Development of a High-Dose Infant Air-Jet Dry Powder Inhaler (DPI) with Passive Cyclic Loading of the Formulation

Area of Science:

• Pharmaceutical Sciences
• Biomedical Engineering
• Pediatric Medicine

Background:

• Dry powder inhalers (DPIs) are crucial for delivering respiratory medications to infants.
• Optimizing aerosol lung delivery in infants is challenging due to unique physiological differences.
• Existing DPI technologies may not consistently achieve efficient drug deposition in the infant lung.

Purpose of the Study:

• To develop and evaluate a passive cyclic loading strategy for an infant air-jet dry powder inhaler (DPI).
• To ensure high aerosol lung delivery efficiency that is independent of powder mass and infant pulmonary mechanics.
• To assess the performance of the modified DPI with different formulations.

Main Methods:

• Four air-jet DPI designs were initially compared in a preterm infant in vitro nose-throat (NT) model.
• The most effective passive design (PD) underwent sensitivity analyses.
• Evaluations included a model spray-dried excipient enhanced growth (EEG) formulation and a Surfactant-EEG formulation.

Main Results:

• Two DPI designs (PD-2 and PD-3) achieved an estimated 60% lung delivery efficiency with the EEG formulation.
• Performance was insensitive to powder mass loadings between 10-30 mg.
• The PD-3 device showed minimal sensitivity to downstream infant lung models and powder reservoir volume.

Conclusions:

• The modified infant air-jet DPI platform effectively utilizes a passive cyclic loading strategy.
• The system provides >60% lung delivery efficiency for a model spray-dried formulation.
• The DPI demonstrates negligible sensitivity to powder mass and potential for high-dose delivery.