quality control tests for packaging materials in pharmaceutical industry

1. Quality control test: Containers, Closures and
Secondary packing materials
Name of student:
Miss. Pranali Polshettiwar
M. Pharm 1st yr.
Name of guide:
Mrs. S. S. Gaikwad
Assistant Professor M. Pharm (QAT)

2.  Packing materials
 Quality control test for containers and closures
 Quality control test for secondary packing materials

3. Packing materials
• Any material that is used for packaging of products for their distribution and sale
is said to be packing material.
• Primary packing:- comes in direct contact with the product e.g. bottles, vials,
ampoules, tin, etc.
• Secondary packing:- used to cover primary packs e.g. cartons, boxes, etc.
1

4.  Different types of materials used for container
1. Glass container
2. Plastic container
3. Metal container
 Different types of materials used for closures
1. Rubber closures
2. Plastic closures
3. Metal closures
 Different types of materials used for secondary packaging
1. Paper
2. Cartons/cardboards
2

5. Quality control test for containers and closures
 Quality control test for glass containers
1. Chemical resistance test
a)Powdered attack test
b)Water attack test
2. Hydrolytic resistance test
3. Arsenic test
4. Thermal shock test
5. Internal bursting pressure test
3

6. Powdered glass test
 It is done to estimate the amount of alkali leached from the powdered glass,
which happens at elevated temperatures.
Sample containers are rinsed with purified water and dried
The containers are grinded in a mortar to a fine powder and passed through
sieve no. 20 & 50
10 gm of the sample is washed with acetone and dried
50 ml of purified water is added to the dried sample and autoclaved at
121°C 30 min and cooled and decanted
The decanted liquid is titrated with 0.02N H2SO4 using methyl red as indicator
4

7. 5
Test Container Vol. of 0.02N H2SO4 (ml)
Powdered glass
test
Type I (borosilicate glass)
Type II (soda-lime glass)
Type N.P (general purpose soda-lime
glass)
1.0
8.5
15.0
Limits:-
Sample with methyl red indicator

8. Water attack test
 This test is for type II glass. The principle involved in this is whether the alkali
leaches from surface of container.
The container is rinsed thoroughly with high purity water.
It is then filled with water upto 90% of its capacity
It is then autoclaved at 121°C for 30 min.
Then it is cooled and liquid is decanted
Decanted liquid is titrated with 0.02N H2SO4 using
methyl red as an indicator
The volume of H2SO4 consumed is recorded and compared with limits
6

9. 7
Test Container Vol. of 0.02N H2SO4 (ml)
Water attack test Type II
Size-100 ml
Less than 100 ml
1.0
0.7
0.2
Limits:-

10. Hydrolytic resistance test
The test is directly related to the stability of pharmaceuticals packed in it.
•Test 1: Type I and Type II glass containers to distinguish from Type III glass
containers
•Test 2: Type I and Type II glass containers where it is necessary to determine
whether the high hydrolytic resistance is due to the chemical composition or the
surface treatment
Nominal capacity of
container (ml)
No. of containers to be used Volume of test solution to
be used for titration(ml)
Up to 3 At least 20 25.0
5 or less At least 10 50.0
6 to 30 At least 5 50.0
More than 30 At least 3 100.0 8
Limits:-

11. Test 1
Each container is rinsed at least three times with CO2 free water
and filled with the same to their filling volume
Vials and bottles are covered and autoclaved at 100°C for 10 mins.
and the steam is allowed to displace from the vent cork
The temp. is risen from 100°C to 121°C over 20 mins.
The temp. is maintained at at 121°C to 122°C for 60 mins.
The temp. is lowered from 121°C to 100°C over 40 min.
venting to prevent vaccum
9

12. 10
The containers are removed from autoclave, cooled and the liquids are combined
in a conical flask and the volume is measured.
This test solution is titrated with 0.01M HCl using methyl red as an indicator
(methyl red is red in alkaline pH and pink in acidic)
A blank titration is performed with water and the difference between the titration
represents the volume of HCl consumed by the test solution
Test 2
•Rinse the container twice with water and fill completely with 4% v/v solution of
Hydrofluoric acid and allow to stand at room temperature for 10 mins.
•Empty containers and rinse 5 times with water.
•Rest procedure are same as in test 1.

13. Limits:-
Capacity of container
(corresponding to 90% average
flow volume)(ml)
Volume of 0.01M HCl
Type I or Type II glass(ml)
Volume of 0.01M HCl
per 100 ml of test
solution
Type III glass(ml)
Not more than 1 2.0 20.0
More than 1 but NMT 4 1.8 17.6
More than 2 but NMT 5 1.3 13.2
More than 5 but NMT 10 1.0 10.2
More than 10 but NMT 20 0.80 8.1
More than 20 but NMT 50 0.60 6.1
More than 50 but NMT 100 0.50 4.8
More than 100 but NMT 200 0.40 3.8
More than 200 but NMT 500 0.30 2.9
11

