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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5724_Библиотеки_им_академика_М_И_Перельмана.pdf
35
Packaging Materials
instead of sodium carbonate, a hard glass is produced which
is used for the preparation of laboratory glass apparatus.
Special types of glass, e.g. coloured glass or heat-resistant
glass can be produced by adding certain other substances
to the three basic components.
Various types of glass used for pharmaceutical purposes are:
a. Type I: Borosilicate glass
b. Type II: Treated soda-lime glass
c. Type III: Soda-lime glass
d. Type NP: Non-parenteral glass
e. Coloured glass
f. Neutral glass
a. Type I (borosilicate glass): Borosilicate glass is produced by
replacing the sodium oxide flux by boric oxide (B
2
O
3
) and
some of lime by alumina (Al
2
O
3
) in the basic components
of glass. It has a high melting point and can withstand
high temperatures hence it does not crack when used for
boiling the water and even for cooking. It is also resistant
to chemical substances. This type of glass is mairly used for
making laboratory glass apparatus, in factories, kitchens
and ovens.
b. Type II (treated soda-lime glass): It is prepared from commercial
soda-lime glass by treating it with sulphur dioxide by
which surface alkali is de-alkanised and such glass can be
used for alkali sensitive products.
Sometimes inner surface of glass is treated with silicones
and the glass so treated can be used for alkali sensitive
products. Silicon treated glass is not very popular with
pharmaceutical manufacturers due to flaking.
c. Type Ill (soda lime-glass): It is an ordinary glass prepared
from silicon dioxide, soda ash (Na
2
O) and lime stone (for
CaO) and is generally referred to as soda-lime glass. It
is ·the cheapest quality and most common form of glass.
It contains a high concentration of alkaline oxides and
imparts alkalinity to aqueous substances readily which
can adversely effect the quality of the product contained
therein. So these types of glasses are not suitable for alkali
sensitive products. They should not be used for parenteral
Introduction to Pharmaceutics
36
preparations. These types of containers are generally used
for dry powders and oily preparations.
d. Type NP (General purpose glass or non-parenteral glass): It is
general purpose soda-lime glass used for oral and topical
preparations.
e. Coloured glass: Coloured glass is obtained by adding small
amounts of metal salts during fusion of glass. Coloured
glass is used for light sensitive products. For this purpose
amber coloured glass is generally used which does not
allow the UV rays to pass through it. Preferably coloured
glass should not be used for parenteral products because it
becomes difficult to check clarity in such preparations.
f. Neutral glass: It is another commercial variety of glass
available in between sodalime glass and borosilicate glass.
It is resistant to alkalies, weathering; and can withstand
autoclaving. It is used for the manufacture of multidose
vials and transfusion bottles, etc. It is composed of SiO
2
75%, B
2
O
3
7–10%, Na
2
O 6–8%, Al
2
O
3
4–6%, BaO 2–4%, K
2
O
0.5–2%.
For the manufacture of ampoules special glass tubing
having low melting point should be used because after filling
the ampoules are required to be sealed by fusion of glass.
Advantages of Glass Containers
They are transparent which allows the visual inspection of
the contents.
They are economical.
They are readily available in various shapes and sizes.
They are chemically inert.
They are quite strong and rigid.
They possess superior protection properties.
They do not deteriorate with age, with proper closures.
Some glass containers are heat resistant so they can be
readily sterilized by heat.
Glass containers can be easily cleaned without any damage
to its surface, e.g. scratching or bruising.
As the composition of glass may be varied by adding
suitable amounts and types of sand and silica as well as
conditions of heat treatment used, the proper container
according to desired qualities can be produced.
37
Packaging Materials
Disadvantages
They are brittle and break easily.
They may crack when subjected to sudden changes of
temperatures.
Some containers impart alkalinity and insoluble flakes to
the formulations. This type of difficulty can be overcome by
selecting proper type of glass.
