CAJ | 학술논문

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Eudragit RL30D,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y-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.
목적 제비일충신형구복결장정위제제,병고찰기체외석약행위여견체내적결장정위특성.방법 본시험선택4-안기수양산납작위모형약물,응용병희산수지Eudragit RL30D,RS30D화Eudragit FS30D분별작위완석화장용층포의재료,제득포의편제,사계통가의뢰pH화시간쌍중궤제석약.재체외석방시험중,계통재0.1 mol·L-1염산용액중운전2 h후,분별재pH위6.5,7.0혹7.4적린산염완충액중계속운전12 h.체내험증이방사성동위소득(99mTc)주표기,용y-사선현영법래학정계통재위장도내적석약시간화위치.결과 체외실험중,계통재0.1 mol·L-1염산용액중운전2 h후무약물석방,재pH고우6.5적개질중완만석약,개질적pH월고,약물석방월쾌.체내실험중,포의편재위장도상반부무약물석방,도체결장후개시석약;이비포의편재견위부즉신속붕해.결론 본문채용적포의재료사포의편도체승결장시개시석방약물,약물석방시간가체10 h이상.
Aim To prepare a new oral colon-specific delivery formulation and to investigate the release profile in vitro and the colon-specific delivery property in vivo in dogs. Methods Sodium 4-aminosalicylic acid was selected as the model drug. The combination of Eudragit RL30D and RS30D were used as sustained-release film, and Eudragit FS30D used as enteric film, which was expected to release drug depending on pH and time. The release profile of tablets was studied in three phosphate buffers with the pH 6.5, 7.0 or 7.4 for 12 h after a simulated gastric presoak for 2 h in 0.1 mol · L-1 HCl. The tablets were radiolabelled with 99mTc to make their release times and positions in the gastrointestinal tract be followed using a gamma camera. Results For the in vitro study, there was no drug released in 0. 1 mol ·L- 1 HCl for 2 h, and release occurred slowly when pH was above 6.5. Drug was released faster while pH was higher. For the in vivo study, the coated tablets remained intact in the upper gastrointestinal tract, and drug release began after the colonic arrival. The uncoated tablets, however, disintegrated in the stomach of the dogs rapidly. Conclusion The coating could protect the drug until the tablets reached the ascending colon, where drug was released slowly for over 10 h.