics.

Are exposure predictions, used for the prioritization of pharmaceuticals in the environment, fit for purpose?

Science.gov (United States)

Burns, Emily E; Thomas-Oates, Jane; Kolpin, Dana W; Furlong, Edward T; Boxall, Alistair B A

2017-10-01

Prioritization methodologies are often used for identifying those pharmaceuticals that pose the greatest risk to the natural environment and to focus laboratory testing or environmental monitoring toward pharmaceuticals of greatest concern. Risk-based prioritization approaches, employing models to derive exposure concentrations, are commonly used, but the reliability of these models is unclear. The present study evaluated the accuracy of exposure models commonly used for pharmaceutical prioritization. Targeted monitoring was conducted for 95 pharmaceuticals in the Rivers Foss and Ouse in the City of York (UK). Predicted environmental concentration (PEC) ranges were estimated based on localized prescription, hydrological data, reported metabolism, and wastewater treatment plant (WWTP) removal rates, and were compared with measured environmental concentrations (MECs). For the River Foss, PECs, obtained using highest metabolism and lowest WWTP removal, were similar to MECs. In contrast, this trend was not observed for the River Ouse, possibly because of pharmaceutical inputs unaccounted for by our modeling. Pharmaceuticals were ranked by risk based on either MECs or PECs. With 2 exceptions (dextromethorphan and diphenhydramine), risk ranking based on both MECs and PECs produced similar results in the River Foss. Overall, these findings indicate that PECs may well be appropriate for prioritization of pharmaceuticals in the environment when robust and local data on the system of interest are available and reflective of most source inputs. Environ Toxicol Chem 2017;36:2823-2832. © 2017 SETAC. © 2017 SETAC.

Cold compaction behavior and pressureless sinterability of ball milled WC and WC/Cu powders

Directory of Open Access Journals (Sweden)

Hashemi Seyed R.

2016-01-01

Full Text Available In this research, cold compaction behavior and pressureless sinterability of WC, WC-10%wtCu and WC-30%wtCu powders were investigated. WC and WC/Cu powders were milled in a planetary ball mill for 20h. The milled powders were cold compacted at 100, 200, 300 and 400 MPa pressures. The compressibility behavior of the powders was evaluated using the Heckel, Panelli-Ambrosio and Ge models. The results showed that the Panelli-Ambrosio was the preferred equation for description the cold compaction behavior of the milled WC and WC-30%wtCu powders. Also, the most accurate model for describing the compressibility of WC-10%wtCu powders was the Heckel equation. The cold compacts were sintered at 1400°C. It was found that by increasing the cold compaction pressure of powder compacts before sintering, the sinterability of WC-30%wtCu powder compacts was enhanced. However, the cold compaction magnitude was not affected significantly on the sinterability of WC and WC-10%wtCu powders. The microstructural investigations of the sintered samples by Scanning Electron Microscopy (SEM confirmed the presence of porosities at the interface of copper-tungsten carbide phases.

Application-oriented Crystallization of Pharmaceutical Products

DEFF Research Database (Denmark)

Bruun Hansen, Thomas

The purpose of this PhD thesis is to investigate various options for controlling the crystallization process of pharmaceutical products, both with regards to polymorphic control and crystal morphology. During this process, several model compounds were used, depending on the goal of the studies...

Integrating systems approaches into pharmaceutical sciences.

NARCIS (Netherlands)

Westerhoff, H.V.; Mosekilde, E.; Noe, C.; Clemensen, A.M.

2008-01-01

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

The solubility-permeability interplay in using cyclodextrins as pharmaceutical solubilizers: mechanistic modeling and application to progesterone.

Science.gov (United States)

Dahan, Arik; Miller, Jonathan M; Hoffman, Amnon; Amidon, Gregory E; Amidon, Gordon L

2010-06-01

A quasi-equilibrium mass transport analysis has been developed to quantitatively explain the solubility-permeability interplay that exists when using cyclodextrins as pharmaceutical solubilizers. The model considers the effects of cyclodextrins on the membrane permeability (P(m)) as well as the unstirred water layer (UWL) permeability (P(aq)), to predict the overall effective permeability (P(eff)) dependence on cyclodextrin concentration (C(CD)). The analysis reveals that: (1) UWL permeability markedly increases with increasing C(CD) since the effective UWL thickness quickly decreases with increasing C(CD); (2) membrane permeability decreases with increasing C(CD), as a result of the decrease in the free fraction of drug; and (3) since P(aq) increases and P(m) decreases with increasing C(CD), the UWL is effectively eliminated and the overall P(eff) tends toward membrane control, that is, P(eff) approximately P(m) above a critical C(CD). Application of this transport model enabled excellent quantitative prediction of progesterone P(eff) as a function of HP beta CD concentrations in PAMPA assay, Caco-2 transepithelial studies, and in situ rat jejunal-perfusion model. This work demonstrates that when using cyclodextrins as pharmaceutical solubilizers, a trade-off exists between solubility increase and permeability decrease that must not be overlooked; the transport model presented here can aid in striking the appropriate solubility-permeability balance in order to achieve optimal overall absorption. (c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association

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,

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.

Characterization of ceramic powder compacts

International Nuclear Information System (INIS)

Yanai, K.; Ishimoto, S.; Kubo, T.; Ito, K.; Ishikawa, T.; Hayashi, H.

1995-01-01

UO 2 and Al 2 O 3 powder packing structures in cylindrical powder compacts are observed by scanning electron microscopy using polished cross sections of compacts fixed by low viscosity epoxy resin. Hard aggregates which are not destroyed during powder compaction are observed in some of the UO 2 powder compacts. A technique to measure local density in powder compacts is developed based on counting characteristic X-ray intensity by energy dispersive X-ray analysis (EDX). The local density of the corner portion of the powder compact fabricated by double-acting dry press is higher than that of the inner portion. ((orig.))

Operation whey powder

International Nuclear Information System (INIS)

Brunner, E.

1987-01-01

The odyssey of the contaminated whey powder finally has come to an end, and the 5000 tonnes of whey now are designated for decontamination by means of an ion exchange technique. The article throws light upon the political and economic reasons that sent the whey powder off on a chaotic journey. It is worth mentioning in this context that the natural radioactivity of inorganic fertilizers is much higher than that of the whey powder in question. (HP) [de

Modelling and Characterization of Effective Thermal Conductivity of Single Hollow Glass Microsphere and Its Powder.

Science.gov (United States)

Liu, Bing; Wang, Hui; Qin, Qing-Hua

2018-01-14

Tiny hollow glass microsphere (HGM) can be applied for designing new light-weighted and thermal-insulated composites as high strength core, owing to its hollow structure. However, little work has been found for studying its own overall thermal conductivity independent of any matrix, which generally cannot be measured or evaluated directly. In this study, the overall thermal conductivity of HGM is investigated experimentally and numerically. The experimental investigation of thermal conductivity of HGM powder is performed by the transient plane source (TPS) technique to provide a reference to numerical results, which are obtained by a developed three-dimensional two-step hierarchical computational method. In the present method, three heterogeneous HGM stacking elements representing different distributions of HGMs in the powder are assumed. Each stacking element and its equivalent homogeneous solid counterpart are, respectively, embedded into a fictitious matrix material as fillers to form two equivalent composite systems at different levels, and then the overall thermal conductivity of each stacking element can be numerically determined through the equivalence of the two systems. The comparison of experimental and computational results indicates the present computational modeling can be used for effectively predicting the overall thermal conductivity of single HGM and its powder in a flexible way. Besides, it is necessary to note that the influence of thermal interfacial resistance cannot be removed from the experimental results in the TPS measurement.

Quantifying low amorphous or crystalline amounts of alpha-lactose-monohydrate using X-ray powder diffraction, near-infrared spectroscopy, and differential scanning calorimetry.

Science.gov (United States)

Fix, I; Steffens, K J

2004-05-01

Efficient and accurate quantification of low amorphous and crystalline contents within pharmaceutical materials still remains a challenging task in the pharmaceutical industry. Since X-ray powder diffraction (XRPD) equipment has improved in recent years, our aim was 1) to investigate the possibility of substantially lowering the detection limits of amorphous or crystalline material to about 1% or 0.5% w/w respectively by applying conventional Bragg Brentano optics, combined with a fast and simple evaluation technique; 2) to perform these measurements within a short time to make it suitable for routine analysis; and 3) to subject the same data sets to a partial least squares regression (PLSR) in order to investigate whether it is possible to improve accuracy and precision compared to the standard integration method. Near-infrared spectroscopy (NIRS) and differential scanning calorimetry (DSC) were chosen as reference method. As model substance, alpha lactose monohydrate was chosen to create calibration curves based on predetermined mixtures of highly crystalline and amorphous substance. In contrast to DSC, XRPD and NIRS revealed an excellent linearity, precision, and accuracy with the percent of crystalline amount and a detectability down to about 0.5% w/w. Chemometric evaluation (partial least squares regression) applied to the XRPD data further improved the quality of our calibration.

