title: Particle aerosolisation and break-up in dry powder inhalers: evaluation and modelling of impaction effects for agglomerated systems.
abstract: This study utilised a combination of computational fluid dynamics (CFD) and standardised entrainment tubes to investigate the influence of impaction on the break-up and aerosol performance of a model inhalation formulation. A series of entrainment tubes, with different impaction plate angles were designed in silico and the flow characteristics, and particle tracks, were simulated using CFD. The apparatuses were constructed using three-dimensional printing. 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 and CFD simulations indicated that mass deposition on the plate was dependent on the impactor angle (45°-90°) but independent of the airflow rate (60-140 L·min(-1)). In comparison, wall losses, perpendicular to the impactor plate were dependent on both the impactor angle and flow rate. Analysis of the particle size distribution exiting the impactor assembly suggested mannitol aerosolisation to be independent of impactor angle but dependent on the air velocity directly above the impactor plate. It is proposed that particle-wall impaction results in initial agglomerate fragmentation followed by reentrainment in the airstream above the impaction plate. 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: D000280:Administration, Inhalation; D000336:Aerosols; D000704:Analysis of Variance; D002626:Chemistry, Pharmaceutical; D003198:Computer Simulation; D017076:Computer-Aided Design; D058995:Dry Powder Inhalers; D004867:Equipment Design; D008353:Mannitol / Q000008:administration & dosage / Q000737:chemistry*; D008956:Models, Chemical; D010316:Particle Size; D011208:Powders; D012212:Rheology; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D000336:Aerosols; D011208:Powders; D008353:Mannitol