Comparison of Nebulized Particle Size Distribution with Malvern Laser Diffraction Analyzer Versus Andersen Cascade Impactor and Low-Flow Marple Personal Cascade Impactor

Abstract

Particle size of nebulized aerosols can be measured directly using laser diffraction or by evaluating aerodynamic properties by cascade impaction. As of today, there are no generally accepted standards for measuring particle size distribution from nebulizers. Laser diffraction has been questioned because of potential evaporative losses of the small particles at the edge of the plume, causing an apparent shift in the particle size distribution and thus a larger mass median diameter (MMD). When particle-sizing wet aerosols, cascade impaction may give rise to an apparent shift in the distribution, resulting in a smaller mass median aerodynamic diameter (MMAD) due to evaporative losses of aerosol droplets as they enter the impactor at ambient temperature. The modified low-flow Marple 296 Personal Cascade Impactor (MPCI) is currently being proposed as the European standard for wet aerosol analysis to minimize evaporative losses during sampling. The present study compared the particle size distribution of salbutamol and sodium cromoglycate aerosols nebulized by the Pari LC Star, using laser diffraction (Malvern Mastersizer X; MMX) and cascade impaction (Andersen Cascade Impactor [ACI] and the commercially available MPCI), which was either at ambient temperature or cooled to the nebulized aerosol temperature (10 degrees C). MMDs obtained with the MMX were virtually identical to the MMADs measured with both impactors when cooled with no significant differences in geometric standard deviation (sigma(g)). When the impactors were operated at ambient temperature, MMADs were smaller (18 to 30%) with a significantly larger sigma(g) (p < 0.05) compared to the MMX. These findings suggest that droplet distribution data for wet aerosol where evaporation process has not been minimized must be viewed with caution. There was no evidence suggesting a significant evaporative loss of small droplets from the edge of the plume during laser particle sizing. The MPCI does not minimize evaporative losses of aerosol particles during sampling.

Determination of Reference Ultrasound Parameters for Model and Hydrofluoroalkane Propellants Using High-Resolution Ultrasonic Spectroscopy

“…Using linear regression, the ultrasonic velocity of HPFP at 25°C was calculated to be 614.02 m/s, with a temperature velocity increment of −3.77 m s −1°C−1 . This decline in ultrasonic velocity is consistent with temperature ramps conducted on pure hydrocarbons media, indicating that the compressibility of HPFP increases with temperature, resulting in a decrease in ultrasonic velocity (5).…”

“…The majority of the techniques used to analyze characteristics such as particle size and stability are "indirect", e.g. light diffraction (1)(2)(3)(4)(5), light scattering (6,7), post-actuation studies (8)(9)(10) or the use of model propellant (11). Despite their lowtech nature, visual and manual sedimentation analytical methods are still widely employed (12)(13)(14).…”

Respiratory System Deposition with a Novel Aerosol Delivery System in Spontaneously Breathing Healthy Adults

“…The in vitro respirable fraction depends only on measured particle size distribution 21 and is based on the probability that this fraction of the mass of the particles within a certain size range will, if entering the upper airway, deposit below the vocal cords. Based on previous literature, [22][23][24] the in vitro size cutoff was Յ 5 m, and the in vivo agreement is support for this choice.…”

Non-impactor-Based Methods for Sizing of Aerosols Emitted from Orally Inhaled and Nasal Drug Products (OINDPs)

“…However, it is more usual to draw the sample from these products, or from nebulizers through a measurement cell using a vacuum pump, as greater control of the flow of the aerosol through the measurement zone is possible (43). There are several published studies in which various LD systems have been compared with the multi-stage cascade impactor, using the latter as a validation aid, since LD neither determines API mass nor aerodynamic diameter directly (43)(44)(45)(46). An important finding from these investigations was that virtually identical droplet size distributions are obtainable with either technique when sampling aqueous-based solutions, provided precautions are taken to minimize evaporation of the aerosol during sampling (including heat transfer from the impactor to the droplet aerosol), as well as losses associated with different sampling geometries for the CI and LD systems.…”