QUALITY CONTROL: B.Pharmacy, 6th Sem, Unit-3, Pharmaceutical Quality Assurance

QUALITY CONTROL: Quality control test for containers, rubber closures and secondary packing material

1. Quality Assurance and Quality Management concepts
BP606T
Unit-3
Part-1
(QUALITY CONTROL: Quality control test for containers, rubber closures and
secondary packing material)
SnigdhaRaniBehera
Associate Professor
ARKA JAIN UNIVERSITY

2. Quality control test for containers
Definition:
Anymaterialthatisusedforpackagingofproductsfortheirdistributionandsaleis
saidtobepackagingmaterial.
Pharmaceuticalpackagingisthemeansofprovidingprotection,presentation,
identification,informationandconveniencetoencouragecompliancewithacourse
oftherapy.
Thecommonlyusedpackingmaterialsarecontainer,closureandcartoonorouter
box.
Thecontainersmostlymadeofglass,plastic,metalorpaper.
Thematerialforclosuremayincludecork,Glass,Plastic,MetalorRubber.
ARKA JAIN University, Jamshedpur, Jharkhand

3. Therearethreetypeofpackagingmaterial.
1.Primarypackagingmaterial:Comesincontactwiththeproducte.g.Bottles,vials,
ampoules,tinetc.
2.Secondarypackagingmaterial:Usedtocoverprimarypackse.g.Cartons,boxes,
etc.
3.Tertiarypackagingmaterial:Itisusedtobulkhandlingandshipping.E.g.Barrel,
container,edgeprotector.
Therearevarioustestsfordeterminationofquality,integrityandcompatibilityof
packagingmaterials.
Thespecificationandrequirementofqualitytestingdependsontypeof
pharmaceuticalmaterialsused.
ARKA JAIN University, Jamshedpur, Jharkhand

4. ARKA JAIN University, Jamshedpur, Jharkhand
Quality control test for Glass
container
1.Crushed glass test
2.Whole container test
3.Chemical resistant
of glass container
a. Powder glass test
b. Water attack test

5. Quality control test for
Glass Container
4. Hydrolytic resistance of glass
containers
5. Light Transmission test
6.Arsenic test
7. Thermal shock test
8. Internal bursting pressure test
9. Leakage test
ARKA JAIN University, Jamshedpur, Jharkhand

6. Type-I
•NeutralorborosilicateGlass(withahighhydrolyticresistance,suitable
formostpreparationsnotforparenteraluse)
Type-II
•TreatedSodalimesilicaGlass(withahighhydrolyticresistance,suitable
formostacidicandneutral,aqueouspreparations)
Type-III
•SodalimesilicaGlass(withonlymoderatehydrolyticresistance,suitable
fornon-aqueouspreparationsforparenteraluse,forpowdersfor
parenteraluse(exceptforfreeze-driedpreparations))
Type-IV
•GeneralpurposeSodalimeGlass(usedfornon-parenteralproducts(tobe
takenorallyorbyinhalation)asthevial)
ARKA JAIN University, Jamshedpur, Jharkhand

7. 1.Crushed glass test:
Thecontaineriscrushedandsievedtoproduceuniformparticlesofwhichadefinite
weightoftaken.
Thecontroloftheparticlesizeandweightofpowderensuresthataconstantsurface
areaisexposedtothesolution.
Becausealloftheglass(notjustthesurfacelayer)isexaminedandextractionis
enhancedbytheroughsurfacesoftheparticles,thisisaseveretest,and,ifaglass
passes,itisunlikelythatcontainersmadefromitwillgivetroublewhileisuse.
This test can be used for determining the nature of a glass or for distinguish between
two types of glasses, such as neutral or surface –treated.
2.Whole container test:
ItisusedintheUSPfortreatedsoda-limecontainersonly.
Thecontainersaresimplyfilledwiththetestsolutionandexposedtothetest
conditions.
Glasswaremaypassthewholecontainertestmoreeasilybecausethesurfacelayerof
acontainerissmoothandlessreactive.
ARKA JAIN University, Jamshedpur, Jharkhand

8. Inthistest,surfaceareadoesnotincreaseasmuchasvolumewiththeincreasein
containersize,consequently,thesmallsizedcontainersaremoreattackedbythe
leachingofthealkalifromthesurface.
3.Chemicalresistantofglasscontainer:
USPandIPprovidetwoteststodeterminethechemicalresistanceofglass
containers.
Itisdividedintotwotypes.a.Powderglasstest
b.Waterattacktest
a.Powderglasstest:Fromtheglasscontainers,alkalineconstituents(oxidesof
sodium,potassium,calcium,aluminum,etc.)areleachedintopurifiedwaterunder
conditionsofelevatedtemperatures.
Whentheglassispowderedtheleachingofalkalicanbeenhancedinthepowdered
iscritical.
ARKA JAIN University, Jamshedpur, Jharkhand

