不同药典和标准对大输液丁基橡胶瓶塞质量要求的分析
药用丁基橡胶塞残余水分的影响因素分析
（1）烘干前胶塞重量，m1；
A、B、C、D。
（2）在105 ℃条件下热风烘干2 h后的胶塞重
56
Yaobaocai yu Zhuangbei◆药包材与装备
量，m2； （3）重量差Δ＝m1－m2。
1.7 数据计算 胶塞含水率＝Δ/m1×100%
式中 m1———烘干前胶塞重量，g； m2———在105 ℃条件下热风烘干2 h后的胶塞 重量，g； Δ— ——重量差，Δ＝m1－m2，g。
药包材与装备◆Yaobaocai yu Zhuangbei
编号 1 3 5 7 9 11 13
表2 配方B胶塞在各种处理状态下的含水量情况
胶塞状态
每个样品干燥失重平均值 /g 平均含水率 /%
清洗后不烘干
0.018 0
0.151 4
洗后烘干，成品
0.012 4
0.103 9
成品灭菌后，不烘干
0.024 9
配方C胶塞在各种处理状态下的含水量情况如 表3所示，对应的数据图如图3所示。 2.4 配方D
配方D胶塞在各种处理状态下的含水量情况如 表4所示，对应的数据图如图4所示。
从以上图表可以看出： （1）无论何种状态，处理后不烘干时，丁基橡胶 塞的含水量比烘干时要高，且至少高2～3倍； （2）成品胶塞的含水量比处理后再烘干的要高； （3）胶塞灭菌后不烘干与清洗后不烘干的含水 量接近； （4）不同配方的胶塞的含水量由低到高 顺序
每个样品干燥失重平均值 /g 0.015 7 0.066 9 0.066 9 0.008 8 0.066 0 0.010 1
平均含水率 /% 0.165 7 0.563 6 0.563 6 0.075 3 0.556 5 0.085 4
单只胶塞平均含水量值 /g 0.003 9 0.016 7 0.016 7 0.002 2 0.016 5 0.002 5
丁基胶塞对大输液不溶性微粒的影响及解决办法
丁基胶塞对大输液不溶性微粒的影响及解决办法摘要：目的查找丁基胶塞对大输液中不溶性微粒的影响，并提出解决办法。
方法通过调整不同的清洗方法查找最佳的清洗条件，并将清洗后的丁基胶塞使用在不同品种的大输液上，确定特殊品种与丁基胶塞的相容性。
结果不溶性微粒与胶塞汽水混洗的时间有直接的关系。
特殊品种使用覆膜丁基胶塞能有效提高产品的稳定性。
关键词：丁基胶塞；大输液；不溶性微粒；解决方法大输液中的不溶性微粒可造成人体局部循环障碍，引起血管栓塞和供血不足及组织缺氧而产生的水肿及静脉炎。
不溶性微粒对人体产生的危害已引起了广泛的关注【1】。
注射用卤化丁基胶塞直接与药物接触，虽然其具有化学性气密性好，无生理毒副作用等特点，但在使用过程中，仍然存在与药物的相互作用，甚至影响药物的物理性质与治疗作用，故丁基胶赛的质量问题不容忽视，必须对其进行严格的检验和控制。
丁基胶塞在制备过程中需要添加一定量的硅油进行硅化处理，丁基胶塞的包装和硅化等对其都是一种污染，产品高温灭菌后硅油等杂质会从胶塞中释放出来，产生不溶性微粒，严重影响产品的质量。
考察丁基胶塞不同清洗工艺对药品的质量影响，有重要的意义。
本次实验采用过滤后的注射用水和压缩空气对胶塞不同的清洗时间进行清洗，然后115℃水浴灭菌30min后进行可见异物的检查和不溶性微粒的测定，以确定不同的胶塞清洗方法对药液中不溶性微粒的影响。
1仪器和设备ZWF-J6激光注射液微粒分析仪（天津市天河医疗仪器研制中心）。
丁基胶塞由烟台某厂家及江阴某厂家提供（厂家均提供合格证书）。
生产所采用原辅料均符合国家标准。
2方法与结果2.1不同的胶塞漂洗法对不溶性微粒的影响生产中使用胶塞清洗机的标准清洗数量为每罐20 000只，注射用水的温度在80℃左右。
试验26口胶塞清洗方法分别按照淋洗3min，汽水混洗7min，漂洗5min及淋洗3min，汽水混洗5min，漂洗5min进行清洗，对比氯化钠注射液产品灭菌前后不溶性微粒的情况，依照《中国药典》2010年版(二部)附录ⅨC（光阻法）方法测定样品微粒水平，结果见表1。
丁基胶塞的选用及其处理方法对输液不溶性微粒的影响
丁基胶塞的选用及其处理方法对输液不溶性微粒的影响吴建平董永成陈永顺杜士明叶立红2005-10-7 16:23:52 中华实用医药杂志2005 年9 月第5 卷第17 期关键词：丁基胶塞【摘要】目的比较不同厂家丁基胶塞对大输液不溶性微粒的影响，筛选最适用者。
方法保持其他生产条件一致，比较不同厂家丁基胶塞使用不同处理方法对大输液不溶性微粒的影响，并进行分析。
结果与结论采用注射用水煮沸20min的方法处理丁基胶塞可显著降低大输液不溶性微粒。
【关键词】丁基胶塞；输液；不溶性微粒根据国家食品和药品监督管理局（SFDA）［国食药监注（2004）391号］文件的规定，由2005年1月1日起，停用天然胶塞而改用丁基胶塞。
为此，我院对原有输液生产线进行了必要的改进，于1月8日进行试生产。
但在试生产过程中发现不同厂家的丁基胶塞和不同的处理方法对成品不溶性微粒水平影响很大，现报告如下。
1 仪器和设备ZWF-J6激光注射液微粒分析仪（天津市天河医疗仪器研制中心）。
医用丁基胶塞分由下列三个厂家提供（厂家均提供合格证书）：应城某厂(批号0408012)；台州某厂(批号0412004-01)；江阴某厂(批号041225)。
生产所采用原辅料均符合国家标准。
2 方法与结果2.1 注射用水漂洗法对不溶性微粒的影响为了排除干扰，笔者在制剂品种和规格、生产工艺流程、操作人员一致的条件下进行实验，丁基胶塞处理方法按厂家推荐方法，即临用前用注射用水漂洗。
随机抽取盖塞前（A）、盖塞后（B）、消毒灯检合格后（C）的样品，依照《中国药典》2000年版二部附录ⅨC［1］方法测定样品微粒水平，结果见表1。
2.2 注射用水煮沸20min法对不溶性微粒的影响丁基胶塞在临用前采用注射用水煮沸20min，依2.1方法测定微粒水平，结果见表2。
表1 水漂洗法对不溶性微粒的影响略表2 水煮沸法对不溶性微粒的影响略2.3 结果实验表明，盖塞后微粒水平显著增加（P＜0.05），说明在其他条件相同情况下，胶塞是造成微粒增加的直接原因；采用注射用水煮沸20min可以显著降低微粒水平。
丁基橡胶药用瓶塞检测SOP
丁基橡胶药用瓶塞检测SOP1. 目的为规范注射液用卤化丁基橡胶药用瓶塞的检定，特制定本SOP。
2. 范围本SOP适用于直接与注射剂接触的卤化丁基橡胶塞（注射液用卤化丁基橡胶塞、预灌封注射器用氯化丁基橡胶塞、预灌封注射器用溴化丁基橡胶塞）的检定。
3. 定义无4. 职责4.1.QC负责本规程的起草、修订、培训及执行。
4.2.QA、QC组长、质量管理部经理负责本规程的审核。
4.3.质量总监负责批准本规程。
4.4.QA负责本规程执行的监督。
5. 引用标准5.1.注射液用卤化丁基橡胶塞国家食品药品监督管理局直接接触药品的包装材料和容器标准汇编5.2.预灌封注射器用氯化丁基橡胶活塞国家食品药品监督管理局直接接触药品的包装材料和容器标准汇编5.3.预灌封注射器用溴化丁基橡胶活塞国家食品药品监督管理局直接接触药品的包装材料和容器标准汇编5.4.《中华人民共和国药典》6. 材料6.1.仪器设备天平，恒温水浴箱，分光光度计，pH计，恒温干燥箱，变温电炉，干燥器，电导率仪，高温炉。
6.2.试剂溶液标准铅溶液：购入；氯化铵铵溶液：取氯化铵10.5g，加水溶解使成100ml，即得；标准锌溶液：称取硫酸锌（ZnSO4·7H2O）0.440g，置1000ml量瓶中，加水溶解并稀释至刻度，摇匀，即得（每1ml相当于100µg的Zn）；0.02mol/L高锰酸钾滴定液: 按《高锰酸钾滴定液配制及标定SOP》操作；0.1mol/L硫代硫酸钠滴定液：按《硫代硫酸钠滴定液配制及标定SOP》操作；碳酸氢钠：购入；硝酸：购入；硝酸银试液：取硝酸银17.5g，加水适量使溶解成1000ml，摇匀，即得；0.1%氯化钾溶液：取氯化钾0.1g，加水使溶解成100 ml，即得；稀硫酸：取硫酸57ml，加水稀释至1000ml，即得；淀粉指示液：取可溶性淀粉0.5g，加水5ml搅匀后，缓缓倾入100ml沸水中，随加随搅拌，继续煮沸2min，放冷，倾取上层清液，即得，本液应临用新制；碱性碘化汞钾试液：二氯化汞饱和水溶液：取二氯化汞7g，溶于100ml水中，摇匀。
药用丁基胶塞---四大药典检测标准异同
药用丁基胶塞---四大药典检测标准异同Summary1、Penetrability[YBB]Take 10 rubber closures, test according to the second method of YBB60072012, the average puncture force does not exceed 10N.[EP] Fill 10 suitable vials to the nominal volume with water R, fit the closures to be examined and secure with a cap. Using foreach closure a new, lubricated long-bevel(1) (bevel angle 12 ± 2°) hypodermic needle with an external diameter of 0.8 mm, pierce the closures with the needle perpendicular to the surface. The force required for piercing, determined with an accuracy of ± 0.25 N (25 gf), is not greater than 10 N (1 kgf) for each closure.[JP]None[USP]Fill 10 suitable vials to the nominal volume with water, fit the closures to be examined, and secure with a cap. Using a new hypodermic needle as described above for each closure, pierce the closure with the needle perpendicular to the surface.Requirement—The force for piercing is no greater than 10 N (1 kgf) f or each closure, determined with an accuracy of ± 0.25 N (25 gf).2、Fragmentation[YBB]Take 10 rubber closures, test according to the second method of YBB60082012, The total number of fragments does not exceed 5.[EP] For closures intended to be pierced by a hypodermic needle, carry out the following test. If the closures are to be used for aqueous preparations, place in12 clean vials a volume of water R corresponding to the nominal volume minus4 ml, close the vials with the closures to be examined, secure with a cap andallow to stand for 16 h. If the closures are to be used with dry preparations, close 12 clean vials with the closures to be examined. Using a lubricated long-bevel(1) (bevel angle 12 ±2°) hypodermic needle with an external diameter of 0.8 mm fitted to a clean syringe, inject into the vial 1 ml of water R and remove 1 ml of air ; carry out this operation 4 times for each closure,piercing each time at a different site. Use a new needle for each closure and check that the needle is not blunted during the test. Pass the liquid in the vials through a filter having approxi mately 0.5 μm pores. Count the fragments of rubber visible to the naked eye. The total number of fragments does not exceed5. This limit is based on the assumption that fragments witha diameter equal toor greater than 50 μm are visible to the naked eye; in cases of doubt or dispute, the fragments are examined with a microscope to verify their nature and size. [JP] None[USP] Closures for Liquid Preparations—Fill 12 clean vials with water to 4 mL less than the nominal capacity. Fit the closures to be examined, secure with acap, and allow to stand for 16 hours.Closures for Dry Preparations— Fit closures to be examined into 12 cleanvials, and secure each with a cap.Procedure— Using a hypodermic needle as described above fitted to a cleansyringe, inject into each vial 1 mL of water while removing 1 mL of air. Repeat this procedure 4 times for each closure, piercing each time at a different site.Use a new needle for each closure, checking that it is not blunted during the test.Filter the toatal volume of liquid in all the vials through a single filter with a nominal pore size no greater than 0.5 μm. Count the rubber fragments on the surface of the filter visible to the naked eye.Requirement— There are no more than 5 fragments visible. This limit is based on the assumption that fragments with adiameter >50 μm are visible to the naked eye. In case of doubt or dispute, the particles are examined microscopically to verify their nature and size.3、Sealing test of rubber closure and container[YBB] Take 10 rubber closures into the beaker, boil for 5 min , take out and dry 1h at 70℃ and ready to use. Fill 10 suitable vials to the nominal volume with water, fit the closures to be examined and secure with a cap. Heat in an autoclave so that a temperature of 121 ± 2 °C and maintain at this temperature for 30 min.Cool to room temperature and then place 24h, Immerse the vials upside down ina 10% solution of methylene blue R and reduce the external pressure by 25 kPafor 30 min. Restore atmospheric pressure and leave the vials immersed for 30 min. Rinse the outside of the vials. None of the vials contains any trace of colored solution.