Anything that requires doctors prescription, certain OTC drugs, aspirin, ibuprofen, iron, fluoride. Any solid dosage form
Click lok closures are used in case of seeper bottles
It is used to evaluate child resistant packaging and it is similar in all the countries with regulation in the force.
Then test will pass otherwise fails
Containers & closures
M.PHARMACY 1ST YEAR
SUBMITTED TO :
Types Of Containers
Their Good Qualities
Material Used For Manufacture Of Containers And
Container Used For Opthalmic And Parentral
Material Used For Containers And Their Composition
Evaluation Of The Material Used For Making Of
Containers can be defined as an object that can be used to hold
or transport something.
Pharmaceutical container is a device that hold the
pharmaceutical product and it may or may not be in direct
contact with it.
Packaging can be used as the economical means of
providing presentation, protection, identification ,
information, convenience ,compliance (conformity),
integrity and stability of the product.
Why We Do Packing Of Drugs In Containers?
IDENTIFICATION PRESENTATION INFORMATION
CLASSIFICATION OF THE PACKAGING
Blister Pack, Strip Pack, Glass
Bottles, Plastic Bottles
Vials, Ampoules, cartridges,
glass Bottles, Plastic Bottles
Foil, paper Or Plastic Pouch,
Glass Or Plastic Bottles
For Tablets Or Capsules Like Unit
For Liquid Preparations
For Powder Or Granules
For Semisolid Preparations
Containers For Aerosols
Paper and boards
Brown cardboard box
The materials selected must have
They must protect the preparation from environmental conditions.
They must not be reactive with the product.
They must not impart to the product tastes or odors & color change.
Must be non toxic.
They must be “FDA” approved.
They must meet applicable tamper – resistance requirements.
They must be adaptable to commonly employed high-speed packaging
Containers – refers to storage media
in which product is placed & enclosed
& it is in direct contact with the drug.
( glass, plastic)
Closures – is a device tightly pack the
container to exclude O2, co2,
moisture & micro o/s & prevent loss
of water & volatile substance from
the product during transport &
handling. It is a part of container
system but doesn’t come in contact
with drug. (Aluminum, rubber)
Cartons : outer covering which gives
sec. protection against mechanical
and environmental hazards also
display written information . (Cardboard)
o Box :a device which is generally used for
packaging of products. It gives prime
protection against external hazards provided
containment & absorbs shocks .
(Cardboard & wood.)
A device in which drug is enclosed & in direct
contact with the drug
The container must be neutral towards the material
which is stored in it.
The container must not interact physically or
chemically with the substance which it holds.
It should help in maintaining the stability of
product against the environmental factors which
causes its deterioration.
QUALITIES OF GOOD CONTAINER:
It should be made of materials which
can withstand wear and tear during
It should be able to withstand
changes in pressure and temperature.
The materials used for making of the
container must be non-toxic.
Surface of the container must be clear
for easy labelling .
Size of the container must be selected
acc. To the size of preparation
They should not allow any loss of
product during leakage , spoilage or
Types of containers:
Containers are divided into following types on the basis of their utility :
Well – closed containers: A well-closed
container protects the contents from loss
during transportation, handling, storage or
Single dose containers : These containers
are used to supply only one of medicament
and hold generally parenteral products.
E.g. ampoules and vials
Multi dose containers: These
containers allow the withdrawal of dose
at various intervals without changing the
strength, quality or purity of remaining
portion. these containers hold more than
one dose and are used for injectable. E.g.
Light-resistant containers: These
containers protect the medicament from
harmful effects of light. These
containers are used to store those
medicaments which are photo-sensitive.
Air-tight containers: These are also
called hermetic containers. These
containers have air-tight sealing or
closing. These containers protect the
products from dust, moisture and air.
Where as air-tight sealed containers
are used for injectable, air-tight
closed containers are meant for the
storage of other products.
Aerosol containers: These
containers are used to hold
aerosol products. These
containers have adequate
mechanical strength in order
to bear the pressure of
Child-proof containers:-A container that is fitted with
a closure that prevents opening by children.
Child-Resistant Package Testing
Critique of directions for package/product-use
Swallow ability testing
Material Used For Manufacture Of Containers
There are mainly four types of material used in
manufacture of containers:-
Glass has been widely
used as a drug
For a large number of
products for oral and
glass containers are
usually the ﬁrst choice.
(e.g. bottles for tablets,
lotions or inhalers).