9. Theprincipleinvolvedinthepowderedglasstestinestimatetheamountofalkali
leachedformtheglasspowder.
Theamountofacidthatisnecessarytoneutralizethereleasedalkali(aspecified
limit)isspecifiedinthepharmacopoeia.
Thebasicanalysisisacid-basetitrationusingmethylredindicator.
Step-1: Preparation of glass specimen:
ARKA JAIN University, Jamshedpur, Jharkhand
Grind the containers in a mortar to a fine powder and then pass through sieve no,20
and 50.
Few containers are rinsed thoroughly with purified water and dried with stream of
clean air

10. Step-1: Washing the specimen:
ARKA JAIN University, Jamshedpur, Jharkhand
Decant the acetone and dried after which it is used which it is used within 48hr
Repeat the washing
10 gm of the above specimen is taken in to 250 ml conical flask and wash it with 30
ml of acetone

11. Procedure:
ARKA JAIN University, Jamshedpur, Jharkhand
Record the volume of 0.02 N Sulphuricacid
Titrated immediately with 0.02 N Sulphuricacid using 5 drops of methyl red indicator
Then the sample(Residue) washed again with 50 ml of high purity water and again
decanted
Solution decant in to another conical flask
Cooled under running water
Placed in autoclave at 121º c ±2º c for 20 mins
10g specimen/ sample is added with 50 ml of purified water in a 250 ml conical Flask

12. Tests
Powder glass Test
Water attack test
Container
Type-I
Type-II
Type-III
Type-II (100 ml or below)
Type-II (above 100ml)
Volume of 0.02 N
Sulphuricacid
1.0
8.5
15.0
0.07
0.02
ARKA JAIN University, Jamshedpur, Jharkhand
Volume of Sulphuricacid consumed

13. b. Water Attack Test:
Thistestisusedonlywithcontainersthathavebeenexposedtosulphurdioxide
fumesundercontrolledhumidityconditions.
Suchatreatmentneutralizesthesurfacealkali.
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.
Since the inner surface is under test entire container (ampoule) has to be used.
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.
ARKA JAIN University, Jamshedpur, Jharkhand

14. Procedure:
Rinse3ormorecontainerstwicewithhighpuritywater.
Filleachcontainerto90%ofitsoverflowcapacitywithwater.
Capalltheflask,autoclaveat121°Cfor30min.
Thenitiscooledandtheliquidisdecantedwhichistitratedwith0.02Nsulphuric
acidusingmethylredasanindicator.
Measurethevolumeofsulphuricacid.
ARKA JAIN University, Jamshedpur, Jharkhand

15. 4.Hydrolytic Resistance of Glass Container:
ARKA JAIN University, Jamshedpur, Jharkhand
Perform blank titration with water and the difference between the titration represents
the volume of HCL consumed by the test solution.
Measure the volume of test solution in to conical flask and titrate with 0.01N HCL
using methyl red as an indicator.
Remove the container from autoclave, cool & combine the liquids being examined.
Rise the temp. from 100ºc to 121ºc over 20 min. maintain the temp. at121ºc to 122ºc
for 60 min. Lower the temp. from 121ºc to100ºc for 40 min.
Heat to 100ºc for 10 min. and allow the steam to issue from the vent cork.
Rinse container at least 3 times with CO2 free water with the same to their filling
volume . Fill and cover the vials and keep in autoclave.

16. 5. Light Transmission test:
ARKA JAIN University, Jamshedpur, Jharkhand
Measure the transmittance of the section
Place the specimen in a spectrophotometer with its cylindrical walls parallel to the slit
in such a way that the light beam is perpendicular to the surface of the section
Wash and dry each sample taking care not to scratch the surfaces
The glass container is cut circular sections from two or more areas with circular saw

17. The observed light transmission does not exceed the limits given in the below
table intended for parenteral use.
ARKA JAIN University, Jamshedpur, Jharkhand
Size,ml % Light transmission at any
wavelengthbetween 290 to 450
1 25
2 20
5 15
10 13
20 12
50 10

18. 6.Arsenic test:
This test is for glass containers intended for aqueous parenterals.
ARKA JAIN University, Jamshedpur, Jharkhand
The absorbance of the test solution should be less than the absorbance obtained using 0.1 ml of
arsenic standard solution (10 ppm)
It is cooled and absorbance is measured at 840nm
10 ml of hydrogen molybdateis added and refluxed for 25 minutes
10 ml from the final combined volume is pipette out and to it 10ml of HNO3 is added and dried
in an oven at 130ºc
Then similar steps followed as performed in the hydrolytic test, previously described, till
obtaining the final combined solution
The inner and outer surface of the containers is washed with fresh distilled water for 5 mins

