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

Janne Raula (Corresponding Author), Frank Thielmann, Jarno Kansikas, Sami Hietala, Minna Annala, Jukka Seppälä, Anna Lähde, Esko I. Kauppinen

Research output: Contribution to journalArticleScientificpeer-review

38 Citations (Scopus)


Purpose: 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.

Methods: 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).

Results: 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.

Conclusion: 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).
Original languageEnglish
Pages (from-to)2250-2261
JournalPharmaceutical Research
Issue number10
Publication statusPublished - 2008
MoE publication typeA1 Journal article-refereed


  • crystallization
  • humidity
  • l-leucine coating
  • salbutamol sulphate
  • stability


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