Regional Deposition of Spray Dried Trehalose Powders in the Alberta Idealized Nasal Inlet
Kelvin Duong1, Maximilian Aisenstat 1, John Z. Chen3, Brynn Murphy1, Scott Tavernini1, Kyle Kaufman1 Jing Zheng2, Randy Whittal2, Alana Gerhardt3, Christopher Fox3, Warren H. Finlay1, Reinhard Vehring1, & Andrew R. Martin1
1Department of Mechanical Engineering, University of Alberta, Edmonton, AB, T6G 2R3, CA
2Mass Spectrometry Facility, University of Alberta, Edmonton, AB, T6G 2R3, CA
3Access to Advanced Health Institute (AAHI), Seattle, WA, 98102, US
Summary
The present study compares the in vitro regional deposition of spray dried trehalose in the Alberta Idealized Nasal Inlet (AINI) using nominally small (predicted MMAD ~ 5.5 μm) versus large (predicted MMAD ~ 18 μm) primary particle sizes. An active, single dose device was used with automatic actuation to deliver the trehalose powders for both particle sizes at three different loaded doses, 10 mg, 20 mg, and 40 mg. A test flow rate of 7.5 L/min was maintained through the AINI. The interior of the AINI was coated prior to actuation to mitigate particle bounce. Deposition of trehalose in the four regions of the AINI (vestibule, turbinates, olfactory, and nasopharynx), pre-separator, and filter (representing in vitro lung deposition) was determined for each combination of particle size and loaded dose using liquid chromatography coupled with mass spectrometry by multiple reaction monitoring.
In all cases, a high fraction of trehalose powder penetrated past the vestibule into the turbinates and nasopharynx. For all three doses of the small particle size powder, a small yet non-negligible fraction of powder reached the filter, representing lung exposure. In the case of large particles, the fraction depositing on the filter was negligible, less than 0.7% of total recovered dose.
In summary, penetration of trehalose powder through the AINI was eliminated using larger primary particles, while high turbinate deposition was maintained.