In Situ Monitoring of Supersaturation and Polymorphic Form of Piracetam during Batch Cooling Crystallization

In situ Raman spectroscopy, infrared spectroscopy, and focused beam reflectance measurement (FBRM) were used simultaneously to monitor the polymorphic form, supersaturation profile, and chord length distribution, respectively, during a cooling crystallization of piracetam in ethanol. At fast cooling rates and fast generation of supersaturation, the metastable polymorph was observed to nucleate and prevail. On slow cooling, only the stable polymorph was observed. This was attributed to the time available to the system to respond to the generated supersaturation. If sufficient time is allowed, the system will arrange itself into its most stable thermodynamic configuration, and the stable polymorph will be produced. At fast cooling rates, the system is suject to kinetic control, resulting in crystallisation of the less stable polymorph.