The stability of pharmaceutical powders: effect of additives and coating

The decomposition of drugs in the solid state has been studied using aspirin and salsalate as models. The feasibility of using suspension systems for predicting the stability of these drugs in the solid state has been investigated.. It has been found that such systems are inappropriate in defining the effect of excipients on 'the decomposition of the active drug due to chqnges in the degradation pathway. Using a high performance liquid chromatographic method, magnesium stearate was shown to induce the formation of potentlally immunogenic products in aspirin powders. These products which included salicylsalicylic acid .and acetylsalicyclsalicylic acid were not detected in aspirin suspensions which had undergone the same extent of decomposition. By studying the effect of pH and of added excipients on the rate of decomposition of aspirin in suspension systems, it has been shown that excipients such as magnesium stearate containing magnesium oxide, most probably enhance the decomposition of both aspirin and salsalate by alkalinising the aqueous phase. In the solid state, pH effects produced by excipients appear to be relatively unimportant. Evidence is presented to suggest that the critical parameter is a depression in melting point induced by: the added excipient. Microscopical examination in fact showed the formation of clear liquid layers in aspirin samples containing added magnesium stearate but not in control samples. Kinetic equations which take into account both the diffusive barrier presented by the liquid films and the. geometry of the aspirin crystals were developed. Fitting of the .experimental data to these equations showed good agreement. with the postulated theory. Monitorjng of weight issues during the decomposition of aspirin revealed that in the solid systems studied where the bulk of the decomposition product sublimes, it is possible to estimate the extent of degradation from the residual weight, provided the initial weight is known. The corollary is that in such open systems, monitoring of decomposition products is inadequate for assessing the extent of decomposition. In addition to the magnesium stearate-aspirin system, mapyramine maleate-aspirin mixtures were used to model interactive systems. Work carried out in an attempt to stabilise such systems included microencapsulation and film coating. The protection obtained was dependent on the interactive species used. Gelatin for example appeared to stabilise aspirin against the adverse effects of magnesium stearate but increased its decomposition in the presence of mapyramine maleate.

Innovation in the pharmaceutical industry:a study of the effects of regulation on the U.K. pharmaceutical industry

A history of government drug regulation and the relationship between the pharmaceutical companies in the U.K. and the licensing authority is outlined. Phases of regulatory stringency are identified with the formation of the Committees on Safety of Drugs and Medicines viewed as watersheds. A study of the impact of government regulation on industrial R&D activities focuses on the effects on the rate and direction of new product innovation. A literature review examines the decline in new chemical entity innovation. Regulations are cited as a major but not singular cause of the decline. Previous research attempting to determine the causes of such a decline on an empirical basis is given and the methodological problems associated with such research are identified. The U.K. owned sector of the British pharmaceutical industry is selected for a study employing a bottom-up approach allowing disaggregation of data. A historical background to the industry is provided, with each company analysed or a case study basis. Variations between companies regarding the policies adopted for R&D are emphasised. The process of drug innovation is described in order to determine possible indicators of the rate and direction of inventive and innovative activity. All possible indicators are considered and their suitability assessed. R&D expenditure data for the period 1960-1983 is subsequently presented as an input indicator. Intermediate output indicators are treated in a similar way and patent data are identified as a readily-available and useful source. The advantages and disadvantages of using such data are considered. Using interview material, patenting policies for most of the U.K. companies are described providing a background for a patent-based study. Sources of patent data are examined with an emphasis on computerised systems. A number of searches using a variety of sources are presented. Patent family size is examined as a possible indicator of an invention's relative importance. The patenting activity of the companies over the period 1960-1983 is given and the variation between companies is noted. The relationship between patent data and other indicators used is analysed using statistical methods resulting in an apparent lack of correlation. An alternative approach taking into account variations in company policy and phases in research activity indicates a stronger relationship between patenting activity, R&D Expenditure and NCE output over the period. The relationship is not apparent at an aggregated company level. Some evidence is presented for a relationship between phases of regulatory stringency, inventive and innovative activity but the importance of other factors is emphasised.

Molecular architecture influences on material properties of pharmaceutical compounds

