Transdermal delivery of levonorgestrel. IV: Evaluation of membranes

A series of experiments were performed to evaluate the flux of levonorgestrel (LN), ethyl acetate (EtAc), and ethanol (EtOH) through excised rat skin, through a variety of synthetic membranes and through membranes supported on rat skin. Using a donor phase of EtAc:EtOH (7:3) containing excess solid LN, the flux of LN through rat skin was approximately 1.0 microgramc/cm2.h. The normalized fluxes of LN, EtAc, and EtOH through ethylene vinyl acetate (EVAc) copolymers of varying vinyl acetate (VAc) content (12 to 25%) were 1.3 to 3.1 x 10(-8), 2.6 to 6.8 x 10(-4), and 4.8 to 9.9 x 10(-5) g.cm/cm2.h, respectively. Permeability experiments were also performed with the EVAc membranes supported on rat skin. By selecting the VAc content and thickness of the EVAc membranes, it was possible to control the delivery of enhancer (EtAc:EtOH) through rat skin (membrane-rate control) or to let the skin control the overall delivery of enhancer.