Background

Vapor Compression (VC) Distillation has been utilized for decades in producing Water for Injection (WFI), particularly for high-capacity needs. Also, while reverse osmosis and deionization systems have largely dominated the Purified Water (PW) market, VC remains a viable option for specific PW applications, particularly when using softened feed water without the need for RO or DI. These VC systems can achieve sensible water recoveries of 85% or higher (before reclaim).

In contrast to multiple effect distillation systems, which operate at higher temperatures and pressures, VC systems can effectively handle feed waters with relatively high total dissolved solids (TDS) levels. Therefore, the main feed water concern for VC systems isn’t the TDS concentration but the presence of certain contaminants that may compromise pharmaceutical water quality or lead to oxidation or scaling. Six key categories of impurities are the primary concerns for VC systems operating without RO, DI, or Electrodeionization (EDI) pretreatment to meet pharmaceutical water quality standards.

Chlorine & Chloramine

Chloramines are a class of compounds that include monochloramine (NH₂Cl), dichloramine (NHCl₂), and nitrogen trichloride (NCl₃). They are formed by the reaction of chlorine with ammonia. Chlorine is a common disinfectant added by drinking water municipalities, while ammonia may be naturally occurring or added by municipalities to reduce the propensity of chlorine to form unwanted disinfection byproducts. The most common chloramine found in feed waters is monochloramine, which is the predominant species in neutral or slightly basic feed waters.

Both chlorine and chloramines are oxidizing agents. When the feed water is heated in the distillation unit, the conditions become more conducive to stress corrosion and pitting attacks. Therefore, all chlorine species should be removed prior to any distillation unit to prevent these issues. Activated carbon is the preferred method for removing chlorine or chloramines in softened feed VC systems due to its reliability and flexibility in handling fluctuations in flow and impurity levels. Given the variable concentrations of these chlorine species in the feed water, a volumetric flow rate of less than 1.0 gpm per cubic foot of activated carbon and a bed change every six to twelve months is recommended. For total chlorine concentrations (chlorine plus chloramine) greater than 2 or 3 ppm, the use of catalytic activated carbon should be considered. These carbons have a modified surface that increases both the rate of removal and the capacity of the activated carbon.

Ammonia & Ammonium

Ammonia may naturally occur in feed waters, typically at lower concentrations. The presence of higher concentrations (>0.1 ppm) of ammonia is usually a consequence of chloramine removal, either through activated carbon or a chemical reducing agent such as sodium sulfite. This process results in the production of ammonia gas, which in water exists in equilibrium with the ammonium ion (NH₄⁺). The ratio of the two is dependent on the pH and temperature of the solution.

In a distillation column, ammonia, like other dissolved gases, will be carried over with the steam and contaminate the distillate. As equilibrium is established with the ammonium ion, an increase in distillate conductivity will occur. Since the ammonium ion is more conductive than the ionized carbon dioxide species, trace concentrations of feed water ammonium as low as 0.1 ppm can inhibit distillation units from consistently meeting the USP Stage 1 conductivity limit of 2.7 mS/cm at 80°C.

In the absence of any deionization processes employed as pretreatment for the VC still, a sodium cycle ion-exchange is one practical option for ammonia/ammonium removal. To ensure successful removal of ammonia species, the softener must be positioned downstream of the chlorine/chloramine removal step to liberate any present ammonia. Throughout the softener bed, the ammonium ion is exchanged for sodium, competing with other cations (e.g., calcium and magnesium associated with water hardness) for adsorption sites. Therefore, two banks of softeners are generally required: an initial softening step for hardness removal and a polishing softening step for ammonium removal. These are typically positioned upstream and downstream of the activated carbon de-chlorination step to maximize efficiency. Acid injection may also be required to lower the pH, converting ammonia gas to ammonium ion, thereby optimizing ammonium removal in the polishing softener. A process design featuring softener-carbon-softener is a common pretreatment configuration for softened feed VC systems operating in the U.S.

