Pharmaceutical Inorganic Chemistry Unit I Chapter 2 Different official waters used in pharmaceuticals Potable water Purified water Water for injection Sterile water for injection Bacteriostatic water for injection Different parameters for waters

1. Abhishek Rai

2. Water
“Water flows from high in the mountains
Water runs deep in the earth
Miraculously, water comes to us
And sustains all life”
-Thich Nhat Hanh
Most common liquid in surroundings. 70% of the earth is covered by water.
Water makes 60% of human body weights
Water is most widely and abundantly utilized substance in pharmaceutical manufacturing.
For different purposes different grades of water are used.
Based on source, method of preparation and applications water can be classified into several types
viz, potable water, Purified water IP, water for Injections IP, Sterile water for injections IP,
Bacteriostatic water for Injection USP.

3. Water
Natural Water:
Water that occurs in nature in rivers, lakes & wells containing dissolved minerals native to the
region. It may contain clay, sand, microbes and fragments of plants and animals.
Potable Water:
Natural water treated to make fit for drinking.
It is obtained by treating natural water to remove various insoluble matter through coagulation,
settling and filtering process, destruction of pathogenic microbes by chlorination, removal of
obnoxious substances by aeration and filtration through charcoal etc.
As per IP, total aerobic microbial count allowed for potable water is 500 CFU per ml.
Potable water can be used for the synthesis of drugs and additives but should not be used in the
production of dosage forms as well as in analysis.

4. Purified Water I.P.
Purified Water I.P.:
Purified water I.P is prepared by distillation or ion exchange or by any other appropriate means
from suitable Potable water that complies with all the relevant statutory regulations.
Throughout the process of production and during the storage such measures are taken to ensure the
quality in terms of controlling and monitoring microbes. Total viable count should be less than 100
microorganisms per ml determined by membrane filtration.
Purified water IP is used as pharmaceutical functioning as solvent in many preparations as well as
analytical solutions.

5. Purified Water I.P.

6. Water for Injection I.P.
Water of Injections is water intended for use in preparations for parenteral administration
when water is used as vehicle (Water for injections in bulk) and for dissolving or diluting substances
or preparations for injectable preparations (Sterile water for Injections).
➢Water for injection in Bulk
➢Sterile water for injection

7. Water for Injection in bulk
Water for injection in bulk is obtained by distilling potable water/purified water in a neutral
glass/quartz/suitable metal still fitted with an effective device for preventing the entrainment of
droplets.
The still must be maintained such to ensure production of apyrogenic water.
First portion of the distillate is discarded and the remainder is collected and stored in conditions
designed to prevent the growth of microorganisms and to avoid any contamination.
Description: A clear, colorless and odorless liquid
Conductivity: Meets the requirements of the test
Total organic carbon: Not more than 0.5 mg/lit
Storage: In containers designed to prevent the growth of micro-organisms.
Labelling: The label on the container in which the bulk has been distributed states that the contents
have not been sterilized.

8. Water for Injection in bulk
Quality control:
✓Test for acidity or alkalinity
✓Ammonium
✓Calcium and magnesium
✓Heavy metals
✓Chlorides
✓Nitrates
✓Sulphates
✓Aluminum
✓Bacterial endotoxins

9. Sterile Water for Injection
Its water for injections that has been distributed in suitable containers of glass or any other material,
sealed and sterilized by heat under conditions that ensure that the water complies with the test for
bacterial endotoxins.
Its free form any added substances.
Each container contains sufficient quantity of water for injections to permit the withdrawal of
nominal volume.
Storage: Stored in single dose containers of not larger than one liter size.

10. Sterile Water for Injection
Quality control:
Appearance: When examined in suitable conditions of visibility, its clear, colorless and practically
free form suspended particles.
Acidity or alkalinity
Ammonium
Calcium and magnesium
Heavy metals
Chlorides, Nitrates & Sulphates
Oxidisable substances
Residues on evaporation
Particulate contamination
Bacterial endotoxins & Sterility

11. Water Ammonia Free
It is prepared by adding 0.1 ml Sulphuric acid to 100 ml purified water and distilling it. First 10 ml
are discarded and following 50 ml are collected.
Water, ammonia free should comply with following test:
To 50 ml water ammonia free, add 2 ml alkaline potassium mercuri iodide; no color is produced

12. Water Carbondioxide Free
Prepared by boiling purified water vigorously for a few minutes. It is stored such as to prevent from
the atmosphere.

13. Water Nitrate Free
Prepared by adding 5mg each of potassium permanganate and barium hydroxide and distilling. First
10 ml is discarded and following 50 ml is collected.