[EP]None[JP]None[USP] None4、Self-Sealing Capacity[YBB]Take the samples from sealing test of rubber closure and container, using for a hypodermic needle (YBB60082012 method 2), pierce each closure 3 times, change the hypodermic needle after it is used 10 times ,piercing each time at a different site.The vials upside down in a 10% solution of methylene blue R and reduce the external pressure by 25 kPa for 30 min. Restore atmospheric pressure and leave the vials immersed for 30 min. Rinse the outside of the vials. None of the vials contains any trace of colored solution.[EP]For closures intended to be used with multidosecontainers, carry out the following test. Fill 10 suitable vials to the nominal volume with water R, fit the closures to be examined and secure with a cap. Using for each closure a new hypodermic needle with an external diameter of 0.8 mm, pierce each closure 10 times, piercing each time at a different site. Immerse the vials upright in a 1 g/l solution of methylene blue R and reduce the external pressure by 27 kPa for 10 min. Restore atmospheric pressure and leave the vials immersed for 30 min.Rinse the outside of the vials. None of the vials contains any trace of coloured solution.[JP]None[USP]Procedure—Fill 10 suitable vials with water to the nominal volume. Fit the closures that are to be examined, and cap. Using a new hypodermic needle as described above for each closure, pierce each closure 10 times, piercing each time at a different site. Immerse the 10 vials in a solution of 0.1% (1 g per L) methylene blue, and reduce the external pressure by 27 kPa for 10 minutes.Restore to atmospheric pressure, and leave the vials immersed for 30 minutes.Rinse the outside of the vials.Requirement—None of the vials contain any trace of blue solution.5、Total Ash[YBB] Take the rubber closures, test according to YBB600212012, should be comply with the standard.[EP]The total ash (2.4.16) is within ± 10 per cent of the result obtained with the type sample.[JP]None[USP] None6、Volatile Sulfides[YBB]Take the rubber closures, according to the YBB60052012, should be comply with the standard.[EP] Place closures, cut if necessary, with a total surface area of 20 ± 2 cm2 in a 100 ml conical flask and add 50 ml of a 20 g/l solution of citric acid R. Place a piece of lead acetate paper R over the mouth of the flask and maintain the paper in position by placing over it an inverted weighing bottle. Heat in an autoclave at 121 ± 2℃ for 30 min. Any black stain on the paper is not more intense than that of a standard prepared at the same time in the same manner using 0.154 mg of sodium sulphide R and 50 ml of a 20 g/l solution of citric acid R.[JP]None[USP] Procedure—Place closures, cut if necessary, with a total surface area of 20 ± 2 cm2 in a 100-mL flask, and add 50 mL of a 20 g per L citric acid solution. In the same manner and at the same time, prepare a control solution in a separate 100-mL flask by dissolving 0.154 mg of sodium sulfide in 50 mL of a 20 g per L citric acid solution. Place a piece of lead acetate paper over the mouth of each flask, and hold the paper in position by placing over it an inverted weighing bottle. Heat the flasks in an autoclave at 121 ± 2℃for 30minutes.Requirement—Any black stain on the paper produced by Solution S is not more intense than that produced by the control solution.7、Preparation of Solution S[YBB] Put a number of uncut closures corresponding to a surface area of about 200 cm2 in a suitable glass container, cover with purified water( sample: water=1:2), boil for 5 min and rinse 5 times with the same volume of purified water. Place the washedclosures in a conical flask, add the same volume of water and weigh.Cover the mouth of the flask with a borosilicate-glass beaker. Heat in an autoclave so that a temperature of 121 ± 2 °C is reached within 20 min to 30 min and maintain at this temperature for 30 min. Cool to room temperature.Make up to the original mass with purified water. Shake and immediately separate the solution from the rubber by decantation. Shake solution S before each test Blank. Prepare a blank in the same manner using 400 mL of water for purified water.[EP] Solution S.Introduce a number of uncut closures corresponding to a surface area of about 100 cm2in a suitable glass container, cover with water for injections R, boil for 5 min and rinse 5 times with cold water for injections R.Place the washed closures in a wide-necked flask (glass type I, 3.2.1), add 200 ml of water for injections R and weigh. Cover the mouth of the flask with a borosilicate-glass beaker. Heat in an autoclave so that a temper ature of 121 ±2 °C is reached within 20 min to 30 min and maintain at this temperature for 30min. Cool to room temperature over about 30 min. Make up to the original mass with water for injections R. Shake and immediately separate the solution from the rubber by decantation. Shake solution S before each testBlank. Prepare a blank in the same manner using 200 ml of water for injections R.[JP] Wash the rubber closures with water, and dry at room temperature. Place them in a glass container, add water exactly 10 times the mass of the test material, close with a suitablestopper, heat at 121℃ for 1 hour in an autoclave, take out the glass container, allow to cool to room temperature,then take out immediately the rubber closures, and use the remaining solution as the testsolution. Prepare the blank solution with water in the same manner. Perform the following tests with the test solution and the blank solution[USP] Place whole, uncut closures corresponding to a surface area of 100 ± 10 cm2 intoa suitable glass container. Cover the closures with 200 mL of Purified Water orWater for Injection. If it is not possible to achieve the prescribed closure surface area (100 ± 10 cm2) using uncut closures, select the number of closures that will most closely approximate 100 cm2, and adjust the volume of water used to the equivalent of 2 mL per each 1 cm2 of actual closure surface area used. Boil for 5 minutes, and rinse five times with cold Purified Water or Water for InjectionPlace the washed closures into a Type I glass wide-necked flask (see Containers—Glass 660 ), add the same quantity of Purified Water or Water for Injection initially added to the closures, and weigh. Cover the mouth of the flask with a Type I glass beaker. Heat in an autoclave so that a temperature of 121 ± 2℃ is reached within 20 to 30 minutes, and maintain this temperature for30 minutes. Cool to room temperature over a period of about 30 minutes. AddPurified Water or Water for Injection to bring it up to the original mass. Shake, and immediately decant and collect the solution. [NOTE—This solution must be shaken before beingused in each of the tests]Prepare a blank solution similarly, using 200 mL of Purified Water or Water for Injection omitting the closures8、Appearance of solution[YBB]According to the part 2 of Chinese pharmacopoeia, 2010 edition of appendixⅨB and appendix IX A, standard solution is not more opalescent than reference suspension II. Standard solution is not more intensely coloured than No.5 reference solution[EP] Solution S is not more opalescent than reference suspension II for type I closures and is not more opalescent than reference suspension III for type II closures(2.2.1). Solution S is not more intensely coloured than reference solution GY5(2.2.2, Method II).[JP] Place 5 mL of the test solution in a glass-stoppered test tube of about 15 mm in inner diameter and about 200 mm in length, and shake vigorously for 3 minutes.The foam arisen disappears almost completely within 3 minutes.