Ph.D.

L’étape de dissolution des combustibles nucléaires usés, réalisée en milieu nitrique concentré, est complexe notamment du fait de leur complexité chimique et microstructurale à l’issue de leur passage en réacteur. Ainsi, la présence de produits de fission (PF) localisés au sein des différentes phases cristallines constitutives du combustible usé peut en impacter la vitesse de dissolution. Dans ce cadre, trois systèmes représentatifs du matériau combustible initial UO2, de UO2 contenant des PF dissous au sein de la phase fluorine ou formant de précipités métalliques ont été obtenus par conversion de précurseurs préparés par voie humide (oxalate, hydroxyde). Pour chaque système, des pastilles denses et de microstructures proches de celle retrouvée au sein du combustible usé ont été préparées à l’issue d’une étape de mise en forme suivie d’un traitement thermique à haute température.L’étude multiparamétrique de la dissolution (approche macroscopique) conduite dans plusieurs solutions d’acide nitrique et à diverses températures a souligné l’impact important joué par la composition chimique sur la durabilité chimique des échantillons. Ainsi, l’incorporation d’éléments lanthanide a conduit à une augmentation de la vitesse de dissolution par rapport à l’échantillon UO2 de référence, laquelle est demeurée largement inférieure à celle relevée en présence d’éléments platinoïde. Par ailleurs, les effets de l’acidité et de la température du milieu sur la vitesse de dissolution ont été examinés et des modifications significatives dans le mécanisme de dissolution prépondérant ont été suggérées pour des concentrations d’acide nitrique supérieures à 0,5 mol.L-1.Pour les trois systèmes sélectionnés, l’évolution de l’interface solide/solution a également été suivie en cours de dissolution à travers une étude operando, réalisée par Microscopie Electronique à Balayage en mode Environnemental (approche microscopique). En présence d’éléments lanthanide ou à proximité des éléments platinoïde métalliques, ce suivi a démontré l’existence de zones de dissolution préférentielles dont les joints de grains et les jonctions triples. Le couplage des résultats obtenus à travers ces deux approches a permis de fournir des données complémentaires en vue d’une meilleure compréhension des mécanismes de dissolution mis en jeu en présence des différents PF considérés. / The dissolution of spent nuclear fuels, performed in concentrated nitric acid solution, is a complex process due to some chemical and microstructural heterogeneities. As instance, the presence of Fission Products (FP) in various phases constitutive of spent nuclear fuels can affect the chemical durability of the materials. In this context, three systems of interest representing fresh UO2 used as reference material, and UO2 doped with FP products dissolved in the fluorite structure (lanthanide elements) or incorporated as metallic precipitates (platinoids) were prepared by oxalic or hydroxide precipitation. Dense pellets with microstructure representative for spent nuclear fuel were prepared through sintering step at high temperature.The multiparametric study of the dissolution (macroscopic approach) was developed by varying independently several parameters. While incorporation of lanthanide elements induced a significant increase of the normalized dissolution rates, it remained lower compared to that observed for platinoids. Moreover, increase of nitric acid concentration or temperature led to the decrease of the chemical durability of the prepared materials. Additionally, significant modification of the preponderant mechanism of dissolution occurred for nitric acid concentration higher than 0.5 mol.L-1.For the three selected systems, the monitoring of the evolving solid/solution interface (microscopic approach) was performed operando by Environmental Scanning Electron Microscopy. Compared to pure UO2, the presence of FP (lanthanide elements or metallic platinoids) induced preferential dissolution of grain boundaries and triple junctions. Coupling the results obtained from micro- and macroscopic approaches led to complementary data of strong interest in order to improve the understanding of the role of FP during the dissolution of UO2.