14. Bacteriostatic Water for Injection, USP
Water for injection containing one or more suitable antimicrobial agents.
It is stored in single dose/multiple dose containers of not larger than 30 ml size.
It is used for compounding small volumes of extemporaneous parenteral preparations for
Intramuscular injections.
Bacteriostatic water for injection can not be used intravenously as it contains bacteriostatic agents.
Labelling: Its label should contain all the parameters of water for injection and additionally it should
also contains names and concentrations of bacteriostatic agents used.

15. Official Control tests for Purified Water I.P.
Acidity/alkalinity:
To 10ml, freshly boiled and cooled in a borosilicate glass flask, add 0.05ml methyl red solution, the
resulting solution is not red.
To 10ml, freshly boiled and cooled in a borosilicate glass flask, add 0.1ml bromothymol blue
solution, the resulting solution is not blue.
Ammonium:
To 20ml, add 1 ml alkaline potassium mercuri iodide solution and allow to stand for 5 minutes. When
viewed vertically the solution is not more intensely colored than a solution prepared at the same
time by adding 1 ml of alkaline potassium mercuri iodide solution to a mixture of 4 ml of ammonium
standard solution (1 ppm Ammonium) and 16 ml of ammonia free water (0.2 ppm)
Calcium and magnesium:
To 100 ml, add 2ml of ammonia buffer pH 10.0, 50 mg of mordant black II mixture and 0.5
ml 0.01M disodium edetate; a pure purple color is produced

16. Official Control tests for Purified Water I.P.
Heavy metals:
Evaporate 150 ml to 15 ml on a water bath; 12 ml of the solution complies with the limit test for
heavy metals (Method D). Use lead standard solution (1 ppm Pb) to prepare standard.
Chlorides:
To 10ml, add 1 ml 2M Nitric acid and 0.1M silver nitrate; the appearance of the solution does not
change at least for 15 minutes.
Nitrates:
To 5 ml in a test tube immersed in ice add 0.4 ml of a 10% w/v solution of potassium chloride, 0.1 ml
of diphenylamine solution and dropwise with shaking 5 ml of sulphuric acid. Transfer the tube to a
water bath at 500C and allow to stand for 15 mins. Any blue color in the solution is not more intense
than that in a solution prepared at the same time and in same manner using a mixture of 4.5 ml of
nitrate free water and 0.5 ml of nitrate standard solution (2 ppm NO3) (0.2 ppm).
Sulphates:
To 10 ml add 0.1 ml of 2 M HCl and 0.1 ml of barium chloride solution. The appearance of the
solution does not change for at least 1 hour.

17. Official Control tests for Purified Water I.P.
Oxidizable substances:
To 100 ml add 10 ml of 1M H2SO4 and 0.1 ml of 0.02M KMnO4 and boil for 5 mins; the solution
remains faintly pink.
Residues on evaporation:
Evaporate 100 ml to dryness on a water bath and dry to constant weight at 1050C. The residues
weighs not more than 1 mg (0.001%).

18. Official Control tests for Purified Water I.P.
Purified water intended for use in the manufacture of dialysis solutions and also without a
further procedure for removal of the removal of bacterial endotoxins complies with the following
additional requirements
Aluminum: Not more than 10 ppb,
Test Solution: To 400 ml of water under examination, add 10 ml of acetate buffer solution pH
6.0 and 100 ml of distilled water
Reference solution: Mix 2 ml of aluminum standard solution (2ppm Al), 10 ml acetate buffer
solution pH 6.0 and 98 ml of distilled water.
Blank solution: Mix 10 ml of acetate buffer solution pH 6.0 and 100 ml distilled water.
Bacterial endotoxins:
Not more than 0.25 endotoxin unit per ml.

19. Official Control tests for Water for Injection I.P.
Bacterial endotoxins:
Not more than 0.25 endotoxin unit per ml.
Total organic carbon:
Not more than 0.5 mg per liter.
Sterile Water for Injection:
Chloride test for sterile water for injection for containers with volume less than 100 ml
15 ml complies with the limit test for chlorides using a standard solution prepared by mixing 1.5 ml
of chloride standard solution (5 ppm) and 13.5 ml of water.
Oxidizable substances:
Boil 100 ml with 10ml 1M Sulphuric acid, add 0.4ml 0.02M Potassium permanganate (For sterile
water for injection with fill volume less than 50 ml) or 0.2ml 0.02M potassium permanganate (For
sterile water for injection with fill volume 50ml or more) and boil for 5 min. If a precipitate
forms, cool in a ice bath to room temperature and filter through a sintered glass filter (porosity No.
3). The pink color of the solution does not disappear completely.

20. Official Control tests for Water for Injection I.P.
Sterile Water for Injection:
Residues on evaporation:
Evaporate 100ml to dryness on a water bath and dry the residue to constant weight at 1050C.
For containers with a nominal volume of 10 ml or less, the residue weighs not more than
4ml(0.004%).
For containers with nominal volume greater than 10 ml, the residue weighs not more than
3mg(0.003%).

21. Thank You