Preparation and characterization of medium-chain triglyceride lipid emulsion of propofol

Objective: To prepare medium-chain triglyceride lipid emulsion of propofol and investigate its physical properties. Methods: An orthogonal experiment was designed to optimize the formulation and the preparation procedures were optimized through a single factor experiment. The properties of the lipid emulsion,such as particle size,particle size distribution index,pH value and the stability after centrifugation were studied. The final formulation with the best preparation procedures was obtained. Results: The final formulation with the best preparation procedures,including an aqueous phase containing Poloxamer 188( 3. 60 g),glycerol( 2. 25 g) and appropriate amount of injectable water,was stirred at room temperature until all ingredients were dissolved. In parallel to above procedures,the oil phase containing propofol( 1 g),soya bean lecithin( 1. 2 g),oleic acid( 0. 16 g),VE( 0. 08 g) and medium-chain triglyceride( 10 g) were stirred until all ingredients were dissolved. Both the aqueous phase and the oil phase were maintained at a temperature of approximately 60 ℃. Then the oil phase was added to the aqueous phase. The mixture was dispersed with 500 W ultrasonic cell disruptor for 10 min. The crude emulsion was diluted to 100mL with injectable water and its pH was adjusted to 8 ~ 9 with 0. 1 mol·L- 1NaOH. Then the diluted crude emulsion was circulated ten times through a high pressure homogenizer under the pressure of 400 bar.The resultant lipid emulsion was filtered through 0. 45 μm millipore filter,and then filled into containers and autoclaved at a temperature of 115 ℃ for 30 min. Conclusion: The prepared medium-chain triglyceride lipid emulsion of propofol meets the requirements of intravenous injection preparations with a mean particle size of( 129. 87 ±0. 85) nm,a mean particle size distribution index( 0. 20 ± 0. 03) and a mean pH value( 8. 45 ± 0. 01).