Transdermal penetrants estradiol

When the transdermal penetration of a drug is inadequate to achieve and maintain a plasma concentration above the minimum therapeutic concentration required to produce the desired effect, a lipophilic prodrug that will be metabolized in the epidermis to the active drug could be used in the development of a controlled-release transdermal delivery system. This approach has been applied to estradiol esters (diacetate and valerate) which are rapidly converted by esterases in the skin tissue to estradiol (Chien et al, 1985). The prodrug serves to increase the transdermal bioavailability of the active drug to which it is converted by metabolism (generally ester hydrolysis) during the percutaneous absorption process. 

Figure 8.8 Serum levels of estradiol and its major metabolite, estrone, during the continuous wearing of consecutively-applied transdermal systems (Ciba-Geigy, 0.05 mg/day) (Modified from Topical Drug Bioavailability, Bioequivalence, and Penetration (Shah, V.P. and Maibach, H.I. eds). Plenum Press, New York, 1993, pp. 17-68)...

An approach published in 2001 based on research out of the Klibanov laboratory at MIT is to use ethanol [5]. Ethanol, isopropanol, and other alcohols have long been used successfully as penetration enhancers for medical applications. Ethanol is one of the first molecules to have been used as a transdermal enhancer, because its effects are so easily and well characterized and its systemic and local toxicities are understood. It is currently contained in commercial delivery systems for estradiol [17] and other bioactive molecules. Ethanol and isopropanol have been used in a variety of studies based on their effects on drug transport. More applications can be found in the patent literature [18]. 

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