Quality control tests for containers

RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 1
Presented by
P . Sudheer Kumar
(Reg. No: 20L81S0712)
Under the guidance of
Dr. k . vinod Kumar, M. Pharm., PhD
Professor of Pharmaceutical Analysis,
Head of department – PA&QA.
Quality control tests for containers
A seminar as a part of curricular requirement for 1st year
M. Pharm 1st semester

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AUTONOMOUS
NAAC &
NBA (UG)
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• Quality control test for glass container
Hydrolytic resistance (chemical resistance tests)
Arsenic test
Light transmission for colored light- protecting glass containers
Containers for blood and blood components
• Quality control test for plastic container
Test for injectable preparation
Test for non- injectable preparation
Contents

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A container for pharmaceutical use is an article that contains or is intended to
contain a drug substance or a dosage form and is, or may be in direct contact with it.
Types of containers:
• Primary packaging components
which are or may be in direct contact with the dosage form. These include
ampoules, vials, bottles and container liners.
• Secondary packaging components
which are not or will not be in direct contact with the dosage form. These include
container labels, administration accessories, shipping containers, etc.
Container

RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
• 1.Hydrolytic resistance (chemical resistance tests)
• Surface test (water attack test)
• Powdered glass test
• Etched surface (distinction between types I & II glass )
• 2.Arsenic Test
• 3.Light transmission for colored light- protecting glass containers
• 4.Containers for blood and blood components
• Resistance to thermal shock
• Resistance to centrifugation
Quality control test for glass container

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SURFACE TEST (WATER ATTACK TEST)
• The degree of attack being determined by the amount of alkali released from the
glass under the conditions specified.
• The number of containers to be examined and the volumes of test solution to be
used are
Hydrolytic resistance
(chemical resistance tests)

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• The test is carried out on the unused containers and the ampoules are filled with
freshly prepared distilled water to the maximum volume and are sealed. Bottles or
vials are filled to 90% of their calculated overflow volume and covered.
• Containers are placed in an autoclave at a temperature of 121°c for 60 mins and the
cooled under running tap water
• The water content is collected and titration is carried out within one hour by adding
methyl red to it and titrated against 0.01M hydrochloric acid .
• The volume of 0.01M hydrochloric acid required for each 100 ml of test solution is
calculated.
PROCEDURE

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POWDERED GLASS TEST
• Powdered glass test is done to estimate the amount of alkali leached from
the powdered glass, which usually happens at elevated temperatures.
• Glass containers are classified according to their resistance to chemical attack,
a test executed by heating the glass in contact with water for 30 min at 121
degrees.
• The USP powdered glass test for glass containers was applied to different
kinds of glasses used as containers for parenteral formulations.
• The decanted liquid is titrated with 0.01 M HCL using methyl red as indicator.

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• Rinse the containers to be tested with water & dry in the hot-air oven.
• Powder the glass container to grains and pass through the 425- µm sieve but
that is retained on the 250-µm sieve are taken.
• Remove any metal particles from the glass grains by passing a magnet over
them
• Transfer about 22 g to a conical flask and wash with 60 ml of acetone for five
time & then evaporate the acetone.
• Dry in an oven at 110°c for 20 minutes and allow to cool.
Procedure

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• 20 g of the treated grains were taken in a 250- ml conical flask and 100 ml of carbon
dioxide-free water added and weighed. In a second identical flask 100 ml of carbon
dioxide-free water was taken to serve as the blank and weighed.
• Flasks were kept in the autoclave and maintained at 121°c for 30 minutes. After
cooling weight was adjusted to the original weight by the addition of carbon dioxide-
free water. Then the water is decanted and the alkali content is determined by titrating
with 0.01 M Hcl using methyl red as indicator.
• Blank was prepared in the same manner and added methyl red and titrated against
0.01M hcl.
Procedure

