ESTRADIOL PERMEATION ACROSS HUMAN SKIN, SILASTIC AND SNAKE SKIN MEMBRANES - THE EFFECTS OF ETHANOL-WATER COSOLVENT SYSTEMS

Considerable interest in using the transdermal route for drug administ ration has strengthened the need for investigations of vehicle effects . The influence of ethanol on the in vitro transport behaviour of satu rated oestradiol (OE) solutions through excised human skin and model m embranes (silastic, human skin-silastic sandwich and snake skin) was i nvestigated over 0-90% w/w ethanol/water vehicle compositions. Human s kin showed a maximum flux of OE (1.45 +/- 0.39 mu g cm(-2) h(-1)) at e thanol vehicle contents between 40 and 60% w/w. Silastic membranes wer e used to help elucidate the mechanisms of ethanol as an enhancer. Par tition coefficients and uptake of OE by stratum corneum and silastic m embranes from the co-solvent systems were determined and the results s uggested that the enhanced permeation of OE from vehicles with ethanol concentrations up to 60% w/w was partially related to increased drug solubility in the stratum corneum. The other part was related to ethan ol effects on stratum corneum components. The decrease of OE flux from vehicles with higher ethanol concentrations was due to ethanol dehydr ation effects on the stratum corneum. This was confirmed by measuring the uptake of ethanol and water from different concentrations of ethan ol; increasing ethanol concentration in the donor produced a significa nt decrease in the stratum corneum water content. Also, when the skin hydration was controlled using the skin-silastic sandwich model, the O E flux did not significantly decrease at high ethanol concentration. E thanol actions were further investigated by measuring the permeation r ate of OE through a model animal membrane, shed snake skin. Different results were obtained than for human skin and silastic membrane. The m aximum flux of OE through dorsal snake skin appeared at higher ethanol vehicle concentration (80% w/w) when compared with human skin. Ventra l snake skin showed increasing OE flux up to 40% w/w ethanol which rem ained essentially constant up to 90% ethanol. The results obtained wit h snake skin were attributed to the lower water content of this membra ne.