Semester –VII UNIT 3(a): Quality Control Tests for Packaging materials

SHREE H. N. SHUKLA INSTITUTE OF

PHARMACEUTICAL EDUCATION AND
RESEARCH

B.PHRAM
(SEMESTER –VII)

SUBJECT NAME: QUALITY ASSURANCE

SUBJECT CODE: BP706TT

UNIT 03 (a): QUALITY CONTROL TESTS FOR PACKAGING

MATERIALS

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Semester –VII UNIT 3(a): Quality Control Tests for Packaging materials

Content
Quality Control: Quality control test for containers, rubber closures and secondary packing
materials.

Packaging of pharmaceutical products gives an adequate degree of protection, minimizes the loss
of constituents and should not interact physically or chemically with products. Any material which
is used for packing of product for sale and transportation is said to be packing material.
The commonly used packaging materials are Container, Closure and Carton. The containers mostly
made of glass, plastic, metal or paper. The material for closure may include cork, glass, and plastic,
metal or rubber.
There are two types of packing materials which are as below.
1. Primary packaging
Primary packing materials which comes directly contact with products. e.g. bottles, vials,
ampoules, tin, Blister package, Strip package etc.

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Semester –VII UNIT 3(a): Quality Control Tests for Packaging materials

2. Secondary Packaging
Secondary Packaging is outside the primary packaging perhaps used to group primary packages
together and cover it. e.g. cartons, boxes, etc.

3. Tertiary Packaging
Tertiary Packaging is used for bulk handling, warehouse storage and transport shipping.

QUALITY CONTROL TEST FOR CONTAINERS

 Quality Control Tests for Glass containers

1. Chemical Resistance Test
A. Powdered Glass Test
B. Water Attack Test
2. Hydrolytic Resistance Test
3. Arsenic Test
4. Thermal Shock Test
5. Internal Bursting Pressure Test

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Semester –VII UNIT 3(a): Quality Control Tests for Packaging materials

1) Chemical Resistant Test:

The following tests are designed to determine the resistance to water attack of new glass containers.
The degree of attack is determined by the amount of alkali released from the glass under the
influence of the attacking medium under the conditions specified.
A. Powdered Glass Test: It is done to estimate the amount of alkali leached from the powdered
glass, which usually happens at elevated temperature. When glass is powdered, leaching of
alkali is enhanced, which can be titrated with 0.02 N sulphuric acid using methyl red as an
indicator.
Step 1: Preparation of glass specimen
Few containers are rinsed thoroughly with purified water and dried with stream of clean air.
Grind the containers in a mortar to a fine powder and pass through sieve no. 20 and 50.
Step-2: Washing the specimen:
10 gm of the above specimen is taken into 250 ml conical flask and wash it with 30 ml acetone.
Repeat the washing, decant the acetone and dried after which it is used within 48hr.
Procedure: 10 gm sample is added with 50 ml of high purity water in a 250ml flask. Place it
in an autoclave at 121 ⁰C ± 2 ⁰C for 30 min. cool it under running water. Decant the solution
into another flask, wash again with 15 ml high purity water and again decant. Titrate
immediately with 0.02 N sulphuric acid using methyl red as an indicator and record the volume.

Glass container rinse with water, dried with steam.

Grinding of container to a fine powder

Wash 10 gm of above sample with acetone and dry

50 ml of purified water is added to the dried sample and autoclaved at

121°C for 30 minutes and cooled and decanted.

The decanted liquid is titrated with 0.02 N H2SO4 using methyl red as
indicator.

Tests Container Vol. of 0.02 N H2SO4

Powdered Glass Type I 1.0
Test
Type II 8.5

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Semester –VII UNIT 3(a): Quality Control Tests for Packaging materials

Type III 15.0

B. Water Attack Test:

This test is used only with containers that have been exposed to sulphur dioxide fumes under
controlled humidity conditions. Such a treatment neutralizes the surface alkali. Now the glass
becomes chemically more resistant.

Principle: The principle involved in the water attack test is to determine whether the alkali
leached form the surface of a container is within the specified limits or not. The amount of acid
that is necessary to neutralize the released alkali from the surface is estimated, the leaching of
alkali is accelerated using elevated temperature for a specified time. Methyl red indicator is
used to determine the end point. The basic is acid-base titration.

Procedure:

Rinse the glass container with high purity water

Container fill up to 90 % of its overflow capacity with water and autoclaved at 121
°C for 30 min.

Cool and then decant liquid

The decanted liquid is titrated with 0.02 N H2SO4 using methyl red as indicator.

The volume of H2SO4 consumed is the measure of the amount of

alkaline oxides present in the glass containers.

