Pharmaceutical Research

, Volume 19, Issue 6, pp 875–880 | Cite as

A Novel Phase Inversion-Based Process for the Preparation of Lipid Nanocarriers

  • Béatrice Heurtault
  • Patrick Saulnier
  • Brigitte Pech
  • Jacques-Emile Proust
  • Jean-Pierre BenoitEmail author


Purpose. To develop and subsequently evaluate a novel phase inversion-based method used to formulate lipidic nanocapsules.

Methods. Mechanical properties of emulsions prepared by multi-inversion phase processes were investigated using a drop tensiometer. Based on the results obtained, a formulation process was developed and a new type of nanocarrier was prepared. These particulates were sized by photon correlation spectroscopy and were visualized by atomic force microscopy and transmission electronic microscopy. Differential scanning calorimetry was also performed.

Results. The marginally cohesive but stable interfacial properties of the initial system led to the formulation of lipidic nanocapsules that were composed of a liquid core surrounded by a cohesive interface and were dispersed in an aqueous medium. These related suspensions were stable upon dilution for several months. The control of the formulation parameters allowed an adjustment of the particle mean diameter in the range of 25-100 nm with a monodisperse size distribution.

Conclusions. A novel and convenient process for the preparation of lipidic nanocapsules is described. The structure of these particulates resembles a hybrid between polymeric nanocapsules and liposomes. Such nanocapsules display a strong potential for drug delivery.

phase inversion process elasticity lipidic nanocapsules 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    J. P. Benoit, H. Marchais, H. Rolland, and V. Vande Velde. Biodegradable microspheres: Advances in production technology. In S. Benita (ed.), Microencapsulation: Methods And Industrial Applications, Marcel Dekker Inc., New-York, 1996 pp. 35–72.Google Scholar
  2. 2.
    M. Boisdron-Celle, P. Menei, and J. P. Benoit. Preparation and characterization of 5-fluorouracil-loaded microparticles as biodegradable anticancer drug carriers. J. Pharm. Pharmacol. 47:108–114 (1995).Google Scholar
  3. 3.
    W. Mehnert and K. Mader. Solid lipid nanoparticles: production, characterization and applications. Adv. Drug Deliv. Rev. 47:165–196 (2001).Google Scholar
  4. 4.
    M. R. Gasco. Solid lipid nanospheres from warm microemulsions. Pharm. Technol. Eur. 9:52–59 (1997).Google Scholar
  5. 5.
    C. Witschi and E. Doelker. Residual solvents in pharmaceutical products: Acceptable limits, influences on physicochemical properties, analytical methods and documented values. Eur. J. Pharm. Biopharm. 43:215–242 (1994).Google Scholar
  6. 6.
    P. Saulnier, F. Boury, A. Malzert, B. Heurtault, T. Ivanova, A. Cagna, I. Panaïotov, and J. E. Proust. Rheological model for the study of dilational properties of monolayers: Comportment of dipalmitoylphosphatidylcholine (DPPC) at the dichloromethane/ water interface under ramp type or sinusoidal perturbations. Langmuir 17:8104–8111 (2001).Google Scholar
  7. 7.
    D. J. Miller, T. Henning, and W. Grünbein. Phase inversion of w/o emulsions by adding hydrophilic surfactant: A technique for making cosmetics products. Colloids Surf. 183-185:681–688 (2001).Google Scholar
  8. 8.
    A. J. Sing. Thèse pour le grade de docteur en physique, University of Pau, France, 1997.Google Scholar
  9. 9.
    T. Förster, F. Schambil, and H. Tesmann. Emulsification by the phase inversion temperature method: The role of self-bodying agents and the influence of oil polarity. Int. J. Cosmet. Sci. 12: 217–227 (1990).Google Scholar
  10. 10.
    T. Förster, F. Schambil, and W. von Rybinski. Production of fine disperse and long-term stable oil-in-water emulsions by the phase inversion temperature method. J. Dispers. Sci. Technol. 13:183–193 (1992).Google Scholar
  11. 11.
    K. Shinoda and H. Takeda. Effect of added salts in water on the hydrophile-lipophile balance of non-ionic surfactants: The effect of added salts on the phase inversion temperature of emulsions. J. Colloid Interface Sci. 32:647–651 (1970).Google Scholar
  12. 12.
    B. Heurtault, P. Saulnier, B. Pech, J. E. Proust, J. Richard, and J. P. Benoit. Nanocapsules lipidiques, procédé de préparation et utilisation comme medicament, Patent No. 0002688000, 2000.Google Scholar
  13. 13.
    J. M. Solletti, M. Botreau, F. Sommer, W. L. Brunat, S. Kasas, T. M. Duc, and M. R. Celio. Elaboration and characterization of phospholipid Langmuir-Blodgett films. Langmuir 12:5379–5386 (1996).Google Scholar
  14. 14.
    N. H. Thomson, I. Collin, M. C. Davies, K. Palin, D. Parkins, C. J. Roberts, S. J. B. Tendler, and P. M. Williams. Atomic force microscopy of cationic liposomes. Langmuir 16:4813–4818 (2000).Google Scholar
  15. 15.
    C. Freitas, W. Mehnert, and R. H. Müller. Effect of storage conditions on long-term stability of solid lipid nanoparticles (SLN) in aqueous dispersion. Eur. J. Pharm. Sci. 2:177 (1994).Google Scholar
  16. 16.
    L. M. Crowe, J. H. Crowe, R. Rudolph, C. Womersley, and L. Appel. Preservation of freeze-dried liposomes by trehalose. Arch. Biochem. Biophys. 242:240–247 (1985).Google Scholar
  17. 17.
    R. Cavalli, O. Caputo, M. E. Carlotti, M. Trotta, C. Scarnecchia, and M. R. Gasco. Sterilization and freeze-drying of drug-free and drug-loaded solid lipid nanoparticles. Int. J. Pharm. 148:47–54 (1997).Google Scholar
  18. 18.
    C. Schwarz and W. Mehnert. Freeze-drying of drug-free and drug-loaded solid lipid nanoparticles (SLN). Int. J. Pharm. 157: 171–179 (1997).Google Scholar

Copyright information

© Plenum Publishing Corporation 2002

Authors and Affiliations

  • Béatrice Heurtault
    • 1
  • Patrick Saulnier
    • 1
  • Brigitte Pech
    • 1
  • Jacques-Emile Proust
    • 1
  • Jean-Pierre Benoit
    • 1
    Email author
  1. 1.Inserm ERIT-M 0104, ‘Ingénierie de la Vectorisation Particulaire’ Immeuble IBT 10, rue A. BoquelAngers CedexFrance

Personalised recommendations