plastic and glass containers and its evaluation test, drug plastic consideration .

quality control test test for glass and plastic containers.

1. QUALITY CONTROL TEST FOR PLASTIC
CONTAINER
DRUG-PLASTIC CONSIDERATION
DRUG-GLASS CONSIDERATION
PRESENTEDBY:-
RAJUDHUNGEL
17HPH074
B.PHARM5thSEM
INDUSTRIAL PHARMACY-I
HPI

2. PLASTICCONTAINERS:
Plasticcontainersforpharmaceuticalproductsaremadefromplasticsbasedonthe
followingpolymers:polyethylene(loworhighdensity),polypropylene,polyvinyl
chloride,polystyreneandtoalesserextentpolyethyleneterephthalate.
Thecontainersconsistofoneormorepolymerstogetherwithcertainadditivesif
necessary.Additivesmayconsistofantioxidants,lubricants,plasticisersandimpact
modifiersbutnotantistaticagentsandmouldreleaseagents.
Theplasticcontainerchosenforanyparticularproductshouldbesuchthatthe
ingredientsoftheproductincontactwiththeplasticmaterialarenotsignificantly
adsorbedonitssurfaceanddonotsignificantlymigrateintoorthroughtheplastic.
Typesamplesoftheintendedcontainershouldbepackedwiththeproductandtested
underconditionsthatreproducethosethatwouldbeencounteredinuse.Thesetests
shouldincludeexaminationoftheproducttoensureabsenceofanysensory,chemical
orphysicalchange,anassessmentofchangesinthequantityofcontentsdueto
permeabilityoftheplastic,detectionofchangesinpH,anassessmentoftheeffectsof
light,chemicaltestsandwherenecessary,biologicaltests.

3. QUALITYCONTROLTESTFORPLASTICCONTAINERSASPERIP:-
A.FORNON-PARENTERALPREPARATIONS:
Leakagetest
Collapsibilitytest
Clarityofaqueousextract
Non-volatileresidue

4. Leakagetest:Filltencontainerswithwater,fitwiththeintendedclosuresandkeepthem
invertedatroomtemperaturefor24hours.Iftherearenosignsofleakagefromany
containerthetestissaidtobepassed.
Collapsibilitytest:Thistestisapplicabletocontainerswhicharetobesqueezedin
ordertoremovethecontents.
Acontainerbycollapsinginwardduringuse,yieldatleast90%ofitsnormalcontentsat
therequiredrateofflowatambienttemperature.

5. Clarityofaqueousextract:Selectunlabelled,unmarkedandnon-laminatedportions
fromsuitablecontainers,takenatrandom,sufficienttoyieldatotalareaofsample
required,takingintoaccountthesurfaceareaofbothsides.Cuttheseportionsinto
strips,noneofwhichhasatotalareaofmorethan20cm
2
.Washthestripsfreefrom
extraneousmatterbyshakingthemwithatleasttwoseparateportionsofdistilledwater
forabout30secondsineachcase,thendrainingoffthewaterthoroughly.Selectcutand
washedportionsofthesamplewithatotalsurfaceareaof1250cm
2
,transfertoaflask,
previouslycleanedwithchromicacidmixtureandrinsedwithseveralportionsof
distilledwaterandadd250mlofdistilledwater.Covertheflaskwithabeakerand
autoclaveat121ºCfor30minutes.Carryoutablankdeterminationusing250mlof
distilledwater.Coolandexaminetheextract;itiscolourlessandfreefromturbidity.
Non-volatileresidue:Evaporate100mloftheextractobtainedinthetestforClarityof
aqueousextracttodrynessanddrytoconstantweightat105ºC.Theresidueweighsnot
morethan12.5mg.

6. B.FORPARENTERALPREPARATIONS:
Forparenteralpreparationsthepolymersmostcommonlyusedarepolyethylene,
polypropyleneandpolyvinylchloride.Onlyvirginplasticmaterialwhichhasneverbeenused
orprocess,whichispracticallyodourlessisusedinthemanufactureofcontainers.Additives
suchasantioxidants,lubricants,plasticisers,stabilisers,etcmaybeusedbutnopigmentsmay
beusedforthepurposesofcolouring.
Followingtestsareappliedfortheinjectablepreparationcontainers-
Leakagetest
Collapsibilitytest
ClarityandcolourofsolutionS.
Acidityoralkalinity
Lightabsorption
Reducingsubstances
Transparency