14. Arsenic test
 This test is for glass containers intended for aqueous parenterals.
The inner and outer surface of container is washed with fresh distilled
water for 5 min.
containers are covered and autoclaved at 100°C for 10 mins.
The temp. is risen from 100°C to 121°C over 20 mins.
The temp. is maintained at at 121°C to 122°C for 60 mins.
The containers are cooled and the liquids are combined
and volume measured.
12

15. 10 ml from the final combined volume is pipetted out and
to it 10 ml of HNO3 is added and
dried in an oven at 130°C
10 ml of hydrogen molybdate is added and refluxed for 25 mins
It is cooled and absorbance is measured at 840nm
A Blank test is performed with 10 ml hydrogen molybdate.
Limits:- The absorbance of the test solution should be less than the absorbance
obtained using 0.1 ml of arsenic standard solution (10 ppm)
13

16. Thermal shock test
Sample container is placed in upright position in tray and the tray is
immersed in hot water for a given time
The container is then transferred in cold water bath and temp. should be controlled.
Cracks are examined before and after test (45°C temp. difference should be there)
14

17. 15
The amount of thermal shock a bottle can withstand is based on construction
Small bottles- 60°C to 80°C
Pint bottles- 30°C to 40°C

18. Internal bursting pressure test
Instrument used American glass research increment pressure tester.
The test bottle is filled with water and placed inside test chamber
The internal pressure automatically raised by series of increment at set time
Bottle are checked at preselected pressure level until container finally burst
https://youtu.be/VH6I1wy9UPU
Test chamber
Glass bottle burst tester
16

19.  Quality control test for plastic containers
1. Leakage test
2. Collapsibility test
3. Clarity of aqueous extract
4. Water vapour permeability test
5. Transparency test
17

20. Leakage test
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
Plastic containers kept inverted 18

21. • 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.
Collapsibility tester 19
Collapsibility test

22. Clarity of aqueous extract
A suitable container is taken at random, and unlabeled, unmarked
and non-laminated portions is selected
These portions are cut into strips, none of which has a total surface area of 20 cm2
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 colourless and free from turbidity.
20

23. Water vapour permeability test
5 containers are filled with nominal volume of water and heat sealed with an
aluminium foil, poly ethylene laminate or other suitable seal
Then each container is weighed and allowed to stand (without any overwrap) for 14
days at a relative humidity of 60+5% and a temperature between 20 and 25°C
Containers are reweighed (the loss in weight in each container is not more
than 0.2%)
Water vapour permeability tester 21

24. Transparency test
• 5 containers are filled to their normal capacity with dil. suspension as per IP
1996
• The cloudiness of suspension is observed when viewed through the container
and compared with a similar container filled with water
22

25. 23
 Quality control test for metal containers
The metals commonly used for construction of containers
are aluminium, tin plated steel, stainless steel, tin and lead.
Test:
Take 50 empty tubes filled with ointment base, sealed and kept overnight.
A metal bacteriological filter assembly is fitted with with 4.25cm filter paper of
suitable porosity and heated to melting range of ointment base.
Base from all tubes squeezed at certain rate and extruded base is collected.
Walls of the filter and filter paper is washed with 3 successive quantities of each of
30 ml, of chloroform, and filter paper is allowed to dry.
Filter paper is then examined under oblique lighting using a magnifying glass.

26. Each metal particle detected on the filter paper is given a score as follows:
•Particles 1mm and above 50
•Particles 0.5mm but less than 1mm 10
•Particles 0.2mm but less than 0.5mm 2
•Particles less than 0.2mm nil
Limit
If total score is <100 = comply
If total score is >150 = fail
If score is 100-150 = repeat
24

27.  Quality control test for
closures
1. Residue on evaporation
2. pH of aqueous extract
3. Reducing substance test
4. Sterility test
5. Fragmentation test
6. Residue on evaporation
7. Penetrability test
25

28. Preparation of sample solution:
The closures are washed in 0.2% w/v of anionic surface active agents for 5 mins.
Rinsed 5 mins with distilled water and subjected to a flask with 200 ml water.
Subjected to autoclave at 119°C to 123°C for 20-30 mins covering with
aluminium foil.
Cooled and solution is separated from closures.
26
Residue on Evaporation
•50 ml of sample solution is evaporated at 105°C.
•Residue obtained should be not more than 4 mg.

29. pH of Aqueous extract
20 ml of sample solution is taken and 0.1 ml of bromothymol blue is added to it
The sample solution is titrated with 0.01M NaOH
till colour changes from blue to yellow
Volume is measured after the colour change
Limits:- Vol. of NaOH – not more than 0.3 ml
If HCl is used – not more than 0.8 ml
27

30. Reducing substance test
20ml of sample solution + 1M H2SO4 + 0.002M KMnO4
Boiled for 3 min and cooled down
Add 1 gm of Potassium iodide
Treat the solution with Sodium Thiosulphate using starch solution as indicator
Blank titration is done and
difference of sample and blank should be not more than 7.0 ml
28

31. 29
Container closure integrity testing (CCIT) is an assay that evaluates the adequacy
container closure systems to maintain a sterile barrier against potential
contaminants.
Closures are subjected for sterilization
Autoclaved at 64-66°C and pressure 0.7kPa
Further testing is carried out by using culture media
Sterility test

