QC of Packaging Material
CONTENTS
INTRODUCTION
PARAMETERS FOR TESTING
CLASSIFICATION OF TESTS
TESTS FOR GLASS
TESTS FOR PLASTICS
TESTS FOR RUBBERS
TESTS FOR METALS
TESTS FOR PAPER AND
BOARDS
INRTODUCTION-
Selection of materials for manufacture of packages is
governed by chemical and physical properties of material and product.
Quality control of these materials is very important aspect
for packaging process, various tests are employed to determine the quality of
theses packaging materials.
Quality control forms the backbone of pharmaceutical
industry. Quality control starts at design stage.
TYPES OF
PACKAGING MATERIALS USED
METALS
GLASS
PLASTIC
PAPER AND CARD- BOARD
RUBBER
PARAMETERS
FOR TESTING
IDENTITY Critical
identifaction, inspection and analysis certified from suppliers
LIGHT TRANSMISSION
In case of strips and somelight sensitive substances, light transmission limits
have to assured. It should not be more than 10% of limit in case of light
sensitive conpounds
EXTRACTABLES to
assure that contents of material do not leach out. It is very important in case
of inhalation, injectables and implant products
PERMEATION There
are two ways of permeation check: For solid dosage form it is measured as
moisture moving into container. For liquids it is measured as water migrating
from product to container
CLASSIFICATION
OF TESTS
Chemical
The pH value of materials, chloride and sulphate in paper or
board, alkalinity of glass, compatibility test with chemicals or medicament are
typical of chemical tests
Mechanical
Standard tests are available for effect of creasing, folding
and so on
Environmental
Materials may be tested by standard methods of absorption of
water, permeability to water vapours, gases, oils, odours etc and for
characteristics such as light transmission
QUALITY
CONTROL TESTING OF GLASS
Glass is one of most widely used materials for parenteral products,
each glass container must be to be tested by following manner.
Pharmacopoeial tests:
Test for surface hydrolytic resistance
Test for hydrolytic resistance of powdered glass
Light transmission test for coloured glass
Test for resistance to thermal shock
Surface hydrolytic resistance test
Powder
glass hydrolytic resistance test
Principle
Amount of alkali leached from glass is determined in this
test. The container is filled with pure water and maintained at specified
autoclaving condition for specified time period. The leached alkalis titrated
against the acid at neutralization point it will give the amount of alkali
leached.
|
Nominal capacity of container (ml) |
number of containers to be used |
Volume of test solution to be used for titration (ml) |
|
Up to 3 |
20 |
25 |
|
5 or less |
10 |
50 |
|
6 to 30 |
5 |
50 |
|
More than 30 |
3 |
100 |
Procedure
Wash with CO2 free water
Fill it with CO2 free water (up to maximum volume) Autoclave
(120 degree C for 60 min)
Take sample of water and titrate against 0.01N HCL (Blank
reading)
Amount of acid required must meet the specification of IP
POWDERED
GLASS TEST
Hammer the container and collect 100g glass (fragments
should not be greater than 25mm)
Powder it to obtain 20g fragment on retain on 250 micron
sieve but pass through 425 micron sieve (as per IP )
Magnet passing to purify
Now perform as per previous test by adding 100ml CO2 free
water and match the result with IP specifications
LIGHT
TRANSMISSION TEST FOR COLOURED GLASS
Break the glass with carborundum or diamond wheel
Select wall section
Put 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 290-240 nm
TEST FOR
THERMAL SHOCK RESISTANCE
Particularly used for blood products or biological products
Empty container in autoclave (140◦ C for 30min)
Place in oven (2500C
for 1 hour)
Fill 70% container with 0.9% NaCl and cool to – 20 degrees C
for 1 hr
After restoring to room temperature the container must
comply with test for resistance to centrifugation.
TEST FOR
ARSENIC
Carry out test on ampoules, inner and outer surfaces are
washed five times with distilled water
Prepare a test solution as described for adequate ampoules
to 50ml
Pipette 10ml of test solution from combined contents of all
ampoules into flask
Add 10ml of nitric acid and evaporate to dryness on water
bath
Dry the residue in an oven at 1300C for 30 min
Cool, add to the residue to 10 ml of hydrazine molybdate
reagent
Heat under reflux on water bath for 20 min
Cool to room temperature. Determine absorbance of resulting
solution at 840 nm using 10.0 ml of hydrazine molybdate reagent as blank
The absorbance of test should not exceed that obtained by
0.1ml of arsenic standard solution.
