Construction of a Full Airway Volume “Total Inhalable Deposition in an Actuated Lung” (TIDAL) Model for Approximating Spatial Deposition Under Breathing Profiles

Ian R. Woodward¹ & Catherine A. Fromen¹

¹University of Delaware, Department of Chemical and Biomolecular Engineering,
150 Academy St. Newark, DE 19808, USA

Summary

New preclinical experimental approaches are needed to measure the spatial deposition of inhaled aerosols and improve evaluation of orally inhaled and nasal drug products, leading to the development of new vaccines and therapeutics, as well as bioequivalent assessments of generic options. To address this, our lab has created a multiscale dynamic preclinical tool to spatial measure deposition as a function of patient-specific breathing, anatomy, and disease state. Coined the “total inhalable deposition in an actuated lung” (TIDAL) model, this platform leverages advances in additive manufacturing to recreate spatial aerosol collection efficiencies across the five lung lobes. TIDAL represents an innovative life-size physical model built of moving, modular, plug-and-play components that faithfully recreates the essential physical phenomena occurring in both inhaled formulation and the lung. A full TIDAL model representing an adult male has been fabricated and used to assess spatial deposition under physiological breathing conditions. Five sealed elastic lobe units filled with latticed parts actuated to create independent airflow by expansion and contraction under cycles of compression and release within the sealed compartment. We have successfully achieved breathing profiles with asymmetric lobe involvement, tunable flow rates and volume exchange, and breath holds. Aerosols are introduced at the mouth inlet and following designated breathing cycles, deposition is quantified on the latticed parts following a wash. Differential lattice structures provide spatial collection, where finer lattices increase the local deposition to benchmark to clinical observations. Overall, this work demonstrates important proof-of-concept towards developing the preclinical TIDAL model.

Key Message

We have developed a new preclinical experimental model to measure spatial deposition of inhaled aerosols that is built of moving, modular, plug-and-play components that faithfully recreates the essential physical phenomena occurring in both inhaled formulation and the lung to improve in vitro assessments of inhaled therapeutics.