Introduction

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, carbindioxide, moisture, micro-
organisms and prevent the loss of volatile
substances.
It also prevents the loss of medicament during
transport and handling.
 The qualities of good containers and
closures/ideal properties of containers and
closures
• An ideal container must meet the following criteria.
• It must preserve the physical properties of all dosage
forms and protect them against damage or breakage.
• It should protect the contents from the physical and
mechanical hazards. These include vibration,
compression, shock, puncture, abrasion etc.
• It must protect the product against undesirable or
adulterating chemical, biological or physical entities.
• It should protect the contents from the atmospheric
factors. For e.g. oxygen, Carbon dioxide.
• It should protect the contents from the loss of product
due to leakage, spillage or permeation.
• It should not interact with the contents. This includes
migration, absorption, adsorption or extraction.
• It should protect the contents from the loss of water and
volatile materials.
• The container must not impart its own color, test or odor
to the preparation.
• It should be capable of withstanding extremes of
temperature and pressure as well as to withstand
handling while empty, while filling, closing, sterilizing,
labeling, transport, storage and use by the customer.
• It must not alter the identity of the product.
• The container and closure must not react either
with each other or with the preparation.
• The closure must be easy to remove and
replace.
• The cost of the container and closure is an
integral part of overall cost of the preparation, so
it should not be high.
• Apart from all these a container and closure
should be attractive in appreance and must have
sale promotion and marketing value.
 TYPES OF CONTAINER

The containers can be classified into the following types.

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.

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.
• 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.

• 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.
• 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.

• 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.
• 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 OF PACKAGING
Primary packaging is the material that first envelops the product and holds
it. This usually is 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.
Secondary packaging -
Is outside the primary packaging perhaps used to
group primary package together.
Ex. Boxes, cartons
Tertiary packaging is used for bulk handling ,
warehouse storage and transport shipping. The most
common form is a palletized unit load that packs tightly
into containers.
Apart from primary and secondary packaging, two types of special
packaging are currently in use, as follows:

• Unit-dose packaging. This packaging guarantees safer

medication by reducing medication errors; it is also more practical
for the patient. It may be very useful in improving compliance with
treatment and may also be useful for less stable products.

• “Device” packaging. Packaging with the aid of an administration

device is user-friendly and also improves compliance. This type
of packaging permits easier administration by means of devices
such as prefilled syringes, droppers, transdermal delivery systems,
pumps and aerosol sprays. Such devices ensure that the medicinal
product is administered correctly and in the right amount
TYPES OF PACKAGING MATERIAL

I) Glass

II) Metals

III) Rubbers

IV) Plastics

V) Fibrous material

VI) Films, Foils and laminates

 GLASS:
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
• They are hygienic and suitable for sterilization
• They are relatively non reactive ( depending on the grade
chosen)
• They can be used on high speed packaging lines
• They can be easily labeled.
• They are transparent.
• They are available in various shapes and sizes.
• They can withstand the variation in temperature and
pressure during sterilization.
• They are economical and easily available.
• They can protect the photosensitive medicaments from light
during their storage.
• They are neutral after proper treatment.
• They are impermeable to atmospheric gases and moisture.
• They have good protection power.
• They do not deteriorate with age.
• They can be sealed hermetically or by removable closures.
 DISADVANTAGES
• It is relatively heavy
• Glass is fragile so easily broken.
• Release alkali to aqueous preparation.
• They may crack when subjected to sudden changes of
temperature.
• Some containers can impart alkalinity and insoluble flakes to
the formulations.
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.
 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.

TYPES OF GLASS:
• Type I ( Neutral or Borosilicate Glass)
• Type II ( Treated Soda-lime glass)
• Type III ( Soda-lime glass)
• NP—soda glass (non parenteral usage)
• Colored glass
• Neutral glass
 MINIMUM
TYPE OF
QUALITY OF
PACKAGE TYPE FORMULATION
GLASS THAT CAN
CAN BE PACKED
BE USED
Aqueous Injectables Of Any Type I
pH

Ampoule Aqueous Injectables Of pH

Type II
Less Than 7

Non-Aqueous Injectables Type III

Aqueous Injectables Of Any

Type I
pH

Aqueous Injectables Of pH
Type II
Less Than 7
Vial

Non-Aqueous Injectables Type III

Dry Powders For Parenteral

Use (Need To Be Type IV
Reconstituted Before Use)
 MINIMUM
TYPE OF
QUALITY OF
PACKAGE TYPE FORMULATION
GLASS THAT CAN
CAN BE PACKED
BE USED
Tablets, Capsules, Oral Solids
& Other Solids For Type IV
Reconstitution

Oral Liquids (Solutions,

Type IV
Suspensions, Emulsions)
Bottles
and
Nasal & Ear Drops Type IV
Jars
Certain Types Of External
Type IV
Semisolids (Rubeficients,
Local Irritants)

