WATER FOR

PHARMACEUTICAL USE
Introduction
As a compound water exists in all the three states
of matter i.e. liquid, vapor & solid .
About 75% of earth is covered by aqueous water.
In vapour form water is an important constituent of earth
atmosphere. Water also occurs in all animals and vegetable
tissues
water constitutes 70% of human body weight .
PROPERTIES OF WATER
Water is distinguished from other covalent hydrides by its strong hydrogen bonds
which exist between neighboring molecules.
 Although oxygen is second to fluorine in the strength of the hydrogen bond, it forms
hydrogen bonding, reaches its peak in water because of the two protons per molecule
available for hydrogen bonding.
 Ammonia and hydrogen fluoride are limited to one hydrogen bond per molecule.
Because of its multiplicity and strength of hydrogen bonds in water many of its
physical properties are of much greater magnitude than would normally be expected.
HYDRIDES
Hydride- any of a class of chemical compounds in which hydrogen is
combined with another element.
Three basic types of hydrides;
1. saline (ionic)- alkali metals and  alkaline-earth metals (with the
possible exception of beryllium hydride, BeH2, and magnesium
hydride, MgH2)
2. Metallic -transition metals and inner transition metals( (the 
scandium, titanium, and vanadium families)
3. Covalent-rest of main groups
may be distinguished on the basis of type of chemical bond involved
Unusual properties of water
 Water is a unique liquid and its properties do not follow those of other hydrides.
 For example, ammonia and hydrogen fluoride are classical examples of covalent hydrides.
 Water is distinguished from other covalent hydrides by its strong hydrogen bonds which exist between
neighboring molecules. Although oxygen is second to fluorine in the strength of the hydrogen bond, it forms
hydrogen bonding, reaches its peak in water, because of the two protons per molecule available for
hydrogen bonding.
 Ammonia and hydrogen fluoride are limited to one hydrogen bond per molecule.
 Because of hydrogen bonding ( multiplicity and strength of hydrogen bonds in water), many of its physical
properties are of much greater magnitude than would normally be expected.
Comparison of boiling points of NH3 ,H2O
and HF r.t.p(20 c,1atm)
0

NH3 H2O HF

Boiling Point(oC) -33.34 100 19.5

State at r.t.p Gas liquid Gas/liquid

Hydrogen bond
• Hydrogen bonding is a special type of dipole-dipole attraction
between molecules, where hydrogen is covalently bonded to two
other electronegative atoms( examples , N,O, or F atom).
• The bond is weaker than ionic and covalent bond but stronger than
Van der Waals forces.
• hydrogen bonding doesn’t occur in molecules with non-polar covalent
bonds because it is formed when electrons are unequally shared
between hydrogen and an electronegative atom.
• As a result hydrogen atom carries a weak positive charge (Hδ+) and
remains attracted to negatively charged atoms
Comparison of water with other hydrides
PHYSICAL PROPERTIES OF WATER
Water has unusually high;
Boiling point
Melting point
Specific heat
Heat of vaporization
Surface tension
Viscosity
Dielectric constant
Significance of unusual properties of water
• This plays an important role in both the biological & chemical
Processes;

a) Water is responsible for milder climate difference because of high

specific heat and density inversion. Crust of ice which form floats on
water surface (since its less dense) in the temperate zone during
cold seasons prevent water from freezing into a single solid mass.
This coupled with the insulating effect of the upper layer protect
the fresh layer water from freezing.
• High specific heat of water makes it possible to store large quantities
of heat in the oceans in hotter regions and give it up to the other
colder air in the temperate zones. This is responsible for the
temperature moderation.
• Body temperature is also regulated as 1g of water evaporates from
the body in form of perspiration, it carries with it 2.2kj of heat(specific
heat capacity of water).Other liquids have only 1/10 of this heat per
gram under similar conditions
SOLVENT PROPERTIES OF WATER
For most liquids preparations it is the solvent of choice because:
a) Forms the predominant constituent of the body (60-70%) and therefore presents no problems
with regards to metabolism, toxicity, excretion when used in making preparations.
b) Cheap and readily available
c) Excellent solvent properties
Non-aqueous system solvents are usually resorted to only after all possible aqueous systems.
Mixtures of aqueous- organic solvents have been tried and found unsatisfactory.
Water-ethanol system is frequently useful solvent for substances slightly soluble in water e.g.
hydrobromides.The disadvantage is that alcohol promotes the saline taste of bromides and other
salts(antihistamine based salts)
UNUSUAL SOLVENT ACTION OF
WATER
The unusual solvent action is due to/ the properties that
constitute to excellent actions of water are:
1.High dielectric constant-ability to insulate the charges
2.Small size of water molecule
3.Strong permanent dipoles of water molecules hence high
hydration energy
4.Availability of its protons for hydrogen bonding
Water acts as a solvent for a wide range of substances..
• Because of high dielectric constant, it will bring insulating effect during
penetration which will then reduce electrostatic attraction between the opposite
charges involved.
• Because of the strong dipoles, water will form ligands with opposite charges and
the hydration energy produced as a result will enhance the separation of
opposite charges
• Because of the availability of protons for hydrogen bonding, more water
molecules will attach and facilitate further separation leading to what is
commonly describe as ‘like dissolves like'. Water dissolves polar
compounds ,which form hydrogen bonds and ionic compounds
 CHEMICAL PROPERTIES OF WATER
Water is chemically stable compound; however two types of equilibrium exist;
a) Disproportionation of water (Decomposition into elements)
2A A1 + A11where A,A1 and A11are all different chemical species e.g.
2H2O 2H2+ O2. For practical purposes, this reaction is nonexistent at ordinary
temperatures. Even at 20000 C, less than one per cent of the product will be formed.

