A Practical Approach for Using Solubility to Design Cooling Crystallisations

Crystallisation and recrystallisation are important unit operations in the pharmaceutical industry. In our experience cooling crystallisations are preferred to other ways of generating supersaturation because they are quicker to develop and provide better control of purity and polymorph and particle properties. There is, however, a perception that the yield from cooling crystallisations is low. This work presents an approach to designing cooling crystallisations based on a review of the temperature dependence of solubility for over 100 systems. This methodology is demonstrated with a case study of an in-house development compound. The conclusion is that cooling crystallisations are generally viable.