Pharmaceutical Packaging

1. Write a short note on evaluation tests of p’ceutical packaging

materials?
2. Discuss regulatory requirements in packaging?
3. Define packaging. Discuss types of packaging?
4. Discuss different methods for evaluation of packaging?
5. Write a note on different types of packaging material?
6. Write a note on influence of packaging components on dosage
form stability?
7. Differentiate Primary and secondary packaging with examples.
8. What is temper evident container’s and closures?

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 Define packaging. Discuss types of packaging?
 Packaging define as art & science which involve preparing article
for transport, storage , display & use.

TYPES

PRIMARY
SECONDRY TERTIARY

 Primary Packaging
 It is the material that first envelops the product and holds it. This is
usually the smallest unit of distribution or use and is the package
which is in direct contact with the contents.
Examples: Ampoules, Vials, Containers, Dosing dropper,
Closures (plastic, metal), Syringe, Strip package, Blister
packaging.

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 Secondary Packaging
 It is outside the primary packaging –and used to group primary
packages together.
 Example: Paper and boards, Cartons ,Corrugated fibres ,Box

o Paper- This can be used as flexible wrap for the product or

closure material for jars.
o Corrugated Fibre’s – It is a paper based material consists
of corrugated sheet widely used in manufacturing corrugated
box.

 Tertiary Packaging
 It is used for bulk handling, warehouse storage and transport shipping.
The most common form is a palletized unit load that packs tightly into
containers.

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 Symbols of Packages & labels

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 Special Types of Packaging

TYPES OF SPECIAL PACKAGING

Collapsible Tubes. Child resistant packaging

Tamper – resistant packaging

 Tamper – resistant packaging or Temper evident

 Temper resistant package is one having an indicator to entry in
which,if missing or broken , provide visible evidence to consumers
that tempering has occurred.

Types of Tamper – resistant

Packaging

Film wrapper Blister packaging

Bubble pack
Strip package

Tape seal
Shrink seal and bands
Sealed tubes
Breakable caps

Sealed cartons
Aerosol containers 5

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 Film wrapper
 Film wrapping has been used extensively over the years for
products requiring package integrity or environmental protection.

Sub-Type-1

End-Folded Wrapper

Sub-Type-2

Fin seal Wrapper

Sub-Type-3

Shrink wrapper

 END-FOLDED WRAPPER
 The end folded wrapper is formed by passing the product into a
sheet of over wrapping film, which forms the film around the
product and folds the edges in a gift wrap fashion.
 The folded areas are sealed by pressing against a heated bar. The
materials commonly used for this purpose are cellophane and
polypropylene.

 FINE SEAL WRAPPER

 The seals are formed by crimping the film together and sealing
together the two inside surfaces of the film seal.
 Fin sealing is superior than end folded wrapper with good seal
integrity the over wrap can removed or opened by tearing the
wrapper
 Shrink wrapper
 The wrap concept involves the packaging of the product in a
thermoplastic film that has been stretched and oriented during its
manufacture.
 An L shaped sealer seals the over wrap.
 The major advantage of this type of wrapper is the flexibility and
low cost of packaging equipment.

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 BLISTER PACKAGING
 The blister package is formed by heat softening sheet of
thermoplastic and vaccum drawing the softened sheet is released
from the mould and proceeds to the filling station of the packaging
machine.
 The semi rigid tray is previously formed is filled with
tablets/capsules and lidded with a heat sealable backing material
The backing material is usually heat seal coated aluminium foil.
The plastic material used includes PVC, polyethylene combination.
For added moisture protection polyvinyledene fluoride or poly
chloro trifluoroethylene films may be laminated to PVC.
 Advantage-
o Unit dosage
o Convenience
o Child resistant
o Pleasing appearance
o Tamper resistant

Blister packaging

 Strip Packaging
o Strip package is a form of unit dose packaging that is commonly
used for the packaging of tablets and capsules. A strip package is
formed by feeding two webs of a heat sealable flexible film through
a heated crimping roller.
o The product is dropped into the pocket formed prior to forming the
final set of seals. A number different packaging. For high barrier
applications a proper/polyethylene/foil/polyethylene laminations
commonly used.

