title: The effect of device resistance and inhalation flow rate on the lung deposition of orally inhaled mannitol dry powder.
abstract: The present study investigates the effect of DPI resistance and inhalation flow rates on the lung deposition of orally inhaled mannitol dry powder. Mannitol powder radiolabeled with99mTc-DTPA was inhaled from an Osmohaler™ by healthy human volunteers at 50-70L/min peak inhalation flow rate (PIFR) using both a low and high resistance Osmohaler™, and 110-130L/min PIFR using the low resistance Osmohaler™ (n=9). At 50-70L/min PIFR, the resistance of the Osmohaler™ did not significantly affect the total and peripheral lung deposition of inhaled mannitol [for low resistance Osmohaler™, 20% total lung deposition (TLD), 0.3 penetration index (PI); for high resistance Osmohaler™, 17% TLD, 0.23 PI]. Increasing the PIFR 50-70L/min to 110-130L/min (low resistance Osmohaler™) significantly reduced the total lung deposition (10% TLD) and the peripheral lung deposition (PI 0.21). The total lung deposition showed dependency on the in vitro FPF (R2=1.0). On the other hand, the PI had a stronger association with the MMAD (R2=1.0) than the FPF (R2=0.7). In conclusion the resistance of Osmohaler™ did not significantly affect the total and regional lung deposition at 50-70L/min PIFR. Instead, the total and regional lung depositions are dependent on the particle size of the aerosol and inhalation flow rate, the latter itself affecting the particle size distribution.
authors.affiliation: Advanced Drug Delivery Group, Faculty of Pharmacy (A15), Science Road, University of Sydney, NSW 2006, Australia.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Yang
authors.affiliation: Department of PET and Nuclear Medicine, Level 7, Building 63, Royal Prince Alfred Hospital, NSW 2050, Australia.
authors.forename: Jordan
authors.initials: J
authors.lastname: Verschuer
authors.affiliation: School of Information Technologies, University of Sydney, NSW 2006, Australia.
authors.forename: Yuyu
authors.initials: Y
authors.lastname: Shi
authors.affiliation: School of Information Technologies, University of Sydney, NSW 2006, Australia.
authors.forename: Yang
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of PET and Nuclear Medicine, Level 7, Building 63, Royal Prince Alfred Hospital, NSW 2050, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Katsifis
authors.affiliation: Department of PET and Nuclear Medicine, Level 7, Building 63, Royal Prince Alfred Hospital, NSW 2050, Australia; School of Information Technologies, University of Sydney, NSW 2006, Australia.
authors.forename: Stefan
authors.initials: S
authors.lastname: Eberl
authors.affiliation: Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, and Central Clinical School, University of Sydney, Camperdown, NSW 2050, Australia.
authors.forename: Keith
authors.initials: K
authors.lastname: Wong
authors.affiliation: Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton, NSW 2305, Australia.
authors.forename: John D
authors.initials: JD
authors.lastname: Brannan
authors.affiliation: School of Information Technologies, University of Sydney, NSW 2006, Australia.
authors.forename: Weidong
authors.initials: W
authors.lastname: Cai
authors.affiliation: Department of Mechanical Engineering, University of Alberta, Edmonton, AB T6G2G8, Canada.
authors.forename: Warren H
authors.initials: WH
authors.lastname: Finlay
authors.affiliation: Advanced Drug Delivery Group, Faculty of Pharmacy (A15), Science Road, University of Sydney, NSW 2006, Australia. Electronic address: kim.chan@sydney.edu.au.
authors.forename: Hak-Kim
authors.initials: HK
authors.lastname: Chan
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols; D016503:Drug Delivery Systems / Q000295:instrumentation*; D058995:Dry Powder Inhalers; D004867:Equipment Design; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008297:Male; D008353:Mannitol / Q000008:administration & dosage*; D010316:Particle Size; D011208:Powders; D013147:Spirometry; D016284:Technetium Tc 99m Pentetate; D055815:Young Adult
chemical_list: D000336:Aerosols; D011208:Powders; D008353:Mannitol; D016284:Technetium Tc 99m Pentetate
keywords: Dry powder inhaler; Flow rate; Lung deposition; Mannitol; Resistance