扫码关注我们

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

玻璃类注射剂用药包材内表面耐受性测试研究

聂蕾 范旭

聂蕾, 范旭. 玻璃类注射剂用药包材内表面耐受性测试研究[J]. 分析测试技术与仪器, 2022, 28(2): 210-221. doi: 10.16495/j.1006-3757.2022.02.016
引用本文: 聂蕾, 范旭. 玻璃类注射剂用药包材内表面耐受性测试研究[J]. 分析测试技术与仪器, 2022, 28(2): 210-221. doi: 10.16495/j.1006-3757.2022.02.016
NIE Lei, FAN Xu. Test and Study on Inner Surface Tolerance of Drug Packaging Materials for Glass Injection[J]. Analysis and Testing Technology and Instruments, 2022, 28(2): 210-221. doi: 10.16495/j.1006-3757.2022.02.016
Citation: NIE Lei, FAN Xu. Test and Study on Inner Surface Tolerance of Drug Packaging Materials for Glass Injection[J]. Analysis and Testing Technology and Instruments, 2022, 28(2): 210-221. doi: 10.16495/j.1006-3757.2022.02.016

玻璃类注射剂用药包材内表面耐受性测试研究

doi: 10.16495/j.1006-3757.2022.02.016
详细信息
    作者简介:

    聂蕾(1982-), 女, 高级工程师, 主要从事药品包装材料及医疗器械检验检测及安全性研究, E-mail: 40179764@qq.com

  • 中图分类号: TN16

Test and Study on Inner Surface Tolerance of Drug Packaging Materials for Glass Injection

  • 摘要: 为筛选出快速有效的玻璃脱片检出方法, 初步建立玻璃内表面耐受性的测试方法以供药品研发人员选择参考. 采用目检、亚甲基蓝染色试验、不溶性微粒、扫描电子显微镜、离子检测等测试方法, 从不同角度考察玻璃类注射剂用药包材内表面耐受性. 试验结果表明, 玻璃安瓿的内表面耐受性要强于玻璃注射剂瓶, 中硼硅玻璃的内表面耐受性要好于低硼硅玻璃, 钠钙输液瓶的最差. 氢氧化钠溶液对玻璃容器的腐蚀能力要远远强于其余4种腐蚀溶液, 并且氢氧化钠的浓度越高, 腐蚀能力越强. 使用5种不同的检测方法进行考察, 从不同角度发现玻璃形制、材质、腐蚀溶液性质、浓度及时间均对玻璃内表面耐受性有影响. 5种方法各有优缺点, 可供药品研发人员在药品研发的初期对玻璃类包材材料进行筛选时参考选择.
  • 图  1  不同腐蚀溶液在121 ℃,2 h腐蚀条件下,5种材质玻璃容器的内表面亚甲基蓝染色试验结果

    (a) 低硼硅玻璃安瓿,(b) 中硼硅玻璃安瓿,(c)低硼硅玻璃管制注射剂瓶,(d)中硼硅玻璃管制注射剂瓶,(e) 钠钙输液瓶

    Figure  1.  Results of methylene blue staining on inner surface of different glass containers at different corrosive solutions under corrosive conditions of 121 ℃, 2 h

    (a) low borosilicate glass ampoules, (b) medium borosilicate glass ampoules, (c) low borosilicate glass injection bottles made of glass tubing, (d) medium borosilicate glass injection bottles made of glass tubing, (e) sodium calcium glass infusion bottles

    图  2  不同时间条件下,5种材质玻璃容器在121 ℃,0.001 mol/L NaOH溶液腐蚀后的内表面亚甲基蓝染色试验结果

    (a) 低硼硅玻璃安瓿,(b) 中硼硅玻璃安瓿,(c)低硼硅玻璃管制注射剂瓶,(d)中硼硅玻璃管制注射剂瓶,(e) 钠钙输液瓶

    Figure  2.  Results of methylene blue staining on inner surface of five glass containers at different times after corrosion of 0.001 mol/L NaOH at 121 ℃

    (a) low borosilicate glass ampoules, (b) medium borosilicate glass ampoules, (c) low borosilicate glass injection bottles made of glass tubing, (d) medium borosilicate glass injection bottles made of glass tubing, (e) sodium calcium glass infusion bottles

    图  3  不同时间条件下,5种材质玻璃容器在121 ℃, 0.01 mol/L NaOH溶液腐蚀后的内表面亚甲基蓝染色试验结果

    (a)低硼硅玻璃安瓿,(b) 中硼硅玻璃安瓿,(c)低硼硅玻璃管制注射剂瓶,(d)中硼硅玻璃管制注射剂瓶,(e) 钠钙输液瓶

    Figure  3.  Results of methylene blue staining on inner surface of five glass containers at different times after corrosion of 0.01 mol/L NaOH at 121 ℃