[USP] Determination of Turbidity (Opalescence)Procedure A: Visual Comparison— Use identical test tubes made of colorless, transparent, neutral glass with a flat base and an internal diameter of 15 to 25 mm. Fill one tube to a depth of 40 mm with Solution S, one tube to the same depth with water, and four others to the same depth with Reference Suspensions A, B, C,and D. Compare the solutions in diffuse daylight 5 minutes after preparation of the Reference Suspensions, viewing vertically against a black background. The light conditions shall be such that Reference Suspension A can be readily distinguished fromwater and that Reference Suspension B can be readily distinguished fromReference Suspension A.REQUIREMENT—Solution S is not more opalescent than Reference Suspension B for Type I closures, and not more opalescent than Reference Suspension C for Type II closures. Solution S is considered clear if its clarity is the same as that of water when examined as described above, or if its opalescence is not more pronounced than that of Reference Suspension A (refer to Table 3).Procedure B: Instrumental Comparison—Measure the turbidity of theReference Suspensions in a suitable calibrated turbidimeter (see Spectrophotometry and Light Scattering 851 ). The blank should be run and the results corrected for the blank. Reference Suspensions A, B, C, and D represent 3, 6, 18 and 30 Nephelometric Turbidity Units (NTU), respectively. Measure the turbidity of Solution S using the calibrated turbidimeter. REQUIREMENT—The turbidity of Solution S is not greater than that for Reference Suspension B (6 NTU FTU) for Type I closures, and is not greater than that forReference Suspension C (18 NTU FTU) for Type II closures (refer to Table 3).Determination of ColorColor Standard—Prepare a solution by diluting 3.0 mL of Matching Fluid O (see Color and Achromicity 631 ) with 97.0 mL of diluted hydrochloric acid. Procedure—Use identical tubes made of colorless, transparent, neutral glass with a flat base and an internal diameter of 15 to 25 mm. Fill one tube to a depth of 40 mm with Solution S, and the second with Color Standard. Compare the liquids in diffuse daylight, viewing vertically against a white background. Requirement—Solution S is not moreintensely colored than the Color Standard.9、Acidity or Alkalinity(PH)[YBB]Take each of 20 ml blank solution and solution S, respectively with KCl solution1 ml, According to the part2 of Chinese pharmacopoeia, 2010 edition ofappendixⅥH, the difference between the two may not be over 1.0.[EP] To 20ml of solution S add 0.1ml of bromothymol blue solution R1. Not more than 0.3ml of 0.01 M sodium hydroxide or 0.8 ml of 0.01 M hydrochloric acid is required to obtain either a blue or a yellow colour, respectively.[JP] T o 20 mL each of the test solution and the blank solution add 1.0 mL each of potassium chloride solution, prepared by dissolving 1.0 g of potassium chloride in water to make 1000 mL. The difference of pH between the two solutions is not more than 1.0[USP] Bromothymol Blue Solution—Dissolve 50 mg of bromothymol blue in a mixture of 4 mL of 0.02 M sodium hydroxide and 20 mL of alcohol. Dilute with water to 100 mL.Procedure—To 20 ml of Solution S add 0.1 ml of Bromothymol Blue Solution.If the solution is yellow, titrate with 0.01 N sodium hydroxide until a blue endpoint is reached. If the solution is blue, titrate with 0.01 N hydrochloric acid until a yellow endpoint is reached. If the solution is green, it is neutral and no titration is required.Blank Correction—Test 20 mL of Blank similarly. Correct the results obtained for Solution S by subtracting or adding the volume of titrant required for the Blank, as appropriate. (Reference Titrimetry 541 .)Requirement—Not more than 0.3 ml of 0.01 N sodium hydroxide produces a blue color, or not more than 0.8 ml of 0.01 N hydrochloric acid produces a yellow color, or no titration is required.10、Absorbance[YBB] Filter solution S on a membrane filter having approximately 0.45 μm pores.Measure the absorbance of the filtrate at wavelengths from 220 nm to 360 nm using the blank as compensation liquid. At these wavelengths, the absorbance does not exceed 0.1(according to the part 2 of Chinese pharmacopoeia, 2010 edition of appendixⅣA).[EP] Carry out the test within 5 h of preparation of solution S. Filter solution S on a membrane filter having approximately 0.45 μm pores rejecting the first few milliliters of filtrate. Measure the absorbance (2.2.25) of the filtrate at wavelengths from 220 nm to 360 nm using the blank (see solution S) as compensation liquid. At these wavelengths, the absorbance does not exceed 0.2 for type I closures or 4.0 for type II closures. If necessary, dilute the filtrate before measurement of the absorbance and correct the result for the dilution. [JP] Read the absorbance of the test solution between 220 nm and 350 nm against the blank solution as directed under Ultraviolet-visible Spectrophotometry <2.54>: it is not more than 0.20.[USP] Procedure — [NOTE—Perform this test within 5 hours of preparing Solution S.] Filter Solution S through a 0.45-μm pore size filter, discarding the first few mL of filtrate. Measure the absorbance of the filtrate at wavelengths between 220 and 360 nm in a 1-cm cell using the blank in a matched cell in the reference beam. If dilution of the filtrate is required beforemeasurement of the absorbance, correct the test results for the dilution.Requirement—The absorbances at these wavelengths do not exceed 0.2 for Type I closures or 4.0 for Type II closures.11、Reducing Substances[YBB] To 20.0 mL of solution S add 1 mL of dilute sulfuric acid R and 20.0 mL of0.002 M potassium permanganate. Boil for 3 min. Cool. Add 0.1 g of potassiumiodide R and titrate immediately with 0.01 M sodium thiosulfate until the colorturned light brown , using 5 drops of starch solution R as indicator. Carry out atitration using 20.0 mL of the blank. The difference between the titrationvolumes is not greater than7.0mL.[EP] Carry out the test within 4 h of preparation of solution S. To 20.0 ml of solution S add 1 ml of dilute sulphuric acid R and 20.0 ml of 0.002 M potassium permanganate. Boil for 3min. Cool. Add 1 g of potassium iodide R and titrate immediately with 0.01 M sodium thiosulphate, using 0.25 ml of starch solution R as indicator. Carry out a titration using 20.0 ml of the blank. The difference between the titration volumes is not greater than 3.0 ml for type I closures and7.0 ml for type II closures.[JP] Measure 100 mL of the test solution in a glass-stoppered,Erlenmyer flask, add10.0 mL of 0.002 mol/L potassium permanganate VS and 5 mL of dilutesulfuric acid, and boil for 3 minutes. After cooling, add 0.10g of potassium iodide,stopper, mix by shaking, then allow to stand for 10 minutes,and titrate<2.50> with 0.01 mol/L sodium thiosulfate VS(indicator: 5 drops of starch TS).Perform the blank test in the same manner, using 100 mL of the blank solution.The difference in mL of 0.002 mol/L potassium permanganate VS required between the tests is not more than 2.0 mL.[USP] Procedure— [NOTE—Perform this test within 4 hours of preparing Solution S.] T o 20.0 mL of Solution S add 1 mL of diluted sulfuric acid and 20.0 mL of0.002 M potassium permanganate. Boil for 3 minutes. Cool, add 1 g ofpotassium iodide, and titrate immediately with 0.01 M sodium thiosulfate, using0.25 mL of starch solution TS as the indicator. Perform a titration using 20.0mL of blank and note the difference in volume of 0.01 M sodium thiosulfaterequired.Requirement—The difference between the titration volumes is not greater than 3.0 mL for Type I closures and not greater than 7.0 mL for Type II closures.12、Residue on evaporation[YBB]Evaporate 100 mL of solution S and blank solution to dryness on a water-bath and dry at 100 °C to 105 °C. The residue weighs not more than 4.0 mg. [EP]Evaporate 50.0 ml of solution S to dryness on a water-bath and dry at 100 °C to 105 °C. The residue weighs not more than 2.0 mg for type I rubber and notmore than 4.0 mg for type II rubber.[JP]Measure 100 mL of the test solution, evaporate on a water bath to dryness, and dry the residue at 1059 C for 1 hour.The mass of the residue is not morethan 2.0 mg.