Modeling and prediction of thermodynamic phase behaviors of oxaprozin and irbesartan in biorelevant media

The in vitro solubility of poorly water-soluble drugs is one of the key parameters required for the development of the oral delivery system, but the determination of the solubility often relies on extensive experiments, which are time-consuming and costly. Therefore, it is meaningful to accurately model and predict the solubility of drugs in biorelevant media. Two insoluble drugs, oxaprozin and irbesartan , were selected and their solubilities in surfactant solutions, buffer solutions and biorelevant media were measured in this work. The thermodynamic phase behaviors of oxaprozin and irbesartan were modeled and predicted using Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) combined with pH-dependent and micellar solubilization models. The good agreement between the experimental results and the predicted values indicates the success of the model predictions, which provides the solubility database and good theoretical guidance for drug development and formulation selection.