Hygroscopic trend of lyophilized ‘mangaba’ pulp powder

Directory of Open Access Journals (Sweden)

Juliana Conegero

Full Text Available ABSTRACT Mangaba is a widely-consumed fruit in the Northeast of Brazil, which is usually exploited through extractivism. This fruit is rich in various nutrients, especially in vitamin C, with pleasant taste and aroma. The lyophilization process transforms these fruits into amorphous powders, which must be analyzed regarding their properties and hygroscopic trend. Thus, the objective of this study was to characterize and evaluate the physico-chemical properties of adsorption isotherms of the lyophilized ‘mangaba’ pulp powder, with addition of maltodextrin (DE 20. The pH, titratable acidity, soluble solids, ascorbic acid and water activity were analyzed. Regarding the isotherms, the mathematical models of GAB, BET, Oswin, and Henderson were used at temperatures of 25, 30, 35 and 40 °C. The obtained powder presented pH of 3.14, titratable acidity of 1.95 mg of citric acid 100g-1 of powder, soluble solid contents of 99 ºBrix, ascorbic acid content of 55.97 mg 100g-1 and water activity of 0.16. Henderson was the mathematical model that best fitted the data of the adsorption isotherms at the four evaluated temperatures, with average errors ranging from 5.76 to 9.70% and R2 from 0.9974 to 0.9995.

Nuclear fuel powder transfer device

International Nuclear Information System (INIS)

Komono, Akira

1998-01-01

A pair of parallel rails are laid between a receiving portion to a molding portion of a nuclear fuel powder transfer device. The rails are disposed to the upper portion of a plurality of parallel support columns at the same height. A powder container is disposed while being tilted in the inside of the vessel main body of a transfer device, and rotational shafts equipped with wheels are secured to right and left external walls. A nuclear powder to be mixed, together with additives, is supplied to the powder container of the transfer device. The transfer device engaged with the rails on the receiving side is transferred toward the molding portion. The wheels are rotated along the rails, and the rotational shafts, the vessel main body and the powder container are rotated. The nuclear powder in the tilted powder container disposed is rotated right and left and up and down by the rotation, and the powder is mixed satisfactory when it reaches the molding portion. (I.N.)

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

Science.gov (United States)

Lutka, Anna; Maruszewska, Małgorzata

2011-01-01

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

The Purpose and Scope of Pedagogy in Pharmaceutical Education.

Science.gov (United States)

Nakamura, Akihiro

2017-01-01

The WHO and International Pharmaceutical Federation (FIP) introduced the concept of the "seven-star pharmacist" in which a pharmacist is described as a caregiver, communicator, decision-maker, teacher, lifelong learner, leader and manager. In six-year pharmaceutical education programs, which have been provided in schools of pharmacy since 2006, 5th year students participate in on-site practice experiences in hospitals and community pharmacies. Thus, Japanese pharmacists also began to have a role in pharmaceutical education as teachers in clinical settings. Not only pharmacists in clinical settings, but also faculty members of pharmacy schools, had not previously been familiar with evidence-based education, and therefore they often teach in the way they were taught. Since research on teaching and learning has not been well developed in Japanese pharmaceutical education, both the model core curriculum for six-year programs and the subject benchmark statement for four-year programs are based on insufficient scientific evidence. We should promote the scholarship of teaching and learning, which promotes teaching as a scholarly endeavor and a worthy subject for research. In this review, I will summarize the needs and expectations for the establishment of pedagogy in pharmaceutical education.

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.

Presentation of a Novel Model for Evaluation of Commercialization of Research and Development: Case Study of the Pharmaceutical Biotechnology Industry.

Science.gov (United States)

Emami, Hassan; Radfar, Reza

2017-01-01

The current situation in Iran suggests an appropriate basis for developing biotechnology industries, because the patents for the majority of hi-tech medicines registered in developed countries are ending. Biosimilar and technology-oriented companies which do not have patents will have the opportunity to enter the biosimilar market and move toward innovative initiatives. The present research proposed a model by which one can evaluate commercialization of achievements obtained from research with a focus on the pharmaceutical biotechnology industry. This is a descriptive-analytic study where mixed methodology is followed by a heuristic approach. The statistical population was pharmaceutical biotechnology experts at universities and research centers in Iran. Structural equations were employed in this research. The results indicate that there are three effective layers within commercialization in the proposed model. These are a general layer (factors associated with management, human capital, legal infrastructure, communication infrastructure, a technical and executive infrastructures, and financial factors), industrial layer (internal industrial factors and pharmaceutical industry factors), and a third layer that included national and international aspects. These layers comprise 6 domains, 21 indices, 41 dimensions, and 126 components. Compilation of these layers (general layer, industrial layer, and national and international aspects) can serve commercialization of research and development as an effective evaluation package.

[An example of self-evaluation of a sense of achievement by students in 6-year pharmacy school with the model core curriculum of pharmaceutical education].

Science.gov (United States)

Shingaki, Tomoteru; Koyanagi, Jyunichi; Nakamura, Hiroshi; Hirata, Takahiro; Ohta, Atsutane; Akimoto, Masayuki; Shirahata, Akira; Mitsumoto, Atsushi

2013-01-01

In March 2012, the first students, finishing the newly introduced 6-year-course of pharmaceutical education, have graduated and gone out into the world. At this point, the Ministry of Education, Culture, Sports, Science and Technology (MEXT) is going to revise the model core curriculum of pharmaceutical education to be more suited for educating students to achieve their goal of becoming the clinical pharmacist standard defined by the revised School Education Act. Here we report the self-evaluation study based on the survey using questionnaire about a sense of achievement with Visual Analog Scales, regarding the fundamental quality as a pharmacist standard proposed by the Professional Activities Committee in the MEXT. The sample size of survey was about 600 of students studying in the Faculty of Pharmaceutical Sciences in Josai International University (JIU) and the survey was carried out during the period of March-April in 2012. The study suggested that the majority of graduates were satisfied with the new education system and marked as a well-balanced quality to be a pharmacist standard, after completing the 6-year pharmaceutical education based on "the model core-curriculum". It would be worthwhile to perform this kind of survey continuously to monitor the student's self-evaluation of a sense of achievement to verify the effectiveness of 6-year-course pharmaceutical education based on the newly establishing core curriculum in Japan.

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 The paper captures the effect of structure and the applicability of compaction models using the cold compaction of a TiH2-SS316L composite powder prepared by high energy mechanical milling. The composite blend was cold pressed uniaxially...

Model for absorption-modified multiplication effects in the assay of HEU-containing powders in a random driver

International Nuclear Information System (INIS)

Winslow, G.H.

1981-01-01

A model has been developed which describes the enhancement of the response, in a random driver, of a ''stack'' of highly enriched uranium of arbitrary height over the integral of the response of infinitessimal layers that would be produced solely by the interrogating sources which are external to the stack. It has been suggested that this method of modeling should also be applicable to powders. This paper is a report on the form the model takes for that application. 4 refs

Investigation of metal ions sorption of brown peat moss powder

Science.gov (United States)

Kelus, Nadezhda; Blokhina, Elena; Novikov, Dmitry; Novikova, Yaroslavna; Chuchalin, Vladimir

2017-11-01

For regularities research of sorptive extraction of heavy metal ions by cellulose and its derivates from aquatic solution of electrolytes it is necessary to find possible mechanism of sorption process and to choice a model describing this process. The present article investigates the regularities of aliovalent metals sorption on brown peat moss powder. The results show that sorption isotherm of Al3+ ions is described by Freundlich isotherm and sorption isotherms of Na+ i Ni2+ are described by Langmuir isotherm. To identify the mechanisms of brown peat moss powder sorption the IR-spectra of the initial brown peat moss powder samples and brown peat moss powder samples after Ni (II) sorption were studied. Metal ion binding mechanisms by brown peat moss powder points to ion exchange, physical adsorption, and complex formation with hydroxyl and carboxyl groups.

Preparation of tris(8-hydroxyquinolinato)aluminum thin films by sputtering deposition using powder and pressed powder targets

Science.gov (United States)

Kawasaki, Hiroharu; Ohshima, Tamiko; Yagyu, Yoshihito; Ihara, Takeshi; Tanaka, Rei; Suda, Yoshiaki

2017-06-01

Tris(8-hydroxyquinolinato)aluminum (Alq3) thin films, for use in organic electroluminescence displays, were prepared by a sputtering deposition method using powder and pressed powder targets. Experimental results suggest that Alq3 thin films can be prepared using powder and pressed powder targets, although the films were amorphous. The surface color of the target after deposition became dark brown, and the Fourier transform infrared spectroscopy spectrum changed when using a pressed powder target. The deposition rate of the film using a powder target was higher than that using a pressed powder target. That may be because the electron and ion densities of the plasma generated using the powder target are higher than those when using pressed powder targets under the same deposition conditions. The properties of a thin film prepared using a powder target were almost the same as those of a film prepared using a pressed powder target.

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.

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

International Nuclear Information System (INIS)

Vamathevan, Jessica J.; Hall, Matthew D.; Hasan, Samiul; Woollard, Peter M.; Xu, Meng; Yang, Yulan; Li, Xin; Wang, Xiaoli; Kenny, Steve; Brown, James R.; Huxley-Jones, Julie; Lyon, Jon; Haselden, John; Min, Jiumeng; Sanseau, Philippe

2013-01-01

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

Influence of Ultrafine 2CaO·SiO₂ Powder on Hydration Properties of Reactive Powder Concrete.

