In situ monitoring, control and optimization of a liquid–liquid phase separation crystallization

Abstract The oiling out and crystallization behavior of a pharmaceutical compound from acetone and water was studied using a range of in-situ tools to qualitatively describe the oiling out phenomenon. Using a single peak height in the IR spectral region, the liquid phase concentration could be tracked during the liquid–liquid phase separation and also during the subsequent crystallization. This allowed the oiling out region of the system to be properly understood at a mechanistic level and also allowed for the implementation of a control technique that would control the particle size over regular seeding and maintain supersaturation at a constant level.