Dans le cadre de la loi du 30 décembre 1991 relative à la gestion à long terme des déchets nucléaires, plusieurs matrices de confinement spécifique des actinides, dont la monazite et la solution solide monazite/chéralite associée ont été étudiées au cours de ce travail en vue de leur stockage en formation géologique profonde. Ainsi, différentes monazites LnPO4 (Ln = La → Gd) ont été préparées par conversion thermique de rhabdophanes, LnPO4 , 0,667H2O, précipitées à basse température. Sur la base d’expériences menées sous rayonnement synchrotron, la structure cristallographique de la rhabdophane a d’abord été résolue dans un système monoclinique (groupe d’espace C2) tout comme la monazite (groupe d'espace P21/n) puis sa conversion thermique en monazite a été étudiée. Une étude multiparamétrique de la vitesse de dissolution de la monazite LnPO4 (Ln = La → Gd) dans l’acide nitrique a été réalisée en conditions dynamiques. Les valeurs de vitesses de dissolution normalisées sont demeurées très faibles quelles que soient l'acidité du milieu, la température et la nature de l’élément lanthanide, confirmant l’excellente durabilité chimique des matériaux préparés. Des ordres partiels relatifs à l'activité du proton compris entre 0,7 ± 0,2 et 1,5 ± 0,3 ont été relevés. Parallèlement, la diminution de l’énergie d’activation apparente pour T ≥ 313 K a souligné une modification de l’étape cinétiquement limitante du mécanisme de dissolution, liée à l'impact de l’indice de saturation de la solution par rapport à la précipitation de la phase rhabdophane.Les produits de solubilité des rhabdophanes (La → Dy) ainsi que les grandeurs thermodynamiques associées ont été déterminés via des expériences de sur- et de sous-saturation. Le bon accord entre les valeurs obtenues par ces deux approches a confirmé la réversibilité de l’équilibre de solubilité associé à la rhabdophane. Une faible variation du produit de solubilité et des grandeurs thermodynamiques de formation de la rhabdophane a été observée le long de la série des éléments lanthanide (-2151±13 ≤ Df H^o (298K) ≤ -2130±12 kJ.mol-1, -2004±2 ≤ Df G^o (298K) ≤ -1984±2 kJ.mol-1 et -504±11≤ DS^o (298K)≤ -473±12 J.mol-1.K-1), à l’exception de l’europium qui présente des valeurs nettement supérieures d'énergie libre (-1896 ± 2 kJ.mol-1), d'enthalpie (-2057 ± 9 kJ.mol-1) et d'entropie (–538 ± 11 J.mol-1.K-1) de formation. Par ailleurs, une relation directe entre les enthalpies obtenues pour les rhabdophanes et les monazites a été démontrée ; les données associées aux rhabdophanes étant obtenues par simple ajout de la contribution de 0,667 molécule d'eau. Cette observation corrobore aussi bien la structure monoclinique de la rhabdophane que le nombre de molécules d'eau constitutionnelles.Parallèlement, l'évolution structurale et microstructurale de la surface de monazites frittées a été suivie en cours de dissolution par plusieurs techniques complémentaires (MEBE, AFM, XRR, et DRX en mode d’incidence rasante). La très bonne durabilité chimique de ces céramiques préparées a été confirmée : seulement 0,04% et 0,3% en masse de matériau ont été dissous après 300 jours de lixiviation, respectivement dans HNO3 0,1M et 0,25M à 363K. Des analyses de surface, il est apparu que les défauts préexistants (fissures, défauts liés au polissage, pores) constituaient des zones préférentielles de dissolution tandis qu’aucune phase secondaire n'a été clairement mise en évidence malgré un indice de saturation en solution traduisant un état proche de l'équilibre de précipitation de la rhabdophane.Enfin, un protocole original de synthèse d’échantillons de rhabdophane dopés en thorium (Nd1-2xCaxThxPO4 , 0,667H2O) par voie humide a été développé au cours de ce travail. Les premières expériences de solubilité, menées en conditions de sous-saturation dans HCl 0,25 M, ont conduit à une estimation des produits de solubilité apparents, lesquels présentent une faible variation sur l’intervalle de températures considéré. / In the context of the French research law dedicated to the radioactive waste management, several ceramics were proposed for the specific conditioning of actinides. Among them, monazites and monazite/cheralite solid solutions were particularly considered in this work.Thus, monazites LnPO4 (Ln = La → Gd) were prepared by thermal conversion of low-temperature rhabdophane precursors, LnPO4•0.667H2O. From synchrotron experiments, the crystal structure of rhabdophane was solved. It was found to be monoclinic (space group C2) as monazite (space group P21/n).The multiparametric study of the kinetics of dissolution of monazites LnPO4 (Ln = La → Gd) was performed in nitric acid solutions and using dynamic conditions. The normalized dissolution rates remained very low whatever the acidity, the temperature, and the lanthanide element considered. The partial order of the reaction related to the protons activity varied from 0.7 ± 0.2 to 1.5 ± 0.3. Moreover, the apparent activation energy of the dissolution mechanism was found