Study of Crystal Structures, Properties, and Form Transformations among a Polymorph, Hydrates, and Solvates of Apatinib

Apatinib (APA) is a targeted anti-neoplastic drug by inhibiting the vascular endothelial cell growth factor receptor of tyrosine kinase. Its therapeutic solid form, apatinib mesylate (ATM), is dissociated to APA neutral form instantaneously in aqueous solution. Hereby, we undertook a form screen of APA. A polymorph, two hydrates, and three solvates of APA were discovered and characterized by single-crystal X-ray diffraction, powder X-ray diffraction, Fourier-transform infrared, and Raman spectroscopy. The relationships of phase transformation were assessed by differential scanning calorimetry, thermogravimetric analysis, and dynamic vapor sorption. Their thermal and hygroscopic stabilities were elaborated and found to be dependent on intermolecular interaction and crystal packing. Form A with superior solubility and stability appeared to be a promising alternative form to overcome the disproportionation of ATM