Containers and closures for injectable

dosage form
Processing of containers and closures for injection
Container for injectable dosage form is a device which holds the
content of product in it , closure is a device which seals the
container to exclude oxygen , carbon dioxide and moisture and
microorganisms, at the same time preventing the loss of volatile
components from preparation of a injectable dosage form.
Commonly used containers are ampoules for unit dosage form ,
Vials for multiple dosage and Bottles/Bags for large volume
parenterals .

What are the desirable features of containers

and closures for Injectable dosage form?
1.Containers and closures should be inert , should be non reactive with
the content of injectable dosage form.
2.Containers and closures should not leach out its contents from surface
into the product.
3.Should not show any absorbtion or adsorbtion of ingredients of the
preparation of a injection.
4.Containers and closures for injection should be sturdy enough to with
stand the rigours of processing handling and shipping .
5. Containers and closures for injection should offer complete protection
against physico- chemical agents and microorganisms.
6.Containers and closures for injection should have transparancy to
facilitate visual inspection.
7.Containers and closures for injection should have uniform dimentions
to facilitate processing by automated unit.

Steps in processing for terminally sterilised

injections.
1.Washing of containers 2.Rinsing 3.Dry heat
sterilisation of containers 4. Filling
5. Sealing
6.Sterilisation
Steps in processing for aseptically processed
injectable dosage form.
1.Washing of containers-->2.rinsing--> 3.Dry heat
sterilisation of containers --->4.Aseptically filling of
sterile product and Sealing .

1.Washing of containers for injectable dosage

form
Washing containers is done in an environment controlled area
where particle count is controlled and is within 1000
class.Water used for washing is a purified water meeting the
Pharmacopoeial standards.Water should be filtered before it is
supplied for washing through prefilter and then through
sintered glass filters of 0.45 m , to get rid of microorganisms
and particles.
Automatic washing machines used contains series of jets over
which containers are placed in inverted position and purified
water is forced in the form of jet stream through needles which
cleans inner surface of containers ,automatic washing
machines may be rotary or conveyer type.
mostly detergent is not required , and if it is required example
in hospitals for Large volume paranterals manufacturing, a
nonionic detergent is used e.g. Teepol.

2.Rinsing of Containers is done with water for injection

which obviously is free from pyrogens and
microorganisms.
3.Drying is done as per below mentioned conditions which
ensures the sterility as well as freedom from pyrogens
A. 180 C FOR 3 to 4 Hours
B. 269 C FOR 45 mins
C. 600 C for 1 mins

Filling of injectable dosage form

Is carried out by automated filling machines while
feeling of injection liquid, needle should not touch
the wall of containers .
There is a specification for net fill volume of a given
injection in respective pharmacopoeia's. The net
extractable volume should be achieved - to attain
that we have to fill little excess than what is required
as per the overages specified.

3.Sealing of injection containers and closures

Neck of ampoule is sealed by fusion by heating in a flame ,
tip of the ampoule is placed in oxidizing flame and rotated
and a capillary is gradually formed while pulling out which
subsequently fuses and then is rounded.
In case of vials and large volume parenteral bottles, they are
closed by placing a rubber stopper , and then sealed by
means of a aluminium cap.

4.Leak Test for injectable dosage from ampoules :

Finally sealed ampules are tested for leaks, the ampoules are
placed in die solution of methylene blue and vacuum is applied
for 1 min, the vacuum is released slowly and ampoules are
allowed to stand in solution at atmospheric pressure .
If there are leaks due to initial displacement of of air ,the
coloured solution will enter the ampoule imparting blue colour
to entire preparation.
Leak test can be done by making use of similar principle in
autoclave , while the preparation is being terminally sterilised
by using an autoclave.

CHARACTERISTIC

GLASS

PLASTIC

TRANSPARENCY

HIGHLY AUTOMATED LEVEL

CONTROL AND PROBLEM FREE PARTICLE
EXAMINATION

MODERATE AUTOMATED TEST DIFFICULT

UV-LIGHT PROTECTION

GUARANTEED

GUARANTEED

STERILISABILITY THROUGH

-200 C TO +500 C
LYOPHILISATION, HOT-AIR
STERILIZATION, GAMMA RAY
IRRADIATION

-20 C TO ? LYOPHILISATION POSSIBLE/CERTAIN

CONDITIONS HOT AIR STERILIZATION NOT
POSSIBLE GAMMA-RAY IRRADIATION POSSIBLE
UNDER CERTAIN CONDITIONS.

AGEING

CANNOT BE PROVED

DEPENDING ON STORAGE
CONDITIONS(ENVIRONMENT, STERILISATION)

COMPACTNESS
(PERMEATION)

ABSOLUTELY GAS-TIGHT

PERMEABLE FOR GASES

INTERACTION PACKING/CONTENTS
(MIGRATION)

KNOWN IF PRESENT, EASY TO

PRESENT DIFFICULT EXAMINATION
REGULATE

INTERACTION CONTENTS/PACKING
(SORPTION)

NEGLIGIBLE

PRESENT (CHANGE IN THE CONCENTRATION OF

THE AGENT)

DISPOSAL

RECYCLING POSSIBLE

DOWN CYCLING POSSIBLE

OUTER PACKING/TRANSPORT MEASURE PROTECTION AGAINST

AGAINST BREAKAGE
BREAKAGE NECESSARY

PROTECTION AGAINST SCRATCHES AND

EMBRITTLEMENT NECESSARY

LETTERING/PRINTING/LABELLING

SCREEN
PRINTING+LABELLING
PROBLEM-FREE

LABELLING+RELIEF-PRINTING PROBLEM FREE.

MECHANICAL STABILITY
(SHORT-TERM COMPRESSIVE
STRENGTH)

GOOD

PARTIAL CRITICAL

EXPERIENCE WITH THE MATERIAL

VERY HIGH

LOW

CONCLUSION: AS COMPARED TO PLASTICS GLASS HAS DISTINCT

ADVANTAGES IN
1) TRANSPARENCY
2) AGEING
3) LEACHABILITY
4) PERMEABILITY
5) STERILISABILITY BY AUTOCLAVING AND DRY HEAT
STERILIZATION.