Pharmaceutical Research

, Volume 25, Issue 10, pp 2250–2261 | Cite as

Investigations on the Humidity-Induced Transformations of Salbutamol Sulphate Particles Coated with l-Leucine

  • Janne RaulaEmail author
  • Frank Thielmann
  • Jarno Kansikas
  • Sami Hietala
  • Minna Annala
  • Jukka Seppälä
  • Anna Lähde
  • Esko I. Kauppinen
Research Paper



The crystallization and structural integrity of micron-sized inhalable salbutamol sulphate particles coated with l-leucine by different methods are investigated at different humidities. The influence of the l-leucine coating on the crystallization of salbutamol sulphate beneath the coating layer is explored.


The coated particles are prepared by an aerosol flow reactor method, the formation of the l-leucine coating being controlled by the saturation conditions of the l-leucine. The coating is formed by solute diffusion within a droplet and/or by vapour deposition of l-leucine. The powders are humidified at 0%, 44%, 65% and 75% of relative humidity and the changes in physical properties of the powders are investigated with dynamic vapour sorption analysis (DVS), a differential scanning calorimeter (DSC), and a scanning electron microscope (SEM).


Visual observation show that all the coated particles preserve their structural integrity whereas uncoated salbutamol sulphate particles are unstable at 65% of relative humidity. The coating layer formed by diffusion performs best in terms of its physical stability against moisture and moisture-induced crystallization. The degree of crystallization of salbutamol in the as-prepared powders is within the range 24–35%. The maximum degree of crystallization after drying ranges from 55 to 73% when the salbutamol crystallizes with the aid of moisture. In addition to providing protection against moisture, the l-leucine coating also stabilizes the particle structure against heat at temperatures up to 250°C.


In order to preserve good flowability together with good physical stability, the best coating would contain two l-leucine layers, the inner layer being formed by diffusion (physical stability) and the outer layer by vapour deposition (flowability).


crystallization humidity l-leucine coating salbutamol sulphate stability 



We thank the Academy of Finland for financial support. Graduate student Raita Heiskanen is thanked for assistance with the experimental work.


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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Janne Raula
    • 1
    Email author
  • Frank Thielmann
    • 2
  • Jarno Kansikas
    • 3
  • Sami Hietala
    • 4
  • Minna Annala
    • 5
  • Jukka Seppälä
    • 5
  • Anna Lähde
    • 1
  • Esko I. Kauppinen
    • 1
    • 6
  1. 1.NanoMaterials Group, Laboratory of Physics and Center for New MaterialsHelsinki University of Technology (TKK)TKKFinland
  2. 2.Surface Measurement Systems Ltd.LondonUK
  3. 3.Laboratory of Inorganic ChemistryUniversity of HelsinkiHelsinkiFinland
  4. 4.Laboratory of Polymer ChemistryUniversity of HelsinkiHelsinkiFinland
  5. 5.Laboratory of Polymer TechnologyHelsinki University of Technology (TKK)TKKFinland
  6. 6.VTT Biotechnology (VTT)EspooFinland

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