container-n-closure-

1. PACKAGING MATERIALS SCIENCES
PRESENTED BY: Mariyambibi Mandarawala
1

2. TABLE OF CONTENTS
 INTRODUCTION
 QUALITIES OF ANIDEAL CONTAINER
 SELECTION OF PACKAGINGMATERIAL
 CONTAINERS
 FACTORS INFLUENCING THE CHOICE OF PACKAGE
 PACKAGINGMATERIALS
2
•GLASS CONTAINERS
•PLASTICS
•DRUGPLASTIC
CONSIDERATIONS
 FIBROUSMATERIALS
 FILMS FOILS ANDLAMINATES
 TAMPER RESISTANT PACKAGING
•METALS
•CLOSURES
•CLOSURE LINERS
•RUBBERS

3.  QUALITY ASSURANCE ASPECTS OF PACKAGING
 SAMPLING AND TESTING OF PACKAGING MATERIALS
 PACKAGE VALIDATION
 QUALIFICATION &QUALITY CONTROL OF PACKAGING COMPONENTS
 PACKAGE INSPECTION
 PHARMACEUTICAL PACKAGE TESTING/TRANSPORT
PACKAGING TESTING
 FLEXIBLE PACKAGING
 SUMMARYOF ICH GUIDELINES ONSTABILITY ANDPOSSIBLE
INFLUENCE ONTHE PACK
3
 QUALITY CONTROL TESTS FOR
•GLASS
•PLASTICS
•CLOSURES
•COLLAPSIBLE
TUBES
•METALLIC TINS
•STRIPS AND
BLISTERS
•CARTONS
•PAPER AND BOARD

4. INTRODUCTION
 Packagingis theprocessbywhichthepharmaceuticalsare
suitablyplacedsothattheyshouldretaintheirtherapeutic
effectivenessfromthetimeoftheirpackagingtill theyare
consumed.
 Definition:
“Packing is theartandsciencewhichinvolvespreparingthe
articlesfortransport,storage,displayanduse.”
 Pharmaceuticalpackagingisthemeansofprovidingprotection,
presentation,identification,informationandconvenienceto
encouragecompliancewithacourseoftherapy.
 Compositionof package:
(a) Container
(b) Closure
(c) CartonorOuter
(d)Box 4

5. Theidealcontainerorpackageshould:
1.Protectthecontentsfromthefollowingenvironmental
hazards:
Light- protectthecontentsfromlight
Temperature- becapableofwithstandingextremesof
temperature.
Moisture- becapableofwithstandingextremesofhumidity.
Atmospheric gases- protectthecontentsfromtheeffectof
atmosphericgases(e.g.aerialoxidation).
Particles- protectfromparticulatecontamination.
Microorganisms- protectfrommicrobialcontamination.
5

6. 2.Protectsthecontentfromthefollowingmechanicalhazards
 Vibration- Usuallyduetotransportation
 Compression- thisusuallyincludespressureappliedduringstacking.
 Shock- suchasimpact,dropsorrapidretardation.
 Puncture- penetrationfromsharpobjectsorduringhandling
operations.
 Abrasion- thismaycreateelectrostaticeffects.
3.Theymustnotaddorpermitlosstoitscontents:
 Protectthecontentsfrombothlossandgainofwater.
 Protectthecontentsfromlossofvolatilem
aterials
 Mustnotshedparticlesintothecontents.
 Mustnotleachanythingtothecontents.
6

7. 4.Musthaveapharmaceuticallyelegantappearance:
Inacompetitivemarkettheappearanceofapackagefirst
drawstheattractionoftheconsumersthanitscontents.
Mustbeeasytolabelandthustoidentifytheproduct.
5. Mustbeconvenientandeasytousebythepatient.
6. Mustbecheapandeconomical.
7. Mustnotreactwiththecontent.
8. Mustbebiodegradable.
7

8. SELECTIONOF PACKAGING MATERIAL
 Thematerialsselectedforpackagingmusthavethefollowing
characteristics:
 Theymustprotectthepreparationfromenvironmentalconditions.
 Theymustnotbereactivewiththeproduct,
 Theymustnotimparttastesorodorstotheproducts,
 Theymustbenon-toxic,
 TheymustbeFDA (Food&DrugAdministration)approved,
 Theymustmeetapplicabletamper-resistancerequirements
 Theymustbeadaptabletocommonlyemployedhigh-speed
packagingequipment. and
 Theymusthavereasonablecostinrelationtothecostofthe
product.
8

9. Categoricallydifferentiatingpharmaceutical packaging:
• Primary Packaging: This is the first packaging envelope
which is in touch with the dosage form or equipment (i.e.
bottle, cap, cap liner, label etc). The packaging needs to be
such that there is no interaction with the drug and will
providepropercontainm
entofpharmaceuticals.
E.g.Blister packages,Strippackages,etc.
9

12. •Secondary Packaging: This is consecutive covering or
package which stores pharmaceuticals packages in it for their
grouping.
E.g.Cartons,boxes, etc. OR
•Thepackagingexternaltotheprimarypackageis knownasthe
secondarypackaging.
•Tertiary packaging: This is to provide bulk handling and
shippingofpharmaceuticalsfromoneplacetoanother.
E.g.Containers,barrels, etc. 10

13. FACTORS INFLUENCING THE CHOICE OF PACKAGE:
 Theproduct:
Thephysicalandchemicalcharacteristicsofthedrugentity,the
excipients,theformulation,route of deterioration of theproduct,
typeofpatient(baby,child,teenager,adult,elderly,infantsetc)must
beconsideredwhiledealingwiththepharmaceuticalproduct.Apart
fromtheproperties of drug,packagestyletoattract patient and
otherlegal requirementsshouldalsobeconsideredduringselection.
 Themarket:
Thechannelofsaleshouldbeconsidered,i.e.where,when,howand
bywhomitistobeusedoradministered(e.g.doctor,dentist,nurse,
patientsetc),whetherfor hometrade and/orexport. The quantity
perpackageandfollowupsalemustall becarefullyconsidered
duringpackagedesignandselection. 17

14. Thedistributionsystem:
Thedistributionsystemshouldbecarefully monitored,e.g.
conventionalwholesale/retailoutletordirectorselective
outlets.Lesssophisticatedtransportsystemslikemules,
donkeys,camelsetcrequiresadditionalprotectionif
intermediatestoragefacilitiesarenonexistent.
Manufacturingfacilities:
Thestabilityofthemanufacturingfacilitiesshouldbe
consideredduetonewpackage,increasedsale,improvements
inGoodManufacturingPractice,revisedproduct,new
productetc. 18

15.  PACKAGINGMATERIALS
Thefollowingmaterialsareusedfortheconstructionofcontainersandclosures
Borosilicateglass
Treatedsodalimeglass
Regularsoda-limeglass
General purposesodalimeglass
1.Glass: - (i) Type-I
(ii)Type-II
(iii)Type-III
(iv)Type-NP
(v)Colouredglass
(ii) Urea
(iv) Lead.
(i) Phenolics
(i)Polyethylene
(iii)Polyvinylchloride(PVC)
(v)Polycarbonate
(vii)Polyethyleneterephthalate
2. Metals:(i) Tin (ii) Iron (iii) Aluminium
3.Plastics: (a)Thermosettingresins:
(b)Thermoplastic resins:
(ii)Polypropylene
(iv) Polystyrene
(vi)Polyamide(Nylon)
(PET)
4.Rubber: (i) Naturalrubber (ii)Neoprenerubber (iii)Butylrubber.
19

16. GLASS CONTAINERS:
Glassis thepreferredpackagingmaterial.
COMPOSITIONOF GLASS
 Sand(silicondioxide)Sodaash(sodiumcarbonate)
Limestone(calciumcarbonate)Cullet(brokenglass)-
aluminium,boron,potassium,magnesium,zinc,barium,
Amber:lightyellowishtodeepreddishbrown,carbonand
sulphurorironandmanganesedioxide
Yellow: Compoundsofcadmiumandsulphur
Blue: Variousshadesofblue,cobaltoxideoroccasionally
copper(cupric) oxide
Green:ironoxide, manganesedioxideandchromiumdioxid2
e
0

17.  ADVANTAGES
• Theyarehygienicandsuitableforsterilization
• Theyarerelativelynonreactive( dependingonthegradechosen)
• Itcanacceptavarietyofclosures
• Theycanbeusedonhighspeedpackaginglines
• Theyaretransparent.
• Theyhavegoodprotectionpower.
• Theycanbeeasily labeled.
 DISADVANTAGES
• Itisrelativelyheavy
• Glassisfragilesoeasilybroken.
• Releasealkali toaqueouspreparation
22

18. TypeI glass:
Composition: Neutralglass, borosilicate glass (silica (silicon dioxide, SiO2) andboron
oxide).
Advantages:
 Itpossessesahighhydrolyticresistance.
 Itisthemostinerttypeofpharmaceutical glass.
 Ithasthelowestcoefficientof thermalexpansion(and hencesuitable for sterilizationby
heat…..forampoulesandvials).
Disadvantages:
 It hasveryhighglasstransitiontemperaturesoneedscomplicatedprocessing.
 Andthereforeexpensive.
Uses:
 TypeI glassissuitableforpackingall pharmaceutical preparations.
 It is widelyusedasglassampoulesandvialstopackagefluidsforinjection.

