pamarcuetical packaging materials
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GMP 6 (11 2551)
Packaging material
PIC/S GMP
Any material employed in the packaging of a
medicinal products, excluding any outerpackaging used for transportation or shipment.
Packaging materials are referred to as primaryor secondary according to whether or not theyare intended to be in direct contact with theproduct.
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Packaging component
Any single part of a container closure system.
Typical components are
Containers , Container liners
Closures, Closure liners
Stopper overseals, Container inner seals
Administration ports overwraps
Administration accessories
Container labels
US FDAContainer Closure Systems for Packaging Human Drugs and Biologics
Primary packaging component
Packaging component that is or
may be in direct contact with thedosage form.
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Secondary packaging component
Packaging component that is not and
will not be in direct contact with the
dosage form.
Container closure system
The sum of packaging components that togethercontain and protect the dosage form.
This includes primary packaging components &secondary packaging components, if the latter areintended to provide additional protection to the drugproduct.
Packaging system is equivalent to a containerclosure system
US FDA Container Closure Systems for Packaging Human Drugs and Biologics
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Containers
A containers for Pharmaceutical use is an article
which holds or is intended to contain and protect
a drug and is or may be in direct contact with it .
The closure is a part of the container.
The container and its closure must not interact
physically or chemically with the substance
within in any way that would alter its quality.
WHO Guidelines on packaging for pharmaceutical products, TRS, No.902, 2002
Containers
General requirements for the permeability of
containers
Well-closed containers Tightly closed containers
Hermetically closed containers
Light-resistant container
WHO Guidelines on packaging for pharmaceutical products, TRS, No.902, 2002
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Containers (EP)
Single-dose container
Multidosecontainer
Well-closed container
Airtight container
Sealed container Tamper-proof container
Child-proof container
Containers ( USP31)
Tamper-Evident Packaging
Light-Resistant Container
Well-Closed Container
Tight Container Hermetic Container
Single-Unit Container
Single-Dose Container
Unit-Dose Containers
Unit-of-Use Containers
Multiple-Unit Containers
Multiple-dose Containers
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Tamper- evident packaging
Having an indicator or barrier to entry which, if
breached or missing, can reasonably be
expected to provide visible evidence to
consumers that tampering has occurred.
Packaging concerns
Depend on
Dosage form Route of administration
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Examples of Packaging Concerns for Common
Classes of Drug Products
Oral Tablets & Oral(Hard & SoftGelatin) Capsules
Topical Powders;
Oral Powder
Topical Solutions &Suspensions;
Topical & Lingual Aerosols;
Oral Solutions & Suspension
Low
Ophthalmic Solutions &Suspension;
Transdermal Ointments &
Patches;Nasal Aerosol & Sprays
High
Sterile Powders &Powders forInjection;
Inhalation Powders
Inhalation Aerosols &Solutions;
Injection & InjectableSuspension
Highest
LowMediumHigh
Likelihood of Packaging Component-Dosage Form InteractionDegree of Concern
Associated with the
Route of Administration
General consideration of
container closure system
1. Suitability for Intended Usea) Protection
b) Compatibilityc) Safety
d) Performance
2. Quality Control of Packaging Componentsa) Physical Characteristic
b) Chemical Composition
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General consideration ofcontainer closure system
Suitability tests and studies and accepted for
the initial qualification of a component or a
container closure system for its intend use.
Quality control tests typically used and
accepted to established that the components
and container closure system continue to posses
the characteristics established in the suitability
studies
Functionality (improved patient compliance
or use)
Delivery (transfer dose in right amount or
rate)
Container closure system
fuctionality,
drug deliveryPerformance
Extraction study (USP Physicochemical
Tests-Plastics), USP Elastomeric Closures
for Injections, Toxicological Evaluation, USPBiological Reactivity and complied with CFR
additives and purity
No leached harmful or
undesirable amounts of
substances to expose patientstreated with drug
Safety
Leachability Study (Migration of chemicals
into drug product) using LC/MS, GC/MS,
ICP/AA, pH, appearance of drug and
container, Thermal analysis (DSC, TGA), IR
Leachable induced degradation,
absorption or adsorption of drug,
precipitation, changes in pH,
discoloration, brittleness ofpackaging materials
Compatibility
USPLight Transmission and Water
Vapor Permeation, Container Integrity
(Microbial ingress, Dye Penetration, Helium
Leak)
Exposure to light, moisture,
microbial ingress, and oxidation
from presence of oxygenProtection
Proposed MethodsConcerns and InteractionAt tr ibutes
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Quality control of packaging components
a) Physical Characteristics
Dimensional criteria
Physical parameters critical to the consistentmanufacture of the packaging component
Performance characteristics
b) Chemical Composition
May affect the safety, compatibility,functional characteristics or protectiveproperties of a packaging components.
