Comparison of the transdermal delivery of estradiol from two gel formulations.
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.


CONCLUSIONS
The results suggest that the two formulations are bioequivalent at the recommended dose levels.
Walters
K A
KA
Organon Laboratory, Cambridge, UK.
Brain
K R
KR
Green
D M
DM
James
V J
VJ
Watkinson
A C
AC
Sands
R H
RH
D000279:Administration, Cutaneous; D004958:Estradiol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015914:Estrogen Replacement Therapy; D005260:Female; D005782:Gels; D006801:Humans; D066298:In Vitro Techniques; D012869:Skin Absorption
D005782:Gels; D004958:Estradiol