19. TypeII glass
Composition:soda-lime-silicaglass.
Soda (Na2CO3) is used to decrease the glass transition temperature of silica.
However, soda would increase water solubility of silica, so lime (CaO) is used to
increasethehydrolyticresistance.Thistypewouldalsocontainotheroxides.
Advantages:
 This glass hasalowermeltingpointthanTypeI glass. It is thuseasier to produce
andconsequentlycheaper.
 Highhydrolyticresistanceduetosurfacetreatmentoftheglass.
Uses:
 TypeII glassusedtopackageaqueouspreparations.
 However,asitcontainsbasic oxides,it is notusedtopackageparenteral formulations
withapH<7 (i.e.acidic);thiswouldincreasethepHoftheformulation andcouldaffect
thedrugstabilityandpotency.
 It is theglass used to produce containers for eye preparations and other dropper
bottles. 24

20. Type-III regular sodalimeglass
 Containersareuntreatedaremadeofcommercialsodalimeglassof
averagearebetterthanaveragechem
ical resistance.
 Itcontainshighconcentrationofalkalineoxidesandimpartsalkalinityto
aqueoussubstances.
 Uses:
 For all soliddosageforms.
 For oilyinjections.
TypeNP-general purposesodalimeglass
 Containersaremadeofsodalimeglasssuppliedfornonparentalproducts,
intendedfororal or topicaluse.
 Uses:
 For oral use.
 Topical purpose.
25

21. PLASTICS
AccordingtoBritishstandardsinstitutesplasticsrepresents;
“ Awiderangeofsolidcompositematerials whichare
largelyorganic,usuallybaseduponsyntheticresinsor
uponmodifiedpolymersofnaturaloriginandpossessing
appreciablemechanicalstrength.
Atasuitablestagein theirmanufacturing,mostplastics
canbecast,moldedorpolymerizeddirectlyintoshape”.
26

22.  Classesof plastics:
Therearetwoclassesofplastics,reflectingthebehaviorwithrespectto
individualorrepeatedexposuretoheatingandcooling.
 Thermoplastics
 Capableofbeingshapedafterinitialheatingandsolidifyingbycooling.
 Resistant to breakage and cheap to produce and providing the right
plastics are chosen will provide thenecessary protection of theproduct
inanattractivecontainers.
 E.g.Polystyrene,polyethyleneandpolyvinyl chloride.
 Thermosets
 They need heat for processing intoa permanent shape. During heating
such materials form permanent crosslinks between the linear chains,
resultinginsolidification andlossofplasticflow.
 E.g. Phenolic,ureaandmelaminearerepresentativeofthermosets.
27

23.  USES
Used for many types of pack including; rigid bottles for tablets and capsules,
squeezablebottlesfor eyedropsandnasalsprays, jars, flexible tubesandstrip
andblisterpacks.
 ADVANTAGES
• Leastexpensivethanglasses
• Easeoftransportation
• Noriskofbreakage
• Flexible
• Lightinweight
 DISADVANTAGES
• TheyarenotaschemicallyinertasType-I glass.
• Theyarenotasimpermeabletogasandvapourasglass.
• Theymaypossessanelectrostaticchargewhichwillattractparticles.
28

24. TYPES OF PLASTICS
 POLYETHYLENE
 Thisis usedashighandlowdensitypolyethylene
 Low density polyethylene (LDPE) is preferred plastic for
squeezebottles.
Properties: Ease of processing , barrier to moisture, strength
/toughness,flexibility, easeofsealing.
 Highdensitypolyethylene(HDPE) is lesspermeabletogases
andmoreresistanttooils, chemicalsandsolvents.
Properties:Stiffness,strength/toughness,resistance tochemicals.
Itis widelyusedinbottlesforsoliddosageforms.
Drawback: pronetostress cracking in thepresenceof surfactant2
s9
orvegetableormineral oils.

25.  POLYPROPYLENE
 Ithasgoodresistancetocrackingwhenflexed.
 Goodresistancetoheatsterilization.
 It is colorless,odorlessthermoplasticmaterialwithexcellenttensilepropertiesevenat
hightem
perature.
 Excellent resistancetostrongacidsandalkalis.
 Lowpermeabilitytowatervapour
 Permeability togases is intermediate between polyethylene HD and un-plasticized
PVC
 Suitableforuseinclosures, tabletcontainersandintravenousbottles.
 POLYSTYRENE
 Versatility,insulation,clarity,easilyfoamed(“Styrofoam”).
 It isalsousedforjarsforointmentsandcreamswithlowwatercontent.
 Drawback:Chemicals likeisopropylmyristateproducecrazing(afinenetwo3
r0
kofsurface
cracks)followedbyweakeningandeventuallycollapsibleofthecontainer.

26.  POLYVINYL CHLORIDE
 Versatility,easeofblending, strength/toughness, resistancetogrease/oil, resistanceto
chemicals,clarity.
 Usedasrigidpackagingmaterialandmaincomponentofintravenousbags.
 Drawback: Poor impact resistance which can be improved by adding elastomers to
theplasticsbutitwillincreaseitspermeability.
 POLY VINYLEDENE CHLORIDE:
• Excellentbarrierpropertiesagainst:moisture,watervapour,UVlight,aroma, inorganic
acids, alkalies, aqueous salt solutions, organic water soluble acids, aliphatic
hydrocarbons , esters of long chain fatty acids, detergentbase materials, em
ulsifying
agentsandwettingagents.
• Goodthermoformability.
• PVDC is very cost-effective, as coating weight can be customized depending on the
requirementsofthebarrierproperties.
• Medical gradeandnon-toxic.
• Highlevelsoftransparencywhichimprovestheaestheticsoftheproduct.
31

27.  DRUG-PLASTIC CONSIDERATIONS
 Apackagingsystemmustprotectthedrugwithout
alteringthecompositionoftheproductuntil thelast
doseisremoved.
 Drug-plasticconsiderationshavebeendividedintofive
categories:
1. Permeation
2. Leaching
3. Sorption
4. Chemical reaction
5. Alteration
32

28.  Permeation:
• Itis thetransmissionofgases,vaporsorliquidsthroughplastic
packagingmaterial.
• Permeation of watervapor andoxygenthrough plasticwallintothe
drugis amajorproblemis thedosageformis sensitivetohydrolysisand
oxidation.
• Thevolatile ingredientsmightchangewhenstoredin plastic containers
andthetasteofthemedicinalproductsmaychangeforthesamereason
ofpermeation.
 Leaching:
• Someplasticcontainershaveoneormoreingredientsaddedtostabilize
it, thesemayleachintothedrugproduct.
• Problemsmayarisewithplasticswhencoloringagentsareaddedin
smallquantitiestotheformula.
• Particulardyesmaymigrateintotheparentalsolutionandcauseatoxic
effect.
33

29.  Sorption:
• Thisprocessinvolvestheremovableofconstituentsfromthedrugproductbythe
packagingmaterial.
• Thetherapeuticefficacyoftheproductmaybereducedduetosorption.
• Sorptionmaychangethechemicalstructure,pH,solventsystem,concentrationof
activeingredientsandtemperatureetc…
 Chemical reactivity:
• Certainingredientsinplasticformulationsmayreactchemicallywithoneormore
componentsofthedrugproduct.
• Eveninmicroquantitiesif incompatibilityoccursmayaltertheappearanceofthe
plasticorthedrugproduct.
 Modification:
• Thephysicalandchemicalalterationofthepackagingmaterialbythedrugproductis
calledmodification.
• Somesolventsystemsfoundtobeconsiderablechangesinthemechanicalpropertiesof
theplastics.
• For exampleoilshaveasofteningeffectonpolyethylene,hydrocarbonsattack
polyethyleneandPVC.
34

30. METALS
 Metal containers are used solely for medicinal products for non-
parenteraladministration.
 Metal is strong, opaque, impermeable to moisture, gases, odors,
light, bacteria, and shatterproof, it is the ideal packaging material
forpressurizedcontainers.
 Itis resistanttohighandlowtemperatures
 They include tubes, packs made from foil or blisters, cans,
and aerosol andgascylinders.
 Aluminium and stainless steel are the metals of choice for
both primaryandsecondarypackagingformedicinalproducts.
 Formanexcellenttamperevidentcontainers.
35

31.  ALUMINIUM
• Itis relativelylightyetstrong
• Barrier tolightandchemicals
• Impermeableandeasytoworkinto avariety offormats,dependingon
itsthickness.
• Thickest aluminium is used for rigid containers such as aerosol cans
andtubesforeffervescenttablets.
• Intermediatethickness are whenmechanical integrity is still important
butthepack should becapable of being reformed under areasonable
force.
e.g. Collapsible tubes for semi solid preparations or roll on screw
caps.
• Thinnest aluminium is used in flexible foil that are usuall3
y6 a
componentoflaminatedpackagingmaterial.

