Nasal and Olfactory Deposition with Normal and Bidirectional Intranasal Delivery Techniques:In VitroTests and Numerical Simulations

Background: Intranasal delivery protocols that can effectively deposit drugs to the olfactory region are severely lacking. Furthermore, it is still challenging to quantify nasal deposition on a regional or local basis, which is crucial in assessing the performance of targeted olfactory drug delivery. Objectives: To visually and quantitatively compare drug depositions in the nose and olfactory region with normal and bidirectional breathing patterns with vibrating mesh and jet nebulizers. Methods: A sectional nose cast was developed based on an anatomically accurate nasal airway model to visualize deposition patterns and quantify regional doses. Sar-Gel was used to visualize the deposition pattern inside the nose and the delivered doses were measured using a high precision scale. Numerical modeling was performed to understand the underlying mechanisms in both the normal and bidirectional deliveries. Results: Results show that the bidirectional technique yielded higher deposition in both the nasal cavity and the olfactory region for both nebulizers. However, the vibrating mesh nebulizer was found to be more responsive to the bidirectional breathing and elicited more increase in the olfactory delivery than the PARI Sinus. The deposition patterns under the bidirectional breathing are highly different between the two nasal passages, with more dispersed distributions in the nasal passage with exiting flows. For both nebulizers, reducing the inhalation flow rates increased the nasal dose, but decreased the olfactory dose, which was consistent between in vitro measurements and numerical simulations. Conclusions: The bi directional technique with a vibrating mesh nebulizer is recommended for both nasal systematic and olfactory drug deliveries. The Sar-Gel based method in combination with sectional nasal casts appears to be a practical approach to visualize local depositions.