(57e) Simulation of Anti-Solvent Crystallization by Cfd-Pbe Approach

Crystallization from solution by anti-solvent addition is simulated by coupling Computational Fluid Dynamics (CFD) and Population Balance Equation (PBE). CFD is used to study the effect of agitation rate, anti-solvent feeding rate and feeding location on supersaturation distribution inside the crystallizer. PBE is solved to obtain the crystal size distribution by considering nucleation kinetics and crystal growth kinetics. Simulation results show that seeding is an efficient way to suppress spontaneous nucleation, and hence, to ensure the crystal growth is the dominant process. The mean size of the product increases as the seed concentration increases up to a critical amount of seeds after which it declines. Anti-solvent feeding rate is a critical process parameter for anti-solvent seeded crystallization, and slow-dosing is always preferable to fast-dosing rate. Screening DOE is undertaken to determine the effect of seed amount, mixing, nucleation kinetics, metastable zone width on crystallization process, and therefore, to develop a guideline for anti-solvent crystallization scale up.