Of the nine South African provinces, Limpopo Province has produced the worst Grade 12 results in the ten years between 1996 and 2006. Yet Thohoyandou and Mutale districts in that province performed outstandingly well from 1994 to 2006. This study aimed to find out what influential factors made the difference within these two districts between high-performing and poorly performing schools, by comparing those that performed well with those that performed badly. Data were gathered by means of questionnaires completed by a total of 87 teachers, and structured interviews were conducted with principals. The sample of 24 schools was divided into two types, ‘high performing’ and ‘poorly performing’. By means of the questionnaires, a total of 114 variables were explored, encompassing a number of different factors, from which a total of 18 hypotheses were derived: three concerning teacher factors (qualifications, home language), 10 concerning school factors (locality, number of classrooms, assembly hall, library etc. and teacher-generated problems), one concerning parental involvement, two concerning teacher motivation and management (frequency and scheduling of staff meetings), and two concerning learner motivation and management (including performance with notes and summaries). The data from both groups of schools were compared in order to test the 18 hypotheses on the influence of different variables upon Grade 12 results, the null hypothesis being, of course, that there was no influence. Before this was done, pairs of variables were also compared and subjected to chi-square testing for each of the two groups of schools to see which of the factors might be related to one another in some way, thus impacting on interpretation of the results of the hypothesis testing. For each of the two groups of schools, results from the questionnaires were analyzed by means of: <ul> <li>Frequency analyses and descriptive statistics extracted from the tables of results where they were of possible interest. Variables such as the gender of teachers were, for example, included.</li> <li>Contingency tables with chi-square analysis testing the independence of the variables where possible relationships between the variables could emerge.</li> <li>Contingency tables with chi-square analysis where the connection was not significant and independence of the variables from each other could therefore be assumed.</li></ul> The chi-square analysis tested the difference between the variables at a 0.5% level of significance. Results of the various analyses were not particularly conclusive. Those with the most reliable levels of significance suggested that the most important variables were those relating to interpersonal relationships, specifically those involving different types of contact. Where staff meetings were scheduled and not particularly frequent, Grade 12 results were better. These results were also better where there was frequent contact between parents and teachers. The results of this study and in this sample area suggest that a school’s management style is more important to Grade 12 performance than the provision of funding and facilities. Further investigation is needed before these conclusions can be generalized to other districts and provinces. / Thesis (PhD)--University of Pretoria, 2008. / Curriculum Studies / unrestricted

Poorly water-soluble drugs (PWSDs), to date, require advanced formulation techniques to improve solubility and achieve the required plasma concentration to show a therapeutic effect when orally administered. Lipid-based formulations (LBFs) are an enabling strategy that is being used to improve the oral delivery of PWSDs. The aim of this study was to investigate the effect of lipid-based formulation, Type IIIA-LC, on the solubilization patterns of PWSDs, namely, carvedilol and felodipine. Solubility studies, for both drugs, were performed with LBF dispersed in -1) dog intestinal fluid (DIF), and 2) water, to identify and compare the extent of solubility in different matrices, and in silico to identify interesting patterns with any correlations in experimental and computational data. Solubility studies showed that carvedilol had better solubility in LBF when compared to felodipine. Computational studies showed that both drugs solubilized in the colloid in both digested and undigested states. Effect of drug loading had no significant difference on the solubilization patterns of both drugs. The maximum drug loading done was for 100 molecules though there is the possibility of the colloid having a higher capacity. Digestion did not seem to have a significant effect on the distribution of both drugs. In vitro and in silico data were in qualitative agreement and therefore, this computational model can be further used to study the specific processes causing solubilization, improvement, and development of new LBFs.

