Purified Water and Water for Injection System Design

Water in the pharmaceutical and biotechnology industry is the most widely used substance both for production (manufacture of Active Pharmaceutical Ingredients (API), intermediates, and finished dosage forms) and for washing equipment, containers, or vessels.

As a raw material, high purity water is unique in that it is the only component that must be produced by the manufacturer, because it is not available from a vendor in a ready-to-use form. Water does not exist in the pure form in nature as it has the ability to absorb, suspend or dissolve various compounds - these need to be removed to produce WPU.

The major factors for designing a purified water system include:
Capacity of purified water required
Water quality attributes
Selection of membrane

Pure Water System Configuration
1. Feed water
2. Pretreatment
3. Primary Treatment
4. Optional Polishing
5. Storage and Distribution

Type of Water for Pharmaceutical Industry

Water for pharmaceutical use is classified according to how the pharmaceutical product is administered to the patient. They are regulated in the various pharmacopoeias (European Pharmacopoeia, United States Pharmacopoeia, Japanese Pharmacopoeia, etc.).

The types of pharmaceutical water are :
  1. Bulk forms :
    • Purified Water (PW)
    • Highly Purified Water (HPW) (European Pharmacopoeia)
    • Water For Injection (WFI)
    • Water For Hemodialysis
  2. Packaged Forms :
    • Bacteriostatic WFI
    • Sterile Water for Inhalation
    • Sterile Water for Injection
    • Sterile Water for Irrigation
    • Sterile Purified Water
Purified water 
  • Used as excipients in manufacturing of pharmaceuticals
  • Used for equipment cleaning esp. product contact surfaces of nonsterile chemicals
  • Preparation of bulk chemicals
  • Contains no added substance
  • Not for use in parenteral or sterile dosage
  • Prepared using potable water as feed
  • Type of purifications: Deionisation, distillation, Ion exchange, Reverse Osmosis, Filtration
  • Purified Water Quality Requirements :
    1. Conductivity: 3 stage measurement procedure
      No temperature compensation allowed
      Stage 1 online or lab test
      Stage 2 and 3 lab tests
    2. Total Organic Carbon: 500 ppb limit response
    3. Microbial Action Limit: 100 cfu / ml maximum - may be lower for specific process and product applications
    4. TOC < 500 ppb or oxidizable substance test

Manufacturing and Formulation of Paracetamol Elixir

Each 5 ml of Paracetamol Elixir contains :

Ingredients Weight Function
Paracetamol 120 mg Active ingredient
Glycerolum 2.5 ml Solubelizer
Propyleneglycol 0.5 ml Diluent
Sorbitol solution 70% 1.25 ml Sweetening agent
Ethanol 0.5 ml Diluent
Flavoring agent qs
Coloring agent qs
Preservative agent qs
Purified agent qs
  • Paracetamol solubility: Soluble in 70 parts of water, and in 7 parts ethanol (95%) P, in 13 parts of acetone P, in 40 parts of glycerol P, and in 19 parts propylenglycol P, soluble in alkali hydroxide solution.
  • Sorbitol: is hygroscopic, easily soluble in water and sparingly soluble in ethanol.
  • Propylenglycol: can be mixed with water and ethanol 95%.
  • Glycerol: can be mixed with water and ethanol.
Solubility data is very useful in preparations, which include sequences or a mix of each ingredient must be strictly in accordance with the nature and solubility. If seen from the solubility then we know that the function of glycerol and propylenglycol is to enhance the solubility of the medicine that is useful to maintain the stability of the drug.

Pharmaceutical Liquid Dosage Form : ELIXIRS

An elixir is a hydro-alcoholic solution of at least one active ingredient. Elixirs consist of alcohol and water and are sweet in taste and have a nice flavor. The alcohol is mainly used to:
  • Solubilize the active ingredient(s) and some excipients
  • Retard the crystallization of sugar
  • Preserve the finished product
  • Provide a sharpness to the taste
  • Aid in masking the unpleasant taste of the active ingredient(s)
  • Enhance the flavor.
The lowest alcoholic quantity that will dissolve completely the active ingredient(s) and give a clear solution is generally chosen. High concentrations of alcohol give burning taste to the final product.

Elixirs have low viscocity than syrups and they can flow more freely as there will be very less use of agents that increase viscocity like sucrose. To call a formulation as elixir, it must be hydroalcoholic and the amount of alcohol may vary greatly.

Solvents for Liquid Preparations and Liquid Pharmaceutical Dosage Form

Solvents for Liquid Preparations
The following agents find use as solvents in the preparation of solutions.
  1. Purified Water, H2O
    Purified water has the widest range of usefulness of all the solvents employed in pharmaceutical dispensing or manufacturing, because of lack of toxicity, physiological compatibility, and its ability to dissolve a wide range of materials. It is a good solvent for most inorganic and organic

    Purified Water, USP, is obtained by distillation, ion exchange treatment, reverse osmosis, or other suitable process. When evaporated to dryness, it must not yield more than 0.001% of residue (1 mg of solids per 100 mL of water). Thus, purified water has only 1% as much dissolved solids as tap water. Purified Water, USP, is intended for use in the preparation of aqueous dosage forms except those intended for parenteral administration (injections). Water for Injection, USP; Bacteriostatic Water for Injection, USP; or Sterile Water for Injection, USP, is used for injections.
  2. Alcohol USP, Ethyl Alcohol, Ethanol (C2H5OH)
    Primary and good solvent for many organic substances both natural and synthetic. Together with water it forms a hydroalcoholic mixture that dissolves both alcohol-soluble and water-soluble substances, a feature especially useful in the extraction of active constituents from crude drugs. A most widely used solvent particularly for external application.

    Alcohol has been well recognized as a solvent and excipient in the formulation of oral pharmaceutical products. Certain drugs are insoluble in water and must be dissolved in an alternative vehicle. Alcohol is often preferred because of its miscibility with water and its ability to dissolve many water-insoluble ingredients, including drug substances, flavorants, and antimicrobial preservatives. Alcohol is frequently used with other solvents, such as glycols and glycerin, to reduce the amount of alcohol required. It is also used in liquid products as an antimicrobial preservative alone or with parabens, benzoates, sorbates, and other agents.

    It is particular useful for the extraction of crude drugs being more selective than water. Alcohol, USP, is 94.9 to 96.0% by volume (i.e., v/v) when determined at 15.56°C. Concern has been expressed over the undesired pharmacologic and potential toxic effects of alcohol when ingested in pharmaceutical products, particularly by children. For OTC oral products intended for children under 6 years of age, the recommended alcohol content limit is 0.5%; for products intended for children 6 to 12 years of age, the recommended limit is 5%; and for products recommended for children over 12 years of age and for adults, the recommended limit is 10%.