Colored Glass Containers
Is obtained by the addition of small
metal oxides, chosen according to the
desired spectral absorbance
Principally glass is silicon dioxide
tetrahedron whose physiochemical
properties are altered by adding oxides
of sodium ,iron, magnesium etc.
Types Of Glass
Type I-borosilicate glass(neutral
It is highly inert type of
It has high melting point so can with
stand high temperatures range
It can resist strong acids, alkalies and
all types of solvents
Reduced leaching action.
Laboratory glass apparatus.
For injection and water for
Widely used as glass ampoule
and vials. 19
Except for type I glass containers, glass containers for
pharmaceutical preparations are not to be re-used.
Containers for human blood and blood components
must not be re-used.
Type II-treated soda lime glass
Type II containers are made of commercial soda lime glass
that has been Dealkalised or treated to remove surface alkali.
The de-alkalizing process is know as sulphur treatment.
Sulphur treatment neutralizes the alkaline oxides on the surface,
rendering the glass more chemically resistant.
Used for alkali sensitive
Infusion fluids, blood and
Large volume container.
Used to produce container for
Type-III regular soda lime glass
Containers are untreated are made of commercial soda
It contains high concentration of alkaline oxides and
imparts alkalinity to aqueous substances
Flakes separate easily
For all solid dosage forms.
For oily injections
For non aqueous
Type 4 NP-general purpose soda lime glass
Containers are made of soda lime glass supplied for
non parenteral products, intended for oral or topical
For oral use.
For solid, liquid
Overview of Glasses Used In
Glass type General
Test method Uses
TYPE 1 Highly resistant
For buffered and
soda lime glass
Water attack test For buffered
with pH below 7
and for dry
TYPE 3 Soda lime glass
For dry powders
solutions, not for
TYPE 4 General purpose
soda lime glass
Not for parenterals
and for suspension
Types of Glass Containers
Used in the dispensary for packaging of medicine which
are available in sizes from 50 ml to 500 ml.
Amber metric medical bottles:- Widely used for
packaging of oral medicines.
Ribbed (fluted) oval bottles:- are used to package various
product that should not be taken orally.
Widely used for packing of liniments ,lotion, inhalation and
The parenteral products are packed and administered
in large volumes i.e. 100 ml to 1000 ml per day.
For LVP, type 2 glass is used but type 1 can also be
used for the products having high pH.
Large Volume Parenteral Glass Bottles
Eye drop and dropper bottles for ear and nasal use are
hexagonal- shaped amber color glass containers
They are fitted with cap, rubber teat and dropper as the closure.
The bottles are used at a capacity of 10ml to 20ml
Powders and semisolid preparations are generally
packed in wide mouthed cylindrical jars made of clear
or amber glass.
Jars varies from 15ml to 500 ml.
Jars are used for packing prepared ointments and
An ampoule (also ampule, or ampulla) is a small
sealed vial which is used to contain and preserve a
sample, usually a solid or liquid. Ampoules are
commonly made of glass, although plastic ampoules do
These are used for packing of parenteral solution
intended for single use. Glass ampoules are more
expensive than bottles and other simple containers
Types Of Ampoules
One Point Cut Ampoules
Before opening One-Point
Cut (OPC) Ampoule
Use an antiseptic to clean
Gently tap the top part of
the ampoule to get all the
liquid into the bottom part
Directions for Use of One-Point Cut (OPC)
Hold the bottom part of the ampoule with the
colored dot facing you.
Put the other hand on the top of the ampoule as shown.
Apply pressure to the top part and snap the ampoule away from
Features: Long lasting structure
Resistance to chemicals.
Flat Based And Constricted Neck Ampoule
Optimum hygiene level
Longer service life
Flame Cut Ampoules
Ease in sterilization
Can be easily broken
to take out the
A glass or plastic
container closed with a
rubber stopper and sealed
with an aluminum crimp.
Vials are available for
dosing or for multiple
Injection vials can be
obtained in either neutral
or soda glass and
occasionally in treated
Advantages And Disadvantages of Glass Vial
Glass vial has increased dose flexibility
Has decrease cost per unit dose
Cost of handling, transportation and storage is
Closures fragment may be released into the
product when needle is inserted through the
Risk of interaction between product and
Repeated withdrawn of injection solution
increase the risk of microbial contamination
Advantages of Glass Containers
1. It allows easy inspection of the containers
2. It also have the great advantage of preserving a
certain temperature for a longer period of
time. They do not dilate when it is too warm or
shrink when exposed to lower temperature
3. They are available in various shapes and sizes
4. They are economical and readily available
5. They can protect the photosensitive
medicaments from light during their storage
6. They do not deteriorate with age 38
Disadvantages of Glass Containers
1. They are brittle and break easily
2. They may crack when subject to
sudden changes in temperatures
3. They are heavier in comparison to
4. They can cause light transmission
Plastics are synthetic polymers of high molecular
Plastics as packaging have proved useful for a number
of reason i.e.
