Experimental study reveals up to 34-fold aqueous solubility enhancement of ibuprofen using novel surface-active ionic liquids, indicating their potential as green drug solubilizers.
Key Points
To evaluate renewable (2-hydroxyethyl)amine-based surface-active ionic liquids as green solubilizing agents to improve the aqueous solubility and thermodynamic properties of ibuprofen.
Synthesized three surface-active ionic liquids: [2-HEA][Ole], [BHEA][Ole], and [THEA][Ole].
Measured equilibrium solubility of ibuprofen across temperatures from 298.15 to 313.15 K and varied ionic liquid mass fractions using the saturation shake-flask method and UV–vis spectrophotometry.
Modeled thermodynamic phase behavior using the Wilson and electrolyte nonrandom two-liquid (e-NRTL) activity coefficient models, and simulated intermolecular interactions via density functional theory (DFT) with the COSMO solvation model.
Ibuprofen aqueous solubility increased with higher ionic liquid concentrations and rising temperatures following the order [2-HEA][Ole] < [BHEA][Ole] < [THEA][Ole], with [THEA][Ole] achieving up to a 34-fold enhancement.
Thermodynamic modeling confirmed an endothermic and entropy-driven dissolution process, with the Wilson model correlating experimental data more accurately than the e-NRTL model (average relative deviations of ~0.20% vs. 5.34%).