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TEST FOR HYDROLYTIC RESISTANCE OF THE ETCHED
SURFACE
• The hydrolytic resistance is determined by the quantity of alkali released from the
glass under the conditions specified.
• The surface etching test may be used to determine whether high hydrolytic
resistance is due to chemical composition or due to surface treatment.
• Test results distinguishes between types I and ii glass
(chemical resistance tests)

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• Examined the number of containers indicated before and rinsed them twice with
water and then filled completely with a 4% v/v solution hydrofluoric acid and
allowed to stand at room temperature for 10 minutes and rinsed again.
• Then autoclaved the treated containers and titration is carried out as described in
test for surface hydrolytic resistance.
• Titration is carried out within one hour by adding methyl red to it and titrated
against 0.01M hydrochloric acid .
Procedure

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• Glass containers contain arsenic and it is released during heating. The amount
of arsenic release is determined.
PROCEDURE
• Prepare a test solution as described in the test for hydrolytic resistance for an
adequate number of ampoules to produce 50 ml.
• Pipette 10 ml of the test solution into a flask, add 10 ml of nitric acid and
evaporate to dryness on a water-bath.
• Dry the residue in an oven at 130° for 30 minutes. Cool, add to the residue 10
ml of hydrazine-molybdate reagent, mix and heat under reflux on a water bath
for 20 minutes.
• Cool to room temperature. Determine the absorption of the resulting solution at
840 nm, using hydrazine-molybdate reagent as the blank. The absorbance of
the test solution should not exceed the absorbance obtained by using arsenic
standard solution (0.1 ppm).
Test for arsenic

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• Light transmission test is done to determine the effect of light passing through
the bottle wall on the product stability and appearance. The bottle wall
thickness can have a significant effect on the results obtained.
Procedure
• A piece of glass container is mounted on specimen holder (care is taken to
avoid fingerprints or other marks)
• Place the specimen in the spectrophotometer.
• Measure the transmission of the specimen in the spectral region of 290 to 450
nm.
Light transmission for colored
light- protecting glass containers

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• The observed light transmission in colored glass containers for parenteral
preparations should not exceed the limits given in the following table

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• Resistance to thermal shock
• Thermal shock resistance test is carried out to measure the ability to withstand a
rapid and significant temperature change.
• Procedure
• The containers are placed empty in an autoclave and the temperature is raised to
140°c and kept at this temperature for 30 mins.
• The empty container is treated to temperature of which is raised in to 250° and kept
at this temperature for 1 hour.
• Filled to 70% of the maximum marked volume with a 0.9% w/v solution of sodium
chloride and gradually cooled to –20° and kept at this temperature for 24 hours
• Submitted to a rapid drop of temperature the test is done to check whether the
container can resists this temperature change.

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• Resistance to centrifugation
• This test is carried out to check the ability of containers to withstand extreme
conditions.
• Procedure
• Fill the container with water to the maximum marked volume and place in a
suitable centrifuge.
• Balance the centrifuge and accelerate to 2000rpm over a period of at least 1 minute.
• The container pass the test if it resists these conditions for at least 30 minutes.

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• Plastic containers for pharmaceutical products are made from plastics based on the
following polymers: polyethylene (low or high density), polypropylene, polyvinyl
chloride and polystyrene.
• The containers may consist of one or more polymers together with certain additives
if necessary. Additives may consist of antioxidants, lubricants, plasticizers and
impact modifiers but not antistatic agents and mould-release agents.
• They should be made of materials that do not leach out any ingredient into contents
in such quantities so as to alter the efficacy or stability of the product or to present a
toxic hazard.
• The plastic container chosen for any particular product should be such that the
ingredients of the product in contact are not significantly adsorbed on its surface and
do not significantly migrate into or through the plastic.
Plastic containers

RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
• 1.Leakage test
• 2.Collapsibility test
• 3.Clarity of aqueous extract
• 4.Non-volatile residue
Tests for Plastic Containers For
Non- injectable Preparations

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LEAKAGE TEST
• Fill ten containers with water, fit with closures and keep them inverted at room
temperature for 24 hours.
• If there are no signs of leakage from any container, then the containers are passed.
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, should yields at least 90% of its
nominal contents at the required rate of flow at ambient temperature.
• The following tests are applicable to containers intended for filling oral liquids.

