Water is a key fixing utilized as a part of numerous pharmaceutical and life sciences operations. Various grades of water are utilized as a crude material, fixing, and dissolvable in the handling, definition, and make of pharmaceutical items, dynamic pharmaceutical fixings (APIs) and intermediates. Control of the nature of water all through the generation, stockpiling and dispersion forms, counting microbiological and compound quality, with proper storage and distribution is a noteworthy concern. Water can be utilized as a part of an assortment of uses, some requiring outrageous microbiological control and others requiring none. Pharmaceutical water generation, stockpiling and circulation frameworks ought to be outlined, introduced, authorized, qualified and kept up to guarantee the solid generation of water of a fitting quality. It is important to validate the water creation and purifying procedures to guarantee the water produced and purified, put away and conveyed is not past the planned limit and meets its particulars. If, by any chance, the water used in pharmaceutical processes doesn’t meet its specifications/particulars as defined by different monographs, there are various water treatment methods that can be used to bring the water for pharmaceutical use within the range specified by different official monographs has been described detail in this article.

Keywords: Water for Injection; Purified Water; Water Treatment; Reverse Osmosis; Chlorination; Validation; Qualification

Introduction

The Indian pharmaceutical industry is a big consumer of water. As per estimates by Frost & Sullivan, the water and waste water treatment market for the pharmaceutical industry in India earned revenues of Rs 5.08 billion in 2011 and this is expected to move up to Rs 9.47 billion by 2016, growing at a compounded annual growth rate of 13.3 per cent [1]. Manufacturing of medicines require high-purity water in the production process and the waste water stream can be heavily laden with toxins, contaminants and organic nutrients which needs to be treated before disposal, requiring water and waste water treatment equipment. Government support for India’s pharmaceutical sector will be accompanied by stricter governance on water and wastewater usage.

Today’s pharmaceutical companies have invested considerable capital in state-of-the-art instrumentation, purification equipment, storage and distribution loops, and importantly in the calibration and certification of their water systems. By understanding water, its sources and impurities, and the capabilities and limitations of purification methods, a water system can be designed to meet not only pharmaceutical companies’ requirements but to meet global pharmacopeia regulations.

Water is a substantial ingredient used in Pharmacy. It is used as a raw material, an excipient, used for reconstitution of products, in synthesis and production of finished products and APIs, as solvent in processing and formulation. Water [2] is also used as an analytical reagent, cleansing agent for rinsing vessels, equipment’s and packaging material. There are two major grades of water used in pharmaceuticals: - Bulk waters, which are typically produced on site where they are used; and packaged waters, which are produced, packaged and sterilized to preserve microbial quality throughout their packaged shelf life. Control of the quality of water throughout the production, storage and distribution processes, including microbiological and chemical quality is a major concern. The waters can be used in a variety of applications, some requiring extreme microbiological control and others requiring none. There may be some contaminants that may represent hazards in themselves or that may be able to react with intended product substances, resulting in hazards to health. Control of the quality of water throughout the production, storage and distribution processes, including microbiological and chemical quality, are a major concern.

Types of Water Used in Pharmacy

There are many different grades of water used for pharmaceutical purposes. Several are described in USP monographs [3] that specify uses, acceptable methods of preparation and quality attributes. There are several specialized types of packaged water, differing in their designated applications, packaging limitations, and other quality attributes. There are also other types of water for which there are no monographs. These are all bulk waters, with names given for descriptive purposes only. Many of these waters are used in specific analytical methods. These are all bulk waters, with names given for descriptive purposes only. Many of these water are used in specific analytical methods.

Various types of waters for pharmaceutical use are:-

Purified Water

Purified water is used as an excipient in the production of nonparenteral preparations and in other pharmaceutical applications, such as cleaning of certain equipment and non-parenteral productcontact components. Purified waters also to be used for all tests and assays for which water is indicated. Purified water must meet the requirements for ionic and organic chemical purity and must be protected from microbial contamination. This source water may be purified using unit operations that include deionization, distillation, ion exchange, reverse osmosis, filtration, or other suitable purification procedures. Purified water systems must be validated to reliably and consistently produce and distribute water of acceptable chemical and microbiological quality. Purified water systems that function under ambient conditions are particularly susceptible to the establishment of tenacious bio films of microorganisms, which can be the source of undesirable levels of viable microorganisms or endotoxins in the effluent water.

Purposes

Production of non-parenteral preparations/formulations
Cleaning of non-parenteral product contact components
Cleaning of certain equipment’s used in non-parenteral product preparation
All types of tests and assays
Preparation of some bulk chemicals
Preparation of media in microbiology laboratories

Production

Purified water is commonly produced by ion exchange, reverse osmosis (RO), ultra filtration or electrode ionization processes and distillation. Ambient temperature systems such as ion exchange, RO and ultrafiltration are especially susceptible to microbiological contamination. It is essential to consider the mechanisms for microbiological control and sanitization.