<p>The dissolved concentration of an active pharmaceutical ingredient in biological fluids is of significant importance for establishing a therapeutic effect in patients. However, the current pharmaceutical landscape is abundant in poorly soluble drugs that require solubility enhancing techniques to enable their administration. A promising technique, with increasing commercial success, is to molecularly mix drug and polymer to create an amorphous solid dispersion (ASD). While these mixtures provide enhanced drug solubility and dissolution in aqueous solutions, the mechanistic processes by which they release drug into solution are not well understood. Some unexplained behaviors include rapid drug release even at the maximum supersaturated concentration and spontaneous formation of drug-rich nanoparticles. These are beneficial for rapidly achieving and maintaining a highly supersaturated drug concentration during absorption, if crystallization is inhibited. However, the phenomena occur at typically low drug loading and are abruptly lost above a certain threshold termed the ‘limit of congruency’ (LoC), which has been reported to vary based on the drug-polymer system. In this research, the mechanisms underpinning ASD release at low and high drug loading were studied, and the factors affecting LoC were mechanistically explored by performing dissolution experiments and utilizing imaging, separation, thermal analysis, and spectroscopy methods to characterize the materials in the presence and absence of water. The results show that ASDs developed a gel layer on the surface when exposed to aqueous solution. This water-rich environment was thermodynamically unstable and phase separated into hydrophilic and hydrophobic phases. The morphology of the hydrophobic phase was directly related to the ASD release behavior, where ASDs below the LoC exhibited a dispersed and stable hydrophobic phase morphology, and ASDs above the LoC displayed a continuous or aggregated morphology. In cases where thermodynamic factors were rate limiting, LoC was inferred from features on the ternary phase diagram. Moreover, drug-polymer interactions and polymer molecular weight were demonstrated to affect the morphology of the hydrophobic phase and ultimately the LoC. The conclusions from this work provide the basis of a theoretical framework for rationally designing ASDs and optimizing their release. </p>

One of the challenges of biopharmaceutics research is correlating in vitro drug release information with the in vivo drug profiles often known as in vitro-in vivo correlations (IVIVC). These have huge cost savings in pharmaceutical industry. This dissertation describes the development of a novel in vitro dissolution model that has been designed to evaluate the in vitro release of poorly water-soluble model compounds so as to predict their in vivo behavior. The flow through apparatus (USP 4) has been coupled with the compendial dissolution apparatus (USP 2). A bi-phasic dissolution medium has been used to achieve sink conditions. The dissolved drug from the aqueous phase is continuously extracted into the organic phase of the biphasic dissolution medium, mimicking the dynamic process of in vivo absorption. The model can successfully discriminate between the bioequivalent and non-bioequivalent formulations and can be used to establish IVIVC. It was concluded that the model will serve as a surrogate for bioequivalence studies and to support biowaivers.

No description available.

Pharmaceutical companies and FDA (Federal Drug Administration) rules rely heavily on crystalline active pharmaceutical ingredients delivered as tablets and powders in the form of neutral compounds, salts and solvates of neutral compounds and salts. About half of all drugs sold in the market are in the form of salts which are held together by ionic bonds along with some other forces. Recently, Ionic liquids (ILs) an interesting class of chemical compounds have offered potential opportunity for exploration as novel drug ionic liquid salts, particularly in the field of transdermal/topical drug delivery. Due to the multifunctional nature of these salts they could allow generation of new pathway to manipulate the transport and deposition behaviour of the drug molecule. It is this modular approach of IL that forms the basis of the research presented here, in which pharmaceutically acceptable compounds are combined with selected drugs with known problems. IL salts were generated by combining at least one drug molecule with FDA approved compounds and were assessed for physicochemical properties, skin deposition and permeation studies. Skin deposition data suggested that these systems exhibit high skin retention, which was found to correlate with the molecular weight. On the other hand, permeation data displayed an inverse relationship between flux values and molecular weight of the permeant. Similar work was extended with ILs with mixed anions containing two drugs. The benzalkonium-sulfacetamide ILs were investigated for synergism and the biological studies data display no synergistic effect. It was also illustrated that in-situ IL based ibuprofen hydrogels systems could be manipulated via IL approach for topical application. These findings suggest the potential applicability of IL based formulations for topical delivery of drugs.