Tests to be done on different type of glass materials.

Type General Description Type of Test

I Highly resistant, borosilicate glass Powdered Glass

II Treated soda-lime glass Water Attack

III Soda-lime glass Powdered Glass

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Semester –VII UNIT 3(a): Quality Control Tests for Packaging materials

Tests Container Vol. of 0.02 N H2SO4

Water Attack Test Type II (100 ml or below) 0.07
Type II (above 100 ml) 0.02

2) Hydrolytic Resistance of Glass Containers:

Rinse each container at least 3 times with distilled water and fill with the same to their filling
volume. Heat to 100 ⁰C for 10 min and allow the steam to issue from the vent cork. Rise the temp
from 100 ⁰C to 121 ⁰C over 20 min. Maintain the temp at 121⁰C to 122⁰C for 60 min. Lower the
temp from 121⁰C to 100 ⁰C over 40 min venting to prevent vacuum.

Remove the container from autoclave, cool and combine the liquids being examined. Measure the
volume of test solution into a conical flask and titrate with 0.01M HCl using methyl red as an
indicator. Perform blank with water and the difference between the titration represents the volume
of HCl consumed by the test solution.

Rinse each container and

fill wiith water

Heat to 100 ⁰C & Rinse at

121 ⁰C in autoclave

Remove from autoclave &

combine all liquids

Titrate with 0.01M HCl using

methyl red as an indicator.

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Semester –VII UNIT 3(a): Quality Control Tests for Packaging materials

Nominal Capacity of Number of containers Volume of test solution to be

container (ml) to be used used for titration (ml)
5 or less at least 10 50.0

6 to 30 at least 5 50.0

More than 30 at least 3 100.0

3) Arsenic test:
This test is for glass containers intended for aqueous parenterals.

Wash the inner and outer surface of container with fresh distilled water for 5 min. Then similar
steps are followed as performed in the hydrolytic test, previously described, till obtaining the final
combined solution.

Pipette out 10 ml solution from combined contents of all ampoules to the flask. Add 10 ml of HNO3
to dryness on the water bath, dry the residue in an oven at 130⁰C for 30 min cool and add 10 ml
hydrogen molybdate reagent .Swirl to dissolve and heat under water bath and reflux for 25 min.
Cool to room temp and determine the absorbance at 840 nm.

Do the blank with 10ml hydrogen molybdate. The absorbance of the test solution should not exceed
the absorbance obtained by repeating the determination using 0.1 ml of arsenic standard solution
(10 ppm) in place of test solution.

Wash the inner and outer

surface of container with
fresh distilled water

Prepare the test solution

same as the hydrolytic test

10 ml of test sol. + 10 ml of
HNO3 -dried at 130 ⁰C in
oven

cool and add 10 ml

hydrogen molybdate
reagent

Heat under water bath. Cool &

absorbance is measured at
840 nm.

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Semester –VII UNIT 3(a): Quality Control Tests for Packaging materials

4) Thermal Shock Test:

• Place sample container in upright position in

tray & immersed tray in hot water for a given
Step 1 time.

• Transfer the container in cold water bath &

temperature should be controlled. Examine
cracks before & after test.(45 °C temp.
Step 2 difference should be there.)

The amount of thermal shock a bottle can withstand is based on construction. Small bottles
withstand a temp differential of 60 °C to 80 °C and 1 pint bottle 30 °C to 40 °C.

5) Internal Bursting Pressure Test

The most common instrument used is American glass research increment pressure tester.

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Semester –VII UNIT 3(a): Quality Control Tests for Packaging materials

STEP 2
• The test bottle
is filled with • Bottle are checked
water and • A scaling head is at preselected
placed inside applied and the pressure level
the test internal pressure until container
chamber automatically raised finally burst.
by a series of
STEP 1 increments each of STEP 3
which is held for a set
of time

6) Leakage Test:
Drug filled container is placed in a container filled with coloured solution (due to the addition of
dye) which is at high pressure compared to the pressure inside the glass container so that the
coloured solution enters the container if any cracks or any breakage is present.

 Quality Control Tests for Plastic containers:

 For Non-injectable preparation:
1. Collapsibility test :
This test is applicable to containers which are to be squeezed in order to remove the contents.
A container by collapsing inward during use, yield at least 90% of its normal contents at the
required rate of flow at ambient temperature.

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Semester –VII UNIT 3(a): Quality Control Tests for Packaging materials

2. Clarity of aqueous extract:

A suitable container is taken at random, and

unlabeled, unmarked and nonlaminated portions is
selected.

