The research addressed in this thesis focuses on monitoring and characterization of pharmaceutical compounds by laser backscattering. In particular, this study covers two topics: (1) the determination of naproxen sodium solubility in water, and its phase transition; and (2) comparisons of batch and laminar flow tubular crystallizers for the production of paracetamol (acetaminophen) and D-mannitol. Using a Lasentec™ Focused Beam Reflectance Measurement (FBRM) device, the solubility of naproxen sodium in aqueous solutions was determined over a temperature range from 15.2 to 39.7 ℃ With the determination of the solubilities of two pseudopolymorphs, anhydrous and dihydrated naproxen sodium, the phase transition point between these two forms of the pharmaceutical compound was determined to occur at 30.3 ℃ Enthalpy of solution and metastable zone widths were also determined for the experimental conditions. Crystallizations of paracetamol and D-mannitol were performed in a batch crystallizer and in a laminar flow tubular crystallizer (LFTC) system. In the latter system, supersaturation was generated rapidly in the solution being transported through a temperature-controlled tube and recovered in a batch vessel where product crystals were grown to equilibration. Because of the rapid rate at which supersaturation was generated in the LFTC, the resulting crystals were of smaller mean size than those obtained from batch crystallizations. The total time required for crystallization was significantly less with the LFTC than with the batch unit. Additionally, the rapid cooling in the LFTC led to the formation of two different polymorphs of paracetamol, Forms I and II.

Proper disposal of industrial brine has been a critical environmental challenge. Driven by the even-tightening environment protection regulations, the Zero-Liquid-Discharge (ZLD) has gradually become mandatory option for brine disposal, but its application is limited by the intensive energy consumption. The recent development of solar crystallizer provides a new strategy to achieve ZLD brine disposal. However, the research on solar crystallizer, employing photothermal material to convert solar energy to heat for interfacial brine evaporation and crystallization, is still at the early stage. This dissertation thoroughly investigated the solar crystallizer-based ZLD technology in a broad scientific and application context. The scaling formation while treating real brine, which has been the major barrier to the application of solar crystallizer, was confirmed first with a solar crystallizer device. With a rational designed anti-scaling mechanism, the scaling-free crystallization behavior and stable high water evaporation rate of 2.42 kg m-2 h-1 was achieved when treating real seawater brine. After verifying the feasibility of solar crystallizer towards real brine treatment, its performance was further improved by integrating convective airflow, which provided considerable environmental energy for water evaporation. Both experiment results and COMSOL simulation results confirmed that the maximum environmental energy harvesting can be achieved with the proper size of solar crystallizer. At last, this dissertation pioneered a novel concept of integrating adsorption process into solar crystallizer for simultaneously ZLD brine treatment and potassium extraction. Owing to the special ion concentration behavior of solar crystallizer, the adsorption capacity and selectivity coefficient of absorbent was enhanced by 19.5% and 48.8%, respectively, comparing with traditional bulk adsorption. This dissertation potentially unlocks a new generation of ZLD technology with low carbon footprint and source recovery. More research efforts will be inspired on its applications in real scenarios.

Proteins are important biological products with unique functions, annually produced at the hundreds of millions of dollars value on a worldwide basis. The application of crystallization for these materials primarily was led by structural biologists and crystallographers who are keen on obtaining large and well-ordered crystals for protein structure determination via X-ray diffraction. Usually for this, crystallization is done on a small scale by vapor diffusion using a supersaturated solution of the material. In the past decades, production crystallization has slowly received increasing attention for the large-scale recovery of proteins. Among the numerous products, an industrial enzyme (alpha-amylase) that is extensively involved in food processing and laundry products was chosen for examination due to the lack of relevant data in the literature and the potential industrial interest in crystallizing this material. The chosen alpha-amylase is a product of Genencor International (the Danisco division) and is derived from a genetically modified Bacillus licheniformis. In parallel to the underlying principles that govern the bulk crystallization of small molecules, the broad topics of investigation for this macromolecular material included determination of solubility, studies of nucleation thresholds, and investigation of crystal growth kinetics and special phenomena accompanying the crystallization process. All these studies were preceded by a series of characterization tests conducted for the material. On the whole, this study aimed to extend the existing fundamental knowledge of bulk crystallization for biological macromolecules. Specifically, it intended to enrich the solubility and crystallization kinetic data for the alpha-amylase. The experimental data of this study were all obtained at conditions in line with industrial practice, which included the use of moderate temperatures, mild pH conditions and simple inorganic salts ((NH4)2SO4, Na2SO4 and NaCl) in order for the findings to be transferred to the industry directly. In a 20 mM sodium phosphate buffer (with no added salts), alpha-amylase solubility increased with solvent temperature and had a minimum at pH between 6.4 and 7.1. A generalized equation (as a function of pH and temperature) was obtained to correlate the data. The three inorganic salts examined affected the alpha-amylase solubility in a different manner, both qualitatively and quantitatively. Evidently, the interaction effect of a salt varied with solution pH. This confirms the importance of studying solubility with the two or more condition parameters at the same time. With relevance to crystal growth, the metastable region of the material was relatively wide at (NH4)2SO4 and Na2SO4 concentrations corresponding to maximum solubility. For example, σSNT was 1.2  0.2 in solutions with 5 wt% ammonium sulfate at pH 7.0 and 25oC. A wide metastability range is useful for the practical operation of batch crystallizers as nucleation can be minimized. This range, however, diminished as the salt concentration increased beyond the maximum solubility points, imposing a limit on the range of salt concentration favorable for growth processes. In systems with no added salts at pH 7.0, the solution metastability was slightly higher at 10oC than at 40oC. This would suggest a future further examination of the salt system at a lower temperature, say of 10oC. To develop a batch crystallizer, the growth kinetic data of the material have to be known. Throughout the growth studies, the alpha-amylase crystals obtained were lozenge-shaped thin plates. Apparently, habit was not influenced by the crystallization conditions chosen. Similar to other proteins crystallized in bulk, the growth rate of alpha-amylase demonstrated a second-order dependence upon supersaturation. Importantly, the alpha-amylase demonstrated crystal growth rate dispersion (GRD) under all the conditions tested. To simplify the analysis of growth kinetic results, the seed crystals used were common history (CH) seeds whose growth rates are proportional to their sizes. The spread of growth rates (CV) was 0.54 for the unsieved CH seeds used. Due to GRD, growth rate coefficient data varied with crystal size. For instance, in solutions containing 5 wt% ammonium sulfate at pH 7.0 and 25oC, the growth rate coefficient for seed crystals initially at 20 m was 2.47 m/hr. This order of magnitude was equivalent to that of many other proteins. Although being small, industrial crystallization was feasible with these kinetics, as demonstrated by the sample design calculations included. To improve the design, it is recommended to further examine the solubility, metastability and growth kinetics of the above system at other temperatures to obtain a wider growth rate range. As the important phenomenon of growth rate dispersion has seldom been examined for protein and enzyme materials in the crystallization literature, this study is a significant contribution to this area.

