The chemical resistance of glass is an important property for many applications. This property has been extensively studied for many types of glass under static conditions (no liquid is removed during the experiment). There has been little research conducted on the effects of additional stimuli on the dissolution of glass. For this research lithium disilicate was leached in deionized water at multiple temperatures while microwave radiation, ultrasonication or flow conditions were also applied to the system. These results were then compared to static baseline to determine if these stimuli would cause any change to the mechanisms and kinetics of the reaction. It was determined that for the experimental conditions used there was little to no change in dissolution when 2.45 GHz microwave radiation instead of conventional methods was used to heat the reaction. Results from ultrasonication found that samples that experienced erosion showed an increase in dissolution with an increase in dissolution following heavier erosion. This was thought to be due to both an increase in the surface area of the sample to volume of solution (SA/V) ratio (erosion would modify the surface area and release small particulates) and the accelerated removal of the depleted layer due to erosion. Stereoscopic reconstruction was used to semi-quantitatively measure the change in surface area. Regions that experienced minor erosion showed a 3-6% increase in surface area while those that experienced heavy erosion showed a 29-35% increase in surface area. Due to inconsistencies in the size of the eroded area it was not possible to determine the effects of power intensity with this research. Flow dissolution showed similar trends in concentration and different trends for the total normalized mass loss (TNL) to previously published research on more complex glasses. The elemental concentration initially increased before reaching a peak and decreasing to steady state. This peak was thought to be caused by the combination of flow, increasing thickness in the depleted layer, and an initial fluctuation in the forward reaction rate due to changes in pH. For the lithium disilicate glass used in this research both the elemental concentration and the TNL increased with increasing temperature and decreasing flow rate (silica dissolution was an exception as it did not show any change in TNL due to flow). All experimental conditions were shown to achieve steady state (dC/dt~0) by the seventh day of leaching. The contrast in the observed TNL trends between lithium disilicate and more complex glasses was thought to be due to differences in reaction rates and the presence of an additional surface layer in the complex glasses due to precipitation. Microscopy of the leached glass showed that surface features introduced during grinding (scratch lines and microcracks) were preferentially leached and grew in size and number visible during dissolution. A semi-quantitative model was created using stereoscopic reconstruction to describe the preferential leaching of the microcracks as there was little available discussion found in literature outside of associating the growth of these features with localized network dissolution. In this model the microcracks experience preferential dissolution leading to a change in size and shape. The SA/V ratio inside the crack would be much larger than the bulk system (calculated to initially be ~768,000cm-1 compared to the bulk's 0.1cm-1). This would cause massive acceleration in the initial ion exchange, raising the pH of the solution which would in turn cause network dissolution to occur much faster inside the crack. Based on static experiments on lithium disilicate frit (SA/V of 1,010cm-1) the pH inside the crack would jump to above 11 in minutes. As the crack grows, the SA/V ratio inside it would decrease (largest cracks were found to have a ratio ~100,000cm-1). The accelerated leaching caused by these features could have a noticeable effect on the dissolution results. In addition to the accelerated leaching inside a crack, the size of the depleted layer under the crack would be different from the bulk glass. / Doctor of Philosophy / The chemical resistance of glass is an important property for many applications. This property has been extensively studied for many types of glass under static conditions where no liquid was removed and temperature was the major variable. For this research lithium disilicate was leached in deionized water at multiple temperatures while the additional stimuli of microwave radiation, ultrasonication or flow conditions were also applied to the system. The question that this research addressed was how does the aqueous dissolution of glass change when a system is exposed to these additional stimuli? Although glasses are subjected to these stimuli in many everyday applications, their influence on dissolution has not been studied extensively. Lithium disilicate glass was selected because it contains components used in many commercial glasses, has sufficient reactivity in water to allow experiments to be completed in a reasonable time, and because its mechanisms for dissolution under static conditions were well known. Glass is frequently selected to be the container when microwaves are used to heat food or materials. Flow is an important part of many applications involving glass including the storage of nuclear waste glass, glass-lined tanks used in the chemical industries, in the use of glass in the human body (bioglass and dental crowns), and in typical window and laboratory glasses where intermittent aqueous contact and runoff may occur. Examining how cavitation via ultrasonication can be controlled to either minimize or maximize element extraction is important, with the removal of rare earth elements from fly ash being one example.