32.  Disadvantagesandtheirovercomesolution
• Major disadvantage is its reactivity in raw state, although it
rapidly forms a protective film of aluminium oxide it is still
liable to corrosion ( when exposed to some liquids and semi
solid formulations, particularly at extreme pH or if the product
containselectrolytes.
 To overcome this problem, Aluminium is lined with epoxide,
vinyl orphenolic
 resins.
• They are work hardening like collapsible tubes are made by
impactextrusionwhichtendstomakealuminiumlessflexible.
 To overcome, flexibility has to restored by an annealing
stage. 37

33.  TIN
 Advantages:
• Thismetal is veryresistanttochemicalattack.
• Readilycoatsanumberofthemetalse.g.tin-coatedleadtubes
combinethesoftnessofleadwiththeinertnessoftinandforthis
reasonitwasformerlyusedforpackagingfluoridetoothpaste.
 Disadvantages:
Tinis themostexpensivemetalamongtin,lead,aluminiumandiron.
 Uses:
• Tincontainersarepreferredforfoods,likemilkpowdercontainers
arecoatedwithtin.
• Currently,someeyeointment still packagedinpuretinointment
tubes. 38

34.  IRON
 Advantages:
Ironassuchisnotusedforpharmaceuticalpackaging,large
qualitiesoftin-coatedsteel,popularly called‘tin’, combinesthe
strengthofsteelwiththecorrosionresistanceoftin.
 Disadvantages:
If anaqueousliquid canpenetrateapinholeorotherfaultinthe
layeroftin,whichisvirtuallyashort-circuited galvanic cellis
setupandtheintensechemicalreactionwhich resultsbrings
aboutrapidcorrosionofunderlyingsteel.Asafurther measure
thetinsurfaceis lacquered.
 Uses:
Fabricationofmilkcontainers,screwcapsandaerosolcans. 39

35.  LEAD
 Advantages:
• Lowestcostofall them
etalsusedinpharmaceutical containers.
• Softm
etal.
 Disadvantages:
Leadwhentakeninternallythereisriskofleadpoisoning.So
leadcontainersandtubesshouldalwayshaveinternalliningof
inertmetalorpolymer.
 Uses:
Withliningleadtubesareusedforsuchproductasfluoride
toothpaste.
35

36. CLOSURES:
 Aclosureis thepartofthepackagewhichpreventthecontents
fromescaping andallownosubstancetoenterthecontainer.
 Closuresareavailableinfivebasicdesigns:
1. Screwon,threadedorlug
2. Crimpon(crowns)
3. Presson(snap)
4. Roll on and
5. Friction
36

37.  Threadedscrewcap:
 Whenascrewcapis applied,itsthreadsengagedwiththe
correspondingthreadsmoldedontheneckofthebottle.
 Aliner in thecap,pressedagainsttheopeningofthecontainer,
seals theproductin thecontainerandprovide theresistance to
chemicalandphysicalreactionwiththeproduct.
 Thescrewcapis commonlymadeofmetalorplastics.Themetalis
usuallytinplateoraluminumandinplasticisthermoplasticand
thermosettingmaterial.
37

38. Lugcap:
 Thelugcapis similartothethreadedscrewcapandoperates
onthesameprinciple.
 It is simplyaninterruptedthreadontheglassfinish,insteadof
acontinuousthread.
 Unlikethethreadedclosure,itrequiresonly aquarterturn.
 Thelugcapis usedforbothnormalatmospherepressureand
vacuumpressureclosing.
38

39.  Crowncaps:
 Thisstylecapis commonlyusedasacrimpedclosureforbeverage
bottles.
 Roll-onclosures
 Thealuminumroll oncapcanbesealsecurely,openedeasilyand
resealedeffectively.
 Resealable,nonresalableandpilferprooftypesofroll onclosures
areavailableforuseonglassorplasticbottles.
39

40.  Pilfer proof closures
 Itis similartoroll onclosurebuthasagreaterskirtlength.
 Thisadditionallengthextendsbelowthethreadedportion
andfastenedtothebasiccapbytheseriesofnarrow
bridges.
 Whentheclosureis removedtheextraportionremainsinthe
space onneck of thecontainer,thisindicatesthatthe
packagehasbeenopened.
40

41.  CLOSURE LINERS:
 Alinermaybedefinedasanymaterialthatinsertedinacaptoeffectaseal
betweentheclosureandthecontainer.
 Itis oftwotypes:
1. Homogeneousliner
 Theseareonepiecelinersavailableasdiskoraringofrubberorplastic.
 Itcanbewithstandhightemperaturesterilization.
2. Heterogeneousliners
 Thesearecomposedoflayersofdifferentmaterialschosenforspecific
requirements.
 Itconsistsoffacingandbacking.Facingisincontactwithproductand
backingprovidesquestioningeffect.
41

42.  Factorsinselectingaliner:
• Chemicalinertness shouldbechemicallyinert
• Appearance,thicknessetc.
• Gasandwater-vapourtransmissionrates shouldbelow.
• Torquerequiretoremovethecap shouldbeoptimum.
• heatresistance e.g.duringautoclavingshouldbe
thermostable.
• Shelf-life shouldnotchangetheirshapeduringstorage.
• Economics shouldbecheap.
42

43. RUBBERS (Elastomers):
• Excellent material for forming seals, used to form closures such as
bungs for vials or in similar applications such as gaskets in aerosol
cans.
 Categoriesof Rubbers:
1) Natural rubbers;
• Suitable for multiple use closures for injectable products as rubber
resealsafter multipleinsertionofneedle.
• Disadvantagesare;
i. It doesn't well toleratemultiple autoclaving becomingbrittle and
leads to relative degree of extractable material in presence of
additives.
ii. Riskofproductabsorbingonorintoarubber.
iii. It hascertaindegreeofmoisture&gaspermeation.
48

44. 2) Synthetic rubber:
• Have fewer additives and thus fewer extractable and tends to
experiencelesssorptionofproductingredients.
• Are less suitable for repeated insertions of needle because they
tend to fragment or core pushing small particles of the rubber
intotheproduct.
• E.g.Silicone,butyl,bromobutyl,chlorobutyletc.
• Silicone is least reactive but it does experience permeability to
moistureandgas.
 Softer rubbers experience less coring and reseal better, harder
rubbersareeasiertoprocessonhighspeedpackaginglines.
49

45. TYPES OF RUBBER
1.BUTYL RUBBER
Thesearecopolymersofisobutylenewith1-3%ofisopreneorbutadiene.
 Advantages:-
• Aftervulcanization butylrubberpossessesvirtuallynodoublebond,consequentlytheyaremost
resistanttoagingandchemical attack.
• Permeability towatervapourandair is verylow.
• W
ater absorptionis verylow.
• Theyarerelatively cheapercomparedtoothersyntheticrubbers.
 Disadvantages
• Slowdecompositiontakesplaceabove1300C.
• Oil andsolventresistanceis notverygood.
2.NITRILE RUBBER
 Advantages:
• Oil resistantduetopolar nitrilegroup.
• Heatresistant.
 Disadvantage
• Absorptionofbactericide andleachingofextractives areconsiderable.
50

46. 3.CHLOROPRENE RUBBERS (NEOPRENE)
Thesearepolymers of1:4chloprene.
 Advantages
• DuetothepresenceofCl group closetothedouble bondsothebondisresistant
tooxidationhencetheserubbersagewell.
• Thisrubberis morepolarhenceoil resistant.
• Heatstabilityis good(upto1500C).
• Waterabsorptionandpermeabilityarelessthanfornaturalrubbers.
4.SILICONE RUBBERS
 Advantages
• Heatresistance(upto2500C).
• Extremelylowabsorptionandpermeabilityofwater.
• Excellentagingcharacteristicsduetotheirsaturatedchemicalstructures.
• Poor tensilestrength.
 Disadvantages
• Theyareveryexpensive.
51

47.  FIBROUS MATERIAL
 Thefibrousmaterialsaretheimportantpartofpharmaceuticalpackaging.
 Fibrousmaterialsinclude:Papers,Labels,Cartons,Bags,Outers, TraysForShrink
Wraps,LayerBoardsOnPallets, etc.
 TheApplicationsaswell asAdvantagesofCartonsinclude:
 Increasesdisplayarea
 Providesbetterstackingfordisplayofstockitems
 Assemblesleaflets
 Providesphysicalprotectionespeciallytoitemslike metalcollapsibletubes.
 Fiberboardouterseitherassolidor corrugatedboardalsofindsubstantial
applicationfor bulkshipments.
 Regeneratedcellulose film, tradenamesCellophane&Rayophane,is usedfor
eitherindividual cartonsortoassembleano.ofcartons.
47

48.  FILMS FOILS AND LAMINATES
• Regenerated cellulose film based on viscose ( chemical used for
manufacturingofrayon) & laminatingtwoor moretypesoffilms, cellulose
coatings, foil and paper play diff roles such as supportive, barrier, heat
seal&decorative.
• For Exam
ple:
Aluminumfoil evenin thethinnestgaugesoffersthebestbarrier properties,
whicharenotapproachedevenbythemostimpermeableplastics.
• “Metallization”: A relatively new process whereby particles of metal are
laid down onto a surface under vacuum, can significantly improve the
barrier propertiesofamaterialbutthesedonotapproach thepropertiesof
apurefoil.
• In the newer technology “Co-Extrusion”, a number of plastic plies are
extrudedincombinationtoproducecheaperlaminations.
48

49. • Usesoffilms, foils, laminations:
 Strippacks
 Blisterpacks
 Sachets
 Diaphragmsealsfor bottles
 Linersforboxeseitherattachedorloosebag-in-boxsystems&bags.
 Foil blisters:
When sealed with a metal foil-cover, the blister can provide a hermetic pack i.e. an isolated
system, which excludes any exchange of gases between the product & surrounding
atmosphere.
 Alu-alu foil is thebestpharmaceuticalpackagingfilmfortablets,capsules,whichis taking
placeofPVC film.
⚫ Applicabletotablets,capsules,pills, etc.
⚫ It'sagoodsubstituteforPVC sheet.
⚫ Nocracking,delaminationorpinholes
⚫ It hasthe quite good blocking properties effectively protecting drugs from water vapor,
oxygenandultraviolet.
⚫ It is particularly suitableforpackingmoisture-sensitive drugsorthosesoldin thehotand
humidareas.
54

50.  TAMPER RESISTANT PACKAGING:
 Therequirementfortamperresistantpackagingis nowoneofthe
majorconsiderationsinthedevelopmentofpackagingfor
pharmaceutical products.
 Atamperresistantpackageisprovidedwithanindicatoror
barrierbeforeenteringthepackage, sothatif thisindicatoror
barrier is broken,thebuyerimmediatelygetstheevidencethat
theproducthasbeenopenedortampered.
 Especiallyoverthecounterproductsrequiretamperresistant
packaging.
50

51. ThefollowingpackagesareapprovedbyFDAas
tamperresistantpackagingsystems:
Film wrappers
Blisterpackage
Strippackage
Bubblepack
Shrinksealsandbands
Foils, paperorplasticpouches
51
Bottleseals
Tapeseals
Breakablecaps
Sealedtubes
Aerosol containers
Sealedcartons.

