Medicinal Polyisoprene Rubber Pad

Test basis:YBB00232004-2015
[Appearance]Take several samples of this product and check them according to table 1 , which
should meet the regulations.
Table 1 Appearance inspection rules
Item Appearance
AQL 0.40 1.5 6.5
TYPE A TYPE B TYPE C
There are stains and There are stains, The colors that the
impurities in the impurities, rubber defects caused by the
Classification acupuncture ring or filaments, rubber edge removal and the
of unqualified the contact surface crumbs, sponge-like, marks caused by the
with the content, and rough edges on the saw teeth are
there are bubbles and surface, plug neck obviously uneven
cracks in the rough, obvious lack of
acupuncture ring or rubber
the sealing surface

PHYSICAL FUNCTION
Take several of this product,and assemble them with a plastic outer caps and inner caps to
form Combination cap.Use damp heat sterilization at 121 ℃ ± 2 ℃ for 30 minutes (if the product
is not suitable for sterilization at 121 ℃ for 30 minutes, the sterilization conditions used in the
production of the product can be used for the test), cool to room temperature, then the products for
test can be made. The following tests are then carried out.
[FALLING LEFTOVER AFTER PUNCTURE ]Take 10 samples of this product and measure
them according to the third method of the injection rubber plug and rubber pad puncture chip
dropping method (YBB00332004-2015). The number of chip dropping shall not exceed 20 pcs.
The third method of the injection rubber plug and rubber pad puncture chip dropping method
(YBB00332004-2015) is as follows.
YBB00332004-2015
Scope of application: rubber pad for injection.
Instrument device,rubber pad support device: This device is a steel bottle with a rubber pad holder.
When the rubber pad is held on the top of the device by the holder, the device can support and fix
the rubber pad to ensure that not punctured into the bottle when punctured. The content of the
bottle should be more than 50ml (including 50ml); this method can also be carried out by using
other suitable rubber pad support devices. The rubber support device is shown in Figure 2.
Puncture devices: metal puncture devices can refer to (Figure 1) and plastic puncture devices can
refer to (Figure 3).
 Unit:mm
Figure 1. Metal puncture device

Unit:mm Unit:mm
figure 2. rubber pad support device figure 3.plastic puncture device

