Water for Injection in Pharmaceutical Industry: Introduction and Methods of Production

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WFI (Water for Injection)

Water for Injection is used as solvent for the manufacture for the parenteral drugs or for diluting the drugs in parenteral resulting in better dissolution through intravenous, intramuscular or subcutaneous route.

In this the endotoxin limit is the main specification that is needed to be controlled to make it available for the use in pharmaceutical preparations.

Water for Injection could be further sterilized and packed to obtain following types:

• Water for Injection (bulk packaged)
• Sterile Water for Injection
• Sterile Water for Irrigation
• Bacteriostatic Water for Injection
• Sterile Water for Inhalation

Why Water for Injection to dissolve the drug?

As it is well known that human body is made up of 70 % of water by body weight. It is very essential to make water balance through regulatory mechanisms; therefore whenever parental is used water for injection helps to dilute the drugs and it does not exert significant effect on the equilibrium.

PREPARATION OF WATER FOR INJECTION: 

It is well known that the source water from any place is contaminated with various substances that include: suspended material, organic substances, colloidal substances, viable bacteria, endotoxins, chemicals, particulate matter etc. These need pretreatment to obtain standardized level of purified water which is further converted to Water for Injection.

water

USP 37, <1231> WATER FOR PHARMACEUTICAL PURPOSE

Water for Injection can be prepared through different methods which are accepted by different pharmacopeias as follows:

Method of Preparation European Pharmacopeia USP Japanese Pharmacopeia
Distillation
Ultrafiltration ×

DISTILLATION PROCESS: 

It is process that involves the separation of constituents based on the differences in the boiling point. The water is boiled and converted into the gaseous (H2 & O2) form, leaving the impurities behind in the feed water and thereby condensing the pure gaseous form (steam).

There are two different types of distillation stills to produce water for injection: Vapour Compression and Multiple Effect Still.

However mostly stills consist of a evaporator (in which feed water is boiled also known as distilland), source to heat the water, headspace above the distilland and a condenser for removing the heat of vaporization.

Several factors must be kept in mind before selecting the type of still that includes:

  1. Material of the Still: Should be constructed by using 304 or 316 stainless steel, metal coated with pure tin or of chemically resistant glass. They provide high resistance to contamination of vapor and distillate from any metal parts of the still.
  2. Quality of feed water: The grade of water that is utilized as source water should pass the requirements of the drinking water as per US Environmental Protection Agency (EPA), EU, Japan or WHO. This water can only be subjected to further treatments to obtain water for injection.
  3. Size of the Evaporator: The capacity of evaporator should be such that it is efficient in reducing the withdrawal of the distilland either as droplets or in the form of vapors bubbles.
  4. Condensing Surfaces: Also known as baffles, determine the effectiveness of refluxing of the droplets contaminated with the distilland.
  5. Vents: They should be checked thoroughly as they remove the volatile impurities from the hot water vapors thereby enhancing the purity.

VAPOUR COMPRESSION STILLS:

This process was designed for desalination process earlier. In this the source water is heated in the evaporator to its boiling point and the vapors are produced which are separated in the separator from the distilland and send to the compressor to obtain compress the vapors and the temperature is raised to approximately 107°C. It reaches the steam chest for condensation and distillate is drawn off. In this process the latent heat of steam helps in heating the distilland in the tubes to reach its boiling point. Capacity available: 50-2800 gal/hr.

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VAPOUR COMPRESSION STILL

MULTIPLE EFFECT STILL:

In this a series of single effect stills are connected which runs at different pressures resulting in the changes of the phases of water. First still which is run at highest pressure is used to generate steam from feed water which is used as power source for second effect results in condensation by giving heat of vaporization thus forming distillate. This carries forward through the number of stills installed until the last one where steam is subjected to atmospheric pressure and is condensed in heat exchanger. Capacity: 50-7000 gal/hr (as could be increased by adding number of stills).

Multiple Stills

MULTIPLE EFFECT STILL

 

ULTRAFILTRATION: 

Most of the industries use one pass or two pass RO followed by ultrafiltration as final polishing step to generate water for injection.

This method is along with RO is employed by many pharmaceutical industries these days as the cost reduction is by the factor of 7.5 from 5.5 making it as a clear beneficial step. It is also a membrane technology like reverse osmosis in which membrane is utilized to separate extremely small particles and endotoxins produced by bacteria by applying pressure around the membrane. The pore size of membrane varies from 20 nm and 0.1 micron. The basis of separation is molecular size, molecular shape and sometimes molecular charge. Simply the molecules that are larger in the size than the pore size of membrane are retained at the surface and concentrate at that point during the process. Being advantageous in providing the less expensive method without any chemical involved for the water purification, ultrafiltration does not remove dissolved inorganics.

Earlier only two pass RO was utilized for the WFI configurations until the requirements of the conductivity and TOC tests. Typically two pass RO was fulfilling all the specification for WFI but conductivity was sometimes an issue.

This made the changes to involve one final step to meet not only  the required conductivity and TOC counts but also it assured compliance with the endotoxin and microbial requirements.

PICTURE COURTESY:

VAPOUR COMPRESSION AND MULTIPLE EFFECT STILL

PICTURE COURTESY

Also Read:

Reverse Osmosis System for Water Purification in Pharmaceuticals

Introduction to Water for Pharmaceutical Purpose

Sampling Plan for Water system- From initial to routine