Vehicle and enhancer effects on transdermal permeation of estradiol from gel formulations: evaluation in vitro

In continuation of a previous study dealing with the promoting effect of niaouli essential oil (NIA) on transdermal permeation of estrogens, the effect of vehicle composition on permeation of estradiol (ES) ex vivo across hairless mouse skin was investigated using a diffusion cell technique. Three types of gel vehicles possessing suitable esthetic and spreading characteristics, formulated with Carbopol1342 and containing NIA at two concentrations (1.0 and 10.0%) were tested. Promoter-free vehicles and two commercial alcohol-based gels (Gelestra and Sandrena) were used as reference. The solubility of ES in the solvent phase of the gels and the rheological properties of all formulations were also evaluated. The mean transdermal fluxes of ES at steady state from Gelestra and Sandrena were not significantly different, although Gelestra showed a shorter lag time and a greater amount of ES permeated after 30 h compared with Sandrena. In the gels under test, the presence of 1.0% NIA significantly increased the ES transdermal flux over the reference vehicles only when in association with ethanol and water. The present results may warrant further investigations on other drugs and skin models, aimed at optimizing the promoting activity of NIA, and the synergistic effect of solvents.