Science.gov (United States)

Sun, Hongfang; Li, Zishanshan; Memon, Shazim Ali; Zhang, Qiwu; Wang, Yaocheng; Liu, Bing; Xu, Weiting; Xing, Feng

2015-09-17

In this research, we assessed the influence of an ultrafine 2CaO·SiO₂ powder on the hydration properties of a reactive powder concrete system. The ultrafine powder was manufactured through chemical combustion method. The morphology of ultrafine powder and the development of hydration products in the cement paste prepared with ultrafine powder were investigated by scanning electron microscopy (SEM), mineralogical composition were determined by X-ray diffraction, while the heat release characteristics up to the age of 3 days were investigated by calorimetry. Moreover, the properties of cementitious system in fresh and hardened state (setting time, drying shrinkage, and compressive strength) with 5% ordinary Portland cement replaced by ultrafine powder were evaluated. From SEM micrographs, the particle size of ultrafine powder was found to be up to several hundred nanometers. The hydration product started formulating at the age of 3 days due to slow reacting nature of belitic 2CaO·SiO₂. The initial and final setting times were prolonged and no significant difference in drying shrinkage was observed when 5% ordinary Portland cement was replaced by ultrafine powder. Moreover, in comparison to control reactive powder concrete, the reactive powder concrete containing ultrafine powder showed improvement in compressive strength at and above 7 days of testing. Based on above, it can be concluded that the manufactured ultrafine 2CaO·SiO₂ powder has the potential to improve the performance of a reactive powder cementitious system.

Current Status and Issues in Basic Pharmaceutical Education.

Science.gov (United States)

Yasuhara, Tomohisa

2017-01-01

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

Application of laser in powder metallurgy

International Nuclear Information System (INIS)

Tolochko, N.K.

1995-01-01

Modern status of works in the field of laser application in powder metallurgy (powders preparation, sintering, coatings formation, powder materials processing) is considered. The attention is paid to the new promising direction in powder products shape-formation technology - laser layer-by-layer selective powders sintering and bulk sintering of packaged layered profiles produced by laser cutting of powder-based sheet blanks. 67 refs

A polychromator-type near-infrared spectrometer with a high-sensitivity and high-resolution photodiode array detector for pharmaceutical process monitoring on the millisecond time scale

OpenAIRE

Murayama, Kodai; Genkawa, Takuma; Ishikawa, Daitaro; Komiyama, Makoto; Ozaki, Yukihiro

2013-01-01

In the fine chemicals industry, particularly in the pharmaceutical industry, advanced sensing technologies have recently begun being incorporated into the process line in order to improve safety and quality in accordance with process analytical technology. For estimating the quality of powders without preparation during drug formulation, near-infrared (NIR) spectroscopy has been considered the most promising sensing approach. In this study, we have developed a compact polychromator-type NIR s...

Supramolecular Pharmaceutical Sciences: A Novel Concept Combining Pharmaceutical Sciences and Supramolecular Chemistry with a Focus on Cyclodextrin-Based Supermolecules.

Science.gov (United States)

Higashi, Taishi; Iohara, Daisuke; Motoyama, Keiichi; Arima, Hidetoshi

2018-01-01

Supramolecular chemistry is an extremely useful and important domain for understanding pharmaceutical sciences because various physiological reactions and drug activities are based on supramolecular chemistry. However, it is not a major domain in the pharmaceutical field. In this review, we propose a new concept in pharmaceutical sciences termed "supramolecular pharmaceutical sciences," which combines pharmaceutical sciences and supramolecular chemistry. This concept could be useful for developing new ideas, methods, hypotheses, strategies, materials, and mechanisms in pharmaceutical sciences. Herein, we focus on cyclodextrin (CyD)-based supermolecules, because CyDs have been used not only as pharmaceutical excipients or active pharmaceutical ingredients but also as components of supermolecules.

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.

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

Science.gov (United States)

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

2015-01-15

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

Simulation of hypothetical criticality accidents involving homogeneous damp low-enriched UO2 powder systems

International Nuclear Information System (INIS)

Basoglu, B.; Brewer, R.W.; Haught, C.F.; Hollenbach, D.F.; Wilkinson, A.D.; Dodds, H.L.; Pasqua, P.F.

1994-01-01

This paper describes the development of a computer model for predicting the excursion characteristics of a postulated, hypothetical, critically accident involving a homogeneous mixture of low-enriched UO 2 powder and water contained in a cylindrical blender. The model uses point neutronics coupled with simple lumped-parameter thermal-hydraulic feedback. The temperature of the system is calculated using a simple time-dependent energy balance where two extreme conditions for the thermal behavior of the system are considered, which bound the real life situation. Using these extremes, three different models are developed. To evaluate the models, the authors compared the results with the results of the POWDER code, which was developed by the Commissariat a l'Energie Atomique/United Kingdom Atomic Energy Authority (CEA/UKAEA) for damp powder systems. The agreement in these comparisons is satisfactory. Results of the excursion studies in this work show that approximately 10 19 fissions occur as a result of accidental water ingress into powder blenders containing 5,000 kg of low-enriched (5%) UO 2 powder

Risperidone – Solid-state characterization and pharmaceutical compatibility using thermal and non-thermal techniques

Energy Technology Data Exchange (ETDEWEB)

Daniel, Josiane Souza Pereira; Veronez, Isabela Pianna; Rodrigues, Larissa Lopes [Laboratório de Análise e Caracterização de Fármacos – LACFar, Instituto de Química, Universidade Federal de Alfenas, Alfenas, Minas Gerais (Brazil); Trevisan, Marcello G. [Laboratório de Análise e Caracterização de Fármacos – LACFar, Instituto de Química, Universidade Federal de Alfenas, Alfenas, Minas Gerais (Brazil); National Institute of Bioanalytics Science and Technology – INCTBio, Institute of Chemistry – UNICAMP, 13084-653, Campinas, São Paulo (Brazil); Garcia, Jerusa Simone, E-mail: jerusa.garcia@unifal-mg.edu.br [Laboratório de Análise e Caracterização de Fármacos – LACFar, Instituto de Química, Universidade Federal de Alfenas, Alfenas, Minas Gerais (Brazil)

2013-09-20

Highlights: • DSC was used to characterize Risperidone and study its compatibility with excipients. • FT-IR associated with PCA was used to complement DSC data. • LC analyzes confirmed the DSC and FT-IR/PCA results. • Risperidone was incompatible with three among five excipients evaluated. - Abstract: A full solid-state characterization of risperidone was conducted using differential scanning calorimetry (DSC), thermogravimetry (TG), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM) to examine its physicochemical properties and polymorphism. The primary aim of this work was to study the compatibility of risperidone with pharmaceutical excipients using DSC to obtain and compare the curves of the active pharmaceutical ingredient (API) and the excipients with their 1:1 (w/w) binary mixtures. These same binary mixtures were turned to room temperature and analyzed by FT-IR combined with principal component analysis (PCA) to evaluate solid-state incompatibilities. The chemical incompatibilities of these samples were verified using a stability-indicating liquid chromatography (LC) method to assay for the API and evaluate the formation of degradation products. All of these methods showed incompatibilities between risperidone and the excipients magnesium stearate, lactose and cellulose microcrystalline.

Solvent selection methodology for pharmaceutical processes: Solvent swap

DEFF Research Database (Denmark)

Papadakis, Emmanouil; Kumar Tula, Anjan; Gani, Rafiqul

2016-01-01

A method for the selection of appropriate solvents for the solvent swap task in pharmaceutical processes has been developed. This solvent swap method is based on the solvent selection method of Gani et al. (2006) and considers additional selection criteria such as boiling point difference...... in pharmaceutical processes as well as new solvent swap alternatives. The method takes into account process considerations such as batch distillation and crystallization to achieve the swap task. Rigorous model based simulations of the swap operation are performed to evaluate and compare the performance...

[Hospital pharmaceutical practice in prison].

Science.gov (United States)

Harcouët, L

2010-09-01

Since 1994, hospital pharmaceutical teams have been in charge of pharmaceutical tasks in "unités de consultation et de soins ambulatoires" (UCSA), which are hospital consulting care units in French prisons. In 2008, pharmaceutical team in Parisian prisons received 6500 prescriptions and prepared 85,000 nominative bags containing drugs. Prisoners were 1.3% to receive treatments against HIV, 8.2% cardiovascular drugs, 7.2% opioid substitution treatments, and 52.9% psychoactive drugs, including 39.3% hypnotics, 40.5% anxiolytics, 11.3% antidepressants and 12.2% neuroleptics. In prison, the dichotomy between somatic and mental care is marked, attitudes of prisoners about their medicines are complex (important claims, embezzlement, etc.) and it is difficult for law defendants to maintain treatment confidentiality and to prepare prison outing in terms of health. To attenuate the heterogeneity of drug distribution systems in French prisons, we propose pharmaceutical analysis of prescriptions and nominative dispensation, computerization in UCSA in coordination with hospitals, a better contribution of prison medical and pharmaceutical staff in hospital "drug committees" and the redaction of pharmaceutical guidelines. Acting in concert with multidisciplinary medical staff in UCSA, pharmaceutical teams have to develop epidemiological studies to improve knowledge in prisoner's health and also prevention and health care in prison. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Ceramic Inclusions In Powder Metallurgy Disk Alloys: Characterization and Modeling

Science.gov (United States)

Bonacuse, Pete; Kantzos, Pete; Telesman, Jack

2002-01-01

Powder metallurgy alloys are increasingly used in gas turbine engines, especially as the material chosen for turbine disks. Although powder metallurgy materials have many advantages over conventionally cast and wrought alloys (higher strength, higher temperature capability, etc.), they suffer from the rare occurrence of ceramic defects (inclusions) that arise from the powder atomization process. These inclusions can have potentially large detrimental effect on the durability of individual components. An inclusion in a high stress location can act as a site for premature crack initiation and thereby considerably reduce the fatigue life. Because these inclusions are exceedingly rare, they usually don't reveal themselves in the process of characterizing the material for a particular application (the cumulative volume of the test bars in a fatigue life characterization is typically on the order of a single actual component). Ceramic inclusions have, however, been found to be the root cause of a number of catastrophic engine failures. To investigate the effect of these inclusions in detail, we have undertaken a study where a known population of ceramic particles, whose composition and morphology are designed to mimic the 'natural' inclusions, are added to the precursor powder. Surface connected inclusions have been found to have a particularly large detrimental effect on fatigue life, therefore the volume of ceramic 'seeds' added is calculated to ensure that a minimum number will occur on the surface of the fatigue test bars. Because the ceramic inclusions are irregularly shaped and have a tendency to break up in the process of extrusion and forging, a method of calculating the probability of occurrence and expected intercepted surface and embedded cross-sectional areas were needed. We have developed a Monte Carlo simulation to determine the distributions of these parameters and have verified the simulated results with observations of ceramic inclusions found in macro

Influence of Powder Injection Parameters in High-Pressure Cold Spray

Science.gov (United States)

Ozdemir, Ozan C.; Widener, Christian A.

