PP EURO CAP

(Combinational Closures of PP for Plastic Infusion Containers with ring-pull)

Test basis:YBB00242004-2015
This standard applies to Combinational Closures of PP for Plastic Infusion
Containers with ring-pull . The combinational cap is made of out cap(with
polypropylene as the main raw material), inner cap (with polypropylene as the main
raw material), and a particle. The polyisoprene particle in the combinational closure
should meet the requirements of the pharmaceutical synthetic polyisoprene particle
YBB00232004-2015

Part 1 Out Cap

【Appearance】Take 125 pcs of the product, Look straight in bright nature light.
There must be no scars, splits, bubbles, foreign matter, burrs, etc. No more than 10
samples do not meet the above requirements.
【Cap-ring opening force】Take 10 pcs of the product, Place it in a high-pressure
steam sterilizer and heat it to 121 ° C ± 2 ° C for 30 minutes. After cooling to room
temperature, fix it on the fixture of the stretcher, and fix the pull ring on another
moving fixture.Apply pressure to the pull ring in a direction at an angle of 23 ° to the
vertical at a speed of 200mm / min ± 20mm / min, record the force of the pull ring,
and the opening force must not exceed 80N. During the test, it should not tear The
other area around the puncture area, and the pull ring must not break (during the test,
if the pull ring breaks in the fixture, take another sample and retest).
【 Sealing at the cut of the pull ring 】 Take 10 pcs of the product, Place it in a
high-pressure steam sterilizer and heat it to 121 ° C ± 2 ° C for 30 minutes,
After cooling to room temperature, fill it with a penetrant (65% ethanol: 10g / L
methylene blue solution: 100: 5) to a height of 2/3, and place it on filter paper for 60
minutes. The cut must not leak.
【Leachables test】Preparation of test solution: Take 40.0g of outer cover, wash with
water, dry at room temperature, put in 500ml conical flask, add 200ml of water, seal,
place in high-pressure steam sterilizer, heat to 121 ° C ± 2 ° C for 30 minutes, Cool to
room temperature as the test solution; take the same operation with other water and use
it as a blank solution for the following tests.
Easy oxide Precisely measure 20ml of the test solution, add 20ml of potassium
permanganate titration solution (0.02mol / L) and 2ml of dilute sulfuric acid, boil for 3
minutes, quickly cool, add 0.1g of potassium iodide, place in the dark for 5 minutes,
use sulfur Titrate sodium thiosulfate (0.01mol / L) to a light brown color, then add 5
drops of starch indicator solution to the colorless. Take another blank solution in the
same way, the difference between the two consumption of sodium thiosulfate titration
solution (0.01mol / L) should not exceed 3.0ml.
Non-volatile matter Precisely measure 50ml of the test solution and blank
solution, Place in a constant weight evaporation dish, evaporate to dryness in a water
bath, and dry to constant weight at 105 ° C. The difference between the two should
not exceed 12.5mg.
Heavy metal Precisely measure 10ml of the test solution, Add 2ml of acetate
buffer (PH3.5), check for heavy metals according to the heavy metal inspection
method ("Chinese Pharmacopoeia" 2015 edition of the fourth general rule 0821the
first method) ,heavy metals must not exceed one millionth.
0821 Heavy Metal Inspection
The heavy metals referred to in this method refer to the metal impurities that can
react with thioacetamide or sodium sulfide under specified experimental conditions.
Preparation of standard lead solution Weigh 0.1599g of lead nitrate, put it in a
1000ml measuring bottle, add 5ml of nitric acid and 50ml of water to dissolve it,
dilute it to the mark with water, and shake it as a stock solution.
Precisely measure 10ml of the stock solution, place it in a 100ml measuring bottle,
dilute with water to the mark, and shake to obtain (each 1ml is equivalent to 10μg of
Pb). This solution is for same day use only. Glass containers for preparation and
storage must not contain lead.
The first method
Unless otherwise specified, take three 25ml Nessler colorimetric tubes, add a
certain amount of standard lead solution and 2ml of acetate buffer solution (pH3.5) to
tube A, Add 25ml of the test solution made according to the method specified in each
item to tube B, add the test product of the same weight as tube B to tube C, and add an
appropriate amount of the solvent for the test solution to dissolve. After the same
amount of standard lead solution and acetate buffer solution (pH3.5) 2ml in tube A,
dilute tube C to 25ml with solvent; if the test solution is colored, a small amount of
diluted caramel solution or Other non-interfering colored solutions can be added to
tube At to make it consistent with tubes B and C; then add 2 ml of thioacetamide test
solution to tubes A, B and C respectively, shake well, and place for 2 minutes on the
same white paper. Watch from the top to the bottom, when the color displayed in the
tube C is not lighter than the tube A, the color displayed in the tube B must not be
darker than the tube A.

