A propofol microemulsion with low free propofol in the aqueous phase: formulation, physicochemical characterization,...

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems

Background:

• Propofol is a widely used intravenous anesthetic agent.
• Current propofol emulsions can have limitations related to free propofol concentration and stability.
• Developing improved formulations is crucial for enhanced patient outcomes.

Purpose of the Study:

• To formulate a propofol microemulsion with a minimized concentration of free propofol in the aqueous phase.
• To characterize the physicochemical properties and stability of the developed microemulsion.
• To evaluate the in vivo pharmacokinetic behavior of the propofol microemulsion in beagle dogs.

Main Methods:

• Single-factor experiments and orthogonal design were employed for formulation development.
• Physicochemical properties including pH, osmolarity, particle size, zeta potential, and morphology were assessed.
• Concentration of free propofol, long-term stability, and pharmacokinetic profiles were evaluated and compared to a commercial product (Diprivan®).

Main Results:

• The optimal microemulsion exhibited comparable pH and osmolarity to Diprivan®.
• Spherical microemulsion particles with an average size of 22.6±0.2 nm were observed.
• The developed microemulsion contained 21.3% less free propofol than Diprivan®, showed good long-term stability at room temperature, and demonstrated rapid distribution and elimination in beagle dogs.

Conclusions:

• The developed propofol microemulsion possesses desirable physicochemical and pharmacokinetic properties.
• The reduced free propofol concentration and favorable stability suggest potential advantages over existing formulations.
• This novel microemulsion may serve as a clinically valuable carrier for propofol delivery.