Pharmaceutical Water

Introduction.

Regulatory Standards of Pharmaceutical Water.

Design of Water Purification System.

Introduction
Water is one of the key utilities in
pharmaceutical facilities and used as solvent,
product ingredient, cleaning agent, etc
Pharmaceutical water:
Also called compendial water because their
quality is specified in an official nationally
recognized standard: USP,EP, BP, etc.

Purified water
Purified water is water from any source
that is physically processed to remove
impurities.
Distilled water and deionized (DI) water
have been the most common forms of
purified water, but water can also be
purified by other processes including
reverse osmosis, filtration, microfiltration,
ultrafiltration and electrodialysis

Water Purification by Distillation

Distilled water is water that has many of its
impurities removed through distillation.
Distillation involves vaporization of water
(steam) and condensation of steam into a clean
container.

Simple distillation
It is a process of converting a liquid into its
vapors, transferring the vapor to another
place and recovering the liquid by condensing
the vapor by its contact which cold surfaces .

 Simple distillation can be carried out under

atmospheric pressure. The apparatus used for
simple distillation consists of
Heating source
Still
Condenser
Receiver
Distilled water

Distillation is highly wasteful of energy and

water, wasting as much as 95% of the feed water

and leaving only about 5% as pure product.

Any contaminant that vaporizes at lower

temperature will not be removed in distillation

process.

Deionized water, also known as demineralized

water from which mineral ions such as cations like
sodium, calcium, iron, and copper, and anions such
as chloride and sulfate are removed.
Deionization is a chemical process which uses
specially manufactured ion-exchange resins which
exchange hydrogen ion and hydroxide ion for
dissolved minerals

Because the majority of water impurities

are dissolved salts, deionization produces a
high purity water that is generally similar to
distilled water, and this process is quick and
without scale buildup.
However,
deionization
does
not
significantly remove uncharged organic
molecules, viruses or bacteria, except by
incidental
trapping
in
the
resin.
Deionization can be done continuously and
inexpensively using electrodeionization

 Deionized water is used in water-fog fireextinguishing systems used in sensitive

environments, such as where high-voltage
electrical and sensitive electronic equipment is
used
Experiments in humans found that demineralized
water increased diuresis and the elimination of
electrolytes, with decreased serum potassium
concentration.

Introduction: PW & WFI

USP purified
pharmaceutical
applications

water has a number of

and
cosmetic
water

such as in the manufacturing of tablets,

capsules, creams, lotions, etc, including higher
volume uses such as container-rinsing (NOT for
use in parenterals or sterile dosage forms).

Water for injection(WFI) must meet a bacterial

& endotoxin (pyrogen) specifications.

WFI is used for the preparation of parenteral
(injectable)
processing

solutions
of

and

parenterals,

all
e.g.

downstream
rinsing

of

equipments that come into direct contact with the

products,

preparation

inhalation products.

of

ophthalmic

and

Requirements for Pharmaceutical

Water

Low Conductivity: contains minimal amount of

ions Ca, Mg, Na, Fe, Cl, SO4, etc.
The conductivity depend upon the concentration of
ions already present.
Low total organic compound (TOC) contains
minimal organic compounds which may either be
toxic or serve as a source of nutrition for microbes.
Low microbial count.
Low endotoxin level.
Conductivity: Its units are Siemens per meter [S/m]

Regulatory: Purified Water

USP: obtained by a suitable process
Conductivity 1.3 S/cm @ 25 C.
Total Organic Compounds (TOC) 500 ppb.
Microbial 100 cfu/ml.
No endotoxin requirement .

EP: prepared by distillation, by ion- exchange,

by reverse osmosis or by any other suitable
method .

Regulatory: Water for Injection (WFI)

USP: distillation or a purification process
that is equivalent to or superior to distillation
Conductivity 1.3 S/cm @ 25 C.
Total Organic Carbon (TOC) 500 ppb.
Microbial 10 cfu/100 ml.
Endotoxin requirement < 0.25 EU/ml .

EP: distillation
JP: distillation or by the Reverse Osmosis
/Ultrafiltration of Purified Water

USP 23 Standards
Purified Water (topical
solution and cosmetics)

PW

SWFI
(Sterile water for
injection)

Organics

<0.5 ppm TOC

<0.5 ppm TOC

Conductivity

<1.3 S/cm at 25C

<1.3 S/cm at 25C

Endotoxin by LAL

No specification

<0.25 EU/ml

Bacteria

100 cfu/ml

10 cfu/100 ml

Impurities of water
Water is composed of (H+) and (OH-).
Anything in water that is not (H+) and (OH-) is
an impurity.
The objective of water purification is removal of
impurities from the water.
Design of Water Purification System
Consideration of water Contaminants.
Sources of Feed Water.
Stages of water purification/treatment.

Water Contaminants

Contaminants found in water

Atmospheric gases
Minerals
Organic materials (natural and man-made),
materials used for storage of water.
Bacterial contamination: nutrients in water
provides a medium for bacterial growth.
Pyrogenic contamination.

Sources of feed water

Surface water .
Ground water aquifers.
Surface water: river, lake, reservoir.
Did not pass through earths soil .
Less mineral contamination.
Have higher levels of organics and undissolved
particles because water contacted vegetation
and surface debris.

Ground water aquifers: Tube-well

Most particulate matter removed.
Much of organic contamination consumed by
bacterial activity of soil.
Mildly acidic solution results.
Dissolves many minerals (especially limestone)
which contributes calcium, magnesium, iron,
sulfates and chlorides.

