This document discusses pharmaceutical packaging. It begins by defining packaging and explaining that pharmaceutical packaging provides protection for drugs, devices, blood products, and other items. It then categorizes packaging into primary, secondary, and tertiary levels. The document outlines various purposes of pharmaceutical packaging, including protecting contents from environmental and mechanical hazards, preventing loss or addition of contents, and providing identification. It also discusses important properties of packaging materials and containers, factors that influence packaging choice, and common types of containers.

2. Packaging is an economical means of providing
presentation, protection, identification/information,
containment, convenience and compliance for a
product during storage, carriage, display and use
until such time as the product is used or
administered.
Pharmaceutical packaging provides protection for
lifesaving drugs, surgical devices, blood and blood
products, neutraceuticals, powders, poultices, liquid
and dosage forms, solid and semisolid dosage
forms.
Introduction

3. Packaging
Packaging is the process by which the pharmaceuticals are
suitably packed so that they should retain their therapeutic
effectiveness from the time of their packaging till they are
consumed.
It is the art and science which involves preparing the articles
for transport, storage, display and use.
Container
A container may be defined as a device in which the drug is
enclosed and is in direct contact with the drug.
Closures
A closure is a device which seals the container to exclude
oxygen, carbon-dioxide, moisture, micro-organisms and
prevent the loss of volatile substances.
Definitions

4. Primary Packaging: This is the first packaging envelope
which is in touch with the dosage form or equipment. The
packaging needs to be such that there is no interaction with
the drug and will provide proper containment of
pharmaceuticals. E.g. Blister packages, Strip packages, etc.
Secondary Packaging: This is consecutive covering or
package which stores pharmaceuticals packages in it for
their grouping. e.g. Cartons, boxes, etc.
Tertiary packaging: This is to provide bulk handling and
shipping of pharmaceuticals from one place to another. e.g.
Containers, barrels, etc.
Categorically differentiating
pharmaceutical packaging

5. The package passes through a number of stages, beginning with
the container manufacturer, thence to the product manufacturer,
wholesaler, retailer and finally the consumer.
Therefore the packaging should perform the following purposes
1. Protect the contents from the environmental hazards:
This includes
a) Light - protect the contents from light.
b) Temperature - withstand extremes of temperature.
c) Moisture - withstand extremes of humidity.
d) Atmospheric gases - protect the contents from the effect of
atmospheric gases (e.g. aerial oxidation).
e) Particles - protect from particulate contamination.
f) Microorganisms - protect from microbial contamination.
Purposes of packaging

6. 2. Protects the content from the mechanical hazards: This includes
a) Vibration - Usually due to transportation.
b) Compression - this usually includes pressure applied during
stacking.
c) Shock - such as impact, drops or rapid retardation.
d) Puncture - penetration from sharp objects or during handling
operations.
e) Abrasion - this may create electrostatic effects.
3. To prevent the addition or loss of its contents: This includes
Protect the contents from both loss and gain of water.
a) Protect the contents from loss of volatile materials.
b) Must not shed particles into the contents.
c) Must not leach anything to the contents.

7. 4. Provide pharmaceutically elegant appearance: This
includes
a) In a competitive market the appearance of a package first
draws the attraction of the consumers than its contents.
b) Must be easy to label and thus to identify the product.
5. Product identification
The package must also give clear identification of the product
at all stages and again the life of the patient may depend upon
rapid and correct identification in emergencies.
6. Convenience
The form of the package should be such that, it offers
convenience at all stages of its life history.

8. The good packaging materials i.e. the containers and closures must meet
the following criteria. (Ideal properties of containers and closures)
1. The material must give the container sufficient strength to withstand the
extremes of temperature and pressure as well as to withstand handling
while empty, while filling, closing, sterilizing, labelling, transport, storage
and use by the consumer.
2. The material should be impervious to any possible contaminants; for
example solids, liquids, gases vapours or microorganisms.
3. It should not interact with the contents. This includes migration,
absorption, adsorption or extraction. e.g. Absorption of water from
creams into cardboard boxes.
4. It should protect the contents from the loss of product due to leakage,
spillage or permeation.
5. It should protect the contents from the loss of water and volatile
materials.
6. The container must not impart its own colour, test or odour to the
preparation.
7. It must not alter the identity of the product.
Properties of packaging materials

9. 8. They must be FDA (Food & Drug Administration) approved,
9. They must meet applicable tamper-resistance requirements
10. They must be adaptable to commonly employed high-speed
packaging equipment.
11. Must be cheap and economical i.e. they must have
reasonable cost in relation to the cost of the product.
12. They must be convenient and easy to use by the patient.
13. They must be non-toxic and biodegradable.
14. The container and closure must not react either with each
other or with the preparation.
15. Apart from all these a container and closure should be
attractive in appearance and must have sale promotion and
marketing value.
Properties (cont….)