PACKAGING MATERIALS
Glass
Plastics Metal
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PACKAGING MATERIALS
The choice of primary and/or secondarypackaging materials will depend on Degree of protection required
Compatibility with the contents
Filling method
Cost Presentation for OTC drug
Convenience of packaging for user
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GLASS used for pharmaceutical
containers (EP)
Glass containers are classified according to their hydrolytic
resistance
Type I Glass : Neutral glass, with a high hydrolytic
resistant due to the chemical composition of the glass
itself.
Type II Glass : usually of soda-lime-silica glass with ahigh hydrolytic resistance resulting from suitable treatment
of the surface.
Type III Glass : Soda-lime glassusually of soda-lime-
silica glass with only moderate hydrolytic resistance.
Glass type & recommendation for used
Type I glass : suitable for most preparations whether
or not for parenteral use.
Type II glass : suitable for most acidic & neutral,aqueous preparations whether or not for parenteral
use.
Type III glass : general suitable for non-aqueous
preparations for parenteral use, for powders for
parenteral use (except for freeze-dried preparations)
and for preparations not for parenteral use.
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GLASS
Composition
Silica (SiO2) 59-75 %
Calcium oxide (CaO) 5-12 %
Sodium oxide (Na2O) 12-17 %
Alumina (Al2O3) 0.5-3.0 %
Other oxide Barium oxide (BaO)
Boric oxide (B2O2)
Potassium oxdie (K2O)
Magnesium oxide (MgO)
Glass type & recommendation for used
Except for type I glass containers, glass
containers for pharmaceutical preparation are
not to be re-used Containers for human blood and blood
components must not be re-used.
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Quality of glass container
Test for hydrolytic resistance
To define the glass type (I, II or III)
To control its hydrolytic resistance
Containers for aqueous parenteral preparations
are tested for arsenic release Colouredglass containers are tested for spectral
transmission.
Hydrolytic Resistance (EP)
Test A and B or
Test A and C
Type I & Type II glass containers where it is
necessary to determine whether the high
hydrolytic resistance is due to the chemical
composition or to the surface treatment
Test B (glass grains
test) or Test C (etching
test)
Type I glass containers
( to distinguish from Type II and type III glass
container)
Test A
(surface test)
Type I & Type II glass containers
( to distinguish from Type III glass container)
Test to be performedType of glass container
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Hydrolytic Resistance (EP)
By titration of the extract solutions obtained underthe conditions described for test A, B and C
TEST A : SURFACE TEST (hydrolytic resistance ofthe inner surfaces of glass container)
TEST B : GLASS GRAINS TEST (hydrolytic
resistance of glass grains) TEST C : ETCHING TEST ( To determine whether
the containers have been surface-treated)
Limit values in the test for Surface Glass Test
(Test A)
2.20.20Above 500
2.80.30Above 200 and up to 500
3.80.40Above 100 and up to 200
4.80.50Above 50 and up to 100
6.10.60Above 20 and up to 50
8.10.80Above 10 and up to 20
10.21.0Above 5 and up to 10
13.21.3Above 2 and up to 5
17.61.8Above 1 and up to 2
20.02.0Up to 1
Type IIIType I and II
Glass containers
Maximum volume of 0.01 M HCl per 100 ml of test liquid (ml)
Filling volme(ml)
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Limits for Glass Grains Test (Test B)
Not more than 8.5Type II and Type III
Not more than 1.0Type I
ml of 0.02 MHClGlass Containers
Chemical Resistance (USP 31)
Powdered Glass Test
Surface Glass Test Water Attack at 121o
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Glass
Other factors to be considered in glass containerselection process are
Thermal expansion properties (:- freeze-drying)
If a product is sensitive to particular ions :-
bariumor calcium If the glass is to be sterilized by radiation, a
special formulation containing cerium oxidemust be use.
