Doctor of Philosophy(PhD) / Particle formation in RAFT-mediated emulsion polymerization has been studied using reaction calorimetry. By measuring the heat flow during controlled feed ab-initio emulsion polymerization in the presence of amphipathic RAFT agents, particle formation by self-assembly of these species could be observed. Two different monomer systems, i.e. styrene and n-butyl acrylate, and various degrees of hydrophobicity of the initial macro-RAFT agents have been studied and compared. The different macro-RAFT agents were synthesized by first forming a hydrophilic block of poly(acrylic acid) that would later on act as the electrosteric stabilizing group for the particles. Subsequently, different lengths of hydrophobic blocks were grown at the reactive end of the poly(acrylic acid) hydrophilic block via the RAFT-mediated controlled radical polymerization, either comprised of n-butyl acrylate or styrene. Two processes govern particle formation: adsorption of macro-RAFT agents onto growing particles and formation of new particles by initiation of micellar aggregates or by homogeneous nucleation. Competition between these processes could be observed when monomers with a relatively high (n-butyl acrylate) or low (styrene) propagation rate coefficient were used. A model describing particle formation has been developed and the results of model calculations are compared with experimental observations. Preliminary modeling results based on a set of reasonable physico-chemical parameters already showed good agreement with the experimental results. Most parameters used have been verified experimentally. The development of the molecular weight distribution of the macro-RAFT agents has been analyzed by different techniques. Quantification of the particle formation process by analytical techniques was difficult, but qualitative insights into the fundamental steps governing the nucleation process have been obtained. The amount of macro-RAFT agents initially involved in particle formation could be determined from the increase of molecular weight. The particle size distribution has been measured by capillary hydrodynamic fractionation, transmission electron microscopy and dynamic light scattering. From the data obtained from these particle-sizing techniques, the number of particles during the reaction could be monitored, leading to an accurate estimate for the particle formation time. Upon implementation of the experimental data obtained for the surface active macro-RAFT systems, the model demonstrated to be very sensitive towards the “headgroup” area of the macro-RAFT species. Three nucleation cases based on the initial surface activity of the macro-RAFT species in the aqueous phase are proposed to explain the deviations from the assumptions of the nucleation model. Even though the macro-RAFT species have a narrow molecular weight distribution, they are nevertheless made up of a distribution of block lengths of polystyrene upon a distribution of block lengths of poly(acrylic acid). The resulting differences in initial surface activity are the most probable reason for the observed differences between model calculations and experimental results for the nucleation time and particle size distribution of the final latex product. With the procedure described above, latexes have been synthesized without using conventional surfactants and the mechanisms involved in the particle formation for these systems have been elucidated. The results of this work enable production of latex systems with well defined molecular mass distributions and narrow particle size distributions. Furthermore, the technique based on the application of amphipathic RAFT agents is promising for the production of complex polymeric materials in emulsion polymerization on a technical scale.