– Control of temperature in the system by heat exchanger or plant room cooling to reduce the

risk of microbial growth (guidance value < 25 °C)
– Provision of ultraviolet disinfection
– Selection of water-treatment components that can periodically be thermally sanitized
– Application of chemical sanitization (including agents such as ozone, hydrogen peroxide and/or Peracetic acid); – thermal sanitization at > 65 °C

Other preparation techniques can be:-

-Deionization
-Distillation
-Reverse osmosis
-Filtration, etc

Water for Injection (Wfi)

Water for Injection (WFI) is a solvent or excipient used in the production of parenteral and other where product endotoxin content must be controlled, and in other pharmaceutical applications, such as cleaning of certain equipment and parenteral product-contact components. The minimum quality of source or feed water for the generation of Water for Injection is Drinking Water as defined by the U.S. EPA [4], EU, Japan, or the WHO. This source water may be pre-treated to render it suitable for subsequent distillation (or whatever other validated process is used according to the monograph). The finished water must meet all of the chemical requirements for Purified Waters well as an additional bacterial endotoxin specification. Since endotoxins are produced by the kind 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. Water for Injection systems must be validated to reliably and consistently produce and distribute this quality of water.

Purposes

For the production of parenteral products/formulation
For cleaning of parenteral product-contact components

Production

Control of the chemical purity of WFI presents few major problems. The critical issue is ensuring consistent microbiological quality with respect to removal of bacteria & bacterial endotoxin. Distillation has a long history of reliable performance &can be validated as a unit operation; hence it currently remains the only official method for WFI. WFI in bulk is obtained from water or from purified water by distillation in an apparatus of which the parts in contact with water are of neutral glass, quarts or suitable metal & which is fitted with an effective device to prevent the entrainment of droplets. The correct maintenance of the apparatus is essential during production & storage; appropriate measures are taken to ensure that the total viable aerobic count is adequately controlled & monitored. WFI complies with test for purified water with additional requirements for bacterial endotoxins (not more than 0.25 IU of endotoxin per ml), conductivity & total organic carbon.

Control of temperature in the system by heat exchanger or plant room cooling to reduce the risk of microbial growth (guidance value < 25 °C)

Provision of ultraviolet disinfection

Selection of water-treatment components that can periodically be thermally sanitized

Application of chemical sanitization (including agents such as ozone, hydrogen peroxide and/or peracetic acid); – thermal sanitization at > 65°C

Other techniques for the production of WFI are:-

Reverse osmosis

Membrane process

Water for Hemodialysis

Water for haemodialysis is used for haemodialysis applications, primarily the dilution of haemodialysis 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 surfaces, are not changed in any way by the water, such as by leaching of contain irrelated 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

Purpose

For the dilution of haemodialysis concentrate solution

Production

Water for haemodialysis is produced on-site and is made from EPA Drinking water through reverse osmosis units. Then the water is further purified to reduce chemical and microbiological components.

Pure Steam

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 co deposited impurity residues.

Purpose

To remove any co-deposited impurity residues
For air humidification in controlled manufacturing environments
Used in steam sterilization of equipments and porous loads
For cleaning the places where condensate directly comes in contact
with articles, product contact containers and surfaces

Production

There are well defined manufacturing processes with respect to the requirements of the applicable pharmaceutical regulations, we see that both the United States Pharmacopeia (USP) and the Japanese Pharmacopeia (JP) permit, in addition to the classical distillation process, a membrane process with at least two stages. Two physically similar systems with completely different principles are used for distillation, namely vapour compression (VC) and multiple effect distillation (ME) systems. Both methods are based on the physical law that any particles, endotoxins, pyrogens or other contaminants remain in the water during the phase transition from water to steam. Unfortunately, large amounts of energy must be transferred to the water in order to achieve this phase transition and this input of energy causes the water to move rapidly. This is, in fact, necessary in order to transfer the heat from the secondary medium (normally hot steam) to the water to be evaporated. However, this movement of the water can cause droplets of fluid to be formed and carried away with the water vapour. These droplets may contain undesirable contaminants and must be removed from the water vapour.

Sterile Purified Water

Sterile Purified Water is Purified Water, packaged and rendered sterile. It is used in the preparation of non-parenteral compendia 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.

Purpose

For the analytical applications requiring purified water
For the preparation of non-parenteral compendial dosage forms

Production

Sterile Purified Water is manufactured using our proprietary ninestep proprietary system. These closely regulated processes include primary filtration, deionization, UV treatment, multiple effect distillation and hot storage, while culminating in passage through circulation systems before final filtration.

Sterile Water for Injection

Sterile water for injection is Water for Injection packaged and rendered sterile. It is used for extemporaneous prescription compounding and as a sterile diluents for parenteral products. It may also be used for other applications where bulk Water for Injection or Purified Water is indicated but where access to a validated water system is either not practical or where only a relatively small quantity is needed. Sterile Water for Injection is packaged in single-dose containers not larger than 1 L in size.

Purpose

Used for extemporaneous preparation compounding

Used as a sterile diluents for parenteral preparation

Production

By distillation of Water for injection (WFI).

