Enzymatically degraded Eurylon 6 HP-PG: ethylcellulose film coatings for colon targeting in inflammatory bowel disease patients
Enzymatically degraded Eurylon 6 HP-PG: ethylcellulose film coatings for colon targeting in inflammatory bowel disease patients
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DOI：
10.1111/j.2042-7158.2010.01165.x
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发表时间：
2010-12-01
影响因子：
3.3
通讯作者：
Siepmann, Juergen
中科院分区：
文献类型：
--
作者：
Karrout, Youness;Neut, Christel;Siepmann, Juergen
基于Eurylon 6 HP-PG（一种羟丙基化和预糊化的高直链淀粉）和乙基纤维素混合物的薄膜涂层作为一种有前景的涂层材料，用于炎症性肠病患者的结肠部位特异性药物递送。方法采用挤压/滚圆法制备5-氨基水杨酸含量为60%的球团起动机芯，并以不同包覆水平的Eurylon 6 HP-PG：乙基纤维素共混物包覆。在模拟上胃肠道内容物的介质（存在和不存在酶）以及模拟结肠内容物的介质中测量药物释放。主要发现5-氨基水杨酸的释放在0.1 N HCl和pH为6.8的磷酸盐缓冲液（可选含有胃蛋白酶或胰酶）中得到有效抑制，但一旦颗粒与接种了炎症性肠病患者粪便样本的培养基接触就会发生释放。这可归因于这些患者结肠中存在的细菌分泌的酶对淀粉衍生物的部分降解。结论该给药系统适应炎症性肠病患者的病理生理状况。此外，药物释放在1年的开放储存中保持不变。
Objectives Film coatings based on blends of Eurylon 6 HP-PG (a hydroxypropylated and pregelatinized high amylose starch) and ethylcellulose were to be evaluated as promising coating materials for site-specific drug delivery to the colon of patients suffering from inflammatory bowel diseases.Methods Pellet starter cores containing 60% 5-aminosalicylic acid were prepared by extrusion/spheronization and coated with different Eurylon 6 HP-PG : ethylcellulose blends at various coating levels. Drug release was measured in media simulating the contents of the upper gastrointestinal tract (in the presence and absence of enzymes) as well as in media simulating the contents of the colon.Key findings 5-Aminosalicylic acid release could effectively be suppressed in 0.1 N HCl and phosphate buffer pH 6.8, optionally containing pepsin or pancreatin, but occurred as soon as the pellets came into contact with culture medium inoculated with faecal samples from inflammatory bowel disease patients. This can be attributed to the partial degradation of the starch derivative by enzymes secreted by bacteria present in the colon of these patients.Conclusions The presented drug delivery system is adapted to the pathophysiological conditions in inflammatory bowel disease patients. Furthermore, drug release remained unaltered upon 1 year open storage.