Niaouli oil as enhancer for transdermal permeation of estradiol Evaluation of gel formulations on hairless rats in vivo

In a previous study, niaouli essential oil (NIA) was found to enhance the permeation of estradiol (ES) through hairless mouse skin in vitro. In this study we evaluated in vivo, on female hairless rats, the trandermal penetration of ES from alcoholic gel-vehicles containing 1.0 or 5.0% NIA (Gel 2 and 3, respectively). One NIA-free gel (Gel 1) and a commercial formulation, Sandrena gel, were used as reference. The ES serum levels after single or multiple cutaneous application of the gel-vehicles were determined, and the in vivo data were compared with new in vitro data obtained using hairless mouse skin. Both the in vitro and the single-dosing in vivo tests demonstrated the superiority of Gel 2 over all other gels. When tested in the multiple-dosing study against Sandrena gel, Gel 2 produced a 0-96 h plasma AUC two times greater than that of the reference. The absolute bioavailability values of ES from the vehicles under investigation were also in the order Gel 2 > Gel 3 > Sandrena gel > Gel 1. This study indicates that, in the presently investigated animal species, a relatively small percentage of NIA (1.0%) in association with ethanol (57.8%) promotes transdermal penetration of ES to a greater extent than ethanol (65%) in association with propylene glycol (10.5%), the enhancers present in the commercial gel Sandrena.