<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>

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. 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. 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. 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.

The chemistry of mineral surfaces is of great importance in many different areas including natural processes occurring in oceans, rivers, lakes and soils. Manganese (hydr)oxides are one important group to these natural processes, and the thermodynamically most stable trivalent manganese (hydr)oxide, manganit (γ-MnOOH), is studied in this thesis. This thesis summarises six papers in which the surface chemistry of synthetic manganite has been investigated with respect to surface acid-base properties, dissolution, and adsorption of Cd(II) and the herbicide N-(phosphonomethyl)glycine (glyphosate, PMG). In these papers, a wide range of analysis techniques were used, including X-ray photoelectron spectroscopy (XPS), extended X-ray absorption fine structure (EXAFS) spectroscopy, Fourier transform infra-red (FTIR) spectroscopy, atomic force microscopy (AFM), scanning electron microscopy (SEM), X-ray diffraction (XRD), potentiometry, electrophoretic mobility measurements and wet chemical techniques, in order to obtain a more complete understanding of the different processes occurring at the manganite-water interface. From the combined use of these techniques, a 1-pKa acid-base model was established that is valid at pH&gt;6. The model includes a Na+ interaction with the surface: =MnOH2+½ --&gt; =MnOH-½ + H+ log β0 (intr.) = -8.20 = -pHiep =MnOH2+½ + Na+ --&gt; =MnOHNa+½ + H+ log β0 (intr.) = -9.64 At pH&lt;6 the manganite crystals dissolve and disproportionate into pyrolusite (β-MnO2) and Mn(II)-ions in solution according to: 2 γ-MnOOH + 2H+ --&gt; β-MnO2 + Mn2+ + 2H2O log K0 = 7.61 ± 0.10 The adsorption and co-adsorption of Cd(II) and glyphosate at the manganite surface was studied at pH&gt;6. Cd(II) adsorption displays an adsorption edge at pH~8.5. Glyphosate adsorbs over the entire pH range, but the adsorption decreases with increasing pH. When the two substances are co-adsorbed, the adsorption of Cd(II) is increased at low pH but decreased at high pH. The adsorption of glyphosate is increased in the entire pH range in the presence of Cd(II). From XPS, FTIR and EXAFS it was found that glyphosate and Cd(II) form inner sphere complexes. The binary Cd(II)-surface complex is bonded by edge sharing of Mn and Cd octahedra on the (010) plane of manganite. Glyphosate forms inner-sphere complexes through an interaction between the phosphonate group and the manganite surface. The largest fraction of this binary glyphosate complex is protonated throughout the pH range. A ternary surface complex is also present, and its structure is explained as type B ternary surface complex (surface-glyphosate-Cd(II)). The chelating rings between the Cd(II) and glyphosate, found in aqueous complexes, are maintained at the surface, and the ternary complex is bound to the surface through the phosphonate group of the ligand.

Le stockage géologique du dioxyde de carbone (CO2) est une des options envisagées à moyen terme pour limiter les émissions de gaz à effet de serre. Or, le CO2 n'est pas un gaz inerte et aura tendance à acidifier l'eau en place dans les sites de stockage. Cette acidification de l'eau est alors susceptible de modifier la structure de cette roche ainsi que les propriétés de transport des espèces chimiques. Le but de cette étude est de quantifier l'impact du transport réactif sur la répartition d'une espèce chimique et sur la modification de la structure du milieu poreux de l'échelle du pore à celle du réservoir. Nous nous sommes focalisés dans cette étude sur le transport réactif monophasique d'une espèce dissoute aux temps longs. Pour ce faire, nous avons opté pour une approche multi-échelles considérant successi- vement (i) l'échelle locale, où les phénomènes d'écoulement, de réaction et de transport sont connus ; (ii) l'échelle du pore, où le transport réactif est représenté par des équations issues de l'écriture moyennée des équations locales ; (iii) l'échelle de Darcy (ou échelle de la carotte), où la structure de la roche est retranscrite par un réseau tridimensionnel de pores interconnectés par des canaux ; et (iv) l'échelle du réservoir, où les phénomènes physiques, au sein de chaque maille constituant le modèle réservoir, sont pris en compte par l'introduction de coefficients macroscopiques issus de l'étude de ces même phénomènes à l'échelle de Darcy, comme par exemple la perméabilité, la vitesse de réaction apparente, la vitesse apparente du soluté et sa dispersion.

