Using Lung Regional Deposition Modeling as Model-Integrated Evidence for Locally Acting Orally Inhaled Drug Products.

Abstract

Evaluation of drug delivery for locally acting orally inhaled drug products (OIDPs) is challenging because there are no routinely conducted studies that directly quantify drug concentration in specific regions of the human lungs. In vivo regional deposition studies are helpful for understanding region-specific drug delivery to the lungs but are limited by a variety of factors including small population samples, long study duration, and representation of results in two-dimensional rather than three-dimensional frameworks. Lung regional deposition modeling (RDM) can provide useful insights on region-specific drug delivery to the lungs for locally acting OIDPS because it can be used to understand many of the underlying physical processes that influence drug delivery, and it can be used to develop in vitro in vivo correlations. When RDM is combined with in vitro and/or in vivo data that serve as model validation comparators as well as sources for model parameter inputs, and model credibility is established, it may be considered model-integrated evidence (MIE) when it is used to facilitate generic locally acting OIDP development and approval and thereby improve accessibility of OIDPs.