Stochastic modeling of nonisothermal antisolvent crystallization processes

In this Thesis a stochastic approach to model antisolvent crystallization processes is addressed. The motivations to choice a stochastic approach instead of a population balance modeling has been developed to find a simple and an alternative way to describe the evolution of the Crystal Size Distribution (CSD), without consider complex thermodynamic and kinetic aspects of the process. An important parameter to consider in crystallization process is the shape of the CSD (in terms of variance) and the mean size of crystals in order to optimize the filtering of the final product and then increase the production. The crystallization processes considered in this Thesis are the antisolvent crystallization processes used in particular when the solute is weakly temperature-sensitive and then a second solvent, properly called antisolvent, is added in the solution favoring the crystallization of the solute. In antisolvent crystallization processes it is important the consumption of the second solvent added, in particular, optimizing the feed-rate and coupling the process in synergy with cooling crystallization in order to improve the production and the quality of the desired product. The stochastic approach used in this Thesis is based on the Fokker Plank Equation (FPE), which has allowed finding an analytical solution of the model, with some assumptions, and obtaining an analytical model able to describe the evolution of the mean size of crystals and the variance of the CSD. This analytical solution has leaded to develop an analytical relationship between the evolution in time of the first two stochastic moments of the FPE, such as mean and variance, and the manipulated variables, such as antisolvent feed-rate and temperature, obtaining as a result a map showing the asymptotic moments obtainable within a certain range of operating conditions. This Thesis also analyzes the physical-chemical aspects of the antisolvent crystallization processes, including the temperature effects, finding a strong influence onto the nucleation and growth rate of crystals due by the hydrogen bond strength between solventantisolvent molecules despite of the molecular interaction in a solvated system.The physical-chemical consideration concerning the antisolvent crystallization processes allowed to better understand the influence of the second solvent added, consequently optimizing the choice for the proper antisolvent to use with a proper feed-rate and temperature profile, minimizing the energy consumptions, in order to obtain the desired product. The stochastic model and the physical-chemical considerations have been validated with experimental data performed in a laboratory scale crystallizer. The experimental samples have been analyzed using an optical microscope and then the images taken have been manually processed in order to obtain the experimental CSDs.