Quality Contril Analysis of Containers.pdf

Quality Control Analysis
of
Pharmaceutical Containers
Dr Bindiya Chauhan

INTRODUCTION
❑ DEFINITION OF PACKAGING :
• Packaging is the science, art, and technology of enclosing or protecting products for
distribution, storage, sale, and use.
• Packaging also refers to the process of designing ,evaluating, and producing packages.
• Packaging can be described as a coordinated system of preparing good for transport,
warehousing logistics, sale, and end use.
OR
Packaging is also defined as “The process by which the pharmaceuticals are suitably
packed so that they should retain their therapeutic effectiveness from the time of their
packaging till they are consumed“.

INTRODUCTION
❑ IMPORTANCE OF PACKAGING:
• Protect against all adverse external influences that can alter the properties of the
product.
• Protect against biological contamination.
• Protect against physical damage.
• Carry the correct information and identification of the product
• Tamper evident / Child resistance/ Anti counterfeiting

INTRODUCTION
❑ FUNCTIONS OF PACKAGING:
Packaging provides protection against:
• Light
• Moisture
• Oxygen
• Biological contamination
• Mechanical damage etc.

INTRODUCTION
❑ PRIMARY AND SECONDARY PACKAGING:
1. Primary packaging: Packaging which is in direct contact with the product, e.g.
bottle, closure, blisters etc.
2. Secondary packaging: These additional packaging materials that improve the
appearance of the product and do not make direct contact with the product e.g.
Wrappers, labels etc.

INTRODUCTION
Table: Types and Examples of uses of packaging materials
Material Type Examples of Use
Glass Primary: Metric medical bottle, ampoule, vial
Plastic Primary: Ampoule, vial, infusion fluild container
Metal Primary: collapsible tubes
Plastic Secondary: Wrapper to contain primary pack
Board Secondary: Box to contain primary pack
Paper Secondary: Labels , patient information leaflet

INTRODUCTION
❑ Q.C TESTS FOR GLASS CONTAINERS :
• Chemical resistance of glass containers
✓ Powdered Glass test
✓ Water attack test
• Hydrolytic resistance of glass containers
• Arsenic test
• Thermal shock test
• Internal bursting pressure test
• Leakage test
• Light transmission test (For coloured glass containers)

QC TESTS FOR CONTAINERS
❖Chemical resistance of glass containers:
A. Powdered glass test :
This test is done to estimate the amount of alkali leached from the powdered glass which
usually happens at the elevated temperatures. When the glass is powdered, leaching of
alkali is enhanced, which can be titrated with 0.02N sulphuric acid using methyl red as an
indicator.

Step-1: Preparation of glass specimen: Take Few containers rinse them thoroughly
with purified water and dry 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: Take 10gm of the above specimen in 250 ml conical
flask and wash it with 30 ml of acetone. Repeat the washing decant the acetone, dry
it and use within 48hrs.

➢ Procedure:
• Take 10 gm of sample in 250ml of flask; add 50 ml of highly purified water.
• Place the flask in autoclave at 121p C+2p C for 30min.
• Remove the flask after 30 minutes and cool it under running water.
• Decant the solution in other flask and again wash with 50ml of highly purified water.
• Then titrate the above solution immediately with 0.02N sulphuric acid using methyl
red as an indicator and record the volume.

Limits of 0.02N sulphuric acid for different types of Glasses
TESTS CONTAINER VOL.OF 0.02N H2SO4
Powdered glass
test
Type I 1.0 ml
Type II 8.5 ml
Type III 15.0 ml

B. Water attack test:
This test is only for treated soda lime (Type II) glass containers under
the controlled humidity conditions and the basic principle involved in
this test is that whether the alkali is leaching or not from the surface
of the container.
Procedure:
• Rinse the container thoroughly with high purity water.

• Fill each container to 90% of its overflow capacity with water and
autoclave at 121p C for 30 min.
• Then cool the liquid and titrate with 0.02N sulphuric acid using methyl
red as an indicator.
• The volume of sulphuric acid consumed is the measure of the amount of
alkaline oxides present in the glass containers.

