Optimization of two-stage cooling profile in unseeded batch crystallization∗

A two-stage cooling protocol for batch cooling crystallization was optimized to maximize mean crystal size while minimizing the variance in size. A population balance model represents the crystallization process, incorporating crystal growth and nucleation, for use in a multi-objective optimization. At all points along the Pareto front, the optimal strategy has the nucleation event occurring on the temperature plateau between the two cooling stages. This shortens the nucleation period–supersaturation is rapidly depleted, ultimately generating fewer crystals of larger size. In comparison to a simple linear cooling profile, the two-step strategy produces crystals of larger size with smaller variance.