Pharmaceutical Research

, Volume 25, Issue 1, pp 242–245 | Cite as

A Novel Gas Phase Method for the Combined Synthesis and Coating of Pharmaceutical Particles

  • Janne Raula
  • Anna Lähde
  • Esko I. KauppinenEmail author
Short Communication



A novel aerosol flow reactor method for the combined gas phase synthesis and coating of particles for drug delivery has been developed.

Materials and Methods

As an example, micron-sized salbutamol sulfate particles were produced via droplet-to-particle conversion and in-situ coated by the physical vapor deposition (PVD) of l-leucine vapor.


During the deposition, l-leucine vapor crystallized on the surfaces of amorphous salbutamol particles. The size of l-leucine crystallites increased with increasing vapor concentration of l-leucine. The salbutamol particles with rough l-leucine surfaces exhibited good flowability enabling to them to be dispersed into air flow without the delivery aid of coarse lactose carriers.


The fraction of particles smaller than 5 micrometers varied between 0.35 and 0.48 when dispersed into 60 l/min air flow having a jet Reynolds number of 30700. When the coated fine particles were blended with lactose carriers, the fine particle fraction was as high as 90%. The l-leucine coating also improved the stability of salbutamol particles when stored at 45% relative humidity atmosphere.

Key words

aerosol coating evaporation gas phase deposition inhalation l-leucine pharmaceutical powder production salbutamol sulfate surface modification vapor 



Financial support from the Finnish Academy is gratefully acknowledged. We thank Dr. Hua Jiang for the TEM analysis and Mr. Raoul Järvinen for assistance in building the experimental set-up.


  1. 1.
    S. Budavari, M. J. O’Neil, A. Smith, and P. E. Heckelman (eds.), The Merck Index, 11th edition, 1989.Google Scholar
  2. 2.
    N. Y. K. Chew, B. Y. Shekunov, H. H. Y. Tong, A. H. L. Chow, C. Savage, J. Wu, and H.-K. Chan. Effect of amino acids on the dispersion of disodium cromoglycate powders. J. Pharm. Sci. 94:2289–2300 (2005).PubMedCrossRefGoogle Scholar
  3. 3.
    S. Chungi, and T. I. Iorio. Method for coating drug-containing particles and formulations and dosage units formed therefrom. WO 04/84866 (2004).Google Scholar
  4. 4.
    H. Eerikäinen, W. Watanabe, E. I. Kauppinen, and P. P. Ahonen. Aerosol flow reactor method for synthesis of drug nanoparticles. Eur. J. Pharm. Biopharm 55:357–360 (2003).PubMedCrossRefGoogle Scholar
  5. 5.
    R. Hillamo, and E. I. Kauppinen. On the performance of the Berner low pressure impactor. Aerosol Sci. Tech 14:33–47 (1991).CrossRefGoogle Scholar
  6. 6.
    J. N. Israelachvili. Intermolecular & surface forces. St Edmundsbury, Suffolk, 1991.Google Scholar
  7. 7.
    J. A. Kurkela, D. P. Brown, J. Raula, and E. I. Kauppinen. Studies on powder deagglomeration into turbulent jet flow. In C. Kanaoka, H. Makino, and H. Kamiya (eds.), Advanced Gas Cleaning Technology, Jugei Shobo, Tokyo, 2005pp. 249–255.Google Scholar
  8. 8.
    D. Lechuga-Ballesteros, and M.-C. Kuo. Dry powder compositions having improved dispersivity. WO 01/32144 (2001).Google Scholar
  9. 9.
    Q. Li, V. Rudolph, and W. Peukert. London-van der Waals adhesiveness of rough particles. Powder Technol 161:248–255 (2006).CrossRefGoogle Scholar
  10. 10.
    P. Lucas, K. Anderson, U. J. Potter, and J. N. Staniforth. Enhancement of small particle size dry powder aerosol formulations using an ultra low density additive. Pharm. Res 16:1643–1647 (1999).PubMedCrossRefGoogle Scholar
  11. 11.
    F. Podczeck. The influence of particle size distribution and surface roughness of carrier particles on the in vitro properties of dry powder inhalations. Aerosol Sci. Technol 21:301–321 (1999).CrossRefGoogle Scholar
  12. 12.
    J. Raula, H. Eerikäinen, and E. I. Kauppinen. Influence of the solvent composition on the morphology of polymer drug composite nanoparticles. Int. J. Pharm 284:13–21 (2004).PubMedCrossRefGoogle Scholar
  13. 13.
    J. N. Staniforth, and D. A. V. Morton. Magnesium stearate, a phospholipid, or an amino acid in preparation of pharmaceutical particles for inhalation. WO 02/43700 (2002).Google Scholar
  14. 14.
    S. Watano, H. Nakamura, K. Hamada, Y. Wakamatsu, Y. Tanabe, R. N. Dave, and R. Pfeffer. Fine particle coating by a novel rotating fluidized bed coater. Powder Technol 141:172–176 (2004).CrossRefGoogle Scholar
  15. 15.
    B. Yue, J. Yang, Y. Wang, C.-Y. Huang, R. Dave, and R. Pfeffer. Particle encapsulation with polymers via in situ polymerization in supercritical CO2. Powder Technol 146:32–45 (2004).CrossRefGoogle Scholar
  16. 16.
    X. M. Zeng, G. P. Martin, S.-K. Tee, and C. Marriott. The role of fine particle lactose on the dispersion and deagglomeration of salbutamol sulfate in an air stream in vitro. Int. J. Pharm 176:99–110 (1998).CrossRefGoogle Scholar
  17. 17.
    X. M. Zeng, G. P. Martin, and C. Marriott. Particular interactions in dry powder formulations for inhalation. Taylor & Francis, London, 2001.Google Scholar
  18. 18.
    Y. Zhu, and K. W. Lee. Experimental study on small cyclones operating at high flow rates. J. Aerosol Sci 30:1303–1315 (1999).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.NanoMaterials Group, Laboratory of Physics & Center for New MaterialsHelsinki University of TechnologyEspooFinland
  2. 2.VTT BiotechnologyEspooFinland

Personalised recommendations