湿法研磨结合挤出滚圆法制备非诺贝特缓释微丸及工艺考察

Preparation of fenofibrate sustained-release matrix pellets by wet milling combined with extrusion-spheronization

目的湿法研磨结合挤出滚圆法制备稳定性良好的非诺贝特骨架型缓释微丸。方法将微粉化非诺贝特与亲水性载体共研磨,研磨液用固体辅料吸收,通过挤出滚圆法制备缓释微丸。以制剂体外释放度及加速试验中制剂稳定性为指标,筛选了研磨混悬液中亲水性载体的种类,考察了微晶纤维素用量、乳糖用量、挤出次数、滚圆时间等对药物释放的影响。结果以质量浓度为0.1 kg·L^-1聚维酮（K30）为亲水载体溶液,药物与载体质量之比为10∶1时,制备微丸的释放度符合中国卫生部颁发标准（1 h释放10%-30%;4 h释放50%-75%;7 h释放75%以上）,体外释药过程符合Higuchi方程。结论成功地制备了非诺贝特骨架型缓释微丸,该制备工艺重现性好,具有理想的缓释效果,加速试验稳定性良好。

Objective To investigate the preparation and storage stability of the fenofibrate matrix sustained release pellets by wet milling and extrusion-spheronization.Methods Suspension of micronized fenofibrate with hydrophilic vehicle solution was prepared by wet milling technology in a mill,and then fenofibrate pellets was prepared by extrusion-spheronization process.The release properties and storage stability of the preparation were investigated to select the best vehicle.Several factors that affected the sustained release characteristics,such as the amounts of MCC and lactose,times of extrusion,spheronization time were assessed.Results 0.1 kg·L^-1polyvidone（K30） was applied to hydrophilic vehicle,the ratio of fenofibrate to vehicle was 10∶1,prepared stable fenofibrate pellets,release of the fenofibrate from pellets was in accordance with Higuchi equation.Conclusions Combined wet milling technology with extrusion-spheronization process,good and stable fenofibrate matrix sustained-release pellets can be prepared.