Box-Behnken设计-响应面法优化雷贝拉唑钠肠溶微丸片的处方  

Optimization of Rabeprazole Sodium Enteric-coated Pellets-type Tablets by Box-Behnken Design-response Surface Methodology

作　　者：刘珊珊 吴琼珠[2] LIU Shanshan;WU Qiongzhu(School of Health Science,Jiangsu Vocational Institute of Commerce,Nanjing 211168;College of Pharmacy,China Pharmaceutical University,Nanjing 211198)

机构地区：[1]江苏经贸职业技术学院健康学院,江苏南京211168 [2]中国药科大学药学院,江苏南京211198

出　　处：《中国医药工业杂志》2021年第8期1041-1048,共8页Chinese Journal of Pharmaceuticals

摘　　要：采用挤出滚圆-流化床包衣法,以Eudragit■L30D-55为包衣材料制备雷贝拉唑钠(1)肠溶微丸,再以流化床制粒-压片法制成肠溶微丸片。以耐酸力和在pH 8.0介质中30 min的累积释放率(Q_(30min))为评价指标,利用单因素试验和Box-Behnken设计-响应面法优化处方和工艺参数,如肠溶层增重、增塑剂和填充剂用量等。结果表明,先将肠溶微丸与微晶纤维素(MCC)PH101进行流化床制粒、再外加MCC KG-802压片的工艺对肠溶微丸衣膜起到了保护作用。3批优化的1肠溶微丸片的耐酸力良好,Q30 min大于90%,与压片前的肠溶微丸、市售1肠溶片的释放行为一致(相似因子均大于50)。并且,显微镜检也证实肠溶微丸压片后衣膜完整。The rabeprazole sodium enteric-coated pellets were prepared by extrusion-spheronization and fluid-bed coating technique with Eudragit■L30D-55 as the coating material.Then,these pellets were granulated with microcrystalline cellulose(MCC)PH101 in a fluidized bed to prepare the enteric-coated pellets-type tablets.The process and formulation parameters,such as weight gain of the enteric-coated layer,amounts of plasticizer and fillers,were optimized by single factor test and Box-Behnken design-response surface methodology with acid resistance and cumulative release at 30 min in pH 8.0 medium(Q_(30min))as the indicators.The results showed that the enteric-coated layer would not be destroyed during the tableting process of the granules manufactured with the enteric-coated pellets and MCC PH101 by fluidized bed granulation and MCC KG-802 as another filler.All the three batches of the optimal enteric-coated pellets-type tablets had good acid resistance and the Q30 min data were above 90%,and their release behaviors were similar to those of the enteric-coated pellets and the commercial rabeprazole sodium enteric-coated tablets according to the calculated similarity factors(f2>50).In addition,the microscopic observation also confirmed that the enteric film of the pellets remained intact after compression.

关 键 词：雷贝拉唑钠 挤出滚圆 流化床包衣 肠溶微丸 微丸片 响应面法 

分 类 号：R944.4[医药卫生—药剂学]