pharmaceutics

1. Water purification system
By Anteneh Belayneh (B.pharm,MSc in pharmaceutics)
Debre Markos University, Ethiopia
belaynehante@gmail.com

2. Outline
 Introduction
 Types of water
 Water purification method
 Advanced water purification technique
 Water storage and distribution system
 Summary
 Reference

3. Introduction
 Water is a key ingredient used in many pharmaceutical and life sciences
operations.
 It is extensively used as a raw material, ingredient, and solvent in the
processing, formulation, and manufacture of pharmaceutical products, active
pharmaceutical ingredients and intermediates.
 It also used for washing equipment, rinsing containers or as an analytical
reagents, must meet quality requirements as dictated in different Pharmacopeias.
 Water has unique chemical properties due to its polarity and hydrogen bonds.
 This means it is able to dissolve, absorb, adsorb or suspend many different
compounds including contaminants (2).

4. Contd…
 Different grades of water quality are required depending on the route of
administration of the pharmaceutical products.
 Water can be contaminated by the following agents:
 Pathogens – disease-causing organisms that include
bacteria, amoebas and viruses, as well as the eggs and
larvae of parasitic worms.
 Harmful chemicals from human activities (industrial
wastes, pesticides, fertilizers).
 Chemicals and minerals from the natural environment, such
as arsenic, common salt and fluorides (4).

5. Types of water
 Major differences among these grades of water consist of the
following quality attributes:
 Microbial counts
 Endotoxin, which is due to the presence of
microbes
 Organic and inorganic impurities
 The USP identifies several grades of water that are acceptable
for use in pharmaceuticals, and also defines the quality
attributes for the manufacturing of pharmaceuticals (6).

6. Drinking water
 Drinking water can be referred as Potable Water.
 The condition of the source water will dictate the treatment required
to render it safe for human consumption (drinking).
 It may be used in the early stages of cleaning pharmaceutical
manufacturing equipment and product-contact components (4).
 It is the minimum quality of water that should be used for the
preparation of official substances and other bulk pharmaceutical
ingredients.
 Typical treatment includes desalinization, softening, removal of
specific ions, particle reduction and antimicrobial treatment (3).

7. Purified Water
 Purified Water is used as an excipient in non-parenteral
preparations and in other pharmaceutical applications, such as
cleaning of certain equipment’s and non-parenteral product-
contact components.
 It must meet the requirements for ionic and organic chemical
purity and must be protected from microbial contamination (8).
 Purified water is commonly produced by ion exchange, reverse
osmosis (RO), ultrafiltration or electrode ionization processes and
distillation (4).

8. Highly purified water (HPW)
 Highly purified water is a unique specification for water found
only in the European Pharmacopoeia.
 This grade of water must meet the same quality standard as
water for injections (WFI), including the limit for endotoxins,
but the water-treatment process used may be different.
 HPW may be prepared by a combination of different methods
such as double-pass RO, ultrafiltration and deionization.
 HPW should also be protected from recontamination and
microbial proliferation (7).

9. Water for Injection
 Water for injection (WFI) is used as an excipient in the production of
parenteral and other preparations, also as cleaning of certain equipment and
parenteral product-contact components.
 It is an intermediate bulk product and suitable to be used as an ingredient
during formulation.
 WFI should be protect from recontamination and microbial proliferation (3).
 The critical issue is ensuring consistent microbiological quality with respect
to removal of bacteria & bacterial endotoxin (not more than 0.25 IU of
endotoxin per ml), conductivity & total organic carbon.
 Distillation currently remains the only official method for WFI.

10. Methods of water purification
 Different grades of water are produced according to USP and EP requirements,
usually by: distillation, reverse osmosis, deionization and ultrafiltration (9).
 The following should be considered when planning a water purification system:
 The feed-water quality and its variation over seasons;
 The required water-quality specification;
 The sequence of purification stages required;
 The energy consumption;
 The extent of pretreatment required protecting the final purification steps;
 Yield and efficiency of unit treatment process steps; and
 Appropriately located sampling points to avoid potential contamination (7).

11. Deionization
 Deionization is a chemical process which removes ionic contamination.
 The most common ions found in water are Ca2+,Cl-, Mg2+ , Na+, NO3,
K+ and Carbonate.
 Because majority of water impurities are dissolved salts, deionization
produces a high purity water and this process is quick and without scale
buildup (10).

