Thermodynamics Research Center / ThermoML | Journal of Chemical Thermodynamics

ABSTRACT

This work measured the solubility of forms I and II of anticoagulant drug rivaroxaban in a series of organic solvents in which the solubility of form II was firstly reported as supplementary to the work of Zhang et al. [22]. A dynamic dissolution method was used to determine the solubility of both forms in acetonitrile, methyl acetate, acetone, 2-butanone, 3-pentanone and 2-hexanone from (273.15 to 318.15) K and in 1,4-dioxane from (288.15 to 333.15) K. The results showed that, the solubility of both forms generally increased with the temperature and decreased with an increase in the carbon number of ketones at the same temperature. The two forms were monotropically related and form II was the metastable form giving a higher solubility than form I. Meanwhile, such semiempirical thermodynamic models based on local composition concept as Wilson, nonrandom two-liquid (NRTL) and universal quasi chemical (UNIQUAC) equations with the correlation between model parameters and temperature were employed to model the studied solid-liquid equilibrium. It was found that UNIQUAC was the most appropriate model among the selected thermodynamic equations for the correlation of the solubility of rivaroxaban polymorphs in organic solvents. Finally, the apparent standard enthalpy change of dissolution was acquired from the experimental solubility data and the positive values of the apparent standard enthalpy change revealed that the dissolution of both forms of rivaroxaban in the selected solvents was an endothermic process.