Blood & Related Products Type I

Auxiliary Packaging Device

Dropper With Certain Kind Of Products
Type IV

Aerosol product ( solution,

suspension, emulsion or
Aerosol container
semisolid Type I
type)
 METALS :
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:
• They are impermeable to light, moisture and gases.
• They are sturdy.
• They are made into rigid unbreakable containers by impact
extrusion.
• They are light in weight compared to glass containers.
• Labels can be printed directly on to their surface.
Disadvantages:
• They are expensive.
• They react with certain chemicals
COLLAPSIBLE TUBES METAL
• The collapsible metal tube is an attractive container that
permits controlled amounts to be dispensed easily, with
good reclosure, 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:
• Tin containers are preferred for food, pharmaceuticals and any
product for which purity is considered.
• Tin is the most chemically inert of all collapsible metal tubes .
Aluminium:
• Aluminium tubes offer significant savings in product shipping
costs because of their light weight .
• They are attractive in nature
Lead:
• Lead has the lowest cost of all tube metals and is widely used
for non food products such as adhesives, inks. paints and
lubricants.
• Lead should never be used alone for anything taken internally
because of the risk lead poison .
• With internal linings, lead tubes are used for products such as
chloride tooth paste.
 PLASTIC
 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
• They are light in weight than glass and can be handled easily.
• They are poor conductor of heat.
• They have sufficient mechanical strength.
• They can be transported easily.
• Extremely resistant to breakage
• They are available in various shapes and sizes.
• They are resistant to inorganic chemicals.
• They have good protection power.
• Flexible
• Variety of sizes and shapes
• Essentially chemically inert, strong, rigid Safety use, high quality, various designs
Disadvantages
• Absorption permeable to moisture
• Poor printing, thermostatic charge
• They are permeable to water vapour and atmosphere gases.
• They cannot withstand heat without softening or distorting(বিকৃত করা,)
• They may interact with certain chemical to cause softening or distortion.
Classes of plastics:
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 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. Polystyrene, polyethylene and polyvinyl chloride.
 Thermosets
• 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.
• E.g. Phenolic, urea and melamine are representative of
thermosets.
 TYPES OF PLASTICS
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.
 FIBROUS MATERIALS
 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.
 CLOSURES
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 are;

The closures for containers meant for storage of pharmaceutical
products are generally made from the following basic materials.
– Cork
– Glass
– Plastic
– Metal
– Rubber
• 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.
 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.

Butyl rubber
Nitrile rubber
Chloroprene rubbers
Silicon rubbers
 SYMBOLS USED ON PACKAGES
AND LABELS
Many types of symbols for package labeling are nationally
and internationally standardized. For product certifications,
trademarks, proof of purchase, etc. identification code .

Fragile This way up Keep away from sunlight Keep away from water
 Unit Dose packaging
• 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.
 Advantages of blister packaging
1. Prevention of broken glass bottles
2. Reduced costs and higher packaging speeds relative to other
packaging materials.
3. Blister packaging helps retain product integrity because drugs
that are prepackaged in blisters are shielded from adverse
conditions.
4. Furthermore, opportunities for product contamination are
minimal.
5. Each dose is identified by product name, lot number, and
expiration date.
6. Blister packaging protects pharmaceuticals in the home better
than bottles do.
7. Tamper evidence is another strength of blister packaging. The
dosage units are individually sealed in constructions of plastic,
foil, and/or paper. With blister packaging, however, each tablet or
capsule is individually protected from tampering until use, so any
form of tampering with a blister package is immediately visible.
 Two basic types of pharmaceutical
blister packages exist
1. In one variety the cavity is constructed of clear,
thermoformed plastic, and the lid is formed of clear plastic
or a combination of plastic, paper, and/or foil.
2. The other type of package contains foil as an essential
component of both webs, and its cavity is created by cold
stretching.
 Blister Packaging machine
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
1. Bottom foil uncoiler 6. Cover foil uncoiler 11. Discharge conveyor
2. Cold forming station 7. Cooling & slitting
3. Feeding device 8. Draw Off
4. Empty checker 9. Punching
5. Sealing & Embossing 10. Waste foil coiler
 Blister Packaging machine
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
 STRIP PACKING
• It 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 .
• The product is dropped into the pocket formed before
forming the final set of seals. A continuous strip of
packets is formed which is cut to the desired number of
packets in length.
• The materials used for strip package are cellophane,
polyester, polyethylene, polypropylene,
polyvinylchloride.
REFERENCES :-
– Dean DA, Evans ER, Hall H. Pharmaceutical packaging
technology ,1st ed,Pg:210-65.
– Remington.The Science and Practice of Pharmacy,
21st ed,Vol-1;Pg:1047-10 .
– Indian Pharmacopiea,2007,Vol-1;Pg:599-25
– Leon Lachman, Liberman AH, Kanig JL.The Theory
and Practice of Industrial pharmacy,4thed,Pg:711-22.
– Hanlon J. Handbook of Packaging
Engineering.4thed;Pg:412-49

42
 References:-

• Pharmaceutics-1 by R.M.Mehta, Page No.:-

74-85
• The Theory and Practice of Industrial
Pharmacy by Leon Lachman, Page No.:-711-
724
• Pharmaceutical Product Development by
N.K.Jain, Page No.:-341-377
• Aulton’s Pharmaceutics by Michael E. Aulton,
Page No.:-626-638
Design validation results shall include: the design identification, name of the
individual(s) performing the validation, method(s) used, and the date. All of this
information should be recorded in the design history file. If any significant change is
made in the packaging or packaging operation after validation, the new process will
need to be revalidated.

One of the most difficult aspects of package validation is determining how many
samples to test. The goal is not to over test because of cost considerations while still
running sufficient tests to provide statistically valid sampling. Statistical methods of
analysis are important in process validation. The following decision tree from Medical
Device and Diagnostic Industry, "Streamlining Package-Seal Validation," October
1992, provides various methods of statistical analysis. The manufacturer is challenged
with determining which statistical method is most applicable to their individual needs.
The resulting validation plan should identify, measure, and evaluate the key processes
and variables that will require assessment to complete a validation or revalidation of
the packaging and the packaging process.