52.  Filmwrappers
 Atransparentfilmwithdistinctivedesigniswrappedsecurelyaroundthe
entireproductcontainer.Thefilmmustbecutortorntoremovetheproduct.
Thewrappermusthaveanidentifyingcharacteristic(e.g.apattern,name,
registeredtrademark,logo,orpicture)thatcannotbereadilyduplicated.
Tintedwrappersarenotacceptable as anidentifyingcharacteristicbecause
ofthepossibilitythattheirmaterialmaybeavailabletothepublic.A
reasonablytight"fit"ofthefilmaroundthecontainermustbeachieved,e.g.
byaheatshrinktypeprocess.
 Sealingofafilmwrapperwithoverlappingendflaps
is acceptable only if theendscannotbeopenedand
resealedwithoutleavingvisibleevidenceoftampering.
Theuseofcellophanewithoverlappingendflapsisnot
acceptablebecauseofthepossibilitythattheendscan
beopenedandresealedwithoutleavingvisible evidence
thattam
peringhasoccurred. 57

53.  Althoughfilmcanbeaccomplishedinseveralwaysandvariesin
configurationfrompackagingequipmenttopackagingequipment,it
canbegenerallycategorizedintofollowingtypes:
 Fin sealwrapper
 End-foldedwrapper
 Shrinkwrapper
 Finseal wrapper:
Thesesealsareformedbycrimpingthefilmtogetherandsealing
togetherthetwoinsidesurfacesof thefilm,producing a“fin” seal.
Theoverwrapcanberemovedoropenedonlybytearingthewrapper.
Materials:PolyethyleneorSurlyn(DuPont’sIonomerresin)
58

54.  End-foldedwrapper:Thiswrapperisformedbypushing theproduct into
sheetofoverlappingfilm,whichformsthefilmaroundtheproductandfoldthe
edgesingiftwrapfashion.Filmusedmustbeheat-sealable onbothsurfaces.
Tobetamper-resistant,theoverwrapmustbewellsealedmustbeprintedor
uniquelydecoratedtoexcludethepossibilityofhavinganalternateoverwrap
substitutedinitsplace.Theprintedsurfaceofthecarton being wrappedmay
alsobecoatedwithheatsensitivevarnish,whichcausesoverwraptobond
permanentlytothepaperboard carton duringsealingof overwrap. The
removal oftheoverwrapwoulddefacethecarton, makingthecarton
unsuitableforreuse.
Materials:
•Cellophanecoatedinbothsidebyheatsealable
polyvinylidenechloride(PDVC) ornitrocellulose-PDVC
providesdurablemoisturebarrier.
•Polypropylenecoatedwithheatsealableacrylic coating
orpolypropyleneis addedwithheatsealablemodifiers.
59

55.  Shrinkwrapper: Theshrinkwrapconceptinvolvesthepackaging
ofaproductinthermoplasticfilmthathasbeenstretchedand
orientedduringitsmanufactureandthathasthepropertyof
revertingback toitsunstretcheddimensions as thefilmunwinds
ontheoverwrappingmachine,apocketis formedinthefoldofthe
sheet,intowhichtheproductis inserted.AnL shapedsealerseals
theremainderof overwrapandtrimsoff theexcessfilm.The
looselywrappedproductisthenmovedthrough heatedtunnel
whichshrinkstheoverwrapintoatightlywrappedunit.
Materials:Heatshrinkablegradesofpolypropylene,polyethylene
andpolyvinylchloride(PVC).
60

56.  Blister or strippacks:
 It is apackaging configuration capable of providing excellent environmental
protection,coupledwithanestheticallypleasinganefficacious appearance.it
alsoprovides user functionalityin terms of convenience, child resistance, and
nowtemperresistance.
 Theblisterpackageisformedbyheat-softeningasheetofthermoplastic resin
andvacuumdrawingthesoftenedsheetofplasticintoacontouredmold.After
cooling,thesheetisreleasedfromthemoldandproceeds tothefillingstation
ofthepackaging machine. The semi-rigidblisterpreviouslyformedisfilled
withproductandliddedwithaheat-sealablebackingmaterial.Thebacking
material,orlidding,canbeofeitherapushthroughorpeelabletype.
Dosageunits(forexample,capsulesortablets)are
individuallysealedinplasticorfoil.Theindividual
compartmentmustbetornor brokentoobtainthe
product.Thebackingmaterialscannotbereadily
separatedfromtheblistersoreasily replacedwithout
leavingevidenceoftampering.
61

57.  Strippackage
 Astrippackageis aformofunitdosepackagingoftabletor
capsules.Astrippackageisformedbyfeedingtwowebsofheat
sealableflexiblefilmthrougheitheraheatedcrimpingrollerora
heatedreciprocatingplaten.Theproductisdroppedinto the
pocketformedpriortoformingthefinalsetofseals.Sincethe
sealingisusuallyaccomplishedbetweenpressurerollers,ahigh
degreeofseal integrityis possible.
57

58.  Bubblepacks
 Thebubblepackcan bemadeinseveralwaysbutisusually
formedbysandwichingtheproductbetweenathermoformable,
extensible,orheat-shrinkableplasticfilmandarigidbacking
material,thisis passedthroughaheatedtunnel,whichshrinksthe
filmintobubbleorskinovertheproduct,firmlyattachingittothe
backingcard.
 Theproductandcontaineraresealed inplasticandmountedinor
onadisplaycard.Theplasticmustbetornorbrokentoremovethe
product.The backing material cannotbereadilyseparated from
thebubble oreasilyreplaced withoutleaving evidence of
tampering
58

59.  Heatshrinkbandsor w
rappers
 Theshrinkbandconceptmakesuseoftheheat-shrinkingcharacteristicofa
stretchorientedpolymerusuallyPVC. Thepolymerismanufacturedasan
extruded,orientedtubeinadiameterslightlylargerthanthecap andneck
ringofthebottletobesealed.Bandsorwrapperswithadistinctivedesign
(e.g.,apattern,name,registeredtrademark,logo,orpicture)areshrunkby
heattosealtheunionofthecapandcontainer.Thesealmustbecutortorn
torem
ovetheproduct.
 Thebandorwrappercannoteasily beworkedoffandreappliedwithout
visibledamagetotheband.Useofaperforatedtearstripcanenhance
tamperevidence.Cellulosewetshrinksealsarenotacceptableasthe
knowledgeofhowtoremoveandreapplythesesealswithoutevidenceof
tam
peringis widespread.
59

60.  Foil, paper,orplasticpouches
 Theflexiblepouchispackagingconceptcapableofprovidingnotonlya
packagethatistamperresistant,butalso,bytheproperselectionof
material,apackagewithahighdegreeofenvironmentalprotection.A
flexiblepouchisusuallyformedduringtheproductfillingoperationby
eithervertical orhorizontalforming,filling,sealing(f/f/s) equipment.
 Theproductisenclosedinanindividualpouchthatmustbetornor
brokentoobtain theproduct. Thepouchshouldhaveadistinctive
design(e.g.,apattern, name,registeredtrademark,logo,or
picture).Theendsealsofthepouchescannotbeseparatedandresealed
withoutshowingvisibleevidenceofentry.
60

61.  Bottlemouthinner seals
 Abottlemaybemadetamper-resistantbybondinganinnersealtotherimofthe
bottleinsuchawaythataccesstotheproductcanonlybeattainedbyirreparable
destroyingtheseal.
 Variousinnersealcompositionsmaybeusedlike:
• Glassineandfoillaminations.
• Gluem
ounted.
• Pressuresensitiveadhesive.
• Heatsensitiveadhesive.
 Paper,thermalplastic,polystyrenefoam(exceptthoseappliedwithpressure
sensitiveadhesive),plasticfilm,foil,orcombinationsthereof,withadistinctive
design(e.g.,apattern,name,registeredtrademark,logoorpicture)is sealedtothe
mouthofacontainerunderthecap.Thesealmustbetornorbrokentoopenthe
containerandremovetheproduct.Sealsappliedbyheatinductiontocontainers
appeartoofferahigherdegreeoftamperevidencethanthosethatdependonan
adhesivetocreatethebond.
 Tomeettamper-resistantcriteria,theinnersealmustbeprintedordecoratedwith
uniquedesign.Thesealmustalsobebondedsufficientlytoensurethatitsremoval
wouldresultindestructionoftheseal. 66

62.  Tapeseals
 Tapeinvolvestheapplicationofagluedorpressuresensitivetape
orlabelaroundorovertheclosureofthepackage,whichmustbe
destroyedtogainaccesstothepackagedproduct.Thepaperused
mostoftenishighdensitylightweightpaperswithpoor tear
strength.
 Paperorfoilwithadistinctive design issealed over allcarton
flapsorabottlecap.Thesealmustbetornorbrokentoremovethe
productTapesealsareacceptableonlyiftheycontainaunique
featurethatmakesitapparentifthesealshavebeenremovedand
reapplied, e.g., apermanentadhesive.
62

63.  Breakablecaps
 Breakableclosurescomeinmanydifferentdesigns.The rolloncap design
usedinthepastforcarbonatedbeveragesusesanaluminumsheet,which
placedoverbottleneckduringcapping operation. The cap blank isheld on
thebottleunderpressurewhilerollerscrimpandcontourthebottletreadinto
thecapblank.Thebottomportionof cap isrolledaroundandunderthe
lockingringonthebottleneckfinish.Thislowerportionofthecapblankis
usuallyperforatedsothatitbreaksawaywhenthecapisunscrewed,which
servesasvisiblesignofprioropening.
 Aratchet-styleplasticcapisalsocommonlyusedforanumberofdifferent
products.Inthisdesignthebottomportionofclosurehasatear-awaystrip,
whichengagesaratchetonthebottleneck.Toremovetheclosure,thebottom
portionoftheclosuremustbetornawaytodisengagetheratchet andallow
theremoval ofthecap.
63

