Quality standard of butyl rubber stopper for most

Quality standard for pharmaceutical butyl rubber stopper

standard for pharmaceutical chlorinated butyl rubber stopper (Trial) YBB

this standard is applicable to chlorinated butyl rubber stopper in direct contact with injection

[appearance] take several pieces of this product and conduct visual inspection. The surface color should be uniform, without stains, impurities, bubbles, cracks, lack of glue, roughness, glue silk, glue crumbs, spongy, rough edges; There shall be no mutilation or sawtooth caused by edge removal; There shall be no obvious marks caused by the mold

[identification] (1) weigh 5 ~ 20g of this product, put it in a dry test tube, put a piece of sodium about 4mm long in a fixed and inclined test tube, make it just above the sample, heat the test tube with the tip of the flame, melt the sodium on the sample, continue to heat for 2 minutes, make it dark red, add ethanol after cooling, alcoholize the excess sodium, add about 10ml of water to dissolve, filter, and reserve the filtrate

a: take 1.5ml of filtrate and put it into the test tube, add nitric acid for acidification, boil for 1 ~ 2 minutes, add 1 drop of silver nitrate, and white sediment should be produced

b: take 0.2ml of filtrate, put it in a micro test tube, add 1 drop of chloroform, 1 drop of dilute sulfuric acid, and 1 drop of ammonia (or 2-3 drops of 3%h2o2 solution) prepared for salary increase. After shaking and mixing, stand still for 5 minutes, and the chloroform layer should not show color

(2) take about 3G of this product and cut it into 3mm by infrared spectrum × 3mm small pieces are placed in Soxhlet extractor and extracted with acetone or suitable solvent reflux for 8 hours. Take the residue and dry it at 80 ℃, take 0.1 ~ 0.2g and put it at the bottom of the cracking tube, and then horizontally move the cracking tube to an alcohol lamp with a test tube clamp to heat it. When the cracking product condenses at the cold end of the cracking tube, continue to heat it until the cracking is basically complete but not carbonized. Take a little of the cracking product and drop it on the potassium bromide sheet and dry it at 80 ℃, The determination by spectrophotometry (Pharmacopoeia of the people's Republic of China, 2000 edition, Part II, Ⅳ C) should be basically consistent with the reference map

[puncture and chip dropping] rubber plugs for infusion bottles: take 10 rubber plugs to be tested and 10 rubber plugs with known number of chips to be punctured and dropped and put them on the matching infusion bottles respectively, and inject half a bottle of water into each bottle. In addition, the aluminum cap should implement the development strategy of efficient and green plastic granulator, seal with manual capping machine, and open the puncture part of the aluminum cap. Puncture the rubber plugs alternately in the order of being tested first and then knowing the number of chips. During puncture, keep the rubber plug upright, hold the metal puncture device (see Figure 1) and puncture vertically into the marked area of the rubber plug, shake it for a few seconds, and then pull out the puncture device. Wipe the puncture device with acetone or methyl isobutyl ketone before each puncture

the puncture device shall not be damaged and shall be kept sharp (if the puncture device is damaged, it must be replaced with a new one). Until all rubber plugs are punctured once. Remove the rubber stopper to be tested, and filter all the water in the bottle through the quick filter paper to ensure that there is no debris left in the bottle. Under normal conditions, the distance between the eyes and the filter paper is 25cm, and the number of puncture debris on the fast filter paper is observed with the naked eye. The same method is used for rubber plugs with a known number of punctured chips. The total number of chips falling from the tested rubber plug shall not exceed 20 (Note: if the result of the known number of chips falling from the puncture rubber plug is consistent with the previously measured result, the measured result of the tested rubber plug shall be judged to be valid. Otherwise, it is invalid)

rubber stopper for antibiotic bottle: rubber stopper pretreatment: take an appropriate amount of rubber stopper plus water (2aml) twice the total surface area of rubber stopper (acm2). Boil for 5min, rinse with water for 5 times, put the rubber plug into a triangular flask, add 2 AML of water, cover the beaker mouth with aluminum foil or a silicoborate beaker, heat it in a high-pressure steam sterilizer, raise the temperature to 121 ℃ ± 2 ℃ within 30 minutes, keep it for 30 minutes, cool it to room temperature within 20 ~ 30 minutes, take it out, bake it at 60 ℃ for 60min, and store it in a sealed glass container for standby