[USP]None13、Ammonium[YBB] Precision measuring 10 ml of solution S, adding alkaline potassium iodide solution 2 ml, place 15 minutes, should not be color; if it colored , compare with reference solution (with 2.0 ml ammonium chloride solution (take ammoniumchloride 31.5 mg, add right amount chlorine free water and dissolve diluted to1000 ml), 8 ml blank reference solution, 2ml alkaline potassium mercuric iodide solution for mixing), should not be more intensely colored (0.0002%)[EP] maximum 2 ppm.Dilute 5 ml of solution S to 14 ml with water R. The solution complies with limit test A.[JP]None[USP] Alkaline Potassium Tetraiodomercurate Solution—Prepare a 100 mL solution containing 11 g of potassium iodide and 15 g of mercuric iodide in water.Immediately before use, mix 1 volume of this solution with an equal volume ofa 250 g per L solution of sodium hydroxide.Test Solution— Dilute 5 mL of Solution S to 14 mL with water. Make alkaline if necessary by adding 1 N sodium hydroxide, and dilute with water to 15 mL.Add 0.3 mL of Alkaline Potassium TetraiodomercurateSolution, and close the container.Ammonium Standard Solution—Prepare a solution of ammonium chloride in water (1 ppm NH4). Mix 10 mL of the 1 ppm ammonium chloride solution with5 mL water and 0.3 mL of Alkaline Potassium Tetraiodomercurate Solution.Close the container.Requirement—After 5 minutes, any yellow color in the Test Solution is no darker than the Ammonium Standard Solution (no more than 2 ppm of NH4 in Solution S).14、Extractable Zinc[YBB] Filter solution S on a membrane filter having approximately 0.45μm pores, Precision measuring filtrate 10 ml, add 1 ml 2 mol/L of hydrochloric acid and 3 drops of potassium ferrocyanide test solution(weight 4.2 g potassium ferrocyanide trihydrate, dissolve and diluted with water to 100 ml, shake evenly, this product should be new prepared) for mixing, should not be color; if it colored, compare with reference solution( with 3 ml standard zinc solution (weight 44.0g Zinc sulfate seven hydrated compounds, with new boiled and cooled purified water dissolved and diluted to 1000 ml, this product should be new prepared), shall not be deeper(0.0002%)，7ml blank reference solution, 1ml 2mol/L hydrochloric acid and 3 drops of potassium ferrocyanide solution for mixing), should not be more intensely colored.(0.0003%)[EP] maximumof 5 μg of extractable Zn per millilitre of solution S.Atomic absorption spectrophotometry (2.2.23, Method I). Test solution. Dilute10.0 ml of solution S to 100 ml with 0.1 M hydrochloric acid.Reference solutions. Prepare the reference solutions using zinc standard solution(10 ppm Zn) R diluted with 0.1 M hydrochloric acid.Source: zinc hollow-cathode lamp.Wavelength: 213.9 nm.Flame: air-acetylene.[JP]T o 10.0 mL of the test solution add diluted dilute nitric acid (1 in 3) to make 20 mL, and use this solution as the sample solution. Further, to 1.0 mL of Standard Zinc Solutionfor atomic absorption spectrophotometry add diluted nitricacid (1 in 3) to make exactly 20 mL, and use this solution asthe standard solution. Perform the tests according to the Atomic Absorption Spectrophotometry <2.23>,using these solutions, under the following conditions.The absorbanceof the sample solution is not more than that of the standardsolution.Gas: Combustible gasóAcetylene.。
丁基橡胶塞 质量标准
丁基橡胶塞质量标准一、外观质量1.丁基橡胶塞表面应光滑、平整，无明显的气泡、裂纹和杂质。
2.丁基橡胶塞的色泽应均匀，符合设计要求。
3.丁基橡胶塞的形状和尺寸应符合设计图纸要求。
二、尺寸精度1.丁基橡胶塞的尺寸应符合设计图纸要求，误差不超过±0.1mm。
2.丁基橡胶塞的孔径和孔深应符合设计图纸要求，误差不超过±0.2mm。
三、物理性能1.丁基橡胶塞应具有良好的弹性和回弹性，以满足使用要求。
2.丁基橡胶塞应具有较好的耐温性能，能在规定的使用温度下保持其物理性能不变。
3.丁基橡胶塞应具有较好的耐老化性能，经过规定的老化试验后，仍能保持良好的使用性能。
四、化学性能1.丁基橡胶塞应具有较好的化学稳定性，能耐受常见的化学物质的侵蚀。
2.丁基橡胶塞应不含有对人体有害的物质，符合相关卫生标准。
五、密封性能1.丁基橡胶塞应具有较好的密封性能，能够有效地防止液体和气体的泄漏。
2.在规定的使用压力下，丁基橡胶塞不应出现明显的变形或损坏。
六、耐老化性能1.丁基橡胶塞应能在规定的温度和湿度条件下，经过一定时间的老化试验后，仍能保持良好的使用性能。
2.丁基橡胶塞的老化试验包括但不限于热老化、紫外线老化、臭氧老化等。
七、无毒无害1.丁基橡胶塞应采用无毒、无害的原材料制作，不含有对人体有害的物质。
2.丁基橡胶塞应符合相关的卫生标准和环保要求。
3.八、符合设计要求4.丁基橡胶塞应满足设计图纸中的各项技术要求，包括但不限于材质、结构、尺寸、性能等。
5.在生产和检验过程中，应严格遵守相关的工艺流程和检验标准，确保产品质量符合设计要求。
药用丁基胶塞---四大药典检测标准异同
Summary1、Penetrability[YBB]Take 10 rubber closures, test according to the second method of YBB60072012, the average puncture force does not exceed 10N.[EP] Fill 10 suitable vials to the nominal volume with water R, fit the closures to be examined and secure with a cap. Using for each closure a new, lubricated long-bevel(1) (bevel angle 12 ± 2°) hypodermic needle with an external diameter of 0.8 mm, pierce the closures with the needle perpendicular to the surface. The force required for piercing, determined with an accuracy of ± 0.25 N (25 gf), is not greater than 10 N (1 kgf) for each closure.[JP]None[USP]Fill 10 suitable vials to the nominal volume with water, fit the closures to be examined, and secure with a cap. Using a new hypodermic needle as described above for each closure, pierce the closure with the needle perpendicular to the surface.Requirement—The force for piercing is no greater than 10 N (1 kgf) for each closure, determined with an accuracy of ± 0.25 N (25 gf).2、Fragmentation[YBB]Take 10 rubber closures, test according to the second method of YBB60082012, The total number of fragments does not exceed 5.[EP] For closures intended to be pierced by a hypodermic needle, carry out the following test. If the closures are to be used for aqueous preparations, place in12 clean vials a volume of water R corresponding to the nominal volume minus4 ml, close the vials with the closures to be examined, secure with a cap andallow to stand for 16 h. If the closures are to be used with dry preparations, close 12 clean vials with the closures to be examined. Using a lubricated long-bevel(1) (bevel angle 12 ±2°) hypodermic needle with an external diameter of 0.8 mm fitted to a clean syringe, inject into the vial 1 ml of water R and remove 1 ml of air ; carry out this operation 4 times for each closure, piercing each time at a different site. Use a new needle for each closure and check that the needle is not blunted during the test. Pass the liquid in the vials through a filter having approxi mately 0.5 μm pores. Count the fragments of rubber visible to the naked eye. The total number of fragments does not exceed5. This limit is based on the assumption that fragments with a diameter equal toor greater than 50 μm are visible to the naked eye; in cases of doubt or dispute, the fragments are examined with a microscope to verify their nature and size. [JP] None[USP] Closures for Liquid Preparations— Fill 12 clean vials with water to 4 mL less than the nominal capacity. Fit the closures to be examined, secure with acap, and allow to stand for 16 hours.Closures for Dry Preparations— Fit closures to be examined into 12 cleanvials, and secure each with a cap.Procedure— Using a hypodermic needle as described above fitted to a cleansyringe, inject into each vial 1 mL of water while removing 1 mL of air. Repeat this procedure 4 times for each closure, piercing each time at a different site.Use a new needle for each closure, checking that it is not blunted during the test.Filter the toatal volume of liquid in all the vials through a single filter with a nominal pore size no greater than 0.5 µm. Count the rubber fragments on the surface of the filter visible to the naked eye.Requirement— There are no more than 5 fragments visible. This limit is based on the assumption that fragments with a diameter >50 µm are visible to the naked eye. In case of doubt or dispute, the particles are examined microscopically to verify their nature and size.3、Sealing test of rubber closure and container[YBB] Take 10 rubber closures into the beaker, boil for 5 min , take out and dry 1h at 70℃ and ready to use. Fill 10 suitable vials to the nominal volume with water, fit the closures to be examined and secure with a cap. Heat in an autoclave so that a temperature of 121 ± 2 °C and maintain at this temperature for 30 min.Cool to room temperature and then place 24h, Immerse the vials upside down ina 10% solution of methylene blue R and reduce the external pressure by 25 kPafor 30 min. Restore atmospheric pressure and leave the vials immersed for 30 min. Rinse the outside of the vials. None of the vials contains any trace of colored solution.