RESUMEN
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, 16011.2 ng x 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 x h/mL for chitosan capsule, 1887.9 ng x h/mL for CMC suspension p and 2163.5 ng x 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 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.
Asunto(s)
Alanina/análogos & derivados , Antiulcerosos/farmacocinética , Quitosano/química , Colon/metabolismo , Portadores de Fármacos , Absorción Intestinal , Quinolonas/farmacocinética , Administración Oral , Alanina/administración & dosificación , Alanina/sangre , Alanina/química , Alanina/farmacocinética , Animales , Antiulcerosos/administración & dosificación , Antiulcerosos/sangre , Antiulcerosos/química , Cápsulas , Química Farmacéutica , Colon/efectos de los fármacos , Difusión , Gelatina/química , Glicéridos , Íleon/metabolismo , Absorción Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Yeyuno/metabolismo , Ácidos Láuricos/química , Ácidos Láuricos/farmacología , Masculino , Compuestos Orgánicos/química , Compuestos Orgánicos/farmacología , Permeabilidad , Quinolonas/administración & dosificación , Quinolonas/sangre , Quinolonas/química , Ratas , Ratas Wistar , SolubilidadRESUMEN
The objective of this study is to investigate the permeabilities of rebamipide across the jejunal, ileal and colonic membranes in rat. The permeability (Papp) of rebamipide via rat intestinal membranes at concentration of 80 micromol L(-1) was evaluated by an in vitro diffusion chamber system after the membranes were isolated from the rat intestine. And the concentration of rebamipide in the receptor was determined by HPLC. As a result, the permeability of rebamipide across the jejunal or ileal membrane was higher than that across the colonic membrane, and the permeability of rebamipide in the ileal tissue from the serosal to mucosal direction was greater than that from the mucosal to serosal direction. Therefore, there was a regional difference in the permeability of rabamipide across the jejunum, ileum and the colon in rat. Also, the transporters in the intestinal mucosa as p-glycoprotein may not be involved in the transport of rebamipide.