Transdermal Contraceptive Patches

Abstract

Many contraceptive methods have been developed for fertility regulation, either reversible or irreversible, in males and females. Oral contraceptives have been considered the most popular form of reversible contraception. However, they must be taken consistently, on a daily basis for 21 or 28 days of each menstrual cycle, in order to achieve the maximal outcomes of contraception. Moreover, their contraceptive efficacy has been reportedly affected by their interactions with many drug products taken concurrently for other conditions. To resolve the dilemma of daily compliance and the risk of potential interactions with drugs taken orally, several non-traditional delivery systems have been developed to permit contraceptive agents and their combinations to be administered via a non-oral route, and also at a lesser frequency of administration, so as to enhance treatment compliance, maximize therapeutic outcomes, and minimize adverse effects. One typical example is the successful development of the ethinylestradiol/norelgestromin patch for achieving contraception in females via transdermal delivery. With topical application on intact skin, each patch delivers a combination of norelgestromin and ethinylestradiol for a week. With a treatment schedule of 3 weeks with a patch on and 1 week without a patch for each menstrual cycle, the ethinylestradiol/norelgestromin patch has achieved a clinical efficacy that is considered bioequivalent to oral contraceptives (with an unintended pregnancy rate of 0.8% per woman-year for the patch versus 0.1% per woman-year for the combined oral contraceptive).Stimulated by the marketing success of the ethinylestradiol/norelgestromin transdermal contraceptive patch, and a growing recognition of the therapeutic benefits realized by delivering an orally inactive progestin via a transdermal route, other transdermal drug delivery systems (DDS), such as transdermal gels and a metered-dose transdermal spray system, have also been developed. Further transdermal contraceptive patches have also been developed. One of these is similar to the ethinylestradiol/norelgestromin patch, in that it is fabricated from an adhesive polymer matrix diffusion-controlled DDS; however, it has a two times smaller patch size (to minimize localized reactions at the application site). This was made possible by substituting norelgestromin with a more potent progestin called gestodene, that has a higher skin permeation rate. The other transdermal patch that has been developed employs a microreservoir partition-controlled delivery system, to provide dual-controlled delivery of estradiol (a natural estrogen) and levonorgestrel (another potent synthetic progestin) at constant rates (zero-order kinetics). Clinical studies have demonstrated that these two new patch systems may be attractive alternative forms of contraception, since ovulation inhibition has been achieved in all subjects who wear the transdermal patch for 3 weeks, replacing it on a weekly basis.A transdermal gel has been formulated to contain elcometrine, which has a progestational potency that is 100 times that of progesterone but is orally inactive, in an alcoholic solution. Preliminary clinical studies have indicated that suppression of ovulation was achieved in the majority of subjects receiving daily application of the transdermal gel. To address the problems associated with the dosing accuracy of the transdermal gel, due to difficulty controlling the area and size of the application site, the feasibility of delivering the transdermal gel from a metered-dose transdermal spray system is currently under evaluation by the Population Council.