Limits of 0.02N Sulphuric acid for type II of Glass having different capacities
TESTS CONTAINER VOL.OF 0.02N
H2SO4
Water attack test
Type II (100ml or below) 0.7
Type II (above 100ml) 0.2

❖Hydrolytic resistance of glass containers:
Procedure:
• Rinse each container at least 3times with CO2 free water and fill with the same
to their filling volume, also fill & Cover the vials and bottles and keep in
autoclave.
• Heat up to 100p for 10min and allow the steam to issue from the vent cork.
• Raise the temperature from 100p C to 121pC over 20min.
• Maintain the temperature at 121p C to 122p C for 60 min.

• Lower the temperature from 121p C to 100C 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
HCI using methyl red as an indicator.
• Perform blank titration with water and the difference between the titration
represents the volume of 0.01M HCL consumed by the test solution.

❑ Arsenic test : This test is for glass containers intended for aqueous
parenterals.
Procedure:
• Wash the inner and outer surface of container with fresh distilled water for
5min.
• Prepare test solution as described in the test for hydrolytic resistance for an
adequate number of samples to produce 50ml.
• 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 and dry the residue in an oven
at 130p C for 30 min cool and add 10 ml hydrazine molybdate reagent.
• Swirl the solution till it is dissolved and heat under water bath and reflux for 25
min.
• Cool at room temperature and determine the absorbance at 840 nm.
• Determine the blank with only 10 ml hydrazine 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
(10ppm) in place of test solution.

❑ Thermal shock test :
Procedure:
• Place the samples in upright position in a tray.
• Immerse the tray into a hot water for a given time and transfers to cold water bath,
temperature of both should be closely controlled.
• Examine cracks or breaks before and after the test.
• The amount of thermal shock a bottle can withstand depends on its size, design and
glass distribution.

• Small bottles withstand a temp differential of 60 to 80 p C and I point bottle
30 to 40p C.
• A typical test uses 45p C temperature difference between hot and cold
water.

❑ Internal bursting pressure test : The most commonly used instrument for this test is
American glass research increment pressure tester.
Procedure:
• The test bottle is filled with water and placed inside the test chamber.
• A scaling head is applied and the internal pressure automatically rives by a series of
increments each of which is held for a set of time.
• The bottle can be checked to a preselected pressure level and the best continues
until the container finally bursts.

❑ Leakage test:
Procedure:
• Drug filled container is placed in a container filled with coloured solution
(Containing dye e.g Methylene blue), which is at high pressure as compared
to the pressure inside the glass container.
• Coloured solution enters the container, if any cracks or any breakage is
present.

• Measure the transmission of specimen with reference to air in spectral
region of the 290- 450 nm continuously or with interval of 20 nm.
• The observed light transmission for colored glass should be not more
than 10 at any wavelength in the range of 290-450 m, irrespective of
the type and capacity of container.

❑ Light transmission test (For coloured glass container) :
Procedure:
• Break glass container with carborundum (very hard solid of Silicon carbide used as
an abrasive) or diamond wheel.
• Select wall section and Put it in specimen holder of spectrometer with care.
• Place test specimen in the spectrometer with its cylindrical axis parallel to the slit
and in such a way light beam is perpendicular to the section.

• Measure the transmission of specimen with reference to air in spectral
region of the 290- 450 nm continuously or with interval of 20 nm.
• The observed light transmission for colored glass should not be more
than 10 at any wavelength in the range of 290-450 nm, irrespective of
the type and capacity of container.

❑ Q.C TEST FOR METAL CONTAINERS :
Procedure:
• Select a sample of 50 tubes from the lot to be tested and clean each tube by
vibration and/blowing.
• Fill the tubes with a suitable molten ointment base, close the open end of each tube
by a double fold and allow the filled tubes to cool overnight at a temperature of 15
to 20˚C.
• Take a metal bacteriological filter with 4.25cm filter paper of suitable porosity
supported on suitable perforated plate and heat it above the melting range of the
ointment base.

• Remove the caps and apply uniform pressure to the closed end of each tube in
turn, in such a manner that the time taken to express as much of the base as
possible through each nozzle is not less than 20 seconds.
• Collect the extruded base from the 50 tubes on the heated filter by applying
suction.
• Wash the walls of the filter and the filter paper with three successive quantities,
each of 30 ml of chloroform, allow the filter paper to dry.
• Examine the filter paper under oblique lighting with the aid of magnifying glass
with a graticule of 1 mm squares, one of which should be sub-divided into 0.2mm
sequares.

