An in vitro technique for evaluating inhaled nasal delivery systems

This report describes a novel technique for delivering aerosols to the surface of respiratory epithelial cells cultured tit an air-liquid interface. A model microsphere formulation for nasal delivery was aerosolised using the glass impinger of the British Pharmacopoeia and delivered to a layer of 16HBE14o- cells incorporated into the upper impingement chamber. The deposition of the powder formulation, delivered as an aerosol of 20-30 mum diameter particles, was even and reproducible. No metabolic or permeability changes were detected in the cell layers following the deposition procedure. An application of this technique was demonstrated by measuring the transfer of gentamicin from hyaluronic acid-based microspheres across a layer of epithelial cells. The quantification of drug dissolution from the drug transfer data was illustrated. This technique will allow the biopharmaceutics and toxicology of inhaled nasal formulations to be examined in vitro, using more physiological and pharmaceutically-relevant methods of application of the drug than currently, available.