1. Pharmaceutical Packaging
Rakesh Kumar Sharma

2. In the pharmaceutical industry it is vital that the
package selected adequately preserve the
integrity of the product.
The selection of a package therefore begins
with a determination of the product’s physical
and chemical characteristics, its protective
needs and its marketing requirements.

4.  The material selected must have the following
characteristics
 They must protect the preparation from
environmental conditions
 Must not reactive with the product
 Must not impart odor/taste to the product
 Must be non-toxic
 Must be FDA approved
 Must meet tamper-resistance requirements

5.  Glass containers
 Glass is commonly used in pharmaceutical
industry because it possesses superior
protective qualities, economical and containers
are readily available in variety of sizes and
shapes
 Chemically inert, impermeable and with proper
closure system it provides excellent barrier
protection except light (amber color can give
protection against light).
 Disadvantage: its fragility and weight.

7.  Composition of glass: glass is
composed principally of sand, soda ash,
lime stone, alumina and cullet. The sand
is almost pure silica, the soda ash is
sodium carbonate and lime stone,
calcium carbonate. The cullet is broken
glass that is mixed with the batch and
acts as fusion agent for the entire
mixture. Reduction in the proportion of
sodium ion makes glass chemically
resistant.

8.  However without sodium, glass is
difficult, expensive to melt. Boron
oxide is incorporated mainly to aid
in the melting process through
reduction of the temperature
required. Lead gives the clarity.
Alumina to increase the hardness
and resistance to chemical action.

9.  Colored glass
 Only amber glass and red glass are
effective in protecting the contents of a
bottle from the effects of sunlight by
screening out harmful ultraviolet rays.
 USP specification for light resistant
container requires the glass to provide
protection against 290-450nm of light.
Amber color meets these above
specifications but iron oxide added to
produce this color, leach in to the product.

10.  Glass for drugs
 USP describes the various types of glass
and provide the powder glass and water
attack tests for evaluating the chemical
resistance of glass. The test results are
measures of the amount of alkaline
constituents leached from the glass by
purified water under autoclave
temperature conditions. Powder glass test
is performed on glass particles and water
glass test is performed on whole

11.  The water attack test is used only
with type II glass that has been
exposed to SO2 fumes under
controlled conditions to remove the
surface alkali, thereby rendering the
glass more resistant chemically.
However this resistance is lost if the
container is subjected to repeated
autoclaving, hot air sterilization

13.  Plastic container
 Plastic in packaging have proved useful
for a number of reasons including the
ease with which they can be formed, their
high quality and freedom of design.
 Plastic containers are extremely resistant
to breakage and thus offer safety to
consumers along with reduction in weight
and breakage losses.
 Plastic containers for pharmaceutical
products are primarily made from the
following polymers

14.  Polyethylene,
 polypropylene,
 polyvinylchloride,
 polystyrene,
 polyamide (Nylon),
 polycarbonate.

15.  The principle ingredients of the
various plastic materials used for
containers is the thermoplastic
polymer along with substantial
amount of plasticizer, fillers,
antioxidants etc. these ingredients
are not usually chemically bounded
in the formulation and therefore may
migrate out of the plastic and in to
the product.

16.  Thermoplastic polymers melt at
elevated temperature. All plastic
materials listed in the table except
low density polyethylene and
polystyrene can be autoclaved but
almost all softens at autoclaving
temperatures..

17.  Polypropylene and the copolymer
polyethylene-polypropylene is most
widely used in parenteral because
high melting point 165 0C, low
permeability to gases and water
vapor. It is translucent. It will
withstand autoclaving temperature.
 Flexiblepolyethylene containers are used
for ophthalmic solutions and flexible PVC
bags for intravenous solutions

19.  The density of the plastic material directly
determines the four basic physical
characteristics
 Stiffness
 Moisture
 Stress cracking
 Gas
 As the density increases the material becomes
stiffer, has higher melting temperature, become
less permeable to gases and vapor and
become less resistant to stress cracking.

20.  Polytetraphthalate (PET): PET is a
condensation polymer typically
formed by reaction of tetraphthalic
acid. Its excellent impact strength,
gas barrier make it attractive for use
in cosmetics and mouth washes as
well as in other products.

21.  Drug – Plastic considerations
 A packaging system must protect the
drug without in any way altering the
composition of the product until the
last dose is removed and or till the
expiry date of the product .

