R457 – Paranasal Aerosol Delivery of Budesonide Using PARI VibrENT

Problem Nasal sprays containing inhaled corticosteroids are widely used for the treatment of chronic, allergic and acute sinusitis. However, nasal sprays deposit mainly on the nasal valve and on the anterior portion of the nose, and are rapidly cleared from there. Clinical efficacy data are equivocal which might be caused by the inability of nasal sprays to reach into the posterior regions of the nose. Hence, a drug delivery system such as the PARI VibrENT designed to target the deep nose and the paranasal cavities via a pulsating aerosol may offer substantial benefits. Methods Nebulization efficiency was investigated by a novel cast deposition model of the upper airway including paranasal sinuses developed by PARI GmbH (Munich, Germany). 0.5 mL of a captisol enabled budesonide inhalation solution (CBIS, 480 μg Budesonide/ml) was completely aerosolized into each nostril. Consequently, in total 1 ml or 480 μg of Budesonide were administered in about 3 minutes. Sinus deposition was measured by extracting the deposited drug with a defined volume of solvent and assayed by HPLC. Results The mean values are as follows: the mean paranasal deposition was 15.9% of the initially charged budesonide amount. Only about 2% of the initial budesonide charge remained in the nebulizer, whereas 57.7% deposited in the nasal cavity, 15.2 % were expelled and 90.8 % of the drug was recovered. Deposition in the single sinus cavities ranged from 0.1% up to 7% depending significantly on sinus volume (p<0.01) and ostium diameter (p<0.01). Conclusion Relevant drug amounts could be delivered by the VibrENT into the nose and paranasal cavities of the nasal cast. Sinus deposition depends on its anatomy and was highest with ostium diameters from 1.5 to 3 mm. Significance Significant sinus deposition of abudesonide solution may be attainable through the use of the VibrENT nebulizer system. Clinical studies are warranted.