10.22376/ijpbs.2019.10.1.p1-12 Volume 6 Issue 1 2015 (January - March) For reducing the gastrointestinal (GI) toxicity associated with lessThan b greaterThan flufenamic acid lessThan /b greaterThan lessThan b greaterThan ( lessThan /b greaterThan FA), its carboxylic group was masked by synthesizing its mutual prodrugs with propyphenazone by direct coupling and by using spacer technique. The structures of the synthesized mutual prodrugs (FE and FG) were confirmed by IR, lessThan sup greaterThan 1 lessThan /sup greaterThan H lessThan sub greaterThan lessThan /sub greaterThan NMR, lessThan sup greaterThan 13 lessThan /sup greaterThan C lessThan sub greaterThan lessThan /sub greaterThan NMR, mass spectroscopy and their purity were established by elemental analysis. lessThan i greaterThan In vitro lessThan /i greaterThan hydrolysis study of both prodrugs (FE & FG) in enzyme-free simulated intestinal fluid (SIF, pH 7.4) furnished 43.97% and 53.46% release of parent drug FA with a half life of 9.13 and 7.54 hours respectively, following first order kinetics. While in simulated gastric fluid (SGF, pH 1.2) they were found to be stable. Both FA prodrugs were retaining anti-inflammatory activity intact and exhibited better analgesic activity along with much reduced ulcerogenicity as compared to parent drug. However prodrug FE showed better percentage anti-inflammatory activity (61.91%) than FG (45.22%) at the end of 6 lessThan sup greaterThan th lessThan /sup greaterThan h and it also exhibited better percentage analgesic activity (76.85%) than FG (71.12%) at the end of 2 lessThan sup greaterThan nd lessThan /sup greaterThan h. Hence FE could be considered as a better candidate for prodrug among the two. MEENU PALIWAL, SUCHETA, RUCHITA, HIMANSHU, MONIKA AND SHILPA JAIN Flufenamic acid, NSAIDs, Mutual prodrug and Ulcerogenicity. 12-25