Equilibrium solubility, solvation and dissolution thermodynamics, and density functional theory study of albendazole in solutions of acetone/methanol/isopropanol + water

Abstract

In this work, albendazole was dissolved in mixtures of acetone/methanol/isopropanol + water to examine its solubility, dissolution thermodynamics, solvation behavior, and intermolecular interactions. The shake-flask method was used to conduct solubility tests at a pressure of 101.0 kPa and temperatures from 278.15 to 323.15 K. In water and pure organic solvents, respectively, the lowest and greatest levels of albendazole solubility were found. XRD analysis-based experiments found no evidence of crystal solvation or transition. Jouyban-Acree, modified Wilson, QSPR and modified van't Hoff-Jouyban-Acree models correlated the solubility to solvent composition and temperature with the relative average deviations (RAD) of no more than 8.99 %. The equilibrium solubility at 298.15 K was examined using the approach of extended Hildebrand solubility parameter, which produced an average relative deviation of 3.63 %. The dipolarity-polarizability and solubility parameter of solutions have a considerable impact on the solubility fluctuation, according to the analysis of linear solvation energy relationship. The preferred solvation of albendazole by water and different organic solvents was quantitatively examined with the help of the inverse Kirkwood-Buff integrals. Albendazole was preferentially solvated by the organic solvents in moderate and rich organic solvent compositions in blends, where albendazole served as a Lewis acid. An enthalpy-driven mechanism and an endothermic process were identified by thermodynamic analysis of the entropy-enthalpy compensation and dissolution properties for albendazole dissolving in blends. The electrostatic characteristics of albendazole acidity/basicity were highlighted using analysis of Hirshfeld surface and molecular surface. The primary targets of nucleophilic and electrophilic assault are the –NH and -S-groups. An independent gradient model based on Hirshfeld partition analysis was used to visual the weak interactions between albendazole and different solvents.