Coloured Glass
Is obtained by the addition of small amounts of
metal oxides, chosen according to the desired
spectral absorbanceIron and manganese dioxide
Iron oxide, manganese dioxide, chromium dioxide
Cobalt oxide
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Light Transmission
Light resistant container
EP 3.2 Container
Glass Container for Pharmaceutical Test Spectral Transmission for Coloured Glass
Container
USP Container Performance Testing
Light Transmission Test
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Light resistant container
Limits
Colouredglass containers for
preparations that are not for parenteral
use does not exeed10 %at any
wavelength in the range of 290 nm to450 nm, irrespective of the type and the
capacity of the glass container
Limit of spectral transmission for coloured
glass containers for parenteral preparations
25
20
15
13
12
10
50
45
40
35
30
25
Up to 1
Above 1 and up to 2
Above 2 and up to 5
Above 5 and up to 10
Above 10 and up to 20
Above 20
Container with
closure
Flame-sealed
containers
Max. percentage of spectral
transmission at any wavelength
between 290 nm and 450 nmFilling volume
(ml)
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PLASTICS
A plastic is a material that contains anessential ingredient one or more
polymeric organic substances of largemolecular weight.
Classification of polymer types
1. Thermosets (Thermosetting plastics)
2. Thermoplastics
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PLASTICS
1. Thermosets (Thermosetting plastics)
Consist of those plastics that, when subjected toheat, normally will become infusible or insoluble,and as such cannot be remelted.
2. Thermoplastics
Consist of those plastics that normally are rigidat operating temperatures but can be remeltedand reprocessed
POLYMER
Homopolymer: involve one type of monomer
Copolymer: involve 2 or more monomers of different
chemical substance
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Plastics
Factors responsible for plastics properties
Chemical structure
Molecular weight
Crystallinity and orientation
Cross-linking
Addition of other agents
Plastics
Chemical Structure
Linear polymer chain
Branchedpolymer chain
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Plastics
Molecular weight Melt flow index (MFI)
Useful factor for characterization of polyolefins
High melt (flow) indicate lower molecular weights & lowmelt (flow) indicate high molecular weights.
Increase in MFI is related to : Ease of moulding
Impact strength (decreases)
Stress cracking resistance (decreaes)
Plastics
Crystallinityand orientation
Crystallinity
Orderly compact structureof the molecular chain
Polymer chain may
twisted and tangled
formation given an
amorphous type polymer
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Plastics
Orientation The alignment of crystalline structure in polymeric materials so as to
produce a highly aligned molecular structure.
Materials are stretched just below or above their softening point .
Depending on the degree of orientation, significant changes can
occur in both the physical & chemical properties.
Improving clarity
Reducing to moisture & gas permeation
improvingchemical resistant
Plastics
Cross-linking
Joints between chains which occur in three
dimensions.
Reflected in physical properties, increasing,
for example, polymer rigidity.
Thermoset are cross-link.
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Plastics
Addition of other agents Antioxidants
Stablizers
Plasticizers
UV absorbers
Antistatics
Dyes or pigments Lubricants
Etc.
Plastics
Important problems
1. Sorption
2. Desorption (Leaching)
3. Permeation
4. Photodegradation
5. Polymer Modification
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Thermosets
Phenol Formaldehyde
Urea FormaldehydeMelamine Formaldehyde
Thermosets
These plastics are used when good dimensional
and temperature stability are required.
The formaldehyde plastics have been found themost used in the pharmaceutical industry as
closures for glass and /or plastics containers.
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Thermosets
Melamine Formaldehyde Good-to-excellent dimensional stability
When used in the manufacture of closures, hightorque strength and good impact strength.
Good resistance to oils, grease, and many organicsolvent
Phenol Formaldehyde Good scratch-resistant parts.
Very low shrinkage and low water-absorptionproperties
Thermosets
Urea Formaldehyde
Good dimensional stability as well as good strength
properties Highly rigid and provide good resistance to alcohols,
oils, grease, and some weak acids.
Use for injection-molded heads for collapsible tubes
used to contai liquid-based topical product.
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Thermoplastics
Polyethylene
Polypropylene
Polyethylene Terephthalate (PET)
Polyvinyl chloride
Polyvinylidenechloride Polystyrene
Polycarbonate
Polyethylene (PE)
Properties vary according to molecular weight and type. Low density polyethylene (LDPE) branched chain
High density polyethylene(HDPE) linear chain
Linear type is more crystalline, more heat resistant, andstiffer
As crystallinityand density increase, opacity, stiffness,tensile strength, surface hardness, and chemicalresistance increase.
Both have low water absorption, high resistant to mostsolvents and chemicals and are tasteless and odorless.
