title: Synthesis and hydrolytic behaviour of 2-mercaptoethyl ibuprofenate-polyethylene glycol conjugate as a novel transdermal prodrug.
abstract: 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 degrees 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.
authors.affiliation: Drug Applied Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Soodabeh
authors.initials: S
authors.lastname: Davaran
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Rashidi
authors.forename: Mahdi
authors.initials: M
authors.lastname: Hashemi
mesh_terms: D000279:Administration, Cutaneous; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D005079:Excipients / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007052:Ibuprofen / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D011355:Prodrugs / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: C479464:2-mercaptoethylibuprofenate; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005079:Excipients; D011355:Prodrugs; D011092:Polyethylene Glycols; D007052:Ibuprofen