INVESTIGATION OF THE PERCUTANEOUS PENETRATION OF PROSTAGLANDIN E-1 AND ITS ETHYL-ESTER

The optimization of percutaneous delivery of PGE(1) and its ethyl eate r in alcoholic buffer solution through hairless mouse skin was investi gated. A reversed-phase HPLC system with a photodiode array detector w as used to differentiate the UV spectra of the penetration products. B y comparison of the UV spectrum for each chromatographic peak, the con version of PGE(1) ethyl ester to PGE(1) by enzymatic hydrolysis was fo und to be the predominant degradation pathway during the in vitro pene tration. The quantification of ethyl ester was developed based on the same principle as that for PGE(1). It was then applied to monitor the penetration of prostaglandins through hairless mouse skin from the veh icles containing various fractions of alcohol. Results demonstrated th at the alkyl group promoted the penetration mainly as a result of enha ncing the drug partitioning into the stratum corneum at its maximal th ermodynamic activity. The alcohol fraction around 20% seemed to be opt imal for the percutaneous delivery of the ethyl ester. The use of coll agen gel to carry PGE(1) ethyl ester for percutaneous application was included for comparison. The effect of adding alcohol in the collagen gel on the penetration of PGE(1) ethyl ester was found to be slightly lower than that from the same vehicle without collagen. (C) 1998 Elsev ier Science B.V. All rights reserved.