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 Strip packaging

 Bubble packing
o The bubble pack can be made in several ways but is usually
formed by sandwiching the product between a thermoplastic film
and a rigid packing material similar to a sin blister.

 Tape seal
o It involves the application of glued or pressure sensitive tape or
label around or over the closure of the package which is to be
destroyed to obtain the product.

 Shrink banding
o The heat shrinkable polymer-PVC is manufactured as a tube in a
diameter slightly larger than the cap and neck ring of the bottle to
be sealed.
o This is the placed over the bottle cap and the package through a
heated tunnel, which shrinks the plastic cover around the cap ,
preventing the disengagement of the cap without destroying the
shrink band .

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  Breakable Caps
o Breakable closures come in many different designs.
o The roll-on cap design of aluminium shell used for carbonated
beverages.
o The bottom portion of the cap is rolled around the bottle neck
finish.
o The lower portion of the cap blank is usually perforated so that it
breaks away when the cap is unscrewed. The bottom portion of
the closure has a tear away strip.

 Sealed Tubes.
o Collapsible tubes used for packaging are constructed of metal,
plastic or lamination of foil, paper and plastic.
o Metal tubes are still used for products that required high degree of
barrier protection

Significance –
1. Extra strong and secure packaging.
2. Regulations for some pharmaceuticals require it.
3. Extra layers of packaging.
4. Packages cannot be resealed

Packaging material
TYPES OF PACKAGING MATERIAL

Rubber
Plastic
Metal
Fibrous Material

Glass Film, Foil, Laminates

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 Glasses
o Glass has been widely used as a drug packaging material.
o Glass is composed of sand, soda ash, limestone,& cullet.
o Si, Al, Na, K, Ca, Mg, Zn & Ba are generally used into preparation
of glass.

 Advantage
o They are hygienic and suitable for sterilization.
o They are relatively non-reactive.
o It can accept a variety of closures.
o They can be used on high speed packaging lines.
o They are transparent.
o They have good protection power.
o They can be easily labelled.

 Disadvantage
o It is relatively heavy.
o Glass is fragile so easily broken.
o Release alkali to aqueous preparation.

 Metals
o Metal containers are used solely for medicinal products for non-
parenteral administration.
o Metal is strong, opaque, impermeable to moisture, gases, odour’s,
light, bacteria, and shatterproof, it is the ideal packaging material
for pressurized containers.
o It is resistant to high and low temperatures.
o They include tubes, packs made from foil or blisters, cans, and
aerosol and gas cylinders.
o Aluminium and stainless steel are the metals of choice for both
primary and secondary packaging for medicinal products.

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o Example - Aluminium
 Thickest aluminium is used for rigid containers such as aerosol
cans and tubes for effervescent tablets.
 Intermediate thickness are used to made Collapsible tubes for
semi solid preparations or roll on screw caps.
 Thinnest aluminium is used in flexible foils that are usually a
component of laminated packaging material.
 Rubber
o Excellent material for forming seals, used to form closures such
as bungs for vials or a gaskets in aerosol cans.
o Categories of Rubbers
 Natural Rubber- Suitable for multiple use closures
for injectable products as rubber reseals after multiple
insertion of needle.
 Synthetic rubber- Have fewer additives and thus
fewer extractable and tends to experience less sorption of
product ingredients.
 Are less suitable for repeated insertions of needle
because they tend to fragment or core pushing small
particles of the rubber in to the product.
 Silicone is least reactive but it does experience
permeability to moisture and gas.
 Ex- Silicone, butyl, bromobutyl, chlorobutyl etc.

 Plastic
o There are two classes of plastics, reflecting the behaviour with
respect to individual or repeated exposure to heating and cooling.

1. Thermoplastic
2. Thermosets

 Themoplastic-
 Capable of being shaped after initial heating and solidifying by
cooling.
 Resistant to breakage and cheap to produce and providing the
right plastics are chosen will provide the necessary protection of
the product in an attractive containers.
 Ex- Polystyrene, polyethylene and polyvinyl chloride.

