Comparison of the transdermal delivery of estradiol from two gel formulations

Abstract

Objective: Conventional oral oestrogen replacement therapy can relieve postmenopausal symptoms but is associated with undesirable side-effects which can be minimised by avoiding the fluctuating hormonal blood levels resulting from oral therapy and eliminating hepatic first-pass metabolism by the use of the transdermal route. The two commercially available transdermal gel formulations differ in composition and application recommendations. Sandrena Gel contains 0.1% (w/w) and Oestrogel 0.06% (w/w) estradiol and recommended dosages are 0.5-1.5 g over 200-400 cm2 (Sandrena Gel) and 2.5 g gel over 720 cm2 (Oestrogel). In transdermal therapy the formulation composition may have a significant effect on drug delivery and we have therefore compared the permeation of estradiol from these formulations across human skin in vitro.

Methods: The in vitro percutaneous penetration of estradiol from the formulations through epidermal membranes prepared from excised female human thing skin was assessed over a 24 h period using static type Franz diffusion cells.

Results: Permeation of the active was similar from each formulation representing (at 24 h) 18.2 +/- 3.5% of the applied dose from Sandrena Gel and 17.4 +/- 4.8% of the applied dose from Oestrogel. These percentages equate to cumulative skin permeations of 0.65 +/- 0.15 microgram/cm2 and 0.45 +/- 0.15 microgram/cm2 respectively.

Conclusion: The results suggest that the two formulations are bioequivalent at the recommended dose levels.