    (a) low borosilicate glass ampoules, (b) medium borosilicate glass ampoules, (c) low borosilicate glass injection bottles made of glass tubing, (d) medium borosilicate glass injection bottles made of glass tubing, (e) sodium calcium glass infusion bottles

    图  4  腐蚀前样品SEM结果

    (a)低硼硅玻璃安瓿,(b) 中硼硅玻璃安瓿,(c)低硼硅玻璃管制注射剂瓶,(d)中硼硅玻璃管制注射剂瓶,(e) 钠钙输液瓶

    Figure  4.  SEM test results of sample before corrosion

    (a) low borosilicate glass ampoule, (b) medium borosilicate glass ampoule, (c) low borosilicate glass injection bottle made of glass tubing, (d) medium borosilicate glass injection bottle made of glass tubing, (e) sodium calcium glass infusion bottle

    图  5  0.001 mol/L NaOH腐蚀后的玻璃样品的SEM结果

    (a)低硼硅玻璃安瓿,(b) 中硼硅玻璃安瓿,(c)低硼硅玻璃管制注射剂瓶,(d)中硼硅玻璃管制注射剂瓶,(e) 钠钙输液瓶

    Figure  5.  SEM test results of five glass container samples after corrosion of 0.001 mol/L NaOH

    (a)low borosilicate glass ampoules, (b) medium borosilicate glass ampoules, (c) low borosilicate glass injection bottles made of glass tubing, (d) medium borosilicate glass injection bottles made of glass tubing, (e) sodium calcium glass infusion bottles

    图  6  0.01 mol/L NaOH腐蚀的玻璃样品的SEM结果

    (a)低硼硅玻璃安瓿,(b) 中硼硅玻璃安瓿,(c)低硼硅玻璃管制注射剂瓶,(d)中硼硅玻璃管制注射剂瓶,(e) 钠钙输液瓶

    Figure  6.  SEM test results of five glass container samples after corrosion of 0.01 mol/L NaOH

    (a) low borosilicate glass ampoules, (b) medium borosilicate glass ampoules, (c) low borosilicate glass injection bottles made of glass tubing, (d) medium borosilicate glass injection bottles made of glass tubing, (e) sodium calcium glass infusion bottles

    图  7  其他腐蚀溶液的玻璃样品的SEM结果

    (a)低硼硅玻璃安瓿,(b) 中硼硅玻璃安瓿,(c)低硼硅玻璃管制注射剂瓶,(d)中硼硅玻璃管制注射剂瓶,(e) 钠钙输液瓶

    Figure  7.  SEM test results of five glass container samples after corrosion of other solutions

    (a) low borosilicate glass ampoules, (b) medium borosilicate glass ampoules, (c) low borosilicate glass injection bottles made of glass tubing, (d) medium borosilicate glass injection bottles made of glass tubing, (e) sodium calcium glass infusion bottles

    图  8  中、低硼硅玻璃安瓿在0.001 mol/L NaOH溶液不同时间浸蚀后的离子检测结果

    Figure  8.  Ion detection results of medium and low borosilicate glass ampoules corroded in 0.001 mol/L NaOH solution for different corrosion times

    图  9  中、低硼硅玻璃注射剂瓶在0.001 mol/L NaOH溶液不同时间浸蚀后的离子检测结果

    Figure  9.  Ion detection results of medium and low borosilicate glass injection bottles made of glass tubing corroded in 0.001 mol/L NaOH solution for different corrosion times

    图  10  钠钙玻璃输液瓶在0.001 mol/L NaOH溶液不同时间浸蚀后的离子检测结果

    Figure  10.  Ion detection results of sodium calcium glass infusion bottles corroded in 0.001 mol/L NaOH solution for different corrosion times

    图  11  中、低硼硅玻璃安瓿在0.01 mol/L NaOH溶液不同时间浸蚀后的离子检测结果

    Figure  11.  Ion detection results of medium and low borosilicate glass ampoules corroded in 0.01 mol/L NaOH solution for different corrosion times

    图  12  中、低硼硅玻璃注射剂瓶在0.01 mol/L NaOH溶液不同时间浸蚀后的离子检测结果

    Figure  12.  Ion detection results of medium and low borosilicate glass injection bottles made of glass tubing corroded in 0.01 mol/L NaOH solution for different corrosion times