19. 7. Thermal shock test:
ARKA JAIN University, Jamshedpur, Jharkhand
A typical test uses 45ºc temp difference between hot and cold water
Small bottles withstand a temp differential of 60ºc to 80ºc and 1pint bottle 30ºc to
40ºc.
The amount of thermal shock a bottle can withstand depends on its size, design and
glass distribution
Examine cracks or breaks before and after test
Immerse the tray into a hot water for a given time and transfers to cold water bath,
temp of both are closely controlled.
Place the glass containers in upright position in a tray

20. 8. Internal bursting pressure test:
ARKA JAIN University, Jamshedpur, Jharkhand
The bottle can be checked for predetermined pressure level and test continues until
the container finally bursts
A scaling head is applied and the internal pressure automatically raised by a series
of increments each of which is held for a set of time
The test container is filled with water and placed in side the glass chamber

21. 9. Leakage test:
ARKA JAIN University, Jamshedpur, Jharkhand
Then it conclude leakage is there
Which is at high pressure compared to the pressure inside the glass container so that
the colored solution enters the container if any cracks or any breakage is present
Drug fill container filled with colored solution (due to the addition of dye)

22. Quality control test for Plastic container
Quality control test for plastic may be done by any / both of the procedure.
1. ChemicalExamination 2. Biological Test
ARKA JAIN University, Jamshedpur, Jharkhand
1. Leakage
test
2. Collapsibility
test
3. Clarity of
aqueous
extract
6. Water vapor
permeability test
5.Transparency
test
1. Implantation
test
Systemic
injection test
Intra -cutaneous
test

23. ARKA JAIN University, Jamshedpur, Jharkhand
1. 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.

24. ARKA JAIN University, Jamshedpur, Jharkhand
2. 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

25. 3. 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
20cm²
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
250ml 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.
ARKA JAIN University, Jamshedpur, Jharkhand

26. 4. Water vapor
Permeability test
Fill five containers with nominal
volume of water and heat seal
the bottles with an aluminum
foil or other suitable seal
Weigh accurately each container
and allow to stand (with out any
overwrap) for 14 days maintaining
humidity of 60 ±5 % and temp
between 20ºand 25º
Reweigh the containers
The loss in weight in each
container is not more than 0.2%
ARKA JAIN University, Jamshedpur, Jharkhand

27. 5. Transparency test
Fill five 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
ARKA JAIN University, Jamshedpur, Jharkhand

28. b. Biological Test:
The USP has provided the biological test procedures for evaluating the toxicity of
plastic materials.
This test consist of three phases
ARKA JAIN University, Jamshedpur, Jharkhand
Implantation Test
•Small pieces of
plastic material
implanted intra-
muscularly in rabbits.
Systemic injection
Test
•Elutes using sodium
chloride injection are
injected with and
without alcohol
intravenously in mice
and injecting, eluates
using poly ethylene
glycol 400 and
sesame oil intra-
peritoneallyin mice.
Intra-cutaneous
Test
•Injecting all four
eluates
subcutaneously in
rabbits. The reaction
from test samples
must not be
significantly greater
than nonreactive
control samples.

29. Quality control test for Metal container:
ARKA JAIN University, Jamshedpur, Jharkhand
Take 50 empty tubes filled
with ointment base, sealed &
kept overnight
A metal bacteriological filter
assembly fitted with filter
paper & heated to melting
range of ointment base
Base from all tubes squeezed
at certain rate & passed
through filter under vaccum
Further wash with CHCL3 and
observed for particles.

30. Quality control test for Closures:
Closures are used to prevent loss of material by Volatization, deterioration of the
product from moisture, oxygen or carbon dioxide.
ARKA JAIN University, Jamshedpur, Jharkhand
1. Penetrability
Test
•It is measured by
using the piercing
machine.
•Piercing force must
not exceed a stated
value.
Compatibility Test
•This test is performed
to check the
compatibility of the
rubber closures with
various types of the
substance.
•Since it is necessary to
ensure that there is no
interaction between
the contents of the
bottle and the clouser.
Extractive Test
•In this test, the
closure is boiled
with water for four
hours under reflux
and the water
evaporated to
dryness.
•The residue must
not exceed the
specified amount.

31. Quality control test for Closures:
Preparation of sample:
ARKA JAIN University, Jamshedpur, Jharkhand
The closures are washed in 0.2% w/v of anionic surface
active agents for 5 mins.
Rinsed five times with distilled water and 200ml water is
added to it.
It is subjected to autoclave at 119ºc to 123ºc for 20 to 30
min and covered with aluminum foil.
Cooled and solution is separated from closures
(Solution A).

