Nitrogen sparging and blanketing for pure processing: ensuring continuous supplies of near-pure nitrogen to deoxygenate water can be a time-efficient and cost-effective way to formulate today's medicines.
So to ensure purity in the manufacture of medicines, dissolved oxygen and CO2 must be removed from and prevented from contaminating the water supply. This is especially true of water stored in tanks. Oxygen in water can lead to microbial growth and C02 can affect water's pH.
One procedure to remove these impurities is called sparging, and typically, nitrogen is used not only to deaerate water, but to prevent oxygen and C02 reabsorption.
While nitrogen makes up 78% of the air we breathe, harnessing its properties for pharmaceutical manufacturing can be problematic and expensive. Nitrogen can be ordered from outside vendors but delivery, storage and handling high pressure cylinders in the working environment can be costly and hazardous. It also represents a finite supply that can be exhausted quickly when there's an unexpected demand.
The costs to address these issues can be high and difficult to budget for, while the price of gas and supplier rates continually increase and the environmental impact of truck based deliveries gain significance.
An alternative would be to generate the nitrogen needed on demand. In the pharmaceutical world, this investment is easily justified considering the value of the product, and the potential harm that introducing contaminated water into a process can do to consumers.
DYNAMIC DUO: SPARGING-BLANKETING
Nitrogen sparging and blanketing practices can prevent oxidation in the manufacturing process. Sparging and blanketing practices introduce near-pure nitrogen into the water tanks and maintain a protective layer of nitrogen. In other words, nitrogen sparges the water to remove any dissolved oxygen and C02, and humid air in the head space is replaced by pure, inert nitrogen. This may be maintained by a precise valve-control system that automatically adjusts the nitrogen content to maintain the protective blanket as the tank is filled or emptied or by simply having a continuous purge of low pressure nitrogen.
The nitrogen--when bubbled through water--agitates it and forces out oxygen and C02 dissolved in it to prevent bacterial and algae growth. This can supplement the use of pumps that serve this purpose. However, a 500-gallon tank pumping at a gallon a minute can take up to 10 hours to churn its contents. Sparging increases the rate of agitation in the tank, with sintered stainless steel plates or rods (called sparging elements) purging the water on a continuous basis.
In addition to preserving pH and eliminating microbial growth, deaerated water containing low concentrations of oxygen and carbon dioxide minimizes corrosion and iron and copper oxide scale.
Supplier sourced or make your own nitrogen?
There are two ways pharmaceutical plants may obtain nitrogen. The nitrogen can be received from a supplier as a gas in high-pressure cylinders or as a liquid in micro-bulk tanks (dewars) and bulk tanks. Relying on an outside supplier, however, is subject to price increases, rental agreements, hazmat fees, surcharges and taxes. Deliveries are made by heavy trucks that contribute to CO2 emissions and wear and tear on roads and highways. Delivery of gas also requires access to facility by a third party, and creates a security issue for the plant to manage.
A cost-effective energy-efficient alternative to sourcing is to generate the nitrogen on-site via PSA (Pressure Swing Adsorption) nitrogen generators. Payback on such equipment can be two years or less. Nitrogen can be generated for eight to 12 cents per 100 cu. ft., while gas-utility companies charge 50 cents to a dollar or more per 100 cu. ft. Making your own nitrogen uses less energy than traditional manufacturing at an air liquefaction plant. The plant relies on an energy-intensive cryogenic process to cool air to extremely low temperatures to separate the nitrogen from air.
Furthermore, nitrogen generators exceed industry standards. They are capable of producing up to 99.999% pure compressed nitrogen at dewpoints to -58 degrees F (-50 degrees C) from nearly any compressed air supply. The generators are designed to continually transform standard compressed air into nitrogen at safe, regulated pressures without operator attention, thereby eliminating unexpected shutdowns due to "bad" or empty cylinders.
Technical standards on water quality have also been established. The American Society for Testing and Materials (ASTM), the U.S. Clinical and Laboratory Standards Institute and the International Organization for Standardization (ISO 3696) classify purified water into Grade 1-3 or Types I--IV depending upon the level of purity. These organizations have similar, although not identical, parameters for highly purified water. Many laboratory, pharmaceutical, medical, research and dialysis applications require ultrapure water to meet one of these standards.
Nitrogen generators such as those from Parker use high-efficiency pre-filtration to remove all contaminants down to 0.01 micron from the compressed air stream. The filters are followed by dual pressure vessels filled with carbon molecular sieves (CMS). In one vessel at operating pressure, the CMS adsorb oxygen, carbon dioxide, and water vapor. The other vessel, operating at low pressure, releases the captured oxygen, carbon dioxide, and water. Cycling the pressures in the CMS vessels causes all contaminants to be captured and released while letting the nitrogen pass through. A final sterile-grade filter ensures removal of any microbial contamination. Nitrogen purities can be set with a flow control valve. Reducing the flow increases purity while increasing flow decreases purity.
For example, a system that produces a flow of nitrogen as high as 1,530 std. ft3/h at 99.9% purity can achieve even higher flow rates--if gas of lower purity is acceptable for that application. A built-in oxygen analyzer measures the oxygen concentration of the nitrogen stream. The system requires a minimum feed pressure of 110 psi and can operate at pressures up to 140 psi. The resulting nitrogen has a dewpoint as low as -58[degrees]F (-50[degrees]C).
In addition to being precise, on-site nitrogen generators are also compact, thus freeing up valuable floor space. They're typically freestanding, housed in a cabinet, or skid-mounted. They come as complete packages with prefilters, final filters, and a buffer tank. They are also simple to install, maintain and operate. The plant only needs to connect a standard compressed air line to the inlet of the generator (after ensuring that a sufficient supply of compressed air is available) and attach the outlet to a nitrogen line. Furthermore, such generators serve to eliminate the hassles and safety issues of handling dangerous, high-pressure cylinders
When connecting a generator to a large tank of water, it is important to prevent back-flow of the water into the generator if compressed air is lost. A check valve may be used, but a more reliable method is to run a vertical leg above the level of the water overflow pipe (the highest water level in the tank) and then back down again into the nitrogen generator. With this plumbing configuration, if the compressor goes down, water in the line would only rise as high as the level of the water in the tank. Therefore, water would not back flow into the generator and cause damage. (See diagram)
Pharmaceutical manufacturers rely on a continuous supply of purified water for their operations. They must also ensure the purity of water stored for intermittent needs. Therefore, these plants need to have in place FDA-compliant nitrogen sparging and blanketing practices to ensure high purity demineralized water.
In short, on-site nitrogen generation has several advantages over relying on a gas supplier, including a lower cost nitrogen supply, less energy consumption vs delivered gases, quicker water tank agitation, facility and employee safety and elimination of truck delivery miles.
David J. Connaughton, Product Manager; Parker Hannifin Corporation; Filtration and Separation Division
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|Author:||Connaughton, David J.|
|Date:||Apr 1, 2015|
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