22.  Drug plastic considerations have
been divided in to separate
categories
 Permeation
 Leaching
 Sorption
 Chemical reaction
 Alteration in the physical properties
of plastic or products.

23.  Permeation:- The transmission of gases,
vapor or liquids through plastic packaging
materials can have an adverse effect on
the shelf life of a drug. Permeation of
water vapor and oxygen through the
plastic wall in to the drug can present a
problem if the dosage form is sensitive to
hydrolysis and oxidation. Temperature
and humidity are important factors
influencing the permeability of oxygen and
water through plastic. An increase in the
temperature reflects an increase in the
permeability of the gas.

24.  Material such as nylon which is
hydrophilic in nature is a poor barrier
to water vapor.
 The formulations containing volatile
ingredients might change when
stored in plastic containers

25.  Leaching:- since most plastic containers have
one or more ingredients added in small quantity
to stabilize or impart a specific property to the
plastic, the prospect of leaching or migration
from the container to the drug product is
present problems may arise with plastics when
coloring agent in relatively small quantities are
added to the formula. Release of a constituent
from the plastic container may leads to drug
contamination and necessitate removal of the
product from the market.

26.  Sorption:- this process involves the removal of
constituents from the drug product by the
packaging material. Sorption may lead to
serious consequences for drug preparation in
which important ingredients are in solution.
Since the drug substances of high potency are
administered in small doses, losses due to
sorption may significantly affect the therapeutic
efficacy of the preparation.

27. A problem commonly encountered in practice
is the loss of preservatives from the
formulation. These agents exert their activity
at low concentration their loss through the
sorption leave the product unprotected against
microbial growth.

28.  Chemical reactivity:- certain ingredients
that are used in plastic formulation may
react chemically with one or more
components of a drug product and
subsequently alter the appearance of
plastic or drug product.

29.  Modification:-the physical and
chemical alterations of the packaging
material by the drug product is called
modification. Deformation in
polyethylene containers is often
caused by permeation of gases and
vapor from the environment or by loss
of contents through the container
walls.

30.  Some solvent systems have been
found to be responsible for
considerable change in the
mechanical properties of plastic. Oils
for example have softening effect on
polyethylene. Changes in the
polyethylene caused by some surface
active agents have been noted.
Fluorinated hydrocarbon attack
polyethylene and PVC

31.  Quality control tests for plastic containers
 Containers for Non-injectables:
 Leakage test: Hold the pack under the
water, apply the vacuum and observe
for leakage.
 Clarity test: washed portion of the
sample, add 250ml of distilled water,
autoclave at 121oc for 30 minutes.
The absorbance at 640 nm should be
0.37 to 0.43.

32.  Non volatile residue: evaporate
100ml of the extract obtained in
the test for clarity of aqueous
extract to dryness and dry to
constant weight at 105oc. the
residue weight not more than 12.5
mg.

33.  Containers for injectables: In addition to the
above tests
 Water vapor permeability:
5 containers filled to nominal volume,
wt accurately and allow to stand for
14 days with relative humidity 60%
and temperature 20-25oc. reweigh
the containers. The loss in weight in
each container should not be more
than 0.2%.

34. Collapsible tubes
 Metal: - Thecollapsible metal tube is
an attractive container that permits
controlled amounts to be dispensed
easily, with good reclosure and
adequate protection of the product.
The risk of contamination of the
portion remaining in the tube is
minimal because the tube does not
suck back. It is light weight and
unbreakable.

35.  Tubes of tin, aluminum and lead are
most commonly used. Laminates of
tin coated lead provides the
appearance and oxidation
resistance. Aluminum hardens in use
causing tubes to develop leaks.

36. Tin containers are preferred for food,
pharmaceuticals because it is inert
and compatible with a wide range of
products.
 Lining: - if the product is not
compatible with bare metal, the
interior can be flushed with wax type
formulations or with resin solutions. A
tube with epoxy lining cost 25% more
than the same tube uncoated.

37.  Plastic:-Plastic tubes have a number of
practical advantages over other containers
they are low in cost, light wt, flexible,
odorless and inert, unbreakable, they
have a unique suck-back features which
prevents product ooze. but this feature
has a disadvantage of fear for
contamination. The most common
material currently employed in plastic
tubes are low and high density
polyethylene.