[EP]None[JP]None[USP] None4、Self-Sealing Capacity[YBB]Take the samples from sealing test of rubber closure and container, using for a hypodermic needle (YBB60082012 method 2), pierce each closure 3 times, change the hypodermic needle after it is used 10 times ,piercing each time at a different site.The vials upside down in a 10% solution of methylene blue R and reduce the external pressure by 25 kPa for 30 min. Restore atmospheric pressure and leave the vials immersed for 30 min. Rinse the outside of the vials. None of the vials contains any trace of colored solution.[EP]For closures intended to be used with multidose containers, carry out the following test. Fill 10 suitable vials to the nominal volume with water R, fit the closures to be examined and secure with a cap. Using for each closure a new hypodermic needle with an external diameter of 0.8 mm, pierce each closure 10 times, piercing each time at a different site. Immerse the vials upright in a 1 g/l solution of methylene blue R and reduce the external pressure by 27 kPa for 10 min. Restore atmospheric pressure and leave the vials immersed for 30 min.Rinse the outside of the vials. None of the vials contains any trace of coloured solution.[JP]None[USP]Procedure—Fill 10 suitable vials with water to the nominal volume. Fit the closures that are to be examined, and cap. Using a new hypodermic needle as described above for each closure, pierce each closure 10 times, piercing each time at a different site. Immerse the 10 vials in a solution of 0.1% (1 g per L) methylene blue, and reduce the external pressure by 27 kPa for 10 minutes.Restore to atmospheric pressure, and leave the vials immersed for 30 minutes.Rinse the outside of the vials.Requirement—None of the vials contain any trace of blue solution.5、Total Ash[YBB] Take the rubber closures, test according to YBB600212012, should be comply with the standard.[EP]The total ash (2.4.16) is within ± 10 per cent of the result obtained with the type sample.[JP]None[USP] None6、Volatile Sulfides[YBB]Take the rubber closures, according to the YBB60052012, should be comply with the standard.[EP] Place closures, cut if necessary, with a total surface area of 20 ± 2 cm2 in a 100 ml conical flask and add 50 ml of a 20 g/l solution of citric acid R. Place a piece of lead acetate paper R over the mouth of the flask and maintain the paper in position by placing over it an inverted weighing bottle. Heat in an autoclave at 121 ± 2℃ for 30 min. Any black stain on the paper is not more intense than that of a standard prepared at the same time in the same manner using 0.154 mg of sodium sulphide R and 50 ml of a 20 g/l solution of citric acid R.[JP]None[USP] Procedure— Place closures, cut if necessary, with a total surface area of 20 ± 2 cm2 in a 100-mL flask, and add 50 mL of a 20 g per L citric acid solution. In the same manner and at the same time, prepare a control solution in a separate 100-mL flask by dissolving 0.154 mg of sodium sulfide in 50 mL of a 20 g per L citric acid solution. Place a piece of lead acetate paper over the mouth of each flask, and hold the paper in position by placing over it an inverted weighing bottle. Heat the flasks in an autoclave at 121 ± 2℃for 30minutes.Requirement—Any black stain on the paper produced by Solution S is not more intense than that produced by the control solution.7、Preparation of Solution S[YBB] Put a number of uncut closures corresponding to a surface area of about 200 cm2 in a suitable glass container, cover with purified water( sample: water=1:2), boil for 5 min and rinse 5 times with the same volume of purified water. Place the washed closures in a conical flask, add the same volume of water and weigh.Cover the mouth of the flask with a borosilicate-glass beaker. Heat in an autoclave so that a temperature of 121 ± 2 °C is reached within 20 min to 30 min and maintain at this temperature for 30 min. Cool to room temperature.Make up to the original mass with purified water. Shake and immediately separate the solution from the rubber by decantation. Shake solution S before each test Blank. Prepare a blank in the same manner using 400 mL of water for purified water.[EP] Solution S.Introduce a number of uncut closures corresponding to a surface area of about 100 cm2in a suitable glass container, cover with water for injections R, boil for 5 min and rinse 5 times with cold water for injections R.Place the washed closures in a wide-necked flask (glass type I, 3.2.1), add 200 ml of water for injections R and weigh. Cover the mouth of the flask with a borosilicate-glass beaker. Heat in an autoclave so that a temperature of 121 ±2 °C is reached within 20 min to 30 min and maintain at this temperature for 30min. Cool to room temperature over about 30 min. Make up to the original mass with water for injections R. Shake and immediately separate the solution from the rubber by decantation. Shake solution S before each testBlank. Prepare a blank in the same manner using 200 ml of water for injections R.[JP] Wash the rubber closures with water, and dry at room temperature. Place them in a glass container, add water exactly 10 times the mass of the test material, close with a suitable stopper, heat at 121℃ for 1 hour in an autoclave, take out the glass container, allow to cool to room temperature,then take out immediately the rubber closures, and use the remaining solution as the testsolution. Prepare the blank solution with water in the same manner. Perform the following tests with the test solution and the blank solution[USP] Place whole, uncut closures corresponding to a surface area of 100 ± 10 cm2 intoa suitable glass container. Cover the closures with 200 mL of Purified Water orWater for Injection. If it is not possible to achieve the prescribed closure surface area (100 ± 10 cm2) using uncut closures, select the number of closures that will most closely approximate 100 cm2, and adjust the volume of water used to the equivalent of 2 mL per each 1 cm2 of actual closure surface area used. Boil for 5 minutes, and rinse five times with cold Purified Water or Water for InjectionPlace the washed closures into a Type I glass wide-necked flask (see Containers—Glass 660 ), add the same quantity of Purified Water or Water for Injection initially added to the closures, and weigh. Cover the mouth of the flask with a Type I glass beaker. Heat in an autoclave so that a temperature of 121 ± 2℃ is reached within 20 to 30 minutes, and maintain this temperature for30 minutes. Cool to room temperature over a period of about 30 minutes. AddPurified Water or Water for Injection to bring it up to the original mass. Shake, and immediately decant and collect the solution. [NOTE—This solution must be shaken before being used in each of the tests]Prepare a blank solution similarly, using 200 mL of Purified Water or Water for Injection omitting the closures8、Appearance of solution[YBB]According to the part 2 of Chinese pharmacopoeia, 2010 edition of appendixⅨB and appendix IX A, standard solution is not more opalescent than reference suspension II. Standard solution is not more intensely coloured than No.5 reference solution[EP] Solution S is not more opalescent than reference suspension II for type I closures and is not more opalescent than reference suspension III for type II closures(2.2.1). Solution S is not more intensely coloured than reference solution GY5(2.2.2, Method II).