Synthesis and stability of two indomethacin prodrugs
Shyamala Chandrasekaran1, Abeer M Al-Ghananeem, Robert M Riggs
1Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0082, USA.
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.
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