Ease with which it can be formed
Durability and Flexibility
The freedom to design.
Plastic containers are extremely resistant to breakage
and offer safety consumers
A packaging system must protect the drug without altering
the composition of the product until the last dose is
Drug-plastic considerations have been divided into five
4. Chemical reaction
It is the transmission of gases, vapors or liquids through
plastic packaging material.
Permeation of water vapor and oxygen through plastic wall
into the drug is a major problem is the dosage form is
sensitive to hydrolysis and oxidation.
The volatile ingredients might change when stored in
plastic containers and the taste of the medicinal products
may change for the same reason of permeation.
Some plastic containers have one or more ingredients
added to stabilize it, these may leach into the drug
Problems may arise with plastics when coloring agents
are added in small quantities to the formula.
Particular dyes may migrate into the parental solution and
cause a toxic effect.
This process involves the removable of constituents
from the drug product by the packaging material.
The therapeutic efficacy of the product may be reduced
due to sorption.
Sorption may change the chemical structure, ph.,
solvent system, concentration of active ingredients and
Certain ingredients in plastic formulations may react
chemically with one or more components of the drug
Even in micro quantities if incompatibility occurs may
alter the appearance of the plastic or the drug product.
The physical and chemical alteration of the packaging material
by the drug product is called modification.
Some solvent systems found to be considerable changes in the
mechanical properties of the plastics.
For example oils have a softening effect on polyethylene,
hydrocarbons attack polyethylene and PVC.
Types of Plastics
There are Two main types of plastics :–
These are softened by heat and can be
moulded. Thermoplastic polymers have
been established as packing material
for sterile preparations such as large
volume parenteral, ophthalmic
solutions, and also small volume
Good examples are acrylic,
polypropylene, polystyrene polythene
Thermo sets Plastics
These are formed by heat process but are then set
(like concrete) and cannot change shape by
Harden reversibly by cross linking
Good examples are Melamine (kitchen worktops),
Bakelite (black saucepan handles), Polyester and
PLASTIC ARE OF TWO FORMS
AMORPHOUS PLASTIC CRYSTALLINE PLASTIC
They give good transparency.
They are hard but posses little
They are more permeable to gases
They are of less inert.
They are opaque
They are more flexible
They are less permeable to gases and
For photo sensitive drugs this type of
plastics are selected.
Plastic Containers For Pharmaceutical
Products Are Primarily Made From The
Poly Vinyl Chloride
Its is flexible, very light but tough plastic
It is impermeable to water vapour and does not
deteriorate with age unless it is exposed to sunlight for
It has permeability to certain oils and preservatives.
Its melting point being in the range of 1100 to 1500c
It has high melting point and can sterilized by
It is divided into
HDPE (HIGH DENSITY POLYETHYLENE )
LDPE ( LOW DENSITY POLYETHYLENE )
HDPE: -Rigid, withstand temperature up to 120 degree Celsius
LDPE :-Flexible, withstand temperature up to 80 degree Celsius
Uses Of Polyethylene And
Polypropylene and polyethylene are most widely used
in parenteral plastic containers
Low density polyethylene and polystyrene are
generally not autoclavable
Polyethylene containers mostly used for ophthalmic
Polyvinyl Chloride (PVC)
It is less flexible , heavier and more permeable to
water vapors as compared with normal polythene
It has high clarity and not effected by sunlight
It is used for preparing eye ointment tubes
Flexible PVC is main component for intravenous
It is a hard, rigid , light material
It can be easily molded into any shape
So it is used for preparing bottles, tubes ,jars for
ointments and cream ,boxes and syringes.
Polymethyl Methacrylate (PMMA)
It is hard , strong but light, transparent plastic
It softens at about1000c
It is used for preparing bottles and tubes.
It is transparent, has high impact strength and very
good heat resistance.
It is used in the preparation of surgical equipment.
It has been used in blood oxygenators, blood
reservoirs, and blood filters used in the bypass circuit
for more than 20 years.
Types of Plastic Containers
Breaking is easy, no shreds, no sharp edges, no
danger for scars or cuts of the skin.