These portions are cut into strips, none of which has a

total surface area of 20 cm2.

The strips are washed free from extraneous matter by

shaking them with at least two separate portions of
distilled water for about 30 secs.

The processed sample is taken in to the flask,

previously cleaned with chromic acid and rinsed with
distilled water.

250 ml of distilled water is added to the flask, covered

and autoclaved at 121°C for 30 mins.

The extract is cooled and examined. It should be colorless and free from turbidity.

3. Non-volatile residue
Evaporate 100 ml of the extract obtained in the test for Clarity of aqueous extract to dryness
and dry to constant weight at 105º. The residue weighs not more than 12.5 mg.

4. Leakage test:

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Semester –VII UNIT 3(a): Quality Control Tests for Packaging materials

10 containers are filled with water and

fitted with intended closures.

They are kept inverted at room

temperature for 24 hours.

The test is said to be passed if there is

no sign of leakage from any container.

5. Water vapour permeability:

• Fill 5 containers with nominal volume of water and heat

sealed bottles with aluminium foil.
STEP 1

• Weigh accurately each container and allow to stand for

14 days at humidity 60 ± 5% temp. 20 °C to 25°C.
STEP 2

• Reweigh the containers. Loss in wt in each container is

STEP 3 NMT 0.2%

 Quality Control Test for Strip and Blister packing

Strip and Blister

Later on strips, blisters
3/4th of water is were placed inside
were taken out. water
poured in desiccators and vaccum
present over the outer
desiccator. is
surface were wiped out.
applied

If there is no leakage, The content of strips and

content will not be blisters were removed
wetted. It indicate and presence of moisture
perfect sealing. was checked

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Semester –VII UNIT 3(a): Quality Control Tests for Packaging materials

QUALITY CONTROL TEST FOR CLOSURES

1. Sterility Test
2. Fragmentation Test
3. Self-Sealability
4. pH of aqueous extract
5. Light Absorption Test
6. Reducing Substance
7. Residue on Evaporation
8. Penetrability

Preparation of sample:
 The closures are washed in 0.2% w/v of anionic surface active agents for 5 minutes.
 Rinsed five times with distilled water and 200 ml water is added.
 Subjected to autoclave at 119°C to 123°C for 20-30 minutes covering with aluminum foil.
 Cooled and solution is separated from closures (Solution A).

1. Sterility Test:
Procedure: When treated closures are subjected to sterilization test at 64-66 ⁰C and a pressure
of about 0.7 KPa for 24 hr., the closures used for the preparation of the sample solution shall
not soften or become tacky and there shall be no visual change in the closure.

2. Fragmentation Test

Take 12 clean vials and place closures containing 4ml

of water. Allow to stand for 16 hrs.

Use hypodermic needle to inject 1ml of water into

the vial & remove 1ml of air.

Carry this operation for 4 times with new needle each

time.

Pass the water present in vial through a filter with

pore size of 0.5 μm

No. of fragments of closure retain should be as

per the limits

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Semester –VII UNIT 3(a): Quality Control Tests for Packaging materials

No. of fragments is NMT 10 except in the case of butyl rubber closures where the total no. of
fragments is NMT 15.

3. Self-Sealability Test

 This test is applicable to closures intended to be used with water close the vials with the
‘Prepared’ closures

 For each closure, use a new hypodermic needle with an external diameter of 0.8 mm &
pierce the closure 10 times, each time at a different site.

 Immerse the vials upright in a 0.1 % w/v solution of methylene blue & reduce the external
pressure by 27 KPa for 10 min.

 Restore the atmospheric pressure and leave the vials immersed for 30 minutes. Rinse the
outside of the vials.

 None of the vials contains any trace of coloured solution.

Pierce cap for 10 Immerse vials in

Fill 10 vials with
times at different 0.1%w/v solution
nominal volume of
sites with of methylene
water and place
hypodermic blue under
closures.
Needle pressure

Keep the
Wash the vials & none of
container
vials should contain traces
immersed for
of colour solution.
30 minutes

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Semester –VII UNIT 3(a): Quality Control Tests for Packaging materials

4. pH of aqueous extract

20 ml of solution A is added with 0.1ml bromothymol blue when it is added with a small amount
of 0.01M NaOH which changes the colour from blue to yellow. The volume of NaOH required is
NMT 0.3 ml and if it is done with HCl, the volume of HCl needed should NMT 0.8ml.

5. Light Absorption Test

It must be done within 4 hrs of preparing solution A. It is filtered through 0.5μ filter and its
absorbance is measured at 220 to 360 nm. Blank is done without closures and absorbance is NMT
2.0.

