(102b) Thermodynamic Modeling and Prediction of Solubility of Organic Molecules and Pharmaceuticals

A new activity coefficient model was developed from excess Gibbs free energy in the form . The constants of the proposed model were considered to be function of solute and solvents dielectric constants, Hildebrand solubility parameters and specific volumes of solute and solvent molecules. The proposed model obeys the Gibbs-Duhem condition for activity coefficient models. To generalize the model and make it as a purely predictive model without any adjustable parameters, its constants were found using the experimental activity coefficient and physical properties of 20 vapour-liquid systems. The predictive capability of the proposed model was tested by calculating the activity coefficients of 41 binary vapour-liquid equilibrium systems and showed good agreement with the experimental data in comparison with two other predictive models, the UNIFAC and Hildebrand models. Furthermore, the proposed model was used to predict the activity coefficient of an organic compound, stearic acid, whose physical properties were available in methanol and 2-butanone. The predicted activity coefficient along with the thermal properties of the stearic acid were used to calculate the solubility of stearic acid in these two solvents and resulted in a better agreement with the experimental data compared to the UNIFAC and Hildebrand predictive models. The new model was modified as a semi-predictive model with two adjustable parameters. The solubility of three model compounds was predicted in a single solvent and a mixture of two-solvents by three semi-predictive (the models have adjustable parameters that must be estimated using experimental data) activity coefficient models, namely the UNIQUAC, the NRTL and the modified new model. The solubility of a metastable polymorph of stavudine was also predicted using the models and the experimental data of the more stable polymorph.