select 50 injection bottles matching the tested rubber stopper, and inject half a bottle of water into each bottle. Install the tested rubber plugs on 25 bottles, and install 25 rubber plugs with known puncture chip number on the other 25 bottles. The rubber plugs have been pretreated. Add the aluminum cap, seal with the manual capping machine, and open the puncture part of the aluminum cap. Puncture the rubber plugs alternately in the order of being tested first and then knowing the number of chips. During puncture, keep the rubber plug upright, fill the syringe with water and remove the water on the injection needle (outer diameter 0.8mm), puncture vertically into the marked area of the rubber plug, repeat three times, and inject 1ml of water into the bottle before pulling out the needle for the last time. Wipe the injection needle with acetone or methyl isobutyl ketone before each puncture

replace an injection needle every 20 times. Until all rubber plugs are punctured four times. Remove the rubber stopper to be tested, and filter all the water in the bottle through the quick filter paper to ensure that there is no debris left in the bottle. Under normal conditions, the distance between the eyes and the filter paper is 25cm, and the number of chips on the fast filter paper is observed with the naked eye. The same method is used for rubber plugs with a known number of punctured chips. Total number of chips falling from the tested rubber plug: no more than 5. (Note: if the result of the rubber plug with known puncture chip number is consistent with the previously measured result, the measured result of the rubber plug should be judged to be valid. Otherwise, it is invalid)

[puncture force] rubber plugs for infusion bottles: take 10 tested rubber plugs and 10 rubber plugs with known puncture force and install them on their matching infusion bottles respectively, and inject half a bottle of water into each bottle. Cover the aluminum cap, seal it with a manual capping machine, put it into a high-pressure steam sterilizer, keep it at 121 ℃± 2 ℃ for 20min, reduce it to room temperature, and take it out. Wipe the puncture device with acetone, without damaging the sharpness of the needle tip. Install the puncture device on the puncture device, put the bottle into the puncture device, so that the center of the rubber plug can be punctured vertically, and use the puncture device conforming to the provisions of Figure 1 to puncture the rubber plug alternately at the speed of (200 ± 50) mm/min in the order of the rubber plug being tested first and then the rubber plug with known puncture force. Record the force applied to pierce the rubber plug. Replace a puncture device after 10 times of puncture. Until all rubber plugs are punctured once. (Note: if the results of the known puncture force rubber plug are consistent with the previously measured results, the measured results of the tested rubber plug should be judged to be valid. Otherwise, it is invalid). The maximum force required to puncture the measured rubber plug shall not be more than 80N, and the average value shall not be more than 75n. During the puncture process, the rubber plug shall not be pushed into the bottle

rubber stopper for antibiotic bottle: put 10 rubber stoppers tested (all rubber stoppers have been pretreated according to the pretreatment method under the puncture debris item) on the matching injection bottle. Add the aluminum cap, seal with the manual capping machine, open the puncture part of the aluminum cap, put the bottle into the puncture device, so that the center of the rubber plug can be punctured vertically, and puncture with the injection needle (outer diameter 0.8mm) at the speed of (200 ± 50) mm/min. Record the force exerted by penetrating the rubber plug, and repeat the puncture steps until all rubber plugs are punctured once. The force required to puncture the tested rubber plug shall not exceed 10N

[sealing and puncture device retention] rubber plugs for infusion bottles: take 10 rubber plugs and put them into a high-pressure steam sterilizer without soaking in water, keep them at 121 ℃± 2 ℃ for 20min, reduce them to room temperature, and take them out. Take 10 infusion bottles, add water to the marked capacity, cover them with the tested rubber stopper, add the aluminum cap, seal them with the manual capping machine, and open the puncture part of the aluminum cap. Hold a puncture device that conforms to the provisions of Figure 1 and is perpendicular to the top of the bottle, align with the puncture part of the rubber plug, and exert vertical force on the puncture device until it is punctured to the bottom or the hand does not move. Fix the bottle that pierces the rubber stopper with the bottom up. Apply a weight of 0.5kg on the hook of the puncture device, keep it for 4h, and observe. When the rubber plug is punctured with a puncture device, the puncture device should be able to puncture to the end: the puncture device can be kept under the action of a 0.5kg weight for 4 hours without being pulled out, and there should be no leakage at the puncture part of the rubber plug