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• Clarity is a relative term, it mean a clear container having a high polish that
conveys to the observer that the product is of exceptional purity.
Procedure
• Select unlabelled, unmarked and non- laminated portions from suitable
containers, taken at random.
• Cut these portions into strips & wash the strips free from extraneous matter
using distilled water.
• Select cut and washed portions of the sample (1250 cm2), transfer to a clean
flask and add 250 ml of distilled water.
• Cover the flask with a beaker and autoclave at 121° for 30 minutes.
• Carry out a blank determination using 250 ml of distilled water.
• Cool and examine the extract if it is color less and free from turbidity or not.
Clarity of aqueous extract

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• This test is performed to check whether any non volatile material from the
container interacts with the content.
Procedure
• Evaporate 100 ml of the extract obtained in the test for clarity of aqueous extract to
dryness and dry to constant weight at 105°c. The residue should not weighs more
than 12.5 mg.
Non-volatile residue

RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
1.Tests on Containers
I. Leakage test
ii. Collapsibility test
iii. Transparency
iv. Water vapour permeability
V. Extractable di(2-ethylhexyl)phthalate
2.Tests on Container Material
• Barium, heavy metals, tin, zinc, residue on ignition
Plastic Containers for Injectable
Preparations

RIPER
AUTONOMOUS
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SIRO- DSIR
• Test on extracts
• Physico-chemical tests
I. Appearance
ii. Light absorption
iii. Ph
iv. non-volatile matter
v. Buffer capacity
vi. Oxidisable substance
• Biological tests
i. Systemic injection test
ii. Intracutaneous tests

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• Leakage test, Collapsibility test
• Comply with the tests described under plastic containers for non-injectable
preparations.
iii. Transparency
• Prepare a 16-fold dilution of the suspension prepared for the standard suspension
so as to give an absorbance
• Fill five empty containers to their nominal capacity with the diluted suspension
(gives an absorbance of 0.37 to 0.43 at 640 nm).
• The cloudiness of the diluted suspension in each container should be detectable
when viewed through the containers, as compared with a container of the same type
filled with water.
1. Tests on Containers

RIPER
AUTONOMOUS
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• Water vapor permeability is a measure of the passage of water vapor through
a membrane. It is the rate of water vapor transmission per unit area per unit
of vapor pressure differential under test conditions.
Procedure
• Fill five containers with the water and heat-seal the bottles.
• Weigh accurately each container and allow to stand for 14 days at a relative
humidity of 60 ± 5% and a temperature between 20° and 25°.
• Reweigh the containers.
• The loss in weight in each container should not more than 0.2%.
iv. Water vapour permeability

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• Containers of plasticized polyvinyl chloride (PVC) for injectable preparations (i.V.
Infusions) must comply with extractable di(2- ethylhexyl)phthalate test.
Procedure
• Fill the empty container with dilute ethanol (of relative density 0.9373 to 0.9378),
remove the air completely from the container.
• Place container in a horizontal position in a water-bath maintained at 36° to 38° for
60 minutes without shaking.
• Remove the container from the water- bath, invert it gently 10 times and transfer
the contents to a glass flask.
• Immediately measure the absorbance at the maximum at about 272 nm.
• Calculate the percentage of di(2- ethylhexyl)phthalate from a calibration curve
obtained from the absorbance of standard solutions of di (2-ethylhexyl) phthalate in
alcohol.
• It should not more than 0.010% w/v.
v. Extractable di(2-ethylhexyl)phthalate

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• The test is conducted to check whether container material has any impact on the
content
I . BARIUM
• Moisten 2g of sample with hydrochloric acid and ignite in a platinum dish.
• Dissolve the residue in 10 ml of 1M hydrochloric acid, filter and add 1 ml of
1M sulphuric acid to the filtrate.
• Any turbidity produced should not be greater than that produced on adding 1
ml of 1m sulphuric acid to a mixture of 10 ml barium standard solution (10
ppm ba) and 10 ml of 1m hydrochloric acid.
2.Tests on Container Material

