title: Design, characterization, and aerosol dispersion performance modeling of advanced spray-dried microparticulate/nanoparticulate mannitol powders for targeted pulmonary delivery as dry powder inhalers.
abstract: BACKGROUND
  The purpose was to design and characterize inhalable microparticulate/nanoparticulate dry powders of mannitol with essential particle properties for targeted dry powder delivery for cystic fibrosis mucolytic treatment by dilute organic solution spray drying, and, in addition, to tailor and correlate aerosol dispersion performance delivered as dry powder inhalers based on spray-drying conditions and solid-state physicochemical properties.
  
  
  METHODS
  Organic solution advanced spray drying from dilute solution followed by comprehensive solid-state physicochemical characterization and in vitro dry powder aerosolization were used.
  
  
  RESULTS
  The particle size distribution of the spray-dried (SD) powders was narrow, unimodal, and in the range of ∼500 nm to 2.0 μm. The particles possessed spherical particle morphology, relatively smooth surface morphology, low water content and vapor sorption (crystallization occurred at exposure above 65% relative humidity), and retention of crystallinity by polymorphic interconversion. The emitted dose, fine particle fraction (FPF), and respirable fraction (RF) were all relatively high. The mass median aerodynamic diameters were below 4 μm for all SD mannitol aerosols.
  
  
  CONCLUSIONS
  The in vitro aerosol deposition stage patterns could be tailored based on spray-drying pump rate. Positive linear correlation was observed between both FPF and RF values with spray-drying pump rates. The interplay between various spray-drying conditions, particle physicochemical properties, and aerosol dispersion performance was observed and examined, which enabled tailoring and modeling of high aerosol deposition patterns.
authors: 1 University of Kentucky College of Pharmacy , Department of Pharmaceutical Sciences-Drug Development Division, Lexington, KY 40536-0596.
authors: Xiaojian
authors: X
authors: Li
authors: Frederick G
authors: FG
authors: Vogt
authors: Don
authors: D
authors: Hayes
authors: Heidi M
authors: HM
authors: Mansour
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D018360:Crystallography, X-Ray; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000295:instrumentation*; D058995:Dry Powder Inhalers; D004867:Equipment Design; D005100:Expectorants / Q000008:administration & dosage* / Q000737:chemistry; D016014:Linear Models; D008353:Mannitol / Q000008:administration & dosage* / Q000737:chemistry; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D036103:Nanotechnology; D010316:Particle Size; D033362:Powder Diffraction; D011208:Powders; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D014867:Water / Q000737:chemistry
chemical_list: D000336:Aerosols; D004337:Drug Carriers; D005100:Expectorants; D011208:Powders; D014867:Water; D008353:Mannitol