Supersaturation tracking for the development, optimization and control of crystallization processes

In this paper, a method which facilitates the calibration-free use of in situ ATR-FTIR for crystallization development and control is presented. This methodology uses solute-specific ATR-FTIR absorption peak heights to describe solute solubility and dissolved concentration and, in turn, supersaturation, for the optimization of cooling crystallizations of an active pharmaceutical ingredient (API) and benzoic acid. The approach presented facilitates rapid process understanding, design and optimization. Specifically, the potential to significantly reduce cycle time for both systems studies is demonstrated. In addition, the potential of the method to form the basis of a process control strategy for batch crystallization is successfully demonstrated.