Fast-Dissolving and Highly Soluble Dasatinib Multicomponent Crystals Efficiently Inhibit Leukemia Cell Viability

Abstract Dasatinib (DAS) is a biopharmaceutical classification system (BCS) class II drug that is used orally to treat chronic myelogenous leukemia. However, its very low and pH-dependent aqueous solubility severely limits its oral bioavailability. To address this biopharmaceutical limitation, we designed more soluble multicomponent crystalline forms (MCCs) of DAS. Two novel salt solvate forms were successfully obtained via solvent evaporation through reactions with maleic and fumaric acids. A comprehensive solid-state evaluation of these salt solvate forms was conducted by using X-ray diffraction (SCXRD, PXRD), spectroscopy (FT-IR and 1H NMR), and thermal (TG and DSC) analyses. Both MCCs of DAS have displayed substantial enhancements in buffered aqueous solubility (up 1470-fold) and intrinsic dissolution rate (up 312-fold) compared with the parent drug. Furthermore, the DAS MCCs exhibited an increased cytotoxicity and selectivity toward tumor cells. These fulfillments highlight the potential of crystalline salt engineering to enhance the unsatisfactory oral bioavailability and anticancer efficacy of the DAS.