In parenteral formulations, additives (or excipients) are used to ensure the stability, safety, efficacy, and compatibility of the active pharmaceutical ingredients. These additives must meet stringent safety standards due to the direct route of administration into the bloodstream. Below are some common additives used in parenteral formulations:


1. Solubilizers and Co-solvents

  • Purpose: To enhance the solubility of poorly soluble drugs.
  • Examples: Ethanol, polyethylene glycol (PEG), propylene glycol, and glycerin.

2. Buffers

  • Purpose: To maintain the pH of the formulation within an acceptable range to prevent degradation of the active ingredient and reduce irritation at the injection site.
  • Examples: Acetate buffer, citrate buffer, phosphate buffer.

3. Antioxidants

  • Purpose: To prevent oxidative degradation of the active ingredient, which can occur due to exposure to oxygen.
  • Examples: Ascorbic acid, sodium metabisulfite, and tocopherol (vitamin E).

4. Preservatives

  • Purpose: To prevent microbial growth, especially in multi-dose vials.
  • Examples: Benzyl alcohol, phenol, chlorobutanol, benzalkonium chloride.
  • Note: Preservatives are usually not used in single-dose parenteral products.

5. Chelating Agents

  • Purpose: To bind metal ions that may catalyze the degradation of the active ingredient.
  • Examples: EDTA (ethylenediaminetetraacetic acid), citric acid.

6. Tonicity Adjusting Agents

  • Purpose: To make the solution isotonic with body fluids, thus reducing pain or irritation at the injection site.
  • Examples: Sodium chloride, dextrose, mannitol.

7. Surfactants

  • Purpose: To enhance solubility and stabilize emulsions or suspensions by reducing surface tension.
  • Examples: Polysorbate 80 (Tween 80), lecithin.

8. Cryoprotectants and Lyoprotectants

  • Purpose: To protect the drug during freezing and freeze-drying processes for lyophilized formulations.
  • Examples: Sucrose, trehalose, and mannitol.

9. Viscosity Modifying Agents

  • Purpose: To adjust the viscosity of the formulation, particularly in depot injections or suspensions.
  • Examples: Carboxymethyl cellulose, and sodium alginate.

10. Emulsifying Agents

  • Purpose: To stabilize emulsions, ensuring proper mixing of the oil and water phases.
  • Examples: Lecithin, poloxamers.

11. Suspending Agents

  • Purpose: To keep the active ingredient uniformly distributed in suspensions.
  • Examples: Methylcellulose, and xanthan gum.

The choice and concentration of these additives must be carefully balanced to achieve the desired therapeutic effect while maintaining the safety, sterility, and stability of the parenteral product. Each additive also has specific limits and guidelines provided by regulatory bodies such as the FDA or EMA.