In vitro evaluation and pharmacokinetics in dogs of guar gum and Eudragit FS30D-coated colon-targeted pellets of indomethacin

Abstract

A pH- and enzyme-dependent colon-targeted multi-unit delivery system of indomethacin was developed by coating guar gum and Eudragit FS30D sequentially onto drug-loaded pellets in a fluidized bed coater. In vitro studies showed that smaller coating weight gain of guar gum resulted in reduced release lag time t₁₀ (10% release time), but favored degradation by enzymes (galactomannanase). A cumulative weight gain (CWG) of 44% provided sufficient enzymatic sensitivity and protection of the core. Under gradient pH conditions (pH = 1.2, 6.8, 7.4 and 6.5 for 2, 2, 1 and 15 h, respectively), indomethacin was released from Eudragit FS30D-coated pellets quickly after changing pH to 7.4. For guar gum/Eudragit FS30D double-coated pellets, only about 5% of the drug was released after another 1 h, showing retarding effect by guar gum coating. After changing pH to 6.5 and addition of galactomannanase, enzyme-dependent drug release was observed. Pharmacokinetic study in beagle dogs showed that fastest absorption with the smallest T_max and T_lag was observed for uncoated pellets. The T_max and T_lag of Eudragit FS30D-coated pellets were postponed to about 2.5 and 1 h, respectively. After a further guar gum coating, T_lag was further postponed to about 2.8 h, about 2 h of additional lag time on the basis of Eudragit FS30D coating. It is indicated that the guar gum/Eudragit FS30D-coated system has potential to be used to deliver drugs to the colon.

Keywords: :

• Colon-targeted drug delivery system
• pellets
• indomethacin
• guar gum
• Eudragit FS30D