Industrial

Pharmacy
Water For Injection (WFI)
(preparation)

What is Water For Injection

Water for injection is defined as:
Water purified by distillation for the preparation of
products for parenteral use.
OR
Water for parenteral use, prepared by distillation
or reverse osmosis and meeting certain standards
for sterility and clarity.

Preparation of water for

injection:
SOURCE OF WATER: can be expected to
contaminated with
Natural suspended minerals
Organic substances
Dissolved minerals salts
Colloidal materials
Viable bacteria
Bacterial endotoxins
Industrial or agricultural chemicals
And other particulate matters

Continue..
Degree of contamination will VARY with the source
and will be markedly different , whether obtained
from a well or from surface sources , such as
stream or lake.
Hence the source of water usually must be
pretreated by one or combination of the following
treatments:
Filtration
Deionization
Carbon adsorption
Or Reverse osmosis

Preparation of water for

injection:
PRETREATMENT
DEIONIZATION
POLISHING/ Depyrogenation

A : PRETREATMENT:

Multimedia filters
Water softener
Activated carbon bed filter
uv sterilization
5 micron prefilters

MULTIMEDIA FILTERS
Remove suspended solid from feed water
Effective of multiple layer of media within the
filters that are arranged to coarse to fine media.
As water flows downward through the filter, the
large particulate matter is removed at the top of
the filter and small particulate matter is removed
at the bottom of the filter paper
Multimedia filters are used as pretreatment to
water softener , carbon filters and reverse
osmosis to prevent these system from
prematurely clogging with suspended solids.

CARBON BED FILTER

Carbon filtering is a method of filtering that uses a
bed of activated carbon to remove contaminants and
impurities using chemical absorption
Carbon readily absorb organics and chlorine and is
therefor used to filter such elements from feed water.
Activated carbon works via a process called
ADSORPTION , whereby pollutant molecules in the
fluid to be treated are trapped inside the pore
structure of carbon substrate.
Chlorine must be removed from feed water for use in
reverse osmosis and all distillation system. BECAUSE
chlorine will attack membranes and stainless steel.

 Because carbon filter removes chlorine from feed

water bacterial growth and control must be
addresses in the design of carbon filters.
To ensure the breakdown chloramines, carbon bed
should be sized of less than one gallon per minute
of feedwater flow per cubic foot of carbon.
In this process the carbon effectively removes the
chloramine, leaving the ammonium ion in feed
water. Ammonium ions can be removed through
water softening.

WATER SOFTENER:
Water softening removes the hardness from feedwater to
prevent hard water scale from coating evaporator tube.
Overtime, hard water will degrade a distillation units capacity.
Water softening removes calcium and magnesium ions ,the
cause of water hardness , and replaces them with sodium ions.
MECHANISM:
Water softener should be sized for salt brine regeneration
after 12 hours of operation.
The regeneration process involves rinsing the water
softeners cation based resins with a salt brine solution.
The concentrated sodium ions push the calcium and
magnesium

Ions away from the resin to drain , beginning the

softening process all over again.
In some applications , secondary water softener
are installed after a carbon filters to remove
ammonium ions from the feed water.
The cation resins does not attract the ammonium
ions as readily as calcium and magnesium ions,
but if not removed . The ammonium ions will
produce high conductivity distillate.
Therefore, the primary and secondary water
softener are used.

UV STERELIZATION
Germicidal activity.
Ultraviolet light inactivation is a very efficient and
non selective method to remove microorganisms.
Germicidal UV disinfection is most typically
generated by a mercury vapor lamp.
The UV lamp never contacts the water, it is either
housed in quartz glass sleeve inside the water
chamber or mounted external to the water which
flows through the transparent UV tube.
Water passing through the flow chamber is
exposed to UV rays which are absorbed by
suspended solids, such as m.o & dirt.

PREFILTERS.
The term PREFILTER refers to any type of filter
that proceeds the final barrier.
Reduces the quantity of suspended matter in
water prior to other treatments.
Removal of microorganism from water during
treatment(roughing prefilters).

B: DEIONIZATION
Deionized water is also known as demineralized
water. DIW is water that has had almost all of its
mineral ions removed, such as cation like sodium,
calcium, iron, copper and anions such as chloride
and sulphate. Followings are the steps..
Ion exchanger (separate bed & mixed bed)
Reverse osmosis (single pass& double pass)
0.2 micron final filter
Continuous deionization
WHAT IS REVERSE OSMOSIS :the natural process of
selective permeation of molecules through a
semipermeable membrane separating 2 aqueous
soln of different concentration is reversed.

 Ion exchange process will remove carbon dioxide

that can cause two pass reverse osmosis to fail on
line conductivity requirements.
The system designed with ion exchange following
SINGLE & DOUBLE PASS reverse osmosis.
The ion exchange system provide additional
reduction process, generally rendering the water
much lower in conductivity than required
Use of SEPARATE BED for cation and anion resins
provides extreme pH in beds that helps retard
bacterial growth.

 Although DOUBLE PASS RO may provide adequate

ion removal.
The conductivity requirements of USP water
system approximate the capability of DOUBLE
PASS revers osmosis.
It consistently provides required conductivity.
Bacterial colonization of ion exchange bed is
common, particularly in mixed beds which has a
neutral pH.
Furthermore, in DOUBLE PASS RO in front of
MIXED BED resin replacement will b infrequent.

CONTINOUS DEIONIZATION:
Electrodeionization technology provides
CONTINUOUS DEIONIZATION and continuous
regeneration without acid and caustic.
Feed water to the EDI system must be treated by
reverse osmosis.
Depending on raw water quality, single pass RO
may be adequate for EDI pretreatment.

0.2 MICRON FINAL FILTER:

A 0.2 micron or smaller cartridge filtration unit
should be installed at the outlet of the final
deionization system
This will prevent resin or other particulate matter
from contaminating the deionized water.

C: POLISHING/
DEPYROGENATION :
DEPYROGENATION refers to removal of pyrogens
free solution, most commonly from injectable
pharmaceuticals.
Processes involved 1) Distillation 2) Ultrafiltration
DISTILLATION : is natural water purification process
consisting of the vaporization and condensation of
water.
Distillation used after a primary ion reduction
process to reduce the potential for scaling and
fouling of the still.
ULTRAFILTRATION: the process works by excluding
endotoxins by molecular weight using an ultra fine
filters that blocks moecules of 10,000 Daltons or

STORAGE:
Collecting in a holding tank for subsequent use.
In large operations , the holding tanks may have a
capacity of several thousands gallons and be a
part of continuously operating system. In such
instances the USP requires that the water for
injection be held at temperature too high for
microbial growth. Normally , this temperature is a
constant 80C.
Stainless steel tanks are also used.