Part 2 Inner Cap

【Appearance】Take 125 pcs of the product, Look straight in bright nature light.
There must be no scars, splits, bubbles, foreign matter, burrs, etc. No more than 10
samples do not meet the above requirements.
【Residue on ignition】Take 5.0g of the inner cap and weigh it accurately, place it in
a crucible that has a constant weight, and burn to complete carbonization slowly, and
then burn it to a constant weight at 550 °C. The residual residue shall not exceed
0.10%.
【Leachables test】Preparation of test solution: Take several samples of this product
with surface area about 1200 cm2, cut them into small pieces of about 0.5 cm width,
put them in a beaker, add 400ml water to wash, dry at room temperature.Then transfer
them to a conical flask, add 400ml water, Place in a high-pressure steam sterilizer,
heat to 121 ° C ± 2 ° C, hold for 30 minutes, cool to room temperature, and remove it
to obtain a test solution, while preparing a blank solution, and do the following tests.
PH value
Take 20ml of the test solution, add 1ml of potassium chloride solution (1 → 1000),
and measure the PH value. The pH value should be 5.0 ~ 7.0.
 Absorbance
Take an appropriate amount of the test solution and measure it by UV-visible
spectrophotometry "Chinese Pharmacopoeia" 2015 edition of the fourth general rule
0401. Scan the measurement in the wavelength range of 220 ~ 350mm. The maximum
absorption value in the range of 220 ~ 240mm must not exceed 0.08, the maximum
absorption value in the range of 241 ~ 350mm must not exceed 0.05.
the fourth general rule 0401
Ultraviolet-visible spectrophotometry is a method for measuring the absorbance of a
substance in a wavelength range of 190 to 800 nm, which is used for identification,
impurity inspection and quantitative determination. When light passes through the
solution of the substance under test, the degree of absorption of the substance by the
substance varies with the wavelength of the light. Therefore, by measuring the
absorbance of a substance at different wavelengths and plotting the relationship
between its absorbance and wavelength, the absorption spectrum of the substance
under test is obtained. From the absorption spectrum, the maximum absorption
wavelength λmax and the minimum absorption wavelength λmin can be determined.
The absorption spectrum of a substance is related to its structure. Therefore,
substances can be identified by comparing the spectrum of a sample with a control
spectrum or a reference spectrum in a specific wavelength range, or by determining
the maximum absorption wavelength, or by measuring the absorption ratio at two
specific wavelengths. For quantification, the absorbance of a sample solution at a
certain concentration is measured at the maximum absorption wavelength, and
compared with the absorbance of a control solution of a certain concentration, or the
concentration of the sample solution is calculated using the absorption coefficient
method.
Easy oxide
Precisely measure 20ml of the test solution, add 20ml of potassium permanganate
titration solution (0.002mol / L) and 2ml of dilute sulfuric acid, boil for 3 minutes,
quickly cool, add 0.1g of potassium iodide, place in the dark for 5 minutes, and use
thiosulfate Titrate sodium sulfate (0.01 mol / L) to light brown, then add 5 drops of
starch indicator solution to titrate to colorless, take another blank solution and operate
in the same way, the two sodium thiosulfate consumption titration solution (0.01 mol /
L) The difference must not exceed 1.5ml.
Non-volatile matter
Precisely measure 100ml each of the test solution and blank solution, place them in an
evaporation dish with constant weight, evaporate to dryness in a water bath, and dry
to constant weight at 105℃. The difference between the two should not exceed
5.0mg.
Heavy metal
Precisely measure 20m of the test solution, add 2ml of acetate buffer solution (pH3.5),
check for heavy metals according to the heavy metal inspection method ("Chinese
Pharmacopoeia" 2015 edition of the fourth general rule 0821the first method) ,heavy
metals must not exceed one millionth.