38.  Laminations
 Permeation problem associated with plastic
tubes and corrosion problems with metal tubes
have lead to the emergence of a third type of
collapsible tube, the laminated tube. This tube
constructed of a lamination containing several
layers of plastic, paper and foil. This lamination
is welded in to a continuous tube by heat
sealing the edges of the lamination together in
a machine called sideseamer. The tube is cut
in to length and the head is molded on to the
tube.

39.  Closures
 Effective closure must prevent the
contents from escaping and allow no
substance to enter the container. In
evaluating an effective closure system
the major considerations are the type
of container, the physical and
chemical properties of the product
and the stability-compatibility
requirements for a given period under
certain conditions .

40.  closures are available in
 screw on, thread or lug
 crimp-on (crown)
 press-on (snap)
 Roll-on and Pilfer proof roll-on

41.  Thread screw cap: when the screw
cap is applied, its thread engages with
the corresponding threads molded on
the neck of the bottle. A liner in a cap,
pressed against the opening of the
container, seals the product in the
container. The screw cap is
commonly made of metal or plastics.

42.  Lug cap: the lug cap is similar
to the thread screw cap and
operates on the same principle
but it is an interrupted thread
on the glass finish, instead of a
continuous thread

43.  Crown cap: This style of cap is
commonly used as crimped
closure for beverage bottle and
has remained unchanged for more
than 50 years.
 Press-on:- the cap is applied by
application of pressure from the
top.

44.  aluminium
Roll-on and rolled on pilfer proof
metal caps consists of a plain metal shell
containing a wadding or flowed-in system,
which is placed over the container neck
and top pressure applied to give a good
impression on the wad. While the
pressure is still held, the threads are
formed by mechanical inward pressure. In
case of pilfer proof closure an additional
perforated collar is rolled under a lower
bead.

45. Tamper-resistant packaging
 As defined by FDA a temper resistant
package is one having an indicator or
barrier to the entry which if breached
or missing, can reasonably be
expected to provide visible evidence
to consumers that tempering has
occurred.

46.  Tamper resistant packing may involve
immediate container/ closure system
or secondary container closure
systems or any combination thereof
intended to provide a visual indication
of integrity when handled in a
reasonable manner during
manufacturing, distribution and retail
display.

47.  The following package configuration have been
identified by FDA as examples of packaging systems
that are capable of meeting the requirements of
temper resistant packaging.
 Blister package
 Strip package
 Bubble pack
 Shrink banding
 Bottle seal
 Tape seal
 Breakable caps
 Sealed tubes
 Aerosol container

48.  Blister package
 The blister package is formed by heat
softening a sheet of thermoplastic and
vacuum drawing the softened sheet in
to a mould. After cooling the sheet is
released from the mould and
proceeds to the filling station of the
packaging machine.

49.  The semi rigid tray previously formed
is filled with the tablets/ capsules and
lidded with a heat sealable backing
material. The backing material is
usually heat seal coated aluminium
foil. The plastic material used
includes PVC, PVC/ polyethylene
combination. For added moisture
protection polyvinylidene fluoride

50.  (saran) or polychlorotrifluoroethylene
(aclar) films may be laminated to
PVC. The moisture barrier of PVC/
Aclar is superior to that of saran
coated PVC.
 Advantages:-Unit dosing,
convenience, child-resistant, pleasing
appearance, tamper-resistant

52.  Strip package
 Strip
package is a form of unit
dose packaging that is commonly
used for the packaging of tablets
and capsules. A strip package is
formed by feeding two webs of a
heat sealable flexible film through
a heated crimping roller.

53.  The product is dropped in to the
pocket formed prior to forming the
final set of seals. a number of
different packaging materials are
used for strip packaging. For high
barrier applications a
paper/polyethylene/foil/polyethyle
ne laminations commonly used.

55.  Bubble pack
 The bubble pack can be made in
several ways but is usually formed by
sandwiching the product between a
thermoplastic film and a rigid backing
material similar to as in the blister.

56. Shrink banding
 The shrink band concept makes
use of the heat shrinking
characteristics of a stretch
oriented polymer usually PVC.
The heat shrinkable polymer-PVC
is manufactured as a tube in a
diameter slightly larger than the
cap and neck ring of the bottle to
be sealed.

57.  Thisis then placed over the bottle cap
and the package is passed through a
heated tunnel, which shrinks the
plastic cover around the cap,
preventing the disengagement of the
cap without destroying the shrink
band.