Thermodynamic study of benzimidazole solubility and preferential solvation in binary alcohol-water systems

The solubility of benzimidazole (BZI) in aqueous-alcohol blends (water with methanol (MeOH), or ethanol (EtOH)) was measured by a gravimetric method at temperatures ranging from 288.15 to 323.15 K. This research is the first systematic report on BZI solubility in these binary mixed solvents, thus filling a considerable gap in the literature. The study found that BZI solubility was higher at elevated temperatures in all the binary solvent systems. The kamlet-abboud-taft linear solvation energy relationship (KAT-LSER) model was employed to evaluate the role of solute-solvent contacts in solubility behavior. Three thermodynamic models (Jouyban-Acree, Jouyban-Acree-van’t Hoff, and Apelblat-Jouyban-Acree) were employed to connect experimental solubility data with the models. The models are in strong agreement with the experimental results, as indicated by the low average relative deviation (RAD%) values (≤ 1.52, ≤ 1.34, and ≤ 2.78, respectively). Inverse Kirkwood-Buff integrals (IKBI) were used to obtain dissolution parameters, which indicated positive preferential solvation values for the alcohol components in alcohol aqueous solutions, with the strength of preferential solvation following the order EtOH > MeOH and showing a significant dependence on both solvent composition and temperature. These results augment the knowledge of BZI dissolution thermodynamics and serve as very dependable reference data for its separation, formulation, and pharmaceutical processing.