Insight into the Dissolution Behavior of Benzimidazole in 19 Monosolvents: Solubility, Characterization, Determination, Analysis, and Model Correlation

Benzimidazole has many biological activities and is widely used in the pharmaceutical and chemical industries. Under the conditions of P = 101.2 kPa and T = 273.15–323.15 K, the solubility of benzimidazole in 19 monosolvents was determined using the static gravimetric method. The solubility was positively correlated with temperature and varied among solvents, with n-pentanol having the highest value. Four models (modified Apelblat, NRTL, UNIQUAC, and Margules) were used to correlate the solubility data, with the modified Apelblat model having the best fitting effect. Then, the thermodynamic properties of the mixing process were estimated by the NRTL model. In addition, the internal interactions of benzimidazole were analyzed using molecular electrostatic potentials (MEPs) and Hirshfeld surface (HS), revealing a strong solvent-benzimidazole hydrogen-bonding tendency. Furthermore, Hansen solubility parameters (HSPs), interaction region indicator (IRI), and interaction energy were used to evaluate benzimidazole’s solubility in 19 monosolvents. Results show that the main factors influencing the solubility behavior include solvent polarity (ET(30)) and HSPs. These experimental results can be used for the purification, crystallization, and industrial applications of benzimidazole as well as similar substances.