In vitro skin penetration and pharmacodynamic evaluation of prostaglandin E-1 ethyl ester, a vasoactive prodrug of prostaglandin E-1, formulated into alcoholic hydrogels

Abstract

Alcoholic hydrogels containing prostaglandin E-1 ethyl ester (PGE(1)-EE), a prodrug of PGE(1) as a therapeutic agent for erectile dysfunction, were formulated. The prodrug was stable against chemical hydrolysis in aqueous solution (pH 7.4), devoid of esterase activities, but was hydrolyzed to the parent drug in rat skin homogenates within 240 min. In the rat skin penetration study for 24 h, the steady-state flux values (mu g/cm(2)/h) of PGE(1)-EE and PGE(1) from alcoholic hydrogels having 20% ethanol content were 7.6 and 1.8, respectively. PGE(1)-EE was superior to PGE(1) from a skin penetration point of view due to its increased lipophilicity. The fastest skin penetration rate was obtained for PGE(1)-EE in 20% alcoholic hydrogel together with limonene or cineole. These formulations increased the flux of PGE(1)-EE up to about 4-fold compared to control hydrogel in the absence of penetration enhancers. In the pharmacodynamic study using a cat, alcoholic hydrogel with limonene or cineole showed a significant effect in terms of increasing intracavemosal pressure compared to control hydrogel. Therefore, the transdermal alcoholic hydrogel formulation of PGE(1)-EE with limonene or cineole can be a promising transdermal delivery system to overcome inconvenience associated with frequent intracavernosal injections for the treatment of erectile dysfunction.