[JP] Place 5 mL of the test solution in a glass-stoppered test tube of about 15 mm in inner diameter and about 200 mm in length, and shake vigorously for 3 minutes.The foam arisen disappears almost completely within 3 minutes.[USP] Determination of Turbidity (Opalescence)Procedure A: Visual Comparison— Use identical test tubes made of colorless, transparent, neutral glass with a flat base and an internal diameter of 15 to 25 mm. Fill one tube to a depth of 40 mm with Solution S, one tube to the same depth with water, and four others to the same depth with Reference Suspensions A, B, C,and D. Compare the solutions in diffuse daylight 5 minutes after preparation of the Reference Suspensions, viewing vertically against a black background. The light conditions shall be such that Reference Suspension A can be readily distinguished from water and that Reference Suspension B can be readily distinguished fromReference Suspension A.REQUIREMENT—Solution S is not more opalescent than Reference Suspension B for Type I closures, and not more opalescent than Reference Suspension C for Type II closures. Solution S is considered clear if its clarity is the same as that of water when examined as described above, or if its opalescence is not more pronounced than that of Reference Suspension A (refer to Table 3).Procedure B: Instrumental Comparison—Measure the turbidity of theReference Suspensions in a suitable calibrated turbidimeter (see Spectrophotometry and Light Scattering 851 ). The blank should be run and the results corrected for the blank. Reference Suspensions A, B, C, and D represent 3, 6, 18 and 30 Nephelometric Turbidity Units (NTU), respectively. Measure the turbidity of Solution S using the calibrated turbidimeter. REQUIREMENT—The turbidity of Solution S is not greater than that for Reference Suspension B (6 NTU FTU) for Type I closures, and is not greater than that forReference Suspension C (18 NTU FTU) for Type II closures (refer to Table 3).Determination of ColorColor Standard— Prepare a solution by diluting 3.0 mL of Matching Fluid O (see Color and Achromicity 631 ) with 97.0 mL of diluted hydrochloric acid. Procedure—Use identical tubes made of colorless, transparent, neutral glass with a flat base and an internal diameter of 15 to 25 mm. Fill one tube to a depth of 40 mm with Solution S, and the second with Color Standard. Compare the liquids in diffuse daylight, viewing vertically against a white background. Requirement—Solution S is not more intensely colored than the Color Standard.9、Acidity or Alkalinity(PH)[YBB]Take each of 20 ml blank solution and solution S, respectively with KCl solution1 ml, According to the part2 of Chinese pharmacopoeia, 2010 edition ofappendixⅥH, the difference between the two may not be over 1.0.[EP] To 20ml of solution S add 0.1ml of bromothymol blue solution R1. Not more than 0.3ml of 0.01 M sodium hydroxide or 0.8 ml of 0.01 M hydrochloric acid is required to obtain either a blue or a yellow colour, respectively.[JP] To 20 mL each of the test solution and the blank solution add 1.0 mL each of potassium chloride solution, prepared by dissolving 1.0 g of potassium chloride in water to make 1000 mL. The difference of pH between the two solutions is not more than 1.0[USP] Bromothymol Blue Solution—Dissolve 50 mg of bromothymol blue in a mixture of 4 mL of 0.02 M sodium hydroxide and 20 mL of alcohol. Dilute with water to 100 mL.Procedure— To 20 ml of Solution S add 0.1 ml of Bromothymol Blue Solution.If the solution is yellow, titrate with 0.01 N sodium hydroxide until a blue endpoint is reached. If the solution is blue, titrate with 0.01 N hydrochloric acid until a yellow endpoint is reached. If the solution is green, it is neutral and no titration is required.Blank Correction—Test 20 mL of Blank similarly. Correct the results obtained for Solution S by subtracting or adding the volume of titrant required for the Blank, as appropriate. (Reference Titrimetry 541 .)Requirement— Not more than 0.3 ml of 0.01 N sodium hydroxide produces a blue color, or not more than 0.8 ml of 0.01 N hydrochloric acid produces a yellow color, or no titration is required.10、Absorbance[YBB] Filter solution S on a membrane filter having approximately 0.45 μm pores.Measure the absorbance of the filtrate at wavelengths from 220 nm to 360 nm using the blank as compensation liquid. At these wavelengths, the absorbance does not exceed 0.1(according to the part 2 of Chinese pharmacopoeia, 2010 edition of appendixⅣA).[EP] Carry out the test within 5 h of preparation of solution S. Filter solution S on a membrane filter having approximately 0.45 μm pores rejecting the first few milliliters of filtrate. Measure the absorbance (2.2.25) of the filtrate at wavelengths from 220 nm to 360 nm using the blank (see solution S) as compensation liquid. At these wavelengths, the absorbance does not exceed 0.2 for type I closures or 4.0 for type II closures. If necessary, dilute the filtrate before measurement of the absorbance and correct the result for the dilution. [JP] Read the absorbance of the test solution between 220 nm and 350 nm against the blank solution as directed under Ultraviolet-visible Spectrophotometry <2.54>: it is not more than 0.20.[USP] Procedure — [NOTE—Perform this test within 5 hours of preparing Solution S.] Filter Solution S through a 0.45-µm pore size filter, discarding the first few mL of filtrate. Measure the absorbance of the filtrate at wavelengths between 220 and 360 nm in a 1-cm cell using the blank in a matched cell in the reference beam. If dilution of the filtrate is required before measurement of the absorbance, correct the test results for the dilution.Requirement—The absorbances at these wavelengths do not exceed 0.2 for Type I closures or 4.0 for Type II closures.11、Reducing Substances[YBB] To 20.0 mL of solution S add 1 mL of dilute sulfuric acid R and 20.0 mL of0.002 M potassium permanganate. Boil for 3 min. Cool. Add 0.1 g of potassiumiodide R and titrate immediately with 0.01 M sodium thiosulfate until the colorturned light brown , using 5 drops of starch solution R as indicator. Carry out atitration using 20.0 mL of the blank. The difference between the titrationvolumes is not greater than7.0mL.[EP] Carry out the test within 4 h of preparation of solution S. To 20.0 ml of solution S add 1 ml of dilute sulphuric acid R and 20.0 ml of 0.002 M potassium permanganate. Boil for 3min. Cool. Add 1 g of potassium iodide R and titrate immediately with 0.01 M sodium thiosulphate, using 0.25 ml of starch solution R as indicator. Carry out a titration using 20.0 ml of the blank. The difference between the titration volumes is not greater than 3.0 ml for type I closures and7.0 ml for type II closures.[JP] Measure 100 mL of the test solution in a glass-stoppered,Erlenmyer flask, add10.0 mL of 0.002 mol/L potassium permanganate VS and 5 mL of dilutesulfuric acid, and boil for 3 minutes. After cooling, add 0.10 g of potassium iodide,stopper, mix by shaking, then allow to stand for 10 minutes,and titrate<2.50> with 0.01 mol/L sodium thiosulfate VS(indicator: 5 drops of starch TS).Perform the blank test in the same manner, using 100 mL of the blank solution.The difference in mL of 0.002 mol/L potassium permanganate VS required between the tests is not more than 2.0 mL.[USP] Procedure— [NOTE—Perform this test within 4 hours of preparing Solution S.] To 20.0 mL of Solution S add 1 mL of diluted sulfuric acid and 20.0 mL of0.002 M potassium permanganate. Boil for 3 minutes. Cool, add 1 g ofpotassium iodide, and titrate immediately with 0.01 M sodium thiosulfate, using0.25 mL of starch solution TS as the indicator. Perform a titration using 20.0mL of blank and note the difference in volume of 0.01 M sodium thiosulfaterequired.Requirement—The difference between the titration volumes is not greater than 3.0 mL for Type I closures and not greater than 7.0 mL for Type II closures.12、Residue on evaporation[YBB]Evaporate 100 mL of solution S and blank solution to dryness on a water-bath and dry at 100 °C to 105 °C. The residue weighs not more than 4.0 mg. [EP]Evaporate 50.0 ml of solution S to dryness on a water-bath and dry at 100 °C to 105 °C. The residue weighs not more than 2.0 mg for type I rubber and notmore than 4.0 mg for type II rubber.