雷贝拉唑钠肠溶(微粒)胶囊的制备工艺研究

Preparation Technology of Sodium Rabeprazole Enteric-Coated (Microgranules) Capsules

目的优选雷贝拉唑钠肠溶(微粒)胶囊的最佳制备工艺。方法采用挤出造粒-气流包衣法制备。以粘合剂羟丙甲纤维素溶液的浓度、用量以及微晶纤维素用量考察因素,按L9(34)进行正交试验,并评价工艺优劣;在此基础上再次以磷酸氢钙和磷酸氢二钠的用量为考察因素,按L9(34)进行正交试验,用成品在高温条件下10d的有关物质增加值评价其稳定性。按选定的处方制备样品,考察其释放度和加速试验稳定性。结果优选的微粒粒芯处方为每粒含雷贝拉唑钠10mg、磷酸氢钙40mg、磷酸氢二钠15mg、微晶纤维素180mg、羟丙甲纤维素水溶液的质量分数为4%,用量为投料量的12%。制备的样品耐酸性较好,在人工肠液中溶出快而完全,稳定性较好,释放度和稳定性与上市品相当。结论优选的处方工艺可用于制备雷贝拉唑钠肠溶(微粒)胶囊。

Objective To screen the optimum technology for preparing Sodium Rabeprazole Enteric-Coated （Mierogranules） Capsules. Methods Sodium Rabeprazole Enteric-Coated （Microgranules） Capsules were prepared with extruding and air-flow coating methods. The influencing factors such as the concentration and consumption of HPMC liquid,used as binder, the consumption of microcrystalline cellulose were studied and each was arranged 3 levels according to L9（3^4）orthogonal table. The technology was evaluated. Furthermore, 2 influencing factors, the consumptions of CaHPO4 and Na2HPO4, were studied which were also arranged 3 levels according to L9（3^4） orthogonal table. The increase of the relevant substances of the capsules which were kept in high temperature box for 10 d was used to evaluate their stability. The selected technique was validated by preparing a batch of Sodium Rabeprazole Enteric- Coated （Microgranules） Capsules. Their release was checked and their stability was tested via accelerated experiments, the sample products were compared with the same product from the market treated by the same way. Results The optimum technology was that the core of the microgranules of each capsule included： sodium rabeprazole 10 mg, CaHPO4 40 mg, Na2HPO4 15 mg, microcrystalline cellulose 180 mg, the concentration of HPMC liquid was 4% and its consumption weighs 12% to initial total quality. The capsules had nearly no change in acid liquid while the dissolution was quick and complete in artificial intestinal liquid. Their stability was acceptable. The release and stability of the capsules were likely to the same product from the market. Conclusion The selected technology is practicable to prepare Sodium Rabeprazole Enteric-Coated （Microgranules） Capsules.