Plastic ampoule is not fragile, no need for special
handling with care during shipment, storage or the
Filling up doesn’t need the expensive and hazardous
technology of flame welding.
It is easy and energy efficient on automatic process
machines, with high precision of dosing.
The raw material is environment friendly and fully
recyclable polypropylene. Size range is:- 1.5 ml, 3 ml, 5
ml, 7 ml, 11 ml.
DISADVANTAGE OF PLASTIC AMPOULE
Not as transparent as glass.
Leaching may occur
Difficult in sterilization
Can not tolerate high temperature range.
Plastic vials, often used to store medication as
liquids, powders or capsules.
They can also be used as sample vessels, for
instance, in auto sampler devices in
Modern vials are often made of plastics such
During the last decade, plastic blood collection tubes
have been progressively replacing glass tubes.
Plastic tubes are not only less expensive but also safer
than glass tubes, because they are less likely to break.
They have been shown to influence the measured
concentrations or stabilities of several drugs.
A syringe is a simple pump consisting of a
plunger that fits tightly in a tube.
The plunger can be pulled and pushed along
inside a cylindrical tube (called a barrel),
allowing the syringe to take in and expel
a liquid or gas through an orifice at the open
end of the tube.
The open end of the syringe may be fitted
with a hypodermic needle, to help direct the
flow into and out of the barrel.
Syringes are often used to administer
injections, insert intravenous drugs into the
PVC Collapsible Bags
It is the part of large volume parenteral
products (100ml to 1000 ml per day) containers.
These are used to pack most infusion fluids.
They are design with a port for the attachment
of administration set and additive port for the
addition of small volume parenteral fluid.
Durable and light weight
No air interchange. The bag collapses as it empties.
They adsorb some drugs
They permits a high moisture penetration
NOTE:- Ethylene vinyl acetate film(EVA) are also
used in the formation of flexible collapsible bags
Semi Rigid Polythene Containers
These containers are used for different volume of
100ml for electrolyte solution
3 litre for total parenteral nutrition solution
Up to 5ml for dialysis solution.
Sterilization of Plastic Containers
Method of sterilization Sterilization condition
Moist heat 121 degree Celsius for 15 min.
Dry heat 160-180 degree Celsius for 1 to
Ethylene oxide with negative
pressure or inert gas
Chemical disinfectant Formalin
Water Permeability Test
Biological toxicity test
ADVANTAGES OF PLASTICS DISADVANTAGES OF PLASTICS
They are light in weight
and can be handled
They are transported
They are unbreakable.
They available in various
shapes and sizes.
They are resistant to
They are permeable to water
vapour and atmospheric gases.
They are poor conductor to
They may absorb chemical
substances, such as preservative
They are relatively expensive.
Metals are used for construction of containers.
They are impermeable to light, moisture and gases
They are made into rigid unbreakable containers by
They are light in weight
They are expensive
They react with certain chemicals
These metal containers are prepared by using different
METAL COLLAPSIBLE TUBES
TIN ALUMINIUM LEAD
inert of all metal
of tin at low
used alone for
of chances of lead
Aluminium:- is able to resist the corrosion.
Aluminum tubes offer significant savings in product
shipping costs because of their light weight.
They are attractive in nature.
Aluminium foil:- is also called al-foil. It is also
called tin foil but it is not made from tin.
Tin:- Most expensive and can be highly polished
It is used as a protective coat for other metals in
order to prevent corrosion or chemical reaction.
Tin containers are preferred for food,
pharmaceuticals and any product for which purity is
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
Stainless Steel- Chromium (12 to 14 %) and
Nickel up to 0.7%) are widely used for
manufacturing of equipment's
It is an attractive container that permits
controlled amount to be dispensed easily with
adequate protection of product usually made up
of aluminium, lead and tin metals
If product is incompatible with base metal than
interior surface is coated with wax or lacquer.
These are light in weight and unbreakable
Rubber is used in manufacture of closures, caps,
vials wrappers and plungers
Closure is a device tightly pack the container to
exclude oxygen, carbon dioxide, moisture &
microorganisms & prevent loss of water & volatile
substance from the product during transport &
handling. It is a part of container system but doesn’t
come in contact with drug. (Aluminium, rubber)
Ophthalmic preparations are
specialized dosage forms
designed to be instilled onto
the external surface of the
eye, administered inside or
adjacent to the eye or used
in conjunction with an
Ophthalmic products have several types i.e.