    图  13  钠钙玻璃输液瓶在0.001 mol/L NaOH溶液不同时间浸蚀后的离子检测结果

    Figure  13.  Ion detection results of sodium calcium glass infusion bottles corroded in 0.001 mol/L NaOH solution for different corrosion times

    表  1  腐蚀溶液及条件[18]

    Table  1.   Erosion solutions and conditions [18]

    溶液 酸碱度(pH值) 试验温度/℃ 加热时间/h
    0.9%氯化钾 8.0 121 2
    3%柠檬酸 2.0 80 24
    3%酒石酸钠 7.2 80 24
    20 mmol/L甘氨酸 10.0 50 24
    0.001 mol/L氢氧化钠 10.8 121 0, 0.5, 1, 2, 4, 6, 8, 24
    0.01 mol/L氢氧化钠 12.0 121 0, 0.5, 1, 2, 4, 6, 8, 24
    下载: 导出CSV

    表  2  线性关系

    Table  2.   Results of linear equations

    元素 质量数 内标元素 线性方程 r
    Si 28 45Sc y=0.001x+0.022 0.999 9
    Al 27 y =0.002x+0.019 0.999 9
    Ca 43 y =0.000 01x-0.000 2 0.998 7
    B 11 y =0.000 4x+0.004 0.999 9
    下载: 导出CSV

    表  3  检测限、精密度测定结果

    Table  3.   Test results of detection limit and precision

    元素 检测限/(mg/L) 精密度/%
    Si 0.001 2 1.1
    Al 0.024 4 1.3
    Ca 0.010 6 4.8
    B 0.006 5 2.5
    下载: 导出CSV

    表  4  回收率结果

    Table  4.   Results of recovery

    元素 回收率/% 平均回收率/%
    Si 106.95 100.69
    99.06
    96.06
    101.88 101.98
    100.35
    103.70
    105.52 101.48
    97.98
    100.95
    Al 105.48 104.52
    102.18
    105.90
    104.22 104.41
    104.00
    105.00
    107.07 104.15
    101.20
    104.18
    Ca 113.00 105.34
    102.48
    100.55
    103.50 106.21
    105.42
    109.70
    102.13 105.72
    108.28
    106.75
    B 98.38 102.04
    101.55
    106.20
    102.14 102.89
    104.30
    102.24
    105.10 104.31
    101.03
    106.80
    下载: 导出CSV
  • [1] 李烨, 张毅兰. 药用玻璃容器内表面耐受性研究现状[J]. 中国医药工业杂志, 2014, 45(12): 1186-1191. https://www.cnki.com.cn/Article/CJFDTOTAL-ZHOU201412029.htm

    LI Ye, ZHANG Yi-lan. Research status of the inner surface durability of glass containers for pharmaceutical use[J]. Chinese Journal of Pharmaceuticals, 2014, 45(12): 1186-1191. https://www.cnki.com.cn/Article/CJFDTOTAL-ZHOU201412029.htm
    [2] 梁叶, 袁春梅. 药用玻璃包装材料是保证药品质量的重要因素[J]. 轻工标准与质量, 2007(5): 23-27. https://www.cnki.com.cn/Article/CJFDTOTAL-QGBZ200705013.htm

    LIANG Ye, YUAN Chun-mei. Medicinal glass packaging material is an important factor to ensure the quality of drugs[J]. Standard & Quality of Light Industry, 2007(5): 23-27. https://www.cnki.com.cn/Article/CJFDTOTAL-QGBZ200705013.htm
    [3] 刘言. 药品包装材料与药物相容性研究的现状及展望[J]. 天津药学, 2013, 25(6): 56-59. https://www.cnki.com.cn/Article/CJFDTOTAL-TJYA201306024.htm

    LIU Yan. Current situation and prospect of drug packaging materials and drug compatibility research[J]. Tianjin Pharmacy, 2013, 25(6): 56-59. https://www.cnki.com.cn/Article/CJFDTOTAL-TJYA201306024.htm
    [4] Iacocca R G. The causes and implications of glass delamination[EB/OL]. [2011-11-1]. http://www.pharmtech.com/pharmtech/Analytics/The-Causes-and-Implications-of-Glass-Delamination/ArticleStandard/Article/detail/747427
    [5] 李烨, 张毅兰. 通过加速试验考察不同介质对药用玻璃容器形成脱片的影响[J]. 中国医药工业杂志, 2015, 46(3): 293-298. https://www.cnki.com.cn/Article/CJFDTOTAL-ZHOU201503022.htm