2017-10-01

High-pressure cold spray systems are becoming widely accepted for use in the structural repair of surface defects of expensive machinery parts used in industrial and military equipment. The deposition quality of cold spray repairs is typically validated using coupon testing and through destructive analysis of mock-ups or first articles for a defined set of parameters. In order to provide a reliable repair, it is important to not only maintain the same processing parameters, but also to have optimum fixed parameters, such as the particle injection location. This study is intended to provide insight into the sensitivity of the way that the powder is injected upstream of supersonic nozzles in high-pressure cold spray systems and the effects of variations in injection parameters on the nature of the powder particle kinetics. Experimentally validated three-dimensional computational fluid dynamics (3D CFD) models are implemented to study the particle impact conditions for varying powder feeder tube size, powder feeder tube axial misalignment, and radial powder feeder injection location on the particle velocity and the deposition shape of aluminum alloy 6061. Outputs of the models are statistically analyzed to explore the shape of the spray plume distribution and resulting coating buildup.

The oretical foundations for management of environmental risks of pharmaceutical enterprises

Directory of Open Access Journals (Sweden)

Рита Василівна Сагайдак-Нікітюк

2016-01-01

Full Text Available Aim. Significant negative influence of processing waste caused by pharmaceutical enterprises' activity upon the environment and population, and the high requirements for the methods of utilization demands the enterprises to develop an algorithm of ecological risks management.Methods. During the study, the expert method, the content-analysis and generalization method have been applied.Results. An influence of pharmaceutical enterprises' activity on the environment and population of the region the enterprise is located in has been studied. Dynamic of the population morbidity has analyzed associated with a low quality of the human environment. The need has been approved to pay appropriate attention to the treatment of hazardous substances and to minimize environmental risks associated with the pharmaceutical enterprises' activities. It has been proposed to define an environmental risk as a danger of resources loss, income reduction or increase of expenses of subjects of pharmaceutical activity due to its ecologically destructive impact. The classification of environmental risks of pharmaceutical enterprises has been produced. The model of environmental risks' management of pharmaceutical enterprise has been proposed. Directions of the environmental risks' minimizing have been investigated.Conclusions. The need has proved to manage ecological activity of pharmaceutical enterprises that will let to minimize negative influence on the environment

Between pharmaceutical patents and European patients: is a compromise still possible?

Science.gov (United States)

Garattini, Livio; Padula, Anna

2017-10-01

Pharmaceutical regulation has always attempted to balance the public health objective to make safe and effective drugs available for patients while providing commercial incentives through patents. Here we discuss whether it is still possible to find a balance between the incentives on the supply side and the regulatory framework on the demand side. Areas covered: The current regulatory framework on pharmaceutical exclusivity has been harshly criticized by many experts, arguing about whether it is still fit for public purposes and needs. Here we envisage a different scenario without 'revolutionizing' the whole present system. The main radical change should concern the present management of pharmaceutical patents by introducing a specific agency dedicated to them. Secondly, specific pharmaceutical patents could be restricted to compounds for one (or more) declared indication(s). Thirdly, pharmaceutical patents should be kept only for compounds that start a first clinical trial within five years from the granting date. Expert opinion: We think it is time to reconsider the regulation of pharmaceutical patents in the light of their relevance in terms of public health. New models of enhancing research investments are required for long-term sustainability of public pharmaceutical expenditure and the EU can still play a leading role.

[Comparative analysis between origin of cooked traditional Chinese medicine powder and modern formula granules].

Science.gov (United States)

Li, Rui; Zhai, Hua-Qiang; Tian, Wei-Lan; Hou, Ji-Ru; Jin, Shi-Yuan; Wang, Yong-Yan

2016-03-01

Chinese medicine decoctions, which also restricts its clinical application and promotion. ③Both have advantages in the process of clinical application, and shall be used based on syndromes. In conclusion, traditional Chinese medicine formula granules do not have disadvantages of "difficult, complicated, turbid and disorderly" cooked traditional Chinese medicine powder, and solve such problems as "inflexibility, expensiveness, restriction, disorder and inefficacy", which is the important basis for promoting traditional Chinese medicine formula granules. Copyright© by the Chinese Pharmaceutical Association.

Active methodology and blended learning: An experience in pharmaceutical care.

Science.gov (United States)

Czepula, Alexandra Ingrid Dos Santos; Bottacin, Wallace Entringer; Júnior, Edson Hipólito; Pontarolo, Roberto; Correr, Cassyano Januário

The aim of this study was to analyze the implementation of an active methodology in a blended model of education in the teaching-learning processes of students enrolled in two disciplines: Pharmaceutical Care I and Pharmaceutical Care II, both part of the undergraduate Bachelor of Pharmacy program at the Federal University of Paraná. The study design was quasi-experimental, prospective, comparative, following a pre/posttest format, where Pharmaceutical Care classes were the intervention. Identical pre- and post-intervention tests were designed based on Anderson and Krathwohl's (2001) revision of Bloom's taxonomy, and according to the three levels of the cognitive domain: remember and understand; apply and analyze; evaluate and create. Participants were 133 students enrolled in the two Pharmaceutical Care classes. A significant difference between pre- and posttest results was observed, showing an increase in students' performance in the applied tests at all cognitive levels. This is the first study of its kind involving Pharmaceutical Care and Blended Learning. By comparing the results of the diagnostic and summative assessments based on Bloom's taxonomy at all levels of the cognitive domain, positive results were observed regarding the students' performance in the two disciplines (Pharmaceutical Care I and II). Copyright © 2017 Elsevier Inc. All rights reserved.

Container for nuclear fuel powders

International Nuclear Information System (INIS)

Etheredge, B.F.; Larson, R.I.

1982-01-01

A critically safe container is disclosed for the storage and rapid discharge of enriched nuclear fuel material in powder form is disclosed. The container has a hollow, slab-shaped container body that has one critically safe dimension. A powder inlet is provided on one side wall of the body adjacent to a corner thereof and a powder discharge port is provided at another corner of the body approximately diagonal the powder inlet. Gas plenum for moving the powder during discharge are located along the side walls of the container adjacent the discharge port

Optimization of Bread Enriched with Garcinia mangostana Pericarp Powder

Science.gov (United States)

Ibrahim, U. K.; Salleh, R. Mohd; Maqsood-ul-Hague, S. N. S.; Hashib, S. Abd; Karim, S. F. Abd

2018-05-01

The aim of present work is to optimize the formulation of bread enhanced with Garcinia mangostana pericarp powder with the combination of baking process conditions. The independent variables used were baking time (15 - 30 minutes), baking temperature (180 - 220°C) and pericarp powder concentration (0.5 - 2.0%). The physical and chemical properties of bread sample such as antioxidant activity, phenolic content, moisture analysis and colour parameters were studied. Bread dough without fortification of pericarp powder was used as control. Data obtained were analyzed by multiple regressions and the significant model such as linear and quadratic with variables interactions were used. As a conclusion, the optimum baking conditions were found at 213°C baking temperature with 23 minutes baking time and addition of 0.87% for Garcinia mangostana pericarp powder to the bread formulation.

Pharmaceutical cocrystals: an overview.

Science.gov (United States)

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

2011-10-31

Pharmaceutical cocrystals are emerging as a new class of solid drugs with improved physicochemical properties, which has attracted increased interests from both industrial and academic researchers. In this paper a brief and systematic overview of pharmaceutical cocrystals is provided, with particular focus on cocrystal design strategies, formation methods, physicochemical property studies, characterisation techniques, and recent theoretical developments in cocrystal screening and mechanisms of cocrystal formations. Examples of pharmaceutical cocrystals are also summarised in this paper. Copyright © 2011 Elsevier B.V. All rights reserved.

Dynamic plantwide modeling, uncertainty and sensitivity analysis of a pharmaceutical upstream synthesis: Ibuprofen case study

DEFF Research Database (Denmark)

Montes, Frederico C. C.; Gernaey, Krist; Sin, Gürkan

2018-01-01

A dynamic plantwide model was developed for the synthesis of the Active pharmaceutical Ingredient (API) ibuprofen, following the Hoescht synthesis process. The kinetic parameters, reagents, products and by-products of the different reactions were adapted from literature, and the different process...... operations integrated until the end process, crystallization and isolation of the ibuprofen crystals. The dynamic model simulations were validated against available measurements from literature and then used as enabling tool to analyze the robustness of design space. To this end, sensitivity of the design...... space towards input disturbances and process uncertainties (from physical and model parameters) is studied using Monte Carlo simulations. The results quantify the uncertainty of the quality of product attributes, with particular focus on crystal size distribution and ibuprofen crystalized. The ranking...