Suction filter.
Unless otherwise specified in the assay method, we should do the pretreatation of the rubber pads
as follows: Take 10 pcs rubber pads to be tested, put them into a high-pressure steam sterilizer,
keep them at 121 ° C ± 2 ° C for 30 minutes, then take them out, and cool to room temperature. If
the elastomer used in the plastic combination cap for large-capacity injections cannot be
maintained at 121 ° C ± 2 °C for 30 minutes, the rubber pad can be pretreated at the sterilization
temperature used in the actual production.
Add about half volume of the water into the container, take a pre-treated rubber pad, place it in the
support device, wipe the puncture device with acetone, hold the puncture device with hand, and
pierce the marked part of the rubber pad vertically. Withdrew the pucture device after shaking the
support device for a few seconds,then open the support device, remove the rubber pad,and filter all
the water in the bottle through a piece of filter paper to ensure that no falling leftover remains in
the bottle.Observe the number of falling leftover on the filter paper with eyes which are at the
distance of 25 cm to the filter paper.Repeat the above steps to test the remaining 9pcs rubber pads.
The results show that the total number of visible falling leftovers (corresponding to particles above
50 μ m) is recorded for the 10 tested rubber pads, and the type of puncture device used is noted in
the results.
[POWER OF PUNCTURE]Take 10pcs test samples, open the pull ring, use a plastic puncture
device, test them according to the third method of injection plug rubber, rubber pad puncture
force(YBB00322004-2015) .The average puncture force should not exceed 75N, and the puncture
force of each rubber pad should not exceed 80N. During the puncture process, No rubber pad
should be pushed into the bottle.
Third method(YBB00322004-2015)
Scope of application:rubber pad for injection.
Instrument device, material testing machine: This instrument can make the penetrator move
vertically at a speed of 200mm / min ± 20mm / min. The reaction force of the puncture force
during the movement can be recorded with an accuracy of ± 2N; Place the rubber support device
at the suitable position in axial so that the marked part of the rubber on the support device can be
punctured vertically.
Rubber pad support device: The device is a steel bottle with a rubber pad holder. When the rubber
pad is used to clamp the rubber pad on the top of the device, the device can support and fix the
rubber pad without being punctured when it is penetrated Inside, the content of the bottle is more
than 50ml (including 50ml). Other suitable rubber support devices can also be used for this
method. The rubber support devices are shown in Figure 2.
Puncture device: Metal puncture device (Figure 1) and plastic puncture device (Figure 3).
Determination method: Unless otherwise specified, perform the following pretreatment on the
rubber pad. Take 10pcs tested rubber pads in a suitable glass container, put them into a
high-pressure steam sterilizer, and keep at 121 ℃ ± 2 ℃ for 30 minutes .Take out and cool to
room temperature. If the elastomer used in the plastic combination cap for large-capacity
injections cannot be maintained at 121 ° C ± 2 ° C for 30 minutes, the rubber pads can be
pretreated at the sterilization temperature used in the actual production.
Take a pre-treated rubber pad, place it in the support device, place the puncture device on the
material testing machine and fix it, puncture the marked part of the rubber pad at a speed of
200mm / min, and record the maximum force value . Take another rubber pad and repeat the
above steps until 10 rubber pads have been punctured for once. Before using the puncture device,
check the sharpness of the puncture device. The puncture device should keep its original sharpness
without damage.
Express the result with the maximum force applied by the puncturing rubber pad, and note the
type of puncture device used in the result.
[SELF-SEAL FUNCTION AND PUNCTURE RETENTION]Take 10pcs of the above samples,
and assemble them on the set of plastic infusion container. Fill the container with injection water
with the indicated volume and seal. First puncture the marked part on the rubber pad vertically
with plastic piercer device that conforms to Figure 1. The puncture device punctures the rubber
pad,and hang the container upside down. Hang an object of 0.3 kg weight 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.
[ASH]Take 2.0g of this product and measure it according to the determination of ASH for
rubber(YBB00262005-2015). The residual residue should not exceed 25%.
Determination of ASH for rubber(YBB00262005-2015) is as follows:
YBB00262005-2015
This standard is applicable to the determination of ash in pharmaceutical halogenated butyl rubber,
polyisoprene rubber stoppers and rubber pad.
Determination method: Take an appropriate amount of this product, cut it into pieces, take 1.0g,
place it in a crucible which has been blazed to constant weight, accurately weigh it, and slowly
burn it to complete carbonization on an electric furnace (it should be prevented from catching fire),
and let it cool.Burn at a temperature of 800 ° C ± 25 ° C to complete ashing, place in a desiccator,
let it cool, accurately weigh, and then burn to a constant weight at a temperature of 800 ° C ± 25 ° C.
Representation of results
The percentage content of ash “ x” is calculated as follows: X (%) = (m1-m2) / m0 * 100
In the formula: X is the percentage content of ash,%
m0 is the weight of the test product, g
m1 is the weight of the crucible, g
m2 is the weight of crucible with ash, g

CHEMICAL FUNCTION
[VOLATITL SULFDES] Take this product and measure it according to the determination of
volatile sulfide (YBB00302004-2015), which should meet the requirements.
The determination of volatile sulfide (YBB00302004-2015) is as follows:
This method is applicable to the determination of volatile sulfur compounds in various kinds of
medicinal rubber stoppers or rubber pads.
Common vulcanization systems use sulfur or sulfur-containing compounds as crosslinkers. Putting
this compound vulcanized rubber material in the medium of aqueous solution extraction, under a
certain acidity condition, volatile sulfides will be formed. This released sulfide can form sulfur
spots by reacting with lead acetate test paper. The remaining sulfur spots were measured visually.
This method is expressed in terms of sulfur compounds released per 20 cm2 of rubber, and the unit
is μgNa2S / 20cm2.
The test method uses a rubber with a total surface area of 20cm2±2cm2, which can be cut if
necessary, put in a 250 ml conical flask, add 1 ml of water, and then add 50 ml of a 2% citric acid
solution. Place a piece of lead acetate test paper Place the conical flask on the mouth of the conical
flask with a beaker and place it in an autoclave. Heat at 121 °C ± 2 °C for 30 minutes. If the color
is developed, the generated sulfur spots and 1.00 ml of a standard sodium sulfide solution (weigh
an appropriate amount of Na2S.9H2O, add dissolve in the water, so that each 1ml solution contains
0.154 mg of Na2S.9H2O, shake well, that is. the solution should be made for temporary use and
new made.) when "adding 50ml of 2% citric acid solution", compare with the standard sulfur spot
prepared by the method, it must not be deeper(50μgNa2S/20cm2).

