A simple exposure chamber to deposit dry powder particles onto multiple cell layers grown at the air-liquid interface on Transwell® inserts was developed and validated as an in vitro tool to study the fate of inhaled particles in the lung. The system consists of a glass desiccator and the PennCenturyTM dry powder insufflator. Salbutamol sulfate (SS) and indomethacin were used as test dry powders. The system delivered between 0.2 and 1.0 μg of SS and indomethacin particles (size range 3-5μm) per Transwell® insert in a controlled and reproducible manner, depending on the position of the inserts in the deposition chamber and the PennCenturyTM drug loading. Transepithelial electrical resistance (TEER) and lucifer yellow flux measurements confirmed that the integrity of Calu-3 cell layers was maintained after exposure to the particle sprays. The transepithelial transport of salbutamol and indomethacin was measured in solution and after particle deposition onto the cell layers. The apical to basolateral (AB) flux of both drugs delivered to the cell layers as dry powders was significantly higher than when they were applied as solutions. The percentage of drug transported was not dependent on the applied dose in either case but as expected, was greater for the high permeability drug indomethacin. Despite limitations, the deposition system proved helpful in understanding the role of drug particle characteristics on their dissolution/absorption behaviour at the air-epithelium interface.