药用辅料1,1,1,2-四氟乙烷质量对比研究

Comparative research on quality of pharmaceutical 1,1,1,2-tetrafluoroethane from different manufacturers

目的:对药用气雾剂抛射剂1,1,1,2-四氟乙烷进行全面的质量比对。方法:参考国内外1,1,1,2-四氟乙烷相关标准,对4个厂家21批样品的全部检测项目(鉴别、酸碱度、高沸点残留物、氯化物、气相中不凝性气体、有关物质、含量测定、水分)进行测定。结果:4个厂家的样品多数能符合2020年版《中华人民共和国药典》四部四氟乙烷(供外用气雾剂用)规定,但在酸碱度、高沸点残留物、水分、有关物质方面差异较大。部分样品的碱含量、水分、高沸点残留物较高;有关物质尤其是未知杂质的种类多,未知杂质含量高。结论:部分产品质量欠佳,如用于吸入气雾剂,还需进一步优化生产工艺,加强质量控制,此外对于部分产品中检出的含量较高的杂质和未知杂质还应继续研究其毒理和安全性,以提高1,1,1,2-四氟乙烷及用其制备的药用吸入气雾剂的整体质量水平。

Objective:To compare the quality of 1,1,1,2-tetrafluoroethane from different manufacturers.Methods:Refer to the related standards of 1,1,1,2-tetrafluoroethane at home and abroad,the determination of 21 batches samples from 4 manufacturers was performed from all test items:identification,acidity or alkalinity,high boiling residue,chloride,non-condensables,related substances,HFA-134 a content and water content.Results:Most samples of four manufacturers could meet the requirements of tetrafluoroethane(for topical aerosol)in Chinese Pharmacopoeia 2020 VolⅣ,but had large differences in the test items of high-boiling residue,water content and related substances.The alkalinity,water content and the high-boiling residue of samples from some manufacturers were higher;The types of related substances especially unknown impurities of some samples were various,the contents of unknown impurities in some samples were high.Conclusion:There are still some gaps in products.It’s necessary to further optimize the production process and strengthen quality control if the some products are used for metered-dose inhalers.In addition,it’s should continue to study the toxicology and safety of the unknown impurities detected in some products in order to improve the overall quality of 1,1,1,2-tetrafluoroethane and the metered-dose inhalers.