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目的制备一种新型口服结肠定位制剂,并考察其体外释药行为与犬体内的结肠定位特性。方法本试验选择4-氨基水杨酸钠作为模型药物,应用丙烯酸树脂EudragitRL30D,RS30D和Eudragit FS30D分别作为缓释和肠溶层包衣材料,制得包衣片剂,使系统可依赖pH和时间双重机制释药。在体外释放试验中,系统在0.1 mol.L-1盐酸溶液中运转2 h后,分别在pH为6.5,7.0或7.4的磷酸盐缓冲液中继续运转12 h。体内验证以放射性同位素锝(99mTc)做标记,用γ-射线显影法来确定系统在胃肠道内的释药时间和位置。结果体外实验中,系统在0.1 mol.L-1盐酸溶液中运转2 h后无药物释放,在pH高于6.5的介质中缓慢释药,介质的pH越高,药物释放越快。体内实验中,包衣片在胃肠道上半部无药物释放,到达结肠后开始释药;而非包衣片在犬胃部即迅速崩解。结论本文采用的包衣材料使包衣片到达升结肠时开始释放药物,药物释放时间可达10 h以上。
Objective To prepare a novel oral colon preparation and study its in vitro release behavior and colonic colon localization in dogs. Methods In this study, sodium 4-aminosalicylate was chosen as the model drug. Activated resins Eudragit RL30D, RS30D and Eudragit FS30D were used as sustained-release and enteric coating materials to prepare coated tablets, which allowed the system to rely on pH and time Dual mechanism of drug release. In the in vitro release test, the system was operated in 0.1 mol.L-1 hydrochloric acid solution for 2 h, and the system was further operated for 12 h in phosphate buffer solution with pH 6.5, 7.0 or 7.4 respectively. In vivo validation radioisotope technetium (99mTc) labeled with γ-ray imaging to determine the system in the gastrointestinal tract release time and location. Results In vitro experiments, the system in the 0.1 mol.L-1 hydrochloric acid solution after 2 h operation no drug release, the slow release of the medium above pH 6.5, the higher the pH of the medium, the faster the drug release. In vivo experiments, the coated tablets in the upper gastrointestinal tract without drug release, arrived in the colon after the release of drugs; non-coated tablets in the dog’s stomach that is rapidly disintegrated. Conclusion The coating materials used in this study started to release the drug when the coated tablets reach the ascending colon, and the drug release time can reach more than 10 hours.