Direct laser sintering of metal powders: Mechanism, kinetics and microstructural features

International Nuclear Information System (INIS)

Simchi, A.

2006-01-01

In the present work, the densification and microstructural evolution during direct laser sintering of metal powders were studied. Various ferrous powders including Fe, Fe-C, Fe-Cu, Fe-C-Cu-P, 316L stainless steel, and M2 high-speed steel were used. The empirical sintering rate data was related to the energy input of the laser beam according to the first order kinetics equation to establish a simple sintering model. The equation calculates the densification of metal powders during direct laser sintering process as a function of operating parameters including laser power, scan rate, layer thickness and scan line spacing. It was found that when melting/solidification approach is the mechanism of sintering, the densification of metals powders (D) can be expressed as an exponential function of laser specific energy input (ψ) as ln(1 - D) = -Kψ. The coefficient K is designated as 'densification coefficient'; a material dependent parameter that varies with chemical composition, powder particle size, and oxygen content of the powder material. The mechanism of particle bonding and microstructural features of the laser sintered powders are addressed

Preparation of superconductor precursor powders

Science.gov (United States)

Bhattacharya, Raghunath

1998-01-01

A process for the preparation of a precursor metallic powder composition for use in the subsequent formation of a superconductor. The process comprises the steps of providing an electrodeposition bath comprising an electrolyte medium and a cathode substrate electrode, and providing to the bath one or more soluble salts of one or more respective metals which are capable of exhibiting superconductor properties upon subsequent appropriate treatment. The bath is continually energized to cause the metallic and/or reduced particles formed at the electrode to drop as a powder from the electrode into the bath, and this powder, which is a precursor powder for superconductor production, is recovered from the bath for subsequent treatment. The process permits direct inclusion of all metals in the preparation of the precursor powder, and yields an amorphous product mixed on an atomic scale to thereby impart inherent high reactivity. Superconductors which can be formed from the precursor powder include pellet and powder-in-tube products.

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. Copyright © 2011 Elsevier Ltd. All rights reserved.

In silico toxicology for the pharmaceutical sciences

International Nuclear Information System (INIS)

Valerio, Luis G.

2009-01-01

The applied use of in silico technologies (a.k.a. computational toxicology, in silico toxicology, computer-assisted tox, e-tox, i-drug discovery, predictive ADME, etc.) for predicting preclinical toxicological endpoints, clinical adverse effects, and metabolism of pharmaceutical substances has become of high interest to the scientific community and the public. The increased accessibility of these technologies for scientists and recent regulations permitting their use for chemical risk assessment supports this notion. The scientific community is interested in the appropriate use of such technologies as a tool to enhance product development and safety of pharmaceuticals and other xenobiotics, while ensuring the reliability and accuracy of in silico approaches for the toxicological and pharmacological sciences. For pharmaceutical substances, this means active and impurity chemicals in the drug product may be screened using specialized software and databases designed to cover these substances through a chemical structure-based screening process and algorithm specific to a given software program. A major goal for use of these software programs is to enable industry scientists not only to enhance the discovery process but also to ensure the judicious use of in silico tools to support risk assessments of drug-induced toxicities and in safety evaluations. However, a great amount of applied research is still needed, and there are many limitations with these approaches which are described in this review. Currently, there is a wide range of endpoints available from predictive quantitative structure-activity relationship models driven by many different computational software programs and data sources, and this is only expected to grow. For example, there are models based on non-proprietary and/or proprietary information specific to assessing potential rodent carcinogenicity, in silico screens for ICH genetic toxicity assays, reproductive and developmental toxicity, theoretical

Microstructural Development in Al-Si Powder During Rapid Solidification

Energy Technology Data Exchange (ETDEWEB)

Genau, Amber Lynn [Iowa State Univ., Ames, IA (United States)

2004-01-01

Powder metallurgy has become an increasingly important form of metal processing because of its ability to produce materials with superior mechanical properties. These properties are due in part to the unique and often desirable microstructures which arise as a result of the extreme levels of undercooling achieved, especially in the finest size powder, and the subsequent rapid solidification which occurs. A better understanding of the fundamental processes of nucleation and growth is required to further exploit the potential of rapid solidification processing. Aluminum-silicon, an alloy of significant industrial importance, was chosen as a model for simple eutectic systems displaying an unfaceted/faceted interface and skewed coupled eutectic growth zone, Al-Si powder produced by high pressure gas atomization was studied to determine the relationship between microstructure and alloy composition as a function of powder size and atomization gas. Critical experimental measurements of hypereutectic (Si-rich) compositions were used to determine undercooling and interface velocity, based on the theoretical models which are available. Solidification conditions were analyzed as a function of particle diameter and distance from nucleation site. A revised microstructural map is proposed which allows the prediction of particle morphology based on temperature and composition. It is hoped that this work, by providing enhanced understanding of the processes which govern the development of the solidification morphology of gas atomized powder, will eventually allow for better control of processing conditions so that particle microstructures can be optimized for specific applications.

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

OpenAIRE

Gilabert, Francisco; Roux, Jean-Noël; Castellanos, Antonio

2008-01-01

International audience; The quasistatic behavior of a simple 2D model of a cohesive powder under isotropic loads is investigated by Discrete Element simulations. The loose packing states, as studied in a previous paper, undergo important structural changes under growing confining pressure P, while solid fraction \\Phi irreversibly increases by large amounts. The system state goes through three stages, with different forms of the plastic consolidation curve \\Phi(P*), under growing reduced press...

Exposure and food web transfer of pharmaceuticals in ospreys (Pandion haliaetus): Predictive model and empirical data

Science.gov (United States)

Lazarus, Rebecca S.; Rattner, Barnett A.; Du, Bowen; McGowan, Peter C.; Blazer, Vicki S.; Ottinger, Mary Ann

2015-01-01

The osprey (Pandion haliaetus) is a well-known sentinel of environmental contamination, yet no studies have traced pharmaceuticals through the water–fish–osprey food web. A screening-level exposure assessment was used to evaluate the bioaccumulation potential of 113 pharmaceuticals and metabolites, and an artificial sweetener in this food web. Hypothetical concentrations in water reflecting “wastewater effluent dominated” or “dilution dominated” scenarios were combined with pH-specific bioconcentration factors (BCFs) to predict uptake in fish. Residues in fish and osprey food intake rate were used to calculate the daily intake (DI) of compounds by an adult female osprey. Fourteen pharmaceuticals and a drug metabolite with a BCF greater than 100 and a DI greater than 20 µg/kg were identified as being most likely to exceed the adult human therapeutic dose (HTD). These 15 compounds were also evaluated in a 40 day cumulative dose exposure scenario using first-order kinetics to account for uptake and elimination. Assuming comparable absorption to humans, the half-lives (t1/2) for an adult osprey to reach the HTD within 40 days were calculated. For 3 of these pharmaceuticals, the estimated t1/2 in ospreys was less than that for humans, and thus an osprey might theoretically reach or exceed the HTD in 3 to 7 days. To complement the exposure model, 24 compounds were quantified in water, fish plasma, and osprey nestling plasma from 7 potentially impaired locations in Chesapeake Bay. Of the 18 analytes detected in water, 8 were found in fish plasma, but only 1 in osprey plasma (the antihypertensive diltiazem). Compared to diltiazem detection rate and concentrations in water (10/12 detects,

Theoretical and experimental investigation of shock wave stressing of metal powders by an explosion

Directory of Open Access Journals (Sweden)

Lukyanov Ya.L.

2011-01-01

Full Text Available Joint theoretical and experimental investigations have allowed to realize an approach with use of mathematical and physical modeling of processes of a shock wave loading of powder materials. Hugoniot adiabats of the investigated powder have been measured with a noncontact electromagnetic method. The mathematical model of elastic-plastic deformation of the powder media used in the investigation has been validated. Numerical simulation of shock wave propagation and experimental assembly deformation has been performed.

Pharmaceutical pricing: an empirical study of market competition in Chinese hospitals.

Science.gov (United States)

Wu, Jing; Xu, Judy; Liu, Gordon; Wu, Jiuhong

2014-03-01

High pharmaceutical prices and over-prescribing of high-priced pharmaceuticals in Chinese hospitals has long been criticized. Although policy makers have tried to address these issues, they have not yet found an effective balance between government regulation and market forces. Our objective was to explore the impact of market competition on pharmaceutical pricing under Chinese government regulation. Data from 11 public tertiary hospitals in three cities in China from 2002 to 2005 were used to explore the effect of generic and therapeutic competition on prices of antibiotics and cardiovascular products. A quasi-hedonic regression model was employed to estimate the impact of competition. The inputs to our model were specific attributes of the products and manufacturers, with the exception of competition variables. Our results suggest that pharmaceutical prices are inversely related to the number of generic and therapeutic competitors, but positively related to the number of therapeutic classes. In addition, the product prices of leading local manufacturers are not only significantly lower than those of global manufacturers, but are also lower than their non-leading counterparts when other product attributes are controlled for. Under the highly price-regulated market in China, competition from generic and therapeutic competitors did decrease pharmaceutical prices. Further research is needed to explore whether this competition increases consumer welfare in China's healthcare setting.

