Functional Category
Solvent
Applications in Pharmaceutical Formulation
Water is widely used as a raw material, ingredient and solvent in the processing, formulation and manufacture of pharmaceutical products, active pharmaceutical ingredients (API) and intermediates, and analytical reagents. Specific grades of water are used for particular applications in concentrations up to 100%
Description
The term ‘water’ is used to describe potable water that is freshly drawn direct from the public supply and is suitable for drinking. Water used in the pharmaceutical industry and related disciplines is classified as either drinking (potable) water, purified water, sterile purified water, water for injection (WFI), sterile water for injection, bacteriostatic water for injection, sterile water for irrigation, or sterile water for inhalation. Validation is required for all systems producing the water indicated, with the exception of potable water. The chemical composition of potable water is variable, and the nature and concentrations of the impurities in it depend upon the source from which it is drawn. Water classified as potable water for applications such as some initial rinsing and API manufacturing operations, must meet the US Environmental Protection Agency’s National Primary Drinking Water Regulations, or comparable regulations of the EU or Japan. For most pharmaceutical applications, potable water is purified by distillation, ion exchange treatment, reverse osmosis (RO), or some other suitable process to produce ‘purified water’. For certain applications, water with pharmacopeial specifications differing from those of purified water should be used, e.g. WFI; see Sections 9 and 18. Water is a clear, colorless, odorless, and tasteless liquid.
Stability and Storage Conditions
Water is chemically stable in all physical states (ice, liquid, and vapor). Water leaving the pharmaceutical purification system and entering the storage tank must meet specific requirements. The goal when designing and operating the storage and distribution system is to keep the water from exceeding allowable limits during storage. In particular, the storage and distribution system must ensure that water is protected against ionic and organic contamination, which would lead to an increase in conductivity and total organic carbon, respectively. The system must also be protected against physical entry of foreign particles and microorganisms so that microbial growth is prevented or minimized. Water for specific purposes should be stored in appropriate containers;
Incompatibilities
In pharmaceutical formulations, water can react with drugs and other excipients that are susceptible to hydrolysis (decomposition in the presence of water or moisture) at ambient and elevated temperatures. Water can react violently with alkali metals and rapidly with alkaline metals and their oxides, such as calcium oxide and magnesium oxide. Water also reacts with anhydrous salts to form hydrates of various compositions, and with certain organic materials and calcium carbide.
Safety
Water is the base for many biological life forms, and its safety in pharmaceutical formulations is unquestioned provided it meets standards of quality for potability(9) and microbial content; see Sections 9 and 18. Plain water is considered slightly more toxic upon injection into laboratory animals than physiological salt solutions such as normal saline or Ringer’s solution. Ingestion of excessive quantities of water can lead to water intoxication, with disturbances of the electrolyte balance. WFI should be free from pyrogens. LD50 (mouse, IP): 25 g/kg(10)