La contamination des ressources en eaux souterraines par une phase organique non miscible à l'eau couramment appelée NAPL (Non Aqueous Phase Liquid) constitue aujourd'hui un défi scientifique majeur compte tenu de la durée de vie d'un tel polluant. Bien que l'activité bactérienne (généralement présente sous forme de biofilm) joue un rôle crucial dans le devenir à long terme de ces effluents, peu d'études existent à l'heure actuelle sur son impact dans des conditions multiphasiques (i.e., à proximité de la source). En effet, dans la zone saturée, sous l'action des forces capillaires, le NAPL se retrouve souvent piégé, en effet, sous forme de «gouttelettes» au niveau des pores. Ce comportement spécifique au polluant modifie la dynamique du système biofilm/milieu poreux saturé et d'importantes questions restent encore ouvertes : accessibilité du polluant, modification de la tension interfaciale, production de biosurfactant, effet de toxicité (inhibition de la croissance bactérienne). Pour tenter de répondre à ces questions, nous avons adopté une approche aussi bien théorique qu'expérimentale. L'approche théorique porte sur le développement d'un modèle macroscopique décrivant le transport multiphasique en milieu poreux pour un système eau/NAPL/biofilm. Elle repose sur la méthode de prise de moyenne volumique, appliqué aux équations décrivant le couplage écoulement/transport à l'échelle du pore, permettant d'effectuer le changement d'échelle et dériver un modèle à deux équations. Le modèle est établit sous les hypothèses d'équilibre de masse local à l'interface fluide/biofilm et les contraintes associées à ces hypothèses ont étés définies. L'influence des caractéristiques microscopiques (arrangement des grains, fraction volumique du biofilm, distribution des blobs de NAPL, mouillabilité) sur les propriétés effectives du milieu (coefficient de dispersion, coefficient d'échange de masse) est discutée au travers des résultats issus des simulations. Ensuite, le modèle macroscopique a été comparé avec succès à la simulation numérique direct à l'échelle du pore pour la géométrie 2D complexe considérée. Quant à l'approche expérimentale, elle consiste à étudier le transport et la biodégradation du toluène en présence des bactéries Pseudomonas Putida F1 à l'aide d'un milieu poreux transparent 2D (micromodèle). Premièrement, nous avons étudié la dissolution du toluène résiduel sans bactéries et des courbes de dissolution du toluène ont été obtenues. Les résultats de dissolution du toluène en condition abiotique ont été comparés avec succès aux résultats du modèle théorique. Ensuite, l'étude expérimentale en micromodèle a porté sur la dissolution du toluène en condition biotique. Les résultats de ces études (courbes de dissolution et évolution de la saturation résiduelle) ont montré un impact significatif de la présence des bactéries sur les processus de dissolution par comparaison au cas abiotique. / Contamination of groundwater resources by an immiscible organic phase commonly called NAPL (Non Aqueous Phase Liquid) represents a major scientific challenge considering the residence time of such a pollutant. Although bacterial activity (usually in the form of biofilm) plays a crucial role in the long term fate of these effluents, very few works are focused on the study of such processes in multiphase conditions (oil/water/biofilm systems). The NAPL often gets trapped, in fact, under the action of capillary forces in the saturated zone in the form of «droplets» within the pores. This specific pollutant behavior changes the dynamics of biofilm /saturated porous medium system where important questions remain open: accessibility of the pollutant, changes in interfacial tension, biosurfactant production, toxicity effect (inhibition of bacterial growth). Modeling the transport of chemical species in the presence of bacteria is an extremely complex issue in terms of scale. We will use an experimental and theoretical approach to address these questions. In this thesis, we developed a macroscopic model describing multiphase transport in porous media for a water/NAPL/biofilm system. A volume averaging method has been applied here to the equations at the pore scale to make the upscaling and derive the model. This two-equation model is established under the assumptions of local mass equilibrium at the fluid/biofilm interface and the constraints associated with these assumptions were defined. The effect of microscopic features (arrangement of grains, volume fraction of the biofilm, distribution of NAPL blobs, wettability) on the effective properties of the media (dispersion coefficient, mass exchange coefficient) is discussed through some results from simulations. Subsequently, the macroscopic model has been successfully compared with the direct numerical simulation at pore scale for a 2D complex geometry. The experimental approach consists of studying transport and biodegradation of toluene in the presence of bacteria Pseudomonas Putida F1 using a flowcell. First, we studied the dissolution of toluene in abiotic conditions and toluene dissolution curves were obtained. The results of toluene dissolution in abiotic conditions were compared with success the results of the theoretical model. Finally, an experimental study in flowcell on the dissolution of toluene under biotic conditions was performed. The results of these studies (dissolution curve and evolution of toluene saturation) showed a significant impact of the presence of bacteria on the dissolution process compared to the abiotic case.

