In-vitro and In-vivo Pharmacokinetic Evaluation of Guar Gum-Eudragit® S100 Based Colon-targeted Spheroids of Sulfasalazine Co-administered with Probiotics

Background: Polysaccharide based delivery systems have been successfully used to target drugs to colon. In some recent reports, the superiority of concomitant administration of probiotics with such systems has been established. However, the pharmacokinetics of such symbiotic therapy remain unexplored hitherto.

Methods: This study deciphers the pharmacokinetic parameters of guar gum based colon targeted spheroids of sulfasalazine with co-administration of probiotics in experimental rats. Thirty rats were divided into five groups using Latin square design. These were subjected to treatment with delayed release formulation, uncoated spheroids, coated spheroid and coated spheroids along with probiotics.

Results: In case of delayed release formulation, negligible presence of sulfasalazine in plasma was observed in first 2h, followed by significant increase in sulfasalazine concentration after 3h. Higher plasma concentrations of sulfasalazine were detected for uncoated spheroids with and without probiotics. Negligible release of drug upto 5h and delayed Tmax in case of guar-gum coated sulfasalazine spheroids with or without probiotics clearly indicated successful formulation of colon targeted spheroids. Further, for coated spheroids (both with and without probiotics), the value of Tmax is found to be significantly higher than those with the other treatments.

Conclusion: Colon targeted spheroids were therefore, found to reduce absorption of drug which, in turn, is expected to reduce the side effects as only local action in colon is required for treatment of colitis. This is the first report on pharmacokinetic study of a colon targeted delivery system co-administered with probiotics.