Solubility study of m-aminobenzoic acid form III in different mono-solvents by thermodynamic analysis and molecular simulation

The solid-liquid equilibrium behavior of m-aminobenzoic acid (m-ABA) form III in eleven mono-sol-vents (methanol, ethanol, n-propanol, isopropanol, n-butanol, methyl acetate, propyl acetate, butyl acet-ate, acetone, butanone and water) was investigated in the temperature from 283.15 K to 323.15 K. Solubility data were successfully described and correlated by four thermodynamic models, and all calcu-lated ARD% values are lower than 5%. The thermodynamic functions of mixing were calculated and ana-lyzed based on the NRTL model, and the results show that the mixing process is spontaneous and entropy-driving. The characteristics of m-ABA form III both in solution and solid phases were studied. Molecular electrostatic potential surface has been employed to present the overall charge distribution and estimate intermolecular interactions between the form III and solvents. Hirshfeld surface analysis has been applied to visualize various molecular interactions. Besides, the effect of selected solvent prop-erties on the dissolution behavior of m-ABA form III was examined. Finally, molecular simulations have been further applied to disclose the interactions between solute and solvent molecules. This work has guiding significance for the design and optimization of the m-ABA crystallization process.(c) 2022 Elsevier B.V. All rights reserved.

Automated summary

This study investigated the solid-liquid equilibrium behavior of m-aminobenzoic acid form III in eleven solvents. Solubility data was successfully described and correlated using thermodynamic models. The thermodynamic functions of mixing were analyzed and the mixing process was found to be spontaneous and entropy-driving. The characteristics of the compound in both solution and solid phases were studied, and the effect of solvent properties on its dissolution behavior was examined. Molecular simulations were further conducted to explore the interactions between the solute and solvent molecules.