10. The choice of package is governed by the facilities available and by
the ultimate use of the product.
Some of the important aspects include
1. The physical form of the product e.g. solid, semisolid, liquid or
gas.
2. Chemical and physical characteristics of the drug entity, the
excipients and the formulation;
3. Product detail covering any recognized routes of deterioration or
degradation.
4. The dosage form and frequency of dosage,
5. The route of drug administration e.g. oral, parenteral, or external.
6. Type of patient (baby, child, teenager, adult, elderly, infirm etc.),
7. The stability of the product i.e. its protective needs.
Factors influencing the choice of packaging

11. 8. Interaction of the product with the packaging materials.
9. Marketing requirements of the product.
10. The eventual channels of sale, i.e. where, when, how and by whom
it is to be used or administered (e.g. doctor, dentist, nurse, patient
etc.)
11. Whether the product is seasonal or has a year round use may be a
further influence on pack selection.
12. The place of using the product, i.e. Clinic, Home, Hospital etc.
13. The distribution system, for example conventional wholesale/retail
outlets, or direct to selected outlets.
14. The suitability of the manufacturing facilities may have to be
considered for a number of reasons, i.e . New pack increased
sales, improvements in GMP, revised product, new product etc.
15. Over all costs should be considered in order to make a cost
effective quality product.
Factors (Cont….)

12. The containers can be classified into the following types.
1. Well closed containers: A well closed containers is used to
protect the preparation from contamination by extraneous
solids to prevent the loss of potency of active constituents and
to prevent the loss of contents during transport, storage and
handling.
2. Air-tight containers: Air-tight containers are used to protect
the containers from atmospheric contamination of liquids,
solids or vapors. They prevent the drugs due to efflorescence,
deliquescence or evaporation.
3. Hermetically-Sealed containers: Hermetically sealed
container is that which does not allow the air or other gases to
pass through it. They are generally used for injectables.
Types of Container

13. 4. Light-resistant containers: Light resistant containers are
used to protect the drugs which undergo decomposition in the
presence of light. For e.g .Amber colored glass or opaque
glass.
5. Single dose containers: They are used to supply only one
dose of the medicament. They are sealed in such a way that
the contents cannot be removed without removing the seal;
the contents so removed are consumed immediately. e,g.
ampoules.
6. Multi dose containers: A multi dose container should hold a
number of doses. It is sealed in such a way that success
doses can be withdrawn easily without changing the strength,
quality or purity of the remaining contents e.g multi dose vials.
7. Aerosol containers: Containers for aerosols must be strong
enough to withstand the pressure evolved inside the container
at the time of use of preparation.
Types (Cont….)

14. 1. Glass / Polyethene bottles
 Wide mouthed bottles are used for containing solid dosage forms like
powder, capsules, and tablets. To absorb the moisture sometimes silica-gel
bags are given inside the bottle.
 For low viscosity liquids e.g. gargles, mouth washes, mixtures, elixirs narrow
mouthed bottle is used. For high viscosity liquids or for suspensions
wide-mouthed bottles are used.
 Liquid preparations for external uses like lotion, liniments, paints etc. are
supplied in coloured fluted bottles in order to distinguish them from
preparations meant for internal use.
2. Dropper bottles or droptainers: Eye drops, ear drops, nasal drops etc.
should be dispensed in amber colour glass bottles fitted with a dropper. Now-
a-days manufacturers prefer plastic droptainers. It is a single piece of
squeezable container having an in built dropper.
3. Collapsible tubes: Ointments, pastes, gels are packed in plastic or metal
tubes.
Classification of containers according
to their shapes

15. 4. Ampoules: Ampoules are made of special type of neutral glass
having low m.p. so that it can be heat sealed at low temperature.
5. Vials: Used for storing multi dose indictable preparation. The
needle is passed through the rubber closure, the drug is drawn
out. The rubber plug automatically seals the hole. Thus
contamination of bacteria is checked.
6. Polyethene packets for infusion fluid: These flexible bags or
packets are made of PVC, polyethylene or polypropylene.
7. Glass bottles for i.v. fluids: Previously glass bottles with big
rubber stoppers were used.
Classification(Cont…)

