Cyclic auto-seeded polythermal preferential crystallization—Effect of impurity accumulation

Preferential crystallization is a crystallization process where two enantiomers are separated into the pure chiral species. Usually the process is operated in a cyclic mode crystallizing the two species in sequel batches with an intermediate addition of fresh racemate. In this cyclic scheme reproducibility is a key issue. producibility of the preferential crystallization of dl-(±)-threonine out of water using an auto-seeding procedure is investigated in this work. As in many processes that are based on recycling, accumulation of impurities is an issue of importance. In this work 10 separation batches (five cycles) are performed and monitored using a combination of four analytical devices (Polarimeter, densitometer, FBRM, PVM). urity that accumulates over the number of batches is detected using chiral HPLC. The reproducibility of the individual batches also with respect to the accumulating impurity is discussed based on the monitored trajectories.