Optimizing dry powder delivery during invasive mechanical ventilation via circuit absolute humidity control
Journal
International Journal of Pharmaceutics
Journal Volume
699
Start Page
126974
ISSN
1873-3476
Date Issued
2026-06-25
Author(s)
Abstract
Dry powder inhalers (DPIs) are rarely used during invasive mechanical ventilation (IMV) because intubated patients cannot generate sufficient inspiratory effort, and ventilator circuits require heated humidification that may impair powder dispersion. This study evaluated whether a ventilator-actuated, enclosed DPI chamber combined with a rapidly adjustable absolute humidifier can enable efficient DPI delivery under clinically relevant IMV conditions. An in vitro IMV model was operated in volume-controlled ventilation (15 breaths/min; I:E 1:2; square waveform; peak flow 50 L/min). An enclosed delivery chamber housing a capsule DPI (Breezhaler®; indacaterol 150 µg with lactose carriers) was inserted in-line during expiration and actuated for 15 breaths. Circuit humidity was controlled using an Absolute Humidifier Prototype at 0, 11, 22, 33, and 44 mg/L absolute humidity (AH; 0-100% RH at 37 °C) and compared with a pass-over humidifier (MR850; ∼40 mg/L AH). Tidal volume (VT) was 400-800 mL, and endotracheal tube (ETT) size was 7.5 or 9.5 mm internal diameter (ID). Inhaled dose was defined as the drug mass collected on the inspiratory filter distal to the ETT, and the aerodynamic particle size distribution (APSD) of inhaled dose was measured using an NGI. Inhaled dose showed a bidirectional dependence on humidity. At VT 600 mL with a 7.5-mm ETT, the inhaled dose peaked at 39.9 ± 0.9% of the labeled dose at 22 mg/L AH, decreased slightly at 33 mg/L AH (32.0 ± 1.6%), and dropped markedly near saturation at 44 mg/L AH (10.0 ± 2.2%); MR850 produced a similarly low inhaled dose (10.8 ± 1.2%). Increasing ETT ID from 7.5 to 9.5 mm reduced ETT deposition across 0-33 mg/L AH (e.g., 10.3 ± 0.7% to 5.8 ± 0.7% at 0 mg/L, p < 0.05) and increased inhaled dose at low humidity (e.g., 28.4 ± 2.0% to 36.3 ± 2.5% at 0 mg/L, p < 0.05). VT had little influence at 0-22 mg/L AH, but at high humidity, the inhaled dose increased (44 mg/L AH, 9.5-mm ETT: 13.3 ± 1.9 µg at VT 400 vs 37.0 ± 4.2 µg at VT 800, p < 0.05). APSD was largely stable across humidity and VT. Mass median aerodynamic diameter remained 2.76 ± 0.15 to 3.07 ± 0.03 µm, and geometric standard deviation showed no significant humidity effect. Fine particle dose (<5 µm) peaked at 26.1 ± 4.6 µg at 11 mg/L AH and decreased to 8.0 ± 2.7 µg at 44 mg/L AH (p < 0.05). A ventilator-actuated, enclosed chamber, combined with real-time humidity control, enabled efficient DPI delivery during IMV. Delivery was optimized at intermediate humidity (22 mg/L AH) and reduced at both humidity extremes. These data indicated controllable humidification is critical for translating DPI therapy into mechanically ventilated care.
Subjects
Aerosol delivery efficiency
Dry powder inhaler
Humidifier
Humidity
Invasive mechanical ventilation
Powder dispersion
Pulmonary delivery
Type
journal article