Solid–liquid phase equilibrium of mycophenolic acid in 14 mono-solvents: Measurements, correlation, solvent effect and molecular simulation

• 1. The solubility of mycophenolic acid in 14 solvents was determined by the gravimetric static method. • 2. Solubility is positively correlated with temperature and correlated by five thermodynamic models. • 3. Thermodynamic properties of the solution were calculated. • 4. KAT-LSER model was applied to analyze the solvent effect on mycophenolic acid solubility. The solubility of mycophenolic acid in fourteen mono-solvents (ethyl formate, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, pentyl acetate, ethyl propionate, 1-propanol, 2-propanol, 1-butanol, acetonitrile, 2-butanol, 2-methyl-1-propanol, and 1-heptanol) was measured by a static gravimetric analytic method at different temperatures (T=288.15 K to 323.15 K). The experimental results showed that in these selected solvents, the solubility is positively correlated with temperature. The Apelblat equation, λh (Buchowski) equation, NRTL model, Wilson model and Jouyban model were introduced to correlate the experimental solubility data of MPA in solvents, and the Apelblat equation provided the best fitting results as the minimum RMSD and ARD value were obtained when compared with the other models. In addition, the intermolecular interaction and the solvent effect were investigated by Hirshfeld surface analysis, Radial distribution function (RDF) analysis and KAT-LSER model analysis, the results revealed that the solubility of MPA is not decided only by one factor, but by many causes.