Abstract:
The purpose of this research was to develop and optimize a self-microemulsifying delivery system (SMEDS) to improve dissolution rate of poor soluble compound AST by mixture experimental design. The solubility of AST was analyzed with various excipients so that the appropriate oil, surfactant, and cosurfactant were figured out. Through the findings about the microemulsion existence area, the pseudoternary phase diagrams were constructed for selecting the optimum combination of excipients in a formulation of SMEDS. The optimized LCT-SMEDS obtained from the design space was composed of 19.59% castor oil (oil; X1), 62.34% Cremophor® RH 40 (surfactant; X2), and 18.03% Tween® 80 (cosurfactant; X3) as independent variables, which resulted in a droplet size of 20.71 nm (Y1), PDI of 0.28 (Y2), zeta potential of -9.07 mV (Y3), 97.87% active ingredient content (Y4), and 98.38% transmittance (Y5) as response factors. The optimized MCT-SMEDS consisted of 12.39% MCT (oil; X1), 44.98% Cremophor® RH 40 (surfactant; X2), and 44.59% Tween® 80 (cosurfactant; X3) as independent variables, which resulted in a droplet size of 22.02 nm (Y1), PDI of 0.17 (Y2), zeta potential of -10.69 mV (Y3), 98.72% transmittance (Y4), and 97.09% active ingredient content (Y5) as response factors. The desirability function values of LCT-SMEDS and MCT-SMEDS were 0.8074 and 0.7949, respectively, indicating the reliability and accuracy of optimization. In addition, good agreement was found between the model prediction and experimental values of Y1, Y2, Y3, Y4, and Y5. Optimized formulations of LCT-SMEDS and MCT-SMEDS were characterized by visual observation, self-emulsification time, refractive index, transmission electron microscopy (TEM), freeze-thaw stability studies showing rapid microemulsion with good physicochemical properties and stability. The dissolution of the optimized LCT-SMEDS and MCT-SMEDS was pH-independent and reached over 90% within 4 hrs in all the media tested. As stated in the results, the significant improvements of SMEDS formulations were found in dissolution profiles of AST, compared to a marketed preparation and raw AST. Thus, we suggested that SMEDS formulation using the experimental design method might be a promising way to improve the dissolution of poorly water-soluble substance astaxanthin.