Problems
1. Flaking
During flaking the alkali is extracted from the surface of glass
containers and a silica rich layer is formed which sometimes
gets detached from the surface and can be seen in the contents
in the form of shining flakes. This is a serious problem specially
in parenteral preparations. Therefore, glass which does not
flake should be selected.
2. Weathering
Weathering is a common problem with glass containers,
that sometimes moisture condensed on the surface of glass
container, can extract some weakly bounded alkali, leaving
behind a white deposit of alkali carbonate. If this white deposit
is not removed and allowed to remain over there further
condensation of moisture will lead to the formation of an
alkaline solution which will dissolve some silica resulting in
loss of brilliance. This loss of brilliance from the surface of glass
is called weathering. To prevent weathering, the deposited
white layer of alkali carbonates should be removed as early
as possible by washing the container with a dilute solution of
acid and then washing thoroughly with water.
Sometimes glass free from lead and arsenic is used for
those preparations which can extract lead or arsenic from the
containers.
Due to flaking and weathering, all the glass apparatuses
used for pharmaceutical purposes must be free from alkali and
all the containers used therein must have passed the limit tests
for alkalinity as prescribed in various pharmacopoeias.
Introduction to Pharmaceutics
38
B. Plastics
Plastics are high molecular weight polymers possess ing
long carbon chains. They are synthetic polymers which are
converted into different forms. There are two types of plastics—
(i) thermosetting type and (ii) thermoplastic type.
The thermosetting type plastics are usually hard and brittle
at room temperature but become flexible on heating. They are
used for making the closures for bottles and jars.
The thermoplastic type plastics are becoming more popular
day by day. This type of plastic is used for the manufacture of
plastic containers which are mainly used for packing mixtures,
tablets, capsules, ointments, etc. Fluids and retention enemas
are now packaged in plasticised PVC ‘sachet’ packs. These
types of plastics have characteristic property that on heating
they soften to become viscous fluids while on cooling again
hardens. The various thermoplastic polymers used for the
manufacture of containers are:
Low density polythene: It is used for the manufacture of
bottles, jars, collapsible tubes, etc.
High density polythene: It is also used for bottles, jars and
closures.
Polyvinyl chloride (PVC): It is of two types
(a) Unplasticised which is used for bottles and jars.
(b) Plasticised which is used for making extruded tubes
and films.
Polystyrene: It is used for jars tubes and closures, etc. but is
not suitable for the moisture sensitive products.
Polypropylene: It is used for the manufacture of squeeze
bottles. It has a melting point of 170°C and containers made
from it can be sterilized by autoclaving. It has a drawback
that it becomes brittle at low temperatures.
Polymethylmethacrylate (PMMA): It is clear, hard, strong and
light and is used for the manufacture of bottles, tubes, etc.
It has the drawback that at low temperatures it becomes
soft therefore not very suitable for containers of sterile
products.
Polytetrafluoroethylene (PTFE): It has high resistance to heat
and can withstand a temperature up to 250°C. It is also
39
Packaging Materials
resistant to chemicals and its permeability to water vapours
is also very low. It is very costly due to which it is not so
commonly used in pharmaceutical practice.
Polyamides (nylons): Nylons are very tough materials but at
the same time they are also very flexible. They are resistant
to heat with melting point of about 200°C. They are also
resistant to chemicals. Nylons can be easily sterilized by
autoclaving.
Sometimes in addition to above mentioned basic polymers,
other additives such as plasticizers, anti-oxidants, colouring
agents, etc. may be incorporated. Since these additives do not
form bonds with the basic polymers so they may transmit to
the preparation on storage, resulting to spoil the product.
Before packing the pharmaceutical products into the plastic
containers they must be physically, chemically and biologically
tested to ensure safety and stability of the preparation.
The containers must be free from toxicity, irritability and
pyrogens, etc. whenever necessary. Plastic containers meant for
photosensitive materials, should be tested for penetration of
ultraviolet rays. Whenever coloured containers are used, it must
be ensured that the colour is not transmined to the preparation.
Advantages of Plastic Containers
They are cheaper as compared to other containers.
