Anatomically-detailed segmented representative adult and pediatric nasal models for assessing regional drug delivery and bioequivalence with suspension nasal sprays

In vitro nasal models can potentially facilitate development and approval of nasal drug products. This study aims to evaluate the potential for using regional deposition measurements from in vitro nasal models to evaluate nasal spray performance across several products. To accomplish this, the posterior regions of six anatomically realistic nasal airway models of adult and pediatric subjects, representing Low (L), Mean (M) and High (H) posterior drug deposition (PD) for each of the two age groups, were segmented with high anatomical precision into five regions of interest. These models were previously developed with the goal of quantifying the range of intersubject variability of PD following administration of inhaled corticosteroids. The in vitro regional drug deposition values were measured for the reference listed drug (RLD) product for triamcinolone acetonide and two corresponding generic (test) nasal spray products, as well as an RLD product for fluticasone furoate nasal spray. In general, the pediatric models mostly demonstrated higher PD compared to the adult models. The majority (>85 %) of PD was confined to the front and the inferior meatus regions. Subsequent population bioequivalence (PBE) analyses of the regional nasal deposition suggested that the anatomical differences among subjects may impact the nasal spray performance across different nasal products.