12. Contd …..
 The feed water is passed over an ion exchange resin where
cations react with the resin and release hydrogen ions and the
anions release hydroxyl ions.
 These then combine to produce water molecules.
 As this process continues the resin slowly runs out of
available hydrogen and hydroxyl ions and so becomes
exhausted.
 If the resin is not replaced or regenerated the quality of the
output would quickly deteriorate (11).

13. Reverse osmosis
 Reverse osmosis (RO) is a membrane-technology filtration method that removes
many types of large molecules and ions from water by applying pressure to the
solution when it is on one side of a selective membrane.
 The result is that the solute is retained on the pressurized side of the membrane
and the pure solvent is allowed to pass to the other side (12).

14.  In the RO process cellophane-like membranes separate purified water from
contaminated water.
 The rejected impurities from the concentrated side being washed away in the reject
water.
 RO can also act as an ultrafilter removing particles such as some microorganisms
that may be too large to pass through the pores of the membrane (8).
 Its efficiency is dependent on solute concentration, pressure, and water flux rate
(13).
 It will not remove all contaminants from water as dissolved gases such as dissolved
oxygen and carbon dioxide not being removed (14).

15. Double Stage RO System
 Two RO stages in one water treatment system are applied.
 Increased chemical and microbiological permeate quality with
two separate in-line RO filter stages.
 It is closer to ultrapure fluid than ever before (17).

16. Electrodialysis
 This process also uses membranes but direct electrical currents are used to attract ions to one side of
the treatment chamber.
 This system includes a source of pressurized water, direct current power supply and a pair of
selective membranes.
 The membranes adjacent to the influent steam are charged either positively or negatively and this
charge attracts counter-ions toward the membrane.
 These membranes are designed to allow the positive or the negative charged ions to pass through the
membrane, where the ions move from the product water stream through a membrane to the two
rejects water streams (8).

17. Distillation Method
 Many stills in various sizes and styles with capacities ranging from about 0.5 to 100
gallons of distillate per hour are available to prepare purified water.
 The first portion of aqueous distillate (about the first 10% to 20%) must be discarded
because it contains many foreign volatile substances .
 Also, the last portion of water (about 10% ) remaining in the distillation apparatus must be
discarded because decomposition of the remaining solid impurities to volatile substances
(19).

18. Contd ..
 Raw water is boiled to produce steam which is fed to a
condenser where it returns to the liquid state, free of impurity.
 The impurities remain in the boiler and must be removed
periodically, usually by dissolving them in an acid solution.
 The cooling water supply to the condenser is generally used to
feed the boiler with warmed water to increase efficiency.
 For increased purity, a double still is used where the output
from the first stage is then redistilled in the second (16).

19. Ultrafiltration
 Ultrafiltration (UF) is a variety of membrane filtration in
which hydrostatic pressure forces a liquid against a
semipermeable membrane.
 Suspended solids and solutes of high molecular weight are
retained, while water and low molecular weight solutes pass
through the membrane.
 This separation process is used in industry and research for
purifying and concentrating macromolecular (103 - 106 Da)
solutions, especially protein solutions (20).

20.  The type and amount of species left in the permeate will depend
on the characteristics of the membrane, the operating
conditions, and the quality of feed.
 The other liquid stream is called concentrate and gets
progressively concentrated in those species removed by the
membrane (15).

21. Advanced Water Purification Processes
Combined purification technique
 Currently, recycled water is used for irrigation and
industrial purposes.
 The new purification technique will purify water to such
levels that it will be suitable for a variety of future uses (21).

22. Microfiltration
 The recycled water first goes through microfiltration, an initial filtration process where water is pumped
through tubes filled with tiny membranes.
 Each membrane is made up of hollow fibers, perforated with holes 1/300th the width of human hair.
 Solids, bacteria, protozoa, and some viruses are removed from the water as it is drawn through the tubes.
Reverse Osmosis
 The water then goes through reverse osmosis where it is forced under high pressure through membranes
with holes so small that a water molecule is almost the only substance that can pass through.
 As a result, constituents such as salts, viruses, and most contaminants cannot pass through the
membranes and are left behind.
Ultraviolet Light
 Now the water is very clean but as a further safety back-up, the water is sent through
ultraviolet light to break down any remaining trace organic compounds.
 Ultraviolet light is a powerful disinfection process that creates water of a near-distilled quality
(22).