En el caso del almacenamiento de los residuos radioactivos los flujos osmóticos pueden ser relevantes y requieren un análisis en detalle. El residuo nuclear bituminizado (BW) será almacenado mediante contenedores en cavidades excavadas en la Boom Clay, que es una arcilla marina que presenta propiedades favorables para limitar y retrasar la migración de los contaminantes radioactivos. La interacción entre los dos materiales es un proceso acoplado químico-hidro-mecánico y depende de la respuesta hidromecánica de la Boom Clay y del BW. En condiciones de almacenamiento, el contacto del BW, que contienen cantidades importantes de NaNO3, con el agua subterránea induce la hidratación por gradientes osmóticos y el consiguiente hinchamiento, además de la difusión de la sal disuelta hacia la Boom Clay. Se pueden distinguir dos tipos de afecciones: la perturbación geomecánica causada por el hinchamiento del BW y el aumento de presión en el BW y cambio de las distribución de tensiones en la roca, y la perturbación físico química por la migración de grandes cantidades de sales. El objetivo de esta tesis es: (i) Mejorar la comprensión de los procesos que controlan la absorción de agua y el consecuente hinchamiento del BW que contengan sales (NaNO3), y (ii) Investigar los posibles efectos de la concentración de fluidos de los poros sobre el hinchamiento, la compresibilidad y comportamiento de corte de la Boom Clay. En primer lugar, se ha desarrollado una formulación para el análisis de la deformación inducida por la disolución de sales en medio poroso con contacto con agua. Las ecuaciones planteadas incluyen los flujos acoplados de agua y soluto. Se presenta también un trabajo teórico que ayuda a la comprensión del comportamiento mecánico del BW. Se considera este material como una mezcla de bitumen y cristales de NaNO3. Se ha desarrollado un modelo elasto-viscoplástico que describe el comportamiento de fluencia del BW considerando el comportamiento de fluencia de sus constituyentes. El modelo constitutivo elasto-viscoplástico ha sido implementado en el programa CODE_BRIGHT. Los resultados se han comparado con observaciones experimentales. Se ha estudiado el comportamiento a largo plazo del BW en contacto con agua al simular ensayos de hinchamiento por absorción de agua bajo condiciones confinadas. El análisis numérico ha demostrado ser capaz de proporcionar una representación satisfactoria de los principales patrones observados en su comportamiento. En lo que respecta al segundo objetivo de la tesis, se ha propuesto una formulación para el análisis de las deformaciones inducidas por procesos osmóticos en un medio poroso de doble estructura. Esta formulación distingue dentro del material un nivel micro-estructural y otro macro-estructural con cambios químicos que tienen un efecto significativo en la micro-estructura. Se han obtenido las ecuaciones básicas que describen los flujos acoplados de agua y solutos y el transporte de sus componentes a través de los macroporos así como las ecuaciones de balance de masa para agua y soluto en los macroporos y microporos. La formulación propuesta ha sido aplicada particularmente para analizar cualitativamente el efecto de la succión osmótica sobre el hinchamiento de los suelos arcillosos. Se han analizado los efectos a corto y largo plazo. Se ha investigado también la influencia del aumento de la concentración del fluido en los poros sobre las propiedades geotécnicas y el comportamiento de la Boom Clay no saturada. Se ha llevado a cabo un programa sistemático de investigación experimental, con control de succión osmótica y matricial, con el fin de investigar el efecto del incremento de la concentración del fluido de poros sobre la resistencia de corte y el cambio volumétrico bajo condiciones edométricas. Se ha observado, que bajo condiciones parcialmente saturadas, un cambio en la salinidad provoca una disminución en la compresibilidad y en la resistencia de corte del material. / For deep storage of high-level nuclear waste osmotic flows can be significant and so require a careful analysis. In Belgium, The bituminized nuclear waste (BW) named Eurobitum contained in metallic drums will be placed inside a tunnel or a shaft excavated in the Boom Clay, which is 100 m thick marine clay presenting favourable properties to limit and delay the migration of the leached radionuclides over extended periods of time. In Geological disposal conditions, contact of the bituminized radioactive waste which contains high amounts of highly soluble salt (NaNO3) with groundwater will result in water uptake and swelling of the waste and in subsequent diffusion of the dissolved salt through the host clay formation. Basically, two types of disturbance can be distinguished: A geo-mechanical perturbation, caused by the swelling of the waste and the increase of the pressure in and around the waste and a physico-chemical perturbation by the release of large amounts of NaNO3 and other soluble salts. In this context the aim of this thesis is: (i) to improve the understanding of the processes controlling the water uptake and the subsequent swelling of bituminized waste containing soluble salts (NaNO3), and (ii) to investigate of the possible effects of the increase of pore fluid concentration on swelling, compressibility and shear behaviour of Boom Clay. A formulation has been proposed for the analysis of deformation induced by dissolution of salts in porous media in contact with water. The equations include the effect of coupled transport phenomena and the formulation has been included as an extension in the coupled THM program CODE_BRIGHT. A theoretical and experimental work aiming at understanding the mechanical behaviour of the Bituminized Waste has been presented.This material is considered for this purpose as a mixture of bitumen and crystals of NaNO3. An elasto-viscoplastic model has been developed that describes the creep behaviour of BW considering the constituents' creep behaviour. The elasto-viscoplastic constitutive model has been implemented into CODE_BRIGHT. The modelling results have been compared with the experimental data. The impact of osmotic forces on the swelling of the material has been investigated by simulating water uptake swelling tests under confined conditions and comparing the predictions with experimental results. The numerical analysis has proven to be able to furnish a satisfactory representation of the main observed patterns of the behaviour. In regard to the second objective of this thesis, a formulation has been proposed for the analysis of deformations induced by osmotic processes in double structure porous media. The formulation is based on the distinction within the material of a microstructural and a macrostructural levels with chemical changes having a significant effect on the microstructure. A macroscopic description of the system is provided. Then the basic equations describing coupled flows of water and solutes and the transport of its components through macropores and mass balance equations for water and solute in macro and micro pores have been obtained. The proposed formulation has been particularly applied to analyze qualitatively the effect of osmotic suction on swelling of clayey soils. Transient and long term effects have been analyzed. The influence of pore fluid concentration on the geotechnical properties and behavior of Boom Clay under partially saturated conditions has been investigated. A systematic experimental research program involving osmotic suction and matric suction controlled experiments has been carried to investigate the effect of the increase of pore fluid concentration on shear strength and on the volume change behaviour under odometer stress state conditions. It has been observed that under partially saturated conditions a change in salinity causes a decrease in compressibility and shear strength.

