WATER

The Commonest solvent or vehicles for

large number of pharmaceutical

preparations
Naturally occurring water contains many
dissolved impurities.
Absolutely pure water does not occur in
nature.

TYPES OF WATER
Purified Water
Highly Purified Water
Water for Injection
Sterile Water for Injection

CHARACTERISTICS OF WATER
Universal Pharmaceutical solvent.
Water is unique in that it is the only

natural substance that is found in all three

states -- liquid, solid (ice), and gas
(steam) , at the temperatures normally
found on Earth.
Most of the human body consist of water.
Any water is not ideally pure.

WATERS IN
PHARMACEUTICS
(1)
(2)
(3)
(4)

Purified water
Highly purified water
Water for injection
Sterilized water for injection

Purified water
It occurs as clear, colourless, odourless and

is not intended for parentral administration

Need to be sterile and apyrogenic.
Purified water B P is water obtained by
distillation , by ion exchange treatment or
by reverse osmosis.

Test the aerobic count

Storage should be monitored in such a way

that the aerobic count is controlled.

The aerobic count is determined with the
help of agar medium S incubating at 30-35
degree Celsius for 5 days.
The allowable aerobic count is 100 microorganism/ml.

Tests
Organic carbon test: not more than 0.5

mg/l
test for the oxidising substance:

100ml of water+10ml dil. Sulphuric acid+0.1

ml of 0.02M potassium permanganate boil
for 5min and the solution should turn faint
pink.

Nitrate
Maximum 0.2 ppm

5 ml test tube immersed in iced water, add

0.4 ml of 100g/l solution of KCl +0.1 ml of

diphenylamine solution + 5ml nitrogen
free sulphuric acid (dropwise). Warm it for
15 min.
The solution should not be darker than the
standard solution.

Aluminium
maximum 10ppb.
400ml of water+ 10 ml of acetate buffer

solution pH 6. compared to the standard

solution

Heavy metals
Maximum 0.1ppm

Acidity and Alkalinity

To 10 ml of boil WATER in borosilicate flask

add 0.05 ml of methyl red solution .

The solution should not turn red .

CHLORIDES
To 10 ml of water add dilute nitric acid 1 ml

, & 0.2 ml of silver nitrate solution.

The solution should not show any change in
appearance for at least 15 min.

SULPHATES
To 10 ml add 1 ml of HCl add 0.1 ml of

barium chloride solution .

The soluution should not change in
appearance atleast for one hour.

AMMONIUM
Maximum 0.2 ppm .

Labelling
The substance is suitable for use in

manufacture of dialysis solution.

Highly purified water

Water is intended for use in the

preparation of medicinal products where

water of high biological quality is
needed, except for injection.

Production
Highly purified water is obtained from

water that compiles with regulations on

water intended for human consumption laid
down by contempt authority.
Current production methods include:
double pass, R.O., coupled with other
suitable techniques such as ultra filtration
and deionization. Correct operation and
maintenance of the system is essential.

Storage should be monitored in such a way

that the aerobic count is controlled.

The aerobic count is determined with the
help of agar medium S incubating at 30-35
degree Celsius for 5 days.
The allowable aerobic count is 100 microorganism/ml.

The limit test are same for

every water yet the content
of agents that are to be
restricted may change

Labelling
The labels states ,that the substance is

suitable for use in the manufacture of

dialysis solution

Water for injection

For parental administration where water is

used as vehicle.
Highly purified water is obtained from
water that compiles with regulations on
water intended for human consumption
laid down by contempt authority.
oxidizable substances and total solids
should be minimal
Water for Injection U.S.P. is water purified
by distillation.

 The apparatus which are in contact with the water eg.

Neutral glass , quarts should be maintained properly.

Storage should be monitored in such a way that the
aerobic count is controlled.
The aerobic count is determined with the help of agar
medium S incubating at 30-35 degree Celsius for 5
days.
The allowable aerobic count is 10 microorganism/100ml.
Requires for water of Injection be stored at a
temperature below 40C or above 370 C, the range in
which microbial growth occurs.

