Design of constant supersaturation cooling crystallization of a pharmaceutical: A simple approach

This paper describes a simple method for designing a batch cooling crystallization of a pharmaceutical under constant supersaturation. The simple model assumes that crystal growth is the predominant mechanism during the crystallization and requires only two parameters, crystal growth rate constant and solubility. Both parameters are functions of temperature and are obtained simultaneously by conducting a single experiment with multiple-step cooling. The model was validated through additional natural cooling and controlled cooling crystallization experiments. Finally, it was demonstrated experimentally that the supersaturation throughout the crystallization process was effectively kept constant by applying the cooling trajectory predicted by the model.