Experimental Evaluation of Dry Powder Inhalers during Inhalation and Exhalation Using a Model of the Human Respiratory System (xPULM™)

Abstract

Dry powder inhalers are used by a large number of patients worldwide to treat respiratory diseases. The objective of this work is to experimentally investigate changes in aerosol particle diameter and particle number concentration of pharmaceutical aerosols generated by four dry powder inhalers under realistic inhalation and exhalation conditions. To simulate patients undergoing inhalation therapy, the active respiratory system model (xPULM™) was used. A mechanical upper airway model was developed, manufactured, and introduced as a part of the xPULM™ to represent the human upper respiratory tract with high fidelity. Integration of optical aerosol spectrometry technique into the setup allowed for evaluation of pharmaceutical aerosols. The results show that there is a significant difference (p < 0.05) in mean particle diameter between inhaled and exhaled particles with the majority of the particles depositing in the lung, while particles with the size of (> 0.5m) are least influenced by deposition mechanisms. The fraction of exhaled particles ranges from 2.13% (HandiHaler®) over 2.94% (BreezHaler®), and 6.22% (Turbohaler®) to 10.24% (Ellipta®). These values are comparable to previously published studies. Furthermore, the mechanical upper airway model increases the resistance of the overall system and acts as a filter for larger particles (> 3m). In conclusion, the xPULM™ active respiratory system model is a viable option for studying interactions of pharmaceutical aerosols and the respiratory tract regarding applicable deposition mechanisms. The model strives to support the reduction of animal experimentation in aerosol research and provides an alternative to experiments with human subjects.

Positive end‐expiratory pressure and surfactant administration mode influence function in ex‐vivo premature sheep lungs

“…The electromechanical lung simulator xPULM has been described in detail and used in previous studies to realistically replicate the breathing patterns of adults 16,18 . The unique design of the simulator allows to model spontaneous breathing by creating negative alveolar pressure.…”

“…The electromechanical lung simulator xPULM has been described in detail and used in previous studies to realistically replicate the breathing patterns of adults. 16,18 The unique design of the simulator allows to model spontaneous breathing by creating negative alveolar pressure. This approach mimics physiological breathing, unlike typical commercially available lung simulators, which actively pump gas in and out of the lung.…”

Change of Composition, Source Contribution, and Oxidative Effects of Environmental PM2.5 in the Respiratory Tract

“…A recent study experimentally examined powder particles during inhalation and exhalation processes using a 3D-printed mechanical upper airway apparatus. 16 pollutants, a limited number of works developed mathematical models to analyze desorption of semi-volatile organic compounds associated with PM 2.5 as they move through the human respiratory tract and to address inhalation bioaccessibility. 7,17 To our knowledge, there is no experimental study to elucidate how the composition of PM 2.5 changes during the transport process from indoors to the human respiratory tract, or oxidative toxicity which is considered a potential dominant mechanism of adverse health effects of PM 2.5 .…”

“…Researchers developed physiologically relevant air–liquid interface devices to study biological effects (e.g., cell viability) of exposure to particles. − Numerous simulation models about drug delivery efficiency have been developed to investigate hygroscopic growth and deposition of drug particles in the human respiratory tract, − and composition or toxicity variation is not considered. A recent study experimentally examined powder particles during inhalation and exhalation processes using a 3D-printed mechanical upper airway apparatus . While for environmental particulate pollutants, a limited number of works developed mathematical models to analyze desorption of semi-volatile organic compounds associated with PM 2.5 as they move through the human respiratory tract and to address inhalation bioaccessibility. , To our knowledge, there is no experimental study to elucidate how the composition of PM 2.5 changes during the transport process from indoors to the human respiratory tract, or oxidative toxicity which is considered a potential dominant mechanism of adverse health effects of PM 2.5 .…”