16. The following materials are used for the construction of containers and closure
1. Glass:
a) Type I ( Neutral or Borosilicate Glass) b) Type II ( Treated Soda-lime glass)
c) Type III ( Soda-lime glass) d) Type IV- General Purpose soda lime glass
e) NP—soda glass (non parenteral usage) f) Coloured glass g) Neutral glass
2. Metals: a) Tin b) Iron c) Aluminium d) Lead.
3. Plastics: a) Thermosetting resins : (i) Phenolics (ii) Urea
b) Thermoplastic resins: (i) Polyethylene (ii) Polypropylene
iii) Polyvinylchloride (PVC) (iv) Polystyrene (v) Polycarbonate
(vi) Polyamide (Nylon) (vii) Acrylic multipolymers (viii) Polyethylene terephthalate (PET)
4. Rubber: a) Natural rubber b) Neoprene rubber c) Butyl rubber.
5. Fibrous material
6. Films, foils and laminates
Materials used for the making of containers

17. Glass has been widely used as a drug packaging material. Glass is composed of
sand, soda ash, limestone, & cullet. Si, Al, Na, K, Ca, Mg, Zn & Ba are generally
used into preparation of glass.
Advantages
1. They have good protection power as they are impermeable to atmospheric
gases and moisture with a proper closure system.
2. They are relatively non-reactive (depending on the grade chosen).
3. They can be used on high speed packaging lines.
4. They can be easily labeled.
5. They are usually transparent.
6. Colored glass especially amber, can protect the photosensitive medicaments
from light during their storage.
7. They are hygienic and suitable for sterilization; as they can withstand the
variation in temperature and pressure during sterilization.
8. They are neutral after proper treatment.
9. They do not deteriorate with age.
10. They are economical and easily available in various shapes and sizes.
Glass and Glass Containers

18. 1. Glass is fragile so easily broken.
2. They are heavier in comparison to plastic containers.
3. Release alkali to aqueous preparation.
4. They may crack when subjected to sudden changes of temperature.
5. Some containers can impart alkalinity and insoluble flakes to the formulations.
6. Transparent glasses gives passage to UV-light which may damage the
photosensitive drugs
Flaking
During flaking the alkali is extracted from the surface of the glass containers and a
silica rich layer is formed which sometimes gets detached from the surface and can
be seen in the contents in the form of shining flakes. This is a serious problem,
especially in parenteral preparations.
Weathering
Weathering is a common problem with glass containers in which sometimes moisture
condensed on the surface of glass container, can extract some weakly bonded alkali,
leaving behind a white deposit of alkali carbonate. Further condensation of moisture
will lead to the formation of an alkaline solution which will dissolve some silica
resulting in loss of brilliance from the surface of glass called weathering.
Disadvantages

19. 1. Type I ( Neutral or Borosilicate Glass)
2. Type II ( Treated Soda-lime glass)
3. Type III ( Soda-lime glass)
4. Type IV- General Purpose soda lime glass
5. NP—soda glass (non-parenteral usage)
6. Colored glass
7. Neutral glass
Type I-Borosilicate glass:
Highly resistant and chemically inert glass. Alkali’s and earth cations of glass are replaced
by boron and/or aluminum and zinc. These are used to contain strong acids and alkalis.
Type II-Treated soda-lime glass:
These are more chemically inert than Type I glass. The glass surface is de-alkalized by
“Sulfur treatment” which prevents blooming/weathering from bottles.
Type III- Regular soda lime glass:
Untreated soda lime glass with average chemical resistance.
Type IV- General Purpose soda lime glass:
Glass is not used for parenterals, used only for products intended to be used orally or
Types of glass

