Key Laboratory of Drug Targeting, Ministry of Education, Sichuan University, Chengdu, PR China.
Drug Dev Ind Pharm. 2010 Jan;36(1):81-92. doi: 10.3109/03639040903092335.
As conventional pH-controlled colon-targeted system used for oral drug delivery often shows a poor performance, a more effective way to preserve poorly water-soluble drug from releasing in upper gastrointestinal tract should be researched.
The objective of this study was to develop a novel colon-targeted drug delivery system using guar gum and Eudragit as enzyme- and pH-based materials. Lansoprazole, a poorly water-soluble drug was used as model drug. Under three different conditions, the in vitro drug release behaviors of this newly developed system was evaluated, using β-mannanase, rat cecal content, and human fecal media to simulate the pH and enzyme during intestinal transit to the colon.
The released amount of lansoprazole in simulated small intestine fluid (pH 6.8) after 5 hours was less than 10% from the pH- and enzyme-controlled tablets compared with 80.01±0.3% in rat cecal content medium (pH 7.4).The degradation ability of human fecal slurries on PECCT-PT was independent of human age and gender. β-Mannanase did not have a similar effect on the degradation of polysaccharide as rat cecal enzymes and human fecal enzymes in our study. Scanning electron microscope study indicated that the dissolution mechanism of PECCT-PT should be corrosion.
The above results indicated this system could be served as a potential carrier to deliver poorly water-soluble drug specifically to the colon.
由于传统的 pH 控制型结肠靶向给药系统在口服给药时性能往往不佳，因此应该研究更有效的方法来防止水难溶性药物在上胃肠道中释放。
本研究的目的是开发一种使用瓜尔胶和 Eudragit 作为酶和 pH 型材料的新型结肠靶向药物传递系统。以水难溶性药物兰索拉唑为模型药物。在三种不同条件下，用β-甘露聚糖酶、大鼠盲肠内容物和人粪便培养基分别模拟肠道转运至结肠时的 pH 和酶，评估了该新系统的体外药物释放行为。
与在大鼠盲肠内容物培养基（pH7.4）中释放 80.01±0.3%相比，在模拟小肠液（pH6.8）中经过 5 小时后，pH 和酶控制型片剂中兰索拉唑的释放量不到 10%。人粪便悬浮液对 PECCT-PT 的降解能力与人类年龄和性别无关。在我们的研究中，β-甘露聚糖酶对多糖的降解作用与大鼠盲肠酶和人粪便酶没有相似的效果。扫描电子显微镜研究表明，PECCT-PT 的溶解机制应为腐蚀。
上述结果表明，该系统可以作为一种将水难溶性药物特异性递送至结肠的潜在载体。