<p>The object of this work is to obtain a fundamentalunderstanding of the principal issues concerning the handlingof an aqueous WC-Co powder suspension.</p><p>The WO3 surface layer on the oxidised tungsten carbidepowder dissolves at pH>3 with the tungsten concentrationincreasing linearly with time. Adding cobalt powder to thetungsten carbide suspension resulted in a significant reductionof the dissolution rate at pH<10. Electrokinetic studiesindicated that the reduced dissolution rate may be related tothe formation of surface complexes; the experiments showed thatCo species in solution adsorb on the oxidised tungsten carbidepowder.</p><p>The surface forces of oxidised tungsten and cobalt surfaceswere investigated using the atomic force microscope (AFM)colloidal probe technique. The interactions at various ionicstrengths and pH values are well described by DLVO theory. Theadsorption of cobalt ions to tungsten oxide surfaces resultedin an additional non-DLVO force and a reduced absolute value ofthe surface potential. It was shown that the adsorption ofpoly(ethylene imine) (PEI) to the WO3 surfaces induces anelectrosteric repulsion.</p><p>The properties of spray-dried WC-Co granules were related tothe WC primary particle size, and the poly(ethylene glycol)(PEG) binder and PEI dispersant content in aqueous WC-Cosuspensions. The granule characterisation includes a new methodfor measuring the density of single granules. The increase inthe fracture strength of granules produced from suspensionsthat were stabilised with PEI was related to a more densepacking of the WC-Co particles.</p><p>The AFM was used to study the friction and adhesion ofsingle spray-dried WC-Co granules containing various amounts ofPEG binder. The adhesion and friction force between two singlegranules (intergranular friction) and between a granule and ahard metal substrate (die-wall friction) have been determinedas a function of relative humidity. The granule-wall frictionincreases with binder content and relative humidity, whereasthe granule-granule friction is essentially independent of therelative humidity and substantially lower than the granule-wallfriction at all PEG contents.</p><p><b>Key words:</b>Hard Metal, Cemented Carbide, WC-Co, TungstenCarbide, Cobalt, Oxidation, Dissolution, Surface Complexation,XPS, AFM, Colloidal Probe, Hamaker Constant, Cauchy, WO3,CoOOH, ESCA, Zeta-Potential, Surface Potential, Poly(ethyleneimine), PEI, Suspension, van der Waals, Steric, Spray-Dried,Poly(ethylene glycol), Strength, Density, Friction, Adhesion,Granule, PEG, Pressing, FFM.</p>

Intimate relationships function not in isolation, but within a broader social network and social environment, in which the opinions and actions of close network members can play a role in how a relationship develops. The current study investigated how perceiving support for one’s relationship (including same-sex and mixed-sex relationships) from friends and family is associated with not only relationship well-being, but also the mental and physical health of the individuals within the relationship. After establishing that social support specifically for a relationship was indeed a separate and unique construct as compared to more general social support for an individual, the study tested a hypothesized model using structural equation modeling, finding evidence for a model in which the association between support for a relationship and the health outcomes for an individual is fully mediated by relationship well-being. Relationship type (i.e., same-sex versus mixed-sex) was not a significant moderator, indicating that regardless of relationship type, individuals who perceive more support for their relationship are also more likely to report greater relationship satisfaction and better mental and physical health. Furthermore, participants provided data up to three times over a period of three years, allowing for an examination of how social support for a relationship functions as a predictor of relationship well-being and health outcomes over time. Perceived social support for a relationship at Time 1 was found to be a significant predictor of the rate of relationship dissolution over the course of the study as well as relational and health outcomes at later points in time. With respect to the source of support for the relationship, evidence was found that support from parents and friends both have associations with relationship outcomes, but these findings were inconsistent across analyses with support from parents having stronger associations in some analyses and support from friends having stronger associations in others. Reasons for these discrepancies are discussed, as well as theoretical implications concerning the role that perceived social support for relationships plays in the prediction of relationship well-being and mental and physical health. / Thesis (Ph.D, Psychology) -- Queen's University, 2012-05-29 21:04:59.381