32. Fragmentation test
This test is applicable to closures intended to be pierced by a hypodermic needle.
12 clean vials are taken with 4 ml water and closures are placed
Allowed to stand for 16 hrs
A hypodermic needle is used to inject 1 ml of
water into the vial and1 ml of air is removed
This operation is carried out for 4 times with new
needle each time
Water present in vial is passed through a filter with pore size of 0.5 micrometer
No. of fragments of closure retained should be as per the limits
Limits:- No. of fragments- not more than 10 (in case of butyl rubber)
No. of fragments- not more than 15
30

33. Self – Sealability test
10 vials are filled with nominal volume of water and closures are placed
Caps are pierced 10 times at different sites with hypodermic needle
Vials are immersed in 0.1%w/v solution of methylene blue under pressure
Containers are kept immersed for 30 mins
Vials are washed and none of vials should contain traces of colour solution
31
Applicable to multidose containers

34. Penetrability
 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.
 https://youtu.be/ErrHvYiMIHI
Penetratibility test machine 32

35. Quality control test for secondary packaging materials
• Quality control test for cartons
1. Compression
2. Carton opening force
• Quality control test for paper and board
33

36.  Used to assess the strength of erected package there by estimating the degree
of protection that it confers on the contents.
 This is useful for products with no inherent strength in one plane or another.
 https://youtu.be/dYGZYvspfpg
Compression test machines 34
 Quality control tests for Cartons
Compression

37. • The carton should spring open in to its original shape without a need for
unreasonable force.
• If the carton does not spring open buckles in on itself, it may cause problems
on cartooning machine.
Carton opening force tester 35
Carton opening force

38.  Quality control tests for paper and board
Test conditions:
Temperature- 23°C ± 1°C ; Relative humidity- 50% ± 2%
1. Moisture content
2. Folding endurance
3. Air permeability
4. Tensile Strength
5. Tear Strength
6. Stiffness
7. Bursting strength
36

39. Conditioned specimen is weighed and heated to a constant weight to expel the
moisture. The difference of the two weights gives the moisture content of the paper.
Paper moisture meter
Moisture meter for
Carton and paper
37
Moisture content test

40. 38
Folding Endurance
•Fold endurance measures the durability of paper when
repeatedly folded under constant load; determining how many
times the paper can be folded until it breaks.
•Fold the test piece back and forth until rupture occurs.
https://youtu.be/LjyyElAVK-4
Folding endurance test machine

41. 39
Air permeability
Important for using light weight uncoated paper on machine having vacuum
pickup system

42. • Maximum load that a material can support without fracture when being stretched,
divided by the original cross section area of the material.
• Tensile strengths have dimensions of force per unit area.
• These test provides measurement of attributes we can see and feel: strength,
stiffness and resistance to stretching.
40
Tensile strength
Tensile strength formula:
S= F/A
Where, S= Breaking strength
F= Force that caused the failure
A=Least Cross sectional area of material

43. • The mean force required to continue the tearing of an initial cut in a single sheet
of paper.
• Tearing test is a simple method developed in 1940s, usually known as Elmendorf
test, for evaluating a particular type of paper strength, the tear strength.
• In this test method an impact load is applied to pull paper apart perpendicular to
its faces. According to Van den Akkers tear strength theory, it is dependent of two
phenomena.
• The work associated with breaking of fibers and
then pulling fibers out of the fiber network. These
two phenomena of course depend on the degree of
fiber bonding, fiber strength and fiber length in the
paper sheet.
https://youtu.be/VfR8CL7zYa0
41
Tear Strength

44. Stiffness
• Degree of resistance offered by paper/board when it is bent.
• This involves testing a board piece and folding it through 90°.
• It will then try to recover its position when bending force is removed.
https://youtu.be/xI-VSJF-WdM
stiffness test machines 42

45. Digital hydraulic burst tester
43
Bursting strength
•The burst test is used as a general guide to the strength of paper,
solid board and corrugated board.
•Bursting strength is usually quoted in kPa.
•We determine bursting strength using digital
hydraulic board burst tester.
Burst index = burst strength/basis weight
https://youtu.be/Wp7jRO20xE8

46. Key References
1. Roop Khar, S. P. Vyas, Farhan Ahmad, Gaurav Jain, Lachman/Liberman’s The
Theory and Practice of Industrial Pharmacy 4th edition CBS publishers.
2. Sahil Jasuja and Mahesh Kataria., 2013. Quality Control Testing of Packaging
Materials. Pharmatutor, Pharmacy Infopedia.
3. The Indian Pharmacopoeia Commission Ghaziabad, Indian Pharmacopoeia 2007
volume I, pg. no. 363-371.
4. United States Pharmacopoeia 2007, volume I pg. no. 661.
5. Lachman Leon, Liberman H. A. and Kaing J. L., 2013. The Theory and Practice
of Industrial Pharmacy. 3rd edition. New Delhi: CBS Publishers & Distributors
Pvt. Ltd. Pg. no. 711-732.