Bacteriostatic Water for injection

is sterile
water for injection containing one or more
suitable antimicrobial agents and occurs as a
clear, colourless,odourless or having the odor
of the antimicrobial agents
Benzyl alcohol is a Common bacteriostatic
agent.
Most of the specifications such as pH, chloride,

total solids, and oxidizable substances have

been modified to make allowance for the
bacteriostatic agent.

It does have specifications for antimicrobial

agents, pyrogens, and sterility.

Nitrates : maximum 0.2 ppm.

Aluminium : Not more than10 ppb.
Heavy metal : maximum 0.1 ppm.
Bacterial endotoxins : not more than

0.25 IU/ml.

Sterilised water for

injection
Water for injection in bulk that has been distributed into

suitable containers, closed and sterilised by heat in

condition that the product still complies the test for the
bacterial endotoxins.
The container should be such that the withdrawal is easy
and minimum involvement of hand or other instrument
occurs.
Limit tests are same as water for injection.
the tests in Sterile Water for Injection serve as a check
for material extracted from the closures during
sterilization and storage .

lable
The label must indicate that no antimicrobial or

other substance has been added, and that it is

not suitable for intravascular injection without
its first having been made approximately
isotonic by the addition of a suitable solute.

METHOD OF PREPARATIONS
Distillation Method
Ion-Exchange Method
Reverse Osmosis

DISTILLATION
Water--- Vapour----water
Generally the first portion of Aq. Distillate

(about 10-20%) must be discarded & last

10% of distillate is discarded.

Ion-Exchange Method
Water passes through a column of cation

and anion exchangers consisting of water

insoluble resins of high molecular weight.
Two types of Resins
Cation (acid exchangers)
The anion (base exchanger)

Ion-Exchange Resin Bead model

Fixed Anion
Counter Cation
Styrene
Cross linking Agent
(DVB)
Hydrating Water

Cation exchange
H-resin + M+ + X + H2O
H2O

M-resin + H+ + X- +

Anion exchange
Resin-NH2 + H+ + X- + H2O
(Pure)

Resin-NH2. HX + H+ + X- + H2O

Reverse Osmosis
Referred as Cross-flow (tangential flow)

membrane filtration
Pressurized stream of water is passed
parallel to the inner side of a filter
membrane core.
A portion of the feed water permeates
the membrane as filtrate, while the
balance of the water sweeps
tangentially along the membrane to exit
the system without being filtered.

Reverse Osmosis

Reverse Osmosis
Osmosis

Osmotic
pressure
1

Feed water

Purified water

Reverse osmosis
membrane (RO)

Reverse osmosis (RO) theory

Low pressure

High pressure

under
pressure

raw water

Semi-permeable
membrane

Feed
water

Permeate
water

Reject
water
drain or recycle

Purified water

Pyrogens and endotoxins

1. Any compound injected into mammals
which gives rise to fever is a Pyrogen
2. Endotoxins are pyrogenic, come from
Gram negative bacterial cell wall
fragments
3. Detect endotoxins using a test for
lipopolysaccharides (LPS)
rabbit test detects pyrogens
LAL test detects endotoxins

4. Ultrafiltration, distillation, & RO may

remove pyrogens

Testing - setting specifications

for purified water or WFI - (1)

Ph. Eur.
JP
USP Int. Ph.
pH 5.0-7.0 5.0-7.0
5.0-7.0
pass test
Cl < 0.5
pass test
pass test
SO4
pass test
pass test
pass test
NH4 < 0.2
< 0.05
pass test
Ca/Mg pass test
pass test
Nitrates < 0,2
pass test
pass test
Nitrites
pass test
-

Testing - setting specifications

for purified water or WFI - (2)

Ph. Eur.
Conductivity (S/cm)

JP
-

Oxidizable subs. pass test

Solids (ppm)

< 10

TOC (ppm)
CO2

< 10
-

- pass test

- nmt(*) 10

< 0.5

< 1.3

pass test

Heavy metals

USP Int. Ph

< 0.5
pass test

pass test