64.  Sealedmetaltubesorplasticblind-endheatsealedtubes
 Collapsibletubesusedforpackagingareconstructedofmetal,plastic,or
laminationoffoil,paper,andplastic.Metaltubesarestillusedforthose
productsthatrequirehighdegreeofbarrierprotectionaffordedbymetal.
Punctureinserts,whichareusuallymadeofaluminum3to5milthick,are
usedtosealthetubeopeningfortamperresistance.
 Bothendsofthetubearesealed.Themouthorblind-endmustbepuncturedto
obtaintheproduct.Atubewithacrimpedendis acceptableif thecrimpedend
cannotbebreachedbyunfoldingandrefoldingwithoutshowingvisible
evidenceoftam
pering. Directprintingofthelabel onthecontainer is
preferredtousingalabelthatcouldberemovedandsubstituted.
64

65.  Cardboardcartons
 Folding paperboardcartonshavebeenusedassecondarypackage
for OTC productsfor manyyears. Seal endcartonsusesexternally
appliedglueor hotmelttoprovidecartonsealing.
 CardboardCartonsspecificallydesignedtoensurethatinorderto
obtaintheproduct,thecartonsealmustbecutormustbenon-
resealablewithoutshowingvisibleevidence of entorntoremove
theproductandmustnotbeabletobeeasilyworkedopenand
resealedwithoutobviousdamagetothecarton.
65

66.  Aerosol containers
 Theaerosolcontainerusedforpharmaceuticalproductsisusuallymadeof
drawnaluminium.Theinsideofthecontainercanbespeciallycoatedif
productcompatibilityis aproblem.
 Ahydrocarbonpropellantinitscooledliquidphaseisaddedtothecontainer
alongwiththeproduct,andaspraynozzlecontainedinagasketedmetal
ferruleiscrimpedovertheopeningoftheaerosolcontainer.Alengthof
polyethylenetube,calledadip-tube,isattachedtotheinsideof thespray
nozzleanddipsintotheproduct,drawingproductintothespraynozzlewhen
thesprayer is activated.
 Thespraynozzlesareusuallymeteredtoallowaspecificdosetobedispersed
witheachspray.
66

67. QUALITY CONTROL TESTS FOR GLASSES
1) CHEMICAL RESISTANT OF GLASS CONTAINERS
A)POWDEREDGLASS TEST: Itisdonetoestimatetheamountofalkali
leachedfromthepowderedglasswhichusuallyhappensattheelevated
temperatures.Whentheglassis powdered,leachingofalkaliis enhanced,
whichcanbetitratedwith0.02Nsulphuricacidusingmethylredasan
indicator
 Step-1:Preparationofglassspecimen:Fewcontainersarerinsed thoroughly
withpurified wateranddried withstreamof cleanair. Grind thecontainers in
amortartoafinepowderandpassthroughsieveno.20and50.
 Step-2: W
ashingthespecimen: 10gmoftheabovespecimenis takeninto250
mlconicalflaskandwashitwith30mlacetone.Repeatthewashing, decant
theacetoneanddriedafterwhichitis usedwithin48hr.
 Procedure:
10gmsampleisaddedwith50mlof high puritywaterina250mlflask.Placeit
inanautoclaveat121⁰C±2⁰Cfor30min.Coolitunderrunning water.Decant
thesolutionintoanotherflask,washagainwith15mlhigh purity waterand
againdecant.Titrateimmediatelywith0.02N sulphuricacidusingmethylr7
e2
d
asanindicator andrecordthevolume.

68.  PREPARATION OF SPECIMEN FOR POWDERED
GLASS TEST
68

69. POWDEREDGLASS TEST (AccordingtoUSP volume27)
69

70. B) W
ATER ATTACK TEST:
 Thisisonlyfortreatedsodalimeglasscontainersunderthecontrolled
humidityconditionswhichneutralizethesurfacealkaliandglasswillbecome
chem
ically moreresistant.
 Principleinvolvedis whetherthealkalileachedornotfromthesurfaceofthe
container.
 Procedure:Rinsethoroughlywithhighpuritywater.Fill eachcontainerto
90%ofitsoverflowcapacitywithwaterandisautoclavedat121⁰Cfor30min
thenitiscooledandtheliquidisdecantedwhichistitratedwith0.02N
sulphuricacidusingmethylredasanindicator.Thevolumeofsulfuricacid
consumedisthemeasureoftheamountofalkalineoxidespresentintheglass
containers.
TESTS CONTAINER VOL.OF 0.02N
H2SO4
Powdered glass test Type I
Type
II
Type
III
1.0
8.5
15.0
Water attack test Type II(100ml or
below)
Type II(above
0.07
0.02
70

71. WATER ATTACK TEST (USP)
71

72. 2)HYDROLYTIC RESISTANCE OF GLASS CONTAINERS:
 Rinse eachcontainer atleast 3timeswithCO2 free waterandfill withthesameto
their filling volume. Also fill & Cover thevials andbottles and keepin autoclave.
Heatto100⁰C for 10minandallow thesteamtoissue fromtheventcork. Rise the
tempfrom 100⁰C to121⁰C over 20min. Maintain thetempat121⁰C to122⁰C for
60min.Lowerthetempfrom121⁰Cto100Cover40minventingtopreventvacuum.
 Removethecontainerfromautoclave,coolandcombinetheliquidsbeingexamined.
Measurethevolumeoftestsolutionintoaconicalflaskandtitratewith0.01MHCl
usingmethylredasanindicator.Perform blankwithwaterandthedifference
betweenthetitrationrepresentsthevolumeofHCl consumedbythetestsolution.
Nominal capacity
of container (ml)
Number of containers
to
be used
Volume of test
solution
to be used
for
titration
(ml)
5 or less at least 10 50.0
6 to 30 at least 5 50.0
More than 30 at least 3 100.0
72

74. 3)ARSENIC TEST:
 Thistestis forglasscontainersintendedforaqueousparenterals.Wash
theinnerandoutersurfaceofcontainerwithfreshdistilledwaterfor
5min.Preptestasdescribedinthetestforhydrolyticresistanceforan
adequateno.ofsamplestoproduce50ml.pipetteout10mlsolutionfrom
combinedcontentsofallampoulestotheflask.Add10mlofHNO3to
drynessonthewaterbath,drytheresidueinanovenat130⁰Cfor
30mincool andadd10mlhydrogenmolybdatereagent.Swirlto
dissolveandheatunderwaterbathandrefluxfor25min.Cooltoroom
tempanddeterminetheabsorbanceat840nm.Dotheblankwith10ml
hydrogenmolybdate.
 Theabsorbanceofthetestsolutionshouldnotexceedtheabsorbance
obtainedbyrepeatingthedeterminationusing0.1mlofarsenic
standardsolution(10ppm)inplaceoftestsoln.
79

75. 4)THERMAL SHOCK TEST:
 Placethesamplesinuprightpositioninatray.Immersethetrayintoahot
waterforagiventimeandtransferstocoldwaterbath,tempofbothare
closelycontrolled.Examinecracksorbreaksbeforeandafterthetest.The
amountofthermalshockabottlecanwithstanddependsonitssize,design
andglassdistribution.Smallbottleswithstandatempdifferentialof60to
80⁰Cand1pintbottle30to40⁰C.Atypicaltestuses45Ctempdifference
betweenhotandcoldwater.
5)INTERNAL BURSTINGPRESSURE TEST:
 ThemostcommoninstrumentusedisAmericanglassresearchincrement
pressuretester.Thetestbottle isfilledwithwaterandplacedinsidethe
testchamber.Ascalingheadisappliedandtheinternalpressure
automaticallyraisedbyaseriesofincrementseachof which isheldfora
setoftime.Thebottlecanbecheckedtoapreselectedpressureleveland8
0
thetestcontinuesuntilthecontainerfinallybursts.

76. 6)LEAKAGE TEST:
 Drugfilledcontaineris placedinacontainerfilledwithcolouredsolution(duetothe
additionofdye)whichisathighpressurecomparedtothepressureinsidetheglass
containersothatthecolouredsolutionentersthecontainerifanycracksorany
breakageis present.
7)ANNEALING TEST:
 Thesampleisexaminedbypolarizedlightineitherapolariscopeorstrainviewer.
Thestrainpatternis comparedagainststandarddiscsorlimitsamples.
8)VERTICAL LOADTEST:
 Thebottleisplacedbetweenafixedplatform&ahydraulicrampplatformwhichis
graduallyraisedsothataverticalloadis applied.Theloadis registeredonpressure
gauge.
9)AUTOCLAVING(121C for 60min)
 Abilityofafilledoremptycontainertowithstandautoclavingmaybechecked.
81

77. QUALITY CONTROL TESTS FOR PLASTICS:
1)LEAKAGE TEST:
 Fill 10containerswithwater,fitwithintendedclosuresandkeepthem
invertedatroomtemperaturefor24hr.Thetestissaidtobepassedifthereis
nosignsofleakagefromanycontainer.
Leakagetestforplasticcontainers(non-injectables&injectables1996IP):
Fill 10plasticcontainerswithwaterandfittheclosure
Keeptheminvertedatroomtemperaturefor24hrs
Nosignofleakageshouldbetherefromanycontainer
77

78. 2)COLLAPSIBILITY TEST:
 Thistestisapplicabletothecontainerswhicharetobesqueezedfor
removingthecontents.Acontainerbycollapsing inwardduringuse,yield
atleast90%ofitsnormalcontentsattherequiredrateofflowatambient
temperature.
3)WATERPERMEABILITY TEST FOR PLASTIC CONTAINERS
(INJECTABLE PREPARATIONS IP 1996):
78