23. Solar Distillation
 The glass cover allows the solar radiation to pass into the still, which is mostly absorbed by the blackened
base.
 This interior surface uses a blackened material to improve absorption of the sunrays.
 The water begins to heat up and the moisture content of the air trapped between the water surface and the
glass cover increases.
 The heated water vapor evaporates from the basin and condenses on the inside of the glass cover.
 The salts and microbes that were in the original water are left behind.
 Condensed water trickles down the inclined (20° )glass cover to an interior collection trough and out to a
storage bottle (25,26).

24. Advantage
 Free of charge sun energy (during sunlight it eliminates 500 Watt electric
consumption per one hour of sunlight).
 There are no moving parts; it is therefore reliable and almost maintenance
free (cleaning is required though).
 Water taste is claimed to be better since the device act as a Solar Water
Vaporizer and it doesn’t boil the water (resembling rain water).
Disadvantages
 Solar distillers don’t kill bacteria and they don’t break down harmful chemicals
because they don’t boil the water.
 The large area tilted glass cover might be an attraction to bugs and insects.
 Low production capacity (27).

25. Activated carbon filter purifier
 Activated carbon, also called activated charcoal, is a form of carbon processed to
have small, low-volume pores that increase the surface area available
for adsorption or chemical reactions.
 Due to its high degree of microporosity, just one gram of activated carbon has a
surface area in excess of 3,000 m2. (23).
 The carbon filters can remove
 chemicals like chlorine, pesticides
and impurities to a great extent.
 It does not require electricity for operation.
 But it is also not very effective
in removing microbes from water (24).

26. Water storage and distribution system
 Once water for pharmaceutical use has been obtained, it must be
properly stored and distributed to the points of use.
 Systems must be sealed with continuous recirculation and must
have sanitization systems (3).
 The first stage is to automate the water storage & distribution for
various requirements and control the level in the storage tank and
monitoring the PH, conductivity, temperature before distribution.
 The next stage of the work is to control the flow rate of the water
in the distribution line and then water is given to the UV
treatment to minimize contamination and micro-organisms.

27. Contd..
 The materials that come into contact with water for pharmaceutical,
should satisfy the following objectives (4).
 Compatibility: The compatibility and suitability of the materials should
encompass the full range of its working temperature and potential
chemicals that will come into contact with the system at rest, in operation
and during sanitization.
 Prevention of leaching: All materials that come into contact with water in
pharmaceutical plant should be non-leaching at the range of working and
sanitization, temperatures of the system.
 Corrosion resistance: Water used in pharmaceutical plant is highly
corrosive (3, 7).

28. Microbiological test for water:
 Bioburden testing establishes the number of microorganisms in a water sample; ensuring bacterial
loads don’t exceed mandated USP levels (7).
 These criteria required testing for the following.
 The bacteria Escherichia coli (E. coli)
 The bacteria Staphylococcus aureus (S. auseus)
 The bacteria Pseudomonas aeruginosa (Ps.Aeruginosa)
 The fungus Aspergillus niger (A. niger)(3).
Procedure:
 Transfer aseptically 1ml of the sample in each of two sterile petridishes.
 Add to each dish approx. 20ml of sterile nutrient agar and mix by rotating the dishes 3 times.
 Allow the agar to solidify at room temperature.
 Invert the petridishes and incubate them at 37°C for 48 hrs.
 After incubation, examine the plates for growth and count the number of colony forming units in each
plate.
 The average of both the readings is the total microbial count per ml (4).

29. Summary
 Water is widely used as a raw material, ingredient, and solvent in the processing,
formulation, and manufacture of pharmaceutical products.
 Types of water are drinking water, purified water, highly purified water and water
for injection.
 Reverse osmosis, demineralization and ultrafiltration are the most commonly
used water purification techniques.
 There are also some advanced techniques for water purification, like combined
purification technique, solar distillation and filtration by activated carbon.
 Control of the quality of water throughout the production, storage and
distribution processes, including microbiological and chemical quality, is a major
concern.

