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World J Gastroenterol. Aug 21, 2008; 14(31): 4928-4937
Published online Aug 21, 2008. doi: 10.3748/wjg.14.4928
Permeabilities of rebamipide via rat intestinal membranes and its colon specific delivery using chitosan capsule as a carrier
Bei-Bei Huang, Guo-Feng Li, Jing-Hui Luo, Lian Duan, Kishimoto Nobuaki, Yamamoto Akira
Bei-Bei Huang, Guo-Feng Li, Jing-Hui Luo, Lian Duan, Department of pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Kishimoto Nobuaki, Yamamoto Akira, Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashinaku, Kyoto 6078414, Japan
Author contributions: Huang BB, Li GF contributed equally to this work; Li GF, Nobuaki K and Akira Y designed research; Huang BB, Li GF, Luo JH and Duan L performed research; Huang BB, Luo JH, Duan L analyzed data; and Huang BB and Li GF wrote the paper.
Supported by Research Funding of Medical Association of Japanese-Chinese, Japan
Correspondence to: Guo-Feng Li, Department of Pharmacy, Nanfang Hospital, Southern Medical University, 1838 Guangzhou AVE(N), Guangzhou 510515, Guangdong Province, China. lgfnf@fimmu.com
Telephone: +86-20-62787236 Fax: +86-20-87701797
Received: April 18, 2008
Revised: June 30, 2008
Accepted: July 7, 2008
Published online: August 21, 2008
Abstract

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 significantly 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 Rebamipide across the jejunum, ileum and the colon, and passive diffusion seems to be one of the major transport mechanisms of rebamipide. Absorption enhancers can increase the permeability of rebamipide across the colon tissue significantly. In addition, chitosan capsule may be a useful carrier to deliver rebamipide to the colon specifically and the co-administration of C12 with rebamipide may also be very useful in local treatment.

Keywords: Rebamipide; Diffusion chamber; Permeability; Sodium laurate; Chitosan capsule; Colon-specific delivery