Doctor of Philosophy(PhD) / Particle formation in RAFT-mediated emulsion polymerization has been studied using reaction calorimetry. By measuring the heat flow during controlled feed ab-initio emulsion polymerization in the presence of amphipathic RAFT agents, particle formation by self-assembly of these species could be observed. Two different monomer systems, i.e. styrene and n-butyl acrylate, and various degrees of hydrophobicity of the initial macro-RAFT agents have been studied and compared. The different macro-RAFT agents were synthesized by first forming a hydrophilic block of poly(acrylic acid) that would later on act as the electrosteric stabilizing group for the particles. Subsequently, different lengths of hydrophobic blocks were grown at the reactive end of the poly(acrylic acid) hydrophilic block via the RAFT-mediated controlled radical polymerization, either comprised of n-butyl acrylate or styrene. Two processes govern particle formation: adsorption of macro-RAFT agents onto growing particles and formation of new particles by initiation of micellar aggregates or by homogeneous nucleation. Competition between these processes could be observed when monomers with a relatively high (n-butyl acrylate) or low (styrene) propagation rate coefficient were used. A model describing particle formation has been developed and the results of model calculations are compared with experimental observations. Preliminary modeling results based on a set of reasonable physico-chemical parameters already showed good agreement with the experimental results. Most parameters used have been verified experimentally. The development of the molecular weight distribution of the macro-RAFT agents has been analyzed by different techniques. Quantification of the particle formation process by analytical techniques was difficult, but qualitative insights into the fundamental steps governing the nucleation process have been obtained. The amount of macro-RAFT agents initially involved in particle formation could be determined from the increase of molecular weight. The particle size distribution has been measured by capillary hydrodynamic fractionation, transmission electron microscopy and dynamic light scattering. From the data obtained from these particle-sizing techniques, the number of particles during the reaction could be monitored, leading to an accurate estimate for the particle formation time. Upon implementation of the experimental data obtained for the surface active macro-RAFT systems, the model demonstrated to be very sensitive towards the “headgroup” area of the macro-RAFT species. Three nucleation cases based on the initial surface activity of the macro-RAFT species in the aqueous phase are proposed to explain the deviations from the assumptions of the nucleation model. Even though the macro-RAFT species have a narrow molecular weight distribution, they are nevertheless made up of a distribution of block lengths of polystyrene upon a distribution of block lengths of poly(acrylic acid). The resulting differences in initial surface activity are the most probable reason for the observed differences between model calculations and experimental results for the nucleation time and particle size distribution of the final latex product. With the procedure described above, latexes have been synthesized without using conventional surfactants and the mechanisms involved in the particle formation for these systems have been elucidated. The results of this work enable production of latex systems with well defined molecular mass distributions and narrow particle size distributions. Furthermore, the technique based on the application of amphipathic RAFT agents is promising for the production of complex polymeric materials in emulsion polymerization on a technical scale.

L’étude du polymorphisme de composés pharmaceutiques est un domaine en plein essor. Cela est dû d’une part aux pressions économiques exercées par l’industrie pharmaceutique et d’autre part pour une meilleure compréhension des conséquences du polymorphisme sur les propriétés des médicaments (stabilité physique et chimique, solubilité, vitesse de dissolution,biodisponibilité, propriétés mécaniques, etc.). Cette thèse étudie la cristallisation par la technique de nucléation non-photochimique induite par laser (NPLIN) des molécules pharmaceutiques organiques. Dans ce contexte, un nouveau montage expérimental semi-automatisé adapté aux exigences des études NPLIN a été conçu et réalisé, permettant le contrôle de nombreux paramètres et le traitement simultané d’un grand nombre d'échantillons et ainsi réalisé un gain de temps considérable. Une méthode de travail a été également établie afin de limiter l’aléa expérimental. L’étude de l’impact des paramètres du laser sur la cristallisation de la carbamazepine et du sulfathiazole dans différents solvants(méthanol, éthanol, acétonitrile) a été menée. Les résultats obtenus ont permis de démontrer pour la première fois dans la littérature que la NPLIN permet d’obtenir des cristaux de CBZ et de sulfathiazole dont les formes polymorphiques dépendent de la polarisation du laser et du type de solvant. Une approche permettant la prédiction de la forme polymorphique des molécules organiques de la base CSD, dans le cas de l’utilisation de la NPLIN, a été proposée et appliquée pour les molécules CBZ et la sulfathiazole étudiées expérimentalement. A partir de nos résultats expérimentaux, des calculs d’énergie d’interactions ab initio de dimères des molécules de carbamazépine et de sulfathiazole et sur les résultats observés dans la littérature nous avons pu émettre des hypothèses quant au mécanismes impliqués dans la nucléation NPLIN. / Polymorphism study of pharmaceutical compounds is a growing field. This is due, on one hand, to the economic pressure of the pharmaceutical industry and on the other hand, to the more awareness of the polymorphism consequences on the drug properties (chemical and physical stability, solubility, dissolution rate, bioavailibality, mechanical properties,manufacturing process, etc).This thesis studies the crystallisation of organic pharmaceutical molecules by using the Non Photochemical Light Induced technique. Within this context, a new semi-automatic experimental setup suitable to the requirements of NPLIN studies was devised and realised,allowing the control of many parameters and a simultaneous processing of a great number of samples and thus saving a considerable amount of time. A strict working methodology is also established to limit experimental errors. The study of the impact of laser parameters on the crystallisation of carbamazepine and sulfathiazole within different solvents (methanol,ethanol, acetonitrile) was carried-out. The obtained results allowed demonstrating, for the first time in literature, that NPLIN allows to obtain CBZ and sulfathiazole crystals for which the polymorphic forms depend upon the laser polarisation and solvent type. An approach for predicting the polymorphic form of organic molecules in the CSD database, for the case of NPLIN, was proposed and applied for the case of CBZ and sulfathiazole that were studied experimentally. We have also provided hypotheses to explain the mechanisms involved in NPLIN nucleation.

