Aerosol Plumes of Inhalers Used in COPD

Herbert Wachtel; Rachel Emerson-Stadler; Peter Langguth; Jens M Hohlfeld; Jill Ohar

doi:10.1007/s41030-023-00249-5

Aerosol Plumes of Inhalers Used in COPD

Pulm Ther. 2024 Mar;10(1):109-122. doi: 10.1007/s41030-023-00249-5. Epub 2024 Jan 9.

Authors

Herbert Wachtel¹, Rachel Emerson-Stadler², Peter Langguth³, Jens M Hohlfeld^{4

5

6}, Jill Ohar⁷

Affiliations

¹ Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Strasse 173, 55216, Ingelheim am Rhein, Germany. herbert.wachtel@boehringer-ingelheim.com.
² Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Strasse 173, 55216, Ingelheim am Rhein, Germany.
³ Institute for Pharmaceutical and Biomedical Sciences (IPBW), University of Mainz, Mainz, Germany.
⁴ Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Hannover, Germany.
⁵ Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany.
⁶ Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), German Center for Lung Research (DZL), Hannover, Germany.
⁷ Department of Internal Medicine, Section on Pulmonary Medicine, Critical Care, Allergy and Immunologic Diseases, Atrium Health Wake Forest Baptist, Medical Center Boulevard, Winston-Salem, NC, 27157, USA.

Abstract

Introduction: The selection of inhaler device is of critical importance in chronic obstructive pulmonary disease (COPD) as the interaction between a patient's inhalation profile and the aerosol characteristics of an inhaler can affect drug delivery and lung deposition. This study assessed the in vitro aerosol characteristics of inhaler devices approved for the treatment of COPD, including a soft mist inhaler (SMI), pressurized metered-dose inhalers (pMDIs), and dry powder inhalers (DPIs).

Methods: High-speed video recording was used to visualize and measure aerosol velocity and spray duration for nine different inhalers (one SMI, three pMDIs, and five DPIs), each containing dual or triple fixed-dose combinations of long-acting muscarinic receptor antagonists and long-acting β₂-agonists, with or without an inhaled corticosteroid. Measurements were taken in triplicate at experimental flow rates of 30, 60, and 90 l/min. Optimal flow rates were defined based on pharmacopoeial testing requirements: 30 l/min for pMDIs and SMIs, and the rate achieving a 4-kPa pressure drop against internal inhaler resistance for DPIs. Comparison of aerosol plumes was based on the experimental flow rates closest to the optimal flow rates.

Results: The Respimat SMI had the slowest plume velocity (0.99 m/s) and longest spray duration (1447 ms) compared with pMDIs (velocity: 3.65-5.09 m/s; duration: 227-270 ms) and DPIs (velocity: 1.43-4.60 m/s; duration: 60-757 ms). With increasing flow rates, SMI aerosol duration was unaffected, but velocity increased (maximum 2.63 m/s), pMDI aerosol velocity and duration were unaffected, and DPI aerosol velocity tended to increase, with a more variable impact on duration.

Conclusions: Aerosol characteristics (velocity and duration of aerosol plume) vary by inhaler type. Plume velocity was lower and spray duration longer for the SMI compared with pMDIs and DPIs. Increasing experimental flow rate was associated with faster plume velocity for DPIs and the SMI, with no or variable impact on plume duration, whereas pMDI aerosol velocity and duration were unaffected by increasing flow rate.

Keywords: Aerosol; Chronic obstructive pulmonary disease; Dry powder inhaler; Inhalation therapy; Inhaler; Pressurized metered-dose inhaler; Respiratory medicine; Soft mist inhaler.