Solubility, MD simulation, thermodynamic properties and solvent effect of perphenazine (Form I) in eleven neat organic solvents ranged from 278.15 K to 318.15 K

Perphenazine has rather effective in the treatment of mental illness. In this work, the solid-liquid equilibrium data of perphenazine in eleven organic neat solvents were determined by laser dynamic method under the atmospheric pressure and temperature range of 278.15 K similar to 318.15 K. The selected solvents were n-propanol, n-butyl alcohol, methyl acetate, ethyl acetate, n-propyl acetate, n-amyl acetate, N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMAC), acetone, 2-methoxyethanol, glycol ether, respectively. From the results, the solubility of perphenazine is all positively correlated with temperature. Separately, we have adopted the KAT-LSER model and molecular dynamics simulation to investigate the influence of solvent effects and solute-solvent interaction on solute solubility. Meanwhile, there were four activity coefficient models being used to correlate the solubility data and Average relative deviation of models are 4.13% (Margules model), 3.94% (NRTL model), 4.49% (NRTL-SAC model) and 3.06% (UNIQUAC model), respectively, all of which do not exceed 5%. It manifests that the four activity coefficient models can fit the experimental values well, in which the UNIQUAC model gives the best regression effect. Moreover, the apparent thermodynamic properties(Delta(sol)G degrees, 4(sol)H degrees and 4(sol)S degrees) of perphenazine in various solvents were calculated by Van't Hoff equation. In accordance with the analysis and calculation of dissolution, the dissolution process is an endothermic entropy-driven process. This research can provide basic data for the crystallization process of perphenazine. (C) 2021 Elsevier B.V. All rights reserved.