Effects of MDI spray angle on aerosol penetration efficiency through an oral airway cast
Introduction
The American Lung Association (www.lungusa.org) estimated that 26 million Americans have been diagnosed with asthma in their lifetime. Of these 26 million Americans, 10.6 million have had an asthma episode in the past 12 months. An additional 4.9% of the US population has chronic obstructive pulmonary disease (COPD) in their lifetime. Portable inhalers, including metered-dose inhaler (MDI) and dry-powder inhaler (DPI), are popular devices that are used in the treatment of lung diseases. However, the problems that are associated with inhalers are well documented. Typically, only about 5–20% (Johnson, 1995, Newman et al., 1989) of aerosol medicine can be delivered to the lung region, in part due to the substantial aerosol deposition in the oral and throat regions.
Numerous studies on aerosol medicine delivery have been published in the past few decades. It would be a great challenge to name all these studies. Many investigators have examined the effects of air flow rate, particle size, particle density, intra-subject variability, and inter-subject variability on deposition of particles in the oral–pharyngeal–laryngeal (OPL) airways including Newman and Clarke (1983), Yu and Diu (1983), Newman (1985), Swift (1989), Kim and Garcia (1993), Cheng, Zhou, and Chen (1999), Lin, Breysse, Laube, and Swift (2001), Dehaan and Finlay, 2001, Dehaan and Finlay, 2004, Grgic, Finlay, and Heenan (2004), Heenan, Finlay, Matida, and Pollard (2003), and Fadl, Wang, Yang, Zhang, and Cheng (2007). The deposition of monodisperse aerosol particles in the oral airway of healthy adult human volunteers has been reported (Bowes and Swift, 1989, Chan and Lippmann, 1980, Emmett et al., 1982, Foord et al., 1978, Lippmann and Albert, 1969; Stahlhofen et al., 1980, Stahlhofen et al., 1983). A systematic review of the literature and detailed comparison of different inhaler devices are conducted by Brocklebank et al. (2001). Clinical effectiveness, aerosol medicine characterizations, and comparative performances of various aerosol inhalers (MDI and DPI), spacers, and nebulizers are the main themes of the literature.
Knowledge of fluid dynamics is essential for understanding particles transport in the human respiratory system. Because trajectories of inhaled particles reflect the nature of the fluid flow in which they are entrained, additionally, there is a strong connection between local deposition and the local fluid mean velocity (Heenan, Finlay, Grgic, Pollard, & Burnell, 2004); the study of respiratory air flow dynamics may provide important information for inhalation therapy applications. It is generally agreed that the relatively high velocity and the abrupt changes in flow direction in the human upper airway are the major causes for the inertial deposition of particles larger than in diameter.
To minimize the problem and to deliver the aerosol drug in more respirable form, spacer and chambers that are of various physical shapes and designs are developed. Some are as simple and straightforward as extension tubes placing the inhaler at a greater distance from the mouth. Others decelerate the aerosol by means of tortuous flow path routes or bluff body impact areas. While reducing the aerosol deposition at the back of the throat to some extent, the designs used for existing spacers often contribute to the great drug loss within the delivery system.
Inertial impaction is the major cause for aerosol deposition in the human oral airways (Zhang, Chia, & Finlay, 2006). Many parameters can influence the particle impaction such as particle size, density, and air flow rate. Additionally, plume characterization (Barry & O’Callaghan, 1997), type of inhalation device (Dehaan & Finlay, 2001), and the propellant selection in the pressurized MDI (Cheng, Fu, Yazzie, & Zhou, 2001) have an influence on particle deposition in the human oral airway. The effect of the mouthpiece diameter at various inspiratory flow rates is reported by Lin et al. (2001) and Dehaan and Finlay (2004) using radio-labeled particle. In this paper, we are focusing on the effect of the particles entrance/injection angle on the aerosol penetration efficiency of the MDI. The effect of this parameter has not been previously reported in the literature; in addition, this parameter can be easily adjusted and manipulated during the inhaler design and fabrication process, and it will be an important guide for optimum use of the MDI. A computer simulation of the fluid flow and the aerosol transport patterns within a three-dimensional human airway model is first conducted to facilitate the understanding of the aerosol deposition mechanisms, and it is used as a testing tool to qualitatively examine new parameters that may have a potential influence on aerosols deposition in human oral airways. The results of the simulation predictions are then verified by in vitro experiments conducted in the identical airway geometry.
Section snippets
Airway morphology
The oral airway morphology used in this study is provided by the Lovelace Respiratory Research Institute. This oral airway morphology has been used in many previous studies. For detailed descriptions of this oral airway geometry, please refer to the studies published by Cheng et al., 1999, Cheng et al., 2001.
Computer simulations
The objective of this computer simulation is to provide the much needed air flow patterns in the oral airway which are essential in understanding the mechanisms of particles transport.
Results and discussion
Fig. 7 shows the velocity distribution inside the human oral airway. It illustrates the potential mechanism of how entrance angle affects the aerosols velocity and particle deposition patterns in the oral airway. The steady flow rate of 60 L/min is simulated in this figure, and the left panel of Fig. 7 shows the flow pattern when the mouthpiece is positioned horizontally, whereas the right panel shows the flow pattern when the mouthpiece is placed at a upward angle.
It is generally known that
Conclusions
Placing the MDI inhaler with a slightly upward angle can significantly decrease the particle deposition in the oral airway cast. An optimum angle exists which can maximize the particle penetration efficiency through the oral airway. This conclusion is independent of respiratory flow rate and mouthpiece diameter. The experiments are conducted using a single oral airway cast with two tongue positions (natural breathing position and a flatten position), two mouthpiece diameters (16 and 20 mm), and
Acknowledgment
Research described in this article was supported by the Philip Morris USA Inc.
References (27)
- et al.
Predicting extrathoracic deposition from dry powder inhalers
Journal of Aerosol Science
(2004) - et al.
Measurements of total and regional deposition of inhaled particles in the human respiratory tract
Journal of Aerosol Science
(1982) - et al.
Total and regional deposition of inhaled aerosol in humans
Journal of Aerosol Science
(1983) - et al.
In vitro comparison of the amount of salbutamol available for inhalation from different formulations used with different spacer devices
European Respiratory Journal
(1997) - et al.
Deposition of inhaled particles in the oral airway during oronasal breathing
Aerosol Science and Technology
(1989) - et al.
Comparison of the effectiveness of inhaler devices in asthma and chronic obstruction airway disease
Health Technology Assessment
(2001) - et al.
Experimental measurement and empirical modeling of the regional deposition of inhaled particles in human
Journal of Independent Hygiene Association
(1980) - et al.
Respiratory deposition patterns of salbutamol pMDI with CFC and HFA-134a formulation in a human airway replica
Journal of Aerosol Medicine
(2001) - et al.
Particle deposition in a cast of human oral airways
Aerosol Science and Technology
(1999) - et al.
In vitro monodisperse aerosol deposition in a mouth and throat with six different inhalation devices
Journal of Aerosol Medicine
(2001)