国产硝苯地平缓释片的体外溶出度和虚拟生物等效性研究  

In vitro Dissolution and Virtual Bioequivalence of Domestic Nifedipine Sustained Release Tablets

作　　者：孙晓迪[1,2] 张伟[3] 胡爽[1] 刘建芳[2] 

机构地区：[1]山西医科大学药学院,太原030001 [2]白求恩国际和平医院药剂科 [3]中国人民武装警察部队8654部队卫生队

出　　处：《中国药师》2017年第5期791-794,共4页China Pharmacist

基　　金：“重大新药创制”国家科技重大专项(编号:2011ZXJ09202-012)

摘　　要：目的:通过体外溶出试验考察4种国产硝苯地平缓释片的质量一致性,并利用GastroPlus软件进行虚拟生物等效性研究。方法:采用日本橙皮书和中国药典的溶出方法,测定不同厂家硝苯地平缓释片的溶出曲线,利用溶出曲线相似性f2因子法比较溶出曲线相似性。将原研制剂的体外溶出度数据与GastroPlus软件结合计算得到模拟的药物体内吸收曲线,通过与文献实测值比较,选择体内外相关性良好的溶出介质;采用选定的溶出介质进行国产硝苯地平缓释片的溶出试验,得到模拟的体内吸收参数,与原研制剂比较,进行虚拟生物等效性评价。结果:两种溶出方法的考察结果显示,4种国产制剂与原研制剂的f_2因子均小于50;与日本橙皮书方法相比,采用中国药典方法得到的原研制剂溶出曲线的体内外相关性更好。4种国产硝苯地平缓释片的药动学参数C_(max)及AUC_(0~∞)模拟值与原研药的实测值相差在±20%以内。结论:4种国产硝苯地平缓释片与原研制剂相比,体外溶出曲线不相似,但体内模拟生物等效。Objective： To evaluate the quality consistency of four domestic nifedipine sustained release tablets by dissolution test and virtual bioequivalence study by GastroPlus software. Methods： The dissolution curves of the four preparations were determined with the methods described in Japanese orange book and Chinese Pharmacopeia. The f2 factor of dissolution curves was calculated to compare the similarity. The in vitro dissolution data of the original preparation were combined with GastroPlus software to obtain the simulated in vivo absorption curves which were correlated with the actual concentration-time curves. The suitable dissolution medium was selected to evaluate the quality of domestic nifedipine sustained release tablets according to the better in vivo-in vitro correlation （IVIVC）. The simulated in vivo absorption parameters obtained from the dissolution data combined with GastroPlus software were used to conduct the virtual bioequivalence study of domestic nifedipine sustained release tablets compared with the original products. Results ： The f2 similar factors of the four domestic nifedipine sustained release tablets compared with the original preparation were all less than 50. Compared with that from the method in Japanese orange book, the correlation between the dissolution profiles in vitro and in vivo of original nifedipine sustained release tablets obtained from the method in Chinese Pharmacopoeia was better. The deviation be- tween the simulated Cmax and AUC0-∞ values of the four test tablets and the measured values of the original preparation was within the range of ：t： 20%. Conclusion： The dissolution curves of the four domestic nifedipine sustained release tablets are not similar to that of the original preparation, however, the four preparations are all bioequivalent to the original preparation according to the simulated absorption parameters based on the dissolution method in Chinese Pharmacopeia and GastroPlus software.

关 键 词：硝苯地平缓释片 质量一致性评价 溶出度试验 Gastro PLUS软件 

分 类 号：R945[医药卫生—微生物与生化药学]