79. 4)CLARITY OF AQUEOUS EXTRACT:
 Selectunlabelled,unmarkedandnonlaminated portionsfromsuitablecontainers,
takenatrandom.Cuttheseportionsintostrips,noneof which hasatotalsurface areaof
20sq.cm.Washthestripsfreefromextraneousmatterbyshakingthemwithatleast two
separateportionsofdistilledwaterforabout30sec.Ineachcaseanddrainoffthewater
thoroughly.
 Thusprocessedsampleistakenintotheflask,previouslycleanedwithchromicacid
mixturesandrinsedwithseveralportionsofdistilledwaterandadded250mldist
water.Covertheflaskandautoclaveat121⁰Cfor30min.Carryouttheblank
determinationusing250mldistwater.Coolandexaminetheextract,itshouldbe
colourlessandfreefromturbidity.
5)TRANSPARENCY TEST:
 Standardsuspensionpreparation:1gmhydrazinesulphatein100mlwaterandset
asidefor6hr.Take25mlofthissolutionandadd25mlof10%w/vhexamineandstandfor
24hr.
 Testsolutionpreparation:Sampleispreparedby16folddilutionofthestandard
suspension.Fill 5containerscloudinessdetectablewhencomparedtowaterfilled84
containers.Absorbanceis measuredat640nmandtherangeis within0.37and0.43.

80. 6)BIOLOGICAL TESTS:
A) SystemicInjectionTest:
⚫ Testanimal –AlbinoMice
⚫ Injecteachof5miceintestgroupwithsampleorblankobservetheanimals
immediately, againafter4hr&thenat24,48,72hrs.
⚫ If noneofanimalsshowssignificantgreaterbiologicalreactivitythantheblankthe
samplemeetstherequirements.
⚫ Limit-If abnormalbehaviorsuchasConvulsionorProstrationoccursorifbodyweight
lossis greaterthan2g,thesampledoesnotmeettherequirements.
B) IntraCutaneousTest:
⚫ Testanimal- Rabbit
⚫ Examinethesitesofforanytissuereactionlike erythema,oedema,neuosisat24,48,72
hoursafterinjection.
⚫ Limit-differencebetweenthescoresofsampleandblankshouldbelesserthan1.0.
A)EyeIrritationTestOnRabbits:
 Testanimal -albinorabbits
 Limit-Sampleextractshowsnosignificantirritantresponseduringtheobservationperiod85
withblankextract.

81. QUALITY CONTROL OF CLOSURES
 PREPARATION OF SAMPLE(SOL.-A): Washclosuresin0.2%w/vofanionic
surfaceactiveagentsfor5min.Rinse5timeswithdistwaterandadd200mlwater
andis subjectedtoautoclaveat119to123⁰Cfor20to30mincoveringwith
aluminumfoil.Coolandseparatesolutionfromclosure(soln-A).
1)STERILITY TEST:
 Whentreatedclosuresaresubjectedtosterilizationtestat64-66⁰C andapressureof
about0.7KPafor24hr.
2)RESIDUE ONEVAPORATION:
 50mlofsolutionAisevaporatedtodrynessat105⁰C.ThenweightheresidueNMT
4mg.
3)PENETRABILITY:
 Thisismeasuredtochecktheforcerequiredtomakeahypodermicneedlepenetrate
easily throughtheclosure.Itismeasuredbyusingthepiercingmachine.The
piercingforcemustnotexceedastated value. If itexceedsthatstatedvalue,the
hypodermicneedlecanbedamagedasaresultofundesirablehardnessofthe
closures.
86

82. 4)FRAGMENTATIONTEST:
82

83. 5)Self –sealability:Thistestis applicabletoclosuresintendedtobe
usedwithwater.
83

84. 6)pH OF AQUEOUS EXTRACT:
 20mlofsolutionAisaddedwith0.1ml bromothymolblue whenitisaddedwith
asmall am
ountof0.01MNaOH whichchangesthecolour frombluetoyellow.
ThevolumeofNaOHrequiredisNMT0.3mlandifitisdonewithHCl, the
volumeofHCl neededshouldNMT0.8m
l.
7)LIGHT ABSORPTIONTEST:
 It mustbedonewithin4hrsofpreparingsolutionA.It is filteredthrough0.5μ
filteranditsabsorbanceismeasuredat220to360nm.Blankisdonewithout
closuresandabsorbanceis NMT2.0.
8)REDUCING SUBSTANCES:
 20mlof solutionAisaddedwith1mlof 1MH2SO4and20mlof 0.002M
KMnO4andboilfor3minthencoolandadd1gmofpotassiumiodidewhichis
titratedwithsodiumthio-sulphate usingstarchas anindicator.Blankisdon8
9
e
andthedifferencebetweentitrationvolumesis NMT0.7ml.

85. QUALITY CONTROL OF COLLAPSIBLE TUBES
1)LEAKAGE TEST:
 Waterwasfilledinthetubeandtightly closed.Externalsurface waswipedoff andtube
iskeptinvertedonfilterpaperatbase.Allowtostandfor1hr.Filterpaper shows
absorptionatanytimeduringtestperiod.
2)LACQUER CURINGTEST:
A) Power of adhesion:
 Tubewasspittedalongthelengthandflattened.Cottonwoolsoakedinacetonewas
rubbedoverlacquersurfacefor20min.Lacquershouldnotliftfromsurfaceandcotton
wool shall remaincolorless.
B) Flexibilitytest:
 Thetubewasfoldedinsuchamannerthatinternal lacquersurface isoutside. The
lacquercoatingshouldnotbepeeledoffwhenthefoldedposition is rubbedwithfinger.
3) LACQUER COMPATIBILITY TEST:
 10tubesaretakenforthetest.Productwasfilled andcrimpedsubjectedto45⁰C for
72hr.Tubeswereallowedtocool andcutlengthwise.
A) Productcompatibility:
 Contentshouldnotshowanydiscolorationsorchangeincolourorgasformation.
B) Lacquer compatibility:
 Liftingorpeelingoflacqueris checked.
90

86. QUALITY CONTROL OF METALLIC TINS
1)DESCRIPTION:
 Metallictinshavingsmoothinnersurface.Theuppersurfaceis sealed
consistsacliptobreaktheseal.Thelowersurfaceis open.
2)DIMENSIONS:
 Height-Measuretheheightinm
mof10metallictin,individuallyfromthe
lowersurfaceedgetotheupper rim.
 Limit-Specimenmetallictinswithtolerance-170mm±10mm.
3)DIAMETER:
Inner diam
eter- Measuretheinnerdiam
eterof10metallic tins.
Limit- NLT 98mm.
 Outerdiam
eter:Limit-NMT 105m
m.
4)CLEANLINESS CHECK:
 Itshouldnotbedirty, damaged,stainedorconsistofanyforeignparticles.91

87. QUALITY CONTROL OF STRIP AND BLISTERS
Procedure:
 3/4thofwaterispouredindesiccators.Thestripsandblisterswereplaced
insidethedesiccatorsandvacuumisapplied.Aftersometimevacuumwas
releasedandstrips,blistersweretakenout.Thewaterpresentovertheouter
surfaceofthepackageswaswipedoff withtissuepaper. Thecontentsof
stripsandblisterpackageswereremovedandthepresenceofmoisturewas
checked.
 If thereis noleakage,thecontentswillnotbewetted.This indicatesthe
perfectsealingofthepackages.
92

88. QUALITYCONTROL TESTS FOR CARTONS:
 Compression:Thismethodisusedtoassessthestrengthoferected
package.
 Cartonopeningforce:Themethodis usedtoholdtheflatcartonas
delivered,byitscreasesbetweenthumb&firstfingerpress.
 Coefficientoffriction:Bothstatic&kineticcoefficientsoffrictionare
determinedbyslidingthespecimenoveritselfunderspecifictest
conditions.
 Creasestiffness:Thisinvolvestestingacartonboardpiece&folding
itthrough90.Itwillthentrytorecoveritsformerpositionwhen
bendingforceis removed.
 Joint shearstrength:Thisis amethodoftestingthegluedlapseamon
thesideofacartonforstrengthoftheadhesiveusingatensiletesting
machine. 93

89. QUALITY CONTROL OF PAPER AND BOARD
 Thetestspiecesofpaperandboardareconditionedfortheteststobecarriedoutin
standardconditions.
 Theyare:
• Temperature: 23⁰C±1⁰C
• Relativehumidity:50%±2%.
 Someoftheteststobeperformedare:
89

90. 90

91. 91

92.  QualityAssuranceAspectsOf Packaging
 To ensure that patients and consumers receive high-quality drugs, the
quality management system must take the following considerations into
account if the required quality of packaging is to be obtained:
⚫ — the requirements of the national authorities and the relevant
legislation
⚫ — the product
⚫ — the production process
⚫ — the manufacturers’internal policies (safety, marketing, etc.).
 Bad packaging which is the result of deficiencies in the quality assurance
system for packaging can have serious consequences, and packaging
defects can create problems that may result in drug recalls. Such defects
may include breakage, and problems relating to printing or inks, or errors
on labels and package inserts (patient information leaflets). The use of
GMP and quality control will prevent the release of a defective medicinal
product.
 Packaging processes and equipment need validation/qualification in the
same way as any other part of processing within a pharmaceutical facility.
97

93. Samplingandtestingofpackagingmaterials
 Sampling
Sampling is used;
 To check the correctness of the label, packaging material or
container reference, as well as in the acceptance of
consignments,
 Detecting adulteration of the medicinal product, obtaining a
sample for retention, etc.
 The sampling procedure must take into account the
homogeneity and uniformity of the material so as to ensure
that the sample is representative of the entire batch.
 The sampling procedure should be described in a written
protocol.
93