to vary with temperature, suggesting a change in the rate-limiting step. The decrease of the apparent activation energy for T ≥ 313 K was assigned to the impact of saturation processes with respect to the rhabdophane.Thus, the solubility products as well as thermodynamic data associated to the formation of rhabdophanes were evaluated from over- and under-saturation conditions. The similar values obtained by both approaches confirmed the reversibility of the equilibrium associated to the rhabdophane precipitation. Solubility products as well as thermodynamic data only slightly varied along the lanthanide elements series : -2151±13 ≤ Df H^o (298K) ≤ -2130±12 kJ.mol-1, -2004±2 ≤ Df G^o (298K) ≤ -1984±2 kJ.mol-1 and -504±11 ≤ Df S^o (298K) ≤ -473±12 J.mol-1.K-1, excepted for europium that presented the highest values of free energy (-1896 ± 2 kJ.mol-1), enthalpy (-2057 ± 9 kJ.mol-1) and entropy (–538 ± 11 J.mol-1.K-1) of formation. The comparison of the data obtained for rhabdophanes and monazites showed that the values associated to rhabdophane can be deduced from those of monazite by adding the contribution of 0.667 water molecule. It confirms either the monoclinic structure of the rhabdophane and the number of water molecules present in the structure.For the first time, structural and microstructural evolution of monazite pellets was monitored during dissolution thanks to several complementary surface analysis techniques (ESEM, AFM, GI-XRR and GI-XRD). This study confirmed the very good chemical durability of these ceramics (only 0.04 wt.% and 0.3 wt.% of dissolved ceramic in 0.1 M HNO3 and 0.25 M HNO3, respectively, at 363 K after 300 days of dissolution). These different techniques also highlighted that pre-existing defects (pores, cracks, polishing marks) acted as preferential dissolution zones. However, no secondary phase was clearly evidenced onto the surface of the samples even if the solutions were found to be close to equilibrium with rhabdophane.Finally, an original protocol of precipitation of Th-doped rhabdophanes, Nd1-2xCaxThxPO4•0.667H2O, was developed during this work. The first estimation of the apparent solubility constants, performed in under-saturated conditions in 0.25 M HCl solution, did not evidence any significant variation in the temperature range investigated.

When considering oral administration, drug release from its pharmaceutical form and its dissolution into gastrointestinal fluids generally precedes absorption and systemic availability. The solubility-dissolution behaviour of a drug is frequently the rate-limiting step to absorption of drugs from the gastrointestinal tract (BCS class II drugs). Poor aqueous solubility has always been a very challenging obstacle as it is, together with membrane permeability, an essential factor in the limitation of a drug’s bioavailability following oral administration. Since an increasing number of newly developed drug candidates in pre-clinical development phases present poor water-solubility characteristics, there is a great need for formulation approaches to overcome this factor. Out of the many ways to increase a product’s solubility/dissolution rate characteristics with the aim of enhancing its oral bioavailability, drug formulation as nanoparticles has received much-increased interest over the last decade. The hypothesis behind dissolution rate enhancement, considering drug particle size reduction to nanometer range, lies primarily in a much-increased effective surface area (Noyes-Whitney) presented by the resulting drug nanoparticles. Out of the various technologies available for drug particle size reduction to nanometer range, milling using high pressure homogenization is regarded as one of the simplest and most effective techniques. High pressure homogenization is a solvent-free process and is relatively rapid (time-saving). Furthermore, and most importantly, the scaling up of this technique is already established; processing capacities ranging from 3 l/h (e.g. EmulsiFlex C3®: minimum sample volume - 10 ml) to 1000 l/h (e.g. EmulsiFlex C1000®: minimum sample volume - 2 l). Four model drugs were studied in this work. Nifedipine (NIF), an extensively studied poorly water-soluble drug in the literature, was used as the main model on which most of the development was done. In parallel to the work carried out on NIF, three UCB S.A. molecules currently under development were also studied as poorly water-soluble drugs: these being ucb-35440-3, UCB-A and UCB-B (salt of UCB-A). These three UCB S.A. model drugs are, contrarily to NIF, predicted highly dosed drugs and are weak bases, and thus present pH-dependent solubility profiles, which allowed us to investigate model drugs with different profiles. Firstly, investigations regarding appropriate formulation development (stabilizer (surfactant) selection) and appropriate high pressure homogenization operating conditions (pre-milling cycles, influence of the number of high pressure homogenizing cycles, influence of