Hybrid processes:: Design method for optimal coupling of chromatography and crystallization units

A general design method for the hybrid process of a chromatographic and a crystallization unit was developed. The fundamentals for the separate design of chromatographic and crystallization separation processes, as well as modeling approaches for these units, are presented. Four different test systems were chosen to show the applicability of the developed method. A focus was set on the enantioseparation of racemic compounds occurring in the pharmaceutical industry. The development of the flowsheet for the hybrid process shows that a chromatographic unit with a subsequent crystallization and recycle of the crystallizer's mother liquor to the feed of the chromatographic unit is most suitable. The possibilities of racemization and a solvent change are discussed. The influence of important operation parameters are investigated. The results for the test systems show that a hybrid process, in which both units serve as a separation process, is only suitable if the productivity of the chromatographic unit decreases sharply with increasing demands concerning the outlet purity and if the eutectic point of the racemic compound is close to 0.5.