IN-VITRO AND IN-VIVO EVALUATION OF TERPENOID ESTERS OF INDOMETHACIN AS DERMAL PRODRUGS

Indomethacin terpenoids' esters (1-4) were synthesized and assessed bo th in vitro and in vivo as indomethacin dermal prodrugs. Esters 1-4 sh owed high lipophilicity, poor water solubility, good stability in hydr o-alcoholic medium (ethanol/water 1:1) and rapid enzymatic cleavage. R esults from in vitro percutaneous absorption studies showed that ester s 1 and 2 slightly increased the cumulative uptake of indomethacin thr ough excised human skin compared with the parent drug. In vivo results , using methyl nicotinate (MN) induced erythema as an inflammatory mod el in human volunteers, showed an interesting delayed and sustained ac tivity of ester 1 compared with the parent drugs. (C) 1997 Elsevier Sc ience B.V.