Today, orally inhaled drugs found on the market suffer from variable and discontinuous pulmonary drug release which lowers efficacy and patience compliance. This is usually a consequence of the poor understanding of the interaction and dissolution behavior of drug particles in the lung environment. Thus, the aim of this project was to investigate the effect of the dissolution medium on dissolution profiles for the well-known orally inhaled drug budesonide (BD) and fluticasone propionate (FP), in order to assess the importance of a proper selection of dissolution media for in vitro dissolution methods. In order to achieve this a modified Andersen Cascade Impactor was used to simulate deposition of particles onto filters. The dissolution was measured using a Transwell set up with polycarbonate membranes that can hold the filters with the deposited drug on it. Different media were prepared, from simple to more biorelevant. The samples taken during the dissolution experiments were analyzed quantitatively using UPLC-UV and the experimental data was processed by fitting to the Weibull function. The aim of this project was successfully achieved and the dissolution media that worked best for both BD and FP was PBS with the addition of 0.5% SDS. On the other hand, the dissolution media that performed the least for both BD and FP was the simulated lung fluid (SLF) with presence of 0.02% (w/v) DPPC. This may be due to the fact that DPPC forms liposomal aggregates which probably results in the media becoming more viscous and hence the dissolution time becomes slower.

<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>

This study focused on two active pharmaceutical ingredients (APIs) that are used to treat two of the most notorious diseases in Africa, i.e. human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and malaria. It is well known that many African countries lack effective regulatory control over medicines and patients are subsequently at risk of receiving sub-standard treatments. This study set out to investigate how the modification of the crystal packing (i.e. polymorphism) of these APIs may impact on their quality, safety and efficacy. Efavirenz (an antiretroviral) and Pyrimethamine (an antimalarial) were selected as the two model APIs for investigation during this study. It was found that a novel amorphous form (Form A) of Efavirenz had been prepared during this study through quench cooling. Form A was extensively characterised and compared to the preferred crystalline Form I, with the aim of providing a means of distinguishing between these two Efavirenz forms. In contrast to popular belief (that amorphous form should have improved dissolution and solubility properties over the crystalline counterpart), the powder dissolution of Form A was significantly lower than that of Form I. Further investigation indicated that this was due to the occurrence of agglomeration and phase-mediated transformation. This observation had led to the belief that Form A had poor thermodynamic stability. The glass transition temperature and the crystallisation activation energy, required for the recrystallisation of Form A, were subsequently determined in an attempt to elucidate its thermodynamic stability. The glass transition temperature of Form A was found to be unfeasibly low, hence confirming its tendency towards agglomeration. The crystallisation activation energy of Form A was determined by non-isothermal determinations, using differential scanning calorimetry (DSC), hot stage microscopy (HSM) and capillary melting point (CMP) analysis. These studies not only elucidated the required activation energy for the conversion of Form A into Form I, but it also found that the results from CMP were similar to those of the universally accepted DSC technique, allowing for the proposal of CMP as a cost-effective alternative to DSC for the quantitative measurement of the crystallisation of Efavirenz. Isothermal studies revealed that Form A had a short half-life, which, together with its poor dissolution performance, exemplified why this form was unsuitable for pharmaceutical use. The Pyrimethamine study focused on recrystallisation as a means of modifying its crystal packing and on an evaluation of the effect that such crystal modification may have on its safety and manufacturability. Anhydrous Pyrimethamine was recrystallised, using methanol, acetone, n-propanol, ethanol, N,N-dimethylformamide and N,N-dimethylacetamide. Ethanol, acetone and n-propanol altered the crystal habit of Pyrimethamine, without any modification of its crystal lattice. The different habits exhibited clear differences in flowability and compressibility, which could in turn affect manufacturing and therefore the quality of the finished pharmaceutical product (FPP). These habits were subsequently extensively characterised by means of in-silico molecular modelling predictions. It was found that recrystallisation from methanol, N,N-dimethylformamide and N,N-dimethylacetamide had resulted in solvatomorphism. These solvatomorphs contained their respective solvents in concentrations exceeding the allowed residual solvent limits, as set by the International Conference on Harmonisation (ICH) guidelines. These undesirable solvatomorphs were also comprehensively characterised as a service to the pharmaceutical industry, in order to identify the distinct characteristics that distinguish these forms from the preferred non-toxic form, and to provide techniques for transforming the toxic forms into the non-toxic form. / PhD (Pharmaceutics), North-West University, Potchefstroom Campus, 2015