32. •50mlofSolutionAisevaporatedtodrynessonawaterbathand
driedat105ºc.
•Theresidueweighsnotmorethan4gm.
1. Residue on
Evaporation
•Whentreatedclousersaresubjectedtosterilizationtestat64ºcto
66ºcandapressureofabout0.7KPAfor24hr.
2. Sterility Test
•Thistestisapplicabletoclosuresintendedtobepiercedwith
hypodermicneedlecappedandstandfor16hr.
•Fordrypreparationclosevialswithclosures.Injectwith
hypodermicneedle(1ml)andtake1mlair,Passliquidthrough
filter.
•Countnooffragments,mustnotmorethan10andforbutylrubber
closuresitisnotmorethan15.
3. Fragmentation
test
ARKA JAIN University, Jamshedpur, Jharkhand

33. •Pierce10timeswithhypodermicneedleandimmersesin
0.1%methylenebluesolution,maintainthepressureofabout
27KPAandrestoretoatmosphericpressureandstandfor30
min.
•Rinseoutsideandobservedfortracesofcoloredsolution.
•Tracesofcoloredsolutionshouldnotbefound.
4. Self stability Test
•SolutionAisnotmoreopalescentthanopalescentstandard
OS3andnotmorethan0.8ml.
5. Clarity and color of
aqueous extract
•20mlofSolutionAisaddedwith0.1mlbromothymolblue
whenitisaddedwithasmallamountof0.01MNaOHwhich
changesthecolorfrombluetoyellow.
•ThevolumeofNaOHrequiredisnotmorethan0.3mlandifit
donewithHCL,thevolumeshouldnotmorethan0.8ml.
6. PH of aqueous extract
ARKA JAIN University, Jamshedpur, Jharkhand

34. •Itmustbedonewithin4hrsofpreparationof
solutionA
•Itfilteredthrough0.5µfilteranditabsorbance
ismeasuredat220nmto360nm.
•Blankisdonewithoutclosuresandabsorbance
isnotmorethan2.
7.Light absorption test
•20mlofsolutionAisaddedwith1mlof1M
sulphuricacidand20mlof0.002Mkmn04and
boilitfor3minthencoolandadd1gmKI
whichistitratedwithsodiumthiosulphate
usingstarchasanindicator.
•Blankisdoneanddifferencebetweentitration
volumesnotmorethan0.7ml.
8. Reducing substances
ARKA JAIN University, Jamshedpur, Jharkhand

35. Quality Control test of collapsible Tubes:
ARKA JAIN University, Jamshedpur, Jharkhand
•Waterfilledinthetubeandclosedtightly.
•Externalsurfaceiswipedoffandtubeiskeptinvertedonfilterpaperat
base.
•Allowtostandfor1hr.Filterpapershowsabsorptionatanytimeduring
testperiod.
1. Leakage test
•a.Powderofadhesion:Tubewasspittedalongthelengthandflattened.Cotton
woolsoakedinacetonewasrubbedoverlacquersurfacefor20min.Lacquer
shouldnotliftfromsurfaceandcottonwoolshallremaincolorless.
•b.Flexibilitytest:Thetubewasfoldedinsuchamannerthatinternallacquer
surfaceisoutside.Thelacquercostingshouldnotbepeeledoffwhenthefolded
positionisrubbedwithfinger.
2. Lacquer curing test
•10tubesaretakenastestsample.Thenitfilledandcrimpedsubjectedto45cfor
72hr.Tubeswereallowedtocoolandcutlengthwise.
•a.Productcompatibility:Contentshouldnotshowchangeincolororgas
formation.
•b.Lacquercompatibility:Liftingorpeelingoflacquerischecked.
3. Lacquer compatibility
test

36. ARKA JAIN University, Jamshedpur, Jharkhand
Quality control of Strip and blisters:
The 3/4
th
of water is
poured in
desiccators
The strips and
blisters were place
in side the
desiccators and
vacuum is applied
After sometime
vacuum was
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 was
checked for presence
of moisture
If there is no leakage
, the contents will
not be wetted. This
indicates the perfect
sealing of the
packages.

37. Quality control tests for Cartons:
ARKA JAIN University, Jamshedpur, Jharkhand
•Thisisusedtoassessthestrengthoferected
packagetherebyestimatingthedegreeof
protectionthatitconfersonthecontents.
•Thisisusefulforproductswithnoinherent
strengthinoneplaneoranother.1. Compression
•Thecartonshouldspringopenintoitsoriginal
shapewithoutaneedforunreasonableforce.
•Ifthecartondoesnotspringopenorbucklesin
onitself,itmaycauseproblemsoncartooning
machine.
2. Carton opening
force

38. THANK YOU
STAY SAFE
&
STAY HEALTHY
ARKA JAIN University, Jamshedpur, Jharkhand