肠溶性瑞巴派特壳聚糖胶囊的制备及大鼠口服给药吸收评价

目的评价肠溶性瑞巴派特壳聚糖胶囊的释药作用,考察其结肠定位效果。方法将瑞巴派特1 mg装入壳聚糖胶囊中,并用羟丙基甲基纤维素邻苯二甲酸酯(HPMCP)包裹胶囊,观察胶囊的体外释药性能。在乙醚麻醉下通过聚乙烯管大鼠口服给予瑞巴派特壳聚糖胶囊4 mg,对照组口服同剂量的明胶胶囊和羧甲基纤维素溶液。于给定的时间间隔取血,取出结肠组织,分离提取药物,用HPLC法测定大鼠血液及结肠中药物浓度。结果在6 h体外溶出试验中,即人工胃液2 h和人工肠液4 h中,瑞巴派特从壳聚糖胶囊中的释药量的质量分数小于10%。大鼠口服瑞巴派特壳聚糖胶囊时,在结肠黏膜中的药物含量-时间曲线下面积(AUCLI0-9,16.01 mg.h.L-1)分别是明胶胶囊和羧甲基纤维素溶液的2.5倍和4.4倍。口服瑞巴派特壳聚糖胶囊,大鼠血浆药物含量-时间曲线下面积(AUCPL0-9)为1.02 mg.h.L-1,同剂量的明胶胶囊和羧甲基纤维素溶液分别是2.16 mg.h.L-1和1.89 mg.h.L-1,表明在壳聚糖的作用下,与明胶胶囊或羧甲基纤维素溶液比较,瑞巴派特从胃肠道吸收进入血液循环的量较少。结论在HPMCP的保护下,壳聚糖是瑞巴派特在结肠释药的一种有效的载体。

Preparation of enteric coating rebamipide chitosan and its absorption after oral administration in rat

Abstract: Objective To investigate the possibility of chitosan capsules as one carrier for the colon-specific delivery of rebamipide. Methods Rebamipide was filled in the chitosan capsules and coated with HPMCP. Then, the in vitro release tests of the capsules in the artificial gastric juice or in the man-made small intestinal juice were carried out. Four capsules (4 mg rebamipide for each) were administered orally via a polyethylene cannula under light ether anesthesia. Rebamipide gelatin capsules or its carboxymethyl cellulose solutions was given to the control group at the same dose. Blood sample and the colon tissue were taken periodically. The concentration of rebamipide in all of the samples was analyzed using HPLC. Based on these results, the relative targeting drug delivery index of rebamipide was calculated. Results The accumulated release of rebamipide chitosan capsules was no more than 10 % within 6 h in the artificial medium of stomach (2 h) and small intestine (4 h). After oral administration, the area under the curve in the colon (AUCLI0-9, 16.01 mg&;#8226;h&;#8226;L-1) for rebamipide chitosan capsule group was 2.5 times or 4.4 times as large as that of its gelatin capsules or of its carboxymethylcellulose solution group. On the other hand, the area under the curve in the plasma (AUCPL0-9) for rebamipide chitosan capsule group was 1.02 mg&;#8226;h&;#8226;L^-1, while 2.16 mg&;#8226;h&;#8226;L^-1 for the gelatin capsule group and 1.89 mg&;#8226;h&;#8226;L^-1for the carboxymethylcellulose solution group, respectively. Therefore, less rebamipide was absorbed into the blood after administration of its chitosan capsules compared with that in the other test dosage forms. Conclusions Chitosan capsules may be a useful carrier for the colon-specific delivery of rebamipide with the protection of hydroxypropyl methylcellulose phthalate（HPMCP）.