Part 3 Combination cap

【 Appearance 】 Take 125 pcs of this product, look straight in a bright place with
natural light, and . There must be no scars, cuts, bubbles, mixed foreign matter, burrs,
adhesion, etc. No more than 10 samples do not meet the above requirements.
【Use Adaptation Test】Take several samples of the combined cover of the assembly
particle, heat them to 121 ° C ± 2 ° C by moist heat sterilization method, and hold
them for 30 minutes, then perform the following tests
Temperature adaptability
Take 5 samples and place them for 24 hours under the condition of -25℃ ± 2 ℃ then
keep them for 24 hours under the condition of 50℃ ± 2℃, and then leave them for 24
hours under the condition of 23℃ ± 2℃. The samples must not be deformed.
Puncture force
Take 10 of the above samples, and use a plastic puncture device according to Figure 1
to perform a vertical puncture (penetrating the inner cap) on the marked part of the
particle at a speed of 200 mm / min and 20 mm / min. Record the force applied by the
puncture combination cover, and repeat the puncture step until all samples are
punctured once. The average value must not exceed 75N, and the maximum value
must not exceed 80N.
Puncture chip
Take 10 of the above samples and assemble them on the matching container, and
inject about half the volume of water into the container. Divide into two groups, open
the pull ring, use the plastic puncture device according to Figure 1 and metal puncture
device according to Figure 2 (the end is connected with a hose) to perform a vertical
puncture pierce on the marked part of the particle three times (need to pierce the inner
cover), and inject 5 ml of water into the puncture device through a hose before pulling
the puncture device. Repeat the above steps until all combination caps are punctured.
Remove the combination cap and filter all the water in the container through quick
filter paper to ensure that no debris remains in the container. Under natural light, the
number of chips (diameter equal to or greater than 50 um) on the fast filter paper, and
the number of chips on plastic and metal puncture devices must not exceed 20
particles when observing by naked eyes (the distance between the eyes and the filter
paper is about 25cm).
Dynamic holding force of the puncture device
Take 10 of the above samples, and assemble them on the set of plastic infusion
container. Fill the container with water for injection with the indicated volume and
seal. First puncture the particle marked part of the combined cap with a puncture
device in accordance with Figures 1 and 2, and then pull out the puncture device at a
speed of 200 mm / min ± 20 mm / min. The separation force of the plastic puncture
device shall not be less than 5.0N; the separation force of the puncture device shall
not be less than 1.0N.
Static holding force of the puncture device
Take 10 of the above samples, and assemble them on the set of plastic infusion
container. Fill the container with water for injection with the indicated volume and
seal. First use a puncture device that conforms to Figure 1 to pierce the puncture mark
on the particle vertically. The puncture device pierces the rubber pad, the inner cap,
and hang the container upside down. Hang a 0.3kg weight vertically on the puncture
device. The puncture device should be kept for 4 hours without pulling out. and there
must be no liquid leakage at the puncture part.
【 storage 】 The inner packaging is packed with a medicinal low-density
polyethylene bag and kept in a clean and ventilated place.