They can be readily produced on large scale.
They are unbreakable, tough and flexible.
They are light in weight and can be easily transported.
They can be moulded into various shapes and sizes.
Disadvantages of Plastic
Permeation: The transmission of gases, vapours or liquids
through plastic packaging materials can have an adverse
effect on the shelf-life of a drug.
y Permeation of water vapor and O
2
through the plastic
wall into the drug can cause a problem if the dosage form
is sensitive to hydrolysis and oxidation. Temperature
and humidity influence the permeability of oxygen and
water, e.g. nylons are hydrophilic in nature, and are
Introduction to Pharmaceutics
40
poor barrier for water while hydrophobic materials as
polyethylene provide much better barriers.
y Formulations containing volatile ingredients may
change when stored in plastic containers due to the
permeation of one or two ingredients through the walls
of the containers. Often, the aroma of cosmetic products
become objectionable and the taste of medicinal
products changes.
y Certain W/O emulsions cannot be stored in a hydro-
phobic plastic bottle, since there is a tendency for the oil
phase to migrate and diffuse into the plastic.
Leaching: Additives those are added in the plastics may
leach into the content. Particular dyes may migrate into a
parenteral solution and cause a toxic effect.
Release of a constituent from the plastic container to the
drug product may lead to drug contamination, may catalyse
some reaction in the solution which decompose the drugs.
Sorption: This process involves the removal of constituents
from the drug product by the packaging material. Drug
substances of high potency are administered in small doses.
In this case losses due to sorption may significantly affect
the therapeutic efficacy of the preparation.
A common problem is the loss of preservatives. These
agents exert their activity at low concentration, and their
loss through sorption may be great enough to leave a
product unprotected against microbial growth.
Factors influencing the characteristics of sorption from
products are:
y Chemical structure of the solute,
y pH,
y Solvent system,
y Concentration of solute,
y Temperature,
y Time of contact, and
y Area of contact.
Chemical reactivity: Certain ingredients that are used in
plastic formulations may react chemically with one or more
components of a drug. Ingredients in the formulation may
41
Packaging Materials
react with the plastic. Even microquantities of chemically
incompatible substances can alter the appearance of the
plastic or the drug product.
Modification: The physical and chemical alteration of the
packaging material by the drug product is called modi-
fication. Deformation in polyethylene containers is often
caused by permeation of gases and vapours from the
environment or by loss of content through the container walls.
y Oils have a softening effect on polyethylene and PVC.
y Fluorinated hydrocarbons attack polyethylene and PVC.
In some cases the content may extract the plasticizers,
antioxidant or stabilizer, thus changing the flexibility of
the package.
y Plasticizers when extracted by some solvents renders
the wall stiff.
C. Metals
Metal containers are not very popular for packing the pharma-
ceutical products because they may react with the preparations
have considerable weight and are costlier. Metal containers are
however, used for packing aerosols, powders, tablets and food
articles. For this purpose tin plated steel, stainless steel and
aluminium containers are used.
Collapsible tubes made from aluminium, tin and lead are
used but aluminium tubes are most popular because they are
cheap as compared to tubes made from tin. Collapsible tubes
are used for packing ointments, creams, pastes, toothpastes
and cosmetics. They are attractive containers and allow only
the desired amount of the product to be removed. They do
not allow the product to be contaminated as the rest of the
preparation will not come in contact neither with the fingers
nor with the atmosphere. Collapsible tubes are light in weight,
unbreakable and can be filled easily at a high speed with
automatic machines.
Collapsible tubes are available in different sizes. Sometimes
they are supplied with nozzles which can be attached to the
tube for ease in application of the medicament to the nose,
rectum or other body cavities.
Introduction to Pharmaceutics
42
Advantages and Disadvantages of Metal
Metal Advantages Disadvantages
Tin • This metal is very resistant to
chemical attack.
