Design, characterization, and aerosol dispersion performance modeling of advanced spray-dried microparticulate/nanoparticulate mannitol powders for targeted pulmonary delivery as dry Powder inhalers

Xiaojian Li, Frederick G. Vogt, Don Hayes, Heidi M. Mansour

Research output: Contribution to journalArticle

19 Scopus citations


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 ∼500nm to 2.0μm. 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 4μm for all SD mannitol aerosols. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)81-93
Number of pages13
JournalJournal of Aerosol Medicine and Pulmonary Drug Delivery
Issue number2
StatePublished - Apr 1 2014



  • Aerosol performance modeling
  • Confocal Raman chemical imaging
  • DPI
  • Lung
  • Osmotic agent
  • Particle engineering design
  • Respiratory
  • Solid-state
  • cystic fibrosis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Pharmaceutical Science
  • Pharmacology (medical)

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