Conceptual Design and Feasibility Study of Combining Continuous Chromatography and Crystallization for Stereoisomer Separations

Abstract The separation of stereoisomers—diastereoisomers and enantiomers—constitutes an important class of problems in life science applications, namely in drug manufacture. Chromatography is often the method of choice to perform this task. To decrease the typically high investment and operational costs of the chromatographic separation, it can be beneficial to combine this process with a selective crystallization step. This work investigates such process combination of simulated moving bed chromatography and crystallization from solution. A short-cut method, based on only a few fundamental experimental parameters, is applied to evaluate the process combination for one enantiomeric and one epimeric system. While the enantiomeric system is characterized by a simple conglomerate phase diagram, the epimeric system shows some characteristic properties, like incorporation of the counter epimer and an additional impurity into the crystal lattice of the product epimer, that have to be accounted for by more detailed investigations.