Comparison of the transdermal delivery of estradiol from two gel formulations

• Published in: Maturitas 1998-06, Vol.29 (2), p.189-195
• Main Authors: Walters, Kenneth A, Brain, Keith R, Green, Darren M, James, Valerie J, Watkinson, Adam C, Sands, Robert H
• Format: Article
• Language: English
• Subjects: Administration, Cutaneous; Biological and medical sciences; Estradiol; Estradiol - administration & dosage; Estradiol - pharmacokinetics; Estrogen Replacement Therapy; Female; Gels; Hormone replacement therapy; Hormones. Endocrine system; Humans; In Vitro Techniques; Medical sciences; Menopause; Pharmacology. Drug treatments; Skin Absorption; Transdermal drug delivery
• ISSN: 0378-5122; 1873-4111
• DOI: 10.1016/S0378-5122(98)00009-7

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 cm 2 (Sandrena Gel) and 2.5 g gel over 720 cm 2 (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 thigh 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 μg/cm 2 and 0.45±0.15 μg/cm 2 respectively. Conclusion: The results suggest that the two formulations are bioequivalent at the recommended dose levels.