Design and performance assessment of continuous crystallization processes resolving racemic conglomerates

Abstract

Continuous crystallization processes achieving the complete resolution of racemic feed mixtures of conglomerate forming substances are presented. The processes considered rely on the principles of preferential crystallization or attrition-enhanced deracemization (Viedma ripening). A single mechanistic population balance model is shown to describe both operating modes. For the case of isothermal Viedma ripening, a shortcut method is introduced that allows the rapid and computationally efficient design of processes using a single or multiple ripening stages. The achievable productivity and enantiomeric purity are determined for all process variants in a wide range of operating conditions, and Pareto optimal operating points are identified. Since our results are obtained with a consistent set of kinetics for all operating modes, an unbiased comparison is enabled. It is shown that the productivity of the ripening process can be improved by using cascades of multiple crystallizers, but that the preferential crystallization process still achieves higher productivity at full enantiomeric purity.