摘要
目的比较进口参比制剂萘普生片与国产仿制萘普生片的溶出曲线与生物等效性,评价两者质量一致性。为国产萘普生片处方、工艺的优化提出合理建议。方法以日本田边三菱公司生产的萘普生片为参比制剂,测定8种国产仿制药与参比制剂在pH值1.2盐酸溶液、pH值5.5醋酸盐缓冲液、pH值6.0磷酸盐缓冲液、pH值6.8磷酸盐缓冲液以及水等5种溶出介质中的溶出曲线,通过计算f2相似因子评价溶出曲线相似性。应用GastroPlusTM软件结合体外溶出数据,建立萘普生片体内外相关性模型,评价进口萘普生片与仿制萘普生片的生物等效性。结果体外溶出测定实验中,8种国产仿制萘普生片在多种溶出介质中的溶出曲线与参比制剂溶出曲线均不相似(f2因子均<50);体内预测结果,除参比制剂外,各仿制制剂与实测数值差异均较大。结论GastroPlusTM软件建立的体内外相关性模型可很好反映体内溶出情况,国内8种仿制萘普生片与进口参比制剂质量差异较大,制剂处方、工艺有待优化。
Objective Comparing the dissolution curves and bioequivalences of the imported reference naproxen tablets and generic drugs,to evaluate their consistency and give some reasonable suggestions for their formulations and manufacturing.Methods The dissolution curves of the reference listed drug( RLD) produced by Japanese Tanabe Mitsubishi Corporation and the generic drugs produced by 8 pharmaceutical enterprises were determined in five dissolution mediums: hydrochloric acid solution( p H 1.2),acetate buffer( p H 5.5),phosphoric acid salt buffer( p H 6.0),phosphoric acid salt buffer( p H 6.8) and water.The dissolution curves of consistency were evaluated by the f2 similarity factor method.In the meantime,the in vitro-in vivo correlation models were established using Gastro PlusTMcombined with in vitro dissolution data to evaluate the bioequivalence of the RLD and the generic drugs. Results The dissolution curves between generics and RLD were dissimilar( f2<50).There was significant difference between the simulated parameters of generic drugs and the previous reported in vivo values. Conclusion The dissolution behaviors of generic drugs and RLD are dissimilar,which indicates that the formulations and manurfacturing technology of generic drugs should be optimized. And Gastro PlusTMsoftware can be used to predict the bioequivalence of the generic drugs and RLD.
作者
唐婉
尹菁
张圆
石蓓佳
李攀
陆益红
樊夏雷
TANG Wan;YIN Jing;ZHANG Yuan;SHI Beijia;LI Pan;LU Yihong;FAN Xialei(Department of Pharmaceutical Analysis,Xuzhou Medical University, Xuzhou 221004, China;Jiangsu Institute for Food and Drug Control, Nanjing 210009, China;China Pharmaceutical University, Nanjing 210009,China)
出处
《医药导报》
CAS
北大核心
2019年第7期899-905,共7页
Herald of Medicine