b) Ionic dissociation reaction

2H2O H3O+ + OH-
The above equation is equally insignificant. For pure water Kw=1.008x 10 -14 at 250C.This constant varies
with temperature and increasing the temperature to 1000C, the value which we get is 1x 10-12
Despite and because of relative stability of water, it’s a versatile substance. It depends on its ability to act
as a solvent.
3. Despite this relative non reactivity, water is a very versatile
compound and its usefulness depends on the ability to;
i. Act as solvent for most compounds, particularly ionic compounds
ii. Undergo acid-base reaction
iii. Undergoes redox reaction
iv. Serves as a catalyst
(I) Redox properties of water
 This is generally of minor importance in pharmaceutical systems.
 As an oxidizing agent, hydrogen can act with any metal above hydrogen. However, at room
temperature; this reaction is negligible for most metals encountered e.g. Fe, Al, Zn
 Active elements such as sodium, lithium and calcium which are capable of reacting with water at
room temperature are generally not encountered as metals in pharmaceutical works except in
synthetic work.
 Sodium can react with water as follows:
2Na + 2H2O 2NaOH + H2
 This only is only capable at room temperature. Iron is also capable of reacting with steam
2Fe + 3H2O (steam) Fe2O3 + 3H2 at 1000C and above
 For mercury, no reaction at all Hg + H2O No reaction
 Water is also capable of acting as a reducing agent but the possibility of encountering this is even
more remote. Only fluorine is strong enough to bring out the reducing power of water as shown.
2H2O + F2 2H2F2 + O2
HYDRATION (LIGAND)
 Because of its strong permanent dipole water frequently assumes
a role as a ligand in complex substances. Almost all cations form
one or more hydrates or ligands with water. Divalent cations, due
to their stronger electrostatic fields are more highly hydrated than
the monovalent cations of approximately the same size.
CATALYTIC PROPERTIES
 Frequently in traces only, water is essential for very many well-known reactions e.g.,
thoroughly dried hydrogen and oxygen do not react but in the presence of traces of
moisture the reaction is immediate and violent
 Water is considered to have catalytic reaction on quite a number of oxidation reactions
e.g., Iron (II) in the presence of moisture will be oxidized but without moisture will remain
as iron.
WATER FOR PHARMACEUTICAL
USE(WPU)
• The various types of water available include the
following;
1. Natural water
2. Potable water
3. Purified water
4. Water for injection (WFI)
5. sterile water for injection(SWFI)
Natural water

• Water that has not undergone any treatment e.g.

• rain water
• springs
• Wells
• lakes
• sea
• Borehole
Impurities in natural water
Natural water has impurities divided into four categories namely
1) Suspended materials e.g. sand ,clays, living matter, fragment of
plants
2) Dissolved salts- Dissolved bicarbonate constitutes temporary
hardness while sulphates constitute permanent hardness. These
salts dissolved in natural water are normally dilute salts of
Mg,Ca,Na,Fe and K having as anions bicarbonate ,sulphates and
chlorides(Assignment: write short notes on temporary and
permanent hardness of water and how the two types of hardness
can be removed)
Impurities in natural water
3. Dissolved gases e.g. NH3,CO2,O2
4. Dissolved minerals due to organic activities- water in inhabited
areas often contain dissolves minerals such as nitrites sulphates,
organic minerals
Potable water
• This is water that has been treated and rendered safe and suitable for
human consumption. It should be
• palatable and safe to drink
• clear
• tasteless and free from pathogens and toxins.
• This is the water supplied straight from municipal mains and it is the
water of the USP ,B.P ,B.P.C and USP
PREPARATION OF WATER

