title: Aerodynamic factors responsible for the deaggregation of carrier-free drug powders to form micrometer and submicrometer aerosols.
abstract: OBJECTIVE
  To employ in vitro experiments combined with computational fluid dynamics (CFD) analysis to determine which aerodynamic factors were most responsible for deaggregating carrier-free powders to form micrometer and submicrometer aerosols from a capsule-based platform.
  
  
  METHODS
  Eight airflow passages were evaluated for deaggregation of the aerosol including a standard constricted tube, impaction surface, 2D mesh, inward radial jets, and newly proposed 3D grids and rod arrays. CFD simulations were implemented to evaluate existing and new aerodynamic factors for deaggregation and in vitro experiments were used to evaluate performance of each inhaler.
  
  
  RESULTS
  For the carrier-free formulation considered, turbulence was determined to be the primary deaggregation mechanism. A strong quantitative correlation was established between the mass median diameter (MMD) and newly proposed non-dimensional specific dissipation (NDSD) factor, which accounts for turbulent energy, inverse of the turbulent length scale, and exposure time. A 3D rod array design with unidirectional elements maximized NDSD and produced the best deaggregation with MMD<1 μm.
  
  
  CONCLUSIONS
  The new NDSD parameter can be used to develop highly effective dry powder inhalers like the 3D rod array that can efficiently produce submicrometer aerosols for next-generation respiratory drug delivery applications.
authors.affiliation: Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, Virginia, USA. pwlongest@vcu.edu
authors.forename: P Worth
authors.initials: PW
authors.lastname: Longest
authors.forename: Yoen-Ju
authors.initials: YJ
authors.lastname: Son
authors.forename: Landon
authors.initials: L
authors.lastname: Holbrook
authors.forename: Michael
authors.initials: M
authors.lastname: Hindle
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols / Q000737:chemistry*; D002214:Capsules / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000295:instrumentation* / Q000379:methods*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods; D058995:Dry Powder Inhalers / Q000295:instrumentation* / Q000379:methods*; D004867:Equipment Design / Q000295:instrumentation / Q000379:methods; D057446:Hydrodynamics; D010316:Particle Size; D011208:Powders / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods
chemical_list: D000336:Aerosols; D002214:Capsules; D004337:Drug Carriers; D011208:Powders