This study focused on two active pharmaceutical ingredients (APIs) that are used to treat two of the most notorious diseases in Africa, i.e. human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and malaria. It is well known that many African countries lack effective regulatory control over medicines and patients are subsequently at risk of receiving sub-standard treatments. This study set out to investigate how the modification of the crystal packing (i.e. polymorphism) of these APIs may impact on their quality, safety and efficacy. Efavirenz (an antiretroviral) and Pyrimethamine (an antimalarial) were selected as the two model APIs for investigation during this study. It was found that a novel amorphous form (Form A) of Efavirenz had been prepared during this study through quench cooling. Form A was extensively characterised and compared to the preferred crystalline Form I, with the aim of providing a means of distinguishing between these two Efavirenz forms. In contrast to popular belief (that amorphous form should have improved dissolution and solubility properties over the crystalline counterpart), the powder dissolution of Form A was significantly lower than that of Form I. Further investigation indicated that this was due to the occurrence of agglomeration and phase-mediated transformation. This observation had led to the belief that Form A had poor thermodynamic stability. The glass transition temperature and the crystallisation activation energy, required for the recrystallisation of Form A, were subsequently determined in an attempt to elucidate its thermodynamic stability. The glass transition temperature of Form A was found to be unfeasibly low, hence confirming its tendency towards agglomeration. The crystallisation activation energy of Form A was determined by non-isothermal determinations, using differential scanning calorimetry (DSC), hot stage microscopy (HSM) and capillary melting point (CMP) analysis. These studies not only elucidated the required activation energy for the conversion of Form A into Form I, but it also found that the results from CMP were similar to those of the universally accepted DSC technique, allowing for the proposal of CMP as a cost-effective alternative to DSC for the quantitative measurement of the crystallisation of Efavirenz. Isothermal studies revealed that Form A had a short half-life, which, together with its poor dissolution performance, exemplified why this form was unsuitable for pharmaceutical use. The Pyrimethamine study focused on recrystallisation as a means of modifying its crystal packing and on an evaluation of the effect that such crystal modification may have on its safety and manufacturability. Anhydrous Pyrimethamine was recrystallised, using methanol, acetone, n-propanol, ethanol, N,N-dimethylformamide and N,N-dimethylacetamide. Ethanol, acetone and n-propanol altered the crystal habit of Pyrimethamine, without any modification of its crystal lattice. The different habits exhibited clear differences in flowability and compressibility, which could in turn affect manufacturing and therefore the quality of the finished pharmaceutical product (FPP). These habits were subsequently extensively characterised by means of in-silico molecular modelling predictions. It was found that recrystallisation from methanol, N,N-dimethylformamide and N,N-dimethylacetamide had resulted in solvatomorphism. These solvatomorphs contained their respective solvents in concentrations exceeding the allowed residual solvent limits, as set by the International Conference on Harmonisation (ICH) guidelines. These undesirable solvatomorphs were also comprehensively characterised as a service to the pharmaceutical industry, in order to identify the distinct characteristics that distinguish these forms from the preferred non-toxic form, and to provide techniques for transforming the toxic forms into the non-toxic form. / PhD (Pharmaceutics), North-West University, Potchefstroom Campus, 2015

With the advance of combinational chemistry and high throughput screening, an increasing number of pharmacologically active compounds have been discovered and developed. A significant proportion of those drug candidates are poorly water-soluble, thereby exhibiting limited absorption profiles after oral administration. Therefore, advanced formulation and processing technologies are demanded in order to overcome the biopharmaceutical limits of poorly water-soluble drugs. A number of pharmaceutical technologies have been investigated to address the solubility issue, such as particle size reduction, salt formation, lipid-based formulation, and solubilization. Within the scope of this dissertation, two of the pharmaceutical technologies were investigated names thin film freezing and hot-melt extrusion. The overall goal of the research was to improve the oral bioavailability of poorly water-soluble drugs by producing amorphous solid dispersion systems with enhanced wetting, dissolution, and supersaturation properties. In Chapter 1, the pharmaceutical applications of hot-melt extrusion technology was reviewed. The formulation and process development of hot-melt extrusion was discussed. In Chapter 2, we investigated the use of thin film freezing technology combined with template emulsion system to improve the dissolution and wetting properties of itraconazole (ITZ). The effects of formulation variables (i.e., the selection of polymeric excipients and surfactants) and process variables (i.e., template emulsion system versus cosolvent system) were studied. The physic-chemical properties and dissolution properties of thin film freezing compositions were characterized extensively. In Chapter 3 and Chapter 4, we investigated hot-melt extrusion technology for producing amorphous solid dispersion systems and improving the dissolution and absorption of ITZ. Formulation variables (i.e., the selection of hydrophilic additives, the selection of polymeric carriers) and process variables (i.e., the screw configuration of hot-melt extrusion systems) were investigated in order to optimize the performance of ITZ amorphous solid dispersions. The effects of formulation and process variables on the properties of hot-melt extrusion compositions were investigated. In vivo studies revealed that the oral administration of advanced ITZ amorphous solid dispersion formulations rendered enhanced oral bioavailability of the drug in the rat model. Results indicated that novel formulation and processing technologies are viable approaches for enhancing the oral absorption of poorly water-soluble drugs. / text