Contact Lens Solutions
Ophthalmic Inserts And
containers): Traditionally, glass
bottles with rubber teat dropper
were widely used. Now-a-days,
plastic bottles(LDPE) are widely
Flexible plastic or
tubes are used.
Currently almost all commercially available ophthalmic
products are packaged in plastic containers
Ease Of Use
The plastic bottles for packaging of ophthalmic
products are generally made of:-
Low Density Polyethylene(LDP)
High Density Polyethylene(HDPE)
Parenteral dosage forms differ from all other dosage
forms because they are injected directly into body
tissue through the primary protective system of the
human body, the skin and the mucous membranes.
They must be exceptionally pure and free from
physical, chemical and biological contaminants.
These requirements place A heavy responsibility on the
pharmaceutical industry to practice current good manufacturing
practices(cgmps) in the manufacture and packaging of parenteral
Colorless or colored glass is used for the other pharmaceutical
preparations. It is recommended that all glass containers for liquid
preparations and for powders for parenteral use permit the visual
inspection of the content. ,
Containers for aqueous parenteral preparations are tested for
arsenic release and coloured glass containers are tested for spectral
Small Volume Parenteral Product Containers (volume up to
Single dose containers:-ampoule
Multi dose containers: vials
Large Volume Parenteral Product Containers
PVC Collapsible Bags
Semi rigid Polythene Containers
A parenteral product container made
entirely of glass and intended for single
The ampoules can be broken at the neck
restriction either by scoring or by having a
ceramic point (ring or spot) baked on
during the manufacture thus causing a
weak point. However breaking on the
ceramic point can cause colored particles
to fall into the product. this led to an
alternative where the the ampoule is
scored and then has a colored ring above
or below the score to indicate the break
point( one point cut/open point cut
A glass or plastic container
closed with a rubber stopper
and sealed with an
aluminum crimp. Vials are
available for single
dosing or for multiple
dosing. Injection vials can
be obtained in either neutral
or soda glass and
occasionally in treated soda
HDPE Plastic Vials
Type 1 Glass Vial for multi
Syringes are devices for injecting,
withdrawing or instilling fluids. Syringes
consists of a glass or plastic barrel with a
tight fitting plunger at one end, a small
opening at the other end accomodates the
head of a needle. Needle Gauge is the
outside diameter of the needle shaft; the
larger the number, the smaller the
diameter. Gauges in common use range
from 13 (largest diameter) to 27.
Subcutaneous injections usually require a
24-gauge or 25-gauge needle.
Intramuscular injections require a needle
with a gauge between 19 and 22. Needles
between 18 gauge and 20 gauge are
commonly used for compounding
Powder glass test
Water attack test
Light transmission test
Test for clarity of aq. Extract etc.
EVALUATION OF PACKAGING
TESTS FOR GLASS CONTAINERS:
1) Powdered glass test
2) Water attack test
Preparation of specimen for powdered glass test:
Rinse 6 or more containers and dry them
Crushed in to fragments
Divide 100gms of coarsely crushed glass in to
three equal parts
place 1 portion in a mortar
Crush further by striking 3 or 4 blows with hammer
Nest the sieves (# 20,40 at least)
Empty the mortar in to sieve 20
Shake the sieves and remove the glass particles from # 20
Crush them again and sieve them
Transfer the retained portion on # 50
Spread the specimen on a glazed paper
and remove iron particles with the help of magnet
Wash with 6 portions of 30ml acetone
Dry the contents for 20mins at 140oc
Transfer to weighing bottle and cool in a desiccator
Final specimen should be used in powdered glass test
1) POWDERED GLASS TEST: (according to USP volume
Transfer 10gms of prepared specimen in a 250ml conical flask digested
previously with high purity water in a bath at 90o c
Add to conical flask containing 50ml high purity water
Cap all the flasks and auto clave
Adjust temperature to 150oc
Cold the temperature to 121oc for 30mins
Cool the flasks under running water
Wash the residue powdered glass(4 times with 15ml purity water)
Add the decanted washings to main portion.
add five drops of methyl red solution.
Titrate immediately with 0.02N sulphuric acid.
Record the volume of 0.02N sulphuric acid.