❑ Q.C TESTS FOR PLASTIC CONTAINERS:
• Leakage test
• Collapsibility test
• Clarity aqueous extract
• Water Vapor permeability test
• Transparency test
• Biological test
• Systemic injection test
• Intra-cutaneous test
• Eye irritation test on a rabbit
• Resistance to stress
• Resistance to temperature

✓ Leakage test : Fill 10 containers with water, fit with intended closure and keep them
inverted at room temperature for 24hr. The test is said to be passed if there is no
signs of leakage from
any container.
✓ Collapsibility test: This test is applicable to the containers which are to be squeezed
for removing 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.

✓ Clarity of aqueous extract:
• Randomly select unlabeled, unmarked and non laminated portions from suitable
containers. Cut these portions into strips, none of which has a total surface area of
20 sq.cm. Wash the strips and free it from extraneous matter by shaking them with at
least two separate portions of distilled water for about 30sec and drain off the water
thoroughly.
• Thus processed sample is taken in to the flask, previously cleaned with chromic acid
mixtures and rinsed with several portions of distilled water and added 250 ml distilled
water. Cover the flask and autoclave at 121p for 30 min. Carry out the blank
determination using 250ml distilled water. Cool and examine the extract, it should be
colorless and free from turbidity.

✓Water vapour permeability test:
Fill 5 containers with normal volume of water and heat seal the bottles
with an aluminium foil. Weigh accurately each container and allowed
to stand for 14 days at a relative humidity of 60±5% and a temperature
between 20 and 25p C. Reweigh the containers. The loss in weight in
each container is NMT 0.2%.

✓ Transparency test:
• Standard suspension preparation: 1gm hydrazine sulphate in 100ml water and set
aside for 6hr. take 25ml of this solution and add 25ml of 10%w/v hexamine and
stand for 24hr.
• Test solution preparation: Sample is prepared by 16fold dilution of the standard
suspension.
• Fill 5 containers cloudiness detectable when compared to water filled containers.
Absorbance is measured at 640 nm and the range is within 0.37 to 0.43.

b. Intra-cutaneous test:
• Test animal: Rabbit
• Examine the sites of for any time reaction like erythema, edema, neurosis at 24, 48,72 hours after
injection.
• Limit: - difference between the scores of simple and blank should be lesser than 1.0.
c. Eye irritation test on rabbits: Test animal: Albino Rabbits.
• Limit - Sample extract shows no significant irritant response during the observation period with blank
extract.
✓ Resistance to stress:
• Acidify the water with 2 M HCL Fill the container with this acidified water to its nominal capacity and
apply force to both end of container.
• No break or deterioration should occur.

✓ Resistance temperature variation:
• Firstly place the container in chamber having temperature 20-23%e, then
cool & rapidly maintain -80 c temperature for 24 hrs and them Raise
temperature to 50 c & maintain it for 12 hrs and finally cool container at
room temperature.
• No break or deterioration should occur

❑ Q.C TEST FOR RUBBER CLOSURES:
✓ Sterility test
✓ Fragmentation test : a. For aqueous preparations
b. For dry preparations
✓ Self- seal ability
✓ pH of aqueous extract
✓ Light absorption test
✓ Reducing substances
✓ Residue on evaporation

• Preparation of solution (A) for various tests:
22Wash closures in 0.2% w/w of anionic surface active agents for 5 min, Rinse 5 times
with distilled water and add 200 ml water and it is subjected to autoclave at 119 to
123p C for 20 to 30min covering with aluminium foil. Cool and separate solution from
closure (solution-A).
✓ Sterility test : Subject treated closures to sterilization at and a pressure of about
0.7 Kilo Pascal for 24 hrs. It should not become tacky or soften).

✓ Fragmentation test :
a. For aqueous preparations:
• Place water corresponding to the nominal volume minus 4 ml in each of 12 clean vials.
• Close the vials with the prepared closures & allow it to stand for 16 hours.
• Using a hypodermic needle with an external diameter of 0.8 mm inject 1 ml of water into
the vial and remove 1 ml of air.
• Carry out this operation 4 times with new needle each time.
✓ Pass the liquid in the vials through a filter with a pore size of 0.5 um.
✓ No. of fragments NMT 10 except in the case of butyl rubber closures where the total no. of
fragments NMT 15.

