Development of a High-Dose Infant Air-Jet Dry Powder Inhaler (DPI) with Passive Cyclic Loading of the Formulation
Purpose
The objective of this study was to incorporate a passive cyclic loading strategy into the infant air-jet dry powder inhaler (DPI) in a manner that provides high efficiency aerosol lung delivery and is insensitive to powder mass loadings and the presence of downstream pulmonary mechanics.
Methods
Four unique air-jet DPIs were initially compared and the best performing passive design (PD) was selected for sensitivity analyses. A single preterm in vitro nose-throat (NT) model, air source, and nasal interface were utilized throughout. While the majority of analyses were evaluated with a model spray-dried excipient enhanced growth (EEG) formulation, performance of a Surfactant-EEG formulation was also explored for the lead DPI design.
Results
Two devices, PD-2 and PD-3, evaluated in the preterm model achieved an estimated lung delivery efficiency of 60% with the model EEG formulation, and were not sensitive to the loaded dose (10–30 mg of powder). The PD-3 device was also unaffected by the presence of downstream pulmonary mechanics (infant lung model) and had only a minor sensitivity to tripling the volume of the powder reservoir. When using the Surfactant-EEG formulation, increasing the actuation flow rate from 1.7 to 4.0 L/min improved lung delivery by nearly 10%.
Conclusions
The infant air-jet DPI platform was successfully modified with a passive cyclic loading strategy and capable of providing an estimated > 60% lung delivery efficiency of a model spray-dried formulation with negligible sensitivity to powder mass loading in the range of 10–30 mg and could be scaled to deliver much higher doses.
Howe, C., Momin, M.A.M., Aladwani, G. et al. Development of a High-Dose Infant Air-Jet Dry Powder Inhaler (DPI) with Passive Cyclic Loading of the Formulation. Pharm Res (2022). https://doi.org/10.1007/s11095-022-03409-5