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  Thermostat
 They need heat for processing into a permanent shape. During
heating such materials form permanent crosslinks between the
linear chains, resulting in solidification and loss of plastic flow.
 Ex- Phenolic, urea and melamine are representative of
thermosets.
 Uses- Used for many types of pack including;
 Rigid bottles for tablets and capsules, squeezable bottles for eye
drops and nasal sprays, jars, flexible tubes and strip and blister
packs.
 Advantage of Plastic
 Least expensive than glasses
 Ease of transportation
 No risk of breakage
 Flexible
 Light in weight
 Disadvantage of Plastic
 They are not as chemically inert.
 They are not as impermeable to gas and vapour as glass.
 They may possess an electrostatic charge which will attract
particles.

 Fibrous material
o The fibrous materials are the important part of pharmaceutical
packaging.
o Fibrous materials include: Papers, Labels, Cartons, Bags, Outers,
Trays for Shrink Wraps, Layer Boards On Pallets, etc.

Corrugated Fiber board Paper

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 The Applications as well as Advantages of Cartons include
 Increases display area.
 Provides better stacking for display of stock items.
 Assembles leaflets.
 Provides physical protection especially to items like metal
collapsible tubes.
 Regenerated cellulose film, trade names Cellophane &
Rayophane, is used for individual cartons or to assemble a no.
of cartons.

 FOILS,FILMS & LAMINATES

 Foils- The most important metal for pharmaceutical application is
aluminium.
 Films - Cellophane is an attractive transparent film which can be
colored and printed upon so it useful as outer wrap.
 Laminates- Laminates are used to combine the properties of
individual foil and films and strictly are made by bonding the layer
with adhesive .

Regulatory requirements in packaging

 FDA provides quality of drug product by carefully monitoring of
drug manufacture according to pharmaceutical regulatory
conference as per CGMP.
 Packaging is also is a part of CGMP.
 Legal requirement Acc to FDA…..
 Under the provision of the food drug & cosmetic act 1990
it is responsibility of manufacture to provide safety to get
approval before using any for food and drug product.
 FDA doesn’t approve containers but only the material
used in container.
 List of substance consider generally recognised as a safe
has been published by FDA.
 Material is not include in GRAS section & used with food.
 Must be tested by manufacture & data is submitted to
FDA.

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  Rule & regulation of label & packaging given in D &C act
in part 9
 Acc o FDA guideline for submitted document for
packaging or human drug required following detail.

1. Purpose- Packaging must maintain std identity

strength, quality, & purity through shelf life.
- Provide full information to costumers.
2. Environmental Factor-
- Reduction of quantity of waste.
- Recycling & Recovery of packaging waste.
- Recover of waste packaging.
- Provide protection to product from light,oxygen
etc.
3. Cost-
- Nature of product.
- Quality of material
-Types of transport
- Stability of product.
- Level of protection required.
4. FDA packaging guidelines five the type of
containers
- Parenteral
- Non parenteral
- Bulk
- Child resistance & temper resistance.
 FDA regulation for drug state that container, closure & other
component part of drug package suitable for use must not be
reactive & maintain quality purity, identity strength through the self-
life.

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EVALUATION TEST OF PACKAGING MATERIAL
1.Glass containers.
 Water attack test
 Powdered Glass test
 Hydrolytic resistance of Glass Containers.
 Arsenic Test
 Thermal Shock test
 Internal Bursting test
 Leakage Test
 Water attack test
o This test is used for Type-2 glass.
o This test is used only with containers that have been exposed
to sulphur dioxide fumes under controlled humidity conditions.
o Such a treatment neutralizes the surface alkali & the glass
becomes chemically more resistant.
o The principle involved in the water attack test is to determine
whether the alkali leached form the surface of a container is
within the specified limits or not.
o The amount of acid that is necessary to neutralize the released
alkali from the surface is estimated & the leaching of alkali is
accelerated using elevated temperature for a specified time.
o Methyl red indicator is used to determine the end point. The
basic is acid-base titration.
 Powdered Glass Test
o This test is used for type- 1,3,NP glass.
o It is done to estimate the amount of alkali leached from the
powdered glass.
o Step -1 : Preparation of glass specimen
 Few containers are rinsed thoroughly with
purified water and dried with stream of clean air.
 Grind the containers in a mortar to a fine
powder and pass through sieve no.20 and 50.
o Step -2 : Washing the specimen
 10gm of the above specimen is taken into 250
ml conical flask and wash it with 30 ml acetone.
 Repeat the washing, decant the acetone and
dried after which it is used within 48hr.

