High purity water is waterwhich has been treated and modified to rigorous specifications.
These specificationsinclude the removal of all contaminants (including organic compounds likebacteria and non-organic compounds like ions), total organic carbon (TOC) and dissolvedgases. This creates water with very low conductivity and high resistance andsafe for injections into the bloodstream. Whilst there are many uses for highpurity water in Industry, including semiconductors, power generation (turbinesand super critical boilers) and solar photovoltaics, this report will focus onthe manufacture and application of high purity water in the pharmaceuticalindustry.
High purity water is commonly a diluent for many pharmaceuticalproducts. This include high purity water that is bacteriostatic for injections,sterile water for inhalation of therapy products and sterile water for internalirrigation therapy products (Rowe et al., 2014) In this report I will discussthe process by which high purity water is manufactured including the mainprocess overview, the reactants, and products and by products. I will alsodiscuss criticisms of the process and new manufacture designs being developedS1 . Process overviewThe production of high puritywater is a multi- step process that differs due to the application of the productand the start materials used.
Pre treatmentLarge solid particulates are first to be removedfrom the water using filtration. Clarifiers remove these particles; the numberof clarifiers in a system is dependent on the state of the raw water. Generally,the raw water used to make ultrapure water for pharmaceutical use is of a sufficientquality that only one or two clarifiers are required in pre-treatment. Largegrit is removed before entering the primary clarifier which produces ahomogenous liquid. This can then be biologically treated in the secondary clarifierusing coagulation and flocculation reagents (Mykolaiovch, 2005). This causes any suspendedsolids to clump together and settle at the bottom of the clarifier which arethe removed. At this stage lime softening may also occur to reduce the alkalinityof the water which reduces the probability of scale formation at later stagesof purification, particularly reverse osmosisS2 . Capacitive deionisation (CDI)This is the process by whichthe removal of salt ions from water occurs resulting in water which isdeionised.
This is achieved by applying an electrical potential difference acrosstwo electrodes. Anions in the water are stored in the anode; likewise cationsare stored at the cathode.Porous carbon is normally thepreferred material for the electrodes as it has a high surface area, goodconductivity, and high capacitance. (Anderson, 2010)Commonly used porous carbonsin industry include carbon aerogel, carbon nanotube, graphene (Porada, 2013). In scale up,100,000 tonnes of water can go through a CDI plant daily, with water recoveryat 75%. Whilst CDI is effective at removing large ions in the water, it doesnot necessarily capture smaller ions so further deionisation processes have tooccur down the system line to counter this.
This process is advantageousas it has a low level of energy consumption and is environmentally friendly. (Laxman, 2015). The raw materialfor this process is brackish water, which has lower salinity than seawater. Itis favourable to use this start product as it responds well to treatment viacapacitive deionisation and it a waste product from the semi-conductor industryso can be acquired at a relatively low cost.
(Chong, 2017) Reverse Osmosis (RO)This is another process in theproduction of high purity water involved in removing ions from water. In ROwater is forced from high solute concentration to low solute concentration byapplying a pressure that is in excess of the osmotic pressure. (He, 2016)The start, raw water isinjected with sulphuric acid to lower the Ph then fed into productiontrains. These contain membranes made up of a dense layer or polymer matrix which allow waterto pass through but prevent other solutes from entering. This system produces twoflow streams, one containing the water (permeate stream) and one containing rejectmaterial (concentrate stream) (Yokogawa, 2015).
The movement of the water iscontrolled by high pressure pumps; for brackish water these pumps generallyoperate between 15.5 and 26 bar (Lachish, 2002). The water is then passedthrough cartridge filters which remove sand and silt.
All liquid by-products atthis stage are removed via a pipeline into a deep injection well. (Lachish, 2002).The minimal energy requirements to complete RO is 0.75 kw/m3 ofwater however, normally industry it is around 2 kw/m3 (Lachish, 2002).The efficiency of the RO system in removing particles is determined byconductivity measurements at the inlet and outlet of the tank. Electrodeionisation (EDI)EDI was developed as process,that, coupled with reverse osmosis, in order to achieve maximum purity ofwater. The main function of EDI is to remove ions using anion exchange resin,which is commonly made from a styrene-divinylbenzene copolymer (Szilagyi, 1999).
