Meeting Global Pharmacopeia Requirements for Water Compliance

The preparation of pharmaceutical waters

By Mettler Toledo

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In reverse osmosis for pharmaceutical water production, a membrane is also used for the separation of contaminated water. Membranes can be made from cellulose acetate, polyamide, polysulfone, or a variety of proprietary formulations. Two configurations are common: “hollow fiber” and “spiral wound”. Hollow fiber membranes look like a group of drinking straws gathered into a bunch, the spiral wound resemble a helix.

Because the quality of water produced by a reverse osmosis apparatus is directly dependent upon the quality of the input water and because effective removal of ions rarely exceeds 97%, reverse osmosis is widely used as a pretreatment process to purify feedwater before introduction into an ion exchange unit or a distillation system.

Distillation is the oldest form of water purification and has been utilized by humans since we first boiled wa-ter in a cave. It is a unique process because it removes the water via a phase change and leaves behind the impurities. In distillation, water is heated to itsboiling point and undergoes the first of two phase changes, from a liquid to a vapor. The solid ionic ma-terials, the particulates, the microbials, endotoxins, and most of the dissolved organic contaminants are left behind in the boiler. The pure steam is then passed through a cooling coil where it undergoes a second phase change from a vapor back to a liquid. For the production of WFI, the pharmaceutical distillation system is normally fed water that has been pretreated by a variety of other technologies. The pretreatment is used to reduce the costs of maintenance on the distillation system and to ensure the quality of the distillate. Distillation is the only purification method that removes 100 percent of biological materials whether bacterial, viral, or pyrogenic.

Deionization or ion exchange is a process also mistakenly called demineralization. The Encyclopedia of Chemical Technology defines deionization as:
“The reversible interchange of ions between a solid and a liquid phase in which there is no permanent change in the structure of the solid.”

Deionizers are generally available in two forms: a two-bed and a mixed-bed configuration. In the two-bed configuration, the cation and anion resins are in two discrete columns or in two discrete layers in the same column. The advantage of the two-bed deionizer is that it can purify a greater volume of water than a comparable mixed-bed system; however, they produce lower quality water.

The mixed-bed deionizer contains an integral mixture of anion and cation resins packed in a single column. Only mixed-bed deionization can produce water with a resistivity of 18.178 million ohms, which is theoretically ionically pure.

Ion exchange technology is designed to remove ionized or charged material from water. Even though water will be ionically pure after the deionization process, the water will still contain non-ionized solid and gaseous materials (organics), bacteria, viruses, and pyrogens. These are not ionically charged species and cannot be removed by ion exchange processes.

Electrodeionization (EDI, also known as EDR, CDI, and CEDI) is a technology that combines ion exchange resins, ion-selective membranes and an electrical current to remove ionized contaminants from the water. Reverse osmosis is typically used before EDI to ensure that the EDI stack is not overloaded with high levels of salts. Usually, reverse osmosis removes about 97% of ions. EDI will remove 99% of the remaining ions as well as carbon dioxide, organics, and silica. In electrodeionization, the water passes through multiplechambers filled with ion exchange resins held between cation or anion selective membranes. Under the influence of an electrical field, the anions and cations migrate across the membranes to the anode and cathode. Typically, EDI product water has a resistivity of 11 to 18.2 MΩ-cm (at 25°C) and a total organic carbon (TOC) content below 20 ppb. Bacterial levels are minimized because the electrical conditions within the system inhibit the growth of microorganisms.

Carbon adsorption
In adsorption, the organic impurities in water form a low-energy chemical bond with the surface of activated carbon. Because adsorption is a technique for removing only organics and chlorine, it is most often used as a pretreatment to remove large amounts of organic impurities prior to other purification processes. Activated carbon is very effective at removing chlorine and other oxidants at rates of 2 to 4 times the chemical weight of the oxidant. By removing the oxidants, the opportunity for microbial growth is increased and must be controlled and monitored.

Ultraviolet light
Ultraviolet light at the 254nm wavelength is used asbactericide. This wavelength disrupts the ability of bacteria to reproduce. UV at 185nm will break down organic contaminants to CO2 and water for subsequent removal by ion exchange.

Filtration can be performed by one of two methodologies, either depth filtration or membrane filtration. Depth filters can be made of sand in a container or of fiber wound around a core. Both methods mechanically strain out sediment and particulate matter.

Membrane filtration, on the other hand, is physical straining by a single layer of membrane material. The membrane material is produced from man-made resins and can be either hydrophobic or hydrophillic. The pore size is tightly controlled and therefore absolute removal of particulates with diameters larger than the pore size can be achieved. In pharmaceutical systems, filtration is normally limited to the pretreatment section because although filters trap contaminants, it is possible for bacteria to pass through a membrane filter.

Once the feedwater source is known and the purification technologies have been selected, knowing what parameters need to be utilized to control and monitor the system are critical. By understanding feedwater and the water purification system, a consistent supply of Purified Water, Highly Purified Water or Water for Injection can be ensured.

Download the full Pharmaceutical Waters guide from Mettler Toledo here

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