PHARM CHEM 11 REASONS WHY WATER IS THE SOLVENT OF CHOICE

6D. PHARMACEUTICAL WATERS (OFFICIAL USP/NF) • it is the predominant constituent of the body
WHAT IS WATER? • it has a high dielectric constant
• Of all the molecules in the universe, one of the • it readily forms hydrogen bonds
most important to humanity • it has small molecular size
• A chemical compound consisting of 2 hydrogen
atoms and one oxygen atom forming polar MAJOR CLASSIFICATIONS OF WATER
covalent bond
1. NATURAL WATER- found in indigenous areas
• A colorless, transparent, odorless, flavorless
liquid
2. POTABLE WATER- safe or fit to drink
• Widely used as a raw material, ingredient and
3. PURIFIED WATER- prepared by distillation, ion
exchange and reverse osmosis
solvent in the processing, formulation and
manufacture of pharmaceutical products, active 4. HEAVY WATER- isotopes of H (deuterium, D2O
pharmaceutical ingredients (APIs) and & tritium, H3 )
intermediates, compendial articles, and 5.
analytical reagents. 1. ALKALINE WATER Usually contain
appreciable quantities of
Properties of Water sodium and magnesium
• Water is an excellent solvent because of its sulfates
polarity and high dielectric constant. Polar and 2. CARBONATED Charged with carbon
ionic substances dissolve well in water, WATER dioxide under pressure
including acids, alcohols, and many salts while in earth
• Water is amphoteric. It can act as both and acid
3. CHALYBDEATE Have iron in solution or in
and as a base
WATER suspension and are
• Pure water is an electrical insulator. However,
characterized by a
even deionized water contains ions because
ferrigenous taste
water undergoes auto-ionization. Most water
contains trace amounts of solute. Often the 4. LITHIA WATER Occur in the form of
solute is salt, which dissociates into ions and carbonate or chloride
increases the conductivity of water 5. SALINE WATER Also known as “purgative
• Water displays capillary action because of its waters:, hold relatively
strong adhesive and cohesive forces large amount of
• Water readily forms hydrogen bonds with other magnesium and sodium
water molecules. One water molecule may sulfates with sodium
participate in a maximum, of 4 hydrogen bonds chloride
with other species
6. SULFUR WATER Have hydrogen sulfide
• Hydrogen bonding between water molecules
also gives it high surface tension. This is the 7. SILICEOUS WATER Include very small
reason why small animals and insects can walk amounts of soluble alkali
on water silicates.
• Due to solvent powers and physiological
inertness, water is an extremely important
pharmaceutical agent
2 CATEGORIES OF WATER hard; 120–180 mg/l, hard; more than 180 mg/l,
very hard (McGowan, 2000).
HARD WATER SOFT WATER • Although hardness is caused by cations, it may
• Water that has high • Water that contain few also be discussed in terms of carbonate
mineral contents or (temporary) and non-carbonate (permanent)
(Ca2+ and Mg2+ no calcium or hardness.
ions) also magnesium
bicarbonate and metal cations TYPES OF HARDNESS OF WATER
sulfates  TEMPORARY
• Also called as “bicarbonate hardness”
• Calcium usually • It has low mineral
• Caused by the presence in the water of calcium
enters the water as content or magnesium bicarbonates
either CaCO3+ in the
HOW TO TREAT?
form of limestone
to remove the cations by boiling or addition of a
and chalk, or calcium source of hydroxide
sulfate
 PERMANENT
• Caused by the presence in solution of sulfates,
(CaSO4) chlorides, hydroxides or calcium or magnesium
HOW TO TREAT?
• Hard water is
generally not Cannot be removed by boiling or addition of
hydroxide
harmful to one’s
health
OFFICIAL WATERS
HARDNESS OF WATER There are many different grades of water used for
pharmaceutical purposes. Several are described in USP
• Water hardness is the traditional measure of
monographs that specify uses, acceptable methods of
the capacity of water to react with soap, hard
preparation, and quality attributes. Different grades of
water requiring considerably more soap to
water quality are required depending on the different
produce a lather.
pharmaceutical uses.
• Hard water often produces a noticeable
deposit of precipitate (e.g. insoluble metals, Most liquid injections are quite dilute; the component
soaps or salts) in containers, including “bath present in the highest proportion are:
tub ring”.
1. Purified water
• It is not caused by a single substance but by a
variety of dissolved polyvalent metallic ions, 2. Water for injection
predominantly calcium, iron and magnesium
cations, although other cations (e.g. 1. Purified Water
aluminium, barium, iron, manganese, - clear colorless odorless liquid purified by
strontium and zinc) also contribute. distillation or reverse osmosis and contains no
added substances
• Hardness is most commonly expressed as: - Purified Water must meet the requirements for
milligrams of calcium carbonate / equivalent ionic and organic chemical purity and must be
per litre. protected from microbial contamination.
- The minimal quality of source or feed water for
• Water containing calcium carbonate at
the production of Purified Water is Drinking
concentrations: below 60 mg/l is generally
water.
considered as soft; 60–120 mg/l, moderately
 USES
 as an excipient in the production of non-
parenteral preparations and in other
pharmaceutical applications, such as
cleaning of certain equipment and non-
