Pharmacokinetic evaluation of guar gum-based colon-targeted oral drug delivery systems of metronidazole in healthy volunteers.

Abstract

The present study was carried out to find the in vivo performance of guar gum-based colon-targeted tablets of metronidazole as compared to an immediate release tablets in human volunteers. Six healthy volunteers participated in the study and a crossover design was used. Blood samples were obtained at different time intervals and the plasma concentration of metronidazole was estimated by reverse phase HPLC. The immediate release tablets of metronidazole produced peak plasma concentration (Cmax of 2990 +/- 574.6 ng/mL) within 2.8 +/- 0.6 h. On oral administration of colon-targeted tablets, metronidazole started appearing in the plasma between 5 h and 8 h, and reached the peak concentration (Cmax of 1940.0 +/- 528.4 ng/mL) at 11.1 +/- 2.1 h (Tmax). The AUC(0-infinity) and t(1/2) of metronidazole were unaltered on administering the drug as a colon-targeted tablet indicating that the extent of absorption and elimination were not affected by targeting the drug to the colon. However, colon-targeted tablets showed delayed tmax and absorption time (ta), decreased Cmax and decreased absorption rate constant as compared to immediate release tablets. This in turn indicated that metronidazole was delivered to the colon resulting in a slow absorption of the drug and making it available for local action in the colon.