Introduction:
Respiratory drug delivery is a surprisingly complex process with a number of physical and biological challenges.
Computational fluid dynamics (CFD) is a scientific simulation technique that is capable of providing spatially and temporally
resolved predictions of many aspects related to respiratory drug delivery from initial aerosol formation through respiratory
cellular drug absorption.
Areas Covered:
This review article focuses on CFD-based deposition modeling applied to pharmaceutical aerosols. Areas covered include
the development of new complete-airway CFD deposition models and the application of these models to develop a next generation
of respiratory drug delivery strategies.
Expert Opinion:
Complete-airway deposition modeling is a valuable research tool that can improve our understanding of pharmaceutical
aerosol delivery and is already supporting medical hypotheses, such as the expected under-treatment of the small airways in
asthma. These complete-airway models are also being used to advance next generation aerosol delivery strategies, like
controlled condensational growth. We envision future applications of CFD deposition modeling to reduce the need for human
subject testing in developing new devices and formulations, to help establish bioequivalence for the accelerated approval of
generic inhalers, and to provide valuable new insights related to drug dissolution and clearance leading to microdosimetry
maps of drug absorption.
Objective
A comparison between flow and gas washout data for high-frequency percussive ventilation (HFPV) and pressure control ventilation (PCV) under similar conditions is currently not available. This bench study aims to compare and describe the flow and gas washout behavior of HFPV and PCV in a newly designed experimental setup and establish a framework for future clinical and animal studies.
Approach
We studied gas washout behavior using a newly designed experimental setup that is motivated by the multi-breath nitrogen washout measurements. In this procedure, a test lung was filled with nitrogen gas before it was connected to a ventilator. Pressure, volume, and oxygen concentrations were recorded under different compliance and resistance conditions. PCV was compared with two settings of HFPV, namely, HFPV-High and HFPV-Low, to simulate the different variations in its clinical application. In the HFPV-Low mode, the peak pressures and drive pressures of HFPV and PCV are matched, whereas in the HFPV-High mode, the mean airway pressures (MAP) are matched.
Main results
HFPV-Low mode delivers smaller tidal volume (VT) as compared to PCV under all lung conditions, whereas HFPV-High delivers a larger VT. HFPV-High provides rapid washout as compared to PCV under all lung conditions. HFPV-Low takes a longer time to wash out nitrogen except at a low compliance, where it expedites washout at a smaller VT and MAP compared to PCV washout.
Significance
Various flow parameters for HFPV and PCV are mathematically defined. A shorter washout time at a small VT in low compliant test lungs for HFPV could be regarded as a hypothesis for lung protective ventilation for animal or human lungs.
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