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

计算流体动力学 (CFD) 模型有助于通用计量吸入器的开发

• 批准号: 10459405
• 负责人: P. Worth Longest
• 金额: $ 19.93万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10459405
• 关键词: Computational; Fluid; Dynamics; CFD; Models

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 improve quality of life and the control of multiple lung diseases.

非专利口服吸入药品（OIDPs）有望降低成本，从而提高依从性