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 ([C 4 mim] + ) based ionic liquids (ILs) with different anions (Cl, BF 4 , CF 3 SO 3 , PF 6 , NTf 2 and OS) on micelles of d-α-tocopheryl polyethylene glycol succinate (TPGS). A distinct series of ILs possessing identical anion (Cl − ) but cation [C n mim + ) 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 (C 4 mim), independent of concentration and type counter anions (Cl − , BF 4 − , CF 3 SO 3 − , PF 6 − and NTf 2 − ), and ( b ) steep increase in cloud point, and reduction in size and aggregation number of micelles upon increasing the alkyl chain (C 8 and C 10 ) with concentration (10 to 200 mM). Our observations suggest that C 4 (except C 4 mimOS) and C 6 mim ILs acted as solvent whereas C 8mim Cl , C 10mim Cl and C 4 mimOS served as secondary surfactants, thus promoting mixed micelle formation. For surface active ILs (C 8 and C 10 ), SANS parameters showed a progressive reduction in micelle size and increase in number density. Importantly, TPGS-C 10 mimCl 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.