homogenizing pressure, influence of sample temperature) were made. It has been shown, through this development, for the four studied model drugs, that high pressure homogenization is an appropriate technique for reducing drug particle size to nanometer range (NIF  290 nm, ucb-35440-3  180 nm, UCB-A  350 nm and UCB-B  250 nm). Investigations regarding water-removal from the nanosuspensions obtained and most importantly regarding the redispersion characteristics of the retrieved powders (i.e. nanoparticles) were then carried out. In that regard, it has been shown that the presence of carriers in the formulation is essential for limiting nanoparticles agglomeration during the water-removal operation. Drug crystalline state characterizations before and following particle size reduction were then carried out on the three studied model drugs, mainly through DSC and PXRD studies. In fact, one of the advantages of this particle size reduction approach (using high pressure homogenization), versus other frequently studied solubility/dissolution rate enhancement technologies (e.g. such as solid dispersions), is that original crystalline state shall not be altered in such a way that the achieved increased solubility and dissolution rate characteristics do not rely on the presence of the amorphous form of the drug; this furthermore implying a greater time-stability of the developed formulations. Through the data obtained, it has been shown that original drug crystalline state seems to be unaltered following particle size reduction. In vitro solubility and dissolution characteristics were then evaluated on the formulations developed in order to verify the posed hypothesis regarding effective surface area increase. It has been shown through these studies that drug solubility and most importantly drug dissolution rate can be significantly enhanced for nanoparticulate systems (verified for NIF, ucb-35440-3, UCB-A and UCB-B). For example, solubility was enhanced from 26 µg/ml vs. 19.5 µg/ml for NIF nanoparticles and the dissolution characteristics showed that 100% of the tested dose (equivalent to 10 mg NIF) was already dissolved following 10 min vs. less than 5% for un-milled NIF. Following these very interesting and promising results, and preliminary to the in vivo pharmacokinetic studies carried out, in vitro permeation studies (apical to basolateral transfer studies) across intestinal cell models (Caco-2 and HT29-5M21 cultures and co-cultures) were carried out. This evaluation was only carried out using NIF as a model drug and showed a 6-fold increase in the permeation rate for NIF nanoparticles. The influence of chitosan (permeability enhancer/bioadhesive polymer) in the NIF nanoparticle formulation with regard to in vitro NIF permeation rate was also evaluated. In vivo pharmacokinetic studies in rats were conducted using NIF and ucb-35440-3 as model drugs. The very different profiles of these two model drugs allowed us to retrieve interesting information regarding the in vivo behaviour of the developed formulations. As expected from the in vitro (i.e. solubility/dissolution/permeation) studies and results obtained for NIF, an increased extent of exposure could be observed for NIF nanoparticles versus un-milled NIF; the difference being more pronounced when the formulations were orally administered into capsules (2.5-fold increase in extent of exposure and 6-fold increase in Cmax). For ucb-35440-3, a poorly water-soluble weak base with a reported significant food effect considering oral bioavailability, an increased extent of exposure for nanoparticles, versus the un-milled drug, could only be observed in fasted state (4-fold increase in extent of exposure and 2.7-fold increase in Cmax). These different, diet-relative observations allowed us to put forward some limitations and precautions (considering poorly water-soluble weak bases) relative to the possibility of drug reprecipitation following stomach’s exiting, particularly if dissolution in the stomach is quite fast (e.g. nanoparticulate systems). In parallel to the in vivo pharmacokinetic evaluation of NIF nanoparticles, evaluation of the antihypertensive effect of the systems developed following oral administration, using spontaneously hypertensive rats, was also carried out and compared to un-millled NIF. The results obtained showed a significant drop in systolic blood pressure for NIF nanoparticles (32% reduction of initial SBP following 30 min vs. 1% for un-milled NIF) and nicely complemented the in vitro and in vivo results obtained for NIF nanoparticles. Finally, a stability study of the optimized NIF nanoparticle formulation was carried out with respect to reported ICH conditions (25°C/60% RH; 30°C/65% RH; 40°C/75% RH). The results showed that the studied NIF nanoparticle formulation retains all its original characteristics (dissolution, crystalline state, redispersion characteristics); this being verified over time (12 months) and for each of the three storage conditions studied.