[JP]Measure 100 mL of the test solution, evaporate on a water bath to dryness, and dry the residue at 1059 C for 1 hour.The mass of the residue is not morethan 2.0 mg.[USP]None13、Ammonium[YBB] Precision measuring 10 ml of solution S, adding alkaline potassium iodide solution 2 ml, place 15 minutes, should not be color; if it colored , compare with reference solution (with 2.0 ml ammonium chloride solution (take ammoniumchloride 31.5 mg, add right amount chlorine free water and dissolve diluted to1000 ml), 8 ml blank reference solution, 2ml alkaline potassium mercuric iodide solution for mixing), should not be more intensely colored (0.0002%)[EP] maximum 2 ppm.Dilute 5 ml of solution S to 14 ml with water R. The solution complies with limit test A.[JP]None[USP] Alkaline Potassium Tetraiodomercurate Solution— Prepare a 100 mL solution containing 11 g of potassium iodide and 15 g of mercuric iodide in water.Immediately before use, mix 1 volume of this solution with an equal volume ofa 250 g per L solution of sodium hydroxide.Test Solution— Dilute 5 mL of Solution S to 14 mL with water. Make alkaline if necessary by adding 1 N sodium hydroxide, and dilute with water to 15 mL.Add 0.3 mL of Alkaline Potassium Tetraiodomercurate Solution, and close the container.Ammonium Standard Solution— Prepare a solution of ammonium chloride in water (1 ppm NH4). Mix 10 mL of the 1 ppm ammonium chloride solution with5 mL water and 0.3 mL of Alkaline Potassium Tetraiodomercurate Solution.Close the container.Requirement—After 5 minutes, any yellow color in the Test Solution is no darker than the Ammonium Standard Solution (no more than 2 ppm of NH4 in Solution S).14、Extractable Zinc[YBB] Filter solution S on a membrane filter having approximately 0.45μm pores, Precision measuring filtrate 10 ml, add 1 ml 2 mol/L of hydrochloric acid and 3 drops of potassium ferrocyanide test solution(weight 4.2 g potassium ferrocyanide trihydrate, dissolve and diluted with water to 100 ml, shake evenly, this product should be new prepared) for mixing, should not be color; if it colored, compare with reference solution( with 3 ml standard zinc solution (weight 44.0g Zinc sulfate seven hydrated compounds, with new boiled and cooled purified water dissolved and diluted to 1000 ml, this product should be new prepared), shall not be deeper(0.0002%)，7ml blank reference solution, 1ml 2mol/L hydrochloric acid and 3 drops of potassium ferrocyanide solution for mixing), should not be more intensely colored.(0.0003%)[EP] maximumof 5 μg of extractable Zn per millilitre of solution S.Atomic absorption spectrophotometry (2.2.23, Method I). Test solution. Dilute10.0 ml of solution S to 100 ml with 0.1 M hydrochloric acid.Reference solutions. Prepare the reference solutions using zinc standard solution(10 ppm Zn) R diluted with 0.1 M hydrochloric acid.Source: zinc hollow-cathode lamp.Wavelength: 213.9 nm.Flame: air-acetylene.[JP]To 10.0 mL of the test solution add diluted dilute nitric acid (1 in 3) to make 20 mL, and use this solution as the sample solution. Further, to 1.0 mL of Standard Zinc Solutionfor atomic absorption spectrophotometry add diluted nitricacid (1 in 3) to make exactly 20 mL, and use this solution asthe standard solution. Perform the tests according to the Atomic Absorption Spectrophotometry <2.23>,using these solutions, under the following conditions.The absorbanceof the sample solution is not more than that of the standardsolution.Gas: Combustible gasóAcetylene.Supporting gasóAir.Lamp: Zinc hollow-cathode lamp.Wavelength: 213.9 nm.Standard Zinc Solution for atomic absorption spectrophotometry: Measure exactly 10 mL of the Standard Zinc Stock Solution, and add water to make exactly 1000 mL. Prepare before use. One mL of this solution contains 0.01 mg of zinc(Zn).[USP] Test Solution—Prepare a Test Solution by diluting 10.0 mL of Solution S to 100 mL with 0.1N hydrochloric acid. Prepare a test blank similarly, using the Blank forSolution S.Zinc Standard Solution— Prepare a solution (10 ppm Zn) by dissolving zinc sulfate in 0.1 N hydrochloric acid.Reference Solutions—Prepare not fewer than 3 Reference Solutions by diluting the Zinc Standard Solution with 0.1 N hydrochloric acid. The concentrations of zinc in these Reference Solutions are to span the expected limit of the Test Solution.Procedure—Use a suitable atomic absorption spectrophotometer (see Spectrophotometry and Light Scattering 851 ) equipped with a zinc hollow-cathode lamp and an air–acetylene flame. An alternative procedure such as an appropriately validated inductively coupled plasma analysis (ICP) may be used.Test each of the Reference Solutions at the zinc emission line of 213.9 nm at least 3 times. Record the steady readings. Rinse the apparatus with the test blank solution each time, to ensure that the reading returns to initial blank value.Prepare a calibration curve from the mean of the readings obtained for each Reference Solution. Record the absorbance of the Test Solution. Determine the ppm zinc concentration of the Test Solution using the calibration curve.Requirement— Solution S contains not more than 5 ppm of extractable zinc.15、Cadmium[YBB]None[EP]None[JP]Wash the rubber closures with water, dry at room temperature, cut into minute pieces, mix well, place 2.0 g of them in a crucible of platinum or quartz, moisten them with 2 mL of sulfuric acid, heat gradually to dryness, and ignite between 4509 Cand5009 C until the residue is incinerated. When in cineration was insufficient, moisten the residue with 1 mL of sulfuric acid, heat to dryness, and ignite again. Repeat the above-mentioned procedure if necessary. Cool the crucible,moisten the residue with water, add 2 to 4 mL of hydrochloric acid, heat on a water bath to dryness, add 1 to 5 mL of hydrochloric acid, and dissolve by heating. Then add 0.5 to 1 mL of a mixture of a solution of citric acid monohydrate (1 in 2) and hydrochloric acid (1:1) and 0.5 to 1 mL of a warmed solution of ammonium acetate (2 in 5). When any insoluble residue remains, filter through a glass filter. To the solution thus obtained add 10 mL ofa solution of diammonium hydrogen citrate (1 in 4), 2 drops of bromothymolblue TS and ammonium TS until the color of the solution changes from yellow to green. Then add 10 mL of ammonium sulfate solution (2 in 5) and water to make 100 mL. Next, add 20 mL of a solution of sodium N,N-diethyldithiocarbamate trihydrate (1 in 20), mix, allow to stand for a few minutes,add 20.0 mL of 4-methyl-2-pentanone, and mix by vigorous shaking.Allow to stand to separate the 4-methyl-2-pentanone layer from the solution, filter if necessary, and use as the sample solution. On the other hand, to 10.0 mL of Standard Cadmium Solution add 10 mL of a solution of diammonium hydrogen citrate (1 in 4) and 2 drops of bromothymol blue TS, proceed in the same manner as for the sample solution, and use this solution as the standard solution.Perform the tests according to the Atomic Absorption Spectrophotometry <2.23> under the following conditions, using the sample solution and the standard solution. The absorbance of the sample solution is notmore than that of thestandard solution.Gas: Combustible gas—Acetylene or hydrogen.Supporting gas—Air.Lamp: Cadmium hollow-cathode lamp.Wavelength: 228.8 nm.[USP] None。
欧盟与中国检测方法对比
铵离子
精密量取试验液10ml,加碱性碘化汞钾2ml, 放置15分钟，如显色，与氯化铵溶液（取氯 颜色不得比对照液更深 化铵31.5mg加无氨水适量溶解并稀释至 （0.0002%） 1000.0ml）2.0ml，加空白提取液8ml与碱性 碘化汞钾试液制成的对照液比较。
锌离子
——
