What is the composition of propofol?

Composition of Propofol

Propofol is formulated as an oil-in-water emulsion containing 1% propofol (10 mg/mL), 10% soybean oil, 2.25% glycerol, 1.2% egg lecithin (egg phosphatide), and may contain preservatives such as benzyl alcohol, sodium benzoate, or EDTA. 1, 2

Chemical Structure and Properties

• Chemical name: 2,6-diisopropylphenol
• Physical properties:
  • Highly lipid soluble
  • Slightly soluble in water (hence the emulsion formulation)
  • pKa of 11
  • Octanol/water partition coefficient of 6761:1 at pH 6-8.5 1

Formulation Components and Their Purpose

1. Propofol (1% or 10 mg/mL):

   • Active pharmaceutical ingredient
   • Phenolic derivative that acts as a hypnotic agent 2
   • Binds to multiple CNS receptors including GABAA, glycine, nicotinic, and M1 muscarinic receptors 2

2. Soybean oil (10%):

   • Serves as the oil phase of the emulsion
   • Provides a vehicle for the lipophilic propofol molecule 2, 1

3. Glycerol (2.25%):

   • Isotonicity agent
   • Helps maintain appropriate osmolarity 1

4. Egg lecithin/phosphatide (1.2%):

   • Emulsifier
   • Stabilizes the oil-in-water emulsion 2, 1

5. Preservatives (may include):

   • Benzyl alcohol (1.5 mg/mL)
   • Sodium benzoate (0.7 mg/mL)
   • Disodium edetate (EDTA) or metabisulfite in some formulations
   • Added to retard bacterial and fungal growth 1, 3

6. Sodium hydroxide:

   • pH adjuster
   • Maintains pH between 6-8.5 1

Clinical Implications of Propofol's Composition

1. Allergic reactions:

   • Contraindicated in patients with allergies to eggs, soy, or sulfites
   • Some generic formulations containing metabisulfite may cause allergic reactions including bronchospasm 2, 3

2. Lipid-related considerations:

   • Risk of hypertriglyceridemia with prolonged infusions (>3 days)
   • Potential for acute pancreatitis in rare cases
   • Monitoring of serum triglyceride levels recommended during extended use 2, 3, 4

3. Infection risk:

   • The lipid emulsion can support microbial growth
   • Strict aseptic technique required during handling
   • Isolated reports of sepsis from contaminated vials 2, 4

4. Propofol infusion syndrome (PRIS):

   • Rare but potentially fatal complication
   • Characterized by metabolic acidosis, hypertriglyceridemia, hypotension, arrhythmias
   • May also include acute kidney injury, hyperkalemia, rhabdomyolysis, and liver dysfunction
   • Associated with high-dose, prolonged administration (though can occur with lower doses)
   • Incidence approximately 1%, with mortality up to 33% 2, 3

5. Pain on injection:

   • Reported in up to 30% of patients receiving IV bolus
   • Related to the formulation properties 2, 5

Alternative Formulations

Some alternative propofol formulations have been developed to address limitations of the standard formulation:

• Lower-lipid emulsions (e.g., 5% soybean oil instead of 10%)
• 2% propofol formulations (to reduce lipid load)
• Various non-emulsion formulations have been studied 5, 6

Understanding propofol's composition is essential for safe administration, recognizing contraindications, and monitoring for potential adverse effects related to its formulation components.