Model-Based Optimal Strategies for Controlling Particle Size in Antisolvent Crystallization Operations

In this paper, a model-based optimal strategy is presented for the control of particle size in antisolvent crystallization. Size is controlled on demand by dynamic optimization using a population balance based model. Knowledge of the ternary solute–solvent-antisolvent equilibrium and crystallization kinetics is crucial in this strategy, and these are thus incorporated in the model. The optimization is capable of determining the optimal antisolvent feed profile that achieves a desired particle size. Experimental validation of the strategy is carried out and presented herein. Such a strategy stands as a key solution to antisolvent operations ubiquitous in the pharmaceutical and fine chemicals industries.