Effect of co-administration of probiotics with guar gum, pectin and eudragit S100 based colon targeted mini tablets containing 5-Fluorouracil for site specific release

Oral colon targeted mini-tablets containing 5-Fluorouracil (5-FU) were developed by using guar gum, pectin and Eudragit S100. Probiotics were co-administered to constantly replenish the gut microflora of colon that gets damaged due to pathophysiology of cancer and side effect of 5-FU. Replacement of microbial count ensures that the polysachharide used for sustaining the drug release gets digested to release the drug, once the formulation reaches the colon. The site-specific release of coated tablets was confirmed by dissolution studies in medium containing rat caecal contents (RCC), wherein, the formulation containing Eudragit S100, pectin and guar gum in the ratio of 04:03:03 w/w, showed less than 10% drug release in initial 5 h and immediate burst release (100%) between 5th to 10th hour. The cell line studies carried for pooled dissolution samples indicated that more than 90% cells were viable in all the cases till 5th hour. Significant (p < 0.05) decline in cellular viability was observed in case of coated mini tablets as compared to un-coated one. The pharmacokinetic studies showed a lower as well as delayed plasma concentration in the coated formulations endorsing the original hypothesis of reduction in drug exposure of the non-target sites.