B. For dry preparation:
• Close 12 clean vials with the prepared closures.
• Using a hypodermic needle with an external diameter of 0.8 mm into the vial and
remove 1 ml of air.
• Carry out this operation 4 times with new needle each time
• Pass the liquid in the vials through a filter with a pore size of 0.5 µm.
• No of fragments NMT 10 except in the case of butyl rubber closures where the
total no. of fragments NMT 15.

✓ Self- seal ability:
• 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 27KPa 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.
✓ pH of aqueous extract:
• Take 20 ml of solution A, add 0.1 ml bromothymol blue.
• Add small amount of 0.01M NaOH, after its addition colour changes from blue to
yellow.
• The volume of NaOH required to change the colour should not be more than 0.3ml
and if it is done with HCI, the volume of HCI needed should not be more than 0.8ml.

✓ Light absorption test:
• It must be done within 4 hrs of preparing solution A.
• Solution A is filtered through 0.5u filter and its absorbance is measured at 220
to 360nm.
• Similarly take absorbance of Blank without closures and absorbance should
not be more than 2.0.

✓ Residue on evaporation:
• Take 50ml of solution A and evaporate to dryness at 105p C. Then weigh the
residue ,the amount of residue should not be more than 4mg.

❑ Q.C. CONTROL TESTS FOR SECONDARY PACKAGING :
• Before performing tests on pieces of paper & board, they are conditioned for the
tests to be carried out in standard conditions
• Those conditions are: Temperature - 23°C ± 1°C & Relative humidity -50 % ± 2%

TESTING OF PAPER & BOARD
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 Acidityinpapermaybecausedbypresenceof 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 Extraction Cut 1gm of paper & place in a
100 ml flask, fitted with condenser, add 20 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- 1000c for 1 hr. Cool to 40-
450c, remove the condenser and shake, cool in water bath.
Determine the pH of the supernatent with pH meter.

MOISTURE CONTENT 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.
%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 8000c until all
the carbonaceous burnt matter are off. Cool in
dessicator, 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).
%Alkalinity=1250(B- A)× N
V×w 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 endurance Fold the test piece back and forth until rupture
occurs
Tensile strength The maximum 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
Burst strength The maximum uniformly distributed pressure, applied
at a right angle to surface that a test piece of paper & board
will stand under condition of test

Density For rigid cellular materials
Puncture resistance Energy required to make initial puncture
Rub resistance Resistance of printed test piece to withstand
rubbing against another similar test piece.
Roughness or
smoothness
Important for printability of paper
Ink absorbancy Determination of ink absorbancy by K& N ink

Test of cartons
Compression • This method is used to assess the
strength of erected package
Carton opening force • The method is used to hold the flat
carton as delivered, by its creases
between thumb & first finger press.
Coefficient of friction • Both static and kinetic coefficients
of friction are determined by sliding
the specimen over itself under specific
test conditions

Crease Stiffness This involves testing a carton board
piece & folding it through 900 . It
will then try to recover its position
when bending force is removed
Joint Shear Strength This is a method of testing glued lap
seam on the side of a carton for
strength of the adhesive using a tensile
testing machine.

References:
1. Indian Pharmacopoeia, 2007, Government of Indian ministry of health and family welfare,
The Indian pharmacopoeia commission, Ghaziabad, volume-I, 6.1, 6.2, 6.3, 361-370
2. Pharmaceutics-1 by R. M. Mehta, Page No.:-74-85
3. The Theory and Practice of Industrial Pharmacy by Leon Lachman, Page No.:-711- 724
4.http://www.pharmatutor.org/articles/quality-control-testing-packaging-materials.
5. https://en.wikipedia.org/wiki/Pharmaceutical_packaging.
6. https://www
.deufol.com
7. Kennath, Harburn, Quality Control of Packaging Materials in the Pharmaceutical Industry
1st ed. Marcel Dekker
.INC, P:135-137

Quality Contril Analysis of Containers.pdf

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