Tuning aerosol performance using the multibreath Orbital® dry powder inhaler device: controlling delivery parameters and aerosol performance via modification of puck orifice geometry.
The current study presents a new approach to tackle high-dose lung delivery using a prototype multibreath Orbital® dry powder inhaler (DPI). One of the key device components is the "puck" (aerosol sample chamber) with precision-engineered outlet orifice(s) that control the dosing rate. The influence of puck orifice geometry and number of orifices on the performance of mannitol aerosols were studied. Pucks with different orifice configurations were filled with 400 mg of spray-dried mannitol and tested in the Orbital® DPI prototype. The emitted dose and overall aerodynamic performance across a number of "breaths" were studied using a multistage liquid impinger. The aerosol performances of the individual actuations were investigated using in-line laser diffraction. The emptying rate of all pucks was linear between 20% and 80% cumulative drug released (R(2) > 0.98), and the amount of formulation released per breath could be controlled such that the device was empty after 2 to 11 breath maneuvers. The puck-emptying rate linearly related to the orifice hole length (R(2) > 0.95). Mass median aerodynamic diameters of the emitted aerosol ranged from 4.03 to 4.62 μm and fine particle fraction (≤6.4 μm) were 50%-66%. Laser diffraction suggested that the aerosol performance and emptying rates were not dependent on breath number, showing consistent size distribution profiles.
Respiratory Technology, Woolcock Institute of Medical Research, Glebe, New South Wales, 2037, Australia.
Bing
B
Zhu
Respiratory Technology, Woolcock Institute of Medical Research, Glebe, New South Wales, 2037, Australia.|Discipline of Pharmacology, Sydney Medical School, The University of Sydney, New South Wales, 2006, Australia.
Paul M
PM
Young
Respiratory Technology, Woolcock Institute of Medical Research, Glebe, New South Wales, 2037, Australia.|Discipline of Pharmacology, Sydney Medical School, The University of Sydney, New South Wales, 2006, Australia.
Hui Xin
HX
Ong
Pharmaxis Ltd, Frenchs Forest, Sydney, New South Wales, 2086, Australia.
John
J
Crapper
Pharmaxis Ltd, Frenchs Forest, Sydney, New South Wales, 2086, Australia.
Carina
C
Flodin
Pharmaxis Ltd, Frenchs Forest, Sydney, New South Wales, 2086, Australia.
Erin Lin
EL
Qiao
Pharmaxis Ltd, Frenchs Forest, Sydney, New South Wales, 2086, Australia.
Gary
G
Phillips
Respiratory Technology, Woolcock Institute of Medical Research, Glebe, New South Wales, 2037, Australia.|Discipline of Pharmacology, Sydney Medical School, The University of Sydney, New South Wales, 2006, Australia.
Daniela
D
Traini
D000280:Administration, Inhalation; D000336:Aerosols / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000295:instrumentation / Q000379:methods; D003692:Delayed-Action Preparations / Q000737:chemistry*; D058995:Dry Powder Inhalers / Q000295:instrumentation / Q000379:methods; D004867:Equipment Design / Q000295:instrumentation / Q000379:methods; D008353:Mannitol / Q000737:chemistry; D010316:Particle Size; D011208:Powders / Q000737:chemistry*
D000336:Aerosols; D003692:Delayed-Action Preparations; D011208:Powders; D008353:Mannitol
aerosol performance; aerosols; formulation; high dose dry powder inhaler; orbital; particle size; powder technology; puck orifice geometry; pulmonary drug delivery