Non-electrostatic energies as a metric for prediction of deferasirox solubility in binary solvent mixtures: Polarized Continuum Model tactic

Abstract

The aim of this work is to enhance deferasirox (DFX) solubility by employing the co-solvency approach. Drug solubility was studied in six different binary solvent mixtures including acetone (1) + water, acetone (1) + methanol, acetone (1) + acetonitrile, glycerol (1) + methanol, glycerol (1) + ethanol, glycerol (1) + water at 298.15 ± 0.05 K. Molecular modeling is employed to study the solvent-solvent interactions involved in the co-solvency data using the density functional theory and polarizable Continuum Model (DFT/PCM). The accuracy of the DFT/PCM theory is evaluated by comparison of its prediction values with the experimental solubility data. These results lead to the conclusion that, for acetone + water, acetone + methanol, acetonitrile + acetone and water + glycerol systems non-electrostatic effects are more important in solvent-solvent interactions. While for other solvent systems electrostatic energies are dominant. This work constitutes a major advance in the application of non-electrostatic energiesin DFT/PCM calculation and prediction of drug solubility pattern in some binary solvent mixtures. Semi-empirical models are used to determine the predictability power of the experimental co-solvency data. The combined nearly ideal binary solvent/Redlich-Kister (CNIBS/R-K) and the modified Wilson models were able to predict the experimental solubility data with MRD value of less than 35%.