30. Reference
1. Jadhav V.M., Gholve S.B. and Kadam V.J. Validation of Pharmaceutical Water System–A Review. Journal of Pharmacy Research. 2009; 2(5):231-49.
2. Prachand S.G. and Gupta A.K. Validation: A need for water purification system for pharmaceutical products. International Journal of Pharmacy & Life Sciences.
2013; 4(6):76-97.
3. World Health Organization. WHO Good Manufacturing Practices: Water for pharmaceutical use. Report. Geneva, 2005. WHO technical Report series.
4. Shukshith K.S. and Vishal N.G. Water for Pharmaceutical Use. Int J PharmSci. 2016; 36(1): 199-204.
5. Water treatment - World Health Organization. www.who.int/water_sanitation_health/hygiene/om/linkingchap6.pdf (Accessed date 23-2-2018).
6. Sumanth T. N. and Afrasim M. Pharmaceutical water system–validation aspects. Journal of Chemical and Pharmaceutical Research. 2015; 7(4):42-48.
7. Dela Sante O.M. WHO good manufacturing practices (GMP): water for pharmaceutical use (wpu) 2011 review draft. www.who.int/medicines/.../Water-QAS10-
379Rev1_25082011.pdf (Accessed date 24-2-2018).
8. Reddy B.V., Sandeep P., Ujwala P., Navaneetha K. and Reddy K.V. water treatment process in pharma industry-a review. International Journal of Pharmacy and
Biological Sciences. 2014; 4:2.
9. Water purification in the pharmaceutical industry. https://library.e.abb.com/public/.../AD_RandC_007-EN_A.pdf (Accessed date 25-2-2018).
10. Eniromental fact sheet. Ion exchange treatment of drinking water.2009. https://www.des.nh.gov/organization/commissioner/.../factsheets/.../dw... (Accessed
date 25-2-2018).
11. Deng D., Aouad W., Braff W.A., Schlumpberger S., Suss M.E. and. Bazant MZ. Water purification by shock electrodialysis: Deionization, filtration, separation, and
disinfection. Desalination. 2015 Feb 2; 357:77-83.
12. Dvorak BI, Skipton SO. Drinking water treatment: Reverse osmosis. University of Nebraska–Lincoln Extension, Institute of Agriculture and Natural Resources. 2014.
https://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=5348... (Accessed date 22-2-2018).
13. Wimalawansa S.J. Purification of contaminated water with reverse osmosis: effective solution of providing clean water for human needs in developing countries. J
Emerg Technol Adv Eng. 2013;3(12):75-89.
14. Norouzi S. Suggested Strategies in Water Treatment by Using Situ Pressure in Reverse Osmosis. Open Journal of Geology. 2015 May 6;5(05):367.
15. Membranes for Water Treatment: Properties and Characterization.Advanced Membrane Technologies Stanford University, May 07,
2008.https://web.stanford.edu/group/ees/rows/presentations/Pinnau.pdf (Accessed date 24-2-2018).
16. Shannon M.A., Bohn P.W., Elimelech M., Georgiadis J.G., Marinas B.J. and Mayes A.M. Science and technology for water purification in the coming decades. Nature.
2008 Mar; 452(7185):301.
17. Dialysis water purification.aquaboss, 2018. www.bbraunusa.com/.../AVT002_Aquaboss_Brochure_10-13.pdf (Accessed date 23-2-2018).
18. Oztekin E. and Altin S. Wastewater treatment by electrodialysis system and fouling problems. Turkish Online Journal of Science & Technology. 2016 Jan 1; 6(1):54-
86.
19. Allen L, Ansel HC. Ansel's pharmaceutical dosage forms and drug delivery systems. Lippincott Williams & Wilkins; 2013 Dec 23.
20. Futselaar H., Schonewille H., van Dalfsen H. and Shen L. Ultrafiltration technology for potable, process and wastewater treatment. Membrane science and
technology-lanzhou. 2003; 23(4):246-54.
21. Yorgun M.S., Balcioglu I.A. and Saygin O. Performance comparison of ultrafiltration, nanofiltration and reverse osmosis on whey treatment. Desalination. 2008 Sep
15; 229(1-3):204-16.
22. Advanced Water Purification Processes. www.purewater4u.org/advanced-water-purification-processes (Accessed date 26-2-2018).
23. Activated carbon filtration. https://www.elgalabwater.com/technologies/activated-carbon (Accessed date 26-2-2018).
24. Dvorak B.I and Skipton S. Drinking water treatment: Activated carbon filtration. Water Resource Management Drinking Water. 2013 Nov; 11:1-2.
25. Stonebraker A., Newmeyer J. and Branner M. Parabolic Solar Water Distillation. www.tandfonline.com/doi/pdf/10.1080/19443994.2015.1119746 - (Accessed date
22-2-2018).
26. Mehta A., Vyas A., Bodar N. and Lathiya D. Design of solar distillation system. Advanced Science and Technology. 2011 Apr; 29: 29(1).
www.sersc.org/journals/IJAST/vol29/7.pdf (Accessed date 26-2-2018).
27. Solar distillation https:// www. teachengineering.org/.../cub _waterqtnew _lesson01 _ factsh... (Accessed date 24-2-2018).

31. Thank You