Extending the SAFT-γ Mie approach to model benzoic acid, diphenylamine, and mefenamic acid: solubility prediction and experimental measurement

Abstract The prediction of the solubility of pharmaceutical ingredients (APIs) is a significant challenge of interest in pharmaceutical applications and solvent selection processes. Here, we extend the table of group-group interactions (3 like interactions, 47 unlike interactions) of the SAFT- γ Mie group-contribution equation of state to model the phase behaviour and solubility of mefenamic acid, a nonsteroidal anti-inflammatory drug, in a range of solvents. In addition to mefenamic acid, we also consider its molecular synthons: benzoic acid and diphenylamine. New experimental solubility data are presented for the three molecules in a range of solvents, and three new SAFT- γ Mie groups are defined (aCCOOH, aCNHaC and CH 3 CO) and characterised, together with their unlike interactions with solvent groups. Literature data of vapour pressure, single-phase density, saturation density, vapourisation enthalpy, bubble temperature, dew temperature, and bubble pressure are used to characterise the new group-group interactions. Solubility data are used to characterise the new group-group interactions only if there are no other experimental data available. The transferability and predictive accuracy of the new models are assessed by comparison of the theoretical predictions with the experimental solubility data. Our comparison includes alcohols, ketones, and esters as families of solvents and includes mixed-solvent solubility predictions.