Bacteriostatic Water for Injection

Bacteriostatic water for injection is sterile Water for Injection to which has been added one or more suitable antimicrobial preservatives. It is intended to be used as a diluents 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.

Purpose

Used as a diluents in the preparation of parenteral products

Production

Bacteriostatic water for injection is prepared using sterile water for injection. The sterile water for injection is taken and to it 0.9% (9 mg/mL) of benzyl alcohol is added as a Bacteriostatic preservative.

Sterile Water for Inhalation

Sterile Water for Inhalation is Water for Injection that is packaged and rendered sterile and is intended for use in inhalators and in the preparation of inhalation solutions. It carries a less stringent specification for bacterial endotoxins than Sterile Water for Injection, and therefore, is not suitable for parenteral applications.

Purpose

Use in the preparation of inhalators

Use in the preparation of inhalant solutions

Production

By sterilization of Water for Injection

Sterile Water for Irrigations

Sterile water for irrigations is Water for Injection that is packaged and rendered sterile and is intended for use in inhalators and in the preparation of inhalation solutions. It carries a less stringent specification for bacterial endotoxins than Sterile Water for Injection, and therefore, is not suitable for parenteral applications.

Purpose

To bath and moisten body tissue

Performing urologic procedure for surgeons

Production

From water for injection

Storage and Distribution

Figure 1:

The storage and distribution system [5-8] should be considered as a key part of the whole system and should be designed to be fully integrated with the water purification components of the system. It will be fed into a storage vessel for subsequent distribution to points of use. The following text describes the requirements for storage and distribution systems and point of use (POU). The storage and distribution system should be configured to prevent microbial proliferation and recontamination of the water after treatment. It should be subjected to a combination of online and offline monitoring to ensure that the appropriate water specification is maintained. Materials that come into contact with systems for water for pharmaceutical use. This applies to generation equipment for water and the associated storage and distribution systems.

The materials that come into contact with WPU, including pipe work, valves and fittings, seals, diaphragms and instruments, should be selected to satisfy the following objectives:-

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 WPU should be nonleaching at the range of working and sanitization temperatures of the system.

Corrosion Resistance

Some waters are highly corrosive.

To prevent failure of the system and contamination of the water, the materials selected must be appropriate, the method of jointing must be carefully controlled and all fittings and components must be compatible with the pipe work used. Appropriate sanitary specification plastics and stainless-steel materials are acceptable for water for pharmaceutical use systems. When stainless steel is used it should be at least grade 316. In general, 316L or a higher grade of stainless steel is used. The system should be passivated after initial installation or after significant modification. When accelerated passivation is undertaken the system should be thoroughly cleaned first and the passivation process should be undertaken in accordance with a clearly defined documented procedure.

Smooth Internal Finish

Once water has been purified it is susceptible to microbiological contamination and the system is subject to the formation of bio films when cold storage and distribution are employed. Smooth internal surfaces help to avoid roughness and crevices within the water for pharmaceutical system. Crevices can be the source of contamination because of possible accumulation of microorganisms and formation of bio films. Crevices are also frequently sites where corrosion can commence. The internal material should have an arithmetical average surface roughness of not greater than 0.8 micrometer (Ra). When stainless steel is used, mechanical and electro-polishing techniques may be employed. Electro-polishing improves the resistance of the stainless-steel material to surface corrosion.

Jointing

The selected system materials should be easily joined by welding in a controlled manner. The control of the process should include, as a minimum, qualification of the operator, documentation of the welder set-up, work session test pieces (coupons), logs of all welds and visual inspection of a defined proportion of welds, e.g. 100% hand welds, 10% automatic welds.

Design of Flanges, Unions and Valves

Where flanges, unions or valves are used they should be of a hygienic or sanitary design. Appropriate checks should be carried out to ensure that the correct seals and diaphragms are used and that they are fitted and tightened correctly. Threaded connections should be avoided.

Documentation

All system components should be fully documented and be supported by original or certified copies of material certificates.

Materials

Suitable materials that may be considered for sanitary elements of the system include 316L (low carbon) stainless steel, polypropylene, polyvinylidene-difluoride and perfluoroalkoxy. The choice of material should take into account the intended sanitization method. Other materials such as unplasticized polyvinyl-chloride (uPVC) may be used for treatment equipment designed for less pure water such as ion exchangers and softeners. None of the materials that come into contact with water for pharmaceutical use should contain chemicals that will be extracted by the water. Plastics should be non-toxic and should be compatible with all chemicals used. They should be manufactured from materials that should at least meet minimum food grade standards. Their chemical and biological characteristics should meet any relevant pharmacopoeia specifications or recommendations.

Precautions should be taken to define operational limits for areas where water circulation is reduced and turbulent flow cannot be achieved. Minimum flow rate and change volumes should be defined.

