Structural changes in non-ionic surfactant micelles induced by ionic liquids and application thereof for improved solubilization of quercetin

Abstract

We report the effect of concentration of 1-butyl-3-methylimidazolium ([C4mim]+) based ionic liquids (ILs) with different anions (Cl, BF4, CF3SO3, PF6, NTf2 and OS) on micelles of d-α-tocopheryl polyethylene glycol succinate (TPGS). A distinct series of ILs possessing identical anion (Cl−) but cation [Cnmim+) with increasing alkyl chain length (butyl, hexyl, octyl and decyl) was also tested. TPGS-IL mixed micelles were characterized through small angle neutron scattering (SANS).Depending upon IL-TPGS interaction, two distinct observations were recorded on clouding and aggregation of TPGS; (a) insignificant changes for ILs with short alkyl chain (C4mim), independent of concentration and type counter anions (Cl−, BF4−, CF3SO3−, PF6− and NTf2−), and (b) steep increase in cloud point, and reduction in size and aggregation number of micelles upon increasing the alkyl chain (C8 and C10) with concentration (10 to 200 mM). Our observations suggest that C4 (except C4mimOS) and C6mim ILs acted as solvent whereas C8mimCl, C10mimCl and C4mimOS served as secondary surfactants, thus promoting mixed micelle formation. For surface active ILs (C8 and C10), SANS parameters showed a progressive reduction in micelle size and increase in number density. Importantly, TPGS-C10mimCl association helped in improving the solubilization of quercetin (QCT) up to 700-fold. We speculate that high QCT solubilization resulted from the formation of small sized mixed micelles (hydrodynamic diameter ≈ 10 nm) at a high number density. Solubilization potential of TPGS-IL mixed system is practically exploitable for the development of injectable drug concentrates.