Solid-liquid phase equilibrium and thermodynamic analysis of griseofulvin in twelve mono-solvents

Abstract

The structure and properties of griseofulvin (GSF) were investigated in both solution and solid phases. The intermolecular interactions within griseofulvin crystal structure probed by Hirshfeld surface analysis reveal that the H⋯H and O⋯H contacts apparently dominate in the solid-state structure. The solution thermodynamic properties including solid-liquid phase equilibrium solubility and thermodynamic functions of mixing were determined in twelve solvents (methanol, ethanol, n-propanol, n-butanol, isobutanol, methyl acetate, ethyl acetate, n-propyl acetate, n-butyl acetate, isopropyl acetate, isobutyl acetate and acetonitrile). The equilibrium solubility data was measured by gravimetric method at temperature ranging from 283.15 to 323.15 K, and the measurement results show the solubility is monotonously rising with increasing temperature as expected in all solvents. Besides, the investigations over the effect of solvent properties in terms of solvent polarity, hydrogen bonding donor and acceptor propensity, as well as cohesive energy density on solid-liquid phase equilibrium behaviors reveal that the solvent polarity determines the solubility of griseofulvin in the studied solvent systems. Further, the statistical correlations were well performed by the modified Apelblat equation, λh equation, and NRTL model, in which the modified Apelblat equation receives the best fitting performance. Finally, thermodynamic functions of mixing (enthalpy, entropy, and Gibbs energy) were derived, and the results suggest a spontaneous, exothermic and entropy-driven mixing process. All the thermodynamic data and models presented here will certainly provide fundamental basis for separation and purification of griseofulvin in industrial production.