——
锌离子
取供试品液，用孔径0.45um的滤膜过滤，精 密量取10ml，加2mol/L盐酸1ml和亚铁氰化 钾试液（称取4.2g亚铁氰化钾三水化合物， 用溶解并稀释至100ml，摇匀，即得）3滴混 供试品液不显色或颜色 合，不得显色；如显色，与标准锌溶液（临 不得比对照液更深 用前，称取44.0mg硫酸锌七水化合物，用新 煮沸并冷却的水溶解并稀释至1000.0ml） 3.0ml，加空白对照液8ml与2mol/L盐酸1ml 和亚铁氰化钾试液3滴对照液比较。 在供试品液制备5小时内进行下述试验：用 电导仪测定，用水冲洗测定电极（光亮铂电 极或铂黑电极）数次，取空白对照液冲洗电 极至少2次，测定空白对照液的电导率。。 再用供试品液冲洗电极至少2次，测定供试 品液的电导率。测定温度为20℃±1℃，如 果测定温度不在此条件下，则应对温度进行 校正。
不挥发物
不得过4.0mg
重金属
同空白溶液比较， 如果对照溶液不呈 浅棕色，则测试无 效。供试液的颜色 不得比对照液更深
重金属
精密量取试验液10ml,加醋酸盐缓冲液 （pH3.5）2ml,照重金属检查法（中华人民 含重金属不得过百万分 之一 共和国药典2000版二部附录Ⅷ H第一法测定 。）
铵
在装有14ml纯化水的试管内溶解规定的 所测物质。有必要的话，在纯化水中溶 解氢氧化钠R并定容至15ml。在已配溶液 中滴加0.3ml四碘汞酸钾溶液。将10ml标 测试液颜色不得比 准钠溶液（1ppmNH4)、5ml水和0.3ml四 标准样品颜色更深 碘汞酸钾溶液混合，制得标准溶液，之 后将试管上塞。5分钟，比较测试液和标 准样品颜色。
关于输液制剂使用丁基胶塞的综述
关于输液制剂使用丁基胶塞的综述北京双鹤股份有限公司程秀温国家药品监督管理局于2000年4月29日以第21号局令颁布了《药品包装用材料、容器管理办法》，其中对于输液制剂提出要求“－－－国家药品监督管理局将逐步规定淘汰使用天然胶塞的期限。
所有药用胶塞（包括输液、口服液等各剂型用胶塞）于2004年底前一律停止使用普通天然胶塞。
”对此我专门进行了调查，大多数输液生产厂目前均无准备，由于成本原因，大家也在观望SDA的态度。
为了做好使用丁基胶塞的准备工作，我收集了一些资料，现综述如下：一、丁基胶塞供应商情况企业名称注册号年产量西氏医药服务（新加坡）公司 J2001001Pohl.Gmbh J20010023Helvoetpharma BelgiumN.V J20010019Stelmi Trading International J20010021湖北华强药用包装制品厂国药包字20010024 11亿支石家庄第一橡胶股份有限公司国药包字20020355 10亿只郑州市嵩山集团翱翔医药包装公司国药包字20010021 8亿只中橡集团株洲华益橡塑实业开发公司国药包字20020172 5亿只盛州橡塑胶（苏州）有限公司国药包字20010030 6亿只江阴兰陵胶塞有限公司国药包字20010029 10亿只重庆涪陵海兰陵有限公司国药包字20010027江阴中马橡胶制品有限公司国药包字20010013 8亿只乐清市金泰实业公司国药包字20020029 5亿只台州康龙医药包装有限公司国药包字20020124 5亿只山东药用玻璃股份有限公司国药包字20030224 6亿只宁波兴亚橡塑集团有限公司国药包字20030291安徽华峰医药橡胶制品有限公司 6亿只江苏驰达医用材料厂 5亿只上海新亚医用橡胶有限公司国药包字20030079 8亿只1、原料供应：医用级卤化丁基胶目前在世界上只有两家跨国公司生产，一家为美国的埃克森公司，一家为德国的拜耳公司；我国的燕山石化还不能生产，因此生胶将全部依赖进口，年需求量约为3万吨。
丁基胶塞在注射剂领域中的选用策略思考
丁基胶塞在注射剂领域中的选用策略思考摘要：丁基橡胶塞是医药包装材料的升级换代产品，主要用于替代传统天然橡胶瓶塞。
丁基橡胶瓶塞是一种有诸多优越性能的医药包装材料，比天然橡胶瓶塞具有更好的使用性，其气体透过率约为天然橡胶的1/20，丁基橡胶的耐热性、耐候性和耐臭氧氧化性都很突出，最高使用温度可达200℃，可以长时间暴露于阳光和空气中而不易损坏。
文中对丁基胶塞在注射剂领域中的选用策略进行了分析。
关键词：丁基胶塞；注射剂；选用策略1丁基胶塞的分类及特点1.1将卤素加入到丁基胶塞中就形成了卤化丁基橡胶，根据加入的卤素元素的不同，可以将卤化丁基橡胶分为溴化丁基橡胶和氯化丁基橡胶，两者之间存在着不同的特性，其中氯化丁基橡胶具有更好的耐热性能，将其应用在注射剂中，跟随着对注射剂的高温灭菌不会产生粘连。
溴化丁基胶塞和氯化丁基胶塞对比，具有更高的洁净度，因此对药物产生的影响更小，其在生产过程中只需要采用少量的硫化剂而不需要使用增塑剂，因此其具有更高的安全性。
1.2丁基胶塞分为免洗免灭菌胶塞、免洗待灭菌胶塞和普通胶塞。
其中免洗免灭菌胶塞就是由胶塞厂在制作完成丁基胶塞之后自行进行清洗和灭菌，药物生产厂商在使用时不需要另外进行清洗和灭菌；免洗待灭菌胶塞就是由胶塞厂在制作完成丁基胶塞之后自行进行清洗，但是不灭菌，药物生产厂商在使用时不需要另外进行清洗，但是需要灭菌；普通胶塞就是胶塞厂在制作过程中不进行清洗和灭菌，在使用时需要清洗和灭菌之后才能使用。
从目前的情况来看，药物生产企业使用的为免洗待灭菌胶塞，清洗工作由胶塞生产企业完成，药物生产企业就可以提高生产效率，而胶塞的灭菌工作则由药企完成，可以保障丁基胶塞的灭菌效果和质量。
1.3覆膜丁基胶塞也是一种常见的丁基胶塞类型，其是在胶塞的表面采用一层致密性非常强的惰性材料覆盖，从而将胶塞和药物分隔开，可以一定程度解决药物和胶塞之间的药物相容性问题，因此其和普通的丁基胶塞相比，安全性更高。
保证大容量注射剂压塞封口质量的措施分析
书山有路勤为径；学海无涯苦作舟
保证大容量注射剂压塞封口质量的措施分析
大容量注射剂压塞封口质量是由下面几个方面来保证，一是胶塞的质量；二是合理确定压塞封口后的质量指标；三是压胶塞机的设计结构先进合理，确保压塞封口后的质量指标。
下面从这三方面加以分析。
一、胶塞质量
我国药品使用的胶塞分天然胶塞和丁基胶塞。
大容量注射剂之前使
用的胶塞绝大多数都是天然胶塞，少数使用丁基胶塞的也是独资企业或合资企业。
因为国际上在20 世纪70 年代就淘汰了天然胶塞。
中国对提高药包材质量的认识水平滞后，在90 年代后期才提出推广应用丁基胶塞，但由于价格因素和国产丁基胶塞存在技术质量问题，给推广工作带来了障碍，至今也没有得到很好落实。
随着中国加入WTO ，中国成为了世界贸易组织的成员国，商品的技术质量必须与国际接轨，才能走出国门，进行商品国际流通。
国内的专家们、企业家们强烈呼吁，淘汰天然橡胶塞，采用丁基胶塞，保证药品质量。
淘汰的原因是：天然胶成份不纯，化学稳定性差，易老化，屏蔽性能、密封性能差，含有对人体有害的杂质，胶塞生产工艺中有助剂溢出，影响药品质量并对人体健康存在隐患。
而丁基胶（合成橡胶）由于气密性好，解决了上述问题，成为天然胶塞的替代品。
目前大容量注射剂采用丁基胶塞的呼声己引起了各级管理部门的高
度重视，2004 年国家食品药品质量监督管理局签发了国食药监注[2004] 391号文《关于进一步加强直接接触药品的包装材料和容器监督管理的通
专注下一代成长，为了孩子。
药用丁基胶塞的材质-概述说明以及解释
药用丁基胶塞的材质-概述说明以及解释1.引言1.1 概述药用丁基胶塞是一种常见的医疗器械材料，广泛应用于药品容器的密封和注射器的橡胶塞。
它由丁基橡胶制成，具有良好的柔软性、耐腐蚀性和密封性能。
药用丁基胶塞的主要作用是防止药物在储存和输送过程中的泄漏和污染，确保药品的质量和安全性。
在医药领域中，药用丁基胶塞被广泛用于药瓶、针筒和注射器等容器的密封。
丁基胶塞的材质选择非常重要，它直接影响着药品的稳定性、保存期限和使用效果。
因此，在选择药用丁基胶塞材质时需要考虑多方面因素。
首先，药用丁基胶塞的材质应具有优异的化学稳定性和生物相容性。
医药产品经常与各种药物接触，因此胶塞的材质在接触药物后不应引起有害物质的释放或产生任何不良反应。
此外，药用丁基胶塞应具有良好的耐腐蚀性，能够抵抗药品中的溶剂、溶剂和氧化剂等物质的侵蚀，以确保药品的纯度和效力。
其次，药用丁基胶塞的材质还应具有较好的机械性能。
胶塞的弹性和稳定性是确保其与容器紧密密封的重要特性，不仅要能够顺利穿透瓶口或针头，还要能够防止气体或液体的泄漏。
此外，在长时间使用或高压情况下，胶塞应能够保持一定的形状和稳定性，以确保药品的安全和有效性。
最后，为了满足不同的医药应用需求，药用丁基胶塞的材质还应具有可扩展性。
不同药品对胶塞材质的要求不同，因此需要根据具体的药品性质和应用环境，选择材质的硬度、耐高温性、阻氧性等特性。
这样可以更好地适应各种药品的保存和使用要求，提高药品的质量和稳定性。
综上所述，药用丁基胶塞的材质选择是确保药品质量和安全性的重要环节。
在选择材料时需要考虑化学稳定性、生物相容性、耐腐蚀性、机械性能和可扩展性等因素，以满足不同药品的需求。
随着科学技术的不断进步，我们可以期待药用丁基胶塞材质在未来的发展中更加先进和多样化，为医药行业带来更多的便利和创新。
1.2 文章结构文章结构部分的内容可以包括以下几个方面：（1）本文主要分为引言、正文和结论三个部分，以系统地介绍药用丁基胶塞的材质选择要点以及展望其未来的发展方向。
【免费下载】 药用丁基胶塞质量标准
药用丁基胶塞质量标准药用氯化丁基橡胶塞 标准（试行） YBB 00042002本标准适用于直接与注射剂接触的氯化丁基橡胶塞。
【外观】取本品数个，目视检测，表面色泽应均匀，不得有污点、杂质、气泡、裂纹、缺胶、粗糙、胶丝、胶屑、海绵状、毛边；不得有除边造成的残缺或锯齿现象；不得有模具造成的明显痕迹。
【鉴别】（1）称取本品5～20g ，置于干燥的试管中，将长约4毫米的钠片一片置于固定并倾斜的试管中，使其恰好位于试样之上，用火焰的尖端加热试管，将钠融化在试样上，继续加热2分钟，使呈深红色，冷却后加入乙醇，将过剩的钠醇化，加水约10ml 溶解，过滤，滤液备用。
A ：取滤液1.5ml 置于试管中，加硝酸酸化，煮沸1～2分钟，加入硝酸银1滴，应产生白色沉淀。
B ：取滤液0.2ml ，置于微量试管中，加氯仿1滴，加稀硫酸1滴，加薪配置的氨水1滴（或3％H2O2溶液2～3滴），经振荡混匀后，静止5分钟，氯仿层应不显色。
（2）红外光谱取本品约3g 切成3mm×3mm 小块置索氏抽提器中用丙酮或适宜的溶剂回流浸提8小时，取残渣80℃烘干，取0.1～0.2g 置于裂解管的底部，然后用试管夹水平的将裂解管移到酒精灯上加热，当出现裂解产物冷凝在裂解管冷端时，再继续加热至裂解基本完全但没碳化为止，取少许裂解物滴在溴化钾片上，在80℃烘干，照分光光度法（《中华人民共和国药典》2000年版二部ⅣC ）测定，应与对照图谱基本一致。
【穿刺落屑】输液瓶用胶塞：取10只被测胶塞和10只已知穿落屑数的胶塞分别装在与其相配的输液瓶上，每只瓶中注入半瓶水。
加上铝盖,用手动封盖机封口,打开铝盖穿刺部位。
按先被测胶塞再已知穿刺落屑数胶塞的顺序交替穿刺胶塞。
穿刺时,胶塞保持直立,握持金属穿刺器（见图1）垂直向胶塞标记区域内穿刺，晃动数秒后拨出穿刺器。
每次穿刺前用丙酮或甲基—异丁基酮擦拭穿刺器。
穿刺器不得有损坏，并保持锋利（如穿器损坏，须换用新的）。
药包材标准中丁基胶塞质量要求及测试方法介绍
药包材标准中丁基胶塞质量要求及测试方法介绍药包材标准中丁基胶塞质量要求及测试方法介绍丁基橡胶塞在洁净度、化学稳定性、气密性等方面的性能都非常好，所以广泛应用于输液、口服液等药品包装中。
由于丁基胶塞在药品行业应用广泛，而且胶塞产品直接接触药品，所以国家出台了很多相关标准来控制丁基胶塞的产品质量。
以下我们结合国家药包材标准的要求来介绍丁基胶塞产品的性能要求和测试方法。
一、参考标准（部分）：YBB00042005-2015注射液用卤化丁基橡胶塞YBB00052005-2015注射用无菌粉末用卤化丁基橡胶塞YBB00322004-2015注射剂用胶塞垫片穿刺力测定法YBB00332004-2015注射用胶塞垫片穿刺落屑测定法1.穿刺落屑取样品10个，照注射剂用胶塞、垫片穿刺落屑测定法YBB00332004-2015测定，落屑数应不得过20粒。
测定法：选择20个注射剂瓶，每个瓶内加1/2公称容量的水。
取10个被测胶塞和10个已知穿刺落屑胶塞分别装在注射剂瓶上，盖上铝盖或铝塑组合盖，封口后进行预处理。
预处理完成后用丙酮或其他适当的有机溶剂擦拭金属穿刺器，然后手持穿刺器，垂直穿刺被测试胶塞上的标记部位，刺入后晃动注射剂瓶数秒后拔出穿刺器。
将注射剂瓶中水全部通过一张滤纸过滤，在人眼距离滤纸20cm 的位置，用肉眼观察滤纸上的落屑数，必要时可以通过显微镜进一步证实落屑大小和数量。
附金属穿刺器标准要求1.穿刺力取样品10个。
照注射剂用胶塞、垫片穿刺力测定法YBB00322004-2015第二法测定，穿刺瓶塞所需的力均不得超过10N。
测定法：依据标准要求对胶塞样品进行预处理。
取10个胶塞配套的注射剂瓶，分别加入公称容量的水，装上预处理过的被测胶塞，加上铝盖或者铝塑组合盖，封口。
将一只注射针置于材料试验机上固定，将注射剂瓶放入材料试验机，打开铝盖或铝塑组合盖，漏出胶塞标记部位，穿刺器以200mm/min的速度进行垂直穿刺，记录胶塞穿刺所施加的最大力值。
丁基橡胶药用瓶塞对大输液制剂澄明度影响的试验研究
丁基橡胶药用瓶塞对大输液制剂澄明度影响的试验研究
史云集;程继刚
【期刊名称】《特种橡胶制品》
【年(卷),期】1995(16)4
【摘要】论述胶塞的洁净度、胶塞对大输液澄明度的影响。
【总页数】4页(P19-22)
【关键词】丁基胶塞;澄明度;丁基橡胶;药用瓶塞;输液制剂
【作者】史云集;程继刚
【作者单位】湖北华强化工厂
【正文语种】中文
【中图分类】TQ460.69
【相关文献】
1.MLE用于丁基橡胶药用瓶塞的试验 [J], 史云集;程继刚
2.不同药典和标准对大输液丁基橡胶瓶塞质量要求的分析 [J], 王思涛;张卫东
3.丁基橡胶药用瓶塞与天然橡胶药用瓶塞比较 [J], 程继刚;李吉生
4.丁基橡胶药用瓶塞配方硫化体系对头孢唑啉钠相容性的影响研究 [J], 王飞; 司俊杰
5.不同药典和标准对大输液丁基橡胶瓶塞质量要求的分析 [J], 朱善本; 王飞
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药用丁基胶塞质量标准
药用丁基胶塞质量标准一、引言药用丁基胶塞是药品包装的重要组成部分，其质量直接关系到药品的质量和安全性。
为了规范药用丁基胶塞的生产和质量控制，本质量标准应运而生。
本标准主要包含以下方面：外观、尺寸、物理性能、化学性能和微生物限度。
二、外观药用丁基胶塞的外观应平整、光滑，无明显瑕疵、气泡和颜色不均匀。
胶塞的表面应无残留物、油腻或手印等污染。
三、尺寸药用丁基胶塞的尺寸应符合设计要求，包括直径、高度和厚度等参数。
胶塞的直径应在规定范围内，以确保与药瓶的配合良好；高度和厚度应符合标准，以保证足够的机械强度和密封性能。
四、物理性能1. 拉伸强度：药用丁基胶塞应具有一定的拉伸强度，以保证在正常包装和运输过程中不易破损。
2. 撕裂强度：药用丁基胶塞应具有足够的撕裂强度，以防止在开启药瓶时出现撕裂现象。
3. 压缩永久变形：药用丁基胶塞应具有较小的压缩永久变形，以保证在使用过程中保持良好密封性能。
4. 密度：药用丁基胶塞的密度应均匀一致，且符合标准要求。
5. 热稳定性：药用丁基胶塞应能在药品包装的温度条件下保持稳定，不出现软化、变形等现象。
五、化学性能1. 耐化学腐蚀性：药用丁基胶塞应能耐受药品、消毒剂等化学物质的腐蚀，以确保药品包装的密封性和安全性。
2. 溶出物：药用丁基胶塞在浸泡于药品或其他溶剂中时，应不溶出对人体有害的物质。
3. 蒸发残渣：药用丁基胶塞在高温烘烤或暴露于空气中时，应不产生对人体有害的蒸发残渣。
4. 微生物限度：药用丁基胶塞中不得检出对人体有害的微生物（如细菌、霉菌等）。
5. 无毒无害性：药用丁基胶塞应无毒无害，不会对人体健康造成影响。
6. 透明度：药用丁基胶塞应具有较高的透明度，以便于观察药品包装内部的情况。
7. 耐磨性：药用丁基胶塞应具有较好的耐磨性，以防止在重复使用过程中出现磨损现象。
8. 抗老化性：药用丁基胶塞应具有较好的抗老化性能，以防止在储存和使用过程中出现性能下降现象。
[重点]药用丁基胶塞质量标准
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000药用丁基胶塞质量标准药用氯化丁基橡胶塞标准（试行）YBB 00042002 000本标准适用于直接与注射剂接触的氯化丁基橡胶塞。
【外观】取本品数个，目视检测，表面色泽应均匀，不得有污点、杂质、气泡、裂纹、缺胶、粗糙、胶丝、胶屑、海绵状、毛边；不得有除边造成的残缺或锯齿现象；不得有模具造成的明显痕迹。
000【鉴别】（1）称取本品5～20g，置于干燥的试管中，将长约4毫米的钠片一片置于固定并倾斜的试管中，使其恰好位于试样之上，用火焰的尖端加热试管，将钠融化在试样上，继续加热2分钟，使呈深红色，冷却后加入乙醇，将过剩的钠醇化，加水约10ml溶解，过滤，滤液备用。
A：取滤液1.5ml置于试管中，加硝酸酸化，煮沸1～2分钟，加入硝酸银1滴，应产生白色沉淀。
B：取滤液0.2ml，置于微量试管中，加氯仿1滴，加稀硫酸1滴，加薪配置的氨水1滴（或3％H2O2溶液2～3滴），经振荡混匀后，静止5分钟，氯仿层应不显色。
000（2）红外光谱取本品约3g切成3mm×3mm小块置索氏抽提器中用丙酮或适宜的溶剂回流浸提8小时，取残渣80℃烘干，取0.1～0.2g置于裂解管的底部，然后用试管夹水平的将裂解管移到酒精灯上加热，当出现裂解产物冷凝在裂解管冷端时，再继续加热至裂解基本完全但没碳化为止，取少许裂解物滴在溴化钾片上，在80℃烘干，照分光光度法（《中华人民共和国药典》2000年版二部ⅣC）测定，应与对照图谱基本一致。
000【穿刺落屑】输液瓶用胶塞：取10只被测胶塞和10只已知穿落屑数的胶塞分别装在与其相配的输液瓶上，每只瓶中注入半瓶水。
加上铝盖,用手动封盖机封口,打开铝盖穿刺部位。
按先被测胶塞再已知穿刺落屑数胶塞的顺序交替穿刺胶塞。
穿刺时,胶塞保持直立,握持金属穿刺器（见图1）垂直向胶塞标记区域内穿刺，晃动数秒后拨出穿刺器。
每次穿刺前用丙酮或甲基—异丁基酮擦拭穿刺器。
穿刺器不得有损坏，并保持锋利（如穿器损坏，须换用新的）。