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A Novel, Lipid-Free Nanodispersion Formulation of Propofol and Its Characterization

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Purpose.

Propofol is a widely used anesthetic agent with highly desirable fast “on” and “off” effects. It is currently formulated as lipid emulsions, which are known to support microbial growth. In this study, a novel, lipid-free nanodispersion formulation of propofol was characterized.

Methods.

The formulation was evaluated for its physical and chemical stability, in vitro compatibility with red blood cells, and its antimicrobial effectiveness. In vivo pharmacokinetic and pharmacodynamic properties of the formulation were evaluated in rats.

Results.

Our data suggest that this lipid-free formulation is physically and chemically stable. Compared to the commercial emulsion formulation Diprivan, it causes less hemolysis with red blood cells and has improved antimicrobial activity. In addition, the lipid-free formulation demonstrates similar pharmacological effects to Diprivan in rats.

Conclusions.

This novel, lipid-free formulation exhibits improved in vitro properties without compromising in vivo effects, therefore representing a promising new alternative for propofol.

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References

  1. 1. H. M. Bryson, B. R. Fulton, and D. Faulds. Propofol: an update on its use in anesthesia and conscious sedation. Drugs 50:513–559 (1995).

    CAS  PubMed  Google Scholar 

  2. 2. M. S. Langley and R. C. Heel. Propofol: a review of its pharmacodynamic and pharmacokinetic properties and use as an intravenous anesthetic. Drugs 33:334–372 (1988).

    Google Scholar 

  3. 3. A. W. Doenicke, M. F. Roizen, J. Rau, M. O’Connor, J. Kugler, U. Klota, and J. Babl. Pharmacokinetics and pharmacodynamics of propofol in a new solvent. Anesth. Analg 85:1399–1403 (1997).

    Google Scholar 

  4. 4. S. Dutta and W. F. Ebling. Emulsion formulation reduces propofol’s dose requirement and enhances safety. Anesthesiology 87:1394–1405 (1997).

    Google Scholar 

  5. 5. K. McKeage and C. M. Perry. Propofol: a review of its use in intensive care sedation of adults. CNS Drugs 17:235–272 (2003).

    Google Scholar 

  6. 6. W. Lindholm. Critically ill patients and fat emulsions. Minerva Anestesiol. 58:875–879 (1992).

    Google Scholar 

  7. 7. S. Albrecht, H. Ihmsen, K. Suchodolski, C. Frenkel, and J. Achuttler. Analgo-sedation in intensive care: a quantitative, EEG-based trial with propofol 1% and 2%. Anaesthesist 48:794–801 (1999).

    Google Scholar 

  8. 8. M. Schywalsky, H. Ihmsen, A. Tzabazis, J. Fechner, E. Burak, J. Vornov, and H. Schewilden. Pharmacokinetics and pharmacodynamics of the new propofol prodrug GPI 15715 in rats. Eur. J. Anaesthesiol. 20:182–190 (2003).

    Google Scholar 

  9. 9. Diprivan® 1% injectable emulsion package insert. Available at http://www.astrazeneca-us.com/pi/202014Diprivan.pdf.

  10. 10. I. Wachowski, D. T. Jolly, J. Hrazdil, J. C. Galbraith, M. Greacen, and A. S. Clanachan. The growth of microorganisms in propofol and mixtures of propofol and lidocaine. Anesth. Analg. 88:209–212 (1999).

    Google Scholar 

  11. 11. S. N. Bennett, M. M. McNeil, L. A. Bland, M. J. Arduino, M. E. Villarino, D. M. Perrotta, D. R. Burwen, S. F. Welbel, D. A. Pegues, and L. Stroud. Postoperative infections traced to contamination of an intravenous anesthetic, propofol. N. Engl. J. Med. 333:147–154 (1995).

    Google Scholar 

  12. 12. J. Crowther, J. Hrazdil, D. T. Jolly, J. C. Galbraith, M. Greacen, and M. Grace. Growth of microorganisms in propofol, thiopental, and a 1:1 mixture of propofol and thiopental. Anesth. Analg. 82:475–478 (1996).