System Sanitization and Bio Burden Control

Water treatment equipment, storage and distribution systems used should be provided with features to control the proliferation of microbiological organisms during normal use, as well as techniques for sanitizing the system after intervention for maintenance or modification. The techniques employed should be considered during the design of the system and should take into account the interdependency between the materials and the sanitization techniques. Systems that operate and are maintained at elevated temperatures (e.g. > 65) are generally less susceptible to microbiological contamination than systems that are maintained at lower temperatures. When lower temperatures are required due to the water treatment processes employed or the temperature requirements for the water in use, special precautions should be taken to prevent the ingress and proliferation of microbiological contaminants.

Storage Vessel Requirements

The water storage vessel used in a system serves a number of important functions. The design and size of the vessel should take into consideration the following.

Capacity

The capacity of the storage vessel should be determined on the basis of the following requirements:

It is necessary to provide a buffer capacity between the steadystate generation rate of the water-treatment equipment and the potentially variable simultaneous demand from user points The water-treatment equipment should be able to operate continuously for significant periods to avoid the inefficiencies and equipment stress that occur when the equipment cycles on and off too frequently

The capacity should be sufficient to provide short-term reserve capacity in the event of failure of the water-treatment equipment or inability to produce water due to a sanitization or regeneration cycle

When determining the size of such reserve capacity, consideration should be given to providing sufficient water to complete a process batch, work session, tank turnover by recirculation to minimize stagnation, or other logical period of demand

Contamination Control Considerations

The following should be taken into account for the efficient control of contamination:

The headspace in the storage vessel is an area of risk where water droplets and air can come into contact at temperatures that encourage the proliferation of microbiological organisms. The use of spray-ball or distributor devices should be considered in these systems to wet the surfaces during normal operation, chemical and/or thermal sanitization

Nozzles within the storage vessels should be configured to avoid dead zones where microbiological contamination might be harboured.

Vent filters are fitted to storage vessels to allow the internal level of liquid to fluctuate. The filters should be bacteria-retentive, hydrophobic and should ideally be configured to allow in situ testing of integrity. Offline testing is also acceptable. The use of heated vent filters should be considered for continuous hot storage or systems using periodic heat sanitization to prevent condensation within the filter matrix that might lead to filter blockage and to microbial growth that could contaminate the storage vessels

Where pressure-relief valves and bursting discs are provided on storage vessels to protect them from under- and over-pressurization, these devices should be of a sanitary design. Bursting discs should be provided with external rupture indicators to ensure that loss of system integrity is detected

Requirements for Water Distribution Pipe Work

The distribution of pharmaceutical waters should be accomplished using a continuously circulating pipe loop. Proliferation of contaminants within the storage tank and distribution loop should be controlled. Good justification for using a non-recirculating one-way system should be provided. Filtration should not usually be used in distribution loops or at take off-user points to control bio contamination. Such filters are likely to conceal system contamination.

Temperature Control and Heat Exchangers

Where heat exchangers are employed to heat or cool water for pharmaceutical use within a system, precautions should be taken to prevent the heating or cooling utility from contaminating the water. The more secure types of heat exchangers of the double tube plate or double plate and frame or tube and shell configuration should be considered. Where these types are not used, an alternative approach whereby the utility is maintained and monitored at a lower pressure than the water for pharmaceutical use may be considered. Where heat exchangers are used they should be arranged in continually circulating loops or sub loops of the system to avoid unacceptable static water in systems. When the temperature is reduced for processing purposes the reduction should occur for the minimum necessary time. The cooling cycles and their duration should be proven satisfactory during the qualification of the system

Circulation Pumps

Circulation pumps should be of a sanitary design with appropriate seals that prevent contamination of the system. Where stand-by pumps are provided, they should be configured or managed to avoid dead zones trapped within the system. Consideration should be given to preventing contamination in systems where parallel pump systems are used, especially if there is stagnant water when one of the pumps is not being used.

Bio Contamination Control Techniques

Water purification systems should be sanitized using chemical or thermal sanitization procedures as appropriate (production and distribution). The procedure and conditions used (such as times and temperatures) should be suitable.

The following control techniques may be used alone or more commonly in combination to:

Maintenance of continuous turbulent flow circulation within water distribution systems reduces the propensity for the formation of bio films;

The system design should ensure the shortest possible length of pipe work;

For ambient temperature systems, pipe work should be isolated from adjacent hot pipes;

Dead legs in the pipe work should be minimized through appropriate design, and as a guide should not significantly exceed three times the branch diameter as measured from the ID pipe wall to centre line of the point-of-use valve where significant stagnation potential exists;

Pressure gauges should be separated from the system by membranes;

Hygienic pattern diaphragm valves should be used;

Pipe work for steam-sanitized systems should be sloped and fully drainable;

The growth of microorganisms can be inhibited by:

– ultraviolet radiation sources in pipe work;
– maintaining the system heated (greater than 65 °C);
– sanitizing the system periodically using hot water (Guidance temperature >70’°C);
– sanitizing the system periodically using superheated hot water or clean steam;
Routine chemical sanitization using ozone or other suitable chemical agents
When chemical sanitization is used, it is essential to prove that the agent has been removed prior to using the water
Ozone can be effectively removed by using ultraviolet radiation

Table 1:

Specifications of Various Grades of Water

USP has stipulated the specifications and definitions of the various grades of water suitable for pharmaceutical use. It classifies pharmaceutical water as (i) potable water (ii) purified water, used for the manufacture of oral preparations and other formulations, and (iii) water for injection (WFI) and (iv) sterile water for injection used for injectables, parenteral and intravenous fluids. USP also specifies that purified water and WFI must adhere to the Agency’s (EPA’s) Part l4l, National Interim Regulations.