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 Procedure
 10gm sample is added with 50ml of high purity water in a 250ml
flask. Place it in an autoclave at 121⁰C±2⁰C for 30min.

Cool it under running water.

 Decant the solution into another flask, wash again with 15ml high
purity water and again decant.

 Titrate immediately with 0.02N sulphuric acid using methyl red as

an indicator and record the volume.

 HYDROLYTIC RESISTANCE OF GLASS CONTAINERS:

 Rinse each container at least 3times with CO2 free water .

 Fill & Cover the vials and bottles and keep in autoclave.

 Heat to 100⁰C for 10min and allow the steam to enter from the
vent cork. Rise the temp from 100⁰C to 121⁰C over 20min.

 Maintain the temp at 121⁰C to 122⁰C for 60min.Lower the temp

from 121⁰C to 100C over 40min venting to prevent vacuum.

 Remove the container from autoclave, cool and combine the

liquids, being examined.

 Measure the volume of test solution into a conical flask and

titrate with 0.01M HCl using methyl red as an indicator.

 Perform blank with water and the difference between the titration
represents the volume of HCl consumed by the test solution.

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 THERMAL SHOCK TEST
 Place the samples in upright position in a tray

 Immerse the tray into a hot water for a given time and transfers
to cold water bath, temp of both are closely controlled.

 Examine cracks or breaks before and after the test

 The amount of thermal shock a bottle can withstand depends on

its size, design and glass distribution.

 Small bottles withstand a temp differential of 60 to 80⁰C and 1 pint

bottle 30 to 40⁰C.

 A typical test uses 45C temp difference between hot and cold
water.

 INTERNAL BURSTING PRESSURE TEST

o The most common instrument used is American glass research
increment pressure tester.

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2.Quality test for closuers.

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 3.Test for plastic Containers

4.Test for Paper & boards

1) Air permeability test- Permeability is the main air flow
through unit area under unit pressure difference in unit time , under
specific condition , expressed as Pa-1 S-1
2) Tensile strength- Both wet & dry. The maximum tensile force
per unit width that a paper or board will withstand before breaking.

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 3) Cobb test- this measure the mass of water absorbed by 1cm2
of the test piece in a specified time under a head of 1cm of water.
It is determined by weighing before and after exposure to the
water, and usually quoted in g/m2
4) Specific test for Cartons-
a) Compression- Assessment of the strength of the erected
package, thereby, estimating the degree of protection that it
confers on the content.
b) Crease stiffness- also called the crease recovery test. This
involve testing a carton board piece & folding it through 900. It will
then try to recover its former position when the bending force is
removed. The increase & decrease in the inherent board stiffness
after folding is measured.

Note- Explain answer according to marks & requirement of

question.. but enlist of all parameter is necessary.

Methods for evaluation of packaging.

Chemical Evaluation

Mechanical Evaluation

Environmental Evaluation

 Chemical Evaluation
o The Ph value of material, chloride and sulphate in paper or board
alkalinity of glass, compatibility test with chemical or medicament
are typical of the chemical test.
 Mechanical Evaluation
o Standard test are available for properties, such as the brusting
strength & the tensile strength of paper, film, & foil & for the effect
of creasing, folding and so on.
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 Environmental Evaluation
o Material may be tested by standard method for absorptionof
water, permeability to water vapour, gasses, oils, odour, etc. &
for characteristics such as light transmission.

Note- other test like Water attack test , Power attack test,Air
permeability test. must be write from upper question.

Difference between primary & secondary Packaging.

PRIMARY SECONDRY
It is the material that first envelops the It is outside the primary packaging
product and holds it. This usually is the perhaps used to group primary
smallest unit of distribution or use. package together.

EX-Ampoules, vails, containers, EX- Paper & boards, Cartons,

dosing dropper,syringe,strip corrugated fibers,
package
Kindly add the point in the difference if u get from anywhere.

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IDEAL REQUIREMENT OF PACKAGING

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SELECTION OF PACKAGING MATERIAL

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