Journal of Controlled Release 2002-02-19

Percutaneous penetration and skin metabolism of ethylsalicylate-containing agent, TU-2100: in-vitro and in-vivo evaluation in guinea pigs.

Amnon C Sintov, Clara Behar-Canetti, Yeshayahu Friedman, Dov Tamarkin

Index: J. Control. Release 79(1-3) , 113-22, (2002)

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Abstract

The aim of this study was to investigate the percutaneous penetration and dermal metabolism of a new potential anti-acne prodrug--TU-2100 [bis(o-carboxyphenyl ethyl ester)nonanedioate] in guinea pigs. The fluxes of this agent through excised skin after applications of TU-2100 gels at 3 and 10% concentrations were similar. However, after 24 h from the time of drug application, the total amounts of permeated TU-2100 into the skin compartment and through the skin into the receiver were 271.7 (+/-30.7 S.E.) microg/cm(2) from the 3% gel and 779.4.0 (+/-98.5 S.E.) microg/cm(2) from the 10% gel, demonstrating a relatively high skin accumulation. Higher degradation of TU-2100 to ethylsalicylate occurred after application of drug at 10% concentration than after the application of 3% gel. In contrast, the fraction of permeated drug metabolized was twofold higher after the 3% gel application than after the 10% gel (F(m)=20 vs. 10.5 mole %). Since F(m) is reversibly related to the total permeating drug, the obtained values actually reflect the significant difference in TU-2100 permeation from the 3% (271.7 microg) and the 10% (779.4 microg) gels. An in vivo--in vitro comparison revealed similar drug accumulations in the skin after application of both 3 and 10% gels, however, skin metabolism was found to be significantly higher in vivo than in vitro.