Particle mass-median aerodynamic

FIGURE 5.28 Estimated overall airway deposition as a function of initial particle size and particle hygroscopicity for particles with mass median aerodynamic diameters (MMAD) between 0.1 and 10 p.m. ° Geometric dispersion, a measure of particle size distribution, principally affects only smaller MMAD,... 

Published results on the concentration and size distribution of small particles in mainstream smoke vary widely, with concentrations ranging from 107 to 1011 cm-3 and with NMAD (number median aerodynamic diameter) ranging from 0.2 to 0.7 fim (Ishizu et a/., 1978). The MMAD (mass median aerodynamic diameter) of undiluted mainstream smoke particles ranges between 0.93 and 1.00 finl (Langer and Fisher, 1956 Holmes et a/., 1959). Lower values of the MMAD for diluted mainstream smoke, which decreased with degree of dilution, are reported by Hinds (1978). However, the particle size distributions for mainstream smoke appear to have little relevance to its retention and distribution in the lung, for reasons discussed below. Note that the concentration of tars in mainstream smoke is about 1,000 times that of air in smoke-filled rooms. 

Fig. 1. Deposition of inhaled particles of different sizes (mass median aerodynamic diameters) in the three regions of the respiratory tract. Each shaded area indicates the variability of deposition when the aerosol distribution parameter, o, (geometric standard deviation) was varied from 1.2 to 4.5. The assumed tidal volume was 1450 cm3. (Reproduced from Health Physics, vol. 12, pp. 173-207,1966 by permission of the Health Physics Society).

Both from deposition studies and force balances it can be derived that the optimum (aerodynamic) particle size lies between 0.5 and 7.5 pm. Within this approximate range many different subranges have been presented as most favourable, e.g. 0.1 to 5 pm [24], 0.5 to 8.0 pm [25], 2 to 7 pm [26] and 1-5 pm [27-29]. Particles of 7.5 pm and larger mainly deposit in the oropharynx [30] whereas most particles smaller than 0.5 pm are exhaled again [31]. All inhalation systems for drug delivery to the respiratory tract produce polydisperse aerosols which can be characterized by their mass median aerodynamic diameter (MMAD) and geometric standard deviation (oq). The MMAD is the particle diameter at 50% of the cumulative mass curve. 

Minimal data are available from typical inhalation studies in laboratory animals to allow evaluation of extent or dose-dependency in inhaled arsenic absorption. Beck, Slayton and Farr (2002) reported a study in which rabbits were exposed to 0.05, 0.1, 0.22, or 1.1 mg m-3 of arsenic trioxide 8 hours/day, seven days/week for eight weeks. The particle size (mass median aerodynamic diameter, MMAD) ranged from 3.2 to 4.1pm. On the basis of minimal elevation of inorganic arsenic in plasma until exposure levels were at or above 0.22 mg m-3, the authors concluded that systemic uptake of arsenic trioxide following inhalation exposure was low and did not contribute significantly to body burden until relatively high levels of exposure were achieved. 

Aerodynamic diameter Particles suspended in gases typically have irregular shapes. The aerodynamic behavior of an irregularly shaped particle may be modeled with an idealized sphere of uniform composition. The diameter of the sphere is the aerodynamic diameter (compare with mass median aerodynamic diameter). 

Mass median aerodynamic diameter A measure of particle size related to its mass. The aerodynamic diameter of an aerosol, where 50% of the mass of the aerosol has particles with larger aerodynamic diameters and 50 % has smaller diameters. 

Can failures occur from time to time. The release of fission products from them depends on the temperature and type of fuel. If the fuel is uranium metal, as in the Windscale and Magnox reactors, and the can fails, the uranium will oxidise in air or C02. In laboratory experiments, the mass median aerodynamic equivalent diameter (MMAD) of the particles produced by oxidation of uranium increased from about 40 ptm when the temperature of oxidation was 600°C to 500 jum at 1000°C (Megaw et al., 1961). At high temperature, a coherent sintered oxide layer formed on the uranium and this hindered the formation of particles. 

The various pharmacopoeias outline appropriate methods for aerodynamic assessment of particle size distribution. The USP defines the size distribution through mass median aerodynamic diameter (MM AD) and geometric standard deviation (GSD). None of the pharmacopoeias specify a requirement for particle size. However, the particle size specifications that are set should be appropriate for the intended use of the product. For example, if the particles are intended to reach the deep lung, the MMAD of particles exiting the... 

Aerosol properties, such as particle size distribution, aerosol velocity, and hygroscopicity, affect aerosol deposition in the human lungs. Aerosol size distribution, including mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD), is one of the most important variables in governing the site of droplet or particle deposition in the lungs. ... 

Pulmonary deposition of an aerosol preparation is determined primarily by its size. Aerosols with a mass median aerodynamic diameter of 1-5 xm produce the best therapeutic results and are the target particle size for inhalation therapy. These small particles penetrate deep within the respiratory tract to ensure drug deposition in peripheral airways. The cross-sectional area (cm ) of the lung increases dramatically at the level of the respiratory zone therefore, the velocity of gas flow during inspiration rapidly decreases at this level. Moderate-sized particles (5-10 (xm) frequently settle out by sedimentation in larger more central airways because the velocity of gas falls rapidly in the region of the terminal bronchioles. 

The FisoNeb and Pulmosonic nebulizers both operate at a frequency of 1.3 MHz that generates a mass median aerodynamic diameter (MMDA) of 4-6 pm [9,10]. The Pulmosonic nebulizer has been reported not to deliver many particles smaller than 2 pm and, therefore, is unsuitable for pentamidine administration [10]. The Portosonic (DeVilbiss) device is a 2.3-MHz ultrasonic nebulizer and may offer the combination of less than 2-pm MMAD and a high output. In any study using ultrasonic nebulizers, the output and particle size of each device need to be periodically sampled, because the frequency of the piezoelectric crystal may alter with age [10]. Any MMADs between 0.5 and 2 pm are available. The Respirgard nebulizer II has one-way valves that control a drug reservoir, allow entrainment of room air in patients whose minute ventilation is... 

Unlike the physical diameter, the is a concept incorporating the size, shape and density of particles [2] and so the pharmaceutical performance of a powder or droplets for pntmonary delivery wonld be defined by the mass median aerodynamic diameter (MM AD) of the particles. MM AD is the equivalent aerodynamic diameter in which 50% of the powder mass falls below [4]. Therefore, the MMAD is representative of the aerodynamic particle size of an aerosol formulation. An MMAD of <5 pm is desirable for deep Inng delivery. 

Thus, Eqs. (2) and (3) enable us to convert the volume-equivalent particle size distribution into aerodynamic-equivalent distribution for any flow regime. The characteristic mean diameters are dy (volume geometric) and (volume aerodynamic). Although dp is numerically close to the mass-median aerodynamic diameter (MMAD) often used for the aerosols, it is better defined for asymmetrical distribution, so often observed for respiratory powders. 

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