Flurbiprofen- and suprofen-dextran conjugates: Synthesis, characterization and biological evaluation

Abstract

Purpose: To synthesize and characterize the dextran conjugates of suprofen and flurbiprofen, and also evaluate their biological activities. Methods: Suprofen and flurbiprofen were individually reacted with carbonyldiimidazole to form acylimidazole, which, in turn, was reacted with the dextran of varying molecular weight (40 000, 60 000, and 110 000) to form drug-dextran conjugates. The structures of the synthesized dextran conjugates were confirmed by IR and NMR spectroscopy. In vitro hydrolysis of the conjugates were studied in buffer solutions (pH 7.4 and 9.0) and 80% human plasma (pH 7.4). The analgesic and antipyretic activities, as well as the ulcerogenic index of the conjugates were also evaluated in albino rats. Results: The mean degree of substitution of flurbiprofen and suprofen was between 8.0 to 9.5 % and 7.5 to 9.0 %, respectively. In vitro hydrolysis studies on the conjugates indicate faster hydrolysis at pH 9.0 than in pH 7.4 buffer solution and 80% human plasma (pH 7.4) with the process following First order kinetics. The analgesic activity of flurbiprofen-dextran conjugate (FD-110) suprofen-dextran conjugate (SD-110) was 64.23 and 41.50% which compare well with those of their parent drugs-flurbiprofen (72.60%) and suprofen (44.30%). Similar findings were made in respect of the antipyretic activity. Both flurbiprofen and suprofen showed deep ulceration, swelling and high intensity perforation in the gastric mucosa after seven days administration of flurbiprofen and suprofen with the ulcerogenic indices of 29.69 and 31.0 respectively, cpmpare with 5.88 and 6.06 for FD-110 and SD-110, respectively. Conclusion: Dextran can be employed as a pro-moiety or carrier for the delivery of flurbiprofen and suprofen and showed comparable analgesic and antipyretic activities with the parent drugs but with lower ulcerogenic indices.