Investigation into the Cooling Crystallization and Transformations of Carbamazepine Using in Situ FBRM and PVM

The cooling crystallization of carbamazepine (CBZ) from 1-propyl alcohol has been investigated experimentally using in situ FBRM and PVM to study crystal growth and transformations. The effects of seeding strategies and cooling profiles on nucleation, growth, and polymorphism were investigated. The trigonal form II of CBZ, which has a needle-like morphology, was obtained in 72% yield from an unseeded crystallization process. Block-shaped crystals of CBZ form III were obtained in 86% yield from a crystallization process that was seeded with form III. Both product CSD and crystal form were influenced significantly by cooling profiles. As the cooling rate in the seeded process increased, the levels of form II in the product decreased. The transformation from form II to form III during crystallization was studied using online tools and offline measurements by optical microscopy, X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC).