In vitro and in vivo evaluation of terpenoid esters of indomethacin as dermal prodrugs

Indomethacin terpenoids' esters (1-4) were synthesized and assessed both in vitro and in vivo as indomethacin dermal prodrugs. Esters 1-4 showed high lipophilicity, poor water solubility, good stability in hydro-alcoholic medium (ethanol/water 1:1) and rapid enzymatic cleavage. Results from in vitro percutaneous absorption studies showed that esters 1 and 2 slightly increased the cumulative uptake of indomethacin through excised human skin compared with the parent drug. In vivo results, using methyl nicotinate (MN) induced erythema as an inflammatory model in human volunteers, showed an interesting delayed and sustained activity of ester 1 compared with the parent drugs. (C) 1997 Elsevier Science B.V.