Desolvation of dasatinib methanolate: an improved anhydrous polymorph

Transient solvates are unstable crystals that readily desolvate upon harvesting but can significantly alter the outcome of the crystallization process. In this study, we investigated a new crystal structure of a methanol solvate of dasatinib that shows transient characteristics. Using SC-XRD, PXRD, HSM, and DSC, this new crystal was characterized to shed light on the mechanism of achieving different anhydrous polymorphs of dasatinib upon desolvation. The single-crystal X-ray structure of this methanol solvate was determined for the first time in this work. Via Hirshfeld surface analysis and molecular electrostatic potential maps (MEPs), the intermolecular interactions are discussed. In addition, void map analysis sheds light on the transient nature of the DAS-MeOH solvate crystals. The effect of various crystallization techniques, including slow evaporation and grinding/milling techniques, on the product of desolvation, has also been discussed. Finally, with the aid of particle size distribution measurements, we illustrated the potential benefit of such transient crystals on particle size reduction. A case study portraying how a labile tri-methanol solvate of dasatinib leads to polymorph transformation and particle size reduction.