The effect of individual and combined zirconium and manganese additions have been compared for an AA2198 6 mm thick sheet in T351 temper regarding their influence primarily on recrystallisation resistance and secondly on fracture toughness and overageing resistance. A complete characterisation of the dispersoid distributions was carried out for a deeper understanding of the effects of the Al3Zr and Al20Cu2Mn3 particles, involving studying their formation from the as-cast and homogenised stage.The most important finding in this work was the lower recrystallisation resistance in the alloy containing 0.1 wt%Zr + 0.3 wt%Mn compared to that containing only 0.1 wt%Zr. This result was rather unexpected, if one considers the opposite microsegregation patterns of Zr and Mn during casting, which leads to dispersoids occupying the majority of the grains’ volume and minimising dispersoid-free zones that could be potential sites for nucleation of recrystallisation. The other two alloys with dispersoid additions 0.05 wt%Zr + 0.3 wt%Mn and 0.4 wt%Mn, were partially and fully recrystallised respectively in the rolled T351 condition.Equally important in this work, was the observation that the opposite microsegregation trend of Zr and Mn sufficed to restrict grain growth in unrecrystallised areas. The 0.1Zr-0.3Mn alloy exhibited the lowest grain size of all alloys, both in the T351 temper and after annealing at 535oC for up to 144 hours. The reason for this was the combined action of Al20Cu2Mn3 dispersoids and Mn solute in the regions where the Zr concentration was low (i.e. near the grain boundaries), which offered additional pinning pressure to those areas compared to the 0.1Zr alloy.The lower recrystallisation resistance of the 0.1Zr-0.3Mn alloy was explained on the grounds of two main factors. The first was the lower subgrain size and hence stored energy within bands of Al20Cu2Mn3 dispersoids, which increased the driving force for recrystallisation in these regions. The second was the interaction between Zr and Mn that led to a decrease in the Al3Zr number density and pinning pressure. Since Zr was the dominant dispersoid family in terms of inhibiting recrystallisation, inevitably this alloy became more prone to recrystallisation. The Al3Zr pinning pressure was found to be much lower especially within bands of Al20Cu2Mn3 dispersoids. The detrimental effect of the Mn addition on the Al3Zr distribution was proven not to result from the dissolution of Zr within Mn-containing phases, and several other phases, at the grain interior and also in grain boundaries. The observed effect could not be precisely explained at this stage.Concerning mechanical properties, the 0.1Zr alloy exhibited the best combination of properties in the Kahn tear tests for fracture toughness. Further, it had a higher overageing resistance compared to the 0.1Zr-0.3Mn alloy.As an overall conclusion from this work, considering all the studied properties here that are essential for damage tolerant applications, the addition of 0.1 wt%Zr to the AA2198 6 mm thick sheet was found to be superior to that of the combined addition of 0.1 wt%Zr + 0.3 wt%Mn.