Powder agglomeration in a microgravity environment

Science.gov (United States)

Cawley, James D.

1994-01-01

This is the final report for NASA Grant NAG3-755 entitled 'Powder Agglomeration in a Microgravity Environment.' The research program included both two types of numerical models and two types of experiments. The numerical modeling included the use of Monte Carlo type simulations of agglomerate growth including hydrodynamic screening and molecular dynamics type simulations of the rearrangement of particles within an agglomerate under a gravitational field. Experiments included direct observation of the agglomeration of submicron alumina and indirect observation, using small angle light scattering, of the agglomeration of colloidal silica and aluminum monohydroxide. In the former class of experiments, the powders were constrained to move on a two-dimensional surface oriented to minimize the effect of gravity. In the latter, some experiments involved mixture of suspensions containing particles of opposite charge which resulted in agglomeration on a very short time scale relative to settling under gravity.

Adsorption Studies of Radish Leaf Powder

Directory of Open Access Journals (Sweden)

Ankita

2016-01-01

Full Text Available Radish leaves (Raphanus sativus powder fractions was subjected to moisture adsorption isotherms at different isothermal temperature conditions from 15-45°C with an equal interval of 10°C. The sorption data obtained in gravimetric static method under 0.11–0.90 water activity conditions were subjected for sorption isotherms and found to be typical sigmoid trend. Experimental data were assessed for the applicability in the prediction through sorption models fitting and found that Polynomial and GAB equations performed well over all fitted models in describing equilibrium moisture content – equilibrium relative humidity (EMC–ERH relationships for shelf stable dehydrated radish leaf powder, over the entire range of temperatures condition under study. The net isosteric heat of sorption, differential entropy and free energy were determined at different temperatures and their dependence was seen with respect to equilibrium moisture content.

Influence of Ultrafine 2CaO·SiO2 Powder on Hydration Properties of Reactive Powder Concrete

Directory of Open Access Journals (Sweden)

Hongfang Sun

2015-09-01

Full Text Available In this research, we assessed the influence of an ultrafine 2CaO·SiO2 powder on the hydration properties of a reactive powder concrete system. The ultrafine powder was manufactured through chemical combustion method. The morphology of ultrafine powder and the development of hydration products in the cement paste prepared with ultrafine powder were investigated by scanning electron microscopy (SEM, mineralogical composition were determined by X-ray diffraction, while the heat release characteristics up to the age of 3 days were investigated by calorimetry. Moreover, the properties of cementitious system in fresh and hardened state (setting time, drying shrinkage, and compressive strength with 5% ordinary Portland cement replaced by ultrafine powder were evaluated. From SEM micrographs, the particle size of ultrafine powder was found to be up to several hundred nanometers. The hydration product started formulating at the age of 3 days due to slow reacting nature of belitic 2CaO·SiO2. The initial and final setting times were prolonged and no significant difference in drying shrinkage was observed when 5% ordinary Portland cement was replaced by ultrafine powder. Moreover, in comparison to control reactive powder concrete, the reactive powder concrete containing ultrafine powder showed improvement in compressive strength at and above 7 days of testing. Based on above, it can be concluded that the manufactured ultrafine 2CaO·SiO2 powder has the potential to improve the performance of a reactive powder cementitious system.

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.

Sintered aluminium powders

International Nuclear Information System (INIS)

Stepanova, M.G.; Matveev, B.I.

1974-01-01

The mechanical and physical properties of aluminium powder alloys and the various methods employed to produce them are considered. Data are given on the hardening of the alloys SAP and SPAK-4, as well as the powder-alloy system Al-Cr-Zr. (L.M.)

Powder diffraction

Energy Technology Data Exchange (ETDEWEB)

Hart, M.

1995-12-31

the importance of x-ray powder diffraction as an analytical tool for phase identification of materials was first pointed out by Debye and Scherrer in Germany and, quite independently, by Hull in the US. Three distinct periods of evolution lead to ubiquitous application in many fields of science and technology. In the first period, until the mid-1940`s, applications were and developed covering broad categories of materials including inorganic materials, minerals, ceramics, metals, alloys, organic materials and polymers. During this formative period, the concept of quantitative phase analysis was demonstrated. In the second period there followed the blossoming of technology and commercial instruments became widely used. The history is well summarized by Parrish and by Langford and Loueer. By 1980 there were probably 10,000 powder diffractometers in routine use, making it the most widely used of all x-ray crystallographic instruments. In the third, present, period data bases became firmly established and sophisticated pattern fitting and recognition software made many aspects of powder diffraction analysis routine. High resolution, tunable powder diffractometers were developed at sources of synchrotron radiation. The tunability of the spectrum made it possible to exploit all the subtleties of x-ray spectroscopy in diffraction experiments.

Powder diffraction

International Nuclear Information System (INIS)

Hart, M.

1995-01-01

The importance of x-ray powder diffraction as an analytical tool for phase identification of materials was first pointed out by Debye and Scherrer in Germany and, quite independently, by Hull in the US. Three distinct periods of evolution lead to ubiquitous application in many fields of science and technology. In the first period, until the mid-1940's, applications were and developed covering broad categories of materials including inorganic materials, minerals, ceramics, metals, alloys, organic materials and polymers. During this formative period, the concept of quantitative phase analysis was demonstrated. In the second period there followed the blossoming of technology and commercial instruments became widely used. The history is well summarized by Parrish and by Langford and Loueer. By 1980 there were probably 10,000 powder diffractometers in routine use, making it the most widely used of all x-ray crystallographic instruments. In the third, present, period data bases became firmly established and sophisticated pattern fitting and recognition software made many aspects of powder diffraction analysis routine. High resolution, tunable powder diffractometers were developed at sources of synchrotron radiation. The tunability of the spectrum made it possible to exploit all the subtleties of x-ray spectroscopy in diffraction experiments

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...

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. Copyright © 2016 Elsevier B.V. All rights reserved.

Influences of the Air in Metal Powder High Velocity Compaction

Directory of Open Access Journals (Sweden)

Liu Jun

2017-01-01

Full Text Available During the process of metal powder high velocity impact compaction, the air is compressed sharply and portion remains in the compacts. In order to study the Influences, a discrete density volleyball accumulation model for aluminium powder was established with the use of ABAQUS. Study found that the powder porosity air obstruct the pressing process because remaining air reduced strength and density of the compacts in the current high-speed pressing (V≤100m/s. When speed further increased (V≥100m/s, the temperature of the air increased sharply, and was even much higher than the melting point of the material. When aluminium powder was compressed at a speed of 200m/s, temperatures of air could reach 2033 K, far higher than the melting point of 877 K. Increased density of powders was a result of local softening and even melt adhesive while air between particles with high temperature and pressure flowed past.

A protective effect of epidermal powder immunization in a mouse model of equine herpesvirus-1 infection

International Nuclear Information System (INIS)

Kondo, Takashi; McGregor, Martha; Chu, Qili; Chen, Dexiang; Horimoto, Taisuke; Kawaoka, Yoshihiro

2004-01-01

To evaluate the protective effect of epidermal powder immunization (EPI) against equine herpesvirus-1 (EHV-1) infection, we prepared a powder vaccine in which formalin-inactivated virions were embedded in water-soluble, sugar-based particles. A PowderJect device was used to immunize mice with the powder vaccine via their abdominal skin. We found that twice-immunized mice were protected against challenge with the wild-type virus. This protective effect was equivalent to or better than that observed in mice immunized with other types of vaccines, including a gene gun-mediated DNA vaccine containing the glycoprotein D (gD) gene or conventional inactivated virus vaccines introduced via intramuscular or intranasal injections. These findings indicate that the powder vaccine is a promising approach for the immunological control of EHV-1 infection, either alone or as a part of prime-boost vaccination strategies

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. © 2013.

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

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

International Nuclear Information System (INIS)

Neuwoehner, Judith; Escher, Beate I.

2011-01-01

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 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 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 were

Method to blend separator powders

Science.gov (United States)

Guidotti, Ronald A.; Andazola, Arthur H.; Reinhardt, Frederick W.

2007-12-04

A method for making a blended powder mixture, whereby two or more powders are mixed in a container with a liquid selected from nitrogen or short-chain alcohols, where at least one of the powders has an angle of repose greater than approximately 50 degrees. The method is useful in preparing blended powders of Li halides and MgO for use in the preparation of thermal battery separators.

Pharmaceutical pricing policy in Greece: towards a different path.

Directory of Open Access Journals (Sweden)

Kyriakos Souliotis

2016-08-01

Full Text Available Background: Affordable, accessible and innovation-promoting pharmaceutical care is essential to the operation of a sustainable health system. External reference pricing (ERP, a common pharmaceutical policy in Europe, suffers today from indigenous weaknesses that may cause market distortions and barriers to care, burdening mostly the weak economies, and hence, raising ethical and political worrying. Objectives and Methods: A non-randomized experiment was conducted, in order to examine the influence of flexible and adaptable to health systems’ affordability ERP structures. Outcomes were assessed by measuring deviations from Greek prices’ level ex ante, as well as effects on pharmaceutical markets affiliated to the European ERP system. Results and Conclusions: Pharmaceutical pricing models that fit prices to income and affordability are better in all aspects, as they produce fairer results, while resulting in low external costs for the European ERP network as a whole. Small sets of reference countries are preferred to large baskets, as they produce similar results, while presenting better qualities by increasing the flexibility of the reimbursement system and the transparency of the market.

