title: Synthesis and stability of two indomethacin prodrugs.
abstract: The purpose of this study was to synthesize and study the in vitro enzymatic and non-enzymatic hydrolysis of indomethacin-TEG ester and amide prodrugs. It was found that the ester conjugate 10 was comparatively stable between pH 3 and 6 (half-life>90h), with a half-life equal to 5.2h in 80% buffered plasma. In contrast, the amide conjugate 12 appeared to be stable over the entire pH range studied with the only observed degradation being cleavage of the indolic N-4-chlorobenzoyl moiety.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0082, USA.
authors.forename: Shyamala
authors.initials: S
authors.lastname: Chandrasekaran
authors.forename: Abeer M
authors.initials: AM
authors.lastname: Al-Ghananeem
authors.forename: Robert M
authors.initials: RM
authors.lastname: Riggs
authors.forename: Peter A
authors.initials: PA
authors.lastname: Crooks
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000138:chemical synthesis* / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011355:Prodrugs; D007213:Indomethacin