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One of the most important outstanding problems with the hydrometallurgy of copper is the low temperature leaching of chalcopyrite. In this thesis, a fundamental study at low temperature was undertaken in order to establish a mechanism, which is consistent with the data obtained in an extensive study of the kinetics of dissolution of several chalcopyrite concentrates. It will be demonstrated that enhanced rates of dissolution can be achieved at ambient temperatures by the application of controlled potentials in the range 560-650 mV, depending on the concentration of chloride ions. However, control of the potential by the use of electrochemical or chemical oxidation of iron(II) or copper(I) ions is ineffective unless carried out in the presence of dissolved oxygen. The rates of dissolution are approximately constant for up to 80% dissolution for sized fractions of the concentrates with an activation of energy of about 75 kJ mole-1. Chalcopyrite from different sources appears to dissolve at approximately the same rate which is largely independent of the iron and copper ion concentrations, the acidity and chloride ion concentration but depends in some cases on the presence of additives such as fine pyrite or silver ions. Based on the results of these leaching experiments and detailed mineralogical analyses of the residues, a mechanism involving non-oxidative dissolution of the mineral coupled to oxidation of the product hydrogen sulfide will be proposed. The latter reaction is shown to occur predominantly by a copper ion – catalyzed reaction with dissolved oxygen. The results of an independent study of the kinetics of this reaction will be presented which will demonstrate that the rates are consistent with those obtained for the dissolution of the mineral. The possible involvement of a covellite-like surface layer on the chalcopyrite under some conditions will also be discussed as it relates to the mechanism. It will also be shown that fine pyrite particles can also act as a catalyst surface for the oxidation of hydrogen sulfide. This mechanism is consistent with the mineralogy which confirmed the formation of secondary sulfur which is not associated with chalcopyrite but is associated with fine pyrite if present. A comparison of this mechanism with that proposed in other more limited studies of the dissolution of chalcopyrite under similar conditions in sulfate solutions has been made.

