Patricia S. Campbell

A new transdermal delivery system for estradiol

Abstract The successful introduction of nitroglycerin transdermal delivery systems for the prophylactic treatment of angina pectoris has spawned an explosion of interest in this route of drug delivery in the field of pharmaceutics. Since that time, we have gained a great deal more knowledge concerning the design of membrane controlled delivery systems. This route of administration has been proposed and investigated in a number of disease states using several drugs. We would like to report our experience in investigating the transdermal route for long term treatment of postmenopausal symptoms using estradiol replacement therapy. The rationale for the development of a transdermal estradiol system is associated with the metabolic and pharmacological effects of orally administered estrogen replacement in post-menopausal women. Because estradiol is metabolized almost completely on first pass through the liver, orally administered estrogens result in nonphysiologic levels of the estrogenic metabolites of the natural ovarian hormone. Transdermal delivery of estradiol successfully by-passes the first pass effect and results in a more normal estrogen blood profile. The results of several biopharmaceutics studies demonstrate the characteristics of the membrane controlled delivery system which was designed around pharmacologic principles. In addition, a number of clinical trials have shown that total required doses of estradiol provided transdermally are only a fraction of those required by the oral route. We will also discuss problems associated with adequately defining total drug input from transdermal devices when working in these very small dosing ranges.