94.  Testing programme
Quality control tests are intended to check the identity of the
material concerned. Complete pharmacopoeial or analogous testing
may also be carried out, as may special tests, where necessary. All
written specifications for packaging materials and containers should
include the nature, extent and frequency of routine tests. Routine tests
vary according to the type of material and its immediate packaging,
the use of the product, and the route of administration. Nevertheless,
such tests usually include the following:
⚫ — visual inspection (cleanliness, defects)
⚫ — tests to identify the material
⚫ — dimensional tests
⚫ — physical tests
⚫ — chemical tests
⚫ — microbiological tests
94

95.  PACKAGE VALIDTAION
Packagevalidationinvolvestwoseparatevalidations:
1) Thedesignvalidationofthepackageasacomponentofthedevice
Designvalidationusesevidencetoestablishwhatdesignspecifications will
conformwiththeuserneedsandtheintendeduseand
2) Theprocessvalidationofthepackagingprocess.
Processvalidationestablishesbyobjectiveevidencethataprocessconsistently
producesaresultorproductthatmeetspredeterminedspecifications[820.3(z)(1)].
Theregulation,ofcourse,referstoestablishingevidencethatthemanufacturingsteps
involvedinpackagingthedevicewillconsistentlyproducepackagingwhichmeets
specifications.For example,theprocesscapabilityofpackaging andsealing
equipmentshouldbedeterminedduringprocessvalidationanddocumented.
Validationofthepackagedesignshallbeperformedunderactualorsimulateduse
conditionsthatshowthepackageconformstoitsstatedintendeduses.Risk analysis
shall alsobeincludedwhereappropriate. 100

96. Designvalidationresultsshallinclude:thedesignidentification,nameofthe
individual(s)performingthevalidation,method(s)used,andthedate.All ofthis
informationshouldberecordedinthedesign historyfile.If anysignificant
changeismadeinthepackaging orpackaging operation after validation,the
newprocesswillneedtoberevalidated.
Oneofthemostdifficultaspectsofpackagevalidationisdetermininghowmany
samplestotest.Thegoalis nottoovertestbecauseofcostconsiderationswhile
stillrunningsufficientteststoprovidestatisticallyvalidsampling.Statistical
methodsofanalysisareimportantinprocessvalidation.Thefollowingdecision
treefromMedicalDeviceandDiagnosticIndustry,"StreamliningPackage-Seal
Validation,"October1992,providesvariousmethodsofstatisticalanalysis.The
manufacturerischallengedwithdeterminingwhichstatisticalmethodismost
applicabletotheirindividualneeds.The resultingvalidation plan should
identify,measure,andevaluatethekeyprocessesandvariablesthatwillrequire
assessmenttocompleteavalidationorrevalidationofthepackagingandthe
packagingprocess. 101

97. QUALIFICATIONANDQUALITY CONTROL OF
PACKAGINGCOMPONENTS:
 Apackagingsystemfoundacceptableforonedrugproductisnot
automaticallyassumedtobeappropriateforanother.Eachapplication
shouldcontainenoughinformationtoshowthateachproposedcontainer
closuresystemanditscomponentsaresuitableforitsintendeduse.
 Thetypeandextentofinformationthatshouldbeprovidedinanapplication
will dependonthedosageformandtherouteofadm
inistration.
 For example,thekindofinformationthatshouldbeprovidedabouta
packagingsystemforaninjectabledosageformoradrugproductfor
inhalationis oftenmoredetailedthanthatwhichshouldbeprovidedabouta
packagingsystemforasolidoraldosageform.
102

98. 1.Protection:
 Acontainerintendedtoprovideprotectionfromlightorofferedasalight-resistant
containermustmeettherequirementsoftheUSP<661> LightTransmissiontest.The
procedurerequirestheuseofaspectrophotometer,withtherequiredsensitivityand
accuracy,adaptedformeasuringtheamountoflighttransmittedbytheplastic
materialsusedforthecontainer.
 Theabilityofacontainerclosuresystemtoprotectagainstmoisture can be
ascertainedbyperformingtheUSP <661> WaterVapourPermeationtest.TheUSP
setslimitstotheamountofmoisturethatcanpenetratebaseduponsizeand
compositionoftheplasticcomponents(HDPE, LDPE, orPET).
 Theintegrityofthecontainercanbeevaluatedinseveralways.
 Acoupleofthemostcommontestsaredyepenetrationandmicrobialingress.
Containerclosuresystemsstoredinadyesolutionandexposedtopressureand
vacuumcyclesareexaminedfordyeleakageintothecontainer.
 Themicrobialingressissimilarinfashion,butdeterminesthemicrobial
contaminationofthecontentswhensoakedinamediacontaminatedwithbacteria.
 Otherquantitativeteststhatcanberunarevacuum/pressuredecay,heliummass
spectrometry, andgasdetection. 103

99. 2)Compatibility:
 Componentscompatiblewithadosageformwillnotinteractsufficientlytochange
thequalityoftheproductoritscomponents.
 Aleachabilitystudydesignedtoevaluatetheamountand/ornatureofanychemical
migratingfromtheplasticmaterialtothepharmaceuticalproductshouldbe
implemented.Thestudyshouldevaluatesubstancesthatmigrateintothe
pharmaceuticalproductvehicleforthelengthofshelf-lifeclaim.
 Thedrugproduct shouldbeevaluated atregularintervals,such as atone, three,or
sixmonthsoratoneortwoyears,untilthelengthoftheshelflifeclaimhasbeenmet.
 Analytical techniquessuchas
 LiquidChromatography/MassSpectrometrytoevaluatenon-volatileorganics,
 GasChromatography/MassSpectrometry(GC/MS)toevaluatesemivolatile
organics,and
 InductivelyCoupledPlasma(ICP) spectroscopytodetectandquantitateinorganic
elem
entsshouldbeapartofthisstudy.
 Aninfrared(IR) scanofeachplasticcomponentshouldalsobeincluded.AnIR scan
canfingerprintthematerialsandalsoprovideproofofidentity,whichwilllater
becomepartofqualitycontrol.
104

100. 3)Safety:
 All packagingcomponentsshouldbeconstructed ofmaterials thatwillnotleachharmful
orundesirableamountsofsubstancestowhichapatientwillbeexposedduringdrug
treatment.
 Isolationisaccomplishedthroughsamplepreparation,followed byincubation insolvents
atwell-definedandwell-controlledtimesandtemperatures.
 Somepotentialextractablechemicalsfrompackagingmaterialsarewatersoluble,while
othersaresolubleonlyinnonpolar environments. For thepackaging which are in
contactwiththedrugproducts,extractioninbothpolarandnonpolarenvironmentsis
relevant.
 TheUSP includesphysicochemicaltestsforplasticsbasedonwaterextracts;whilewater,
alcohol,andhexaneextractsarerequiredforpolyethylenecontainersundercontrolled
temperatureandtimeparameters(700Cfor24hours forwaterandalcohol and50°Cfor
24hoursforhexane).
 Biological reactivityis thesecondpartofsafetytestingandis designedtotestextractable
chemicalsfortoxicologicalproperties.FDA'sguidancedocumentsuggeststhattheUSP
biologicalreactivitytestscandeterminethesafelevelofexposureviathelabel-specif1i0e5d
routeofadministration.

101. 4) Performance:
 Thefourthattributeofsuitabilityofthecontainerclosuresystem,
performanceanddrugdelivery,referstoitsabilitytofunctionin
themannerforwhichitwasdesigned.Therearetwomajor
considerationswhenevaluatingperformance.
 Thefirst considerationis functionalitythatmaybetoimprove
patientcompliance,minimizewaste,orimproveeaseofuse.
 Thesecondconsiderationisdrugdelivery,whichistheabilityof
thepackagingsystemtodelivertherightamountorrate.
 Packagingsystemsthataddressthisconsiderationareprefilled
syringes,transdermalpatches,dropperorspraybottles,and
metered-doseinhalers.
101

102. ExamplesofPackagingConcernsforCommonClassesofDrug Products:
102

103. PACKAGE INSPECTION:
 Morecriticalpartofpackagingoperationispackageinspection.Inthepastthiswas
largelycarriedoutbypeopleundertheheadingofqualitycontrol.Withtheincreasein
outputoftypicalpackaginglinestheinspectiontaskhasbecomedifficultforthehuman
persontoaccomplish.Severalimportantelectronicstechniqueshavebeendeveloped
whichallowforthegraphicinspectionof anumberof packagingvariablesandthe
rapidrejectionofthosewhich tonotmeetanestablished standard, andwiththe
passingofthosewhichdo.
 Onenotablevariableistheaccuracyofweightorfill volume.Automaticcheckweight
systemshandleallofthese.Inthecaseaproductsoldbyvolume,amachine-vision
systemcandeterminewhethertheliquidlevelinabottleforexampleisattheproper
level.
 Labelingisanothervariablewhichisregulated.Again machine–visionsystemsare
abletoscaneachlabeltobesurethatitiscorrectlyappliedandthatthetextiscorrect
fortheproductbeingandthatthetextis correctfortheproductbeingpackaged.
 Metaldetectioninaproductand/orpackagecanbeaccomplishedwithseveral
techniqueswithanX-rayabletodetectparticularsassmallas0.01m
mathighline
outputs.
 Leakingpackagescanbedetectedathighspeedwithheliumleakdetection.
108

