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

Abstract

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 (ME0) with a large steady-state simultaneous permeation rate (Js) 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 ME0, which showed a statistical increase in Js and skin retention through the abdominal skin of guinea pigs. The optimized formulation had desirable characterization, good stability and negligible irritation. The large Js 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.