Solid-State Characterization and Insight into Transformations and Stability of Apatinib Mesylate Solvates

Two types of solvates for the antiangiogenesis drug apatinib mesylate were obtained, and their crystal structures were determined by single-crystal X-ray diffraction. The properties of these solvates were fully characterized by powder X-ray diffraction, dynamic vapor sorption, differential scanning calorimetry, and thermogravimetric analysis. Experimental and theoretical studies were performed on the solvates to understand the phase transitions induced by heat and humidity. An irreversible humidity-induced single-crystal-to-single-crystal transformation from ethanol solvate (type II) to monohydrate (type I) was elucidated. The stability of these solvates, including moisture-dependent and thermal stability, was studied. The comprehensive investigation of the solvates and hydrate provided essential knowledge about quality control of this important drug.