Experimental Evaluation of Dry Powder Inhalers During In- and Exhalation Using a Model of the Human Respiratory System (xPULM™)

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 five dry powder inhalers under realistic inhalation and exhalation conditions. The active respiratory system model (xPULM™) was used as a model of the human respiratory system and to simulate a patient undergoing inhalation therapy. 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 the upper airway model increases the resistance of the overall system and act as a filter for bigger particles (>3 µm). Furthermore, 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. The minimum deposition is reached for particle size of 0.5 µm. The mean particle number concentrations exhaled are 2.94% (BreezHaler®), 2.66% (Diskus®), 10.24% (Ellipta®) 2.13% (HandiHaler®) and 6.22% (Turbohaler®). In conclusion, the xPULM™ active respiratory system model is a viable option for studying interactions of pharmaceutical aerosols and the respiratory tract in terms of applicable deposition mechanisms. The model can support the reduction of animal experimentation in aerosol research and provide an alternative to experiments with human subjects.

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Simulations of the deposition of pharmaceutical aerosols in the human respiratory tract by dry powder inhalers (DPIs)

Journal of Drug Delivery Science and Technology ◽

10.1016/j.jddst.2020.101915 ◽

2020 ◽

Vol 59 ◽

pp. 101915 ◽

Cited By ~ 1

Author(s):

Eleftheria Chalvatzaki ◽

Sofia Eirini Chatoutsidou ◽

Mihalis Lazaridis

Keyword(s):

Respiratory Tract ◽

Dry Powder Inhalers ◽

Dry Powder ◽

Human Respiratory Tract ◽

Pharmaceutical Aerosols

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Assessing the performance of two dry powder inhalers in preschool children using an idealized pediatric upper airway model

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2013.01.007 ◽

2013 ◽

Vol 444 (1-2) ◽

pp. 169-174 ◽

Cited By ~ 16

Author(s):

Antje Below ◽

Deborah Bickmann ◽

Joerg Breitkreutz

Keyword(s):

Preschool Children ◽

Upper Airway ◽

Dry Powder Inhalers ◽

Dry Powder ◽

Airway Model

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Effect of Inhaling Patterns on Aerosol Drug Delivery: CFD Simulation

Volume 2: Biomedical and Biotechnology Engineering ◽

10.1115/imece2008-66685 ◽

2008 ◽

Author(s):

Jinho Kim ◽

Jim S. Chen

Keyword(s):

Secondary Flow ◽

Particle Deposition ◽

Cfd Simulation ◽

Dry Powder Inhaler ◽

Upper Airway ◽

Aerosol Deposition ◽

Dose Inhaler ◽

Breath Holding ◽

Pharmaceutical Aerosols ◽

Airway Model

Inhaled Pharmaceutical Aerosols (IPAs) delivery has great potential in treatment of a variety of respiratory diseases, including asthma, pulmonary diseases, and allergies. Aerosol delivery has many advantages. It delivers medication directly to where it is needed and it is effective in much lower doses than required for oral administration. Currently, there are several types of IPA delivery systems, including pressurized metered dose inhaler (pMDI), the dry powder inhaler (DPI), and the medical nebulizer. IPAs should be delivered deep into the respiratory system where the drug substance can be absorbed into blood through the capillaries via the alveoli. Researchers have proved that most aerosol particles with aerodynamic diameter of about 1–5 μm, if slowly and deeply inhaled, could be deposited in the peripheral regions that are rich in alveoli [1–3]. The purpose of this study is to investigate the effects of various inhaling rates with breath-holding pause on the aerosol deposition (Dp = 0.5–5 μm) in a human upper airway model extending from mouth to 3rd generation of trachea. The oral airway model is three dimensional and non-planar configurations. The dimensions of the model are adapted from a human cast. The air flow is assumed to be unsteady, laminar, and incompressible. The investigation is carried out by Computational Fluid Dynamics (CFD) using the software Fluent 6.2. The user-defined function (UDF) is employed to simulate the cyclic inspiratory flows for different IPA inhalation patterns. When an aerosol particle enters the mouth respiratory tract, its particles experience abrupt changes in direction. The secondary flow changes its direction as the airflow passes curvature. Intensity of the secondary flow is strong after first bend at pharynx and becomes weaker after larynx. In flow separation, a particle can be trapped and follow the eddy and deposit on the surface. Particle deposition fraction generally increases as particle size and inhaling airflow velocity increase.

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