20. Type of glass Main Constituents Properties Uses
Type-I
Borosilicate glass
e.g. Pyrex, Borosil
SiO2  80%
B2O3  12
Al2O3 - 2%
Na2O+CaO - 6%
1. Has high melting point so can withstand high temperature
2. Resistant to chemical substances
3. Reduced leaching action
1. Laboratory glass apparatus
2. For injections and
3. For water for injection.
Type-II
Treated soda-lime
glass
Made of soda lime glass. The surface of
which is treated with acidic gas like SO2
(i.e. dealkalised) at elevated temperature
(5000C) and moisture.
1. The surface of the glass is fairly resistant to attack by water for a
period of time.
2. Sulfur treatment neutralizes the alkaline oxides on the surface,
thereby rendering the glass more chemically resistant.
1. Used for alkali sensitive products
2. Infusion fluids, blood & plasma.
3. Large volume container
Type-III
Regular soda-lime
glass
SiO2
Na2O
CaO
1. It contains high concentration of alkaline oxides and imparts alkalinity
to aqueous substances
2. Flakes separate easily.
3. May crack due to sudden change of temperature.
1. For all solid dosage forms (e.g. tablets, powders)
2. For oily injections
3. Not to be used for aqueous injection
4. Not to be used for alkali-sensitive drugs.
Type of glass
Main Constituents Properties Uses
Type NP
Non-parenteral
glass or General
purpose soda-lime
glass.
1. For oral and
2. Topical purpose
3. Not for ampoules.
Neutral Glass SiO2  72-75%
B2O3  7-10%
Al2O3  6%
Na2O  6-8%
K2O  0.5  2%
BaO  2-4%
1. They are softer and can easily be moulded
2. Good resistance to autoclaving
3. Resistant to alkali-preparations (with pH upto 8)
4. Lower cost than borosilicate
1. Small vials (<25 ml)
2. Large transfusion bottles
Neutral Tubing for
Ampoules
SiO2  67%
B2O3  7.5%
Al2O3  8.5%
Na2O  8.7%
K2O  4%
CaO  4%
MgO  0.3%
1. In comparison to neutral glass its melting point is less. After filling the
glass ampoules are sealed by fusion and therefore the glass must be
easy to melt.
1. Ampoules for injection.
Coloured glass Glass + iron oxide 1. Produce amber colour glass
2. Can resist radiation from
290 400 450nm
UV Visible
1. For photosensitive products.

21. Metals are used for construction of containers. The metals commonly
used for this purpose are aluminium, tin plated steel, stainless steel,
tin and lead.
Advantages
1. They are sturdy. (শক্ত)
2. They are impermeable to light, moisture and gases.
3. They can be made into rigid unbreakable containers by impact
extrusion.
4. They are light in weight as compared to glass containers.
5. Labels can be printed directly on to their surface.
Disadvantages
1. They are expensive.
2. They react with certain chemicals
3. They may shed metal particles into the pharmaceutical product.
Metal and metal containers

22. COLLAPSIBLE TUBES METAL
The collapsible metal tube is an attractive container that permits controlled
amounts to be dispensed easily, with good enclosure, and adequate protection of
the product. It is light in weight and unbreakable and lends itself to high speed
automatic filling operations.
Most commonly used are tin, aluminium and lead.
TIN
Advantages:
I. This metal is very resistant to chemical attack.
II. Readily coats a number of the metals e.g. tin-coated lead tubes combine the
softness of lead with the inertness of tin and for this reason it was formerly
used for packaging fluoride toothpaste.
Disadvantage:
I. Tin is the most expensive metal among tin, lead, aluminium and iron.
Uses:
I. Tin containers are preferred for foods, like milk powder containers are coated
with tin.
II. Currently, some eye ointment still packaged in pure tin ointment tubes.

23. ALUMINIUM
Advantages:
1. Aluminium is a light metal-hence the shipment cost of the product is less.
2. They provide attractiveness of tin at somewhat lower cost.
3. The surface of aluminium reacts with atmospheric oxygen to form a thin,
tough, coherent, transparent coating of oxide, of atomic thickness, which
protects the metal from further oxidation.
Disadvantages:
1. Any substance that reacts with the oxide coating can cause corrosion
e.g. products with the oxide coating can cause corrosion e.g. products of
high or low pH, some complexing agents etc.
2. As a result of corrosion process H2 may evolve.
Uses:
1. Aluminium ointment tubes.
2. Screw caps
3. Aluminium strips for strip-packaging of tablet, capsules etc. Sometimes
internally lacquered aluminium containers are used to stop the reaction
with the content.

24. LEAD
Advantages:
1. Lowest cost of all the metals used in pharmaceutical containers.
2. Soft metal.
Disadvantage:
Lead when taken internally there is risk of lead poisoning. So lead containers
and tubes should always have internal lining of inert metal or polymer.
Use:
With lining lead tubes are used for such product as fluoride tooth paste.
IRON
Advantages: Iron as such is not used for pharmaceutical packaging, large qualities of
tin-coated steel, popularly called ‘tin’, combines the strength of steel with the corrosion
resistance of tin.
Disadvantages: If an aqueous liquid can penetrate a pinhole or other fault in the layer of tin,
which is virtually a short-circuited galvanic cell is set up and the intense chemical reaction
which results brings about rapid corrosion of underlying steel. As a further measure the tin
surface is lacquered.
Uses: Screw caps and aerosol cans.