TESTS ON
PLASTIC MATE
PHYSICO-CHEMICAL TESTS:-
The following tests are based on the extraction of the
plastic material, and it is essential that the designated amount of the plastic
be used. Also, the specified surface area must be available for extraction at
the required temperature.
1. Appearance
2. Light
absorption
3. pH
4. Non-volatile
matter
5. Residue on
ignition
6. Heavy metals
7. Buffering
capacity
8. Oxidisable
substances
TESTS FOR
PLASTIC CONTAINERS
Tests comply for non-parenteral preparations
1. Leakage test:
Fill ten container with water. Fit with intended closures and keep tem inverted
at room temperature for 24 hour. There are no signs of leakage from any
container.
2. Collapsibility
Test: This test applicable to containers. Which are to be squeezed in order
to remove the contents. A container by collapsing inwards during use yields at
least 90% of its nominal contents at the required rate of flow at ambient
temperature.
Solution S.
Fill a container to its nominal capacity with water and
close it. If possible using the usual means of closer: otherwise close using a
sheet of pure aluminium. Heat in an autoclave so that a temperature of 121 +
20 is reached within 20to 30 minutes and maintained at this
temperature for 30min. if heating at 1210 leads to deterioration of
the container, heat at 1000 for 2 hours.
Using solution S within 4 hours of preparation
Blank
Prepare a blank by heating water in a borosilicate glass
flask closed by a sheet of pure aluminum at the themeprature and for the time
used for the preparation of solution S.
Clarity and color of
solution S
Solution s is clear and it’s colorless
Acidity and
alkalinity
To a volume of solution S corresponding to 4% of the nominal
capacity of the container add 0.1ml of Phenolphthalein solution. The solution
is colorless. Add 0.4ml of 0.1M sodium hydroxide, the solution is pink. Add 0.8ml
od 0.01M HCl and 0.1ml of methyl red solution, the solution is orange-red or
red.
Light absorption
The light absorption in the
range 230nm to 360nm of solution S using a blank prepared as described under
solution S is not more than 0.20
Reducing Substance
To 20.0ml of solution of S add 1 ml of dilute Sulphuric acid
and 20.0ml of 0.002M potassium permanganate. Boil for 3 min, cool immediately,
add 1gm of potassium iodide and titrate with 0.01M sodium thiosulphate, using
0.25ml of starch solution as indicator, carry out a titration using 20.0ml of
blank prepared as described under solution S, the difference between the titration
volume is not more than 1.5ml.
Transparency
Fill the container previously used for the preparation of
solution S to its nominal capacity with a 1 in 200 dilution of the standard
suspension for a container made from polyethylene or polypropylene. For container
of other material use a 1 in 400 dilution, the cloudiness of the suspension is
perceptible when viewed through the container and compared with a similar
container filed with water.
3. Clarity of aqueous
extract: Select unlabelled, unmarked and non- laminated portions from
suitable containers, taken at random sufficient to yield a total area of sample
required taking into account the surface area of both sides Cut these portions
into strips none of which has a total area of more than 20 cm2. Wash the strips
free from extraneous matter by shaking them with at least two separate portions
of distilled water for about 30 seconds in each case, then draining off the
water thoroughly.
4. Transparency test:
Fill five empty containers to their nominal capacity with diluted. Suspension
as described in IP 1966. The cloudiness of the diluted suspension in each container
is detectable when viewed through the containers as compared with a container
of the same type filled with water.
FOR PARENTERALS
Water Vapour
permeability test: Fill five containers with nominal volume of water and
heat seal the bottles with an aluminum foil- poly ethylene laminate or other
suitable seal. Weigh accurately each container and allow to stand (without any
overwrap) for 14 days at a relative humidity of 60+5% and a temperature between
20 and 25 0C Reweigh the containers. The loss in weight in each container is
not more than 0.2%.
NON VOLATILE RESIDUE
TEST
Fill five containers with dilute suspension. The cloudiness
of diluted suspension in each container is detectable when viewed through
container is detectable when viewed through containers as compared with a
container of same type filled with water. Evaporate 100 ml extract. Allow it to
dry at 105ﹾ C.
residue weighs not more than 12.5mg.
RESIDUE ON IGNITION –
This test is performed when NVR is greater than 5 mg
HEAVY METALS – This
test detects the presence of metals like lead, tin, zinc etc
BUFFERING CAPACITY –
This test measures the acidity or alkalinity of the extract
BIOLOGICAL TESTS: –
The USP has provided its procedures for evaluating the
toxicity of plastic materials Essentially the tests consist of three phases:
Implantation test:
Implanting small pieces of plastic material intramuscularly in rabbits.
