This research aims to formulate and to optimize a nanoemulsion-based formulation containing fullerene, an antioxidant, stabilized by a low amount of mixed surfactants using high shear and the ultrasonic emulsification method for transdermal delivery. Process parameters optimization of fullerene nanoemulsions was done by employing response surface methodology, which involved statistical multivariate analysis. Optimization of independent variables was investigated using experimental design based on Box-Behnken design and central composite rotatable design. An investigation on the effect of the homogenization rate (4,000-5,000 rpm), sonication amplitude (20%-60%), and sonication time (30-150 seconds) on the particle size, ζ-potential, and viscosity of the colloidal systems was conducted. Under the optimum conditions, the central composite rotatable design model suggested the response variables for particle size, ζ-potential, and viscosity of the fullerene nanoemulsion were 152.5 nm, -52.6 mV, and 44.6 pascal seconds, respectively. In contrast, the Box-Behnken design model proposed that preparation under the optimum condition would produce nanoemulsion with particle size, ζ-potential, and viscosity of 148.5 nm, -55.2 mV, and 39.9 pascal seconds, respectively. The suggested process parameters to obtain optimum formulation by both models yielded actual response values similar to the predicted values with residual standard error of <2%. The optimum formulation showed more elastic and solid-like characteristics due to the existence of a large linear viscoelastic region.
Response surface methodology (RSM) was utilized to investigate the influence of the main emulsion composition; mixture of palm and medium-chain triglyceride (MCT) oil (6%-12% w/w), lecithin (1%-3% w/w), and Cremophor EL (0.5%-1.5% w/w) as well as the preparation method; addition rate (2-20 mL/min), on the physicochemical properties of palm-based nanoemulsions. The response variables were the three main emulsion properties; particle size, zeta potential and polydispersity index. Optimization of the four independent variables was carried out to obtain an optimum level palm-based nanoemulsion with desirable characteristics. The response surface analysis showed that the variation in the three responses could be depicted as a quadratic function of the main composition of the emulsion and the preparation method. The experimental data could be fitted sufficiently well into a second-order polynomial model. The optimized formulation was stable for six months at 4 °C.