Salt formation has extensively been studied as a strategy to improve drug solubility but it has not been explored as a strategy to improve mechanical properties. A better understanding of which factors of the solid state can have an influence in the mechanical properties of pharmaceutical powders can help to optimise and reduce cost of tablet manufacturing. The aim of this study was to form different series of amine salts of flurbiprofen, gemfibrozil and diclofenac and to establish predictive relationships between architectural characteristics and physicochemical and mechanical properties of the salts. For this purpose, three different carboxylic acid drugs were selected: flurbiprofen, gemfibrozil and diclofenac, similar in size but varying in flexibility and shape and three different series of counterions were also chosen: one with increasing bulk and no hydroxyl groups to limit the hydrogen bonding potential; a second one with increasing number of hydroxyl groups and finally a third series, related to the latter in number of hydroxyl groups but with different molecular shape and flexibility. Physico-chemical characterization was performed (DSC, TGA, solubility, intrinsic dissolution rate, particle size, true density) and mechanical properties measured using a compaction replicator. Strained molecular conformations produce weaker compacts as they have higher energy than preferred conformations that usually lie close to energy minimums and oppose plastic deformation. It was observed that slip planes, which correspond to regions of weakest interaction between the planes, were associated with improved plasticity and stronger compacts. Apart from hydrogen bonds, profuse van der Waals forces can result in ineffective slip planes. Salts displaying two-dimensional densely hydrogen bonded layers produced stronger compacts than salts showing one-dimensional networks of non-bonded columns, probably by reducing the attachment energy between layers. When hydrogen bonds are created intramolecularly, it is possible that the mechanical properties are compromised as they do not contribute so much to create twodimensional densely bonded layers and they can force molecules into strained conformations. Some types of hydrogen bonding network may be associated with improved mechanical properties, such as type II, or R (10) 3 4 using graph-set notation, versus type III, or R (12) 4 8 , columns. This work clearly demonstrates the potential of investigating crystal structure-mechanical property relationship in pharmaceutical materials.

Social aspects of pharmaceutical innovation: heart disease

This study examines the invention, innovation, introduction and use of a new drug therapy for coronary heart disease and hypertension; beta-blockade. The relationships between drug introductions and changes in medical perceptions of disease are analysed, and the development and effects of our perception of heart disease through drug treatments and diagnostic technology is described. The first section looks at the evolution of hypertension from its origin as a kidney disorder, Bright's disease, to the introduction and use of effective drugs for its treatment. It is shown that this has been greatly influenced by the introduction of new medical technologies. A medical controversy over its nature is shown both to be strongly influenced by the use of new drugs, and to influence their subsequent use. The second section reviews the literature analysing drug innovation, and examines the innovation of the beta-blocking drugs, making extensive use of participant accounts. The way in which the development of receptor theory, the theoretical basis of the innovation,was influenced by the innovation and use of drugs is discussed, then the innovation at ICI, the introduction into clinical use, and the production of similar drugs by other manufacturers are described. A study of the effects of these drugs is then undertaken, concentrating on therapeutic costs and benefits, and changes in medical perceptions of disease. The third section analyses the effects of other drugs on heart disease, looking at changes in mortality statistics and in medical opinions. The study concludes that linking work on drug innovation with that on drug effects is fruitful, that new drugs and diagnostic technology have greatly influenced medical perceptions of the nature and extent of heart disease, and that in hypertension, the improvement in drug treatment will soon result in much of the population being defined as in need of it life-long.

Characterisation and surface-profiling techniques for composite particles produced by dry powder coating in pharmaceutical drug delivery

The production of composite particles using dry powder coating is a one-step, environmentally friendly, process for the fabrication of particles with targeted properties and favourable functionalities. Diverse functionalities, such flowability enhancement, content uniformity, and dissolution, can be developed from dry particle coating. In this review, we discuss the particle functionalities that can be tailored and the selection of characterisation techniques relevant to understanding their molecular basis. We address key features in the powder blend sampling process and explore the relevant characterisation techniques, focussing on the functionality delivered by dry coating and on surface profiling that explores the dynamics and surface characteristics of the composite blends. Dry particle coating is a solvent- and heat-free process that can be used to develop functionalised particles. However, assessment of the resultant functionality requires careful selection of sensitive analytical techniques that can distinguish particle surface changes within nano and/or micrometre ranges.

Pharmaceutical compounding and dispensing

This is a modern, detailed and practical guide to the theory and practice of extemporaneous compounding and dispensing. Fully revised and updated, this new edition will be an indispensable reference for pharmacy students and practicing pharmacists. Pharmacists have been responsible for compounding medicines for centuries. Although most modern medicines are not compounded in a local pharmacy environment, there are still occasions when it is imperative that pharmacists have this knowledge. Pharmaceutical Compounding and Dispensing provides a comprehensive guide to producing extemporaneous formulations safely and effectively.

FASTtrack applied pharmaceutical practice

This is a revision guide for students providing bullet points of basic information on dispensing. "The FASTtrack" series is a series of revision guides directly aimed at pharmacy students. Basic information will be provided on all main areas of study for the MPharm in small concise texts. Each title will provide a summary of all key information along with diagrams, cases and questions and answers for self assessment. The books will be practical, easy to read and well-priced and will complement textbooks and aid students with revision for examinations. This "FASTtrack" is a companion to the larger textbook "Applied Pharmaceutical Practice" (published September 2008) which was designed to guide the student pharmacist or pharmacy technician through the main stages involved in pharmaceutical dispensing. This title provides students with a core reference to accompany the compulsory dispensing courses found in all undergraduate pharmacy programmes. "FASTtrack: Applied Pharmaceutical Practice" is a condensed version with additional examples and questions. A "FASTtrack" website includes MCQs, sample online content and much more.