7. Leakagetest,collapsibilitytest:Complywiththetestsdescribedunderplastic
containersfornon-parenteralpreparations.
*SolutionS.Fillacontainertoitsnominalcapacitywithwaterandcloseit,ifpossible
usingtheusualmeansofclosure;otherwisecloseusingasheetofpurealuminium.Heat
inanautoclavesothatatemperatureof121±2
O
Cisreachedwithin20to30minutes
andmaintainatthistemperaturefor30minutes.Ifheatingat121
O
Cleadsto
deteriorationofthecontainer,heatat100
O
Cfor2hours.
UsesolutionSwithin4hoursofpreparation.
*Blank.Prepareablankbyheatingwaterinborosilicateglassflaskclosedbyasheetof
purealuminiumatthetemperatureandforthetimeusedforthepreparationofthe
solutionS.

8. ClarityandcolourofsolutionS.:SolutionSisclearandiscolourless.
Acidityoralkalinity:ToavolumeofsolutionScorrespondingto4percentofthe
nominalcapacityofthecontaineradd0.1mlofphenolphthaleinsolution.Thesolution
iscolorless.Add0.4mlof0.01Msodiumhydroxide.Thesolutionispink.Add0.8mlof
0.01Mhydrochloricacidand0.1mlofmethylredsolution.Thesolutionisorange-red
orred.
Lightabsorption:Thelightabsorptionintherange230nmto360nmofsolutionS
usingablankpreparedasdescribedunderSolutionSisnotmorethan0.20.
Reducingsubstances:To20.0mlofsolutionSadd1mlofdilutesulphuricacidand
20.0mlof0.002Mpotassiumpermanganate.Boilfor3minutes.Coolimmediately.Add
1gmofpotassiumiodideandtitrateimmediatelywith0.01Msodiumthiosulphate,using
0.25mlofstarchsolutionasindicator.Carryoutatitrationusing20.0mloftheblank
preparedasdescribedunderSolutionS.Thedifferencebetweenthetitrationvolumesis
notmorethan1.5ml.

9. Transparency:FillthecontainerpreviouslyusedforthepreparationofsolutionStoits
nominalcapacitywitha1in200dilutionofthestandardsuspensionforacontainer
madefrompolyethyleneorpolypropylene.Forcontainersofothermaterials,usea1in
400dilution.Thecloudinessofthesuspensionisperceptiblewhenviewedthroughthe
containerandcomparedwithasimilarcontainerfilledwithwater.

10. TESTONCONTAINERMATERIAL:
Thefollowingtestsaredoneonportionsofthecontainerthatareunlabeled,unprinted
ornon-laminatedoronthegranulesofplasticinthecaseofcontainersmadebythe
‘form-fill-seal’process.
Barium:Moisten2gwithhydrochloricacidandigniteinaplatinumdish.Dissolvethe
residuein10mlof1MHCl,filterandadd1mlof1MH
2SO
4tothefiltrate.Any
turbidityproducedisnotgreaterthanthatproducedonadding1mlof1MH
2SO
4toa
mixtureof10mlbariumstandardsolution(10ppmBa)and10mlof1MHCl.
Heavymetals:To2.5ginalong-neckedround-bottomedflaskadd20mlofH
2SO
4and
charforabout10minutes.Addhydrogenperoxidesolution(100Vol)dropwisetothe
hotsolutionuntilitbecomescolourless,heatingbetweeneachadditionuntilwhite
fumesareevolved.Cool,transfertoaplatinumdishwiththeaidof10mlofwaterand
evaporatetodryness.Dissolvetheresiduein10mlof1MHCl,filterifnecessaryand
addsufficientwatertoproduce25ml------(solutionA).

11. Toamixtureof10mlofsolutionAand2mlofacetatebufferpH3.5add1.2mlof
thioacetamidereagent,miximmediatelyandallowtostandfor2minutes.Anyyellow
colourinthesolutionisnotmoreintensethantheyellowcolourobtainedbyrepeating
theoperationusing10mlofcadmiumstandardsolution(10ppmCd)inplaceof
solutionA.Anybrowncolourinthesolutionisnotmoreintensethanthatobtainedby
repeatingtheoperationusingamixtureof5mlofleadstandardsolution(10ppmPb)
and5mlofwaterinplaceofsolutionA.
Tin:To10mlofsolutionAobtainedinthetestforHeavymetalsadd5mlofH
2SO
4
(20%),1mlofa1%w/vsolutionofsodiumdodecylsulphateand1mlofzincdithiol
reagent.Heatinawater-bathforexactly1minute,coolandallowtostandfor30
minutes.Anyredcolourinthesolutionisnotmoreintensethantheredcolourobtained
byrepeatingtheoperationusing10mloftinstandardsolution(5ppmSn)inplaceof
solutionA.
Zinc:To1mlofsolutionAobtainedinthetestforHeavymetalsaddsufficientwaterto
produce100ml.To10mloftheresultingsolution(testsolution)add5mlofacetate
buffersolutionpH4.4,1mlof0.1Msodiumthiosulphateand5mlof0.001%w/v