[self sealing] rubber plugs for antibiotic bottles: pretreat the tested rubber plugs within 2H before the test: boil 10 rubber plugs in water for 5min, take them out, and dry them in a 70 ℃ constant temperature drying oven for 1H. Add half a bottle of water to each of the 10 bottles, seal the rubber stopper and aluminum cap with a manual capping machine, and put them into a high-pressure steam sterilizer at 121 ℃± 2 ℃ for 30 minutes. Mainly replace ITO and metal transparent conductive film, take them out, cool them, and place them for 24 hours. Open the puncture part of the aluminum cover, put the bottle into the puncture device, and puncture three times at different positions in the marked area of the rubber plug with an injection needle (outer diameter 0.8mm) at the speed of (200 ± 50) mm/min. Repeat the puncture steps until all rubber plugs are punctured for 3 times. Change a new injection needle after every 10 times of puncture. Put the punctured rubber plug into a beaker containing 10g/l methylene blue solution to completely immerse it. Put the beaker into the verification and calibration box of the vacuum steel bar bending experimental machine according to the national standard, vacuumize to 75kpa, maintain for 30min, return the vacuum box to normal pressure, and then maintain for 30min. Take it out, rinse the outside of the bottle with water and observe it visually. Methylene blue solution shall not penetrate into the bottle

[tightness of rubber stopper and container] rubber stopper for antibiotic bottle: pretreatment of the tested rubber stopper within 2H before the test: put 10 tested rubber stoppers into water and boil for 5min, then take them out and dry them in a 70 ℃ constant temperature drying oven for 1H. Add half a bottle of water to each of the 10 bottles, seal the rubber stopper and aluminum cap with a manual capping machine, put them into a high-pressure steam sterilizer, 121 ℃± 2 ℃, keep them for 30 minutes, take them out, cool them, and place them for 24 hours. Then put the rubber plug into a beaker containing 10g/l methylene blue solution to completely immerse it. Put the beaker into the vacuum box, vacuum until the vacuum degree is 75kpa, and maintain it for 30min. The vacuum box returns to normal pressure, and then maintain it for 30min. Take it out, rinse the outside of the bottle with water and observe it visually. Methylene blue solution shall not penetrate into the bottle

[residue on ignition] take 0.2g of this product and check according to law (Appendix Ⅷ n of Pharmacopoeia of the people's Republic of China, 2000 edition, Part II). The residue left shall not exceed 45.0%

[volatile sulfide] take 20cm2 of the measured rubber plug surface area (cut it if necessary) and put it into a 100ml conical flask added with 50ml of 2.0% citric acid solution. Compare the gap projection image of a vinegar reconditioning workbench with the standard size of the impact sample gap provided by this instrument, which has also been enlarged by 50 times. Compare the lead acid test paper (cut the white filter paper (80g/m2) to 15mm × 40mm paper strips are immersed in 0.25mol/l lead acetate solution. After 1 hour, take out the filter paper, dry it in the air, and put it into a sealed container for standby. Commercially available lead acetate test paper) can also be used to put it on the mouth of the conical bottle and buckle it upside down with a beaker. Take another 100ml conical flask and add standard sodium sulfide solution (1.0 × G/ml), citric acid (8.0%) 12.5ml and water 32.5ml. Put a piece of lead acetate test paper on the mouth of the conical bottle and buckle it upside down with a beaker. Put the above two conical bottles into the autoclave, 121 ℃± 2 ℃, and keep it for 30min. Lead acetate test paper for test solution shall not be colored. In case of color development, the color shall not be darker than that of standard lead acetate test paper (50 g/20cm2)

[insoluble particles] take 100cm2 of the measured rubber plug surface area, place it in a conical flask, add 50ml of water for injection into the oscillator (oscillation frequency 300 ~ 350 times/min) and oscillate for 20 seconds. Take the above solution and determine it according to the insoluble particle inspection method (Appendix IX C of Pharmacopoeia of the people's Republic of China, 2000 edition, Part II), which should comply with the provisions of Table 1

[chemical properties] preparation of test solution: take 200cm2 of the rubber plug to be tested, put it in a beaker, add 400ml of water to immerse it, boil it for 5min, and then rinse it with 400ml of water each time, for a total of 5 times. Then put it into a conical flask, add 400ml of water, heat it up to 121 ℃± 2 ℃ in an autoclave within 30min, keep it for 30min, and cool it to room temperature within 20 ~ 30 minutes to get the test solution, standby, and prepare the blank solution at the same time. Do the following tests

clarity and color take 10ml of test solution and check it according to law (appendix of Pharmacopoeia of the people's Republic of China, 2000 edition, Part II