    LI Ye, ZHANG Yi-lan. Delamination propensity of pharmaceutical glass containers treated with different extraction media by accelerated testing[J]. Chinese Journal of Pharmaceuticals, 2015, 46(3): 293-298. https://www.cnki.com.cn/Article/CJFDTOTAL-ZHOU201503022.htm
    [6] 赵泽馨, 张迪, 刘巧, 赵龙山. 中性硼硅玻璃安瓿中铝、硅、硼元素的迁移量与其内表面脱片趋势关系的研究[J]. 药物分析杂志, 2019, 39(12): 2214-2220. https://www.cnki.com.cn/Article/CJFDTOTAL-YWFX201912014.htm

    ZHAO Ze-xin, ZHANG Di, LIU Qiao, ZHAO Long-shan. Study on the relationship between the migration of aluminum, silicon and boron in neutral borosilicate glass ampules and the tendency of the inner surface stripping[J]. Chinese Journal of Pharmaceutical Analysis, 2019, 39(12): 2214-2220. https://www.cnki.com.cn/Article/CJFDTOTAL-YWFX201912014.htm
    [7] 吴永坤, 龚方红, 沙德仁. 纤维玻璃耐碱性的研究[J]. 玻璃纤维, 2004(4): 6-14. doi: 10.3969/j.issn.1005-6262.2004.04.002

    WU Yong-kun, GONG Fang-hong, SHA De-ren. Study on alkali resistance of fiber glass [J]. Fiber Glass, 2004(4): 6-14. doi: 10.3969/j.issn.1005-6262.2004.04.002
    [8] 张广湘, 林杨, 陈晓媛, 吴漪, 雷秀峰. 预灌封注射器玻璃针管内表面化学稳定性研究[J]. 临床医学工程, 2016, 23(3): 270-271. doi: 10.3969/j.issn.1674-4659.2016.03.0270

    ZHANG Guang-xiang, LIN Yang, CHEN Xiao-yuan, WU Yi, LEI Xiu-feng. Research on chemical stability of glass needle tube inner surface of prefilled syringe[J]. Clinical Medicine & Engineering, 2016, 23(3): 270-271. doi: 10.3969/j.issn.1674-4659.2016.03.0270
    [9] 孙秀雪, 高洋, 陈振博. 注射剂产品可见异物产生原因的研究[J]. 医药卫生, 2018, 9(1): 112-113.

    SUN Xiu-xue, GAO Yang, CHEN Zhen-bo. Study on the causes of visible foreign matter in injection products[J]. Medical and health, 2018, 9(1): 112-113.
    [10] 许雯雯, 孙震, 孙雨彤, 李金明, 车鑫, 周凤梅, 余飞, 刘万卉. LPM3480392注射液用中硼硅玻璃注射剂瓶的筛选研究[J]. 中国新药杂志, 2020, 29(12): 1425-1433. https://www.cnki.com.cn/Article/CJFDTOTAL-ZXYZ202012017.htm

    XU Wen-wen, SUN Zhen, SUN Yu-tong, LI Jin-ming, CHE Xin, ZHOU Feng-mei, YU Fei, LIU Wan-hui. Screening of medium borosilicate glass vials for LPM3480392 injection[J]. Chinese Journal of New Drugs, 2020, 29(12): 1425-1433. https://www.cnki.com.cn/Article/CJFDTOTAL-ZXYZ202012017.htm
    [11] 潘叙恩, 张译方, 张春华, 肖丽珊, 何志荣. 丙泊酚注射液与中性硼硅玻璃安瓿包材相容性研究[J]. 中国测试, 2017, 43(5): 45-48, 70. https://www.cnki.com.cn/Article/CJFDTOTAL-SYCS201705010.htm

    PAN Xu-en, ZHANG Yi-fang, ZHANG Chun-hua, XIAO Li-shan, HE Zhi-rong. Evaluating compatibility between propofol injection and neutral borosilicate glass ampoule[J]. China Measurement & Test, 2017, 43(5): 45-48, 70. https://www.cnki.com.cn/Article/CJFDTOTAL-SYCS201705010.htm
    [12] 程磊, 金宏, 王丹丹. 甲基红指示剂对玻璃内表面耐水性测定结果的影响[J]. 中国药事, 2014, 28(5): 507-510. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGYS201405012.htm

