Advertisement

Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Development of propofol-loaded microemulsion systems for parenteral delivery

Abstract

The aim of the present study was to develop the aqueous parenteral formulation containing propofol using o/w microemulsion systems. Propofol itself was chosen as the oil phase and its content was fixed to 1%, w/w. Pseudoternary phase diagrams were constructed to obtain the concentration range of surfactant and cosurfacatnt and the optimum ratio between them for microemulsion formation. Consequently, the suitability of the chosen microemulsion system as a parenteral formulation was evaluated from the stability and hemolysis tests on that. Among the surfactants and cosurfactants screened, the mixture of Solutol HS 15-ethyl alcohol (5/1) showed the largest o/w mocroemulsion region in the phase diagram. When 1% (w/w) of propofol was solubilized with 8% (w/w) of Solutol HS* 15-ethyl alcohol (5/1), the average droplet size (150 nm) and the content of propofol in the systems were not significantly changed at 40°C for 8 weeks. The hemolysis test showed that this formulation was nontoxic to red blood cells. In conclusion, propofol was successfully solubilized with the o/w microemulsion systems.

This is a preview of subscription content, log in to check access.

References

  1. Concas, A., Santoro, G., and Mascia, M. P., The general anaesthetic propofol enhances the function of gamma-amino-butyric acid-coupled chloride channel in the rat cerebral cortex.J. Neurochem., 55, 2135–2138 (1990).

  2. Dollery, C., Propofol In: Therapeutic Drugs, 2nd Ed., Churchill Livingstone, Edinburgh, P251-P256 (1999).

  3. Floyd, A. G., Top ten considerations in the development of parenteral emulsions.Pharm. Sci. Technol. Today, 2, 134–143 (1999).

  4. Fu, R. C., Lidgate, D. M., Whatley, J. L, and Mccullough, T., The biocompatibility of parenteral vehicles-invitrolin vivo screening comparison and the effect of excipients on hemolysis.J. Parenter. Sci. Technol., 41, 164–168 (1987).

  5. Kryzaniak, J. F., Raymond, D. M., and Yalkowsky, S. H., Lysis of human red blood cells 2: effect of contact time on cosolvent induced hemolysis.Int. J. Pharm., 152, 193–200 (1997).

  6. Lilley, E. M. M., Isert, P. R., Carasso, M. L., and Kennedy, R. A., The effect of the addition of lignocaine on propofol emulsion stability.Anaesthesia, 51, 815–818 (1996).

  7. Masaki, T., Tanaka, M., and Nishikawa, T., Changes in propofol concentration in a propofol-lidocaine 9:1 volume mixture.Anesth. Analg., 90, 989–992 (2000).

  8. Park, J. W., Park, E. S., Chi, S. C., Kil, H. Y., and Lee, K. H., The effect of lidocaine on the globule size distribution of propofol emulsions.Anesth. Analg., 97, 769–771 (2003).

  9. Reed, K. W. and Yalkowsky, S. H., Lysis of human red blood cells in the presence of various cosolvents.J. Parenter. Sci. Technol., 39, 64–69 (1984).

  10. Tan, C. H. and Onsiong, M. K., Pain on injection of propofol.Anaesthesia, 53, 468–476 (1998).

  11. Tenjala, S., Microemulsions: An overview and pharmaceutical applications.Crit. Rev. Then Drug Carrier Systems, 16, 461–521 (1999).

  12. Trapani, G., Lopedota A., Franco M., Latrofa A., and Liso G., Effect of 2-hydroxypropyl-β-cyclodextrin on the aqueous solubility of the anaesthetic agent propofol (2,6-diisopro-pylphenolj.Int. J. Pharm., 139, 215–218 (1996).

  13. Trotta, M., Cavalli, R., Ugazio, E., and Gaseo, M. R., Phase behaviour of microemulsion systems containing lecithin and lysolecithin as surfactant.Int. J. Pharm., 143, 67–73 (1996).

  14. Yeganeh, M. H. and Ramzan, I., Determination of propofol in rats whole blood and plasma by high performance liquid chromatohraph.J. Chromatogr. B, 691, 478–482 (1997).

Download references

Author information

Correspondence to Hyun-Ki Ryoo or Chun-Woong Park or Sang-Cheol Chi or Eun-Seok Park.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Ryoo, H., Park, C., Chi, S. et al. Development of propofol-loaded microemulsion systems for parenteral delivery. Arch Pharm Res 28, 1400–1404 (2005). https://doi.org/10.1007/BF02977908

Download citation

Key words

  • Propofol
  • Microemulsion
  • Solubility
  • Parenteral delivery
  • Hemolysis
  • Anesthetics