Preparation and Characterization of Apixaban Cocrystals with Coformers for Improving Physical Properties

Background: Cocrystals are stoichiometric, multicomponent crystalline materials composed of an active pharmaceutical ingredient (API) and a coformer arranged in a crystalline structure. Apixaban (APX) is an oral blood thinner that has a low aqueous solubility of 0.028mg/mL at 24 °C and a weak oral bioavailability of about 50% for doses below 10 mg, decreasing as doses above 25 mg are taken. Objectives: To develop and assess APX cocrystal to improve its solubility. Methods: Cocrystals of APX with diverse coformers were synthesized using the solvent evaporation technique in varying molar ratios. The structure of the synthesized cocrystals was validated by DSC, PXRD, and FTIR analyses. Saturation solubility of APX and cocrystals in water was also investigated. Results: APX cocrystals with diverse coformers exhibited distinct physicochemical features. The co-crystal of APX with oxalic acid at a 1:1 ratio exhibited a 2.54-fold enhancement in solubility relative to that of pure APX in water. Each coformer enhanced the solubility of the APX co-crystals. The FTIR spectra of the cocrystals indicated no interaction between the APX and the coformers. The DSC analysis revealed distinct endothermic peaks corresponding to its melting point, indicating the development of cocrystals. The PXRD diffractogram demonstrated fluctuation of 2 theta values of peaks and confirmed cocrystallization of APX. Conclusions: Cocrystallization may serve as a potential method to improve the solubility of APX.