Open AccessSynthesis and hydrolytic behaviour of 2‐mercaptoethyl ibuprofenate–polyethylene glycol conjugate as a novel transdermal prodrug
Author(s) -
Davaran Soodabeh,
Rashidi Mohammad R.,
Hashemi Mahdi
Publication year - 2003
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1211/002235702900
Subject(s) - prodrug , hydrolysis , transdermal , chemistry , polyethylene glycol , ibuprofen , conjugate , polymer , organic chemistry , chromatography , pharmacology , biochemistry , medicine , mathematical analysis , mathematics
Thiolated derivatives of ibuprofen and its polyethylene glycol ester were synthesized via condensation of 2‐mercaptoethyl ibuprofenate with carboxy‐terminated polyethylene glycol. The release of ibuprofen from this polymeric prodrug has been studied under conditions simulating those encountered in the skin. The polymeric prodrug of ibuprofen was found to undergo pH‐dependent hydrolysis, ranging from negligible hydrolysis at pH 4 to 23.9% hydrolysis at pH 8.5 (15% at pH 7.4) after 48 h at 37 °C. The polymer–drug conjugate was subjected to enzymatic hydrolysis in human plasma. The polymer showed considerable enzymatic hydrolysis (68% after 48 h). The results showed that the polymeric prodrug model of non‐steroidal anti‐inflammatory drugs (NSAIDs) described here can be used in topical formulations of NSAIDs. It is expected that the novel thiol derivative will have both enhanced transdermal penetration and stability to oxidation which make it a suitable candidate for transdermal formulations.