Yes / A study has been carried out to investigate controlled release performance of caplet shaped injection moulded (IM) amorphous solid dispersion (ASD) tablets based on the model drug AZD0837 and polyethylene oxide (PEO). The physical/chemical storage stability and release robustness of the IM tablets were characterized and compared to that of conventional extended release (ER) hydrophilic matrix tablets of the same raw materials and compositions manufactured via direct compression (DC). To gain an improved understanding of the release mechanisms, the dissolution of both the polymer and the drug were studied. Under conditions where the amount of dissolution media was limited, the controlled release ASD IM tablets demonstrated complete and synchronized release of both PEO and AZD0837 whereas the release of AZD0837 was found to be slower and incomplete from conventional direct compressed ER hydrophilic matrix tablets. Results clearly indicated that AZD0837 remained amorphous throughout the dissolution process and was maintained in a supersaturated state and hence kept stable with the aid of the polymeric carrier when released in a synchronized manner. In addition, it was found that the IM tablets were robust to variation in hydrodynamics of the environment and PEO molecular weight. / The research was funded by AstraZeneca, Sweden.

L’importance de la documentation du patrimoine culturel croit parallèlement aux risques auxquels il est exposé tels que les guerres, le développement urbain incontrôlé, les catastrophes naturelles, la négligence et les techniques ou stratégies de conservation inappropriées. De plus, la documentation constitue un outil fondamental pour l'évaluation, la conservation, le suivi et la gestion du patrimoine culturel. Dès lors, cet outil majeur nous permet d’estimer la valeur historique, scientifique, sociale et économique de ce patrimoine. Selon plusieurs institutions internationales dédiées à la conservation du patrimoine culturel, il y a un besoin réel de développer et d’adapter de solutions informatiques capables de faciliter et de soutenir la documentation du patrimoine culturel peu documenté surtout dans les pays en développement où il y a un manque flagrant de ressources. Parmi ces pays, la Palestine représente un cas d’étude pertinent dans cette problématique de carence en documentation de son patrimoine. Pour répondre à cette problématique, nous proposons une approche d’acquisition et d’extraction de connaissances patrimoniales dans un contexte peu documenté. Nous prenons comme cas d’étude l’église de la Nativité en Palestine et nous mettons en place notre approche théorique par le développement d’une plateforme d’acquisition et d’extraction de connaissances patrimoniales à l’aide d’un Framework pour la documentation de patrimoine culturel.Notre solution est basée sur les technologies sémantiques, ce qui nous donne la possibilité, dès le début, de fournir une description ontologique riche, une meilleure structuration de l'information, un niveau élevé d'interopérabilité et un meilleur traitement automatique (lisibilité par les machines) sans efforts additionnels.De plus, notre approche est évolutive et réciproque car l’acquisition de connaissance (sous forme structurée) améliore l’extraction de connaissances patrimoniales à partir de texte non structuré et vice versa. Dès lors, l’interaction entre les deux composants de notre système ainsi que les connaissances patrimoniales se développent et s’améliorent au fil de temps surtout que notre système utilise les contributions manuelles et validations des résultats automatiques (dans les deux composants) par les experts afin d’optimiser sa performance. / The importance of cultural heritage documentation increases in parallel with the risks to which it is exposed, such as wars, uncontrolled urban development, natural disasters, neglect and inappropriate conservation techniques or strategies. In addition, this documentation is a fundamental tool for the assessment, the conservation, and the management of cultural heritage. Consequently, this tool allows us to estimate the historical, scientific, social and economic value of this heritage. According to several international institutions dedicated to the preservation of cultural heritage, there is an urgent need to develop computer solutions to facilitate and support the documentation of poorly documented cultural heritage especially in developing countries where there is a lack of resources. Among these countries, Palestine represents a relevant case study in this issue of lack of documentation of its heritage. To address this issue, we propose an approach of knowledge acquisition and extraction in the context of poorly documented heritage. We take as a case study the church of the Nativity in Palestine and we put in place our theoretical approach by the development of a platform for the acquisition and extraction of heritage knowledge. Our solution is based on the semantic technologies, which gives us the possibility, from the beginning, to provide a rich ontological description, a better structuring of the information, a high level of interoperability and a better automatic processing without additional efforts.Additionally, our approach is evolutionary and reciprocal because the acquisition of knowledge (in structured form) improves the extraction of heritage knowledge from unstructured text and vice versa. Therefore, the interaction between the two components of our system as well as the heritage knowledge develop and improve over time especially that our system uses manual contributions and validations of the automatic results (in both components) by the experts to optimize its performance.

