Effects of subject-variability on nasally inhaled drug deposition, uptake, and clearance

Abstract

Accurate and realistic predictions of the fate of nasally inhaled generic drugs provide new physical insight which can be of great importance to toxicologists, drug developers and federal regulators alike. To understand the dynamics of mucociliary clearance (MCC) and subsequent absorption of the dissolved drug by the nasal epithelium, it becomes necessary to model the air-particle-mucus dynamics accurately. The MCC process, including particle dissolution, transport and absorption for a 3-D representative nasal cavity, were established by Chari et al. (2021). In this study, the effects of inter-subject variability of three representative nasal cavities (subjects A, B, C) on deposition and subsequent uptake of the dissolved drug in the nasal epithelium are analyzed for three generic drugs: Mometasone furoate (MF), Flunisolide (FN), and Ribavirin (RB). The computational fluid-particle dynamics (CF-PD) results indicate that smaller sized particles (3 μm) deposit more in the ciliated portion of the nasal cavity where the columnar cells responsible for uptake are present. In contrast, larger particles (10 μm) tend to deposit in the unciliated anterior third of the nose. The epithelial uptake in case of subject A was considerably higher than that in subjects B and C because of the unique anatomical characteristics of subject A. Also, FN and RB were found to have a higher rate of uptake compared to MF due to their considerably higher partition coefficient. As a visualization tool, concentration contours are used to explain regional trends in cumulative drug uptake for all three cases.