104. PHARMACEUTICAL PACKAGE TESTING/TRANSPORT
PACKAGING TESTING:
 Transportpackagingandtheir contentsareinfluencedbythemodesof
transport.Dependingonwhichtransportmodethatis used,packageswillbe
exposedtodifferentkindofstresses.Themainstressesare;
 MechanicalStrains- Themostcommonmechanicalstrainsontransported
goodsareforcestresseslike,stackingpressureandshocksandenergy
stresseslike vibrationanddropping.
 ClimaticStresses- Climateplaysavitalpartforthedurabilityand
performanceofthepackagingduringthetransport.
 TestingMethods
 Packagingis testedintw
oways;
1)regardingtheir materialperformance
2)howtheyperformduringtheactual transportation. 109

105.  CompressionStrengthTesting:Packagesbehavedifferentlywhenexposedto
compressiveforces.Itusestestingcapabilitiestoapplycompressiveforcesto
packagesandproductsandprovideacomprehensivereportwithdataonthe
strengthofapackage.
 DistributionSimulationTesting:Packagesexperiencemanydifferentforces
duringtheshippinganddistributionprocess.Itistheproductmanufacturer’s
responsibilitytoevaluateanddocumenttheabilityofthepackagetowithstand
thedistributionandstorageenvironm
ents.
 PackageIntegrityTesting: Itusesestablishedteststotesttheintegrityofa
pharmaceuticalpackage.Suchtestsincludedyeleak,visualinspection,
vacuumleakandbubbleleaktestingtoinspectthepackage’sintegrity
capabilities.
105

106.  PackageStrengthTesting: Packagestrengthtestingisconductedtomeasure
andensurethatthecomponentsofthepackagewillnotseparatewhenspecific
forcesareapplied.Thetestingofflexiblecomponentssuch as pouches, seal
peelorbursttestingaremethodsusedtoprovethepackagestrength.
 VibrationTesting:Packages andproducts experience awiderange of
dynamicforcesandstressesduringdistributionthatcouldharmtheproduct.It
performsvibrationtestsonsamplestosimulate thestressesandforcesa
packageorproductwouldexperienceduringthedistributionprocess.
 ShockandVibeTesting:Dropping,rotationaledgedroppingandrotational
flatdropteststosimulaterealworldexposureofthepackagetoshockforces
byforklifts,packagehandlingorotherfactorsinthepharmaceutical
package’sdistributioncycle.
106

107. FLEXIBLE PACKAGING:
 TheflexiblepackagingmaterialsarelargelyusedinPharmaceuticalsforblister
packagingoftabletsandsachetpackingofdispersiblepowders.Almost75% oforal
tabletsandpowdersarepackagedinUSarepackagedinflexiblematerials.
 US21CFR andUSP34NF29haveprescribedasetof specificationforcontrolling
thequalityofsuchmaterials.
 FlexiblePackagingincontexttoPharmaceuticalsisnon-rigidpackagingstructures
usedtopackageandprotectvariousdrugproductssuchastablets,capsules,powders
formedicaluse.
 Flexiblepackagingcoversmaterialsthathaveundergoneaconversionprocess
includingprinting,lamination,coatingandextrusion,andcaninvolvedifferent
substratessuchasplasticfilms,paperandfoil.Flexible packtypesincludeplastic
bags,wrappingfilms,lidingfilms,aluminiumfoillaminates;foilliding,blister
packaging,foil bagsandsachets.
 Flexible packagingfilmscanbemadefrom:
*SinglematerialssuchasPE, PP, polyester orPU
*Multiplematerialsbycoating,laminatingorcoextrudingwiththeothermaterials
 Themostcommonformsofflexiblepackagingarethestrippackage,blisterpack
a1
g1
e2
and
thepouch.

108.  Ablisterpackageusuallyconsistsofalidingmaterialandaformingfilm.
 Thelidingmaterialisusuallyalaminatewhichincludesabarrierlayer(e.g.,
aluminiumfoil)withaprintprimerononesideandasealingagent(e.g.,a
heat-sealinglacquer)ontheotherside.
 Thepouchisusuallysealedfrom3sidesandonesideiskeptopenforfilling
andsealingthereafter.Thesealingagentcontactsthedosageformandthe
formingfilm.Theformingfilmmaybeasinglefilm,acoatedfilm,ora
laminate.Leaktestingis usuallyperformedonflexiblepackagesaspartofthe
in-processcontrols
 ThemostcommonexamplesofflexiblePharmaceutical packaging materials
are:AluminiumFoil, BOPP(biaxialorientedpolypropylene),LDPE (low-
densitypolyethylene)LLDPE (linearlow-densitypolyethylene)OPP(oriented
polypropylene)PA(polyamide)PE (polyethylene)PET (polyethylene
terphthalate), PP(polypropylene), PVC (polyvinyl chloride)PVDC
(polyvinylidenechloride),asusedsingly orinlam
inateform. 113

109. THE BASIC REQUIREMENTS FOR FLEXIBLE PACKAGING
MATERIALS AS PER US FDA
 TheproductshallbemanufacturedaspercGMPGuidelinesprovidedunder
directive21CFR parts11.Theproductsusedforasprimarypackagingof
pharmaceuticalproductsshallbemanufacturedundercleanroomconditions
m
eetingClass1,00,000cleanlinessstandards.
⚫ Thecontainershallmeetallrequirementsunder21CFR DirectFood
ContactandphysicaltestsinaccordancetolatestUSP <661>:
⚫ Thecontainer shall protectthecontentsfromenvironm
ental hazardand
externalinfluences(e.g.moisture,light,oxygenandtemperature
variations)duringitsentirelifetimebeginningfrompackaging,
transportation,handlingandstorageuntiluse.
⚫ Itshallnotbecomposed,inwholeorinpart,ofanypoisonousor
deleterioussubstancewhichmayrenderthecontentsinjurioustohealth
⚫ Itshallnotbereactive,additive,orabsorptivesoastoalterthesafety,
identity,strength,quality,orpurityofthedrugbeyondtheofficialor
establishedrequirements.
⚫ Theintegrityoftheflexiblematerialmustbemetthroughoutthewhole1
o
1
4
f
theintendedshelf-lifeoftheproduct.Thematerialsshallbeconditionedto
the23°C and50% RHbeforeconductinganyQC/QAtests.

110. ⚫ Recycledstartingmaterialorfinishedproductis mostlynotallowed.
⚫ TheproductshallbesupportedbyCertificateofAnalysis(COA)or
CertificateofCertification(COC) fromthecomponentsupplierandthe
performanceofanappropriateidentificationtest,providedthesupplier’s
testdataareperiodicallyvalidated(21CFR 211.84(d)(3)).
⚫ All testmethodsshallbefullydescribed.
⚫ If abatchistobeacceptedbasedonasupplier'sCOAorCOC, thenthe
procedureforsuppliervalidationshouldbedescribed.Thedatafromthe
supplier’sCOAorCOC shouldclearlyindicatethatthelotmeetsthe
applicant’sacceptancecriteria.
⚫ Dimensionalinformationshallbeprovidedviaadetailedschematic
drawingcompletewithtargetdimensionsandtolerances
⚫ Descriptionofthequalitycontrolmeasuresusedtomaintainconsistencyin
thephysicalandchemical characteristicsofthematerial.
⚫ Acompletedescriptionoftheprocessanditsvalidationshouldbe
provided.
115

111.  ThefollowingphysicaltestsareperformedinaccordancetolatestUSP
<661>:
 Multipleinternalreflectance’s(toensurethatthematerialofthecontainer
fallswithintherangeofHDPE orLDPE asspecifiedinthetest),
 Thermalanalysis(tocheckcompliancetopredefinedendothermsand
exothermstemperatures),
 Lighttransmission(tocheckprotectionfromlight),
 Watervaporpermeation(tocheckprotectionfrommoisturepermeation)
 Heavymetals,
 Nonvolatileresidue.
116

112. SUMMARY OF ICH GUIDELINES ONSTABILITY AND
POSSIBLE INFLUENCE ONTHE PACK:
 AlthoughtheICH guidelinesmakereferencetostresscondition,involving low
andhightemperatures,lowandhighhumidities,freeze-thaw,varyinglight
intensities,includingcyclingconditions,storageatafixedtemperatureand
humiditymaynotfullychallenge thepack(andtheproduct).Apackmay
thereforewithstandcontinuousstorageat25˚C/60%RH,30˚C/60%RH,
40˚C/75%RHetc.,butfailundercyclingorhighertemperaturestress
conditions.
 However,packsaremorelikelytochangeifexposedtoamultiplicityof
challenges, e.g.TemperatureandRHchanges,vibrationandcompression(on
aproductionline,instorageordistribution),theinfluenceofoxygen,light.
Packswhicharetosomedegreepermeabletomoisture(asare mostplastics)
willloseorgainmoistureaccordingtowhethertheyareexposedtoahighor
lowrelativehumidityrespectively40˚C/75%RHmaybeparticularlysevere1
1
7
on
afullyexposedblisterpackandgiveanartificially lowshelflife prediction.

113.  Packsremovedfromasimulatedclimaticcondition alsoneedtobechecked
foranysignsofchange/deterioration,priortoopening,duringopening(peel
strength,closure,torque/forceetc.)andafterproductremoval.Thisis
particularlyrelevantwhereextrem
esoftem
peratureandcycling conditions
areinvolvedsinceclosureefficiencies mayvaryaccordingtothestorage
temperature.Thiscanbecriticalwhereaproductinitspackisallowedto
equilibratewithbenchconditionsbeforeitissubjected toanalysis,so a
trainedpackagingtechnologistis essentialtothisexamination.
 Theultimatetaskofthepackis toproduceconfidenceintheproductinterms
ofconvenience,preservationandprotectionfromtheenvironment.While
ensuringthattheproduct remains satisfactoryinthefullestsense, i.e.
integrity,identity,uniformity,safety,effectivenessetc.allataneconomically
acceptableart.
113

114. 114