Polymorphs of Imatinib-Gallic Acid Cocrystals: Enhancing Physicochemical Properties and Potentiating Anticancer Activity in Colorectal Cancer Cell Proliferation

Imatinib (IM), a classic oral anticancer drug, suffers from bioavailability limitations due to its low solubility. The commercially available Imatinib Mesylate (IM-Me) takes advantage of the mesylate salt to enable formulation with improved solubility. However, this enhancement comes at the cost of structural stability and introduces a high degree of hygroscopicity, thereby presenting additional challenges for drug processing and storage. To address these challenges, the cocrystallization strategy was employed in our work, and three innovative imatinib-gallic acid (IM-GA) crystalline forms were successfully prepared: IM-GA cocrystal Form I (IM-GA-Form I), IM-GA cocrystal Form II (IM-GA-Form II), and IM-GA ethanol solvate (IM-GA-EtOH). Their crystal structures were determined by single-crystal X-ray diffraction (SCXRD), and IM-GA-Form I was identified as the thermodynamically stable form through thermal analysis and lattice energy calculations. Subsequent experiments demonstrated that IM-GA-Form I increased the drug’s solubility by more than 12-fold, effectively reducing the high hygroscopicity of the mesylate salt. Moreover, the in vitro cancer cell proliferation analysis showed that IM-GA-Form I exhibited a synergistic effect, leading to superior inhibition of human colorectal cancer cells compared to the commercial formulation. These results position IM-GA-Form I as a promising formulation for combination drug therapy. Imatinib (IM) and gallic acid (GA), both anticancer agents, were successfully synthesized into cocrystal IM-GA-Form I. Single-crystal X-ray diffraction (SCXRD) analysis confirmed its crystal structure. Notably, IM-GA-Form I demonstrated enhanced inhibition of human colorectal cancer cells compared to the initial drug forms, validating cocrystallization as an effective strategy to enhance the anticancer efficacy of pharmaceuticals.