The high water solubility of inclusion complex of taxifolin-γ-CD prepared and characterized by the emulsion solvent evaporation and the freeze drying combination method

Abstract

This study selected γ-cyclodextrin (γ-CD) as the inclusion material and prepared inclusion complex of taxifolin-γ-CD by the emulsion solvent evaporation and the freeze drying combination method to achieve the improvement of the solubility and oral bioavailability of taxifolin. We selected ethyl acetate as the oil phase, deionized water as the water phase. The taxifolin emulsion was prepared using adjustable speed homogenate machine in the process of this experiment, whose particle size was related to the concentration of taxifolin solution, the volume ratio of water phase to oil phase, the speed and time of homogenate. We knew through the single-factor test that, the optimum conditions were: the concentration of taxifolin solution was 40mg/ml, the volume ratio of water phase to oil phase was 1.5, the speed of homogenate was 5000rpm, the homogenate time was 11min. Taxifolin emulsion with a MPS of 142.5nm was obtained under the optimum conditions, then the high-concentration taxifolin solution (3mg/ml) was obtained by the rotary evaporation process. Finally, the inclusion complex of taxifolin-γ-CD was prepared by vacuum freeze-dry. The characteristics of the inclusion complex of taxifolin-γ-CD were analyzed using SEM, FTIR, XRD, DSC, and TG. The FTIR results analyzed the interaction of taxifolin and γ-CD and determined the molecular structure of the inclusion complex of taxifolin-γ-CD. The analysis results of XRD, DSC and TG indicated that the inclusion complex of taxifolin-γ-CD was obtained and showed significantly different characteristics with taxifolin. In addition, dissolving capability test, antioxidant capacity test, solvent residue test were also carried out. The experimental datas showed that the solubility of inclusion complex of taxifolin-γ-CD at 25°C and 37°C were about 18.5 times and 19.8 times of raw taxifolin, the dissolution rate of inclusion complex of taxifolin-γ-CD were about 2.84 times of raw taxifolin, the bioavailability of inclusion complex of taxifolin-γ-CD increased 3.72 times compared with raw taxifolin, and the antioxidant capacity of inclusion complex of taxifolin-γ-CD was also superior to raw taxifolin. Furthermore, the amounts of residual solvent of the inclusion complex of taxifolin-γ-CD were suitable for pharmaceutical use. These results suggested that inclusion complex of taxifolin-γ-CD may have potential value to become a new oral taxifolin formulation with high solubility.