The effect of selected water-soluble excipients on the dissolution of paracetamol and ibuprofen

The purpose of this investigation was to study the dissolution behavior of paracetamol and ibuprofen in the presence of a range of selected potential excipients. First, a pH-solubility profile was generated for both drugs, and the effect of changing hydrodynamic conditions on the intrinsic dissolution rate was investigated. It was established that both drugs dissolved according to the diffusion-layer model. Paracetamol solubility (approximately 20.3 mg mL -1) did not vary from pH 1.2-8.0, corresponding to the in vivo range in the gastrointestinal tract. Ibuprofen had an intrinsic solubility of approximately 0.06 mg mL-1, and pKa was calculated as 4.4. Second, the effects of selected potential excipients (lactose, potassium bicarbonate, sodium bicarbonate, sodium chloride, and tartaric acid) were evaluated by measuring the effect of the inclusion of each additive in the dissolution medium on drug solubility, drug intrinsic dissolution rate, and solution viscosity. The results were evaluated using the diffusion-layer model, and it was determined that for paracetamol, the collected data fitted the model for all the excipients studied. For ibuprofen, it was found that there were differences between the excipients that raised the solution pH above the pK a to those that did not. For the excipients raising the pH above the pKa, the effect on intrinsic dissolution rate was not as high as that expected from the change in drug solubility. It was postulated that this might be due to lack of penetration of the excipient into the drug boundary layer microenvironment. Formulators may calculate the effect of adding an excipient based on solubility increases but may not find the dissolution rate improvement expected. Copyright © 2005 Taylor & Francis Inc.

Time series analysis in the assessment of ICT impact at the aggregate level – lessons and implications for the new economy

The major role of information and communication technology (ICT) in the new economy is well documented: countries worldwide are pouring resources into their ICT infrastructure despite the widely acknowledged “productivity paradox”. Evaluating the contribution of ICT investments has become an elusive but important goal of IS researchers and economists. But this area of research is fraught with complexity and we have used Solow's Residual together with time-series analysis tools to overcome some methodological inadequacies of previous studies. Using this approach, we conduct a study of 20 countries to determine if there was empirical evidence to support claims that ICT investments are worthwhile. The results show that ICT contributes to economic growth in many developed countries and newly industrialized economies (NIEs), but not in developing countries. We finally suggest ICT-complementary factors, in an attempt to rectify possible flaws in ICT policies as a contribution towards improvement in global productivity.

The study and characterisation of water-based latices used for can coating interiors

Water-based latices, used in the production of internal liners for beer/beverage cans, were investigated using a number of analytical techniques. The epoxy-graft-acrylic polymers, used to prepare the latices, and films, produced from those latices, were also examined. It was confirmed that acrylic polymer preferentially grafts onto higher molecular weight portions of the epoxy polymer. The amount of epoxy remaining ungrafted was determined to be 80%. This figure is higher than was previously thought. Molecular weight distribution studies were carried out on the epoxy and epoxy-g-acrylic resins. A quantitative method for determining copolymer composition using GPC was evaluated. The GPC method was also used to determine polymer composition as a function of molecular weight. IR spectroscopy was used to determine the total level of acrylic modification of the polymers and NMR was used to determine the level of grafting. Particle size determinations were carried out using transmission electron microscopy and dynamic light scattering. Levels of stabilising amine greatly affected the viscosity of the latex, particle size and amount of soluble polymer but the core particle size, as determined using TEM, was unaffected. NMR spectra of the latices produced spectra only from solvents and amine modifiers. Using solid-state CP/MAS/freezing techniques spectra from the epoxy component could be observed. FT-IR spectra of the latices were obtained after special subtraction of water. The only difference between the spectra of the latices and those of the dry film were due to the presence of the solvents in the former. A distinctive morphology in the films produced from the latices was observed. This suggested that the micelle structure of the latex survives the film forming process. If insufficient acrylic is present, large epoxy domains are produced which gives rise to poor film characteristics. Casting the polymers from organic solutions failed to produce similar morphology.