Maximum allowable concentrations of toxic substances according to the International standards are given in the following table.

Table 2:

Water Treatment Methods

Water treatment [9] comprises of applying known innovation to enhance or update the nature of water. Typically water treatment will include gathering the water in a focal, isolated area and subjecting the water to different treatment forms. Water treatment, in any case, can likewise be sorted out or ordered by the way of the treatment procedure operation being utilized; for instance, physical, substance or organic. Cases of these treatment steps are demonstrated as follows. A total treatment framework may comprise of the utilization of various physical, synthetic and natural procedures to the water.

Some Physical, Chemical and Biological water Treatment Methods:-

Physical

a. Sedimentation (Clarification)
b. Screening
c. Aeration
d. Filtration
e. Flotation and Skimming
f. Degasification
g. Equalization
7.2 Chemical
a. Chlorination
b. Ozonation
c. Neutralization
d. Coagulation
e. Adsorption
f. Ion Exchange

Biological

a. Aerobic
b. Activated Sludge Treatment Method
c. Trickling Filtration
d. Oxidation Ponds
e. Lagoons
f. Aerobic Digestion
g. Anaerobic Digestion
h. Septic Tanks
i. Lagoons

Physical methods

These incorporate procedures where no gross substance or natural changes are done and entirely physical wonders are utilized to enhance or treat the water. Illustrations would be coarse screening to expel bigger entrained articles and sedimentation (or clarification).

a) Coagulation and Flocculation

Coagulation and flocculation one of the initial phases in a customary water cleansing procedure is the expansion of chemicals to aid the evacuation of particles suspended in water. Particles can be inorganic, for example, mud and sediment or natural, for example, green growth, microorganisms, infections, protozoa and characteristic natural matter. Inorganic and natural particles add to the turbidity and shade of water. The expansion of inorganic coagulants, for example, aluminium sulphate (or alum) or iron (III) salts, for example, press (III) chloride cause a few synchronous synthetic and physical collaborations on and among the particles. Inside seconds, negative charges on the particles are killed by inorganic coagulants. Likewise inside seconds, metal hydroxide encourages of the aluminium and iron (III) particles start to frame. These encourages join into bigger particles under normal procedures, for example, Brownian movement and through incited blending which is some of the time alluded to as flocculation. The term frequently utilized for the undefined metal hydroxides is “floc” Large, indistinct aluminium and iron (III) hydroxides adsorb and snare particles in suspension and encourage the expulsion of particles by ensuing procedures of sedimentation and filtration.

b) Sedimentation

During the time spent in sedimentation; physical marvels identifying with the settling of solids by gravity are permitted to work. Generally this comprises of basically holding the water for a brief timeframe in a tank under tranquil conditions, enabling the heavier solids to settle, and expelling the “cleared up” gushing. Waters leaving the flocculation bowl may enter the sedimentation bowl, additionally called a clarifier or settling bowl. It is a vast tank with low water speeds, enabling floc to settle to the base. The sedimentation bowl is best found near the flocculation bowl so the travel between the two procedures does not allow settlement or floc separate. Sedimentation bowls might be rectangular, where water streams from end to end or round where stream is from the inside outward.

c) Aeration

Another physical treatment prepare comprises of air circulation that is, physically including air, as a rule to give oxygen to the water.

d) Filtration

Subsequent to isolating most floc, the water is separated as the last stride to evacuate staying suspended particles and unsettled floc. Quick sand channels: The most widely recognized kind of channel is a fast sand channel. Water moves vertically through sand which frequently has a layer of initiated carbon or anthracite coal over the sand. The top layer expels natural mixes, which add to taste and smell. The space between sand particles is bigger than the littlest suspended particles, so straightforward filtration is insufficient. Most particles go through surface layers yet are caught in pore spaces or cling to sand particles. Powerful filtration reaches out into the profundity of the channel. This property of the channel is vital to its operation: if the top layer of sand were to obstruct every one of the particles, the channel would rapidly stop up. Some water treatment plants utilize weight channels. These takes a shot at an indistinguishable standard from fast gravity channels, contrasting in that the channel medium is encased in a steel vessel and the water is constrained through it under weight. Points of interest:

Filters out substantially littler particles than paper and sand channels can

• Filters out for all intents and purposes all particles bigger than their predefined size

• They are very thin thus fluids course through them decently quickly

• They are sensibly solid thus can withstand weight contrasts crosswise over them of normally 2-5 atmospheres

• They can be cleaned (back flushed) and reused

• Slow sand channels

Moderate sand channels might be utilized where there is adequate land and space, as the water must be gone gradually through the channels. The channels are painstakingly built utilizing reviewed layers of sand, with the coarsest sand, alongside some rock, at the base and finest sand at the top. Channels at the base pass on treated water away for cleansing. Filtration relies on upon the advancement of a thin organic layer, called the zoogleal layer or Schmutzdecke, on the surface of the filter.

