A series of stable, metastable and unstable salts of Imatinib with improved solubility

Pharmaceutical salt formation is the most preferred and effective method to enhance the physicochemical properties of APIs. The aim of the study was to design and synthesize a series of new salts to improve the solubility of Imatinib (IM). Two stable salts with malonic acid (S1) and citric acid (S5), one metastable salt with fumaric acid (S2), two unstable salts with citric acid (S3, S4) were obtained for the first time. Single crystal and powder X-ray diffraction, Fourier transform infrared, differential scanning calorimetry, and thermogravimetric analysis were used to characterize the novel salts. The solubility and stability of the solid were also evaluated, and three salts (S1, S2, S5) had a more than 20 folds of solubility and a faster dissolution rate improved as compared to the pure drug in water and pH 6.8 buffer, respectively. (c) 2022 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Automated summary

Pharmaceutical salt formation is the preferred method to improve the physicochemical properties of APIs. This study designed and synthesized a series of new salts to enhance the solubility of Imatinib. Characterization techniques were used to investigate the salts, and their solubility and stability were evaluated. The results showed significant improvement in solubility and dissolution rate for three salts.