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

Indomethacin polyoxyethylene esters (1-5) were synthesized and assessed both in vitro and in vivo for their usefulness as indomethacin dermal prodrugs. Esters 1-5 showed good water stability and rapid enzymatic cleavage and their hydrolysis rates, both chemical and enzymatic, were not significantly affected by the lengthen of the polyoxyethylenic chain used as promoiety. Results from in vitro percutaneous absorption studies showed that only esters 4 and 5 significantly increased indomethacin cumulative amount penetrated through excised human skin compared to the parent drug. In vivo topical anti-inflammatory activity, using methyl nicotinate (MN) induced erythema as inflammation model in human volunteers, was investigated for ester 5, which showed the best in vitro results. In vivo results showed an interesting delayed and sustained activity of ester 5 compared to the parent drug.