Solid-liquid equilibrium solubility, modeling, Hansen solubility parameter and thermodynamic analysis of 2-Mercaptobenzimidazole in eleven mono-solvents and three binary solvents at different temperatures

The solubility of drugs is an important physicochemical data for its development and design. In this work, the solubility of 2-mercaptobenzimidazole (2-MBI) in eleven mono-solvent solvents (2-propoxyethanol, isopropyl acetate, butyl acetate , 2-methoxyethanol, 2-butanol, ethyl formate , 2-ethoxyethanol, isobutanol , 4-methyl-2-pentanone, 2-butoxyethanol and ethylene glycol) and three binary solvents (2-methoxyethanol + ethyl formate, 2-methoxyethanol + isopropyl acetate, 2-ethoxyethanol+ ethyl formate) was measured by a gravimetric analysis method at the temperatures from 283.15 to 323.15 K. The solubility of 2-MBI in the studied solvents increased with the increasing temperature. The measured solubility data of 2-MBI was described mathematically and back-calculated by CNIBS/R-K model, Margules model, UNIQUAC model, Jouyban-Acree-van't Hoff model and NRTL model. Hansen solubility parameters was calculated to assess the qualitative trend of 2-MBI in all selected mono and binary mixed solvents, analysis results indicating that the solubilization behavior of 2-MBI was intricate and can not only be assessed by one factor. In this study, the apparent thermodynamic parameters including ∆ sol H o , ∆ sol S o , ∆ sol G o , ξ H and ξ TS were investigated, positive values of ∆ sol H o indicating that the corresponding dissolution process of 2-MBI in all selected solvents was endothermic. In conclusion, these experimental and thermodynamic analysis can enrich the database and give support for design and optimize the crystallization process of 2-MBI.