The behaviour of polymer quenchants

The internationally accepted Wolfson Heat Treatment Centre Engineering Group test was used to evaluate the cooling characteristics of the most popular commercial polymer quenchants: polyalkylene glycols, polyvinylpyrrolidones and polyacrylates. Prototype solutions containing poly(ethyloxazoline) were also examined. Each class of polymer was capable of providing a wide range of cooling rates depending on the product formulation, concentration, temperature, agitation, ageing and contamination. Cooling rates for synthetic quenchants were generally intermediate between those of water and oil. Control techniques, drag-out losses and response to quenching in terms of hardness and residual stress for a plain carbon steel, were also considered. A laboratory scale method for providing a controllable level of forced convection was developed. Test reproducibility was improved by positioning the preheated Wolfson probe 25mm above the geometric centre of a 25mm diameter orifice through which the quenchant was pumped at a velocity of 0.5m/s. On examination, all polymer quenchants were found to operate by the same fundamental mechanism associated with their viscosity and ability to form an insulating polymer-rich-film. The nature of this film, which formed at the vapour/liquid interface during boiling, was dependent on the polymer's solubility characteristics. High molecular weight polymers and high concentration solutions produced thicker, more stable insulating films. Agitation produced thinner more uniform films. Higher molecular weight polymers were more susceptible to degradation, and increased cooling rates, with usage. Polyvinylpyrrolidones can be cross-linked resulting in erratic performance, whilst the anionic character of polyacrylates can lead to control problems. Volatile contaminants tend to decrease the rate of cooling and salts to increase it. Drag-out increases upon raising the molecular weight of the polymer and its solution viscosity. Kinematic viscosity measurements are more effective than refractometer readings for concentration control, although a quench test is the most satisfactory process control method.

Adapting an apprenticeship model to the needs of English-medium education at the tertiary level in Turkey

Despite the difficulties that we have regarding the use of English in tertiary education in Turkey, we argue that it is necessary for those involved to study in the medium of English. Furthermore, significant advances have been made on this front. These efforts have been for the most part language-oriented, but also include research into needs analysis and the pedagogy of team-teaching. Considering the current situation at this level of education, however, there still seems to be more to do. And the question is, what more can we do? What further contribution can we make? Or, how can we take this process further? The purpose of the study reported here is to respond to this last question. We test the proposition that it is possible to take this process further by investigating the efficient management of transition from Turkish-medium to English-medium at the tertiary level of education in Turkey. Beyond what is achieved by only the language orientation of the EAP approach, and moving conceptually deeper than what has been achieved by the team-teaching approach, the research undertaken for the purpose of this study focuses on the idea of the discourse community that people want to belong to. It then pursues an adaptation of the essentially psycho-social approach of apprenticeship, as people become aspirants and apprentices to that discourse community. In this thesis, the researcher recognises that she cannot follow all the way through to the full implementation of her ideas in a fully-taught course. She is not in a position to change the education system. What she does here is to introduce a concept and sample its effects in terms of motivation, and thereby of integration and of success, for individuals and groups of learners. Evaluation is provided by acquiring both qualitative and quantitative data concerning mature members' perceptions of apprenticed-neophytes functioning as members in the new community, apprenticed-neophytes' perceptions of their own membership and of the preparation process undertaken, and the comparison of these neophytes' performance with that of other neophytes in the community. The data obtained provide strong evidence in support of the potential usefulness of this apprenticeship model towards the declared purpose of improving the English-medium tertiary education of Turkish students in their chosen fields of study.

