Implementation of focused beam reflectance measurement (FBRM) in antisolvent crystallization to achieve consistent product quality

Abstract

In this study, focused beam reflectance measurement (FBRM) is used to achieve batch-to-batch product quality consistency in terms of crystal size distribution (CSD) in unseeded antisolvent crystallization. The method comprises three regions. Initially, sufficient internal seed crystals are generated through primary nucleation, then the seed crystals generated are conditioned by redissolving the fine crystals, and finally the conditioned seed crystals are grown into final product crystals. Results showed that the product CSD consistency from the proposed control method was much better than that from unseeded antisolvent crystallization, while it was as good as that from externally seeded antisolvent crystallization. The robustness of the proposed control method was also demonstrated by performing experiments with initial concentration disturbances. © 2010 American Chemical Society.