25. Plastics may be defined as any group of substances, of natural or synthetic origins,
consisting chiefly of polymers of high molecular weight that can be moulded into a
shape or form by heat and pressure.
Advantages
1. They are light in weight than glass and can be handled easily.
2. They are poor conductor of heat.
3. They have sufficient mechanical strength.
4. They can be transported easily.
5. Extremely resistant to breakage.
6. They are available in various shapes and sizes.
7. They are resistant to inorganic chemicals.
8. They have good protection power.
9. Flexible.
10. Variety of sizes and shapes.
Plastic and plastic containers

26. Disadvantages
1. All are permeable to some degree to moisture, oxygen,
carbon dioxide etc.
2. Most exhibit electrostatic attraction.
3. Allow penetration of light rays unless pigmented black etc.
4. Poor printing, thermostatic charge.
5. They cannot withstand heat without softening or
distorting.(বিকৃ ত করা,)
6. They may interact with certain chemical to cause softening or
distortion.
7. They may absorb chemical substances, such as
preservatives for solution.
8. Over all they are prone to possible extraction, interaction,
adsorption, absorption, lightness and hence poor physical
stability.
Plastic(Cont….)

27. There are two classes of plastics, reflecting the behavior with respect to
individual or repeated exposure to heating and cooling.
Thermoplastics
Capable of being shaped after initial heating (On heating, they soften to a
viscous fluid) 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.
E.g. Polyethylene, polypropylene, polyvinylchloride, polystyrene, nylon
(polyamide), polycarbonate, acrylic multipolymers, polyethylene
terephthalate etc.
Thermosets
When heated, they may become flexible but they do not become liquid;
usually their shape is retained right up to the temperature of decomposition.
Because of a high degree of cross-linking they are usually hard and brittle at
room temperature.
During heating such materials form permanent crosslinks between the linear
chains, resulting in solidification and loss of plastic flow.
E.g. Phenolic, urea and melamine are representative of thermosets.
Classes of plastics

28. Poly ethylene:
This is used as high and low density polyethylene
Low density polyethylene (LDPE) is preferred plastic for squeeze
bottles.
High density poly ethylene (HDPE) is less permeable to gases
and more resistant to oils, chemicals and solvents. It is widely
used in bottles for solid dosage forms.
Polyvinylchloride (PVC): Used as rigid packaging material and
main component of intravenous bags.
Poly Propylene: It has good resistance to cracking when flexed.
Suitable for use in closures, tablet containers and intravenous
bottles.
Polystyrene: It is also used for jars for ointments and creams
with low water content.
Examples of Plastics

29. Natural rubber consists of long chain polymers of isoprene units linked together in the cis-
position. Its most important source is the tree Hevea braziliensis from which a latex, containing
30 to 40% of rubber in colloidal suspension, exudes when shallow cuts are made in the bark.
The main types of rubber used for pharmaceutical products include natural rubber, neoprene,
nitrile, butyl, chlorobutyl, bromobutyl and silicone rbber.
Categories of Rubbers:
Mainly two types of rubbers are used
Natural rubber: Suitable for multiple use closures for injectable products as rubber reseals
after multiple insertion of needle.
Disadvantages:
– It doesn't well tolerate multiple autoclaving; whereby they become brittle and leads to relative degree of
extractable material in presence of additives.
– Risk of product absorption on or in to a rubber.
– It has certain degree of moisture & gas permeation.
Synthetic rubber: Have fewer additives and thus fewer extractable and tends to experience
less sorption of product ingredients.
Disadvantages:
1. They are less suitable for repeated insertions of needle because they tend to fragment
2. Sometimes the core pushes small particles of the rubber in to the product.
e.g. Silicone, butyl, bromobutyl, chlorobutyl etc.
Rubber

30. BUTYL RUBBER
These are copolymers of isobutylene with 1-3% of isoprene or butadiene.
Advantages
1. After vulcanization butyl rubber possesses virtually no double bond, consequently
they are most resistant to aging and chemical attack.
2. Permeability to water vapour and air is very low.
3. Water absorption is very low.
4. They are relatively cheaper compared to other synthetic rubbers.
Disadvantages
1. Slow decomposition takes place above 1300°C.
2. Oil and solvent resistance is not very good.
NITRILE RUBBER
Advantages:
1. Oil resistant due to polar nitrile group.
2. Heat resistant.
Disadvantage
Absorption of bactericide and leaching of extractives are considerable.
Examples of Rubbers