Volume does not exceed i.e. indicated in the USP as per
the type of glass concerned
WATER ATTACK TEST:(USP)
rinse 3 or more containers with high purity water
fill each container to 90%of its over flow capacity
cap all the flasks and autoclave for 60mints
empty the contents and cool the contents in 250ml
conical flasks to a volume of 100ml
add 5 drops of methyl red solution
titrate with 0.02N sulphuric acid while warm
record the volume of 0.02Nsulphuric acid consumed
volume should not exceed as indicated in USP as for
type of glass
TESTS FOR PLASTIC CONTAINERS
1.Leakage test for plastic containers(non
injectables and injectables 1996 IP):
fill 10 plastic containers with water and fit the
keep them inverted at room temperature for 24
no sign of leakage should be there from any
2.WATER PERMEABILITY TEST FOR PLASTIC
CONTAINERS(INJECTABLE PREPARATIONS IP
fill 5 containers with nominal volume
of water and sealed
allow to stand for 14 days at relative
humidity of 60 % at 20-250ºC
test is applicable to containers of oral liquids, unlabelled,
unmarked portion from suitable containers are randomly
these portion are cut into strips and washed twice with
distilled water for 30 sec. & then water is drained. Strips are
transferred to a clean flask (previously washed with chromic
acid & water). Added 250 ml of distilled water. the flask is
covered & autoclaved for 30 min. at 120c.
Inference- extracts content are cooled & examined. It should
be colorless & free from turbidity.
4. Biological toxicity test-
Invitro test – extract placed in contact with
mammalian cells to check to toxicity.
Invivo test –
systemic inj. Test – mice
intracutaneous inj. – rabbit
implantation test & eye irritation test - rabbit
a container intented to provide protection
from light , or offered as alight resistant must
meet the requirement of the USP light
The ability of a container to protect against
moisture can be identified by performing the
USP water vapour permeation test.
Container component will not interact with
the dosage form & may not show leaching.
Other changes such as pH shift , precipitation ,
discoloration should be evaluated.
Packaging components should be constructed
of material that will not leach harmful or
undesirable amounts of substances.
Purpose of closures
Classification of closures
Material employed for formation of
Quality control of closures
i. Test for alkalinity
ii. Turbidity test
iii. For rubber closure
iv. Child test
Retains the contents
Provides a barrier to dirt, oxygen, moisture,
Keeps the product secure from undesired and
Provides a means of reclosing or reusing the
Assists in dispensing and using of product
Minimizes the effect of change of
surroundings such as changes of relative
humidity, temp. or pressure
Provides a totally hermetic seal. This is a
closure that permits no exchange b/w the
contents and outside of the pack
In this form, closure is an external cap over
These are used to secure the closure to the
container in order to maintain the integrity
of the seal under normal conditions of
handling and storage.
i. Plain or snap fit-
In this the cap is pressed to seal
It closes with a click
Can be applied very quickly
ii. Threaded or Screw cap-
It is a mechanical device which is
screwed on and off a container
Either continuous threads or lugs are
It must be engineered to be cost-
Provide an effective seal
Compatible with the contents
Complies with product, package,
environmental laws and
Screw cap consists of 3 components
Cap:- may be of metal, usually tin plate or
aluminium or may also be a plastic
material which may be of thermosetting
type (for more rigidity)
Plastic caps are more beneficial as
compared to metal caps, as they are
capable of resisting corrosion & do not
contaminate the product.
Wad:- It should be effective to provide
satisfactory seal and inert to avoid
contamination of the product.
Silicon rubber can be used but in practice
wads are commonly of cork composition.
Liner:- must be inert. Material that are used
include metal foils, plastic films, rubber or
paper impregnated with a suitable resin, wax
When cap is applied, its threads are
engaged with the corresponding threads
molded on the neck of the bottle.
For opening, closure is rotated.
b. Lugged- similar to the threaded screw cap
and operates on the same principle.
It is simply an interrupted thread on the glass
finish, instead of a continuous thread.It requires
only 1/4th rotating.
It is a push fit into the neck of
Eg. Cork or glass stopper, but
both of these have been
replaced by plastic stoppers.
Glass stopper Cork stopper Plastic stopper
These are shallow metal caps
that are crimped into locking
position around the head of the
bottle. Generally made up of tin.
Requires a material that is
easy to form.
The roll on caps can be
sealed securely, opened easily
and reclosed effectively.
It is similar to roll on closure but has
a greater skirt length
This additional length extends below the
threaded portion and fastens to the basic
cap by the series of narrow bridges
When the closure is removed the extra
portion remains in the space on neck of the
The user can reseal the closure but the
detached bond indicates that the package
has been opened
These are additional closures for simple
i. Tamper evident-
Having an indicator or barrier
to entry which, if missing, can
reasonably be expected to provide
visible evidence to consumers that
tampering has occurred.
