In vitro evaluations of transdermal levonorgestrel.

Abstract

Transdermal delivery systems were prepared and evaluated for their ability to co-deliver the contraceptive agent levonorgestrel and the penetration enhancer ethyl acetate across hairless guinea pig, hairless mouse, and rat skin. The 24 hr devices were prepared with membranes composed of ethylene vinyl acetate [EVAc, 7.5% vinyl acetate (VAc) content] copolymers, and blends of EVAc (7.5% VAc content) and poly(methyl methacrylate) or poly(ethyl methacrylate). The reservoir phase (levonorgestrel-saturated ethyl acetate gelled with 2 wt% hydroxypropyl cellulose) was also evaluated for drug and solvent delivery with each of the rodent skins. Devices were also tested in which levonorgestrel was suspended in the adhesive. The results indicate that all the devices deliver levonorgestrel and the enhancer at about the same rate regardless of the skin type. It appears that the flux of LN follows the flux of EtAc until the devices are nearly depleted of EtAc, when delivery of LN remains relatively high.