31. CHLOROPRENE RUBBERS (NEOPRENE)
These are polymers of 1:4 chloprene.
Advantages
I. Due to the presence of Cl group close to the double bond, resistant to oxidation.
II. This rubber is more polar hence oil resistant.
III. Heat stability is good (up to 1500°C).
IV. Water absorption and permeability are less than for natural rubbers.
SILICONE RUBBERS
Advantages
I. Heat resistance (up to 2500°C).
II. Extremely low absorption and permeability of water.
III. Excellent aging characteristics due to their saturated chemical structures.
IV. Poor tensile strength.
Disadvantages
I. They are very expensive.
II. experience permeability to moisture and gas
Examples(Cont….)

32. The fibrous materials are the important part of pharmaceutical
packaging.
 Fibrous materials include: Papers, Labels, Cartons, Bags, Outers,
Trays for Shrink Wraps, Layer Boards On Pallets, etc.
 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.
 Fiberboard outers either as solid or corrugated board also find
substantial application for bulk shipments.
Regenerated cellulose film, trade names Cellophane & Rayophane, is
used for either individual cartons or to assemble a no. of cartons
Fibrous Materials

33. Regenerated cellulose film based on viscose ( chemical used for
manufacturing of rayon) & laminating two or more types of films, cellulose
coatings, foil and paper play different roles such as supportive, barrier, heat
seal & decorative.
For Example: Aluminum foil even in the thinnest gauges offers the best
barrier properties, which are not approached even by the most impermeable
plastics.
Plastics, as either films or coatings, can be used for decoration, flexibility, to
provide various barrier properties, heat seal ability, see-through properties
(i.e. transparency), and to protect the other plies within the lamination.
Metallization a relatively new process whereby particles of metal are laid
down onto a surface under vacuum, can significantly improve the barrier
properties of a material but these do not approach the properties of a pure
foil.
In the newer technology Co-Extrusion a number of plastic plies are extruded
in combination to produce cheaper laminations.
Films, Foils & Laminates

34. Uses of films, foils, laminations:
– Strip packs
– Blister packs
– Sachets
– Diaphragm seals for bottles
– Liners for boxes either attached or loose bag-in-box systems &
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.
Both blister and strip packs appear to offer a reasonable degree of
child resistance; particularly if the materials are opaque (opinion based
on actual recorded poisonings or accidents).
Films (Cont….)

35. Alu-alu foil is the best pharmaceutical packaging film for tablets, capsules,
which is taking place of PVC film.
Characteristics:
– Applicable to tablets, capsules, pills, etc.
– It's a good substitute for PVC sheet.
– No cracking, delamination or pinholes.
– It has the quite good blocking properties effectively protecting drugs
from water vapor, oxygen and ultraviolet.
– It is particularly suitable for packing moisture-sensitive drugs or those
sold in the hot and humid areas.
– Taking out a part of the drugs from the drug boards without any impact
on other
well-packaged drugs.
– It is used by cold-moulding packaging machines where it is easily
shaped by changing the mold.
– Nice appearance can upgrade drug's image
Films (Cont….)

36. A tamper resistant package is provided with an indicator or barrier
before entering the package, so that if this indicator or barrier is
broken, the buyer immediately gets the evidence that the product has
been opened or tampered. Especially over the counter products
require tamper resistant packaging.
The following packages are approved by FDA as tamper resistant
packaging systems:
Tamper Resistant Packaging
1. Film wrappers
2. Blister package
3. Strip package
4. Bubble pack
5. Shrink seals and bands
6. Foils, paper or plastic pouches
7. Bottle seals
8. Tape seals
9. Breakable caps
10.Sealed tubes
11.Aerosol containers
12.Sealed cartons.

