Multi-stage crystallization for resolution of enantiomeric mixtures in a solid solution forming system

A systematic procedure for synthesizing the multi-stage crystallization process was developed for resolution of enantiomeric mixtures involving solid solutions in the crystalline phase. The model compound investigated was citalopram oxalate, which revealed a complete solid solution in the solid phase. The counter-current multi-stage batch crystallization was suggested to isolate the target enantiomer from enantiomerically enriched mixtures. The solid–liquid equilibria in the presence of a solvent and the distribution diagrams were quantified and used in designing the crystallization process and defining adequate processing conditions. Different flowsheet schemes were considered and compared with respect to the process performance. The design procedure was verified by the experimental separation of enantiomeric mixtures of citalopram.

► The crystallization process for resolution enantiomeric mixtures involving solid solutions has been designed. ► The resolution strategy has been based on counter-current multi-stage batch process. ► Different flowsheet schemes were considered and compared with respect to the process performance.