    Google Scholar 

  13. 13. G. Trapani, A. Latrofa, M. Franco, A. Lopedota, E. Sanna, and E. Liso. Inclusion complexation of propofol with 2-hydroxypropyl-beta-cyclodextrin. Physicochemical, nuclear magnetic resonance spectroscopic studies, and anesthetic properties in rat. J. Pharm. Sci. 87:514 518–(1998).

    Google Scholar 

  14. 14. J. Han, S. S. Davis, and C. Washington. Physical properties and stability of two emulsion formulations of propofol. Int. J. Pharm. 14:207–220 (2001).

    Google Scholar 

  15. 15. H. Chen, Z. Zhang, C. McNulty, C. Olbert, H. J. Yoon, J. W. Lee, S. C. Kim, M. H. Seo, H. S. Oh, A. V. Lemmo, S. J. Ellis, and K. Heimlich. A high throughput combinatorial approach for the discovery of a Cremophor EL-free paclitaxel formulation. Pharm. Res. 20:1302–1308 (2003).

    Google Scholar 

  16. 16. S. L. Morissette, Ö. Almarsson, M. L. Peterson, J. F. Remenar, M. J. Read, A. V. Lemmo, S. Ellis, M. J. Cima, and C. R. Gardner. High-throughput crystallization: polymorphs, salts, co-crystals and solvates of pharmaceutical solids. Adv. Drug Deliv. Rev. 56:275–300 (2004).

    Google Scholar 

  17. 17. A. J. Bailer. Testing for the equality of area under the curves when using destructive measurement techniques. J. Pharmacokinet. Biopharm. 16:303–309 (1988).

    Google Scholar 

  18. 18. M. T. Baker, M. S. Gregerson, S. M. Martin, and G. R. Buettner. Free radical and drug oxidation products in an intensive care unit sedative: propofol with sulfite. Crit. Care Med. 31:787–792 (2003).

    Google Scholar 

  19. 19. J. J. Smith and B. E. Wayman. An evaluation of the antimicrobial effectiveness of citric acid as a root canal irrigant. J. Endod. 12:54–58 (1986).

    Google Scholar 

  20. 20. M. Georgopoulou, E. Kontakiotis, and M. Nakou. Evaluation of the antimicrobial effectiveness of citric acid and sodium hypochlorite on the anaerobic flora of the infected root canal. Int. Endod. J. 27:139–143 (1994).

    Google Scholar 

  21. 21. M. L. Veyries, F. Faurisson, M. L. Joly-Guillou, and B. Rouveix. Control of staphylococcal adhesion to polymethylmethacrylate and enhancement of susceptibility to antibiotics by poloxamer 407. Antimicrob. Agents Chemother. 44:1093–1096 (2000).

    Google Scholar 

  22. 22. C. Jagannath, M. R. Emanuele, and R. L. Hunter. Activities of poloxamer CRL-1072 against Mycobacterium avium in macrophage culture and in mice. Antimicrob. Agents Chemother. 43:2898–2903 (1999).

    Google Scholar 

  23. 23. M. Jumaa and B. W. Müller. In vitro investigation of the effect of various isotonic substances in parental emulsions on human erythrocytes. Eur. J. Pharm. Sci. 9:207 212 (1999).

    Google Scholar 

  24. 24. I. D. Cockshott, E. J. Douglas, G. F. Plummer, and P. J. Simons. The pharmacokinetics of propofol in laboratory animals. Xenobiotica 22:369–375 (1992).

    Google Scholar 

  25. 25. J. T. Chou and P. C. Jurs. Computation of partition coefficients from molecular structures by a fragment addition method. In S. H. Yalkowsky, A.A. Sinkula, and S.C. Valvani (eds.), Physical Chemical Properties of Drugs, Marcel Dekker, New York, 1980, pp. 163–199.

    Google Scholar 

  26. 26. S. Dutta and W. F. Ebling. Formulation-dependent brain and lung distribution kinetics of propofol in rats. Anesthesiology 89:678–685 (1998).

    Google Scholar 

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Correspondence to Hongming Chen.

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Chen, H., Zhang, Z., Almarsson, Ö. et al. A Novel, Lipid-Free Nanodispersion Formulation of Propofol and Its Characterization. Pharm Res 22, 356–361 (2005). https://doi.org/10.1007/s11095-004-1872-0

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  • DOI: https://doi.org/10.1007/s11095-004-1872-0

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