37. Film wrapper can be categorized into:
I. End-folded wrapper:
This is formed by passing the product into a sheet of overwrapping film, which forms the film around the
product and folds the edges in a gift-wrap fashion. The folded areas are heat sealed by passing against a
heated bar.
Materials:Cellophane coated in both side by heat sealable polyvinylidene chloride (PDVC) or nitrocellulose-
PDVC provides durable moisture barrier.
Polypropylene coated with heat sealable acrylic coating or polypropylene is added with heat sealable
modifiers.
II. Fin seal wrapper
The seals are formed by crimping the film together and sealing together the two inside surfaces of the film,
producing a ‘fin’-seal.
In this case heated bars never comes in contact with the package, hence much greater and more
consistent sealing pressure can be applied and consequently better sealing integrity can be accomplished.
Materials: Polyethylene or Surlyn (Du Pont’s Ionomer resin)
III. Shrink wrapper
In this type of packaging the product is packed within a thermoplastic film that has been stretched and
oriented during its manufacture and that has the property of reverting back to its unstretched dimensions
once the molecular structure is ‘unfrozen’ by application of heat.
As the film unwinds on the over-wrapping machine, a pocket is formed in the center fold of the sheet, into
which the product is inserted. An L-shaped sealer seals the remainder of the overwrap and trims off the
excess film.
Materials: Heat shrinkable grades of polypropylene, polyethylene and polyvinylchloride (PVC).
Film Wrapper

39. 4. Bubble pack
The bubble pack can be made in several ways but is usually formed by
sandwiching the product between a thermoformable, extensible or heat-
shrinkable plastic film and a rigid backing material. This is generally accomplished
by heat-softenting the plastic film and vacuum drawing a pocket into the film in a
manner similar to the formation of a blister in a blister pack-age.
5. Shrink Banding
The heat-shrinkable polymer is manufactured as an extruded oriented tube in a
diameter slightly larger than the cap and neck ring of the bottle to be sealed. The
heat-shrinkable material is supplied to the bottle as a printed, collapsed tube,
either pre-cut to a specified length or in roll from for an automated person.
6. Foil, Paper or Plastic Pouches
The flexible pouch is a packaging concept capable of providing not only a
package that is temper- resistant but also a package with a high degree of
environmental protection. A flexible pouch is usually formed during the product
filling operation.
7. Bottle seal
A bottle may be made temper-resistant by bonding an inner seal to the rim of the
bottle in such a way that access to the product can only be attained by irreparably
destroying the seal. Frequently used inner seals are glassine and foil laminates.

40. 8. Tape Seals
Tape sealing involves the application of a glued or pressure-sensitive tape
or label around or over the closure of the package, which must be
destroyed to gain access to the packaged product. The paper used most
often is a high density lightweight paper with poor tear strength.
9. Breakable Caps
Breakable closures come in many different designs. The roll-on cap
design used in the past for carbonated beverages uses an aluminium
shell, which is placed over the bottle neck during the capping operation.
10. Sealed Tubes
Collapsible tubes used for packaging are constructed of metal, plastic or
lamination of foil, paper and plastic. Metal tubes are still used for those
products that require the high degree of barrier protection afforded by
metal.

41. 11. Aerosol containers
The aerosol container used for pharmaceutical products is usually made of
drawn aluminium. The inside of the container can be specially coated if
product compatibility is a problem. A hydrocarbon propellant in its cooled
liquid phase is added to the container along with the product, and a spray
nozzle contained in a gasketed metal ferrule is crimped over the opening of
the aerosol container.
A length of polyethylene tube, called a dip-tube, is attached to the inside of
the spray nozzle and dips into the product, drawing product into the spray
nozzle when the sprayer is activated.
The spray nozzles are usually metered to allow a specific dose to be
dispersed with each spray.
12. Sealed Cartons
Folding paperboard cartons have been used as a secondary package for
OTC products for many years. The popularity of this packaging mode is
based on both functional and marketing consideration.

42. Closures are the devices by means of which containers can be opened
and closed.
Proper closing of the container is necessary because
– It prevents loss of material by spilling or volatilization.
– It avoids contamination of the product from dirt, microorganisms or
insects.
– It prevents deterioration of the product from the effect of the
environment such as moisture, oxygen or carbon dioxide.
Material used for closures
The closures for containers meant for storage of pharmaceutical products
are generally made from the following basic materials.
 Cork
 Glass
 Plastic
 Metal
 Rubber
CLOSURES

43. • Cork: Cork is essentially a wood obtained from the bark of
oak tree. It is used for the manufacture of stoppers for
narrow mouth bottles.
• Glass: As compared to cork glass is an ideal material for
stoppers but they do not provide leak proof closure as well
as can easily slip out of the neck of the closure during
transport and handling.
• Plastic: As compared to cork, glass, rubber and metal
Plastic closures are becoming popular day by day as they
are unbreakable, light in weight and can be easily molded
into various shapes and sizes.
• Metal: Tin plate and aluminum are mostly commonly used
for the manufacture of closures but aluminum is mostly
used for this purpose.