 The method used and the extent of treatment is determined by several

factors which depend upon the nature and quantity of undesirable
constituents in the available natural water to be used in preparation of
potable water.
 The following must be considered
Taste, colour, odour, PH, total solids and pathogenic micro-organisms
PREPARATION OF WATER
The overall process of preparation involves the following unit operations;
1. Removal of insoluble matter through appropriate coagulation ,settling and filtration
2. Destruction of microorganism by aeration ,chlorination ,and other methods
3. Improvement of taste(palatability) , odour , by aeration or filtration through charcoal
Other unit processes may include the following;
 Hardness removal
 Manganese & iron removal
 Turbidity removal
 Total dissolved solids (TDS) removal
 Control of organic substances
Therefore, the sequence of treatment consists of one or more
of the following;
Coagulation-settling-filtration-chlorination, palatability,
odour & taste improvement OR
Raw water-pretreatment/Preparation-settling-Filtration-
aeration/chlorination-charcoal filtration-portable water
PRETREATMENT
•It includes:
 Coagulation using aluminium sulphate Al 2(SO4)3 or FeSO4

 Fluoridation in some cases using Na2SiF6 or hydrofluorosilicic acid

 Softening using calcium hydroxide, Ca(OH)2

Coagulation
 If suspended materials are exceptionally fine or colloidal a coagulating material should be added and in
most cases it is aluminium and ferrous sulphate.
 Using ferrous, it is first oxidized by the air to form iron (III) and it is the Fe 3+ that is responsible for
coagulation as follows:

Fe2+ Fe3+
The chemistry involved is as follows
FeSO4 Fe2+ + SO42-
Fe2+ + 12𝑂2 +H2O [Fe (H2O) 6]3+
[Fe (H2O) 6]3+ + 3H2O Fe (H2O) 3(OH) 3 + 3H3O+(gelatinous material traps fine
particles)
DISSOLVED SOLIDS
 Dissolved solids are generally not easy to remove and they range from 25 to 1000ppm.If raw water
is exceptionally hard; the ppm goes higher and has to be reduced using lime or ammonia.
 Exceptionally lime or ammonia may be added during pre -treating stage. The base neutralizes the
soluble bicarbonate ion precipitating them in form of Ca2+, Mg2+ and Fe3+ ions.
Chemistry basically can have:
HCO3- + OH- CO32- + H2O
Soluble insoluble

The precipitated normal bicarbonate is removed during settling and filtration. Only bicarbonate hardness is
reduced by the base treatment (lime).Other chemicals such as metaphosphates are available to reduce
hardness more completely if it is necessary
Removal of pathogens
• oxidative procedures used e.g., chlorination, boiling and aeration.
• Aeration will remove anaerobic bacteria. With more polluted water, more action of chlorine is used. Most
compounds used (chlorine, calcium hypochlorite sodium hypochlorite,jik ) are excellent germicides that are
frequently used instead of chlorine. For large scale, chlorine is recommended.

 When chlorine is used, the chemistry is as follows:

Cl2 + 2H2O HOCl + H3O+ + Cl-
 It is the released hypochlorous acid that is responsible for the germicidal action. As seen from the
reaction equation, when chlorine is used, an equivalent amount of hydronium ion is released and
this will then decrease the pH(makes it more acidic)
If very high chlorination is necessary an excess acidity can result and can be reduced when ammonia is
added to increase the pH to a more acceptable level
Taste improvement
 aeration can be used to reduce odours and taste to some degree.
For excessively offensive taste and odours, filtration through charcoal is necessary

HEAVILY COLOURED WATER

 Excessively colored water, though rare but is common in industrial waste and sewage waste, can
be improved upon by adsorption on charcoal or chlorination
Fluoridation
• It is used in communities with fluoride deficient water sources.
• The compounds used are sodium fluorosilicate (Na2SiF6),fluorosilicic acid ,H2SiF6 and in some cases
ammonium fluorosilicate.
• Tablets have been formulated which when added to some amount of water gives the desired concentration

 Fluoride ion becomes available on dissociation of fluorosilicate and releases fluoride as follows:

2(H+ Cl-)
Na2SiF6 H2SiF6 +2NaCl
The fluorosilicic acid can form hydrogen fluoride (H2F2 - a dimer)
H2SiF6 H2F2 + SiF4
H2F2 2H3O+ + 2F-
SiF4 + 4H2O H2F2 + SiO2
Fluoride level of between 0.8-1.3ppm is recommended but 1ppm is the most commonly used.
SELECTION OF WATER
TREATMENT OF WATER
Hard water
Hard water- water that contains salts of calcium and magnesium
principally as:
 Bicarbonates
 Chlorides
 sulfates. 

Water hardness that is caused by calcium bicarbonate is known as

temporary, because boiling converts the bicarbonate to the insoluble
carbonate; hardness from the other salts is called permanent.
Softening hard water
•  Water is softened on a small scale by the addition of;
•  ammonia
• borax, or trisodium phosphate, together with sodium carbonate
(washing soda).
• The latter precipitates the calcium as carbonate and the magnesium as
hydroxide. 
• Water is softened on a large scale by the addition of just enough lime to
precipitate the calcium as carbonate and the magnesium as hydroxide,
whereupon sodium carbonate is added to remove the remaining
calcium salts.