<p>Many banks provide very similar services and that is why creating and maintaining relationships to clients is a differentiation strategy to get customer to return. Private advising is one service provided by banks where much interaction occurs and relationship is of great importance. The relationship between private advisers and their clients is therefore suitable for research.</p><p>Knowing why a relationship ends is a strategic piece of information to improve the firm’s ability to keep customers in a relationship. The purpose of this paper is to identify the issues that lead to dissolution of a relationship and where they occur in the relationship development process between private advisors and clients.</p><p>A pre-study was first made on Swedbank, through interviews, to obtain a holistic view of the situation. More in-depth interviews followed as well as triangulation through a questionnaire.</p><p>The thesis presents seven issues that can lead to dissolution of the relationship: better offering from competitors, availability, personal factors, unachievable demands, no need for service, lack of certain services, and requirement not fulfilled. These issues have also been related to where in the relationship development process they occur and ranked in order to know how common it is for them to occur.</p> / <p>De flesta banker erbjuder sina kunder väldigt snarlika tjänster och därför har skapandet av relationer blivit en differentierings strategi för att få kunder att komma tillbaka. Privatrådgivning är en tjänst som banker erbjuder där mycket interaktion sker och relationer är oerhört viktiga. På grund av detta så är relationen mellan privatrådgivaren och dess klient passande att undersöka</p><p>Att veta varför en relation avslutas är väldigt viktig strategisk information som kan användas för att förbättra en firmas möjlighet att bevara kunder. Syftet med den här uppsatsen är att identifiera de problem som kan leda till att en relation bryts och även att identifiera vart i relationsbyggnads processen dessa problem uppstår.</p><p>En förstudie genomfördes först för att få en överblickande bild över ämnet. Efter denna så följde även mer djupgående intervjuer samt metodtriangulering med hjälp av ett frågeformulär som skickades ut till Swedbanks privatrådgivare.</p><p>Uppsatsen presenterar sju problem som kan leda till upplösningen av en relation: bättre erbjudanden från konkurrenter, tillgänglighet, personliga faktorer, ouppnåeliga krav, inget behov av tjänst, brist på en viss tjänst samt att kunden inte uppfyller krav. Dessa problem har även relaterats till vart I relationsbyggnads processen de uppstår och rankats i ordning beroende på hur vanligt de är att problemen uppstår.</p>

The purpose of this thesis is to explain this evolution of Mobil's corporate identity, and to determine the effect of the 1911 dissolution decree on it.

Master of Science / Department of Family Studies and Human Services / Jared R. Anderson / Amber V. Vennum / The present study sought to extend the research on cyclical, or on-again/off-again relationships, by examining whether a history of cyclicality moderated the association between neuroticism and relationship satisfaction. A second goal of this study was to examine the direct and indirect effects of neuroticism on relationship satisfaction through communication. The sample consisted of cohabiting cyclical (n = 1,055) and noncyclical (n = 2,527) couples from a larger dataset collected by the RELATE Institute. Results showed that cyclical partners reported higher levels of neuroticism, higher levels of conflict, lower levels of positive communication, and lower levels of relationship satisfaction than noncyclical couples. Direct actor paths from neuroticism to satisfaction were significant for cyclical and noncyclical females and males. Only the direct partner path from female neuroticism to male satisfaction was significant, and was only significant for cyclical couples. All indirect actor and partner paths were significant for cyclical and noncyclical females and males. Further, a history of cyclicality significantly moderated the direct paths from male communication to male and female relationship satisfaction, indicating this relationship is stronger for cyclical couples.