Systemic injection
test: Injecting eluates using sodium chloride injection, with and without
alcohol intravenously in mice and injecting eluates using poly ethylene glycol
400 and sesame oil intraperitoneally in mice.
Intracutaneous test:
Injecting all four eluates subcutaneously in rabbits. The reaction from test
samples must not be significantly greater than nonreactive control samples
TESTING FOR OPHTHALM
PLASTIC CONTAINERS
FOR OPHTHALMIC PREPARATIONS:- Plastic containers for ophthalmic
preparations comply with the following tests:
1 Leakage test; Collapsibility test Clarity of aqueous
extract; Non- volatile residue Comply with the tests described under Plastic
containers for Non- parenteral Preparations.
2 Systemic injection test; Intracutaneous test Comply with
the tests described under Plastic containers
for Parenteral Preparations.
3 Eye irritation test. This test is designed to evaluate
responses to the instillation of extracts of material under examination in the
eye of a rabbit.
QUALITY
CONTROL TESTING FOR CLOSURES
The closure is normally the most vulnerable and critical
component of a container as far as stability and compatibility with the product
is concerned.
Suitable closing of the container is necessary because
1. It prevents loss of material by spilling or
volatilization.
2. It prevents the deterioration of product from the effects
of environment such as moisture, oxygen, or carbon dioxide.
3. It avoids contamination of the product from dirt,
microorganism or insects
QUALITY
CONTROL FOR RUBBER CLOSURES
Rubber closures are used to seal the cartridges, vials and
bottles, providing a material soft and elastic enough to permit entry and withdrawal
of a hypodermic needle without loss of integrity of sealed containers.
FRAGMENTATION TESTS
This test is applicable to closure intended to be pierced by
needle and closures used for aqueous preparations
SELF SEALABILITY TEST
This test is applicable to closures intended for multidose
containers
SAMPLE PREPARATION
Wash the closures by agitation in 0.2% w/v solution of
anionic surfactant for 5 minutes and then rinse 5 times with water.
Place number of washed closures (contain 100 cm² surface area)
in suitable borosilicate glass.
Add 200 ml of water per 100cm² surface area of closures and
weigh it
Now cover the mouth of container with aluminum foil and heat
in autoclave and maintain temperature of 119-1230C for 30 minutes
Cool at room temperature for 30 min and make up the original
weight with water
Shake and immediately separate the solution from closures by
decantation
Dry the treated closure 640C, at pressure not more than 0.7 Kpa
for 24 hours
1) STERILITY TEST
When treated closures are subjected to sterilization test at
64 -660C
and pressure of about 0.7 Kpa for24 hours.
2) RESIDUE ON
EAPORATION
50ml of solution A is evaporated to dryness at 1050C. Then weigh the
residue NMT 4mg
3) FRAGMENTATION TEST
1. For closures for aqueous place a volume of water
corresponding to the nominal volume mines 4ml in each of 12 clean vials
2. Close the vials with ‘prepared ‘closures to allow to
stand for 16 hours
3. For closures for dry preparations close 12 clean vials
with prepared closures
4. Using hypodermic needle with an external diameter of 0.8
mm inject 1ml of water into the vial and remove 1ml of air
5. Carry out this operation 4 times with new needle each time.
Pass the liquid into the vials through a filter with pore size of 0.5 micrometer
6. Number of fragments is NMT 10 except in case of butyl
rubber
4) SELF SEALABILITY
TEST
This test is applicable to closures intended to use with
water close the vials with the prepared closures
For each closure, use a new hypodermic needle with an
external diameter of 0.8mm and pierce the closure 10 times, each time at a
different site
Immerse the vials upright in a 0.1% w/ solution of methylene
blue and reduce the external pressure by 27Kpa for 10 minutes
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 colored solution
5) PH OF THE AQUEOUS
EXTRACT
20ml of solution A is added with 0.1ml bromothymol blue when
it is added with a small amount of 0.01ml NaOH which changes the color from
blue to yellow. The volume of NaOH required is NMT 0.3ml and if it is done with
HCl, the volume of HCl needed should not be more than0.8ml
6) LIGHT ABSORPTION
TEST
It must be done within 4 hours of preparing solution A. it
is filtered through 0.5 micron filter and its absorbance is measured at 220nm
to 360nm. Blank is done without closures and absorbance is NMT 2.0
7) REDUCING
SUBSTANCES
20ml of solution A is added with 1ml of 1M H2SO4 and 20ml of
0.002M KMnO4 and boil for 3minutes then cool and add 1gm of potassium iodide
which is titrated with sodium thiosulphate using starch as an indicator . Blank
is done and difference between the titration volumes is NMT 0.7ml.
