Ester Prodrugs of Flurbiprofen: Synthesis, Plasma Hydrolysis and Gastrointestinal Toxicity.

Nine alkyl ester prodrugs of flurbiprofen have been synthesized with an aim to reduce it’s gastrointestinal side-effects. The synthesized prodrugs have been subjected to plasma hydrolysis and gastrointestinal toxicity studies. The chemical structures of the prodrugs have been varied in terms of lipophilicity and reactivity towards hydrolysis. The plasma hydrolysis studies indicate that methyl and propyl prodrugs of flurbiprofen undergo faster hydrolysis as compared to the remaining ester prodrugs. Reduction of ulcer index in rats indicate that n-propyl, iso-propyl, benzyl and cyclopentyl prodrugs of flurbiprofen are significantly (p< 0.05) less irritating to the gastric mucosa as compared to the parent drug, i.e., flurbiprofen.