12. …..dithizoneinchloroform,shakeandallowtostandfor2minutes.Anyvioletcolourin
thechloroformlayerisnotmoreintensethanthatobtainedbyrepeatingtheoperation
usingamixtureof2mlofzincstandardsolution(10ppmZn)and8mlofwaterinplace
ofthetestsolution.Carryoutablankdeterminationusing10mlofwaterinplaceoftest
solution.Thetestisnotvalidunlessthechloroformlayerobtainedintheblank
determinationiscolourless.

13. DRUG-PLASTICCONSIDERATION:
Apackingsystemmustprotectthedrugwithoutinanywayalteringthecomposition
oftheproductuntilthelastdoseisremoved.Theselectionofasuitablepackagefora
drugisnotaneasytask,inasmuchasanerrorcanleadtoseriousconsequences.A
chiefdisadvantageoftheplasticoverglassistheproblemofpermeation,ingredients
mayleachtodrugproductandcontentmayadsorbedintoandontotheplastic
containers,etc.
Drug-plasticconsiderationhavebeendividedintofiveseparatecategories:
1.Permeation
2.Leaching
3.Sorption
4.Chemicalreaction,and
5.Modification

14. Permeation:Thetransmissionofgases,vapours,orliquidsthroughplasticpackaging
materialscanhaveadverseeffectsontheshelf-lifeofadrug.
-Permeationofwatervapourandoxygenthroughtheplasticwallintothedrugarisea
problemofhydrolysisandoxidationifthedrugissensitivetothesereactions.E.g.
Penicillintabletswerefoundtodegradeinpolystyrenecontainers,owingtopermeation
ofwatervapour.Similarlychangeincolourandtasteoftetracyclinesuspensionwas
observedowingpermeationofairfrompolyethylenecontainerswall.
-TemperatureandhumidityarethemajorfactorinfluencingthepermeabilityofO
2and
H
2Othroughplastic.Increaseintemperatureincreasesthepermeabilityofgas.
-Moleculesdonotpermeatethroughcrystallinezone;thus,anincreaseincrystallinityof
thematerialshoulddecreasepermeability.
-MaterialssuchasNylon-hydrophilicinnature-poorbarrierstowaterwhile
hydrophobiclike-polyethylene-muchbetterbarriers.

15. -Studieshaverevealedformulationscontainingvolatileingredientsmightchangewhen
storedinplasticcontainersbecauseoneormoreingredientscanpassfromthewallofit.
Aromaofcosmeticproductandthetasteofmedicinalproductschangeforthesame
reason.
-Plasticcontaineralsomayhaveaninfluenceonthephysicalsystemmakingupofthe
product.E.g.CertainW/Oemulsioncannotbestoredinahydrophobicplasticbottle,
sincethereistendencyofoilphasetomigrateanddiffuseintotheplastic.
Leaching:Mostplasticcontainershaveoneormoreingredientsaddedinsmall
quantitiestostabiliseorimpartaspecificpropertytoaplastic.Theseingredientshave
theprospectofleaching,ormigrationfromthecontainertothedrugpresent.
-Whencoloringagentsareusedinrelativelysmallamountinplasticsformulation,
particulardyesmaymigrateintoaparenteralsolutionandcauseatoxiceffect.
-Releaseofaconstituentsfromthecontainertocontentmayleadtodrugcontamination
andnecessitatetheremovaloftheproductfromthemarket.

16. Sorption:Thisprocessinvolvestheremovaloftheconstituentsfromthedrugproductby
thepackagingmaterial,whichleadstotheseriousconsequencesfordrugpreparation
wheretheimportantingredientsmaylost.
-Sincethedrugofhighpotencyareadministeredinsmalldoses,lossesduetosorption
maysignificantlyaffectthetherapeuticefficacy.
-Aproblemmostlyencounteredinpracticeislossofthepreservativeswhichareusedin
smallquantities.
-Factorsinfluencingsorptionfromtheproductare:pH,solventsystem,concentrationof
activeingredients,chemicalstructure,temperature,lengthofcontactandareaof
contact.

