Seeding and Constant-Supersaturation Control by ATR-FTIR in Anti-Solvent Crystallization

The strategy for seeding and supersaturation control can play a critical role in defining the purity and particle size distribution of crystal products. Previous research has demonstrated that operation of crystallizers at constant supersaturation by feedback control is attractive due to its simplicity and resistance to operating disturbances. In this study, the effects of seed loading and seed size distribution were investigated for anti-solvent crystallization of paracetamol from a water−acetone mixture operated at constant supersaturation. A seeding strategy based on a simple mass balance equation provided a good starting point for the refinement of particle size distribution and adjustment of batch time in different circumstances to obtain a target average crystal size with narrow size distribution.