The Relative Influence of Atomization and Evaporation on Metered Dose Inhaler Drug Delivery Efficiency

Abstract

Factors influencing the delivery efficiency from HFA-134a MDIs were examined theoretically and experimentally. The time required for evaporation of HFA-134a and ethanol droplets were theoretically calculated. HFA-134a droplets were shown to evaporate approximately seven times faster than ethanol droplets of the same size, even though HFA-134a droplets cool to approximately 78 degrees below ambient temperature during evaporation. MDI delivery efficiency was experimentally shown to decrease with increasing ethanol concentration, however, the corresponding decrease in vapor pressure was not the primary variable responsible for the decreased efficiency. Rather, this was shown to be primarily due to the increased time required for the droplets to evaporate as ethanol concentration increased. Droplets that evaporate slowly remain for a longer period in the size range that is more likely to deposit via turbulent deposition in the actuator mouthpiece or USP Inlet during cascade impaction tests. Tests with experimental MDIs using alternative cosolvents confirmed that MDI delivery efficiency is much more sensitive to the time required for evaporation of the droplets than on the formulation vapor pressure or the size of the atomized droplets. This indicates that factors affecting the evaporation of an MDI aerosol play a larger role in determining MDI delivery efficiency than do atomization effects.

Bridging the Gap Between Science and Clinical Efficacy: Physiology, Imaging, and Modeling of Aerosols in the Lung

“…(25)(26)(27) Unfortunately, DPIs and pMDIs use of low inhalation flow rates to reduce inertial impaction is typically compromised by the requirement of reasonably high flow rates needed to fluidize and disaggregate dry powders, (28,29) or by complex interaction between high-speed droplet clouds emitted from pMDIs with enveloping air flow. (19,30,31) Independent of the inhalation flow rate, patients are commonly instructed to perform a breath-hold for several seconds after inhaling, so as to allow aerosols additional time to settle under the influence of gravity in peripheral airways. (32) For nebulizers used to deliver aerosols during controlled tidal breathing, there exists greater opportunity to manipulate regional deposition patterns by varying the breathing pattern and employing the aerosol bolus technique.…”

Advances in Metered Dose Inhaler Technology: Hardware Development

“…6. The influence of valve size and nozzle orifice diameter on the fine particle fraction delivered using HFA 134a solution formulation of 0.167% (w/w) beclomethasone dipropionate and 8% (w/w) ethanol (38)(39)(40)56). The disposition of these droplets depends on a number of factors including the nature of the initial atomized spray (e.g., the initial droplet size, velocity, spray angle, and the overall plume momentum).…”

“…The expansion chamber volume, which is comprised of the volume of the actuator sump and the internal valve stem bore, can influence the ratio of propellant in the liquid and vapor phases during the atomization process (38)(39)(40)(56)(57)(58)(59) and thus has the potential to influence drug delivery. However, in practice the influence of sump volume on delivery is minimal since the sump contributes only a small fraction of the overall expansion chamber volume (46).…”

The Formation of Aerosol Particles from Solution-Based Pressurized Metered Dose Inhalers and Implications of Incomplete Droplet Drying: Theoretical and Experimental Comparison

“…Furthermore, the influence of cosolvents on vapor pressure and aerosol generation have been studied by a number of researchers (Vervaet and Byron 1999;Stein et al 2002;Stein and Myrdal 2004) including cosolvent evaporation on the final median aerodynamic diameter and the influence of drying time and temperature (Stein et al 2002;Haynes et al 2004;Stein and Myrdal 2004;Stein and Myrdal 2006). Here, we focus on the influence of nonvolatile components on the final "maturated" particle diameters collected on cascade impactor stages and compare empirically driven theoretical models with experimental measurements at both ambient and elevated temperatures.…”