Inhalable Spray-Freeze-Dried Powder with L-Leucine that Delivers Particles Independent of Inspiratory Flow Pattern and Inhalation Device

Pharm Res. 2016 Apr;33(4):922-31. doi: 10.1007/s11095-015-1838-4. Epub 2015 Dec 7.


Purpose: The purpose of this study was to develop inhalable particles that can reach deep into the lungs efficiently independent of inhalation patterns of patients and inhalation devices. We prepared porous particles including L-leucine (Leu), a dispersive agent, by a spray-freeze-drying (SFD) method and examined the influence of inspiratory flow patterns and inhalation devices with various inhalation resistances.

Methods: Four types of SFD powder with different Leu contents (0-10%) were prepared. Scanning electron microscopy and laser diffraction were used to measure the morphology and size distribution of the powders. In-vitro inhalation characteristics were determined using a twin-stage liquid impinger equipped with an inspiratory flow pattern simulator. The effects of Leu on the adhesion force and electrostatic property of the particles were evaluated.

Results: The inhalation performance of the powders was improved by the addition of Leu. The powders with Leu showed a high inhalation performance regardless of inspiratory flow patterns and devices. The addition of Leu decreased the adhesion force and increased the surface potential of the powders.

Conclusions: The SFD particles with Leu showed high inhalation performance regardless of the inhalation patterns and devices, which was attributed to the decreased adhesion force between particles and increased dispersibility.

Keywords: L-leucine (Leu); dry powder inhaler (DPI); inhalation device; inspiratory flow pattern; spray-freeze-drying (SFD).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesiveness
  • Administration, Inhalation
  • Excipients / chemistry*
  • Freeze Drying
  • Humans
  • Leucine / chemistry*
  • Nebulizers and Vaporizers*
  • Particle Size
  • Porosity
  • Powders / chemistry
  • Static Electricity


  • Excipients
  • Powders
  • Leucine