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In Vitro Evaluation of Nebulized Pharmaceutical Aerosol Delivery to the Lungs Using a New Heated Dryer System (HDS)

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Abstract

The objective of this study was to develop a new heated dryer system (HDS) for high efficiency lung delivery of nebulized aerosol and demonstrate performance with realistic in vitro testing for trans-nasal aerosol administration simultaneously with high-flow nasal cannula (HFNC) therapy and separately for direct oral inhalation (OI) of the aerosol. With the HDS-HFNC and HDS-OI platforms, new active synchronization control routines were developed to sense subject inhalation and coordinate drug aerosol delivery. In vitro experiments were conducted to predict regional drug loss and lung delivery efficiency in systems that included the HDS with various patient interfaces, realistic airway models, and simulated breathing waveforms. For the HDS-HFNC platform and a repeating breathing waveform, total system loss was < 10%, extrathoracic deposition was approximately 6%, and best-case lung delivery efficiency was 75–78% of nebulized dose. Inclusion of randomized breathing with the HFNC system decreased lung delivery efficiency by ~ 10% and had no impact on nasal depositional loss. For the HDS-OI platform and best-case mouthpiece, total system loss was < 8%, extrathoracic deposition was < 1%, and lung delivery efficiency was > 90% of nebulized dose. Normal vs. deep randomized oral inhalation had little impact on performance of the HDS-OI platform and environmental aerosol loss was negligible. In conclusion, both platforms demonstrated the potential for high efficiency lung delivery of the aerosol with the HDS-OI platform having the added advantages of nearly eliminating extrathoracic deposition, being insensitive to breathing waveform, and preventing environmental aerosol loss.

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Funding

Research reported in this publication was supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number R01HL107333. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, Virginia, USA

    Benjamin M. Spence, Worth Longest, Rabijit Dutta & Sarah Strickler

  2. Department of Pharmaceutics, Virginia Commonwealth University, Richmond, Virginia, USA

    Worth Longest, Mohammad A. M. Momin & Michael Hindle

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  1. Benjamin M. Spence
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  2. Worth Longest
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  4. Mohammad A. M. Momin
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Contributions

Conceptualization: WL, BS, MH; methodology: BS, WL, RD, MH; software: RD; formal analysis: BS, WL, MH; investigation: BS, WL, RD, MM, SS, MH; resources: WL, MH; data curation: BS, MH; writing – original draft preparation: WL, BS; writing – review & editing: BS, WL, MM, SS, MH; visualization: BS, RD, SS; supervision: WL, MH; project administration: WL, MH; funding acquisition: WL, MH.

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Correspondence to Worth Longest.

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Conflict of interest

Virginia Commonwealth University is currently pursuing patent protection of devices and methods described in this study, which if licensed and commercialized, may provide a future financial interest to the authors. MH is a member of the Editorial Board of AAPS PharmSciTech.

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Spence, B.M., Longest, W., Dutta, R. et al. In Vitro Evaluation of Nebulized Pharmaceutical Aerosol Delivery to the Lungs Using a New Heated Dryer System (HDS). AAPS PharmSciTech 24, 10 (2023). https://doi.org/10.1208/s12249-022-02460-0

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