<p>The general aim of the present project was to increase the understanding of the in vivo dissolution of poorly soluble drugs and thereby improve possibility to predict in vivo solubility from substance properties. Increased understanding of the in vivo limitations of drug solubility could potentially also generate ideas for improved formulation principles for poorly soluble compounds and more relevant in vitro dissolution test methods used in formulation development.</p><p>The dynamic gastrointestinal secretory and enzymatic responses to a liquid meal were studied in human intestinal fluid (HIF) by in vivo perfusion of a nutritional drink. The main diversity found compared to simulated intestinal fluids was the presence of dietary lipids in fed human intestinal fluid. This difference was showed to be of importance in the solubility of low soluble drugs, since this parameter was underestimated in the simulated fluid. Thus suggesting that simulated intestinal fluids should be prepared with the addition of dietary lipids for better in vitro in vivo predictions. </p><p>Solubility and dissolution determinations in fasted and fed HIF showed that the solubility was higher in fed state fluid, probably owing to the higher concentration of lipids in this media. The higher solubility was correlated to both the lipophilicity and aqueous solubility of the drug. The dissolution rate also increased, but not to the same extent as the solubility. These findings need to be considered in the design of in vitro models and in the prediction of food effects on oral bioavailability of poorly soluble drugs.</p><p>In addition, an in vivo porcine perfusion study was performed to investigate importance of different mechanisms in food-drug interactions. The results showed that solubilisation might be a more important factor than P-gp inhibition for food-related effects on the intestinal absorption kinetics of Class II drugs. </p>

Large and ever-increasing numbers of chemicals, including large quantities of a broad spectrum of organic compounds are used in modern society. More than 30 000 of the more than 100 000 chemical substances registered in the EU are estimated to be daily used, of which many will be discharged into the waste-streams handled by municipal sewage treatment plants (STPs). The main objective of the work underlying this thesis was to improve understanding of the relationships between the characteristics of sewage contaminants and their sewage treatment efficiency. Further objectives were to examine the relationships between socio-economic uses of chemicals and sludge quality, and the effects of regulatory actions on sludge quality. The quality of the sewage sludge and the levels and distribution patterns of the sludge contaminants, both within and between the STPs, seem to remain quite constant over time. The overall findings indicate that the levels of contaminants in sewage sludge seem to be largely independent of the location, size and treatment techniques applied at the STPs, and generally, of the types of human activity connected to them. The total and relative concentrations of the sludge contaminants were found to be fairly constant on a dry weight basis, with some exceptions, indicating that the pollutants originate from broad usage and diffuse dispersion rather than (industrial) point sources. The proportion of cyclic methylsiloxanes recovered in sludge seems to strongly depend on their vapour pressure, which decreases with the number of siloxane units. The higher water solubility and biodegradability of organophosphorus flame retardants and plasticizers than polybrominated diphenyl ethers (PBDEs) were also reflected in lower percentages (relative to their national use) found in sludge. Significant time-trends in levels of a-third of the sludge contaminants included in the annual national measurement program were detected over a period of seven years. The levels of compounds displaying significant time-trends generally decreased following declines in the quantities used nationally. However, a quarter of these compounds showed increasing trends, of which the linear methylsiloxanes followed the same trend as used quantities. The decaBDE was also found to be increasing in sludge, probably as a result of the phase-out of pentaBDE and octaBDE. The results indicate that the STP removal efficiency of anthropogenic substances, in Sweden, is generally good and that STPs, at least those in cold climates, do not efficiently remove certain polar contaminants. A non-targeted screening (by use of environmetrics and GCxGC-TOFMS) was performed and found to fulfil the objective to assess the STP removal efficiency, with emphasis to systematically analyse which compound classes that are not efficiently removed using the current STP technology. Many polar aromatic compounds were identified to be poorly removed. The acquired data on levels, profiles and variations in sludge contaminants (sludge quality) extend both the available information and understanding of the degree and nature of sludge contamination, which should help attempts to track changes in its contaminants and revisions, if necessary, of guideline values. This thesis also contributes to improve the knowledge base for the development of future STP technologies, and that archived sewage sludge can be used in retrospective analysis of new and emerging pollutants.