TY - JOUR
T1 - Design, characterization, and aerosol dispersion performance modeling of advanced spray-dried microparticulate/nanoparticulate mannitol powders for targeted pulmonary delivery as dry Powder inhalers
AU - Li, Xiaojian
AU - Vogt, Frederick G.
AU - Hayes, Don
AU - Mansour, Heidi M.
N1 - Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 2014/4/1
Y1 - 2014/4/1
N2 - 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.
AB - 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.
KW - Aerosol performance modeling
KW - Confocal Raman chemical imaging
KW - DPI
KW - Lung
KW - Osmotic agent
KW - Particle engineering design
KW - Respiratory
KW - Solid-state
KW - cystic fibrosis
UR - http://www.scopus.com/inward/record.url?scp=84897106239&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84897106239&partnerID=8YFLogxK
U2 - 10.1089/jamp.2013.1078
DO - 10.1089/jamp.2013.1078
M3 - Article
C2 - 24502451
AN - SCOPUS:84897106239
VL - 27
SP - 81
EP - 93
JO - Journal of Aerosol Medicine and Pulmonary Drug Delivery
JF - Journal of Aerosol Medicine and Pulmonary Drug Delivery
SN - 1941-2711
IS - 2
ER -