Oxidation of nano-sized aluminum powders

International Nuclear Information System (INIS)

Vorozhtsov, A.B.; Lerner, M.; Rodkevich, N.; Nie, H.; Abraham, A.; Schoenitz, M.; Dreizin, E.L.

2016-01-01

Highlights: • Weight gain measured in TG oxidation experiments was split between particles of different sizes. • Reaction kinetics obtained by isoconversion explicitly accounting for the effect of size distribution. • Activation energy is obtained as a function of oxide thickness for growth of amorphous alumina. • Oxidation mechanism for nanopowders remains the same as for coarser aluminum powders. - Abstract: Oxidation of aluminum nanopowders obtained by electro-exploded wires is studied. Particle size distributions are obtained from transmission electron microscopy (TEM) images. Thermo-gravimetric (TG) experiments are complemented by TEM and XRD studies of partially oxidized particles. Qualitatively, oxidation follows the mechanism developed for coarser aluminum powder and resulting in formation of hollow oxide shells. Sintering of particles is also observed. The TG results are processed to account explicitly for the particle size distribution and spherical shapes, so that oxidation of particles of different sizes is characterized. The apparent activation energy is obtained as a function of the reaction progress using model-free isoconversion processing of experimental data. A complete phenomenological oxidation model is then proposed assuming a spherically symmetric geometry. The oxidation kinetics of aluminum powder is shown to be unaffected by particle sizes reduced down to tens of nm. The apparent activation energy describing growth of amorphous alumina is increasing at the very early stages of oxidation. The higher activation energy is likely associated with an increasing homogeneity in the growing amorphous oxide layer, initially containing multiple defects and imperfections. The trends describing changes in both activation energy and pre-exponent of the growing amorphous oxide are useful for predicting ignition delays of aluminum particles. The kinetic trends describing activation energies and pre-exponents in a broader range of the oxide

Current Status of Regulatory Science Education in Faculties of Pharmaceutical Science in Japan.

Science.gov (United States)

Tohkin, Masahiro

2017-01-01

I introduce the current pharmaceutical education system in Japan, focusing on regulatory science. University schools or faculties of pharmaceutical science in Japan offer two courses: a six-year course for pharmacists and a four-year course for scientists and technicians. Students in the six-year pharmaceutical course receive training in hospitals and pharmacies during their fifth year, and those in the four-year life science course start research activities during their third year. The current model core curriculum for pharmaceutical education requires them to "explain the necessity and significance of regulatory science" as a specific behavior object. This means that pharmacists should understand the significance of "regulatory science", which will lead to the proper use of pharmaceuticals in clinical practice. Most regulatory science laboratories are in the university schools or faculties of pharmaceutical sciences; however, there are too few to conduct regulatory science education. There are many problems in regulatory science education, and I hope that those problems will be resolved not only by university-based regulatory science researchers but also by those from the pharmaceutical industry and regulatory authorities.

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

Science.gov (United States)

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

2011-08-01

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

Towards the optimisation and adaptation of dry powder inhalers.

Science.gov (United States)

Cui, Y; Schmalfuß, S; Zellnitz, S; Sommerfeld, M; Urbanetz, N

2014-08-15

Pulmonary drug delivery by dry powder inhalers is becoming more and more popular. Such an inhalation device must insure that during the inhalation process the drug powder is detached from the carrier due to fluid flow stresses. The goal of the project is the development of a drug powder detachment model to be used in numerical computations (CFD, computational fluid dynamics) of fluid flow and carrier particle motion through the inhaler and the resulting efficiency of drug delivery. This programme will be the basis for the optimisation of inhaler geometry and dry powder inhaler formulation. For this purpose a multi-scale approach is adopted. First the flow field through the inhaler is numerically calculated with OpenFOAM(®) and the flow stresses experienced by the carrier particles are recorded. This information is used for micro-scale simulations using the Lattice-Boltzmann method where only one carrier particle covered with drug powder is placed in cubic flow domain and exposed to the relevant flow situations, e.g. plug and shear flow with different Reynolds numbers. Therefrom the fluid forces on the drug particles are obtained. In order to allow the determination of the drug particle detachment possibility by lift-off, sliding or rolling, also measurements by AFM (atomic force microscope) were conducted for different carrier particle surface structures. The contact properties, such as van der Waals force, friction coefficient and adhesion surface energy were used to determine, from a force or moment balance (fluid forces versus contact forces), the detachment probability by the three mechanisms as a function of carrier particle Reynolds number. These results will be used for deriving the drug powder detachment model. Copyright © 2014 Elsevier B.V. All rights reserved.

Influence of starting powder milling on magnetic properties of Mn-Zn ferrite

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Miodrag M. Milutinov

2017-06-01

Full Text Available In this paper, the influence of additional sieving and milling of starting industrial Mn-Zn powders on magnetic properties was investigated. The starting powder was milled for 60 minutes, followed by sieving through 325 and 400 meshes. The starting and milled powders were used to fabricate toroid shaped samples sintered at 1200°C for 2 hours. Structural parameters of the fabricated samples were analysed by X-ray diffraction and scanning electron microscopy. Complex permeability, core loss density, and hysteresis were measured using the modified watt-meter method. The complex permeability and hysteresis loop were modelled with a new model proposed in the paper. The core loss density was modelled with the Steinmetz empirical equation. The experimental results and calculations show the significance of the additional milling and sieving process on magnetic properties of Mn-Zn ferrite in the frequency range 0.1-10MHz. These processes increase the relative permeability about 3 times and decrease the core loss 4 times by milling of the starting powder.

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.

Molybdenum plasma spray powder, process for producing said powder, and coating made therefrom

International Nuclear Information System (INIS)

Lafferty, W.D.; Cheney, R.F.; Pierce, R.H.

1979-01-01

Plasma spray powders of molybdenum particles containing 0.5 to 15 weight percent oxygen and obtained by reacting molybdenum particles with oxygen or oxides in a plasma, form plasma spray coatings exhibiting hardness comparable to flame sprayed coatings formed from molybdenum wire and plasma coatings of molybdenum powders. Such oxygen rich molybdenum powders may be used to form wear resistant coatings, such as for piston rings. (author)

SAF line powder operations

International Nuclear Information System (INIS)

Frederickson, J.R.; Horgos, R.M.

1983-10-01

An automated nuclear fuel fabrication line is being designed for installation in the Fuels and Materials Examination Facility (FMEF) near Richland, Washington. The fabrication line will consist of seven major process systems: Receiving and Powder Preparation; Powder Conditioning; Pressing and Boat Loading; Debinding, Sintering, and Property Adjustment; Boat Transport; Pellet Inspection and Finishing; and Pin Operations. Fuel powder processing through pellet pressing will be discussed in this paper

Two layer powder pressing

International Nuclear Information System (INIS)

Schreiner, H.

1979-01-01

First, significance and advantages of sintered materials consisting of two layers are pointed out. By means of the two layer powder pressing technique metal powders are formed resulting in compacts with high accuracy of shape and mass. Attributes of basic powders, different filling methods and pressing techniques are discussed. The described technique is supposed to find further applications in the field of two layer compacts in the near future

SPECTROPHOTOMETRIC DETERMINATION OF ACETYLCYSTEINE IN PHARMACEUTICAL FORMULATIONS USING 2,3-DICHLORO-1,4-NAPTHOQUINONE

Directory of Open Access Journals (Sweden)

A. O. Donchenko

2015-04-01

Full Text Available The aim of research was the development and validation ofspectrophotometric method foracetylcysteine assay in pharmaceutical formulations.Тhe proposed method is based on the reaction with 2,3-dichloro-1,4-naphthoquinone and the formation of colored products that exhibit absorption maxima at 425 nm. Introduction Many analytical methods have been published for acetylcysteine assay in pharmaceutical formulations as high-performance liquid chromatography (HPLC, fluorimetry and chemiluminescence. Some of these methods are time consuming or require expensive equipment. Other published methods suffer from lack of selectivity and sensitivity. Spectrophotometry is the most widely used technique in pharmaceutical analysis because it is simple, economic, and easily available to most quality control laboratories. In the present work, we propose a simple and accurate spectrophotometric method for acetylcysteine assay in pharmaceutical formulations. Materials and Methods Reagents: Reference standard acetylcysteinesubstance; 2,3-dichloro-1,4-naphthoquinone. All chemicals and solvents were of analytical grade. DMFA was used as a solvent. Pharmaceutical preparations:powder for oral solution «ACC 200» 200 mgseries number50026151 (Salutas Pharma CmbH, Germany; effervescent tablets «Fluimucil» 600 mg (Zambon S.P.A., Italy and «ACC LONG» 600 mg (Salutas Pharma CmbH, Germany series numbers 321284 and DH2740; solution for injections «Fluimucil» 100 mg/ml (Zambon S.P.A., Italyseries number28002492. Solutions: Acetylcysteine stock solution (0,16%; DMFAsolution of 2,3-dichloro-1,4-naphthoquinone (4%. Equipment Analytical balance (ABT-120-5DM; UV-VIS spectrophotometer (Specord 200; water bath (MemmertWNB 7-45;quartz cells. Results Acetylcysteine was determined using a spectrophotometric method based on the reaction with 2,3-dichloro-1,4-naphthoquinone to form yellow colored reaction products with absorption maxima at 425 nm. The effect of reaction time and

Characterization of powders up to date laws of compression

International Nuclear Information System (INIS)

Cathala, B.; Nicolas, G.

