Two anhydrous forms and one monohydrate of a cocrystal of axitinib and glutaric acid: characterization, property evaluation and phase transition study.

The polymorphs and hydrates of multi-component crystals have not been studied as extensively as those of single-component crystals. In this work, one anhydrate and one monohydrate of a cocrystal involving axitinib (AXI) and glutaric acid (GA), AXI-GA I and AXI-GA·H2O, were successfully synthesized and fully characterized by single crystal and powder X-ray diffraction, polarizing microscopy, 1H nuclear magnetic resonance, Fourier transform infra-red spectroscopy, differential scanning calorimetry and thermogravimetric analyses. Hirshfeld surface analysis demonstrates that the most prominent contributions of the intermolecular interactions of these two forms are provided by van der Waals interactions, hydrogen bonds/C–H⋯O contacts and C–H⋯π interactions. The hygroscopicity, accelerated stability and powder dissolution behaviors were evaluated. The phase transition relationship under various conditions was also investigated, and a metastable anhydrous form, AXI-GA II, was discovered during this process. The results show that AXI-GA I is the most thermodynamically stable form and has great potential for further development as it exhibits significantly improved solubility with enough stability. [ABSTRACT FROM AUTHOR]