FASTtrack applied pharmaceutical practice

This revision guide takes the student pharmacist or pharmacy technician through the main stages involved in pharmaceutical dispensing. It gives bullet points of basic information on applied pharmacy practice followed by questions and answers. This reference text accompanies the compulsory dispensing courses found in all undergraduate MPharm programmes and equivalent technical training courses. Changes for the new edition include: * Information on revisions to the community pharmacy contract. * Additional content on new advanced community pharmacy services. * Revised worked examples and student questions. * Updated prescription labelling information, including the use of new cautionary and warning labels. * Updated references and bibliography.

Applied pharmaceutical practice

Applied Pharmaceutical Practice is an invaluable resource and will guide the student pharmacist and pharmacy technician through the main stages involved in pharmaceutical dispensing. As a core reference text, it is ideal as a companion to the compulsory dispensing courses found in all undergraduate MPharm programmes and the equivalent technical training courses. Contents include: •medicines classification and standard operating procedures •NHS supply in the community and within hospitals •non-NHS supply •controlled drugs •emergency supply •patient counselling and communication •poisons and spirits This practical textbook contains useful exercises with an answers section and numerous examples and is written by authors with extensive experience within the field. This is a comprehensive guide through the main stages of pharmaceutical dispensing.The textbook is designed to guide student pharmacists or pharmacy technicians through the main stages involved in pharmaceutical dispensing. It provides students with a core reference text to accompany the compulsory dispensing course found in all pharmacy undergraduate programmes, highlighting and explaining all key concepts behind the processes involved in pharmaceutical dispensing.

Faces of pricing and profit planning in innovation at the doorstep of the EU:government pricing policy in the pharmaceutical sector in Turkey

The majority of research on the pharmaceutical sector has focused on an overall micro economic, medical oriented welfare issues, whereas the marketing management role of the innovative drug manufacturer has to a large extent been disregarded. Using the case of Turkey, through a series of in-depth interviews with highly innovative companies, other marketing management possibilities are explored based on broader definitions of value and transparency. Our results suggest that pharmaceutical companies as well as the government might have a too narrow focus of value and underestimate the potential long term benefits of a broader approach to marketing management and long term relationships between the various stakeholders.

Quality control of pharmaceutical ingredients:developing a caking test for industry

Objectives - Powdered and granulated particulate materials make up most of the ingredients of pharmaceuticals and are often at risk of undergoing unwanted agglomeration, or caking, during transport or storage. This is particularly acute when bulk powders are exposed to extreme swings in temperature and relative humidity, which is now common as drugs are produced and administered in increasingly hostile climates and are stored for longer periods of time prior to use. This study explores the possibility of using a uniaxial unconfined compression test to compare the strength of caked agglomerates exposed to different temperatures and relative humidities. This is part of a longer-term study to construct a protocol to predict the caking tendency of a new bulk material from individual particle properties. The main challenge is to develop techniques that provide repeatable results yet are presented simply enough to be useful to a wide range of industries. Methods - Powdered sucrose, a major pharmaceutical ingredient, was poured into a split die and exposed to high and low relative humidity cycles at room temperature. The typical ranges were 20–30% for the lower value and 70–80% for the higher value. The outer die casing was then removed and the resultant agglomerate was subjected to an unconfined compression test using a plunger fitted to a Zwick compression tester. The force against displacement was logged so that the dynamics of failure as well as the failure load of the sample could be recorded. The experimental matrix included varying the number of cycles, the amount between the maximum and minimum relative humidity, the height and diameters of the samples, the number of cycles and the particle size. Results - Trends showed that the tensile strength of the agglomerates increased with the number of cycles and also with the more extreme swings in relative humidity. This agrees with previous work on alternative methods of measuring the tensile strength of sugar agglomerates formed from humidity cycling (Leaper et al 2003). Conclusions - The results show that at the very least the uniaxial tester is a good comparative tester to examine the caking tendency of powdered materials, with a simple arrangement and operation that are compatible with the requirements of industry. However, further work is required to continue to optimize the height/ diameter ratio during tests.

Strategic groups, cognitive groups and environmental change in the UK pharmaceutical industry

This chapter explores the relationship between changes in strategy and environmental pressures within the UK Pharmaceutical Industry during a ten- year period. Two stable strategic time periods (SSTPs) were identified each of five years duration. Within each time period seven strategic groups were found but 11 out of 29 firms (37.9%) changed strategic groups membership during the period studied. The break between these two SSTPs was found to coincide with a sharp increase in the substitution of branded pharmaceuticals by cheaper parallel imports. A significant relationship was found between firms that changed groups and both their continent of origin and nationality. Firms whose home markets are more vulnerable to substitution were more likely to switch strategic groups. © 2011 Nova Science Publishers, Inc. All rights reserved.