唑来膦酸原研药与仿制药质量差异研究

Comparative evaluation of the quality of brand and generic zoledronic acid injection

目的对唑来膦酸注射液原研药与仿制药进行质量差异考察。方法选取不同厂家不同批次唑来膦酸原研药与仿制药,参照唑来膦酸注射液的药品标准,从渗透压、不溶性微粒、有关物质检查、含量测定等方面对比药品质量差异。结果原研药渗透压均近等渗范围,仿制药偏低渗范围,分别为274 m Osmol/kg、260 m Osmol/kg;仿制药中≥1μm的小粒径不溶性微粒显著多于原研药,粒径≥10μm、≥25μm的微粒彼此间差异不大,动态颗粒成像检测技术（Flow CAM）的检测结果普遍略高于光阻法;原研药唑来膦酸含量稳定,仿制药波动较大,分别相当于对照品的99.10%、103.82%;有关物质检查结果差异不大,杂质种类相同,总杂质含量为0.13%~0.18%,仿制药中保留时间（RT）7.15 min杂质高于原研药,RT11.21 min杂质低于原研药。结论唑来膦酸原研药与仿制药各项检查项目均符合药品标准,但仿制药在渗透压、≥1μm的小粒径不溶性微粒及含量稳定性方面,与原研药仍存在一定质量差异。

Objective To comparatively assess the quality of generic zoledronic acid injection against that of the brand. Methods Referring to the drug standard of zoledronic acid injection,to compare the drug quality between the generic and the brand,in terms of osmolality,particulate matter,impurity,mean zoledronic acid content etc. Results The brand was all isotonic,but the generic were hypotonic,with osmolalities of 274 m Osmol/kg and 260 m Osmol/kg,respectively. There were little differences between the brand and the generic in the number of particles with diameters of over 10 μm or 25 μm,but the generic had significantly larger number of particles with diameters over 1 μm compared with the brand. The detection result of FlowCAMwas generally higher than that of light blockage. Contents of zoledronic acid in the brand were stable,but the generic had larger fluctuation between batches and were 99. 10% and 103. 82% of the control,respectively. Both the brand and the generic had the same type of impurities,the contents of total impurities were 0. 13%- 0. 18%. Compared with the brand,the generic had higher content of the impurity of RT7. 15 min but lower content of the impurity of RT11. 21 min. Conclusion The qualities of the brand and the generic both satisfied the drug standard,but the brand was superior in osmolality,particulate matter（≥1 μm） and content stability.