Advancement of a high-dose infant air-jet dry powder inhaler (DPI) with passive cyclic loading: Performance tuning for different formulations

Abstract

There is a current medical need for a dry powder aerosol delivery device that can be used to efficiently and consistently administer high dose therapeutics, such as inhaled antibiotics, surfactants and antivirals, to the lungs of infants. This study considered an infant air-jet dry powder inhaler (DPI) that could be actuated multiple times with minimal user interaction (i.e., a passive cyclic loading strategy) and focused on the development of a metering system that could be tuned for individual powder formulations to maintain high efficiency lung delivery. The metering system consisted of a powder delivery tube (PDT) connecting a powder reservoir with an aerosolization chamber and a powder supporting shelf that held a defined formulation volume. Results indicated that the metering system could administer a consistent dose per actuation after reaching a steady state condition. Modifications of the PDT diameter and shelf volume provided a controllable approach that could be tuned to maximize lung delivery efficiency for three different formulations. Using optimized metering system conditions for each formulation, the infant air-jet DPI was found to provide efficient and consistent lung delivery of aerosols (∼45% of loaded dose) based on in vitro testing with a preterm nose-throat model and limited dose/actuation to <5 mg.

Keywords: Infant DPI; Inline DPI; Nose-to-lung aerosol delivery; Powder insufflation; Trans-nasal aerosol delivery.

Fig. 1

Graphical rendering of the experimental setup including the infant air-jet DPI platform with passive cyclic loading connected to a preterm infant nose-throat (NT) airway model.

Fig. 2

Internal pathways of the infant air-jet DPI with passive cyclic loading. Spray-dried formulation from the powder reservoir (a) passes through the powder delivery tube (PDT) forming a static powder bed on the powder shelf. Jets of air from the inlet flow passages enter the aerosolization chamber, interact with the powder bed and form an aerosol, which then exits the outlet capillary. As illustrated in Panel (b), the inlet air-jets do not directly imping on the initial powder bed. (c) Axial and side views of the air-jet DPI highlighting the PDT and powder shelf (shaded regions).

Fig. 3

Overview of the nasal interface used for aerosol administration. The top rendering highlights the short curved nasal prong and an external wedge to facilitate forming an airtight seal with the infant’s nostril. The bottom rendering has been sectioned along the midline axis to highlight the air-jet outlet capillary, airtight connection and gradual expansion flow passage leading to the nasal prong.

Fig. 4

Graphical renderings of the infant nose-throat (NT) airway geometry with regional sections and model assembly connected to custom low-volume (LV) filter housing. (a) Internal airway geometry of the infant NT model with assessed regions including the anterior nose (AN), middle passage (MP) and throat from multiple views. (b) Assembled infant NT model in connection to LV filter housing with parts and regions labeled from top and side views.

Fig. 5

Renderings of the two powder reservoir configurations. (a) PD2 device with standard (0.55 mL volume) reservoir and (b) PD2 device with adjustable powder reservoir (up to 1.5 mL volume).

Fig. 6

Rendering of the air-jet DPI connected to the aerosol collection assembly for emitted dose (ED) per actuation testing. Panel (a) shows the air-jet DPI connected to the aerosol collection assembly highlighting the entry points for co-flow (make-up) room air to reach a 45 L/min flow through the system. Panel (b) provides an axial cross-sectional view of the inside of the collection assembly.

Fig. 7

Experimental setup for device aerosolization performance as determined by Next Generation Impactor (NGI) testing. Parts labeled including 1. Electronic Timer (automated) air source, 2. Neonatal mass flow meter, 3. Air-jet DPI (PD2 with standard 0.55 mL powder reservoir pictured), 4. NGI adapter, 5. Vacuum line for NGI (operated at 45 LPM), and 6. Guide to angle the NGI at 53° off horizontal

Fig. 8

Plot of experimentally determined mean (and ±1 SD error bars) of emitted-dose (ED) per actuation and total ED (based on loaded dose) of the AS-EEG formulation, at a Q90 flow rate of 4 L/min [n=3]. Results for (a) 10 mg powder loading and (b) 30 mg powder loading