Development of a Transient Flow Aerosol Mixer-Heater System for Lung Delivery of Nasally Administered Aerosols Using a Nasal Cannula

摘要

Previous studies have demonstrated improved nose-to-lung aerosol drug delivery with controlled condensational growth methods using a mixer-heater developed to synchronize aerosol delivery with patient inhalation. The goal of this study was to develop a new mixer-heater that delivers aerosols with a transient flow profile similar to a sinusoidal breathing waveform. The mixer-heater consisted of a chamber with two blowers delivering aerosol during the inhalation cycle of three sinusoidal breathing profiles. The effects of breathing profiles and mode of condensational growth delivery were studied using two in vitro extrathoracic airway models (closed-and open-mouth options). In excipient enhanced growth (EEG) delivery mode, increasing peak exhalation breathing flow rate decreased the emitted dose from the mixer-heater using the closed-mouth model. The mean (SD) emitted doses were 92 (2), 77 (2), and 70 (2), with 23, 35, and 44 L/min peak exhalation breathing flow rates, respectively. Using the in vitro open-mouth model mitigated the effect of breathing and the emitted doses were 93 (0.5), 83 (3), and 90 (4) using the breathing profiles. The emitted doses in enhanced condensational growth (ECG) delivery mode using the breathing profiles with peak flow rates of 23, 35, and 44 L/min were 63 (4), 58 (2), and 58 (1), which were consistently lower than with EEG. Similarly, using the open-mouth model in ECG mode increased emitted doses to 77 (3), 73 (2), and 77 (8), respectively. The developed aerosol mixer-heater delivered greater than 50 of the nominal dose using a flow profile of sinusoidal inhalation, which represents a significant improvement compared to the current methods.