Traditional dissolution models are based in the analyses of bulk solution compositions and ignore the fact that different sites of a surface dissolve at different rates. Consequently, the variation of surface area and surface reactivity during dissolution are not considered for the calculation of the overall dissolution rate, which is expected to remain constant with time. The results presented here show the limitations of this approach suggesting that dissolution rates should be calculated as a function of an overall surface reactivity term that accounts for the reactivity of each of the sites that constitute the surface. In contrast to previous studies, here the focus is put on studying the surface at different dissolution times. Significant changes in surface topography of CaF2 were observed during the initial seconds and up to 3200 hours of dissolution. The observed changes include the increase of surface area and progressive exposure of the most stable planes, with consequent decrease in overall reactivity of the surface. The novelty of a proposed dissolution model for fluorite surfaces, when compared with traditional dissolution models, is that it differentiates the reactivity of each characteristic site on a surface, e.g. plane or step edge, and considers the time dynamics. The time dependency of dissolution rates is a major factor of uncertainty when calculating long term dissolution rates using equations derived from dissolution experiments running for short periods of time and using materials with different surface properties. An additional factor of uncertainty is that the initial dissolution times are the most dynamic periods of dissolution, when significant variations of surface area and reactivity occur. The results are expected to have impact in the field of nuclear waste management and to the larger geological and material science community. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 4: Submitted. Paper 5: Submitted.</p>

The most known regenerated cellulosic fiber is viscose, produced in a wet spinning process, but due to cost and environmental issues other processes have been developed. Lyocell fibers, produced in air-gap spinning, have superior dry and wet strenght and a lower environmental impact compared to viscose. Research in different cellulose solvent has increased significantly tha last decadess, due to an increased cotton price and a decreased paper production, providing more wood pulp to production of regenerated cellulosic fibers.   Inorganic molten salt hydrates have the ability of dissolving cellulose for production of textile fibers. Aqueous zinc chloride was investigated at Swerea IVF from dissolution of cellulose to fiber spinning.   Aqueous zinc chloride has a dissolving capacity of up to at least 13.5 % cellulose, possibly much higher. Dissolving concentration ZnCl2/water range from 65-76 % amd lowest possible ZnCl2 concentration increases as the cellulose concentration increases. Above around 68 % ZnCl2 results in a significantly increased viscosity due to a polymeric structure formed by zinc chloride, creating a network of cellulose-zinc complexes and causing a gel behaviour of the dope difficult to use in spinning processes. The dissolving capacity of 68 % ZnCl2 is only about 8 % cellulose, which is very low compared to other solvents used today e.g. Lyocell and ILs.   Additions of 0.3 % CaCl2 or 0.05-0.1 % NaOH is used to decrease degradation of cellulose. The addition causes ans increased viscosity, which is either a result of less degradation of the interaction of the added molecules to zinc-cellulose complexes. Addition of NaOH results in a temperature dependent geleation at increased temperatures (75˚C and 80˚C), which also might be an effect of the interaction.   Highest tensile strenght was reached for wet spun fibers coagulated in ethanol of 9.5 % cellulose with 0.1 % NaOH addition, with a tenacity of 13-15 cN/tex, elongation of 10-12 % and wet strenght 30 % of dry strenght. Beacuse of many disadvantages of zinc chloride as a solvent, e.g. degradation of cellulose, corrosivity and the viscosity and gel behaviour at cellulose concentrations of 9.5 % and 13.5 % cellulose, a future possibility of a conventional production of textile fibers appears to be quite limited.

Platinum (Pt) alloy nanoparticles are used as catalysts in electrochemical cells to reduce oxygen to water and to oxidize hydrogen; the overall reaction converts chemical energy into electrical energy. These nanocatalysts are deposited on a carbon substrate and their catalytic function takes place in acid medium. This harsh environment causes an undesired reaction, which is the dissolution of the metal atoms into the acid medium; thus affecting the catalyst life. This dissertation aims to investigate the dissolution mechanism of fuel cell cathode catalysts at the atomic level starting from the oxygen reaction intermediates on the cathode catalyst surface and propose guidelines to improve cathode catalysts durability based on our proposed mechanism. Density functional theory is employed to study various possible scenarios with the goals of understanding the mechanism of the metal atom dissolution process and establishing some guidelines that permit a rational design of catalysts with better stability against dissolution. A thermodynamic analysis of potential metal dissolution reactions in acid medium is presented first, using density functional theory calculations to explore the relative stabilities of transition metals in relation to that of Pt. The study is performed by comparing the change in reaction Gibbs free energies for different metals in a given dissolution reaction. Then, a series of density functional theory studies, tending to investigate the adsorbed atomic oxygen absorption process from cathode catalyst surface into its subsurface, includes: 1) the oxygen adsorption on various catalyst surfaces and oxygen absorption in subsurface sites to figure out the minimum energy pathway and energy barrier of on-surface oxygen migration and absorption into subsurface; 2) the oxygen coverage, the other oxygen reduction reaction intermediates, and water effects on the oxygen absorption process according to reaction pathways, energy barriers, and thermodynamic analysis; 3) the oxygen absorption process on several Pt-based alloys with various compositions and components to find out the best alloy to inhibit atomic oxygen absorption including both kinetic and thermodynamic analyses, and the effects of such alloyed species on the inhibition process.