The Alberta Lung Filter Apparatus: A Novel Instrument for Classification of Pharmaceutical Aerosols

This presentation illustrates the design and proof-of-concept of the Alberta Lung Filter Apparatus (ALFA), a novel tool for rapidly estimating regional lung deposition of inhaled pharmaceutical aerosols.

Aerosolized medications have a long history of use treating lung disease and have also been employed to achieve systemic delivery. Due to disease localization within the lungs and the differing physiology of the proximal and distal lung regions, the ideal deposition site of a drug particle within the lungs depends on the drug product in question, and the intended indication. Measuring regional lung deposition in living subjects is largely precluded in early-stage research and development by the complexities and resource requirements associated with such studies. Instead, developers rely on benchtop experiments designed to estimate the dose and aerodynamic size distribution of aerosol that penetrates past the upper airways to enter the lungs. Empirical correlations or computational models of regional lung deposition can then be used to estimate total and regional deposition within the lungs. These methods provide detailed deposition estimates, but are time-consuming and require expert analysis to produce. In response to these challenges, we have developed the ALFA: a simple-to-use benchtop instrument that physically fractionates the inhaled dose into mouth-throat, tracheobronchial (central) and alveolar (peripheral) fractions. The ALFA uses a specially-designed mesh element to mimic the filtration efficiency of the tracheobronchial airways. This element is housed within a purpose-built housing which includes a flow-conditioning geometry to maintain uniform flow across the face of the filter and an electrostatic neutralizer to eliminate artificially high electrostatic deposition. Agreement in regional deposition estimates made using the ALFA versus aerodynamic size measurements coupled with a computational deposition model has been demonstrated for dry powder inhalers and pressurized metered dose inhalers. Case studies demonstrating the utility of the ALFA as a research tool will be presented.