RATE CONTROL IN TRANSDERMAL BETA-ESTRADIOL RESERVOIR MEMBRANE SYSTEMS- THE ROLE OF MEMBRANE AND ADHESIVE LAYER

Purpose, The aim of our study was to clarify the kinetic performance o f a membrane controlled reservoir system (MCRS) for beta-estradiol (E- 2) under in vitro conditions by determination of the role of membrane and adhesive layer on E-2 flux control. Methods. E-2 and ethanol fluxe s across EVA membrane or membrane coated with adhesive from saturated solutions in defined ethanol/PBS mixtures were measured in the symmetr ic and asymmetric configuration. Physicochemical parameters of the EVA membrane were determined. Results. The E-2 flux across the 9% EVA mem brane steadily increased with increasing ethanol concentrations in bot h configurations, due to enhanced uptake of E-2 by the polymer and inc reasing membrane diffusivity. Permeation across the EVA membrane coate d with an adhesive layer in the symmetric and asymmetric configuration increased up to maximum values of 0.80 +/- 0.14 mu g x cm(-2) x h(-1) and 0.37 +/- 0.02 mu g x cm(-2) x h(-1). respectively, at 62.5% (v/v) ethanol. The fluxes then decreased with further increase in the volum e fraction of ethanol due to a dramatically reduced permeability of th e adhesive layer. For the asymmetric case, a linear dependence of E-2 on ethanol fluxes was observed. Conclusions. The E-2 flux from MCRS is strictly dependent on reservoir ethanol concentrations, whereas the a dhesive layer represents the rate controlling barrier at high ethanol levels (>70% v/v).