44. 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.
Categories of Rubbers:
Natural rubbers: 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.

45. Blister Packing: In blister packing the unit dosage forms are
enclosed in between transparent blisters and suitable backing
material usually aluminum foil.
Strip Packing: In strip packing the unit dosage of drugs are
hermitically sealed in between strips of aluminum foil and/or
plastic film.
Blister package
The blister package is formed by heat-softening a sheet of
thermoplastic resin and vacuum drawing the soften sheet into a
contoured mold. After cooling, the sheet is released from the
mold and proceeds to the filling station of the packaging
machine. The semi-rigid blister previously formed is filled with
product and lidded with a heat-sealable backing material.
Unit Dose packaging

46. The backing material may be of two types:
(i) A push-through type or (ii) Peelable type.
Materials
The blister is prepared from polyvinylchloride (PVC)
PVC / polyethylene combinations
polypropylene
polystyrene.
For commercial reason and for machine performance the blisters on most unit dose
packages are made of PVC. For moisture protection PVC may be laminated with
polyvinylidene chloride (saran) or polychlorotrifluoroethylene (Aclar) films. Under
extremely humid condition Aclar coated PVC is preferred.
For push through type backing material aluminium foil coated with heat sealable
coating is used.
For peelable type backing material polyester or paper is used as a component of the
backing lamination. This peelable type backing material is tamper proof and child
resistant.
Blister package (Cont….)

47. Advantages of Blister Package:
1. Reduced costs and higher packaging speeds relative to other
packaging materials. Blister packaging helps retain product integrity
because drugs that are prepackaged in blisters are shielded from
adverse conditions.
2. Opportunities for product contamination are minimal.
3. Each dose is identified by product name, lot number, and expiration
date.
4. Blister packaging protects pharmaceuticals in the home better than
bottles do.
5. Each tablet or capsule is individually protected from tampering until use

48. Two basic types of pharmaceutical blister packaging machine exists
Cold Forming Blistering machine:
In the case of cold forming, an aluminum-based laminate film is simply pressed into a mold by
means of a stamp. The aluminum will be elongated and maintain the formed shape.
Advantage of cold form foil blisters is that the use of aluminum is offering a near complete
barrier for water and oxygen, allowing an extended product expiry date.
The disadvantages of cold form foil blisters are the slower speed of production compared to
thermoforming and the lack of transparency of the package and the larger size of the blister
card.
Example: ALU-ALU Machine
Operation:
The sequence involves;
1. Installing the Aluminium Foil,
2. Cold forming it into blister cavities via punch pins,
3. Loading the blister with the product,
4. Placing lidding material over the blister,
5. And heat-sealing the package.
6. Cutting into individual blisters
Types of pharmaceutical blister packaging machine

50. Thermo-cold forming blistering machine:
In the case of thermoforming, a plastic film or sheet is unwound from the reel and
guided though a pre-heating station on the blister line. The temperature of the
pre-heating plates (upper and lower plates) is such that the plastic will soften and
become moldable.
Example: ALU-Tropical Machine
Operation:
The sequence involves;
1. Heating the plastic,
2. Thermoforming it into blister cavities,
3. Loading the blister with the product,
4. Placing lidding material over the blister,
5. And heat-sealing the package.
6. Installing the aluminium foil
7. Cold forming it into blister Pouch & seal it on thermoformed blister to give extra
protection,
8. Cutting into individual blisters
Blister packaging machine(Cont….)

52. A strip package is a form of unit dose packaging that is commonly used for package is formed by
feeding two webs of a heat-sealable flexible film through either a heated crimping roller or heated
reciprocating plates. The product is dropped into the pocket formed prior to forming the final set of
seals.
A continuous strip is formed, generally several packets wide. The strip packets are cut to the
desired number of packets in length.
The product usually has a seal around each tablet. The seal can be rectangular, or “picture-frame
format” or can be contoured to the shape of the product.
Since the sealing is usually accomplished between pressure rollers, a high degree of seal integrity
is possible.
Materials:
High barrier materials e.g. foil laminations, saran-coated films.
For higher barrier applications a paper/polyethylene/foil/polyethylene lamination is commonly used.
When product visibility is important a heat-sealable cellophane or polyester can be used.
Strip package

54. 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.
Quality Assurance Aspects of Packaging

55. 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.
Sampling and testing of packaging materials

56. 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
Sampling and testing(Cont….)

57. & GOOD LUCK
THANKS