A new method to evaluate plume characteristics of hydrofluoroalkane and chlorofluorocarbon metered dose inhalers
Introduction
Metered dose inhalers (MDIs) have long been a reliable and inexpensive medication delivery form for the treatment of asthma. Two concerns raised when comparing MDIs to other inhalation devices are their relatively high throat deposition (Newman et al., 1981) and the cold-Freon effect seen in a small number of patients (Crompton, 1982, Pedersen et al., 1986). The cold-Freon effect is a result of a forceful blast of cold, liquid propellant impacting on the back of the patient’s throat. In addition to being uncomfortable for the user, this can result in an inconsistent or non-existent dose delivered to the lung. Both adverse conditions, high throat deposition and the cold-Freon effect, share a common cause: a high-velocity, forceful blast of formulation exiting the device. The forceful plume can be especially uncomfortable when using nasal devices.
With the redesign of MDIs to contain hydrofluoroalkane (HFA) propellants instead of the ozone-depleting chlorofluorocarbons (CFCs), system improvements have resulted in MDIs with much lower throat deposition (Leach et al., 1996) and qualitatively different plume characteristics, such as reduced plume force (Purewal et al., 1998).
In this paper, a new method of quantifying the force and temperature of MDI plumes is described. These measurements provide an in vitro method for determining whether an MDI exhibits the plume characteristics associated with the cold-Freon effect and high throat deposition. Several marketed products were tested, including bronchodilators, steroids, press-and-breathe, breath-actuated and nasal MDIs. Spray force measurements are shown to be a good indicator of the amount of drug deposition occurring in the throat. The effects of some MDI design changes on plume dynamics are also discussed.
Section snippets
Description of the data acquisition system
A test apparatus was developed (Fig. 1) to measure the impact force, duration and temperature of an MDI plume as would be sensed by a patient. The MDI was actuated such that the plume would strike the center of a 4.5-cm square plate (0.5 g) located 5 cm from the end of the MDI mouthpiece. A customized data acquisition system (Power Macintosh 8100/80 with NB-MIO-16L DAQ board; National Instruments, Austin, TX) captured the output from a precision miniature load cell (Model 34; Sensotec,
Evaluation of marketed products
The results show that all of the CFC products tested have forceful plumes, with forces ranging from 80 to 117 mN (Table 1). The nasal devices span an even larger range, 55–179 mN. The impact force, temperature and spray duration measurements of the steroid press-and-breathe MDIs are shown in Fig. 2. The results are shown in the form of box plots. Box plots are useful for showing the entire distribution of the data. A line is drawn across each box at the median. The bottom of the box represents
Conclusions
A new method of quantifying the force and temperature of MDI plumes has been described. This method provides an in vitro technique for determining whether an MDI exhibits the plume characteristics associated with the cold-Freon effect and high throat deposition.
Spray force and plume temperature measurements were made on marketed bronchodilators, steroids, press-and-breathe, breath-actuated and nasal MDIs. CFC and HFA products were tested. Spray force measurements ranged from 29 to 179 mN among
References (6)
Problems patients have using pressurized aerosol inhalers
Eur. J. Respir. Dis. Suppl.
(1982)- et al.
Improved lung deposition and decreased oropharyngeal deposition with a new CFC-free beclomethasone metered dose inhaler
Eur. Respir. J.
(1996) - et al.
Deposition of pressurised aerosols in the human respiratory tract
Thorax
(1981)
Cited by (105)
Deposition and Clinical Impact of Inhaled Particles in the Lung
2023, Archivos de BronconeumologiaMetered dose inhalers (MDIs)
2021, Inhaled Medicines: Optimizing Development through Integration of In Silico, In Vitro and In Vivo ApproachesA comparative analysis of changes in pMDI drug dose delivery before and after detergent coating using five antistatic valved holding chambers
2020, Journal of Allergy and Clinical Immunology: In PracticePost-inhalation cough with therapeutic aerosols: Formulation considerations
2020, Advanced Drug Delivery ReviewsEffect of delayed pMDI actuation on the lung deposition of a fixed-dose combination aerosol drug
2018, International Journal of PharmaceuticsMass Median Plume Angle: A novel approach to characterize plume geometry in solution based pMDIs
2018, International Journal of Pharmaceutics