Dissolution behavior and thermodynamic properties of apixaban in pure and mixed solvents

Abstract The solubility profile of apixaban in pure and mixed solvents within the temperature range from (288.15 to 328.15) K under atmosphere pressure (101.3 kPa) was studied and evaluated by some thermodynamics models. The solid state of apixaban in equilibrated form was characterized using powder X-ray diffraction (PXRD) technique. The maximum mole solubility in pure solvents was obtained in 1, 4-dioxane (3.648×10-3) at 328.15K, and followed by methanol (1.967×10-3), acetone (7.885×10-4),ethanol (6.049×10-4), isopropanol (3.806×10-4), ethyl acetate (2.266×10-4), n-hexane (1.883×10-4), water (3.989×10-5). The solubility was quite small. Therefore, the solubility profile of apixaban in mixtures of (1, 4-dioxane + water) was further studied. Moreover, it increased at first and then decreased with the increasing mass fraction of 1, 4-dioxane. Moreover, the extended Hildebrand solubility approach (EHSA) was applied to evaluate the co-solvency phenomenon in mixed solvent at 298.15 K. In the following, the analysis of apparent thermodynamic properties indicates that the dissolution process in all selected solvents is an endothermic and entropy driven process.