Optimization of Preparation Conditions for Quercetin Nanoemulsions Using Response Surface Methodology

Response surface methodology was used to optimize the conditions for quercetin (QT) nanoemulsion preparations. The parameters to produce stable coarse emulsion formulations, which contain limonene oil, emulsifiers consisting of a Tween 80 and Span 20 mixture (1:1 weight ratio), and a water phase, using high-speed homogenization were identified by using the pseudoternary phase diagram. Subsequently, QT loading was kept constant (0.25%, w/w), and the effects of the oil (10–20%, w/w) and emulsifier (5–15%, w/w) concentrations as well as the homogenization pressure (52–187 MPa) on the particle sizes and emulsion stability were investigated. Experimental data could be adequately fit into a second-order polynomial model with a multiple regression coefficient (R2) of 0.9171 for the particle size. R2 values were found to be 0.8545 for the droplet growth ratio during storage and 0.7795 for QT stability. According to the model, major factors affecting particle sizes include the pressure, emulsifier and oil concentrations, and interaction between pressure and oil concentration. The pressure, oil concentration, and interaction terms between the emulsifier and oil concentrations as well as between the pressure and emulsifier concentration had a significant impact on the droplet growth ratio. Regarding the quercetin stability in nanoemulsions, only the oil concentration and interaction term between the oil and emulsifier concentrations had a significant effect. Optimum formulation and conditions for minimum particle size and the highest stability were found at 13% mixed emulsifiers, 17% oil content, and 70 MPa homogenization pressure. This study also suggested that the loading of QT in nanoemulsions could significantly affect the particle sizes and the stability of emulsions depending on the oil:emulsifier ratio in the system.