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High Density Polyethylene (HDPE)
Is the most crystalline material (~ 95%)
Naturally translucent
HDPE has better moisture- barrier properties and
better tensile strength than LDPE.
HDPE is used widely for bottles of solid dosage formproduct.
HDPE is NOT suitable for use with essential oils.
Low Density Polyethylene (LDPE)
Has branched chains and limit crystallinity (60-65%
crystallinity)
More translucent than HDPE LDPE is used when flexibility is required, for
squeeze bottles of spray and drops, as well as
drum liner for bulk solid drugs.
LDPE is significantly more expensive than HDPE
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HDPE bottles
HDPE bottle which provide
protection from light by using
Titanium dioxide as an
opacifyingagent
Polypropylene (PP)
Lighter, much stiffer and more heat resistantthan HDPE
Same chemical resistance properties as HDPE Can be sterilized with steam and ethylene oxide,
but not radiation, unless modified PP are used.
Biaxial orientation PP (BOPP) will improve itsclarity.
Used wildly for solid dosage products.
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POLYPROPYLENE PLASTIC JARS
Vinyl Plastics
Vinyl group (CH2=CH-)
Derivatives
Vinyl chloride (CH2=CHCl) Vinylidenechloride (CH2=CCl2)
Vinyl acetate (CH2=COCOCH3)
Many polymers are made either as homopolymer ofthemselves or as copolymers with other vinylderivatives or other monomer materials.
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Polyvinyl chloride (PVC)
UnplasticisedPVC
Bottle made PVC are naturally clear, have extremely
good resistance to oils, and have very low oxygen
transmission.
PlasticisedPVC
Plasticizer - DEHP (di(2-ethylhexyl)phthalate) isused most often.
Plasticization also reduces chemical resistant and
increases gas and moisture permeation
Polyvinyl chloride (PVC)
Factors to consider when PVC is uses forpharmaceutical
Stablizers Plasticizer
Monomer residue
Modifiers
Lubricants
Catalylic residue
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UPVC Film
Suppositories package
Polyvinylidene chloride (PVdC)
Trade name Saran
Copolymer of vinyl chloride or vinyl acetate and
vinylidenechloride Excellent resistance to permeation by moisture
and gas
Most widely used as a coating
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Polyethylene terephthalate (PET)
USP: Polyethylene terephthalate (PET) and Polyethylene
terephthalate (PETG) bottles that are interchangeably suitable for
packaging liquid oral dosage form.
PET resins are long-chain crystalline polymers prepared by the
condensation of ethylene glycol with dimethyl terephthalate or
terephthalic acid
PET copolymer resinsare prepared in similar way, except that theymay contain a small amount of either isophthalicacid (NMT 3 mole
percent) or 1,4-cyclohexanedimethanol (NMT 5 mole percent)
PET copolymer resins have physical and spectral properties similar
to PET
Polyethylene terephthalate (PET)
PETG resin are high molecular weight polymers
prepared by the condensation of ethylene glycol with
dimethyl terephthalate or terephthalic acid and 15 to 34
mole percent of 1,4-cyclohexanedimethanol. PETG
resins are clear, amorphous polymers.
PET and PETG resins do not contain any plasticizers ,
processing aids, or antioxidants. Colorants,if used in the
manuacture of PET and PETG bottles, do not migrate
into the contained liquid.
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PET bottles and jars
They offer a durable container with excellent gloss, and the
clarity and sparkle of glass. PET plastic bottles and jars are resistant to breakage, have
excellent properties of carbonation retention, have high oxygenbarrier, are l ight to handle and transport,.
Choose PET jars for bath sal ts and bottles for lot ions withessential oils to keep in the aroma.
Polystyrene (PS)
PS has relative low heat resistance and is
attacked by a number of chemical agents.
Conventional grade clearcrystal grade, lack of impact
strength.
Impact-modified graded copolymerized with
acrylonitrile and butadiene, poor optical
properties.
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Polycarbonates
PC are formed by condensation of polyphenols
such as bisphenol-A with phosgene.
PC are transparent thermoplastics with high
strength and high temperatures resistance.
Because they are expensive, their use is imited
to specialty application.
Ionomer (Surlyn)
Are sodium or zinc salts of ethylene/ methacrylic
acid copplymers.
Is used as an inner ply in laminates, offering godheat sealing (even when the seal area is
contaminated by liquid or powder) over a wide
temperature range.
Are clear , semiflexible, tough materials with good
abrasion resistance.
Valued in sachet and pouch packs.
