title: Particle aerosolisation and break-up in dry powder inhalers: evaluation and modelling of the influence of grid structures for agglomerated systems.
abstract: This study aimed to investigate the influence of grid structures on the break-up and aerosol performance of a model inhalation formulation through the use of standardised entrainment tubes in combination with computational fluid dynamics (CFD). A series of entrainment tubes with grid structures of different aperture size and wire diameters were designed in silico and constructed using three-dimensional printing. The flow characteristics were simulated using CFD, and the deposition and aerosol performance of a model agglomerate system (496.3-789.2 µm agglomerates containing 3.91 µm median diameter mannitol particles) were evaluated by chemical analysis and laser diffraction, respectively. Analysis of the mannitol recovery from the assembly indicated that mass deposition was primarily on the grid structure with little before or after the grid. Mass deposition was minimal down to 532 µm; however, for smaller grid apertures, significant blockage was observed at all airflow rates (60-140 L · min(-1)). Analysis of the particle size distribution exiting the impactor assembly suggested that mannitol aerosolisation was dependent on the void percentage of the grid structure. It is proposed that initial particle-grid impaction results in a shearing force causing agglomerate fragmentation followed by immediate re-entrainment into the turbulent airstream within the grid apertures which causes further dispersion of the fine particles. Such observations have significant implications in the design of dry powder inhaler devices.
authors.affiliation: Advanced Drug Delivery Group, Faculty of Pharmacy, University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: William
authors.initials: W
authors.lastname: Wong
authors.forename: David F
authors.initials: DF
authors.lastname: Fletcher
authors.forename: Daniela
authors.initials: D
authors.lastname: Traini
authors.forename: Hak-Kim
authors.initials: HK
authors.lastname: Chan
authors.forename: John
authors.initials: J
authors.lastname: Crapper
authors.forename: Paul M
authors.initials: PM
authors.lastname: Young
mesh_terms: D000336:Aerosols; D058995:Dry Powder Inhalers; D008353:Mannitol / Q000737:chemistry; D008962:Models, Theoretical; D010316:Particle Size
chemical_list: D000336:Aerosols; D008353:Mannitol