In Vitro Analysis of Nasal Interface Options for High-Efficiency Aerosol Administration to Preterm Infants

Background: An infant air-jet dry powder inhaler (DPI) platform has recently been developed that in combination with highly dispersible spray-dried powder formulations can achieve high-efficiency aerosolization with low actuation air volumes. The objective of this study was to investigate modifications to the nasal interface section of this platform to improve the aerosol delivery performance through preterm nose-throat (NT) models.Methods: Aerosol delivery performance of multiple nasal interface flow pathways and prong configurations was assessed with two in vitro preterm infant NT models. Two excipient-enhanced growth (EEG) dry powder formulations were explored containing either l-leucine or trileucine as the dispersion enhancer. Performance metrics included aerosol depositional loss in the nasal interface, deposition in the NT models, and tracheal filter deposition, which was used to estimate lung delivery efficiency.Results: The best performing nasal interface replaced the straight flexible prong of the original gradual expansion design with a rigid curved prong (similar to 20 degrees curvature). The prong modification increased the lung delivery efficiency by 5%-10% (absolute difference) depending on the powder formulation. Adding a metal mesh to the flow pathway, to dissipate the turbulent jet, also improved lung delivery efficiency by similar to 5%, while reducing the NT depositional loss by a factor of over twofold compared with the original nasal interface. The platform was also found to perform similarly in two different preterm NT models, with no statistically significant difference between any of the performance metrics.Conclusions: Modifications to the nasal interface of an infant air-jet DPI improved the aerosol delivery through multiple infant NT models, providing up to an additional 10% lung delivery efficiency (absolute difference) with the lead design delivering similar to 57% of the loaded dose to the tracheal filter, while performance in two unique preterm airway geometries remained similar.

Automated summary

Modifications to the nasal interface of an infant air-jet DPI were found to improve aerosol delivery performance, particularly in preterm nasal-throat models. By using a rigid curved prong and adding a metal mesh to dissipate turbulent jet, lung delivery efficiency was increased while nasal-throat deposition was reduced. The platform performed similarly in two different preterm airway models, with no statistically significant difference observed in performance metrics.