8) RESIDUE ON
EVAPORATION
50ml of solution A is evaporated to dryness at 105℃.
Then weigh the residue NMT 4mg
QUALITY
CONTROL FOR METAL
TINS
DESCRIPTION
Metallic tins having smooth inner surface.the upper surface
sealed consists a clip to break the seal. The lower surface is open
DIMENSIONS
Height – measure the height of in mm of 10 metallic tin,
individually from the lower surface edge to upper rim.
DIAMETER
Inner diameter – measure the inner diameter of 10 metallic tins.
Limit NLT 98mm
Outer diameter – limit NLT 105mm
CLEANLINESS CHECK
Should not be damaged, stained or consist of foreign part.
QUALITY
CONTROL FOR STRIPS AND BLISTERS
PROCEDURE
3/4th of water is poured in desiccators. The strips and
blisters were place inside desiccators and vacuum is applied.
Vacuum was then released and strips, blisters were taken out.
The water present over the outer surface of the packages was wiped off with
tissue paper
The contents of strips and blister packages were removed and
presence of moisture was checked. If there is no leakage, the contents will not
be wetted
This indicates perfect sealing of the packages
QUALITY
CONTROL OF PAPER AND BOARD
The test pieces of paper and board are prepared under
standard conditions such as
Temperature: 23℃± 1℃,
Relative humidity: 50%± 2%
Moisture Content–
Substance will be measured at temperature specified for the test
Folding endurance–
Fold the test piece back and forth until rupture occurs
Air permeability–
Important for using light weight uncoated paper on machine having vacuum pick
up system
Tensile strength–
Maximum tensile force per unit width that a paper will withstand before
breaking
Stiffness- Degree
of resistance offered by paper
TESTING FOR
PHARMACEUTICAL COILS
Table 35-4. Comparison of Pharmaceutical Coils
|
Test |
Cotton |
Rayon |
Polyester |
|
Residual Hydrogen Percxlce |
NMT 50 ppm is found using either method |
Not applicable for rayon |
Not applicable for synthetic coil |
|
Loss on Drying <731> |
Dry 5.00 g of fibers In an |
Dry 5.00 g of fibers in an |
Dry 5.00 g of fibers in an oven at 105° to constant weight: It loses NMT 0.5% of lts wetght |
|
Residue on Ignition <281> |
NMT 0.20% on a 5.0 g sample |
NMT 1.50% on a 5.0 g sample |
NMT 0.5% on a 5.0 g sample |
|
Water-Soluble Substances |
The residue weighs NMT 0.35% |
The residue weighs NMT 1.0% |
Not applicable for synthetic coil |
|
Fatty Matter |
The weight of the residue of a 10.00 g sample does not exceed 0.7% |
The weight of residue of a |
Not applicable for synthetic coil |
|
Possible additives of chemicals |
Bleach and dyes |
Furfural |
Antistatic Agents |
PACKAGING
MATERIAL SPECIFICATIONS:
Printed strip rolls:
Common name, Code number, Description, Color plan and
outline, Quality of printed matter, Seal quality, Effect of warmth, Name of
endorsed supplier, Frequency of re- investigation of put away material,
Precaution, and Date of issue of determination
Containers:
name of the medication and quality, Code number,
Description, Dimensions (length, width, stature), Color plan, Quality of
printed matter, Printed matter, Gram per square meter, Suitability, Name of
affirmed supplier, Frequency of re-assessment of put away material, and Date of
issue of specification
Bottles:
Common name, Code number, Description, Total tallness, Neck
tallness, Body distance across, Type of glass, Overflow limit, Suitability,
Name of affirmed supplier, and Date of issue of particular
CONCLUSION
•THE TESTING OF PACKAGING MATERIALS IS ALMOST REQUIRED FOR
ANY PHARMACEUTICAL INDUSTRY.
•THE MATERIAL OF A PACKAGE AFFECTS QUALITY, STABILITY AND
EFFICACY OF DRUG PRODUCT.
•THE COST OF MATERIAL OF A PACKAGE SHOULD BE AS LOW AS
POSSIBLE WITHOUT COMPROMISING THE QUALITY OF PRODUCT
•IT SHOULD PASS THE SPECIFICATIONS OF TESTS BEFORE IT
REACHES THE MARKET.
•THE TYPE OF TESTS FOLLOWED SHOULD BE ACCORDING TO
REQUIREMENTS OF REGULATORY AGENCIES.