Chemical Treatment

It comprises of utilizing some synthetic response or responses to enhance the water quality. Most likely the most regularly utilized compound process is chlorination

a) Chlorination

The most widely recognized purification strategy includes a few type of chlorine or its mixes, for example, chloramines or, then again chlorine dioxide. Chlorine is a solid oxidant that quickly executes numerous destructive smaller scale life forms. Since chlorine is a poisonous gas, there is a risk of a discharge related with its utilization. This issue is dodged by the utilization of sodium hypochlorite, which is a generally cheap arrangement that discharges free chlorine when broken up in water. Chlorine arrangements can be created nearby by electrolyzing normal salt arrangements. A strong shape, calcium hypochlorite, discharges chlorine on contact with water.

b) Ozone Sanitization

Ozone is a temperamental atom which promptly surrenders one iota of oxygen giving an effective oxidizing operator which is poisonous to most waterborne life forms. It is a powerful technique to inactivate unsafe protozoa that shape blisters. It additionally functions admirably against all different pathogens. Ozone is made by passing oxygen through bright light or a “chilly” electrical discharge. Some of the benefits of ozone incorporate the generation of less unsafe by-items and the nonappearance of taste and scent issues. Another preferred standpoint of ozone is that it leaves no lingering disinfectant in the water.

c) Neutralization

A synthetic procedure normally utilized as a part of numerous modern water treatment operations is balance. Balance comprises of the expansion of corrosive or base to alter pH levels back to nonpartisanship. Since lime is a base it is here and there utilized as a part of the balance of corrosive wastes.

d) Coagulation

Coagulation consists of the addition of a chemical that, through a chemical reaction, forms an insoluble end product that serves to remove substances from the wastewater. Polyvalent metals are commonly used as coagulating chemicals in water treatment and typical coagulants would include lime (that can also be used in neutralization), certain iron containing compounds (such as ferric chloride or ferric sulphate) and alum (aluminium sulphate).

Biological Treatment Strategies

This strategy utilizes microorganisms, generally microscopic organisms, in the biochemical deterioration of wastewaters to stable final results. By and large, organic treatment techniques can be isolated into high-impact and anaerobic techniques, in view of accessibility of broke up oxygen. The solids which are evacuated amid treatment are principally natural however may likewise incorporate inorganic solids. Treatment should likewise be accommodated the solids furthermore, fluids which are evacuated as muck. At long last, treatment to control smells, to impede natural action, or obliterate pathogenic creatures may likewise be required. While the gadgets utilized as a part of wastewater treatment are various and will presumably join physical, substance and natural techniques, they may all be for the most part assembled under six techniques:

1. Preliminary Treatment
2. Primary Treatment
3. Secondary Treatment
4. Disinfection
5. Sludge Treatment
6. Tertiary Treatment

a. Preliminary Treatment

At most plants preliminary treatment is used to protect pumping equipment and facilitate subsequent treatment processes. Preliminary devices are designed to remove or cut up the larger suspended and floating solids, to remove the heavy inorganic solids, and to remove excessive amounts of oils or greases. To affect the objectives of preliminary treatment, the following devices are commonly used:

1. Screens - rack, bar or fine
2. Commenting devices -- grinders, cutters, shredders
3. Grit chambers
4. Pre-aeration tanks

In addition to the above, chlorination may be used in preliminary treatment. Since chlorination may be used at all stages in treatment, it is considered to be a method by itself.

b. Primary Treatment

In this treatment, most of the settle able solids are separated or removed from the wastewater by the physical process of sedimentation. When certain chemicals are used with primary sedimentation tanks, some of the colloidal solids are also removed. The primary devices may consist of settling tanks, clarifiers or sedimentation tanks. Because of variations in design, operation, and application, settling tanks can be divided into four general groups:

1. Septic tanks
2. Two story tanks -- Imhoff and several proprietary or patented units
3. Plain sedimentation tank with mechanical sludge removal
4. Upward flow clarifiers with mechanical sludge removal
When chemicals are used, other auxiliary units are employed. These are:

1. Chemical feed units
2. Mixing devices
3. Flocculators

c. Secondary Treatment

Secondary treatment depends primarily upon aerobic organisms which biochemically decompose the organic solids to inorganic or stable organic solids. The devices used in secondary treatment may be divided into four groups:

1. Trickling filters with secondary settling tanks
2. Activated sludge and modifications with final settling tanks
3. Intermittent sand filters
4. Stabilization ponds

d. Chlorination

This is a method of treatment which has been employed for many purposes in all stages in wastewater treatment, and even prior to preliminary treatment. It involves the application of chlorine to the wastewater for the following purposes:

