Influence of excipients on thermodynamic phase behavior of pharmaceutical/solvent systems: Molecular thermodynamic model prediction

In this work, the influence of polymeric excipients (PEG6000, PEG400, PVPK25, and HPMCE3) on thermodynamic phase behavior of active pharmaceutical ingredients (API) (mesalazine and allopurinol) and its aqueous solution was systematically investigated through experimental measurement and thermodynamic modeling. The API/excipients formulations were prepared by ball milling, and the phase behavior was measured by differential scanning calorimetry (DSC). The results showed that the solubility of API/solvent systems were all increased with higher temperature. Meanwhile, it was found that all four excipients can solubilize mesalazine and allopurinol effectively and the solubilization performance of PVPK25 and HPMCE3 were preferable to PEG. Furthermore, the thermodynamic phase behavior of API in the excipients/water ternary system was predicted by the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT), demonstrating good accordance with the experimental results with low average relative deviations (ARDs). This work was expected to provide theoretical guidance for the screening of pharmaceutical formulation excipients.