The resin bed is continuouslyregenerated using a electrical current which eliminates the need for chemicalregeneration which reduces potential hazards and costs due to regulatory compliancei.e. the disposal of waste products.The water is fedthrough a two-chamber system; the first is where the water is fed into to, andthe second is where the ions are removed. Due to the current flowing throughchambers the bonds in the water molecule break forming a hydrogen and hydroxylion. H2O H++ OH- This occurs withthe contaminant ions also which exchange in the resin bed onto the secondchamber and are trapped into the contaminant stream (Szilagyi, 1999). Commonly, a pump is placed in the chambersto increase mixing in the chambers and reduce the formation of scale so less maintenanceis required for the chambers. UV sterilisationUV radiation isused to sterilise the water of bacteria.
This the most favourable method as UVdoes not remain in the water supply, does not produce drug resistant bacteriaand does not have a large impact on the environment. (Mori, 2007) The water is passedthrough a dual wavelength UV steriliser (185-nm and 254-nm) (Witham, 2007), this generateshydroxyl radicals which, in turn oxidise organic matter and destroy bacteria.The oxidation of the organic matter produces carbon dioxide which is removedthrough an outlet and into the atmosphere. The remnants of the destroyed bacteriaare then removed by a submicron filter (Yokokgawa 2015). UV radiation is instrumentalin the removal of TOC in the water. The level of TOC in the water is crucial indetermining whether the water fits the specifications for high purity water;since the TOC cannot be measured directly, it is determined by the conductivityof the final product. DegasificationDegasificationis a process utilised to remove the gases which have dissolved, like carbondioxide and oxygen from the water.
(Bhaumik, 2004). These gases are present in the water due to natural dissolution from theair and due advanced oxidation processes performed by bacteria in the waterstream. Vacuum degasification is a method that is often used to remove oxygen fromwater despite its shortcomings due to high operational costs (Tai, 1994). Another method toremove oxygen is catalytic reduction which involves utilisation of a reducingagent, namely H2 and N2H4. Both these methodsuse membrane modules which provide a stable interface for gas transfer tooccur. A advantage of the use of membrane modules is that they can be operatedand a range of flow rates.
Process considerationsWhen designing asystem to produce high purity water many factors have to be considered. Thevelocity of the flow rates need to have Reynolds of around 3000to ensureturbulent flow. This is to ensure microbial attachment to pipe surfaces is notlikely and reduce the probability of a biofilm in tanks. (Soini, 2002). The production ofhigh purity water is not produced by batch and is continuous, with steady stateflow to avoid particle bursts which can increase stress on the pipes that theyare flowing through. High purity systems are commonly designed with reversereturn piping incorporated which helps prevent back flow (Siegenthaler, 2016).
In the pharmaceutical industry, pipesare primarily made from stainless steel, which contributes a small amount of metallicsubstances to the water but was deemed low risk in this industry.The membranes andfilters used in the process have to be ultra clean and non-corrosive. Mostfilters are made from a mixture of polymers including polyethylene, nylon and polysulfoneS3 .Membranes and filters are normally welded to their point of action; adhesivesare avoided at all costs as they break down and contaminate the water supplyAnother factor to beconsidered is process size. Typically, larger water production plants are favourablethan smaller lab sized purifications units. This is because larger systems tendto have well trained operators running the plant at all times which allows forthe use of chemical treatments thus increasing efficiency. ConclusionThe continued productionof high purity water is vital for the pharmaceutical industry.
Not only does itserve medical purposes in the industry, for example acting as a diluent forinjections and inhalation therapies, but it is also important in the continuedresearch in the biological field. High purity water is used as basis in growingcell cultures as it provides a good control because it is basically free fromcontaminants (Rathod, 2013). High purity wateralso has applications in Mass Spectroscopy, again providing a contaminant freeliquid so that analysis remain uncompromised (Worley, 2012).
The market for high purity water is expectedgrow to a worth of $7.15 billion by the year 2020 (Markets, 2016)