氟尿嘧啶pH依赖-时滞型结肠定位微丸的制备及释药特性研究  

Study on Preparation and Drug Release of pH-and Time-Based Pellets of Fluorouracil for Colon-Specific Delivery

作　　者：李林军[1] 黄桂华[1] 席延卫[1] 杨心督[1] 顾纪锋[1] 

机构地区：[1]山东大学药学院,济南250012

出　　处：《中国药学杂志》2007年第5期357-361,共5页Chinese Pharmaceutical Journal

基　　金：山东省科技厅科技计划专项资助项目(2005GG4402012)

摘　　要：目的制备pH依赖-时滞型氟尿嘧啶(5-FU)结肠定位微丸并对其体外释药情况及影响因素进行研究。方法采用挤出-滚圆法制备空白丸芯,将药物与溶胀材料和黏合剂混合,采用空白丸芯上药法制备载药丸芯,以乙基纤维素为控释层包衣材料,Eudragit FS 30D为肠溶层材料,流化包衣法制备pH依赖-时滞型5-FU结肠定位释药微丸,以释放度为评价指标,考察影响5-FU微丸体外释药的因素。结果溶胀层材料的种类及厚度、控释层及肠溶层包衣厚度等对释药速率均有影响。将5-FU和羟甲基淀粉酶(CMS-Na)混合作为溶胀层,乙基纤维素有机溶液作为控释层,Eudragit FS 30D为肠溶层制备的结肠定位包衣微丸,当溶胀层增重30%,控释层增重12%和肠溶层增重20%时,在模拟人体胃肠道pH变化条件下,微丸释药特性基本符合设计要求,达到了结肠定位的效果。结论通过调整溶胀层,控释层,肠溶层包衣厚度可以制备5-FUpH依赖-时滞型结肠定位微丸。OBJECTIVE To develop a pH-and time-based pellets of fluorouracil and evaluate their release characteristics in vitro. METHODS The blank pellets were prepared by extrusion-spheronization method; drug containing pellets were prepared by coating the blank pellets using the Fluorouracil-binder and the swelling material suspension in a fluidized bed coater. To achieve the controlling release, the drug containing pellets then were coated with ethyl cellulose as the controlled layer and Eudragit FS 30D as the outer coating enteric layer. The release behaviors of coated pellets for colon-specific delivery were evaluated in vitro. The effects of different swelling materials, the thicknesses of the swelling layer, EC layer and the enteric polymer layer on the release of fluorouracis were evaluated. RESULTS The dissolution rate was decided by the thickness of EC, swelling layer, enteric polymer and by the kinds of the swelling layer. The release characteristics of the fluorouracil pellets, prepared using CMS-Na and drug-binder suspension as the swelling layer with 30% （weight） coating level, using ethyl cellulose as the controlled layer with 12% （weight） coating level and Eudragit FS 30D as outer coating enteric layer with 20% （weight） coating level in the fluidized bed coater,met the requirement of colonspecific pellets. CONCLUSION The pH-and time-based pellets of fluorouracil for colon-specific delivery can be prepared using swelling layer, controlled laver and enteric layer by changing their coating level.

关 键 词：氟尿嘧啶 pH依赖-时滞型 结肠定位 微丸 

分 类 号：R943.4[医药卫生—药剂学]