Different methods of Water Purification

Aeration.
Filtration.
Softening.
UV Disinfection.
RO System.
Purification.

Aeration
Iron, makes up 5% of the earths crust, is a
common water contaminant in deep well water.
Due to water soluble ferrous (Fe2+) is changed
to insoluble ferric (Fe3+):
Oxygen or Oxidizing agent e.g. KMnO4 .
Oxidation of ferrous content to ferric .
Ferric which forms ferric hydroxide
precipitates (rusty red brown).
Ferric contaminants are removed from water.

Filtration/Particle Removal
Depth filtration through a bed of sand are used to
remove turbidity (large particles, suspended solids of
size larger than 10-20 m).

Sand filters
volumes.

can

economically

process

large

Finer sand medium located on top of coarser media

causes the filter to plug quickly, requires back-flush
/backwash.

Coarseness of sand media allows smaller suspended

solids to pass, secondary filters are required.

 Activated charcoal (AC) filter (10 m/5 m

filter) are added to remove smaller particles,
dissolved organics and chlorine (found in
municipal potable water).

In smaller water purification system, a

cartridge-type depth filter may be used instead
of the sand filter. The cartridge is disposed and
replaced when the holding capacity is reached

Sand Filter

Sand filter
ADVANTAGES
DISADVANTAGES
Low operating cost.
Low maintenance.
Media is durable.

Can grow bacteria

Only removes rough
particles

Activated Charcoal Filter

ADVANTAGES
Safe chlorine removal
Remove organics
Some particulate
removal

DISADVANTAGES
Generates fines
Bacteria growth
Must be sanitised

Water Softening
The presence of calcium (Ca2+) and magnesium
(Mg2+) ions in water is known as hardness,
expressed in mg/L or ppm (CaO)
Ion-exchange water softener
Lime-soda ash treatment or lime softening

Lime-soda ash treatment.

Lime (CaO); soda ash (Na2CO3)
Ca and Mg are precipitated, water becomes clear
Advantage: inexpensive.
Disadvantage: pH becomes high 8.5 to 10, needs to
buffer pH

Ion-exchange Water Softener

Ion-exchange: removes Ca and Mg ions.

It is based on the ability of synthetic resins to

adsorb ions and to release (exchange) other
ions.
The resin has greater affinity for multivalent
ions (Ca++, Mg++) than for monovalent Na+.
When water passes through the bed, Ca2+,
Mg2+ are captured and exchanged for the Na+
adsorbed on the fresh resin.

Ion exchange

Once the resin is exhausted, it is regenerated

by a 10% solution of sodium chloride. The
high concentration of sodium ions in such a
solution shifts the equilibrium of the
adsorption-desorption process, resulting in
the displacement of the captured multivalent
ions with sodium ions. Softener resins can
last for years through repeated regeneration
cycles.
Does not remove microorganisms (usually
followed with UV treatment/filtration 0.22m
filter).

Ion-Exchange Resin Bead model

Disinfection
Bacteria fouling is a leading cause of
contamination.
Carefully monitored bacterial control is
necessary

Maintain a continuous biocide residual

throughout the system or sanitisation of
system regularly.
Continuous biocide residual preferable,
avoids the formation of biofilm.

 Heat
Classic form of bacterial control.
Temperature maintained at 80C for storage
and recirculation of USP, PW and WFI.
Heating above 80C is used to control
microorganisms in activated carbon (AC)
systems.
Ozone (O3)
Twice as powerful an oxidant as chlorine, kills
microorganism rapidly by lysing cell walls.
Also used in disinfection of water in storage
and distribution pipe works .

 UV
UV does not sterilize water but deactivates
DNA leading to bacterial reduction it is effective
only when there is direct UV light contact with
microbes.
Flow rate critical.
Post-irradiation recontamination may be an issue.
Other chemicals are chlorine, chlorine gas
Chlorine dosed continually, maintained residual
level
0.2 to 2 ppm.
Chlorine periodic treatments 100-200 ppm for 30
minutes.

Reverse Osmosis (RO)

Reverse Osmosis System.

The pressurized feed water flows across a

membrane (with pore size 1-10), a portion of
the feed permeates across the membrane, the
balance of the feed exits the system without
being filtered.
Driving force: Pressure 100-500 psi.

 Allows continuous removal of contaminants

which in normal flow filtration would have
plug the membrane pores rapidly.
Eliminates most organics (impurities), 99%
ions, 99.9% viruses, bacteria, pyrogens.
Double RO systems are often employed.

Advantages of Reverse Osmosis

Less chemical handling than ion-exchange.
More effective microbial control than ionexchange.
Minimal maintenance .
Integrity test possible.
Removes most of organic and non-organic
contaminants.
Less energy consumption than distillation.
Efficiently and economically removes particles,
microorganisms, dissolved in organics and
dissolved organics .

Disadvantages of Reverse Osmosis

Water consumption higher than ion-exchange
unless waste-water is re-used.
Danger of microbial growth on membrane.
No removal of dissolved gases.
Working at high temperature (>65 C) only
possible with certain types of membrane.
Low flow rate/square foot of surface.
Permeate will concentrate CO2 from feed water.

Use of Reverse Osmosis

purified water: pharmacopoeia
specifications.

feeding of distillation units or ultra-filtration

units.
Water for Final Rinse.
Water for Injections (USP, but not
permissible by EP).