Provide the preparation of test solution: Take several complete rubber stoppers with a surface area
of 200cm2.According to the ratio of sample surface area(cm²) to water(ml) 1:2, and put them into
water，boil for 5 minutes and let them cool down,and then flush them with water for 5 times.Move
them into a conical flask and add the same volume of water,then placed in high pressure steam
sterilizer,hold for 30 minutes at the temperature of 121℃士 2℃,and cool it to room temperature
and remove them out.Prepare the blank solution in the same way and do the following tests.
[CLARITY]Take the test solution and check its clarify with the turbidity standard solution , the
solution should be clear. If it is turbid, it should not be thicker than the No.2 turbidity standard
solution.The method of making the turbidity standard solution is as follows.
Preparation of standard turbidity stock solution: Weigh 1.00g of hydrazine sulfate which is dried at
105 ℃ to constant weight, place it in a 100ml measuring bottle, add appropriate amount of water
to dissolve, and dissolve warmly in 40 ℃ water bath if necessary.Dilute to the mark with water,
shake well, and place for 4 ~ 6 hours. Mix this solution with an equal volume of 10% urotropine
solution. The solution should be stored in a cold place without sunshine, it can be used within 2
months, shake well before use.
Preparation of turbidity standard stock solution: Take 15.0ml of turbidity standard stock solution,
place it in a 1000ml volumetric flask, dilute with water to the mark, shake well, take the
appropriate amount, place it in a 1cm absorption cell.Measure it at a wavelength of 550nm
according to UV-visible spectrophotometry "Chinese Pharmacopoeia" 2015 edition of the fourth
general rule 0401, the absorbance should be in the range of 0.12-0.15. The solution should be used
within 48 hours, shake well before use. Preparation of turbidity standard solution is made with the
standard solution and water as the following table . Turbidity standard solution should be prepared
immediately before use, and shake well before use.
Preparation of turbidity standard solution: Take turbidity standard stock solution and water, and
mix them according to the following table. The turbidity standard solution should be prepared
immediately before using, and shake well before use.
Grade 0.5 1 2 3 4
Turbidity standard stock 2.50 5.0 10.0 30.0 50.0
solution /ml
Water /ml 97.5 95.0 90.0 70.0 50.0

[ PH ]Take 20ml of test solution and blank solution, add 1ml of potassium chloride solution (1 →
1000), and measure the PH value. The difference between the two must not be greater than 1.0
[ULTRAVIOLET ABSORBENCY]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. In the wavelength range of 220 ~ 360nm, the maximum absorbance must not exceed
0.3.
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.

[EASILY OXIDIZABLE SUBSTANCE]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
sodium thiosulfate titrant (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 difference
between the two test consumption of sodium thiosulfate titrant must not exceed 3.0ml.
[NON-VOLATILE MATTER]Precisely measure 100ml each of the test solution and blank
solution, place them in an evaporation dish which has been 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 4.0mg
[HEAVY METALS]Precisely measure 10m 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.
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) totube 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

[AMMONIUM]Precisely measure 10 ml of the test solution, add 2 ml of the alkaline potassium

potassium iodide test solution, and leave it for 15 minutes without color development. If the color
develops , use 2.0ml ammonium chloride solution(Take 31.5 mg of ammonium chloride and
ammonia free water to dissolve and dilute to 1000.0 ml ) to add 8 ml of blank solution and
compare with a control solution made of 2ml of alkaline potassium potassium iodide test solution,
it must not be deeper (0.0002%).
[ZINC]Take the test solution and filter with 0.45μm pore diameter membrane,accurately measure
10ml of continuous filtering solution, add 2mol/L hydrochloric acid 1ml and 3 drops of potassium
ferrocyanide test solution (Weigh 4.2g of potassium ferrocyanide trihydrate,dissolve with water
and dilute to 100ml,then shake well,then get it) and mix them,it should be no turbidity.If it is
turbid, mix with standard 3.0ml zinc solution (weigh 44.0mg zinc sulfate heptahydrate, dissolve
and dilute to 1000.0 ml with freshly boiled and cooled water, the solution should be made for
temporary use and new made) ,add 7ml blank solution and 2mol / 1ml of L hydrochloric acid and
compared with 3 drops of potassium ferrocyanide test solution,the result should not be deeper
(0.0003%).
[ELECTRICAL CONDUCTIVITY]The test solution should be measured with a conductivity
meter within 5 hours of preparation: the conductivity of the blank solution should not exceed
3.0uS / cm (20℃ ± 1℃), and the conductivity of the test solution should not exceed 40.0uS / cm.
If the measurement is not performed at 20 °C ± 1 °C, the temperature should be corrected.