6. Reducing Substance

20 ml of solution A is added with 1ml of 1M H2SO4 and 20 ml of 0.002 M KMnO4 and boil for 3
min then cool and add 1gm of potassium iodide which is titrated with sodium thiosulphate using
starch as an indicator. Blank is done and the difference between titration volumes is NMT 0.7 ml.

20 ml of sample solution + 1M sulphuric acid +

20 ml of 0.002 M
Potassium permanganate

Boil for 3
min. and
cool it.

Add 1 g of Potassium iodide

Treat the solution with Na thiosulphate using starch solution as

indicator.

Blank Titration is done and difference of sample and blank should

be NMT-0.7ml

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Semester –VII UNIT 3(a): Quality Control Tests for Packaging materials

7. Residue on Evaporation

The 50 ml of sample solution is evaporated to dryness at 105 °C. Then weigh the residue.
Residue obtained should not be more than 4 mg.

8. Penetrability Test

 This is to measure the force required to make a hypodermic needle penetrate easily through
closure. It is measured by using piercing machine.

 The piercing force must not exceed a stated value, the hypodermic needle can get damage as a
result of undesirable hardness of closure.

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Semester –VII UNIT 3(a): Quality Control Tests for Packaging materials

QC TEST FOR SECONDARY PACKAGING MATERIALS

Different Types of Secondary Packaging materials

 Paper and Boards
 Cartons
 Corrugated fiberboard

Testing of Paper & Board

The test pieces of paper and board are taken for test to be carried out in standard condition
a) Temperature: 23 °C ± 1°C
b) Relative Humidity: 50% ± 2%
Test Description
Dimensions The physical dimensions of the given paper board is taken and recorded.
Grammage A test piece of suitable size (10cm×10cm) is cut and weighed. The
grammage of the sample is determined by

Grammage = 104×w/a×b
w - weight in grams
a - length
b- breadth
Thickness Measured with a micrometer. Thickness is related to grammage of paper
and its bulk density. It directly influences the physical property of paper
like stiffness, varnishing and cutting.

Surface pH Acidity in paper may be caused by the presence of residual chemical left
in the pulp.

A drop of distilled water is placed on the top of the test piece and the
electrode of pH meter is placed in the drop touching the paper.

The reading is taken after 2 min.

PH after Cut 1gm of paper & place in a 100 ml flask, fitted with condenser, add 20
Extraction ml of boiling distilled water in small portions till the paper is wet.

Add 50 ml of distilled water. Reflux and digest with occasional shaking

at 95-100 °C for 1 hr. Cool to 40-45 °C, remove the condenser and shake,
cool in water bath. Determine the pH of the supernatant with pH meter.

Moisture Conditioned specimen is weighed and heated to a constant weight to expel

Content the moisture. The difference of the two weights gives the moisture content
of the paper.

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Semester –VII UNIT 3(a): Quality Control Tests for Packaging materials

% moisture = 100(A-B) / B
A - Original weight
B - Weight after drying.
Ash content Take about 1g of specimen and make it in to shreds and place in a
previously weighed crucible (C). Heat carefully over a burner till
completely charred. Transfer the crucible in to a muffle furnace at 800 °C
until all the carbonaceous matter are burnt off. Cool in desiccator, weigh
and repeat the experiment to a constant weight (D).

% Ash= 100(C-D)/D

Alkalinity Place about 5g (w) of accurately weighed sample, cut into pieces in a
stoppered flask containing 250 ml of 0.02N HCl. Allow to stand for 1 hr
with occasional shaking.

Decant and titrate a measured quantity (v) against 0.1 N NaOH using
methyl orange as indicator.

Carry out blank (B).

1250 (𝐵−𝐴)× 𝑁
% Alkalinity=
𝑉𝑥𝑤
A- Sample reading
N- Normality of NaOH

Cobb test This measures the mass of water absorbed by 1cm2 of the test piece in a
specified time under a head of 1 cm of water. It is determined by weighing
before and after exposure to the water, and usually quoted in g/m2.

Folding Fold the piece back and forth until rupture occurs.
endurance
Tensile strength The max tensile force per unit width that a paper or board will withstand
before breaking.

Tear strength The mean force required to continue the tearing of an initial cut in a single
sheet of paper.

Air permeability Important for using light weight uncoated paper on machine having
vacuum pick up system.

Stiffness Degree of resistance offered by paper/board when it is bent.

Burst resistance The max uniformly distributed pressure, applied at right angles to the
surface that a test piece of paper and board will stand under conditions of
test, Hydraulic pressure is applied to diaphragm, bulging it until test piece
bursts.

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