Predictive Lung Deposition Models for Safety and Efficacy of Orally Inhaled Drug Products (U01)

The goal of this proposal is to develop a computational fluid dynamics (CFD) model of orally inhaled drug products that can account for drug product characteristics (aerodynamic particle size distribution, APSD) and physiological parameters (breathing pattern and airway geometry) on total and regional deposition in the lungs. Specifically, the CFD model will be capable of predicting highly localized deposition of pharmaceutically relevant polydisperse aerosols from metered dose inhalers (MDIs) and dry powder inhalers (DPIs). The results obtained in this study will be used in developing a linked CFD-compartment model that can predict the effects of lung deposition on safety (systemic exposure) and efficacy (local delivery) for locally acting orally inhaled drugs.This investigation constitutes a critical step toward a better understanding of relationships among APSD, pharmacokinetics (PK) and local delivery for orally inhaled drug products. The outcome of the project will directly have an impact on the bioequivalence (BE) policy development for the generic orally inhaled products. In addition, it will help to (1) develop a quality-by-design (QbD) tool that could be used to improve the performance of orally inhaled drugs during the product development, (2) make accurate dose predictions, and (3) set clinical relevant APSD specifications to ensure product quality, for these drug/device combination products.