Modeling of the solubility of Naproxen and Trimethoprim in different solvents at different temperature

Abstract

The study concerns the prediction of the solubility of pharmaceutical compounds such as Trimethoprim and Naproxen in various solvents like Methanol, Ethanol, 1-Propanol, 2-Propanol, 1-Butanol and 2-Butanol for the first solute and Chloroform, Octanol and Cyclohexane, for the second one. The solubility prediction was performed using thermodynamic models like the UNIFAC, which is a group contribution method, and the semi-predictive model like NRTL. The required interaction parameters for the NRTL are not available and are calculated by optimizing an objective function involving experimental data reported in the literature for the considered systems. Also the obtained results by means of the UNIFAC model for Naproxen showed deviations from the experimental data and therefore new molecular decompositions to generate new groups are proposed and the corresponding interaction parameters are calculated. The influence of the molecular structure on the behavior of the mixture is also discussed. On the other hand a new group representing the Aromatic Nitrogen (AN) present in Trimethoprim is introduced and new interaction parameters concerning these groups are calculated. Finally it may be concluded that the NRTL model led to the best results for the solubility prediction for pharmaceutical compounds. © Owned by the authors, published by EDP Sciences, 2013.