A tamper evident package may involve
systems intended to provide a visible
indication of package integrity.
These are designed to prevent accidents
and malicious tampering to create safe
Each retail package is required to
contain a statement that is prominently
placed so that consumers are altered to
the specific tamper-resistant feature of
Labeling statement is required to be so
placed that it will be unaffected if the
tamper-resistant feature of package is
Breakable cap ring
Heat sealed bands
Inner mouth seals
Cap or part of it must be broken in order to
open the container and remove the
it must not be possible to replace it in its
Sealed metal tubes, plastic heat sealed
must have both ends sealed
mouth has to be punctured to gain access
to the product
crimped ends are only acceptable if they
can’t be unfolded and refolded without
Heat sealed bands or wrappers:-
must be placed over the union of primary
closure (cap, lid, etc.) and container
must have a distinctive design
must get shrunk by heat
must be cut or torn to gave access
must not be worked off without leaving
a perforated tear strip enhances tamper
Whether made of paper, plastic film, foil or
combinations, they must have a distinctive
Must be torn or broken to gain access
Heat induction seals are considered
superior to adhesive seals.
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
if used on cartoons they must be applied
over all flaps.
Considered to be inherently tamper
direct printing on the container is
preferable to a paper label
Cans and composite containers:-
Top and bottom of a composite must be
joined to the walls so that they can’t be
pulled apart and replaced.
ii. Child resistant-
These are difficult for young children
(under 5 years of age) to open but not
difficult for adults to use properly.
These have been produced in response
to demand for greater protection of
children against accidental poisoning
Used for drugs, house cleansing agents,
1. Press and turn
2. Lift and turn
3. Squeeze and turn
4. Line up arrows and flip
5. Pop lock closure
1. Press and turn:-
the cap is removed by applying a
downward pressure while the
closure is rotated.
Click-lock closure is one of the
most successful of this type.
It also incorporates a form of
alarm for an adult in that if
the cap is turned without pressing
then a clicking sound is heard.
2. Lift and turn:-
it involves applying an upward force while rotating
3. Squeeze and turn:-
force is applied to the
sides of the closure while the
screw cap is rotated.
4. Line up arrows and flip:-
once the alignment is
established the miss-fit between
cap and container is removed
and the cap will lift.
5. Pop-lock closure:-
can only be operated after a tab on its top
has been released and then opening is
achieved by pulling on it.
Metals ( aluminium, aluminium alloys,
tinplate, stainless steel)
Rubber ( natural & synthetic)
Plastic ( thermosetting & thermoplastic)
Glass ( used for formation of stoppers)
Metal caps are usually coated on the
inside with an enamel for resistance
Almost all metal crowns and closures are
made from electrolytic tinplate, a tin coated
steel on which the tin is applied by
electrolytic deposition. Tin is most
The two basic types of plastics generally
used for closures are :-
1. Thermosetting Resins-
is used for making screw caps for glass
and metal containers. The thermosetting
plastic first softens under heat and then
cures and hardens to a final state.
2. Thermoplastic Resins-
Polystyrene, polyethylene and
polypropylenes are the materials used in
90% or more of all thermoplastic closures.
Advantages of plastic-
1. Flexible and not easily broken
2. Low density and thus light in weight
3. Easily molded in various shapes
1. Not chemically inert
2. Undergo stress cracking and distortion
from contact with some chemicals
3. Not heat sensitive
4. May possess an electrostatic charge and
will attract particles.
Rubber consists of
one of them is
These closures do
not pose a problem
and can be used in
contact with large
number of drug
1. Butyl rubber (copolymer of isobutylene
and isoprene or butadiene)
2. Nitrile rubber (butadiene-acrylonitrile co-
3. Neoprene rubber
4. Silicon rubber
1. Butyl rubber- cheap, chemical resistant,
low water vapor/air permeability. It is not
good for oils.
2. Nitrile rubber- resistant to oil, heat
treatment, vapor absorption but leaching
and bactericide absorption is high.
3. Neoprene rubber- resistant to heat and
oil with low water absorption permeability
as compared to natural rubbers.
4. Silicon rubber- most heat resistant
(about 250oC) with very low water
absorption and permeability, but costly.
1. Common flanged closure
2. Slotted or freeze dried product
3. Cartilage and Disposable syringe
Most commonly used in closing of vials
These closures has a slot or pathway for
the ice sublimation
Used to seal the freeze dried products or
Cartilage is made of glass, one end of
which is sealed with the rubber piston and
the other end with aluminium over seal
and rubber septum.