17. Chemicalreactivity:Fewingredientsusedinplasticformulationmayreactwiththeone
ormorecomponentofthedrugproductchemically.Attimes,ingredientsinthe
formulationmayreactwiththeplastic.Evenmicro-quantitiesofchemically
incompatiblesubstancescanaltertheappearanceoftheplasticorthedrugproduct.
Modification:Thephysicalandchemicalalterationofthepackagingmaterialbythe
drugproductiscalledmodification.
-Phenomenonlikepermeation,sorptionandleachingplayaroleinalteringthe
propertiesoftheplasticandalsomayleadtoitsdegradation.
-Deformationofpolyethylenecontainer-duetopermeationofgasesandvapoursfrom
theenvironment-orbythelossofcontentthroughthecontainerwalls.
-Somesolventsystem-bringsconsiderablechangesinthemechanicalpropertiesof
plastics.E.g.Oilshavesofteningeffectonthepolyethylene,fluorinatedhydrocarbon
attackspolyethyleneandPVC.

18. -Insomecasesthedrugproductmayextracttheplasticizers,anti-oxidant,orstabilizer
leadingtothedegradationofphysicalandchemicalmodificationofboththecontainer
andthecontentandmaychangetheflexibilityofthepackage.
-Certainmaterialsintheemulsionhavethetendencytomigratetowardthepolyethylene
wall,causingeitherachangeintheemulsionoracollapseinthecontainer.

19. DRUG-GLASSCONSIDERATION:
Althoughglassexhibitsmanyadvantagesoverotherpackagingmaterials,ithastwo
principalfaults,namely,thereleaseofalkaliandthereleaseoftheinsolubleflakesto
liquidsstoredinthecontainer.
-Bydecreasingthesodacontentintheglassorreplacingthesodiumoxidewithother
oxides,ithasbeenpossibletoovercomethepropertyoftheglasstoreleasealkali
cationsintothesolutions.Thisisexemplifiedbytheborosilicateglass(powderedglass
testUSPXX;limits,size:All,mlof0.02NAcid:1.0)ascomparedwiththegeneral
purposesoda-limeglass(powderedglasstestUSPXX;limits,size:All,mlof0.02N
Acid:15.0).
-Toincreasetheresistantoftheglasstoalkalirelease,onemethodconsistsoftreating
thesurfaceofthesodalimeglasstoproducethefinepolishedskinofsilica,whichis
moreresistantthantheinnerlayeroftheglass.Thissurfacetreatedglassisrepresented
bytheTypeIIglass.
-Anotherapproachistotreatthesurfaceoftheglasswithsulfurdioxideinthepresence
ofwatervapourandheat.Thiscausesthesurfacealkalitoreactwiththesulfurdioxide

20. -Sometimes,insolubleflakeshavebeenfoundtoappearinsolutionsstoredinglass
containers.Thetypeofglassemployedplaysamajorroleinwhetherflakeformation
takesplace.E.g.Flakeformationoccurimmediatelyinnon-borosilicateglassafter
autoclaving,whileinborosilicateglassitoccursonlyathighertemperaturethan
normallyusedforautoclaving.
-Flakesarealsolikelytooccurwithphosphate,citrate,tartrate,andalkalinesolutions.
Pre-treatmentofthecontainerswiththedil.acidsolutionwasfoundtodelaytheflake
formation.
-Manypharmaceuticalpreparationsexhibitphysicalandchemicalchangesduetothe
radiantlight.Itcanbemoreadequatelyprotectedbytheuseofspecialglasscontainers.
Likeamberglassisusedinplaceofflintglassastheamberglasshaspropertyof
shuttingoutcertainportionsoflightspectrum(until470mµ)whiletheflintglasshas
disadvantageofbeingtotransparenttolightraysabove300mµ.

21. References:
•IndianPharmacopoeia2007VolI,6.Containers,6.2.Containersfor
pharmaceuticalProduct,
•IndianPharmacopoeia2010VolI,6.Containers,6.2.Containersfor
pharmaceuticalproduct(pg.683-691),
•Lachman/Lieberman’sTheTheoryandPracticeofIndustrialPharmacy,4
th
edition,CBSPublishers&DistributorsPvt.Ltd.,PackagingMaterialScience
(pg.1006,1013-1015)

22. Thank you!!