(258h) Modeling Pharmaceutical Salt Solubility in Mixed Solvents with Enrtl-Sac

The recently developed Nonrandom Two-Liquid Segment Activity Coefficient (NRTL-SAC) model of Chen and Song(refs 1,2) offers a simple and practical thermodynamic framework to correlate and predict drug solubility based on a small initial set of measured solubility data. The model has been shown to yield satisfactory results in first correlating drug solubility in a few representative pure solvents and then qualitatively predicting drug solubility in other pure solvents and in mixed solvents for organic nonelectrolytes (ref 3). Here we investigate the use of the electrolyte NRTL-SAC model (eNRTL-SAC) in correlation and prediction of drug solubility for organic salts in pure and mixed solvents and the model predictions are compared against available data. The study indicates that the model provides qualitative correlation and prediction of solubilities in both pure and mixed solvents for organic pharmaceutical salts and it can be used to support, among others, the early stages of crystallization process development.

1. Chen, C.-C., Song, Y., ?Solubility Modeling with a Non-Random Two-Liquid Segment Activity Coefficient Model,? Ind. Eng. Chem. Res., 2004, 43, 8354. 2. Chen, C.-C., Song, Y., ?Extension of Nonrandom Two-Liquid Segment Activity Coefficient Model for Electrolytes,? Ind. Eng. Chem. Res., 2005, 44, 8909. 3. Chen, C.-C., Crafts, P., ?Correlatoin and Prediction of Drug Molecule Solubility in Mixed Solvent Systems with the NRTL-SAC Model,? paper accepted for publication in Ind. Eng. Chem. Res.