Pamarcuetical Packaging Materials

8/12/2019 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








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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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


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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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.


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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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.


Cold formed

Thermoformed


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25250200PVC / Aclar

1001000500PVC / PVdC

8665003500PVC

% increase from

blister formationBlisterSheet

WVTR (mg/m2/day at 40oC, 80%RH)

Film structure


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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