In-silico quantification of intersubject variability on aerosol deposition in the oral airway

Borojeni, Azadeh Akhavan Taheri; Gu, Wanjun; Asgharian, Bahman; Price, Owen; Kuprat, Andrew P.; Singh, Rajesh K.; Colby, Sean M.; Corley, Richard A.; Corley, Richard A.; Darquenne, Chantal

doi:10.3390/pharmaceutics15010160

In-silico quantification of intersubject variability on aerosol deposition in the oral airway

Journal Article · Tue Jan 03 04:00:00 EST 2023 · Pharmaceutics

DOI:https://doi.org/10.3390/pharmaceutics15010160· OSTI ID:1910049

Borojeni, Azadeh Akhavan Taheri ^[1]; Gu, Wanjun ^[1]; Asgharian, Bahman ^[2]; Price, Owen ^[3]; ^[4]; ^[4]; Colby, Sean M. ^[4]; Corley, Richard A. ^[4]; Corley, Richard A. ^[5]; Darquenne, Chantal ^[1]

University of California, San Diego
Applied Research Associates, INC.
Applied Research Associates, Inc.
BATTELLE (PACIFIC NW LAB)
Greek Creek Toxicokinetics Consulting, LLC

The extrathoracic oral airway I s not only a major mechanical barrier for pharmaceutical aerosols to reach the lung but also a major source of variability in lung deposition. Using computational fluid dynamics, deposition of 1-30 µm particles was predicted in 11 CT-based models of the oral airways of adults (7 healthy subjects and 4 patients with chronic obstructive pulmonary disease). Simulations were performed for mouth breathing during both inspiration and expiration at two steady-state flow rates representative of resting/light activity (18 L/min) and of that typically used during aerosol inhalation from a dry powder inhaler (45 L/min). For each subject, oral deposition increased with increasing particle size and flow rate. When averaged over all subjects, there was no significant difference in oral deposition efficiency between inspiration and expiration, unlike subregional deposition that show significantly different patterns between the two breathing phases. Consistent with previous in-vitro inspiratory studies, our data showed a large intersubject variability in oral deposition. These results highlight the need for incorporating morphological variation of the upper airway in predictive models of aerosol deposition for accurate predictions of particle dosimetry in the intrathoracic region of the lung.

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE

DOE Contract Number:: AC05-76RL01830

OSTI ID:: 1910049

Report Number(s):: PNNL-SA-180130

Journal Information:: Pharmaceutics, Journal Name: Pharmaceutics Journal Issue: 1 Vol. 15

Country of Publication:: United States

Language:: English

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