Transdermal delivery of levonorgestrel. VII. In vivo studies.

This paper describes the results of transdermal experiments performed in vivo using devices designed for delivery of levonorgestrel. To help evaluate the performance of the transdermal devices on rabbits, a constant infusion experiment was performed using osmotic pumps. Reservoir-type transdermal devices were prepared and tested on rabbits for their ability to deliver 30 to 35 micrograms/d of levonorgestrel. Ethyl acetate and ethanol (0.7:0.3) or neat ethyl acetate were used as permeation enhancers. The results indicated that for rabbits, a rate-limiting membrane was required to control the delivery of enhancer(s) to the skin so that constant plasma levels could be maintained. The devices induced mild erythema and very mild edema over the 24-hour exposure period. The potential use of such a transdermal delivery system in humans is discussed.