title: Inhalable Spray-Freeze-Dried Powder with L-Leucine that Delivers Particles Independent of Inspiratory Flow Pattern and Inhalation Device.
abstract: OBJECTIVE
  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.
authors.affiliation: Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya, 468-8503, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Otake
authors.affiliation: Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya, 468-8503, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Okuda
authors.affiliation: Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya, 468-8503, Japan.|Department of Pharmacy, Shiga University of Medical Science Hospital, Setatsukiwa-cho, Ohtsu, 520-2192, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Hira
authors.affiliation: Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya, 468-8503, Japan.
authors.forename: Haruyoshi
authors.initials: H
authors.lastname: Kojima
authors.affiliation: Nano Seeds Corporation, 2266-99 Anagahora, Shimoshidami, Moriyama-ku, Nagoya, 463-8560, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shimada
authors.affiliation: Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya, 468-8503, Japan. okamotoh@ccmfs.meijo-u.ac.jp.
authors.forename: Hirozazu
authors.initials: H
authors.lastname: Okamoto
mesh_terms: D000268:Adhesiveness; D000280:Administration, Inhalation; D005079:Excipients / Q000737:chemistry*; D005612:Freeze Drying; D006801:Humans; D007930:Leucine / Q000737:chemistry*; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D016062:Porosity; D011208:Powders / Q000737:chemistry; D055672:Static Electricity
chemical_list: D005079:Excipients; D011208:Powders; D007930:Leucine
keywords: L-leucine (Leu); dry powder inhaler (DPI); inhalation device; inspiratory flow pattern; spray-freeze-drying (SFD)