2001-01-01

Many studies have been carried out in order to be able to describe the relationship d = f(P) of the compression phase of a powder in a more or less empirical fashion. Among the different laws, that of Heckel is the more frequently applied. The inconvenience of this, however, is that it does not bear witness to the behavior of the powder at extremely low pressure. Two new laws are described hereinafter (a complement to Heckel's Law and a new model), in attempt to solve this problem. The outcome of these equations forms the basis of the identification of the analysed powder, and its statistical sample testing contributes to product quality control. (author)

Electrochemical biosensors in pharmaceutical analysis

OpenAIRE

Gil, Eric de Souza; Melo, Giselle Rodrigues de

2010-01-01

Given the increasing demand for practical and low-cost analytical techniques, biosensors have attracted attention for use in the quality analysis of drugs, medicines, and other analytes of interest in the pharmaceutical area. Biosensors allow quantification not only of the active component in pharmaceutical formulations, but also the analysis of degradation products and metabolites in biological fluids. Thus, this article presents a brief review of biosensor use in pharmaceutical analysis, fo...

Russian Pharmaceutical Companies Export Potential in Emerging Regional Clusters

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Elena Vladimirovna Sapir

2016-12-01

Full Text Available This article analyzes a diverse range of the enterprise’s export potential growth factors in emerging pharmaceutical clusters of Central European Russia. Classification and comparative analysis were used to identify export potential attributes (production, finance, labor and marketing, which have allowed to reveal the strong connection of cluster and regional factor groups with the results of export performance. The purpose of the study is to provide exports-seeking pharmaceutical companies with a set of tools to enhance their export potential. The hypothesis that the cumulative impact of the specified attributes leads to the strengthening of pharmaceutical cluster export potential and promotes an effective integration of the region in the world economic space, is developed and tested. The methodology combines the geo-economy-based theory with the theory of clusters competitive advantages. The impacts of export potential growth factors are estimated by using an econometric model based on math statistics. Thus, five Russian regional pharmaceutical clusters (Belgorod, Kaluga, Moscow, Oryol, Yaroslavl are shown. Findings identify an objective causal link between enterprise export potential growth and competitiveness factors of cluster origin (network business chains, production functions interconnectedness and flexibility, production localization. An action plan for the purpose of the maximum use of competitive advantages of the cluster organization for export activities of the entities of the pharmaceutical industry is developed. Conclusions and recommendations of the study are intended to enterprises in pharmaceutical industry and regions’ public authorities, implementing cluster development strategies. It is thus essential to improve marketing and organizational innovations, reduction of commercial expenses under the cluster environment, development of drugs production and delivery chains from R&D to end-users in order to enjoy greater

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...... to be indistinguishable to X-ray powder diffraction....

The analysis of powder diffraction data

International Nuclear Information System (INIS)

David, W.I.F.; Harrison, W.T.A.

1986-01-01

The paper reviews neutron powder diffraction data analysis, with emphasis on the structural aspects of powder diffraction and the future possibilities afforded by the latest generation of very high resolution neutron and x-ray powder diffractometers. Traditional x-ray powder diffraction techniques are outlined. Structural studies by powder diffraction are discussed with respect to the Rietveld method, and a case study in the Rietveld refinement method and developments of the Rietveld method are described. Finally studies using high resolution powder diffraction at the Spallation Neutron Source, ISIS at the Rutherford Appleton Laboratory are summarized. (U.K.)

Analysis and control of issues that delay pharmaceutical projects

Directory of Open Access Journals (Sweden)

Nallam Sai Nandeswara Rao

2015-10-01

Full Text Available Every project will have certain objectives and service levels to be achieved. The success of a project depends on several dimensions like time, cost/budget, quality, etc. and managing a project involves completing the project within time, within budget and with quality to satisfy the users. Because of the significance of health, pharmaceutical companies realized the importance of project management methods and techniques to make available the life saving drugs in time to the needy patients and hospitals. In literature, there is meager information about pharmaceutical project management oriented towards analysis of issues and factors that contribute to the failure or success of projects. This study attempts to analyse different issues that contribute to time delays in pharmaceutical product-based projects, group them under a finite set of prominent factors and identify remedial measures to control those delays. The feedback of project people of some big pharmaceutical firms of Indian sub-continent was collected for this purpose. Exploratory factor analysis (EFA has been used to reduce the reasons for time delays to a limited number of prominent factors and the EFA model has been further examined by confirmatory factor analysis (CFA for its validation. Remedial measures under each factor of time delays have been gathered and a framework designed to mitigate the time delays in pharmaceutical projects. The derived factors that delay the pharmaceutical projects include resource, monitoring & control, scheduling and planning problems. Important remedial measures like blended resource approach, estimation and forecast of shortage of labour and skills, regular quality training, etc. have been recommended.

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

APPROACHES TO IMPLEMENTATION OF AN INTEGRATED MANAGEMENT SYSTEM IN THE PHARMACEUTICAL INDUSTRY. GALENICAL PHARMACEUTICAL PRODUCTION

Directory of Open Access Journals (Sweden)

Ershova Elena Vladimirovna

2015-10-01

Full Text Available This article reviews the issues associated with development of an integrated quality management system and its implementation into a galenical pharmaceutical company. Recently, the Russian pharmaceutical industry has been developing extensively: pharmaceutical clusters are being formed, new and innovative technologies are being developed. For the enterprises producing galenical pharmaceutical products, which feature low prices and a high level of competition, development and implementation of management systems is a way to prove their competitiveness. The purpose of this article is to review the architecture and the key elements of integrated management systems for pharmaceutical enterprises, develop an integrated management system in terms of the upcoming revision of ISO 9001:2015, as well as to describe the benefits of implementation of such systems. The presented approach is the result of an educational project implemented within the framework of the MBA programme in "Master of Business Administration (MBA" in the Federal State Budgetary Educational Institution of Continuing Professional Education Pastukhov State Academy of Industrial Management.

Black powder in gas pipelines

Energy Technology Data Exchange (ETDEWEB)

Sherik, Abdelmounam [Saudi Aramco, Dhahran (Saudi Arabia)

2009-07-01

Despite its common occurrence in the gas industry, black powder is a problem that is not well understood across the industry, in terms of its chemical and physical properties, source, formation, prevention or management of its impacts. In order to prevent or effectively manage the impacts of black powder, it is essential to have knowledge of its chemical and physical properties, formation mechanisms and sources. The present paper is divided into three parts. The first part of this paper is a synopsis of published literature. The second part reviews the recent laboratory and field work conducted at Saudi Aramco Research and Development Center to determine the compositions, properties, sources and formation mechanisms of black powder in gas transmission systems. Microhardness, nano-indentation, X-ray Diffraction (XRD), X-ray Fluorescence (XRF) and Scanning Electron Microscopy (SEM) techniques were used to analyze a large number of black powder samples collected from the field. Our findings showed that black powder is generated inside pipelines due to internal corrosion and that the composition of black powder is dependent on the composition of transported gas. The final part presents a summary and brief discussion of various black powder management methods. (author)

Pharmaceuticals labelled with stable isotopes

International Nuclear Information System (INIS)

Krumbiegel, P.

1986-11-01

The relatively new field of pharmaceuticals labelled with stable isotopes is reviewed. Scientific, juridical, and ethical questions are discussed concerning the application of these pharmaceuticals in human medicine. 13 C, 15 N, and 2 H are the stable isotopes mainly utilized in metabolic function tests. Methodical contributions are given to the application of 2 H, 13 C, and 15 N pharmaceuticals showing new aspects and different states of development in the field under discussion. (author)

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

Science.gov (United States)

Banerjee, Tannista

2012-01-01

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

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

Idea management in support of pharmaceutical front end innovation

DEFF Research Database (Denmark)

Aagaard, Annabeth

2012-01-01

The pharmaceutical industry faces continuing pressures from rising R&D costs and depreciating value of patents, as patent lives is eroded by testing procedures and pressures from public authorities to cut health care costs. These challenges have increased the focus on shortening development times......, which again put pressure on the efficiency of front end innovation (FEI). In the attempt to overcome these various challenges pharmaceutical companies are looking for new models to support FEI. This paper explores in what way idea management can be applied as a tool in facilitation of front end...... innovation in practice. First I show through a literature study, how idea management and front end innovation are related and may support each other. Hereafter I apply an exploratory case study of front end innovation in eight medium to large pharmaceutical companies in examination of how idea management...

Thermal plasma spheroidization and spray deposition of barium titanate powder and characterization of the plasma sprayable powder

Energy Technology Data Exchange (ETDEWEB)

Pakseresht, A.H., E-mail: amirh_pak@yahoo.com [Department of Ceramics, Materials and Energy Research Center, P.O. Box 31787-316, Karaj (Iran, Islamic Republic of); Rahimipour, M.R. [Department of Ceramics, Materials and Energy Research Center, P.O. Box 31787-316, Karaj (Iran, Islamic Republic of); Vaezi, M.R. [Department of Nanotechnology and Advanced Materials, Materials and Energy Research Center, P.O. Box 31787-316, Karaj (Iran, Islamic Republic of); Salehi, M. [Department of Materials Engineering, Isfahan University of Technology, P.O. Box 84156-83111, Isfahan (Iran, Islamic Republic of)

2016-04-15