Effect of Novel Surface-Active Ionic Liquids Based on 2-Hydroxyethylammonium Oleate on the Solubility and Thermodynamic Properties of Drug Ibuprofen

Abstract

Ibuprofen (IBU), a BCS Class II drug, poses significant challenges in pharmaceutical formulation due to its poor aqueous solubility and low bioavailability. In this study, renewable surface-active ionic liquids (SAILs) based on (2-hydroxyethyl)amine were investigated as green solubilizing agents for enhancing the aqueous solubility of IBU. Three SAILs, (2-hydroxyethyl)ammonium oleate ([2-HEA][Ole]), bis(2-hydroxyethyl)ammonium oleate ([BHEA][Ole]), and tris(2-hydroxyethyl)ammonium oleate ([THEA][Ole]), were synthesized. The equilibrium solubility was determined in aqueous SAIL solutions at various SAIL mass fractions and temperatures (298.15–313.15 K) using the saturation shake-flask method, followed by UV–vis spectrophotometry. The experimental data were correlated using the Wilson and electrolyte nonrandom two-liquid (e-NRTL) activity coefficient models. Density functional theory (DFT) calculations with the DMol³ module and COSMO solvation model were performed to investigate intermolecular interactions. The results show IBU solubility increased with increasing SAIL concentration and temperature, indicating an endothermic and entropy-driven dissolution process. Solubility followed the order [2-HEA][Ole] < [BHEA][Ole] < [THEA][Ole], with [THEA][Ole] providing up to a 34-fold enhancement. The Wilson model correlated the experimental data more accurately than the e-NRTL model, with average relative deviations of approximately 0.20% and 5.34%, respectively.