Measurement and correlation of solubility of rivaroxaban in dichloromethane and primary alcohol binary solvent mixtures at different temperatures

Abstract

The solubility of rivaroxaban in different solvent mixtures consisting of dichloromethane and primary alcohols, including methanol, ethanol, n-propanol, and n-butanol, was evaluated using the solid–liquid equilibrium method at various temperatures (283.15, 288.15, 293.15, 298.15, 303.15, and 308.15 K). The solubility of rivaroxaban increased with increasing temperature for all mono solvents. In the binary solvent mixtures, the solubility of rivaroxaban increased in the range of dichloromethane mass fraction (w) from 0.1 to 0.7. The highest solubility of rivaroxaban was observed at w = 0.8 in all binary mixtures due to the solvent synergistic effect. Particularly, the maximum solubility of rivaroxaban was approximately 11.18 and 85.52 times higher than that of neat dichloromethane and neat methanol at 298.15 K, respectively. The solubility values of rivaroxaban were correlated with the van't Hoff, modified Apelblat, simplified CNIBS/R-K, Jouyban–Acree, Jouyban–Acree–van’t Hoff, Jouyban–Acree-Apelblat, Sun, and Ma models. The thermodynamic parameters, including the dissolution enthalpy (ΔH°), Gibbs free energy (ΔG°), and dissolution entropy (ΔS°), were calculated, and the dissolution of rivaroxaban in the dichloromethane and primary alcohol mixtures was found to be an endothermic process. The experimental and calculated solubility results for rivaroxaban in binary solvent mixtures would be helpful for drug preparation, crystallization, and theoretical research.