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

Cette thèse porte sur l'étude de l'enthalpie de dissolution du dioxyde de carbone dans des solutions aqueuses d'amine. Pour développer des modèles théoriques décrivant les systèmes (CO2-amine-eau) pour les conditions appliquées aux procédés industriels, il est nécessaire d'avoir des données expérimentales reliant la solubilité et l'enthalpie. Dans cette étude, nous avons utilisé une unité de mélange construite au laboratoire que nous avons adapté à un calorimètre SETARAM C-80 pour mesurer l'enthalpie de solution du CO2 dans cinq solutions aqueuses d'amine, (la 2-Amino-2-méthyl-1-propanol (AMP), la monoéthanolamine (MEA), la diéthanolamine (DEA), la triéthanolamine (TEA) et la méthyldiéthanolamine (MDEA) (15 et 30 mass%) à des températures comprises entre 322.5 K et 372.9 K et des pressions allant de 0.5 à 5 MPa. Les données de la littérature ont été utilisées pour ajuster deux modèles thermodynamiques d'équilibre de phases (un simple et un rigoureux). Le premier modèle résume l'absorption du CO2 par une seule réaction, tandis que le second prend en compte toutes les réactions à l'équilibre. Le modèle simple reproduit nos enthalpies expérimentales à plus ou moins 10%, tandis que le modèle rigoureux reproduit nos données avec un écart compris entre 5 et 20% selon l'amine considérée. Le calcul de l'enthalpie dans le modèle rigoureux est fortement dépendant des données de la littérature utilisées pour la réaction de protonation de l'amine. Ceci souligne la nécessité d'acquérir de nouvelles données expérimentales sur ces constantes d'équilibre pour améliorer le modèle.

Le projet de cette thèse concerne l'étude de l'impact de la variabilité initiale des réservoirs géologiques sur le stockage souterrain du CO₂. Nous nous sommes inspirés de réservoirs naturels : le Dogger carbonaté du Bassin de Paris et les réservoirs gréseux de Ravenscar (mer du Nord). Chacun des réservoirs modèles reconstruits a été défini par la liste de ses minéraux (calcite, dolomite, albite, clinochlore, k-feldspath, kaolinite, quartz ... par exemple pour les réservoirs carbonatés) et par ses propriétés pétrophysiques (porosité, perméabilité). La variabilité de ces paramètres a été simulée à l'aide de méthodes géostatistiques multivariables opérant sur leur portée, palier, et seuillage. Nous avons défini des paramètres opérationnels utiles pour résumer les propriétés principales du stockage (à savoir la quantité de carbone stockée dans le réservoir, la quantité de carbone précipité sous forme de dolomie, la quantité de carbone évacuée par l'aquifère mobile, la quantité de carbone contenue dans l'eau du réservoir ainsi que la variation de la porosité dans le réservoir). Des simulations déterministes de transfert réactif ont ensuite été effectuées en suivant différents scénarii de stockage : (Cas de l'injection du CO₂ initial dans le réservoir qui nous a permis de définir l'état initiale du réservoir, cas d'un aquifère mobile se déplaçant dans le réservoir contenant du CO₂ en saturation résiduel et le cas du déplacement d'une eau acide dans un réservoir contenant un aquifère neutre). Nous avons cherché par la suite à étudier l'influence de la variabilité initiale sur les paramètres opérationnels de stockage. Nous avons ainsi mis en évidence que, par rapport au cas homogène, le champ hétérogène favorise le stockage du carbone sous forme de dolomie et diminue la quantité de carbone entrainée par l'aquifère. Les effets des grandes portées de la pétrophysique et de l'aquifère mobile ont a également été étudié. Enfin, nous avons mis en place un modèle de plans d'expériences pour étudier l'effet de la variabilité de toutes les entrées sur les différentes réponses sélectionnées. L'effet de la dispersion numérique a été étudié et nous avons montré leur importance sur certains résultats. Les plans d'expériences ont mis en exergue l'importance des taches de la dolomie (associé ici à la portée du champ de dolomie seuillée) sur le carbone stocké.