Introduction

Packaging is the by which the

pharmaceuticals are suitably packed so that
process
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, carbondioxide, 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.
 Desired Features of Containers and
Closure
Container must be rigid enough to prevent damage to contents i.e. crushing of
capsule, fracture of tablets
The material of the container must be inert i.e. it should not react with the contents
present in it.
The closure must prevent;
Access of moisture.
Loss of moisture in case of creams lotions etc.
Unintentional loss of contents.
Entry of dirt or other contaminants. For example odors or vapors.
The closure must be easily removed and replaced.
 Desired Features of Containers and
Closure
It must not be difficult to abstract the contents or to empty the container
completely.
For many products protection from light must be given.
The BPC defines; A light resistant container as one that doesn’t transmit more
than 10% of incident radiation at any wavelength between 290 nm – 450 nm.
The European Pharmacopoeia specifies uncolored glass for containers of
injectable preparations unless they are extremely light sensitive.
Medicaments or adjuncts must not be absorbed neither by container materials nor
must diffuse through the walls be possible.
It must be easy to label the container easily.
It must be elegant in appearance pharmaceutically.
 Four Groups

Well closed container:

This container protects the contents from contamination with extraneous solids
and under normal conditions of handling storage and transport prevents
unintentional release of contents.
Air tight containers:
Thus containers give protection form extraneous solids, liquids and vapors, under
normal conditions of handling storage and transport prevent changes due to
evaporation.
 Four Groups

Securely tight containers:

This is an air tight container with means of preventing unintentional displacement
of the closures.
Hermetically sealed containers:
This container is impervious to air and other gases under normal conditions of
handling, storage and transport. The most common example in glass ampule
sealed by fusion.
Containers for Liquid Oral Preparations

For “Intended to be swallowed” oral formulations:

Colorless glass bottles, flat from one side and ovoid from the other. The flat side is
for the label.
Screw caps made up of white propylene are available. They are of different sizes
50ml, 100ml, 500ml or 1000ml.
For “Not to be swallowed” oral formulations:
Ribbed or fluted bottle is used with pourable mouth shape. It is used to
differentiate between oral and external preparation.
Containers for Liquid Oral Preparations

Colored or fluted bottle is used for packaging. Some preparations needs an

applicator. For example; brush for paints and such preparations have wide
mouths.
Lotions and liniments and others without applicator must be packed in plastic
collapsible bottle with narrow tips.
Cavities; colored fluted bottle are used. Caps must have nozzle that assist
administration or instillation.
 For Inhaler formulations

Colored or fluted bottle are used for its packing.

Vitrellae inhalation: it is just like an ampule. It must be packed
in boxes for better protection.
 For Semi-Solid Formulations imp.q

Collapsible metal or plastic tube

These prevent contamination. One should not touch the tip of the tube to the
infected area while application to prevent contamination of the product.
These possess narrow orifice.
These prevent serious contamination.
The wastage of the dosage form is reduce.
For their better use, nozzle type applicators can be attached.
Not replaced by air.
Glass or Plastic pot
Plastic is preferred for packing as the metal is reactive to many chemicals. Similarly is
it cheap as compared to the metal bottles and easily available.
 For Solid Unit Dosage Form

“Intended to be swallowed, chewed, sucked, cachets, lozenges, pills,

capsules, tablets” Formulations are packed in
Paper board, Glass, Plastic, Aluminum.
“Intended to be used in body cavities, like; suppositories” formulations are
packed in
They are packed in shallow partitioned paper boxes. They are also wrapped in
aluminum foils individually and then placed in glass bottles.
 Powders

Powders for oral uses:

a) Bulk powders: They are packaged in wide mouth bottles made up of
glass or plastic.
b) Unit dose powders: They are individually packed in sachets. Then these
sachets are packed in hard boxes.
Powders for external use, in body cavities:
They are packed in plastic containers with perforated lids for their easy application.
 TYPES OF CONTAINER

The containers can be classified into the following types.

Well closed containers: A well closed c ontainers is used

to protect the preparation from conta mination by
extraneous solids to prevent the loss o f potency of e
constitu ents and to prevent the loss of activ
t, storage and handling. contents
transpor during
Air-tight containers: Air-tight container
protect the containers from atmospher f
liquids, solids or vapors. They prevent s arerugs
useddue
to to
efflorescence,
the d deliquescence or evaporation.
ic
contamination o
• Hermetically-Sealed containers: Hermetically sealed
is that which does notair orallow
other
container the pass through it. They are for
lly used
gases togenerally s.

• injectable
Light-resistant containers: Light resistant containers
are used toprotect the gs which undergo
decomposition in dru the light. For e.g .Amber
colored glass or presence
o of paque
glass.
• Single dose containers: They are used to s upply only one
dose of the medica ment. They are sealed in such a way that
the contents t be removed without remo ving the seal,
canno the m oved are consumed immediately.e,g .
contents so re
ampoules.
• Multi dose containers: A multi dose container should h old
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
ulti
m 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 een widely used as a drug packaging
b material.
 Glass is mposed of sand, sh, limestone,&
co cullet. soda a
 Si, Al, Na, erally used
K, Ca, Mg, Zn & into
preparation of Ba are gen glass
ADVANTAGES
• They are hygie ion
• They are relat nic and suitable for sterilizatg on the grade
chosen) ively non reactive
• They can be used on high speed packaging lines
( dependin
• 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.
 D ISADVANTAGES
• 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.
T YPES 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
Bottles Suspensions, Emulsions)
and
Jars Nasal & Ear Drops Type IV

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.
• 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 m echanical strength.
• They can be transporte d easily.
• Extremely resistant to breakage
• They are available in various shapes and sizes.
• They are resistant to in organic chemicals.
• They have good protection power.
• Flexible
• Variety of sizes and shapes
• Essentially chemically inert, strong, rigid Safety y, various designs
Disadvantages use, high qualit
• Absorption permeable
• Poor printing, thermo to moisture
• They are permeable tostatic charge
• They cannot withstand heat without softening or distorting
water
• They may interact with certain
vapour chemical to cause softening or distortion.
and
atmospher
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
POLY ETHYLENE:
PLASTICS
 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: P apers, Labels, Cartons, Bags, Ou ters,
Tray s For Shrink Wraps, La yer Boards On Pallets, etc.
 The Applications as well as Advantages of Cartons include:
 I ncreases 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 con nedtainers can
opeand closed. Proper closing of the contain use be er is
beca prevents loss of material by spilling or necessary
zation.
– It volatili avoids contamination of the t fro
– It produc m dirt,
microorganisms or insects. he effect
– Itprevents deterioration of the product from t n dioxid of the
environment such as moisture , oxygen or carbo e.

Material used for closures are; pharma

The closures for containers meant for storage sic ceutical
prodof ucts are generally made from the following mater ials.
– Cba
ork
– Gl
as
s
– Pl
as
• 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 b acking material usually foil.
aluminum

• Strip Packing: In strip packing the unit dosage of

drugs are hermitically sealed in between stri ps 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
 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.
Reference:
• Pharmaceutical Compounding and
Dispensing: Chris Langley and Dawn
Belcher.
• Cooper and Gunn’s : Dispensing for
Pharmaceutical Students
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.