In vitro evaluation and pharmacokinetics in dogs of guar gum and Eudragit FS30D-coated colon-targeted pellets of indomethacin.
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 Tmax and Tlag was observed for uncoated pellets. The Tmax and Tlag of Eudragit FS30D-coated pellets were postponed to about 2.5 and 1 h, respectively. After a further guar gum coating, Tlag 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.
Ji
Chongmin
C
Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 200032, P. R. China.
Xu
Huinan
H
Wu
Wei
W
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003106:Colon / Q000378:metabolism*; D004285:Dogs; D004337:Drug Carriers; D004353:Drug Evaluation, Preclinical; D005685:Galactans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007213:Indomethacin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008351:Mannans; D008855:Microscopy, Electron, Scanning; D053149:Plant Gums; D011109:Polymethacrylic Acids
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D005685:Galactans; D008351:Mannans; D053149:Plant Gums; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; C007894:guar gum; D007213:Indomethacin