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Permeabilities of rebamipide via rat intestinal membranes and its colon specific delivery using chitosan capsule as a carrier

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World Journal of Gastroenterology 2008年第31期14卷 4928-4937页

作者： Bei-Bei Huang Guo-Feng Li Jing-Hui Luo Lian Duan Kishimoto Nobuaki Yamamoto Akira Department of pharmacy Nanfang Hospital Southern Medical University Guangzhou 510515 Guangdong Province China Department of Biopharmaceutics Kyoto Pharmaceutical University Misasagi Yamashinaku Kyoto 6078414 Japan

AIM: To investigate the permeability characteristics of rebamipide across intestinal mucosa, and examine the effects of some absorption enhancers on the permeability across the colonic tissue. Another purpose is to demonstrate the colon-specific delivery of rebamipide with or without absorption enhancers using chitosan capsule as a carrier. METHODS: The permeability of rebamipide was evaluated using an in vitro diffusion chamber system, and the effects of some absorption enhancers on the permeability via colon were further investigated. The release of rebamipide from chitosan or gelatin capsule was studied by Japan Pharmacopoeia rotating basket method. The colonic and plasma concentrations were analyzed by high performance liquid chromatography (HPLC) to evaluate colon-targeting action after oral administration of various dosage forms, and rebamipide with absorption enhancers in chitosan dosage forms. RESULTS: The permeability of rebamipide across the jejunal or ileal membranes was higher than the colonic membranes. Both sodium laurate (C12) and labrasol signifi cantly increased permeability across the colon membranes. On the other hand, the release of rebamipide from chitosan capsule was less than 10%totally within 6 h. The area under concentration-time profile of drug in the colon mucosa using chitosan capsules (AUCLI, 1 6011.2 ng·h/g) was 2.5 times and 4.4 times greater than using gelatin capsules and CMC suspension, respectively. Meanwhile, the area under concentration-time profile of drug in the plasma (AUCPL) was 1016.0 ng·h/mL for chitosan capsule, 1887.9 ng·h/mL for CMC suspension p and 2163.5 ng·h/mL for gelatin capsule. Overall, both AUCLI and AUCPL were increased when C12 was co-administrated, but the increase of AUCLI was much greater; the drug delivery index (DDI) was more than 1 compared with simple chitosan capsule group. CONCLUSION: There was a regional difference in the permeability of Rabamipide across the jejunum, ileum and the colon, and passive

关键词： Rebamipide Diffusion chamber Permeability Sodium laurate chitosan capsule Colon-specific delivery

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