Synthesis and in vitro kinetic study of novel mutual azo prodrug for inflammatory bowel disease
Iraqi Journal of Pharmacy,
2011, Volume 11, Issue 2, Pages 1-11
AbstractBackground: Inflammatory bowel disease (IBD) refers to idiopathic inflammatory
diseases of the intestine, principally ulcerative colitis and Crohn’s disease. IBD is
characterized by chronic inflammation in the mucosal membrane of large intestine. 5-
ASA is the gold standard for the treatment of IBD and when searched for a better 5-
ASA prodrug, a novel mutual azo prodrug was designed and synthesized.
Methods: A mutual prodrug was synthesized by coupling p-phenetidine with
salicylic acid. The stability of this prodrug in HCl buffer, in phosphate buffer and in
rat fecal matter were monitored.
Results: The chemical structure of mutual prodrug was characterized by physical and
spectroscopic techniques using FTIR, UV/Visible, 1H-NMR and 13C-NMR spectra. In
vitro kinetic studies in HCl buffer (pH 1.2) showed negligible release of 5-ASA and
p-phenetidine, whereas in phosphate buffer (pH 7.4) only (22.04 %) release was
observed over a period of (6 hr.). In rat fecal matter, the hydrolysis of mutual prodrug
was almost complete (77.96 %), with a half-life of 182.67 min, following zero order
Conclusion: The mutual prodrug was split in colon by the action of bacterial
azoreductase into 5-ASA and p-phenetidine that constitute two anti-inflammatory
compounds with different mechanisms of action. Therefore, this mutual prodrug is a
promising colon specific prodrug for IBD and worthy of further study.
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