    CHENG Lei, JIN Hong, WANG Dan-dan. Effect of methyl red indicator on the results of hydrolytic resistance tests for internal surface of glass packaging products[J]. Chinese Pharmaceutical Affairs, 2014, 28(5): 507-510. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGYS201405012.htm
    [13] 王蓉佳, 蔡荣. 火焰原子吸收光谱法测定药用玻璃的内表面耐水腐蚀性[J]. 药物分析杂志, 2013, 33(12): 2148-2150. https://www.cnki.com.cn/Article/CJFDTOTAL-YWFX201312027.htm

    WANG Rong-jia, CAI Rong. Determination of hydrolytic resistance of the interior surface of pharmaceutical glass containers by flame atomic absorption spectrometry[J]. Chinese Journal of Pharmaceutical Analysis, 2013, 33(12): 2148-2150. https://www.cnki.com.cn/Article/CJFDTOTAL-YWFX201312027.htm
    [14] 刘兴兰, 张向崇, 兰俊. 药用玻璃包装容器相容性试验中硅、硼迁移量测定的研究[J]. 药物分析杂志, 2015, 35(11): 2024-2027. https://www.cnki.com.cn/Article/CJFDTOTAL-YWFX201511028.htm

    LIU Xing-lan, ZHANG Xiang-chong, LAN Jun. Determination of silicon and boron migration in compatibility experiment of pharmaceutical glass container for packaging[J]. Chinese Journal of Pharmaceutical Analysis, 2015, 35(11): 2024-2027. https://www.cnki.com.cn/Article/CJFDTOTAL-YWFX201511028.htm
    [15] 陈超, 史沛, 程磊, 訾晓伟, 王国勤, 俞辉. SEM-EDS解析药物对玻璃注射剂瓶内表面的腐蚀程度[J]. 中国现代应用药学, 2018, 35(12): 1792-1796. https://www.cnki.com.cn/Article/CJFDTOTAL-XDYD201812009.htm

    CHEN Chao, SHI Pei, CHENG Lei, ZI Xiao-wei, WANG Guo-qin, YU Hui. Analysis of the corrosion degree of drugs on the inner surface of glass injection bottle by SEM-EDS[J]. Chinese Journal of Modern Applied Pharmacy, 2018, 35(12): 1792-1796. https://www.cnki.com.cn/Article/CJFDTOTAL-XDYD201812009.htm
    [16] 郝玉红, 陈鹰, 周莹, 吴立敏, 厉艳君. 扫描电子显微镜标准装置在药用玻璃容器脱片研究中的示范应用[J]. 中国计量, 2021(8): 111-113. https://www.cnki.com.cn/Article/CJFDTOTAL-JILA202108055.htm

    HAO Yu-hong, CHEN Ying, ZHOU Ying, WU Li-min, LI Yan-jun. Demonstration application of scanning electron microscope standard device in the study of separation of medicinal glass containers[J]. China Metrology, 2021(8): 111-113. https://www.cnki.com.cn/Article/CJFDTOTAL-JILA202108055.htm
    [17] 张良明, 晏子俊, 杨波, 文慧英, 徐晓芳. 安瓿瓶内表面与枸橼酸咖啡因注射液的相容性研究[J]. 中国药房, 2018, 29(5): 644-647. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGYA201805017.htm

    ZHANG Liang-ming, YAN Zi-jun, YANG Bo, WEN Hui-ying, XU Xiao-fang. Compatibility study of inner surface of anatomy bottle and caffeine citrate injection[J]. China Pharmacy, 2018, 29(5): 644-647. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGYA201805017.htm
    [18] 孙会敏, 李樾, 赵霞, 贺瑞玲. 注射剂与药用玻璃包装容器相容性研究试验方法指南[J]. 中国药事, 2018, 32(9): 1189-1196. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGYS201809007.htm

    SUN Hui-min, LI Yue, ZHAO Xia, HE Rui-ling. Technical guidelines on experimental methods for the compatibility between injections and pharmaceutical glass packaging containers[J]. Chinese Pharmaceutical Affairs, 2018, 32(9): 1189-1196. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGYS201809007.htm
    [19] 国家食品药品监督管理总局. 化学药品注射剂与药用玻璃包装容器相容性研究技术指导原则[S]. 2015.

    State Food and drug administration Technical guidelines for compatibility research between chemical injection and pharmaceutical glass packaging containers [S]. 2015.
  • 加载中
图(13) / 表(4)
计量
  • 文章访问数:  30
  • HTML全文浏览量:  30
  • PDF下载量:  5
  • 被引次数: 0
出版历程
  • 收稿日期:  2022-02-08
  • 修回日期:  2022-04-02
  • 网络出版日期:  2022-07-07
  • 刊出日期:  2022-06-30

目录

    /

    返回文章
    返回