目的:通过测试盐酸法舒地尔注射液玻璃安瓿包装容器的密封完整性,研究质量提取法在玻璃安瓶包装密封完整性考察上的运用。方法:采用质量提取法测试,进行方法参数开发及检测限、准确度、重复性等方法学验证。采用经过验证的方法,对盐酸法舒地尔注射液玻璃安瓿包装的进行加速和长期0、3月稳定性的密封完整性检测。结果:建立了盐酸法舒地尔注射液玻璃安瓿包装的密封完整性质量提取法测试方法,关键时间参数总泄漏抽真空时间(预抽真空1)、大漏抽真空时间(预抽真空2)、微漏抽真空时间(抽真空2)、微漏稳定时间(稳定2)分别优化确立为4、3、20、8 s;检测限为2 μm;准确度为100%区分阴性阳性样品,重复性好。结论:质量提取法可以应用于小容量玻璃安瓿包装的密封完整性测试,该方法灵敏度高,稳定性好,结果真实可靠,能有效测试注射剂玻璃安瓿包装容器密封完整性。
Objective: To study the application of the mass extraction method in the inspection of the glass ampoule packaging through testing the sealing integrity of fasudil hydrochloride injection packaged in the glass ampoule packaging container. Methods: The mass extraction method was used to test the sealing integrity of injection packaging. The parameters of the method was developed. Detection limit, accuracy and repeatability of the method was verified. The sealing integrity of Fasudil hydrochloride injection packaged in the glass ampoule packaging was tested after 0 and 3 months acceleration and long-term stability experiments. Results: The mass extraction method for the closure integrity testing of Fasudil hydrochloride injection packaged in the glass ampoule packaging container was established and validated. The key time parameters: gross leak check evacuation time (Pre-Evac1), large leak check evacuation time (Pre-Evac2), fine leak check evacuation time (Evac2), fine leak check stability time (Stability 2) were optimized and established as 4 s, 3 s, 20 s and 8 s. The detection limit was 2 μm. The accuracy was 100%. The repeatability was good. Conclusion: The mass extraction method can be applied to the sealing integrity testing of small capacity glass ampoule packaging, This method has high sensitivity, good stability and reliable results, which can effectively test the integrity of injection ampoule packaging containers.
[1] 国家药品监督管理局药品审评中心.化学药品注射剂包装系统密封性研究技术指南(试行)[EB/OL]. 2020[2023-03-03]. https://www.cde. org. cn/main/news/viewInfoCommon/8a4f9f16844fbed617f8e8ed59485c1d
Center for Drug Evaluation,NMPA. Guideline to container closure integrity test for chemical injections(Trial)[EB/OL]. 2020 [2023-03-03]. https://www.cde. org. cn/main/news/viewInfoCommon/8a4f9f16844fbed617f8e8ed59485c1d
[2] 陆维怡,蔡荣.国内外药品包装系统密封完整性研究与保障药品质量安全的思考[J]. 中国药事,2021,35(7):828
LU WY, CAI R. Study on Sealing integrity of drug packaging system at home and abroad and consideration on ensuring drug quality and safety[J]. Chin Pharm Aff,2021,35 (7):828
[3] 杨梦雨,赵霞,孙会敏.无菌制剂容器完整性检测技术和相关法规研究进展[J]. 中国新药杂志,2022,31(3):245
YANG MY, ZHAO X, SUN HM. Research progress on container-closure integrity regulations and detection technology aseptic preparation[J]. Chin J New Drugs, 2022, 31(3):245
[4] 中国食品药品检定研究院. 药用辅料和药品包装材料检验技术[M]. 北京:中国医药科技出版社,2019:11
Institutes of Food and Drug Control.Testing Technology of Pharmaceutical Excipients and Pharmaceutical Packaging Materials[M]. Beijing:China Medical Science and Technonlogy Publishing Materials, 2019:11
[5] 封二飞.无菌药品包装完整性研究[J]. 中国医药工业杂志,2019,(50)11:1352
FENG EF. Research of sterile products packaging integrity[J]. Chin J Pharm, 2019, 50(11):1352
[6] 国家药品监督管理局药品审评中心.化学药品注射剂仿制药质量和疗效一致性评价技术要求[EB/OL]. 2020 [2023-03-03]. https://www.cde.org.cn/main/news/viewInfoCommon/d9c6f118b773f54e8feba3519bf78a11
Center for Drug Evaluation,NMPA.Technical Requirements for Quality and Efficacy Consistency Evaluation of Generic Drugs for Chemical Injections[EB/OL]. 2020 [2023-03-03]. https://www.cde.org.cn/main/news/viewInfoCommon/d9c6f118b773f54e8feba3519bf78a11
[7] ASTM F3287-17:Standard Test Method for Nondestructive Detection of Leaks in Packages by Mass Extraction Method[S]. 2017
[8] MOGHIMI N, SAGI H, PARK SI. Leakage analysis of flexible packaging: establishment of a correlation between mass extraction leakage test and microbial ingress [J]. Food Package Shelf Life, 2018, 16: 225
[9] Y00N SY,SAGI H,GOLDHAMMER C, et al. Mass extraction container closure integrity physical testing method development for parenteral container closure systems [J]. PDA J Pharm Sci Technol, 2012, 66(5):403
[10] 姚琳,咸富荣,张芳芳.质量提取法测试西林瓶包装系统密封性[J]. 中国医药工业杂志,2022,53(7):1352
YAO L, XIAN FR, ZHANG FF. Mass extraction method for the package integrity testing of vials [J]. Chin J Pharm,2022, 53(7):1352
[11] 王颖,杨梦雨,赵霞,等.质量提取法测试直立式聚丙烯输液袋包装的葡萄糖注射液密封完整性[J]. 药学研究,2022,41(5):299
WANG Y, YANG MY, ZHAO X, et al. Mass extraction method for the closure integrity testing of upright polypropylene infusion bag[J]. Pharm Res, 2022, 41(5):299
[12] 郭涤亮,董武军,马骏威,等.《美国药典》<1207>无菌药品包装系统密封性评估的介绍与解读[J]. 中国新药杂志,2021,30(10):880
GUO DL, DONG WJ, MA JW, et al. Introduction and interpretation of USP <1207> package integrity evaluation for sterile products [J]. Chin J New Drugs, 2021, 30(10):880
[13] USP 39-NF 34 [S]. 2016:2
[14] 陈江,王俊苏,关天横,等.注射剂包装密封完整性检测技术研究进展[J]. 中国药业,2021,30 (2):5
CHEN J, WANG JS, GUAN TH, et al. Research progress of container closure integrity test of injections[J]. China Pharm, 2021, 30(2):5
[15] 张艳慧. 无菌制剂容器密封性测试方法[J]. 化工设计通讯,2018,44(8):124
ZHANG YH.Test method of sealing property of sterile formulation container[J]. Chem Engin Design Commun,2018, 4(8):124