• Readily coats a number of the
metals, e.g., tin-coated lead
tubes combine the softness
of lead with the inertness of
tin and for this reason it was
formerly used for packaging
fluoride toothpaste
Tin is the most expensive
metal among tin, lead,
aluminium and iron
Aluminium • Aluminium is a light metal −
hence the shipment cost of the
product is less
• They provide attractiveness of
tin at somewhat lower cost
• The surface of aluminium
reacts with atmospheric
oxygen to form a thin, tough,
coherent, transparent coating
of oxide, of atomic thickness,
which protects the metal from
further oxidation
• Any substance that
reacts with the oxide
coating can cause
corrosion, e.g. products
with the oxide coating
can cause corrosion,
e.g. products of high or
low pH, some com-
plexing agents, etc.
• As a result of corrosion
process H
2
may evolve
Iron Iron as such is not used for
pharmaceutical packaging, large
qualities of tin-coated steel,
popularly called ‘tin’, combines
the strength of steel with the
corrosion resistance of tin.
If an aqueous liquid can
penetrate a pinhole or
other fault in the layer of
tin, which is virtually a
short-circuited galvanic
cell is set up and the
intense chemical reaction
which results brings
about rapid corrosion
of underlying steel. As a
further measure the tin
surface is lacquered
Lead Lowest cost of all the metals used
in pharmaceutical containers
Soft metal
Lead when taken
internally there is risk of
lead poisoning. So, lead
containers and tubes
should always have
internal lining of inert
metal or polymer
43
Packaging Materials
D. Rubber
Natural rubber consists of latex obtained from Hevea
brasiliensis commonly known as rubber plant. This rubber
imparts a characteristic odour to the product, therefore, the
physical and chemical properties of rubber are altered by
the addition of some additives such as:
y Vulcanising agent, e.g. sulphur.
y Accelerators, e.g. thiazoles.
y Activators, e.g. zinc oxide, stearic acid and zinc stearate.
y Fillers, e.g. carbon black, calcium carbonate, zinc oxide,
talc, etc.
y Softners, e.g. mineral oils, etc.
y Antioxidants, BHT, etc.
y Pigments, e.g. oxides and sulphides of iron, cadmium,
etc.
y Lubricants, e.g. zinc stearate, etc.
Rubber closures are mainly used for vials, multidose
containers and IV fluid bottles because of its self sealing
properties and it can withstand sterilization temperatures
better than plastic closures. Rubber is also used for making the
washers required in certain containers.
Since the additives used in the manufacture of rubber
has the tendency to migrate into the product contained in
the container, therefore these closures must be subjected to
extractive test before use. The other tests which should be
performed on rubber closures include: (i) Test for penetrability
force, (ii) fragmentation test and (iii) permeability test and
compatibility with the product.
Advantages of Rubber
Rubber does not deteriorate with age. Under normal
conditions closures prepared from good quality rubber
remain stable for a number of years.
Rubber acts as self seal to the containers.
Rubber is elastic in nature and can be moulded in any form
to make stoppers or closure liners. It is elastic enough that
it provides a snug fit between the closure and the neck and
lip of the glass container. They are soft and elastic enough
Introduction to Pharmaceutics
44
that they allow easy passage to the syringe needle without
blunting and springs back to its original position to close
the hole made by the needle immediately after withdrawal
to prevent the entry of micro-organisms and leakage of the
contents.
Although porous they do not allow the transfer of water
vapours or gases in either direction.
Good quality rubber is resistant to sterilization conditions.
They are unbreakable, tough and can be easily transported.
Disadvantages of Rubber
The composition of rubber stoppers is complex and the
manufacture process is complicate.
When rubber stopper comes in contact with parenteral
solutions, it may absorb the active medicament, preservative
or other materials, and one or more constituents of the
rubber may be extracted into the liquid which may
(a) interfere with the chemical analysis of the active
medicament, (b) affect the toxicity or pyrogenicity of the
parenteral preparation, (c) lose or decrease the preservation
and physical stability of the preparation.
Hard rubber may produce large number of fragments when
the hypodermic needle cuts through the closure and the
fragmented material may appear in the solution.