Particle Aerosolisation and Break-Up in Dry Powder Inhalers: Evaluation and Modelling of Impaction Effects for Agglomerated Systems

被引:17
作者
Wong, William [1 ]
Fletcher, David F. [2 ]
Traini, Daniela [1 ]
Chan, Hak-Kim [1 ]
Crapper, John [3 ]
Young, Paul M. [1 ]
机构
[1] Univ Sydney, Fac Pharm, Adv Drug Delivery Grp, Sydney, NSW 2006, Australia
[2] Univ Sydney, Fac Pharm, Sch Chem & Biomol Engn, Sydney, NSW 2006, Australia
[3] Pharmaxis Ltd, Unit 2, Frenchs Forest, Sydney, NSW 2086, Australia
基金
澳大利亚研究理事会;
关键词
CFD; dry powder inhaler; impaction; agglomerate; deagglomeration; aerosols; in silico modelling; pulmonary drug delivery; simulations; particle size; DISPERSION; AEROSOLS;
D O I
10.1002/jps.22503
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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 mu m agglomerates containing 3.91 mu m 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 degrees-90 degrees) 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. (C) 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100: 2744-2754, 2011
引用
收藏
页码:2744 / 2754
页数:11
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