1. Disinfection or destruction of pathogenic organisms
2. Prevention of wastewater decomposition
(a) Odour control
(b) Protection of plant structures
3. Aid in plant operation -
(a) sedimentation,
(b) Trickling filters,
(c) Activated sludge bulking
4. Reduction or delay of biochemical oxygen demand (BOD).

e. Sludge Treatment

The solids removed from water in both primary and secondary treatment units, together with the water removed with them, constitute water sludge. It is generally necessary to subject sludge to some treatment to prepare or condition it for ultimate disposal. Such treatment has two objectives -- the removal of part or all of the water in the sludge to reduce its volume, and the decomposition of the putrescible organic solids to mineral solids or to relatively stable organic solids. This is accomplished by a combination of two or more of the following methods:-

1. Thickening
2. Digestion with or without heat
3. Drying on sand bed - open or covered
4. Conditioning with chemicals
5. Elutriation
6. Vacuum filtration
7. Heat drying
8. Incineration
9. Wet oxidation
10. Centrifuging

f. Tertiary and Advanced Waste water Treatment

This merely indicates the use of intermittent sand filters for increased removal of suspended solids from the wastewater. In other cases, tertiary treatment has been used to describe processes which remove plant nutrients, primarily nitrogen and phosphorous, from wastewater.

Demineralisation

Demineralisation [10] is the removal of minerals and nitrate from the water. The three that we will be discussing here are, Ion exchange
Reverse osmosis
Electrodialysis
These methods are widely used for water and waste water treatment [11]. Ion exchange is primarily used for the removal of hardness ions like magnesium and calcium and for water demineralization. Reverse osmosis and electrodialysis, which are both membrane processes, remove dissolved solids from water using membranes. Demineralised water also known as deionised water, water that has had its mineral ions removed. Mineral ions such as cations of sodium, calcium, iron, copper, etc and anions such as chloride, sulphate, nitrate, etc are common ions present in water. Deionization is a physical process which uses speciallymanufactured ion exchange resins which provides ion exchange site for the replacement of the mineral salts in water with water forming H+ and OH- ions. 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 build-up. A DM Water System produces mineral free water by operating on the principles of ion exchange, Degasification, and polishing. Demineralised Water System finds wide application in the field of steam, power, process, and cooling.

Ion Exchange

In the context of water purification, ion-exchange is a rapid and reversible process in which impurity ions present in the water are replaced by ions released by an ion-exchange resin. The ion exchange units are used to remove any charged substance from the water but are mainly used to remove hardness and nitrate from groundwater. Raw water is passed via two small polystyrene bead filled (ion exchange resins) beds. While the cations get exchanged with hydrogen ions in first bed, the anions are exchanged with hydroxyl ions, in the second one. The impurity ions are taken up by the resin, which must be periodically regenerated to restore it to the original ionic form.

The following ions are widely found in raw water:-

Table 3:

Ion Exchange Resins

There are two basic types of resins: cation-exchange and anionexchange resins. Cation exchange resins will release Hydrogen (H+) ions or other positively charged ions in exchange for impurity cations present in the water. Anion exchange resins will release hydroxyl (OH-) ions or other negatively charged ions in exchange for impurity anions present in the water.

Reverse Osmosis

Reverse osmosis (RO) is a membrane-technology filtration method that removes many types of large molecules and ions from solutions 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. In the normal osmosis process, the solvent naturally moves from an area of low solute concentration (High Water Potential), through a membrane, to an area of high solute concentration (Low Water Potential). The development of an immaculate dissolvable to adjust solute fixations on each side of a film produces osmotic weight. Applying an outer weight to switch the normal stream of immaculate dissolvable, in this way, is switch osmosis. Invert osmosis, in any case, includes a diffusive instrument so that partition productivity is reliant on solute fixation, weight, and water flux rate. Turn around osmosis is most regularly known for its utilization in drinking water purging from seawater, evacuating the salt and different substances from the water particles. Switch osmosis is a procedure that industry uses to clean water, regardless of whether for mechanical process applications or to change over salty water, to tidy up wastewater or to recoup salts from modern procedures. Turn around osmosis won’t expel all contaminants from water as broke up gasses, for example, disintegrated oxygen and carbon dioxide not being expelled. Be that as it may, invert osmosis can be extremely successful at expelling other items, for example, trihalomethanes (THM’s), a few pesticides, solvents and other unstable natural mixes (VOC’s) and this procedure evacuates over 70% of the accompanying: Arsenic-3, Arsenic-4, Barium, Cadmium, Chromium-3, Chromium-6, Fluoride, Lead, Mercury, Nitrite, Selenium-4 and selenium-6,Silver.

The Reverse Osmosis Process

In the invert osmosis handle cellophane-like films isolate cleaned water from polluted water. RO is the point at which a weight is connected to the concentrated side of the layer compelling cleaned water into the weaken side, the rejected debasements from the concentrated side being washed away in the reject water. RO can likewise go about as a ultra filter expelling particles, for example, a few microorganisms that might be too huge to go through the pores of the membrane.

