title: Respirable low-density microparticles formed in situ from aerosolized brittle matrices.
abstract: OBJECTIVE
  Inhalation of low-density porous particles enables deep lung delivery with less dependence on device design and patient inspiration. The purpose of this study was to implement Thin Film Freezing (TFF) to investigate a novel approach to dry powder inhalation.
  
  
  METHODS
  Powders produced by TFF were evaluated for aerodynamic and geometric particle size by cascade impaction and laser light scattering, respectively. Density measurements were conducted according to USP methods and calculated using data from particle size measurements. Excipient inclusion and its effect on moisture sorption was measured by Dynamic Vapor Sorption (DVS).
  
  
  RESULTS
  TFF-produced brittle matrix powders were sheared apart into respirable microparticles using a passive DPI device, producing fine particle fractions (FPF) up to 69% and mass median aerodynamic diameters (MMAD) as low as 2.6 μm. Particles had a mean geometric diameter ranging from 25 μm to 50 μm and mass densities of approximately 0.01 g/cm(3). Powders were susceptible to moisture-induced matrix collapse, capillary forces and electrostatic charging; although formulations containing mannitol or no sugar excipient proved to be more robust.
  
  
  CONCLUSIONS
  Aerosolized brittle matrices produced by TFF may prove to be a useful platform for highly efficient pulmonary delivery of thermally labile, highly potent, and poorly soluble drugs.
authors.affiliation: Drug Dynamics Institute, The University of Texas at Austin, 1 University Station, Mail Stop A1915, Austin, Texas 78712, USA. abwatts@mail.utexas.edu
authors.forename: Alan B
authors.initials: AB
authors.lastname: Watts
authors.forename: Yi-Bo
authors.initials: YB
authors.lastname: Wang
authors.forename: Keith P
authors.initials: KP
authors.lastname: Johnston
authors.forename: Robert O
authors.initials: RO
authors.lastname: Williams
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols / Q000737:chemistry*; D002241:Carbohydrates / Q000737:chemistry; D058995:Dry Powder Inhalers; D005079:Excipients / Q000737:chemistry; D005615:Freezing; D006801:Humans; D008353:Mannitol / Q000737:chemistry; D010316:Particle Size; D016062:Porosity; D011208:Powders / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D000336:Aerosols; D002241:Carbohydrates; D005079:Excipients; D011208:Powders; D014867:Water; D008353:Mannitol