Cocrystallization of Dasatinib with different acids improves the solubility and physicochemical properties: A combined experimental and theoretical studies

Dasatinib (DAS) is a tyrosine kinase inhibitor that is categorized as a class-II drug by Biopharmaceutical Classification System (BCS). It is used to treat Chronic Myeloid Leukemia (CML). The present work aimed to use the cocrystallization technique to enhance DAS's physicochemical characteristics. By applying the slow evaporation approach, we reported three DAS cocrystals with different structures of co-formers such as 4 hydroxybenzoic acid, 4-chlorobenzene acid, and Sorbic acid. Single Crystal X-ray Diffraction (SCXRD), Powder X-ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC), Thermo Gravimetric Analysis (TGA), and Fourier Transform Infrared Spectroscopy (FT-IR) were used to analyze the three obtained cocrystals. The solubility of DAS cocrystals was investigated and found to be ideally enhanced up to 6-fold, 4.5-fold, and 3.5-fold higher than DAS. According to the findings, the DAS cocrystal system has strong hydrogen bonding and stacking interactions. We also performed quantum chemical calculation and quantum theory of atoms in molecules (QTAIM) analysis to understand the strength of intermolecular interactions. From this study, we observed that cocrystallization was a promising technique for changing the physicochemical properties of DAS.