Abstract:

The aim of the investigation was to assess the effect of oral 5-flourouracil pre-treatment on the in vitro drug release from a model colon-targeted guar gum matrix tablet formulation of mebendazole. Guar gum matrix tablets of mebendazole were subjected to in vitro drug release studies in simulated colonic fluids (4%w/v of rat caecal contents) obtained after oral treatment of rats either with varying doses of 5-fluorouracil (0.3, 1, 3 or 6 mg kg^-1 once daily for 5 days) and 1 ml of 2%w/v of guar gum dispersion or with 1 ml of 2%w/v of guar gum dispersion alone (control study) after completing the dissolution study in 0.1 M HCl (2 h) and pH 7.4 Sorensen’s phosphate buffer (3 h). The mebendazole tablets disintegrated in the presence of simulated colonic fluids releasing about 97% of the drug (control study) at the end of 24 h. However, the release of mebendazole decreased when drug release studies were carried out in caecal contents of rats pretreated with both 5-fluorouracil and guar gum dispersion. The release of mebendazole significantly decreased when pretreated with 1, 3 or 6 mg kg^-1 dose levels of 5-fluorouracil (oral). However, there was no significant effect of 5- fluorouracil on the release of mebendazole when pretreated at a dose level of 0.3 mg kg^-1 (oral). It was concluded that multiple administration of 5-fluorouracil at a dose of 0.3 mg kg^-1 did not affect the drug release from colon-targeted guar gum matrix tablets.