Huang Bei-Bei, Li Guo-Feng, Luo Jing-Hui, Duan Lian, Nobuaki Kishimoto, Akira Yamamoto
Department of Pharmacy, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Ave (N), Guangzhou, Guangdong Province, China.
World J Gastroenterol. 2008 Aug 21;14(31):4928-37. doi: 10.3748/wjg.14.4928.
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.
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.
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.
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.
研究瑞巴派特在肠道黏膜的渗透特性，考察某些吸收促进剂对其在结肠组织渗透的影响。另一个目的是使用壳聚糖胶囊作为载体，证明瑞巴派特在有无吸收促进剂情况下的结肠靶向递送。
采用体外扩散室系统评估瑞巴派特的渗透性，并进一步研究某些吸收促进剂对其经结肠渗透的影响。通过日本药典转篮法研究瑞巴派特从壳聚糖或明胶胶囊中的释放情况。口服各种剂型以及壳聚糖剂型中含有吸收促进剂的瑞巴派特后，采用高效液相色谱法（HPLC）分析结肠和血浆浓度，以评估结肠靶向作用。
瑞巴派特在空肠或回肠黏膜的渗透性高于结肠黏膜。月桂酸钠（C12）和Labrasol均显著增加了其在结肠膜的渗透性。另一方面，瑞巴派特从壳聚糖胶囊中的释放量在6小时内总计不到10%。使用壳聚糖胶囊时，结肠黏膜中药物浓度-时间曲线下面积（AUCLI，16011.2 ng·h/g）分别是使用明胶胶囊和羧甲基纤维素（CMC）混悬液时的2.5倍和4.4倍。同时，壳聚糖胶囊组血浆中药物浓度-时间曲线下面积（AUCPL）为1016.0 ng·h/mL，CMC混悬液组为1887.9 ng·h/mL，明胶胶囊组为2163.5 ng·h/mL。总体而言，同时给予C12时，AUCLI和AUCPL均增加，但AUCLI的增加幅度更大；与单纯壳聚糖胶囊组相比，药物递送指数（DDI）大于1。
瑞巴派特在空肠、回肠和结肠的渗透性存在区域差异；被动扩散似乎是瑞巴派特的主要转运机制之一。吸收促进剂可显著增加瑞巴派特在结肠组织的渗透性。此外，壳聚糖胶囊可能是将瑞巴派特特异性递送至结肠的有用载体，C12与瑞巴派特同时给药在局部治疗中可能也非常有用。