Figure 2:

Electrodialysis

Electrodialysis is viable in expelling fluoride and nitrate from water. This procedure additionally utilizes layers in any case; coordinate electrical streams are utilized to pull in particles to the other side of the treatment chamber. This framework incorporates a wellspring of pressurized water, coordinate momentum control supply and a couple of particular films.

10.6 Electrodialysis Process

In this procedure, the films contiguous the influent steam are charged either decidedly or

Contrarily and this charge pulls in counter-particles around the film. These layers are intended to permit the positive or the negative charged particles to go through the layer, where the particles move from the item water stream through a layer to the two reject water streams.

Figure 3:

Ultra Filtration

Ultrafiltration10 (UF) is a variety of membrane filtration in which hydrostatic pressure forces a liquid against a semi permeable membrane. Suspended solids and solutes of high sub-atomic weight are held, while water and low sub-atomic weight solutes go through the film. This partition handle is utilized as a part of industry and research for purging furthermore, concentrating macromolecular (103 - 106 Da) arrangements, particularly protein arrangements. Ultrafiltration, like switch osmosis, is a crossstream division handle. Here fluid stream to be dealt with (sustain) streams digressively along the film surface, accordingly creating two streams. The flood of fluid that gets through the layer is called saturate. The sort and measure of species left in the penetrate will rely on upon the qualities of the film, the working conditions, and the nature of nourish. The other fluid stream is called focus and gets continuously amassed in those species expelled by the membrane.

11.1 Recovery

Recovery of an ultra-filtration system is defined as the percentage of the feed water that is converted into the permeate,

Where, R= recovery
P=volume of permeate
F=volume of feed

Figure 4:

Validation and Qualification

Validation and qualification of water purification, stockpiling and circulation system are a fundamental part of Good Manufacturing Process (GMP) and shape a necessary piece of the GMP review. The review of water utilized at various stages in the fabricate of the dynamic pharmaceutical fixings and pharmaceutical items ought to be examined in the pharmaceutical dossier. The review of water utilized ought to consider the nature and expected uses of the completed item and the phase at which the water is utilized. In the previous two decades the approval approach in pharmaceutical enterprises has been talked about because of its real importance inside a gainful procedure in connection to the items quality traits; like purity, safety and effectiveness the base of the thought and working of experts required to the procedure approval. The U.S. Food and Drug Administration (FDA) in l987 in its most as of late proposed ‘Rules on General standards of Process validation has offered a definition to handle approval, after a progression of occurrences included cross-defilement issues by a few pharmaceutical assembling foundations:

“Process validation is establishing document evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications quality characteristics”.

Validation is readable through the documentation foundation; the certification of that assembling procedure guarantees the item quality with homogeneity. The approval idea applies to the finished result, and all the past stages are called capability. Along these lines, the approval comprises of a progression of capabilities that includes tests, frameworks confirmations and furthermore basic process parameters that are its managing keys, and can fluctuate inside an acknowledgment restrict. The diverse capabilities frame phases of approval:

Design Qualification,
Installation Qualification,
Operation Qualification and
Performance Qualification.

Everyone must take after its own schedule and convention. The water, in a pharmaceutical industry, is the most essential crude material for the achievement of any procedure. In this manner, it is basic to not just guarantee that water, additionally establishments and systems are approved. In this way, it is important to pick an allaround outlined water framework, by utilizing a mix of techniques that permits achieving the quality levels of water to a determinate application, by streamlining its specific limit of evacuate contaminants. Fruitful accomplishment of validation is guaranteed by different testing stages. Generally, a three-stage testing approach is prescribed over a stretched out period to demonstrate dependability furthermore, vigour of the framework for creating water of determined quality with a high level of confirmation.

Guidelines

The main role of the ‘Guidelines for water quality’, is the assurance of general wellbeing. The Guidelines give the proposals of the World Health Organization (WHO) for dealing with the hazard from risks that mama)’ bargain the wellbeing of water quality. The suggestions ought to be considered with regards to dealing with the chance from different wellsprings of introduction to these risks, for example, waste, air, food and consumer items. Diverse evaluations of water are delivered as per USP and EP necessities, more often than not by: distillation; reverse osmosis; deionisation; or ultra filtration. These procedures should be approved and recorded by particular models. Each arrangement of rules diagram lawful prerequisites for the compound substance of each review of water, including a three phase conductivity test for inorganic intensifies that will decide pH and aggregate natural oxygen (TOC) levels. The FDA expresses that certain in the expression “Purified Water” is that it has some sensible, target level of virtue. TOC testing considers assessing polluting influences in water other than those which are inorganic anions and cations.

Conclusion

From the above survey of information it clearly indicates that it is very important to remove contaminants from water to make it useful for both household and industrial purpose. The available data appear to demonstrate the different methods used in water purification process.

This review provides information on,
Types of water used in Pharmacy
- Purified water
- Water for Injection
- Water for Haemodialysis
- Pure steam
- Sterile purified water
- Sterile water for injection
- Bacteriostatic water for injection
- Sterile water for inhalation
- Sterile water for irrigation
Storage & Distribution
Specifications of various grades of water
Water treatment methods
Validation & Qualification of water purification