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ii. Heavy metals
• Take 2.5 g of sample & add 20 ml of sulphuric acid and heat for 10
minutes.
• Add hydrogen peroxide solution drop wise to the hot solution until it
becomes colorless.
• Cool, transfer to a platinum dish and evaporate to dryness.
• Dissolve the residue in 10 ml of 1M hydrochloric acid and add
sufficient water to produce 25 ml (solution a).
• To 10 ml of solution a, add 2 ml of acetate buffer ph 3.5 add 1.2 ml
of thioacetamide reagent, mix and allow to stand for 2 minutes.
• Any yellow color in the solution should not be more intense than the
yellow color obtained by repeating the operation using 10 ml of
cadmium standard solution (10 ppm cd) in place of solution a.
• Any brown color in the solution should not be more intense than that
obtained by repeating the operation using a mixture of 5 ml of lead
standard solution (10 ppm pb) and 5 ml of water in place of solution
a.

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iii. Tin
• To 10 ml of solution A obtained in the test for heavy metals add 5
ml of sulphuric acid (20%), 1 ml of a 1% w/v solution of sodium
dodecyl sulphate and 1 ml of zinc dithiol reagent.
• Heat in a water-bath for 1 minute, cool and allow to stand for 30
minutes.
• Any red color in the solution should not be more intense than the red
color obtained by repeating the operation using 10 ml of tin standard
solution (5 ppm sn) in place of solution a.
iv. Residue on ignition:
• The residue on ignition/ sulphated ash test is a method to measure the
amount of residual substance not volatilized from a sample when the
sample is ignited in the presence of sulfuric acid
• Take 5 g of the sample in a suitable tared crucible.
• Ignite to constant weight in a muffle furnace at 8000 + 250.
• Allow the crucible to cool in a desiccators.
• It should not be more than 0.1%.

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• The following tests are based on the extraction of the plastic material.
• Take a portion plastic material and sub- divide into strips approximately 5 cm
long and 0.3 cm wide.
• Take the strips in a 250 - ml, graduated cylinder of type I glass, and wash with
purified water
• Transfer to a suitable extraction flask and add 200 ml of purified water and
extract by heating in a water-bath at 700 for 24 hours or heat in an autoclave at
1210 for 30 minutes and cool.
• Transfer 20.0 ml of the extract into a suitable container. Use this portion in the
test for buffering capacity.
• Immediately decant the remaining extract into a suitable clean container and
seal.
• Use purified water where a blank is specified in the following tests
3.Test on extracts

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I . APPEARANCE: the extract is colorless and is clear.
II. LIGHT ABSORPTION: the light absorption of the extract, using water as the
blank should not more than 0.08 in the range 220-240 nm and not more than 0.05 in
the range 240-360 nm.
III. PH: to 20 ml each of the extract and the blank add 1 ml of a 0.1% w/v solution of
potassium chloride and determine the ph of the solutions. The difference in ph of the
two solutions should not > 1.5.
Iv. NON-VOLATILE MATTER: transfer 50.0 ml of the extract to a suitable silica
crucible, evaporate on a water-bath and dry the residue at 1050 for 1 hour. Repeat the
operation with the blank; the difference between the residues obtained form the
extract and the blank should not exceed 15 mg.
4. Physico - chemical tests

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v. BUFFER CAPACITY: The buffer capacity is defined as the amount of acid or
base you can add without changing the ph by more than 1 PH unit
• Titrate the previously collected 20 ml portion of the extract to a ph of 7.0 with
0.01M hydrochloric acid or 0.01M sodium hydroxide, determining the end- point
potentiometrically. Repeat the operation with 20 ml of the blank. The difference
between the two volumes of titrant should not be greater than 10.0 ml.
vi. OXIDISABLE SUBSTANCE: Transfer 20.0 ml of the extract into a glass-
stoppered flask, add 20.0 ml of 0.002M potassium permanganate and 1 ml of dilute
sulphuric acid and boil for 3 minutes.
• Cool, add 0.1 g of potassium iodide, mix by shaking and allow to stand for 10
minutes in the dark. Titrate with 0.01M sodium thiosulphate using 0.25 ml of starch
solution, added towards the end of the titration, as indicator.
• Repeat the operation with the blank; the difference between the two titration should
not be more than 1.0 ml.