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Polymonochlorotr ifluoroethylene (PCTFE)
Aclar film Has extremely low transmission of moisture.
Transparent, and can be heat sealed, laminated,printed, thermoformed, metallized.
Because it is the most expensive plastic used in the
pharmaceutical industry, it is employed only where themost demanding barrier properties are required.
Laminated Aclar/PVC sheet is used widely inthermoformed blister pack for moisture-sensitive soliddosage form.
Polyurethane Foams
Are formed by polymerization in the presence of
a foaming agent.
Used as a replacement for cotton wool in tabletcontainers.
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Material Code System Symbols
PETE
HDPE
PVC
LDPE
PP
PS
Others
1
2
3
4
5
6
7
Comparison of Polymer Material
GF/GE477121.33PETE
FFE/G4.5105241.27PETG
EEE1.85314.41.36OPET
F/GFG/E0.3195680.91OPP
F/GFP0.33901350.91PP
FFE109252341.20PC
F/GFE8.511603301.05PS
F/GGG3.027171.32PVCF/GF/GP0.35801850.98HDPE
F/GF/GP1.327003000.92LDPE
Chemica
l resist.
Drop
impact
ClarityWater
vapor
CO2O2DensityMaterial
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DISCLAIMER :This matrix may only be used as anindication of how different materials relate to each other.
Testing and manufacturing conditions can influence the
properties of the materials and bottles. Preformdesign, mold
and machine maintenance, resin drying time and different
variations of resin can vary the properties drastically.
Density : G/CC
O2 : CC/100 SQ IN. 24 HR (lower = better)
CO2 : CC/100 SQ IN. 24 HR (lower = better)
RATING : P = Poor, F = Fair, G = Good, E = Excellent
Sterilization
Steam sterilization at temperature of 121o
Polypropylene
High density polyehthylene Polycarbonate
PVC for certain application
All thermosets
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Sterilization
Gas sterilization (Ethylene Oxide) Cannot be used for containers of aqueous product because
side-reaction products such as ethylene glycol and 2-chloroethanol are formed.
Ethylene oxide itself is carcinogenic.
Regulatory permissible limit have been established forresidual levels of ethylene oxide. Packaged products are
degassed prior to shipping or use. Degassing properties depend upon geometry, heat history,
storage conditions, contact with other plastics, and type ofsecondary packages used. Because of this complexity,degassing hold times must be determined for each product.
Sterilization
Irradiation Can cause degradation or cross-linking of certain
polymers.
Particularly serious for polyprolylene. Although aradiation stable form of PP has been developed, itmay not suitable for multiple sterilizations.
PVC loses hydrochloric acid upon radiation,decomposing into unstable fragments, which maythen cross-link. This dehydrochlorinationlead to theformation of conjugated double bonds, which impartyellow discoloration.
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Aluminium
Tin
Tinplate
Aluminium
Density of 2.7
Odourless, tasteles, non-toxic and sterilizable
Corrosion Direct chemical attack
Strong acid and alkaline
Mercurrial compound
Galvanic corrosion
Electrolytes
Halogen : chloride
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Tinplate
Mild or low-carbon steel sheet or strip
which is coated on both sides with pure tin
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BLISTER PACKAGE
2 basic packaging components
A. Forming film
Thermoformed
Cold formed
B. LiddingMaterial
Push-through
Peelable
BLISTER PACKAGE MATERIAL
Main consideration in selecting suitable
material
Degree to which the product needs to be
protected from light, moisture & gas
permeation
Differing cost implication
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BLISTER PACKAGE MATERIAL
Choice of film thicknessaffects both materialcost and barrier properties
Other considerations are Machineability
production rate
Depth of the blister Wall thickness and uniformity of the thickness
Sealing properties
BLISTER PACKAGE MATERIAL
Thermoformed Materials UnplasticizedPVC
Most common material because it is thermoformed easily andhas barrier properties that are adequate for many drugs.
Typical film thickness of 250m (10 mil)
PVdC-coated PVC PVC applying a 25 to 50m coating of PVdCcan increase
the water vapor barrier properties 5- to 10 fold.
Aclar / PVC 15 fold less permeable to moisture than is PVC of
comparable thickness.
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BLISTER PACKAGE MATERIAL
PP
Water- vapor permeability of uncoated PP is lower than PVC,
and is comparable to PVdCcoated PVC
One problem posed by PP processing is thermoforming.The
temperature required for thermoforming PP and the
temperature of subsequent cooling process must be precisely
controlled. Another problem is warping of package often resulting in
the requirement for PP formed packages to be straightened
before cartoning.