Actuellement produit à partir du pétrole, une voie de synthèse de l'acide acrylique (AA) à partir du glycérol est envisagée. Cependant, cet AA bio-sourcé contient davantage d'acide propionique (AP) que l'AA issu du propylène. Les techniques classiques de purification ne permettent pas de séparer les deux acides. Le diagramme de phases liquide-solide du binaire AA + AP est déterminé. Il présente un point eutectique à 25,65 % (mol) d'AA, un point péritectique à 50,00 % (mol) d'AA et donc, un large domaine dans lequel l'AA cristallise thermodynamiquement de façon pure. Les essais de purification en mode statique sur paroi froide affichent des résultats prometteurs, une efficacité de séparation correcte pour un rendement de 60 %. Afin d'améliorer les transferts de matière et de chaleur, des dispositifs en mode dynamique sont mis au point dont un cristallisoir en film tombant. Ce dispositif permet de multiplier par 2,8 la productivité, tout en conservant une bonne efficacité de séparation. Afin de diminuer la surfusion et de maintenir un bon transfert thermique malgré une couche cristalline relativement isolante, des surfaces de cristallisation micro- et milli-structurées sont envisagées. La productivité est encore améliorée et la modélisation du transfert thermique confirme ces résultats expérimentaux. Afin de se rapprocher des conditions industrielles, un brut synthétique de bio-AA est purifié. La cristallisation en milieu fondu permet de séparer toutes les impuretés testées. Enfin, un modèle de cascade de cristallisoirs fermés, avec recyclage des différentes phases, est proposé afin de dimensionner le procédé global. Les essais en conditions presque réelles et l'intensification du procédé de cristallisation permettent d'envisager sereinement la mise en oeuvre du procédé industriel / With a global market exceeding four million tons per year, acrylic acid (AA) is a major intermediate chemical. The current AA synthesis is based on propylene, which is produced from oil. Thus, a novel production route is envisioned, based on glycerol, a green byproduct of oleochemistry and biodiesel production. However, current crude biobased AA contains a higher proportion of PA than AA from petrochemical origin. Classical purification techniques of AA cannot efficiently separate these two chemicals. In a first part, liquid-solid phase diagram of the binary system AA + PA is determined. This liquid-solid equilibrium exhibits an peritectic behavior at 50.0% (mol) of AA, a eutectic point at 25.65% (mol) of AA and thus, this diagram is favorable to the purification of AA. First purification tests by static solid layer melt crystallization show promising results: a correct separation efficiency for a yield varying between 60 et 70 %. To improve heat and mass transfer, dynamic crystallization set-up are developed, including a falling film crystallizer. This set-up multiplies by 2.8 the productivity of purification, while keeping a good separation efficiency. To reduce supercooling and to keep a good heat transfer despite the crystalline layer which is a thermal insulator, micro-and milli-structured crystallization surface are considered. Productivity is further improved and heat transfer modeling confirms the experimental results. To be nearer to industrial conditions, synthetic crude bio-AA is purified. Melt crystallization can separate all the impurities which are present in the medium. To scale-up the overall process a cascade model of batch crystallizers with recycling of the differents phases, is proposed. The intensification of the melt crystallization process permits to consider the implementation of the industrial process