Preparation, characterization, transformation and solubility of imatinib-oxalate salt polymorphs

The three polymorphs (I, II, III) and one amorphous (IV) form of imatinib-oxalate new salt were prepared and characterized by powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis and infrared spectroscopy, and transformation rules among the four salts were analyzed. The solubility of polymorph II was investigated by high performance liquid chromatography. The results show that polymorph II was stable but polymorph I, III and amorphous IV were unstable at room temperature. Polymorph I transformed into polymorph II at room temperature. At relative humidity 90%, polymorph I, II and amorphous IV transformed into polymorph III, but polymorph III transformed into amorphous IV at 70 ℃. The solubility of imatinib was significantly improved after being salted with oxalic acid, and the equilibrium solubility of polymorph II in pH 6.8 buffer solution and pure water was increased by 4.1 and 21.2 fold, respectively, as compared to bulk drug. This research provides guidance for the development and quality control of a new salt form of imatinib.