1. It should not become sticky upon storage
2. It should not become hard on exposure to
3. It should not become dark on exposure to
air and light
4. Ease in penetrability and elasticity (in case
5. Ease in sterilization- rubber closure must
withstand heat at least about 1200C
6. It must not become sticky during autoclaving
7. It should not allow water vapor and air to
pass through it
8. It should be free from leaching and sorption.
1. Test for alkalinity (for glass)
2. Test for rubber closures
a. compatibility with contents
b. permeability to water
c. self sealability
g. finish test
3. Child test
Coarsely crush the glass and then crush
Sieve the crushed glass
Take 2 conical flasks, one should be
treated as “blank” while other as “sample
Put the powder in the conical flask and
consider as sample container
Add some distilled water in both of the
Close both the flask with closure
Autoclave both for prescribed period of
Add NaOH solution to both of container
Filter the solution and wash with water
Titrate the filtrate with standard normal
Calculate the normality of alkali and then
the concentration is calculated
The conc. of alkali should not exceed the
a. Compatibility with other
All the sterile products are packed
aseptically in sterile containers and
several are stored under different
At given time intervals up to a year, except for
the 500C test, which are continued for 3
months only, the samples are examined for-
a. Foreign insoluble matter, using standard
conditions of illumination.
b. Loss of potency and preservatives, and
increase in toxicity.
c. Signs of deterioration of the closure, such
as sponginess and discoloration. The latter
should be checked after drying overnight
because absorption of water and certain
solutes often produces a bleached
b. Permeability to water-
Put calcium chloride in vial and close it with
rubber closure and seal it with aluminium seal.
Weigh the vial
Place it for a limited time period
If weight noted down later is more than previous
then test fails as weight is increased due to the
absorption of water vapors.
c. Self sealability test-
Take a vial and filled it with methylene blue
Inset needle into rubber closure 20-25 times
within a circle of 5 mm diameter
Vial is inverted in water in a container to
which a prescribed vacuum is applied for
half an hour
There must be no signs of leakage in the
water or on the closure
d. Fragmentation test for rubber closures (IP
Take 12 clean vials
Place a volume of water corresponding to nominal
volume minus 4ml in each
Close vial with closure and secure caps for
Pierce the closures with hypodermic needle and
inject 1ml water and remove 1ml air
Repeat the above operation 4 times for
Count the number of fragments visible to
the naked eye
Total number of fragments should not be
more than 10 except butyl rubber where
the fragment should not exceed 15
e. Penetrability test (by piercing
inverted vial is fitted on clamp and the
clamp is allow to move downward at a
stand having needle is fitted with piston
as clamp moves downward with vial,
needle will go inside the vial and the piston
force applied on the vial should not exceed
a stated value.
f. Quality test-
Rubber closures must not be tacky after
washing in a detergent, rinsing several
times, autoclaving for half an hour at
1210C in distilled water and drying for a
day at 650C in vacuum.
g. Finish test-
They must be substantially free from
adventitious dust, fibers, loose particles of
rubber, smears of grease and pigment,
and quite free from internal foreign matter.
4. Child test- (Acc. to 1995 US Protocol)
200 children of 42-51 months divided
approximately equally b/w the sexes and 100
normal adults b/w 18 and 65 years of age (70
female and 30 male) are selected
test involving children must be carried out in
familiar environment such as school but the
adults can be polled in any convenient centre
children operate in pairs under a qualified
each child is given a package containing a
placebo drug and allowed 5 minutes to try
and open it
If they are unsuccessful they receive a
non-verbal demonstration and a further 5
minutes to try again
Adults are asked to open the package
individually within 5 minutes using only the
directions that appear on the package
itself and then to reclose it properly if it is
After the full 10 minutes 80% of the
children shall not succeed in opening the
package and after 5 minutes 90% of the
adults must be successful.
1. Pharmaceutical product development by N.K. Jain
2. Cooper and Gunn’s “Dispensing for pharmaceutical
students”,CBS Publishers,page no.-278-345
3. Modern pharmaceutics by G.S. Banker and C.T. Rhodes
4. Leon Lachman ,“The theory and practice of industrial
pharmacy”,Lea &Febiger,U.S,2nd edition,page no.-241-306
5. Remington, “The Science and Practice of Pharmacy”,
published by Lippincott Williams & Wilkins,page no. 356-386