The scope to improve the efficiency of solar-powered reverse osmosis

The aim of this paper is to identify and evaluate potential areas of technical improvement to solar-powered desalination systems that use reverse osmosis (RO). We compare ideal with real specific energy consumption (SEC) to pinpoint the causes of inefficiency. The ideal SEC is compared among different configurations including a batch system driven by a piston, and continuous systems with single or multiple stages with or without energy recovery in each case. For example, to desalinate 1 m3 of freshwater from normal seawater (osmotic pressure 27 bar) will require at least 0.94 kWh of solar energy; thus in a sunny coastal location, up to 1850 m3 of water per year per m2 (m3/m2) of land covered by solar collectors could theoretically be desalinated. For brackish water (osmotic pressure 3 bar), 11570 m3/m2 of fresh water could theoretically be obtained under the same conditions. These ideal values are compared with practically achieved values reported in the literature. The practical energy consumption is found to be typically 40-200 times higher depending on feed water composition, system configuration and energy recovery. For state-of-the-art systems, energy losses at the various steps in the conversion process are quantified and presented with the help of Sankey diagrams. Improvements that could reduce the losses are discussed. Consequently, recommendations for areas of R&D are highlighted with particular reference to emerging technologies. It is concluded that there is considerable scope to improve the efficiency of solar-powered RO system.

Medical error:a discussion of the medical construction of error and suggestions for reforms of medical education to decrease error

Introduction: There is a growing public perception that serious medical error is commonplace and largely tolerated by the medical profession. The Government and medical establishment's response to this perceived epidemic of error has included tighter controls over practising doctors and individual stick-and-carrot reforms of medical practice. Discussion: This paper critically reviews the literature on medical error, professional socialization and medical student education, and suggests that common themes such as uncertainty, necessary fallibility, exclusivity of professional judgement and extensive use of medical networks find their genesis, in part, in aspects of medical education and socialization into medicine. The nature and comparative failure of recent reforms of medical practice and the tension between the individualistic nature of the reforms and the collegiate nature of the medical profession are discussed. Conclusion: A more theoretically informed and longitudinal approach to decreasing medical error might be to address the genesis of medical thinking about error through reforms to the aspects of medical education and professional socialization that help to create and perpetuate the existence of avoidable error, and reinforce medical collusion concerning error. Further changes in the curriculum to emphasize team working, communication skills, evidence-based practice and strategies for managing uncertainty are therefore potentially key components in helping tomorrow's doctors to discuss, cope with and commit fewer medical errors.

Pichia pastoris regulates its gene-specific response to different carbon sources at the transcriptional, rather than the translational, level

Background: The methylotrophic, Crabtree-negative yeast Pichia pastoris is widely used as a heterologous protein production host. Strong inducible promoters derived from methanol utilization genes or constitutive glycolytic promoters are typically used to drive gene expression. Notably, genes involved in methanol utilization are not only repressed by the presence of glucose, but also by glycerol. This unusual regulatory behavior prompted us to study the regulation of carbon substrate utilization in different bioprocess conditions on a genome wide scale. Results: We performed microarray analysis on the total mRNA population as well as mRNA that had been fractionated according to ribosome occupancy. Translationally quiescent mRNAs were defined as being associated with single ribosomes (monosomes) and highly-translated mRNAs with multiple ribosomes (polysomes). We found that despite their lower growth rates, global translation was most active in methanol-grown P. pastoris cells, followed by excess glycerol- or glucose-grown cells. Transcript-specific translational responses were found to be minimal, while extensive transcriptional regulation was observed for cells grown on different carbon sources. Due to their respiratory metabolism, cells grown in excess glucose or glycerol had very similar expression profiles. Genes subject to glucose repression were mainly involved in the metabolism of alternative carbon sources including the control of glycerol uptake and metabolism. Peroxisomal and methanol utilization genes were confirmed to be subject to carbon substrate repression in excess glucose or glycerol, but were found to be strongly de-repressed in limiting glucose-conditions (as are often applied in fed batch cultivations) in addition to induction by methanol. Conclusions: P. pastoris cells grown in excess glycerol or glucose have similar transcript profiles in contrast to S. cerevisiae cells, in which the transcriptional response to these carbon sources is very different. The main response to different growth conditions in P. pastoris is transcriptional; translational regulation was not transcript-specific. The high proportion of mRNAs associated with polysomes in methanol-grown cells is a major finding of this study; it reveals that high productivity during methanol induction is directly linked to the growth condition and not only to promoter strength.