BLISTER PACKAGE MATERIAL
Cyclic Olefin Copolymer (COC)
New high barrier thermoforming film.
Excellent thermoformability and moisture barrier properties.
Its tends to be brittle on its own, so it is usually laminates to
PP to withstand forming.
30 PP / 190 COC / 30 PP
30 PP / 300 COC / 30 PP
Can be thermoformed on existing blister lines for PVC,
PVC/PVdC, and ACLAR/PVC
COC is a candidate for a lamination to cold-form foil as a
sealant side because of its ease of forming.
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BLISTER PACKAGE MATERIAL
Cold formed
Laminated of OPA / aluminium/ PVC
OPA = biaxially oriented polyamide (nylon)
OPA is use primary for it forming capabilities
Enhance the forming process due to its elasticity
As it stretch, it bring the aluminiumwith it to create the cold form cavity.
Almost entirely eliminate water-vapor permeability.
The cost / m2 is equivalent to PVdC- coated PVC.
Required more packaging material than thermoformed plastics
for packaging the same number and the same size of tablets or
capsules.
BLISTER PACKAGE MATERIAL
Cold formed
Thermoformed
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BLISTER PACKAGE MATERIAL
25250200PVC / Aclar
1001000500PVC / PVdC
8665003500PVC
% increase from
blister formationBlisterSheet
WVTR (mg/m2/day at 40oC, 80%RH)
Film structure
BLISTER PACKAGE MATERIAL
LiddingMaterial
Push through simple hard or soft aluminiumfoil Aluminiumfoil usually has thickness varies from 18
to 25m
Heat sealing lacquer must comply with FDAstandard and must precisely match therespectively forming film.
Peeling off paper / aluminiumlaminate
Child resistance paper /PET / Foil
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Strip Packaging
Produced at lower speeds and occupy greater volume than
blister
Pocket area is critical to
diameter, shape and
thickness of the product
If the pocket is too tight, tearing,perforation of the pocket periphery
or wrinkling of the seal area may occur.
Strip Packaging Materials
the choice of laminate structure
Technical requirements
Cost of base materials Cost of lamination processes
Amount of laminate required (quantity)
Yield from which the cost per area of laminate is
derived
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Solid Oral Dosage forms
Fillers, desiccants, andother absorbent material areconsidered primary packaging components.
USP monographs for Purified Cotton and PurifiedRayon sufficient standards to established the safety ofthese materials Cotton need not meet the monograph requirements for
sterility, fiber length or absorbency
Rayon need not meet the monograph requirements for fiberlength or absorbency
Rayon has been found to be a potential source of dissolutionproblem for gelatin capsules and gelatin-coated tablets.
Elastomeric Closures for Injection
Are produced from natural or synthetic substances.
Complex mixture of many ingredients Basic polymer
Vulcanizing agent
Accelerators
Filler
Pigments
Safety USP Elastomeric Closure for Injections testing
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Elastomeric Closures for Injection
Properties are dependent not only upon
those ingredients, but also on processing
procedure :-mixing, milling, dusting agent
used, molding and curing.
Factor such as cleansing procedure,contacting media, and conditions of storage
may also affect the suitability of an
elastomeric closure for a specific use.
Drugselection
Preformulation
Drugstability
Formulation
Dosageform
design
Dosageform
selection
Production
Heat Light Moisture Oxygen
Heat Light Moisture Oxygen
Long term
stability
Packaging
Degradation
pathway
Drugexcipient
interaction
Cool Amber Tight Sealed N2
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Stability testing
Should be conducted on the dosage form
packaged in the container closure system
proposed for marketing ( including, as
appropriate, any secondary packaging and
container label)
Aseanguideline on stability study of drug product
Stability Studies
Ultimate proof of suitability of the
container closure system and the
packaging processes established by
full shelf life stability studies
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Sampling plan for packaging material
Should take account of at least the following
Quantity received
Quality required
Nature of material (:- primary packagingmaterials and/or printed packaging materials)
Production methods Knowledge of Quality Assurance system of the
packaging materials manufacturer based onaudits.
PIC/GMP ANNEX 8
Sampling plan for packaging material
Efficient inspection does not mean large sample sizes,
and it therefore cost effective (as well as logical) for
sample sizes to be as low as possible, but compatiblewith the risk level.
Examples of the factors that quantify sample size are:
Machine performance
New suppliers
Sterile / clean components
Reel fed laminates
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