Particle size study of nine metered dose inhalers, and their deposition probabilities in the airways

Abstract

This study deals with the particle size measurement of nine aerosol metered dose inhalers. Calibration was made possible by the use of a laser particle velocimeter (aerodynamic Particle Sizer from TSI). The count median aerodynamic diameters (CMAD) show little variation, from 0.63 to 0.73 micron, with standard deviations (sigma g) between 1.2 and 1.8. Aerodynamic diameter aerosol diagram analysis showed multimodal mass distribution for all the tested dose inhalers. Calculations for the airway deposition probabilities (extrathoracic, tracheobronchial and alveolar) refer to the studies made by W. Stahlhofen and co-workers. As most aerosol metered dose inhalers have a predominantly bronchial therapeutic destination, the deposition at the bronchial level could be enhanced with the following parameters: inspired volume of 1500 ml, inspiratory time of 2 sec, aerosol mass median aerodynamic diameter (MMAD) of 7.5 microns, with a monodispersed distribution. The respective influences of the excipients and propellents used for the aerosolization of these dose metered inhalers are also discussed.

Comparison of Inhaled Drug Delivery in Patients With One‐ and Two‐level Laryngotracheal Stenosis

“…Unfortunately, it is difficult to determine the exact size of particles released from currently available MDIs, with several studies citing varying results. 36,54 LeBelle et al 55 and Crim et al 56 described sizes between 1.1 and 4.7 μm for cascade impactors, Dolovich 57 reported 0.05-35 μm particle sizes for most inhalers, and two other reports indicated 200 μm as the maximum particle size. 57 Our results indicate that particles 6-10 μm would be ideal for deposition at stenotic regions, thus implying that current inhalers would not deposit drugs effectively in these regions.…”

“…This is important to compare with standard drug particle sizes emitted from common inhalers. Unfortunately, it is difficult to determine the exact size of particles released from currently available MDIs, with several studies citing varying results 36,54 . LeBelle et al 55 and Crim et al 56 described sizes between 1.1 and 4.7 μm for cascade impactors, Dolovich 57 reported 0.05–35 μm particle sizes for most inhalers, and two other reports indicated 200 μm as the maximum particle size 57 .…”

“…17 Commonly prescribed inhalers with corticosteroids are primarily designed for pulmonary drug delivery and may bypass the stenosis and deposit most of their medication in the lower airway. 36,37 Targeting stenotic sites with inhaled corticosteroids or other medications has the potential to be minimally invasive, targeted, and convenient for patients. 17 Computational fluid dynamics (CFD) modeling is a useful approach to study airflow profile and drug delivery in the upper airway for important insights into the impact of stenosis on respiration and stenotic drug delivery.…”

“…Nonetheless, the effectiveness of targeting inhaled corticosteroids to the stenotic region(s) using metered dose inhalers (MDIs) and dry powder inhalers (DPIs) has not been thoroughly investigated 17 . Commonly prescribed inhalers with corticosteroids are primarily designed for pulmonary drug delivery and may bypass the stenosis and deposit most of their medication in the lower airway 36,37 …”

Orally Inhaled Drug Particle Transport in Computerized Models of Laryngotracheal Stenosis

“…In general, it is difficult to determine the precise particle size distribution that is emitted by MDIs. 33,34 Nonetheless, LeBelle et al 35 and Crim et al 36 determined the range of particle sizes of MDIs as 1.1 to 4.7 mm using a cascade impactor. LeBelle et al 35 reported the mass median aerodynamic diameter (MMAD) and geometric standard deviation (sg) of 4 inhalers to lie between 2.28 mm (sg = 2.63) and 4.13 mm (sg = 2.19).…”