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

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. (C) 2012 Elsevier Ltd. All rights reserved.