• Xiaojian Li, Frederick G Vogt, Don Hayes, and Heidi M Mansour.
• 1 University of Kentucky College of Pharmacy , Department of Pharmaceutical Sciences-Drug Development Division, Lexington, KY 40536-0596.
• J Aerosol Med Pulm Drug Deliv. 2014 Apr 1; 27 (2): 81-93.

BackgroundThe 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.MethodsOrganic solution advanced spray drying from dilute solution followed by comprehensive solid-state physicochemical characterization and in vitro dry powder aerosolization were used.ResultsThe 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.ConclusionThe 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.

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