挤出滚圆法制备尼群地平缓释微丸的处方因素考察

Preparation of Nitrendipine Sustained-Release Pellet Using Extrusion-Spheronization Technology and Investigations of Its Formulation

目的对影响药物释放的处方因素进行考察。方法以微晶纤维素(MCC)为成型辅料,乙基纤维素(EC)为缓释材料,可溶性高分子材料为致孔剂,乳糖、十二烷基硫酸钠(SDS)及崩解剂为释药速度调节剂,采用挤出滚圆法制备尼群地平固体分散体及微丸,通过体外释放度试验对各辅料的种类及用量进行详细考察。结果在尼群地平含量为10%的前提下,EC(10cps)用量在20%左右有一定的缓释作用;致孔剂采用PVPk30,用量应在5%以下;崩解剂种类及用量对微丸中药物的释放影响显著,4%～12%的交联羧甲基纤维素钠(CCNa)可使药物释放较为完全;乳糖及SDS对药物释放无明显影响,用量分别为20%和4%较佳;成球辅料MCC型号为AvicelPH101。结论采用上述处方,可制得体外释放度符合要求的尼群地平缓释微丸。

Objective To investigate the formulation factors affecting drug release from Nitrendipine Sustained-Release Pellet prepared by extrusion-spheronization technology. Methods Nitrendipine pellet was prepared by extrusion-spheronization technology. MCC was used as filling substance, EC as matrix material to retain drug release, water soluble polymers as pore-making agents, and lactose, SDS, disintegrants to improve drug release. Types and quantities of all these excipients affecting drug release from the pellets were investigated and optimized through the dissolution test in vitro. Results The profiles of drug release from Nitrendipine Sustained- Release Pellet was well controlled when the content of EC （10 cps） was about 20% and PVPk30 below 5% in formulations. The type and quantity of disintegrants in pellets had magnificent effects on drug release, CCNa added in from 4% to 12% was more preferable than others. However, the quantity of lactose and SDS had little effect on drug release, their content should be 20% and 4%, respectively. Conclusion Using formulations mentioned above, well sustained- release nitrendipine pellets would be prepared by extrusion- spheronization technology.