Three different types of solubilization of thymol in Tween 80: Micelles, solutions, and emulsions- a mechanism study of micellar solubilization

Abstract The micellar solubilization process and mechanism with thymol and Tween 80 as the model drug and surfactant were studied by the tensiometric study, 1H NMR spectroscopy, 2D diffusion ordered spectroscopy (DOSY) and NOESY. First of all, changes in chemical shifts and line shapes of thymol and Tween 80 in mixed solutions compared with those in pure solutions, the co-diffusion of thymol and Tween 80 molecules, and cross peaks between them prove that thymol molecules are solubilized in Tween 80 micelles. The thymol-incorporated Tween 80 micelles forms, and its critical micellar concentration (CMC) was obtained. Almost synchronously, the independent diffusion of thymol molecules was observed. These indicate that when the CMC of thymol-incorporated Tween 80 micelles is reached, a portion of thymol molecules are solubilized in Tween 80 micellar solutions. Finally, with the continuous increase of thymol concentration, there is another resonance group of Tween 80 shown up, accompanied by turbid solutions. The independent diffusion of the new Tween 80 resonance group, and its cross peaks with thymol indicate the formation of another aggregate-emulsions, meanwhile, which are coexisted with thymol molecules solubilized in micelles and those dissolved in solutions. The solubilization of thymol in Tween 80 aqueous solutions follows the order of micelles> solutions> emulsions. Besides, different cross peak patterns suggest that solubilization sites of thymol in micelles and emulsions are different. In micelles, thymol molecules are likely to be wrapped in the folded alkane chains of Tween 80. However, in emulsions, they are possibly solubilized in the core of emulsions made of stretched hydrophobic chains. The surface tension results are consistent with the conclusions obtained from NMR studies.