Endotoxin

An endotoxin specification of 0.25 EU/ml is mandated for WFI and is also a typical limit for high-purity pharmaceutical-grade waters. Properly designed VC units may provide a 3 to 4 log reduction in endotoxin concentrations. This equates to a feed water endotoxin limit of 250-2500 EU/ml—levels that are not common for most municipal sources. However, feed waters from surface water sources may experience endotoxin levels in this range during upset conditions. For lakes or reservoirs, these conditions may include turnover or disruption of thermal stratification, excessive precipitation introducing contamination, or flushing of new or existing distribution pipes. Additionally, endotoxin spikes can be observed in the product of activated carbon units, which are notorious for contributing to increased total viable bacteria levels.

The most practical method for endotoxin removal in pharmaceutical water systems is filtration, preferably via membranes rated in the ultrafiltration (UF) range or tighter. Pretreatment systems for VC stills, particularly those devoid of reverse osmosis (RO), could be supplemented by a UF system to ensure acceptable concentrations of endotoxin, even in upset conditions.

Silica

Silica is often reported as total silica, which is the sum of both reactive (ionic) and non-reactive (colloidal) forms. Reactive silica is in equilibrium with bisilicate ion in water and can be removed by ion-exchange or reverse osmosis (RO). Colloidal silica exists as long polymeric chains and can be removed by ultrafiltration (UF) or, more efficiently, by RO. When the concentration of silica exceeds the saturation level, it can precipitate on the internal surfaces of the VC units and disrupt thermal transfer within the unit. The saturation limit of silica varies based on the silica species, temperature, and pH of the water. It is often reported that silica concentrations in the range of 100 ppm will produce precipitated or amorphous silica.

For softened feed VC systems operating with high silica levels, silica can either be reduced in the feed water, or the unit may be operated at lower recoveries. Like reverse osmosis, distillation units concentrate the feed water and impurities during operation. Maximizing water recovery improves the efficiency of the process but risks exceeding the solubility limits of feed water impurities. At 80% recovery, the nominal concentration factor would be 5X. However, the concentration factor jumps to 10X for a system operating at 90% recovery. Even with silica levels considered manageable at 10-15 ppm in the feed water, high operating recoveries for softened feed VC systems may not be practical without proper feed water silica management.

Hardness

Another class of impurities concentrated during the VC process is calcium and magnesium, which are associated with water hardness. Properly designed water softeners will generally produce water with hardness levels of less than 5 ppm, which may be suitable for VC feed waters. As with any deionization process, feed water hardness will be removed, but excessive hardness can lead to precipitation on the still internals, resulting in an undesirable cleaning or descaling requirement for the still.

In the softener-carbon-softener process mentioned above, the operation of the primary softener is critical to ensure that no hardness ions are competing with ammonium ions in the polishing softener. This competition can lead to short run times and frequent regeneration of the polishing softener. Ammonia breakthrough from the polishing softener will have a deleterious effect on distillate quality.

Carbon Dioxide

Carbon dioxide is a dissolved gas that is not specifically removed in the VC process. Most feed waters have a slightly basic pH, as municipalities increase the pH to minimize corrosion in their piping networks.

Complete removal of carbon dioxide is not required to meet pharmaceutical water quality standards, but it may enhance the performance of the VC unit itself. Carbon dioxide is denser than air (primarily nitrogen) and may accumulate in the VC units, limiting heat transfer. Additionally, the presence of carbon dioxide may lead to localized corrosion or rouge due to the formation of carbonic acid in water. While we have not seen published data to confirm that this occurs in VC units, the implementation of a carbon dioxide management program for VC feed waters is recommended. For softened feed VC systems, a feed water degasser (steam stripper) integral to the VC unit is recommended. This may also assist in the removal of other non-condensable gases from the system.

Summary

Not unlike other primary deionization techniques, the key to successful long-term VC operation for the production of pharmaceutical-grade waters is understanding and monitoring feed water impurities and designing and operating a robust pretreatment system. For VC pretreatment systems that are absent of RO and DI (or EDI), this is absolutely imperative.

Many softened feed VC systems have reliably produced pharmaceutical-grade water, including WFI, for years. Like any high-purity water system, the feed water design should be based on a worst-case scenario, and the system should be designed to handle upset conditions. Specifically for surface water supplies, endotoxin concentrations can vary significantly, and these waters are likely treated with chloramines, consequently containing ammonia species. Implementing sound pretreatment techniques and monitoring the concentrations of these impurities to ensure properly conditioned water is fed to VC units are both critical for reliably maintaining the validated state of a pharmaceutical water treatment system.