Evaluation of Bio-relevant Mouth-Throat Models for Characterization of Metered Dose Inhalers.

ABSTRACT

For inhalation drug characterization, the traditionally used USP induction port provides limited in vivo predictive capability because it does not adequately mimic airway geometry. In this study, various bio-relevant mouth-throat (MT) models, including Alberta Idealized Throat (AIT), and 3D printed large/medium/small-sized VCU (Virginia Commonwealth University) models were evaluated using two metered dose inhaler (MDI) drug products a solution MDI containing beclomethasone dipropionate (BDP-MDI) and a suspension MDI containing fluticasone propionate (FP-MDI). For BDP-MDI, use of VCU large and small MT models resulted in a significantly higher MT deposition and lower fine particle fraction (FPF) compared with the other MT models. In the case of FP-MDI, the three VCU models resulted in higher MT deposition and lower FPF compared with the USP induction port and AIT. Overall, the in vitro testing results for the suspension MDI were more sensitive to geometric differences of the MT models than those for the solution MDI. Our results suggest that in vitro characterization of MDI products can be influenced by many factors, including the type of formulation, the MT geometry, shape, internal space volume, and the material used to make the MT models.