Design, optimization and evaluation of co-surfactant free microemulsion-based hydrogel with low surfactant for...

Microemulsion is the preferred vehicle for local anesthetics; however, the toxicity and irritation associated with a quantity use of surfactants (S) and co-surfactants (CS), i.e., medium- or short-chain alcohols, restrict its commercial application. In this study, efforts have been made to enlarge the CS-free microemulsion area by mixing olive oil (OL) with α-linolenic acid (ALA) and linoleic acid (LA), and by using vitamin E succinate (VES) as an auxiliary oil. Through Box-Behnken design and the optimization of nondominated sorting genetic algorithm II, the optimal microemulsion formulation (M_E0) with a large steady-state simultaneous permeation rate (J_s) and skin retention was screened as 3.23% OL, 0.45% ALA, 1.81% LA, 0.91% VES, 13.60% S, 5% lidocaine and water. Three percent ethanol was screened as a permeability enhancer for the hydrogel of M_E0, which showed a statistical increase in J_s and skin retention through the abdominal skin of guinea pigs. The optimized formulation had desirable characterization, good stability and negligible irritation. The large J_s and skin retention were well reflected in the pinprick test, wherein intensity of anesthetic effect and duration of action were increased significantly over the commercial cream. The developed CS-free microemulsion hydrogel with low S could be a promising strategy for the topical delivery of lidocaine.