parenteral product-contact components.
 used for all tests and assays for which water
is indicated.
2. Sterile Purified Water, USP
• Purified Water sterilized and suitably packaged.
It contains no antimicrobial agent
• It is used in the preparation of non-parenteral
compendial dosage forms or in analytical
applications requiring Purified Water where
access to a validated Purified Water system is
not practical, where only a relatively small
quantity is needed, where sterile Purified
Water is required, or where bulk packaged
Purified Water is not suitably microbiologically
controlled.
• Label should state: NOTE: Do not use Sterile
Purified Water in preparations intended for
parenteral administration.
3. Water for Injection
• clear colorless odorless liquid purified by
distillation or reverse osmosis and contains no
added substances
• is used as an excipient in the production of
parenteral and other preparations where
product endotoxin content must be controlled,
and in other pharmaceutical applications, such
as cleaning of certain equipment and
parenteral product-contact components.
• is a water of extra high quality without
significant contamination
• The finished water must meet all of the
chemical requirements for Purified Water as
well as an additional bacterial endotoxin
specification. Since endotoxins are produced by
the kinds of microorganisms that are prone to
inhabit water, the equipment and procedures
used by the system to purify, store, and
distribute Water for Injection must be designed
to minimize or prevent microbial
contamination as well as remove incoming
endotoxins from the starting water
• must be validated to reliably and consistently
produce and distribute this quality of water.
4. Sterile water for injection
• clear colorless odorless liquid for parenteral
• it is sterile, hypotonic, nonpyrogenic, and
contains no bacteriostatic or antimicrobial
agents
• is used for extemporaneous prescription
compounding and as a sterile diluent for
parenteral products
• it may also be used for other applications
where bulk water for injection or purified
water is indicated but where assess to a
validated water system is either not practical
or where only a relatively small quantity is
needed
• is packages in single-dose container not larger
than 1L in size
5. Bacteriostatic Water for Injection
• Sterile Water for Injection to which has been
added or treated one or more suitable
antimicrobial agents (benzyl alcohol) or
preservatives.
• It is intended to be used as a diluent , vehicle or
carrier in the preparation of parenteral
products, most typically for multi-dose products
that require repeated content withdrawals.
• It may be packaged in single-dose or multiple-
dose containers not larger than 30 mL.
• Not use for neonates cause it can cause “Gas
Pain Syndrome”
• usually bearing or stating in its label a note
• NOTE: as there were problems encountered
with neonates and the toxicity of the
bacteriostat, benzyl alcohol.
Bacteriostatic water vs Sterile water
o Bacteriostatic water is sterile with benzyl
alcohol added to prevent bacteria growth in the
water, making it safe for multiple injections
o A vial of sterile water must be disposed of after
one use only
o A vial of Bacteriostatic water has a 30 day shelf
life
6. Sterile Water for Inhalation
• from Water for Injection that is packaged and
rendered sterile and is intended for use in
inhalators and in the preparation of inhalation
solutions and with no added antimicrobial
agents
• It carries a less stringent specification for
bacterial endotoxins than Sterile Water for
Injection, and therefore, is not suitable for
parenteral applications
• Used for nebule products
surfaces, are not changed in any way by the
water, such as by leaching of container- related
compounds into the water or by any chemical
reaction or corrosion caused by the water. The
water contains no added antimicrobials and is
not intended for injection.
• An average hemodialysis is exposed to
approximately 560 liters of water through their
weekly dialysis treatments. This is more water
than most people in a lifetime
Schematic diagram example of a water treatment
system for hemodialysis

7. Sterile water for irrigation

• Clear, colorless, odorless liquid

• Water for injection that has been sterilized; no
antimicrobial agent or other substances
packaged in single dose containers of larger
than 1L in size that allows rapid delivery of its
contents
• Used for washing tissues and medical
equipments
• USE: an irrigating solution
• NOTE: label must say “for irrigation only and
not for injection”

8. Pure steam

• Is also sometimes referred to as clean steam

• It is used where the steam or its condensate
would directly contact official articles or article-
contact surfaces such as during their
preparation, sterilization or cleaning where no
subsequent processing step is used to remove
any codeposited impurity residues.

9. Water for Hemodialysis

• used for hemodialysis applications, primarily

the dilution of hemodialysis concentrate
solutions
• It is produced and used on-site and is made
from EPA. Drinking Water which has been
further purified to reduce chemical and
microbiological components. It may be
packaged and stored in unreactive containers
that preclude bacterial entry.
• The term “unreactive containers” implies that
the container, especially its water contact