Guar gum as a carrier for colon specific delivery; Influence of metronidazole and tinidazole on in vitro release of albendazole from guar gum matrix tablets

PURPOSE: The present investigation is to study the influence of metronidazo le and tinidazole on the usefulness of guar gum, a colon-specific drug carr ier based on the metabolic activity of colonic bacteria, using matrix table ts of albendazole (containing 20% of guar gum) as a model formulation. METH ODS: The matrix tablets of albendazole were subjected to in vitro drug rele ase studies in simulated colonic fluids (4% w/v of rat caecal contents) obt ained after oral treatment of rats for 7 days either with varying doses of metronidazole/tinidazole and 1 mL of 2% w/v of guar gum or with 1 mL of 2% w/v of guar gum alone (control study) after completing the dissolution stud y in 0.1 M HCl (2 h) and pH 7.4 Sorensen's phosphate buffer (3 h). RESULTS: The guar gum matrix tablets of albendazole were found degraded by colonic bacteria of rat caecal contents and released about 44% of albendazole in si mulated colonic fluids (control study) at the end of 24 h indicating the su sceptibility of the guar gum formulations to the rat caecal contents. Howev er, the release of albendazole decreased when the drug release studies were carried out in caecal contents of rats treated for 7 days with either metr onidazole (10-50 mg/kg once daily) or tinidazole (10-30 mg/kg once daily), and the release of albendazole from the matrix tablets was found to be dose dependent. The release of the drug from guar gum formulations was found to increase with a decrease in the dose of metronidazole/tinidazole administe red. The antimicrobial activity of metronidazole/tinidazole against the ana erobic bacteria of the rat's GI flora might have been inhibited to a varyin g degree depending on the dose of metronidazole/tinidazole administered. CO NCLUSIONS: The results of the study showed that concomitant administration of either metronidazole or tinidazole with guargum based colon-specific dru g delivery systems may interfere with the targeting of drugs to colon.