# Computational Fluid Dynamics (CFD) Models to Aid the Development of Generic Metered Dose Inhalers

> **NIH FDA U01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2022 · $199,329

## Abstract

Generic orally inhaled drug products (OIDPs) are expected to reduce cost and thereby improve compliance with
prescribed dosage regimens, leading to improved control of multiple lung diseases such as asthma and chronic
obstructive pulmonary disease (COPD). Despite these advantages, relatively few generic OIDPs have received
US Food and Drug Administration (FDA) approval and entered the marketplace due to challenges associated
with establishing bioequivalence of inhaled medications, largely related to difficulties in determining regional lung
dose. The objective of this study is to develop and validate new open-source computational fluid dynamics
(CFD) methods for a solution-based metered dose inhaler (MDI) product that can accurately predict regional
drug deposition throughout the airways, and then implement the model to establish in-vitro-in-vivo-correlations
(IVIVCs) between US FDA recommended in vitro test metrics and in vivo regional lung deposition. Innovations
in this project include first translating our existing methods and techniques to open-source CFD software
OpenFOAM. We will improve our existing MDI simulation routines to better capture the physics of MDI spray
plume formation and the evaporation of multicomponent droplets for a small-particle solution-based product
containing ethanol as a co-solvent. Concurrent in-house experiments will be used to broadly characterize the
MDI aerosol and will provide in vitro deposition data in realistic airway geometries to benchmark CFD predictions.
Our complete-airway simulation approach will be significantly expanded to improve model realism and enable
simulation of deposition during exhalation. Finally, the expanded open-source complete-airway model will be
compared with well-documented 2D and 3D validation data of the same MDI product evaluated in human
subjects with mild asthma. The developed and validated complete-airway model will then be implemented to
develop IVIVCs between the in vitro test metric of aerosol size distribution and regional lung deposition across
multiple subject sizes. To accomplish the project objective, the following aims are proposed:
Aim 1. Develop enhanced CFD open-source methods for predicting solution-based MDI aerosol formation,
transport and upper airway deposition and validate model predictions with existing and new in vitro data.
Aim 2. Develop enhanced CFD open-source methods for predicting solution-based MDI transport and
deposition throughout the lungs and validate model predictions with 2D and 3D in vivo data.
Aim 3. Implement the validated open-source complete-airway MDI model to develop IVIVC relationships
between FDA recommended in vitro test metrics and predicted regional lung deposition.
Outcomes. Project outcomes are directed toward an ultimate goal of increasing the number of generic inhaled
medications in the US marketplace and worldwide, which is expected to reduce consumer cost, improve
compliance with prescribed inhaled drug regimens and thereby i...

## Key facts

- **NIH application ID:** 10459405
- **Project number:** 5U01FD007353-02
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** P. Worth Longest
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2022
- **Award amount:** $199,329
- **Award type:** 5
- **Project period:** 2021-08-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10459405

## Citation

> US National Institutes of Health, RePORTER application 10459405, Computational Fluid Dynamics (CFD) Models to Aid the Development of Generic Metered Dose Inhalers (5U01FD007353-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10459405. Licensed CC0.

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