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• The following tests are designed to determine the biological response of animals to
plastics and other polymeric material by the injection or instillation of specific
extracts from the material under test.
• The two biological tests are
• i. Systemic injection test
• ii. Intracutaneous test
5. Biological tests

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• This test is designed to evaluate systemic responses to the extracts of materials
under test following injection into mice.
TEST ANIMALS: albino mice weighing between 17 and 23 g.
EXTRACTING MEDIA:
• Sodium chloride injection (0.9% w/v)
• 5 % v/v solution of ethanol in sodium chloride injection.
• Polyethylene glycol 400
• Vegetable oil – freshly refined & that meets the following requirement.
PROCEDURE
• To three test animals, inject 0.2 ml intracutaneoulsly at each of 10 sites on each
animal and examine the injected sites 24, 48 and 72 hours after injection. No site
should shows a greater reaction, edema or erythema than 0.5cm in diameter
i. Systemic Injection test

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• This test is designed to evaluate local response to the extracts of materials being
examined following intracutaneous injection into rabbits.
TEST ANIMALS: select healthy, thin-skinned albino rabbits whose fur can be
clipped closely and whose skin is free from mechanical irritation or trauma. In
handling the animals, avoid touching the injection sites during observation periods,
except to discriminate between edema and an oil residue.
ii . Intracutaneous test

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Procedure:
On the day of the test, closely clip the fur on the animal’s back on both side of the
spinal column over a sufficiently large test area.
• Avoid mechanical irritation and trauma.
• Remove loose hair by means of vacuum.
• If necessary, swab the skin lightly with diluted ethanol, and dry the skin prior
to injection.
• For each sample use two animals and inject each intracutaneously, using one
side of the animal for the sample and the other side for the blank, as outlined in
table:

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Extract or blank Number of sites
(per animal)
Dose per site
(µl)
Sample 5 200
Blank 5 20

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• Examine injection sites for evidence of any tissue reaction such as erythema, edema
and necrosis. Swab the skin lightly, if necessary, with diluted ethanol to facilitate
reading of injection sites. Observe all animals at 24, 48 and 72 hours after injection.
Rate the observations on a numerical scale for the extract of the sample and for the
blank, using the following table.

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• Reclip the fur as necessary during the observation period. The average erythema and
edema scores for sample and blank sites are determined at every scoring interval (24, 48
and 72 hours) for each rabbit.
• After the 72 hours scoring, all erythema scores plus edema score are totalled separately
for each sample and blank.
• Divide each of the totals by 12 (2 animals x 3 scoring periods x 2 scoring categories) to
determine the overall mean score for each sample versus each corresponding blank.
• The requirements of the test are met if the difference between the sample and the blank
mean score is 1.0 or less.
• If at any observation period the average reaction to the sample is questionably greater
than the average reaction to the blank,
• repeat the test using three additional rabbits. The requirements of the test are met if the
difference between the sample and the blank mean score is 1.0 or less.

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• C.rambabu, V.ananth, R. T.srikanth, S.K.dona, K. G.arun, T.tinu,
manavalan, B. M, venkanna, S. H,viswa, J. K, ghaharin. A concise textbook
of QC & QA. KMCH college of pharmacy, coimbatore. 2011.179-189.
• Government of india, ministry of health. Indian pharmacopoeia volume I.
The indian pharmacopoeia commission, ghaziabad. 2010. 683-692.
References

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AUTONOMOUS
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K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721
THANK YOU

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