Solubility, thermodynamic properties and molecular simulation of tinidazole in fourteen mono-solvents at different temperatures

Abstract

The solubility properties of tinidazole (TNZ) in investigated fourteen mono-solvents were further studied at several temperature points (278.15 K ∼ 323.15 K) under 101.2 kPa using the laser monitoring technique. The selected solvents were acetone, methanol, ethanol, 2-methoxyethanol, 2-ethoxyethanol, 2-propoxyethanol, 2-butoxyethanol, methyl acetate, ethyl acetate, n-propyl acetate, n-butyl acetate, NMP, DMF, DMAC, respectively. The order of solubility of tinidazole in fourteen mono-solvents at 298.15 K is: NMP > DMAC > DMF > acetone > 2-methoxyethanol > methylacetate > 2-ethoxyethanol > ethyl acetate > 2-propoxyethanol > n-propyl acetate > 2-butoxyethanol > n-butyl acetate > methanol > ethanol. As shown by the solubility data of TNZ in chosen fourteen mono-solvents in this work, TNZ is more soluble in higher temperature. The KAT-LSER model and molecular dynamics simulation were adopted to probe the influence of solvent effects and solute–solvent interaction on TNZ solubility. The obtained solubility data of TNZ was fitted by (λh equation, NRTL model, NRTL-SAC model, two-Suffix Margules model, and UNIQUAC model). The results indicate that five models can fit the experimental values well, in which the NRTL-SAC model gives the best regression effect. Moreover, the apparent thermodynamic properties (△solG°, △solH° and △solS°) of TNZ in various solvents were calculated by Van’t Hoff equation. In accordance with the analysis and calculation of dissolution, the dissolution process is is entropy-motivated and endothermal.