Thibodeaux, Stefan, Duong, Lisa, Altinoglu, Erhan, Dimke, Thomas, Shaw, Duncan, Rowlands, David and Growcott, Ellena (2023) Aerosol technology to mimic dry powder inhalation in vitro using pulmonary cell models. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V. ISSN 1873-3441

Abstract

Inhaled therapy confers key advantages for the treatment of topical pulmonary diseases and offers potential for systemic delivery of medicines. Dry powder inhalers (DPIs) are generally the preferred devices for pulmonary delivery due to improved stability and satisfactory patient compliance. However, the mechanisms governing drug powder dissolution and availability in the lung and poorly understood. Here, we report a new in vitro system to study epithelial absorption of inhaled dry powders in lung barrier models of the upper and lower airway. The system is based on a CULTEX® RFS (Radial Flow System) cell exposure module joined to a Vilnius aerosol generator and allows the coupling of drug dissolution and permeability assessments. The cellular models recapitulate the barrier morphology and function of healthy and diseased pulmonary epithelium and incorporate the mucosal barrier to enable the investigation of drug powder dissolution in biorelevant conditions. With this system, we found differences in permeability across the airway tree and pinpointed the impact of diseased barriers in paracellular drug transport. Furthermore, we identified a different rank order of permeability for compounds tested in solution or powder form. These results highlight the value of this in vitro drug aerosolization setup for use in research and development of inhaled medicines.

Item Type:	Article
Date Deposited:	06 Jun 2023 00:45
Last Modified:	06 Jun 2023 00:45
URI:	https://oak.novartis.com/id/eprint/48943