CAJ | 학술논문

体外研究瓜尔胶/乙基纤维素混合包衣小丸的结肠靶向性.以5-氟尿嘧啶为模型药, 采用流化包衣技术以瓜尔胶/乙基纤维素混合物的水/醇混悬液对载药小丸进行喷液包衣.瓜尔胶/乙基纤维素混合包衣小丸的释药行为取决于包衣处方中瓜尔胶与乙基纤维素的比例和包衣厚度.分别以混合包衣液中瓜尔胶与乙基纤维素的比例及包衣增重为自变量, 以T5和T90(药物释放5%和90%所需要的时间)为效应, 进行3×4析因设计/效应面优化, 筛选较优处方.结果表明随着乙基纤维素在衣层中所占比例的增大及包衣厚度的增加, 药物释放时滞增加.当瓜尔胶与乙基纤维素的比例在0.2～0.7, 并且包衣增重在250%～500%时, T5%为5.1～7.8 h, T90%为9.8～16.3 h.并且在释药时滞之后, 进入模拟结肠微菌群酶解作用的释放环境中(pH 6.5)药物释放速度加快, T90%缩短到9.0～14.5 h.由此可以看出适当的瓜尔胶/乙基纤维素混合衣层既可以保护药物顺利通过上消化道而不释放, 达到结肠后药物开始释放, 并且可在结肠微菌群的酶解作用下加速药物的释放, 实现结肠定位释药的目的.
체외연구과이효/을기섬유소혼합포의소환적결장파향성.이5-불뇨밀정위모형약, 채용류화포의기술이과이효/을기섬유소혼합물적수/순혼현액대재약소환진행분액포의.과이효/을기섬유소혼합포의소환적석약행위취결우포의처방중과이효여을기섬유소적비례화포의후도.분별이혼합포의액중과이효여을기섬유소적비례급포의증중위자변량, 이T5화T90(약물석방5%화90%소수요적시간)위효응, 진행3×4석인설계/효응면우화, 사선교우처방.결과표명수착을기섬유소재의층중소점비례적증대급포의후도적증가, 약물석방시체증가.당과이효여을기섬유소적비례재0.2～0.7, 병차포의증중재250%～500%시, T5%위5.1～7.8 h, T90%위9.8～16.3 h.병차재석약시체지후, 진입모의결장미균군매해작용적석방배경중(pH 6.5)약물석방속도가쾌, T90%축단도9.0～14.5 h.유차가이간출괄당적과이효/을기섬유소혼합의층기가이보호약물순리통과상소화도이불석방, 체도결장후약물개시석방, 병차가재결장미균군적매해작용하가속약물적석방, 실현결장정위석약적목적.
The aim of this work was to investigate guar gum/ethylcellulose mix coated pellets for potential colon-specific drug delivery. The coated pellets, containing 5-fluorouracil as a model drug, were prepared in a fluidized bed coater by spraying the aqueous/ethanol dispersion mixture of guar gum and ethylcellulose. The lag time of drug release and release rate were adjustable by changing the ratio of guar gum to ethylcellulose and coat weight gain. In order to find the optimal coating formulation that was able to achieve drug targeting to the colon, the effect of two independent variables (the ratio of guar gum to ethylcellulose and the coat weight gain) on drug release characteristics was studied using 3×4 factorial design and response surface methodology. Results indicated that drug release rate decreased as the proportion of ethylcellulose in the hybrid coat and the coat weight gain increased. When the ratio of guar gum to ethylcellulose was kept in the range of 0.2 to 0.7, and the coat weight gain in the range of 250% to 500%, the coated pellets can keep intact for about 5 h in upper gastrointestine and achieve colon-specific drug delivery. The pellets prepared under optimal conditions resulted in delayed-release sigmoidal patterns with T5% (time for 5% drug release) of 5.1-7.8 h and T90% (time for 90% drug release) of 9.8-16.3 h. Further more, drug release was accelerated and T90% of the optimum formulation pellets decreased to 9.0-14.5 h in pH 6.5 phosphate buffer with hydrolase. It is concluded that mixed coating of guar gum and ethylcellulose is able to provide protection of the drug load in the upper gastrointestinal tract, while allowing enzymatic breakdown of the hybrid coat to release the drug load in the colon.