Aerosols respirable fraction

TB Martonen, I Katz, K Fults, AJ Hickey. Use of analytically defined estimates of aerosol respirable fraction to predict lower lung deposition. Pharm Res 9 1634-1639, 1992. 

In an attempt to increase the amount of particles retained in the lungs, large porous particles with low density (p < 0.1 g/cm2) have been designed (Edwards et al. 1997). The particles were composed of 50% lactide and 50% glycolide. Porous and nonporous particles loaded with testosterone were aerosolized into a cascade impactor system from a dry powder inhaler (DPI) and the respirable fraction was measured. Nonporous particles (d = 3.5 pm, p = 0.8 g/cm3) exhibited a respirable fraction of 20.5 3.5%, whereas 50 + 10% of porous particles (d = 8.5 pm, p = 0.1 g/cm3) were respirable, even though the aerodynamic diameter of the two particle types were nearly identical. Porous particles as a consequence of their large size and low mass density can... 

Thus only aerosols < 5 pm in diameter show efficient penetration into the lungs. The respirable fraction of a therapeutic aerosol is often quoted as the percentage of drug present in aerosol particles less than 5 fim in size. 

Example 8.6 An aerosol made up of unit-density spheres is lognormally distributed with a geometric mean diameter of 2.0 pm and a geometric standard deviation of 2.2. Calculate the respirable fraction of this aerosol as sampled by a sampler which follows the BMRC curve and a sampler which follows the ACGIH curve. 

For this comparison the aerosol is broken down into 15 size increments, as shown in Table 8.1. Respirable fraction is considered to be the fraction of particles falling into the respirable category as defined above. Hence the respirable fraction in a size interval is the product of the fraction in that size interval and the percentage respirable for that size interval as defined either by the ACGIH or BMRC. The overall respirable fraction is the sum of these products over all size intervals. 

During the 1991 Gulf War (Operation Desert Storm), it is estimated that 300 tons of DU were used in the aircraft rounds and tank-fired shells in Kuwait and southern Iraq over an area of 20,000 km (Bern and Bou-Rabee, 2004). Studies have shown that DU penetrators hitting armored targets convert 17-28% of a projectile s mass into DU aerosols (Bern and Bou-Rabee, 2004 Force Health Protection Readiness Policy Programs, 2008 Harley et al, 1999 Parkhurst, 2003). Of these aerosols, 83% are S-type (S for slow dissolution) oxides, while 17% are M-type (M for medium dissolution) oxides, and the respirable fraction... 

Recently, Bustami et al. have investigated the feasibility of the ASES (aerosol solvent extraction system) process to generate microparticles of proteins for inhalation. Protein powders generated were of particle size 100nm-500nm. In vitro performance showed 65, 40, and 20wt.% respirable fraction for lysozyme, albumin, and insulin, respectively. Little or no loss of monomer content was observed for these proteins. 

Surfactant concentration-drug combination gave the greatest respirable fraction of the aerosols. ... 

The MDI may provide up to several hundred actuations, each containing typically from about 10 to 500 pg of drug dispersed in a 25 to 100 pi metered volume of liquid. The discharged liquid undergoes flash evaporation of the propellant to produce a finely dispersed aerosol spray. The deposition, and hence the clinical efficacy, are critically dependent on the mass of inhaled particles, which must have an appropriate aerodynamic size, typically less than 5 pm, to be deposited in the lungs (the respirable fraction). ... 

In addition, because the respirable fraction of the aerosol cloud that is emitted from a suspension MDI is highly dependent on the geometric size of the bulk drug particles (i.e., the aerodynamic size cannot be smaller than the initial geometric size of the primary particles), there are limitations to the respirable fraction that can be achieved. As such, solution formulations offer opportunities to circumvent some of these problems, particularly with drugs that have a significant solubility in the volatile propellants, where greater respirable fractions can be obtained [36]. 

Experimental studies of oil shale combustion fly ash aerosol under simulated day-time and night-time atmospheric-like conditions were performed at NICPB in a 190m outdoor Teflon film chamber. Continuous monitoring of particle size distributions is performed with various optical and electrical devices. The respiration fraction of particles, which contributes most to the health effects of the aerosols, is studied quantitatively. 

For inhalation treatment of respiratory diseases, a pharmaceutical DNase I aerosol is on the market. Pulmozyme is a sterile solution for respiratory use at a concentration of 1000 Genentech Units/mL [22]. It contains 1 mg/mL rhDNase, sodium chloride as a tonicity modifier, calcium chloride as a stabilizer, and water for injection. Since deamidation is rapid at high pH and aggregation occurs at low pH, a nearly neutral solution (pH 6.3) is required. It is administered by means of a compressed air-driven nebulizer. Each 2.5-mL single-unit ampule will deliver 2.5 mg of rhDNase to the nebulizer chamber. The efficacy of DNase inhalation therapy largely depends on the aerosol quality and characteristics, which determine the respirable fraction. Significant differences were found between the different aerosol drug-delivery systems [68,81]. 

The problems associated with conducting inhalation excretion studies with test animals are demonstrated by Langard and Nordhagen ( ), where rats were exposed to zinc chromate aerosol with a respirable fraction of 76%. The rats were exposed to the aerosol using two different techniques the whole body was exposed in the first situation, and the fur coat was protected from direct exposure to the aerosol in the second situation. The results are shown in Table III. 

Program faculty members are developing an automated cascade impactor for collection of task-based size distribution data of beryllium-containing aerosols. Based on the size distribution, the fraction of beryllium-containing aerosol penetrating a respirator and the inhalation and deposition in different regions of the lungs can be estimated. 

Improved control devices now frequently installed on conventional coal-utility boilers drastically affect the quantity, chemical composition, and physical characteristics of fine-particles emitted to the atmosphere from these sources. We recently sampled fly-ash aerosols upstream and downstream from a modern lime-slurry, spray-tower system installed on a 430-Mw(e) coal utility boiler. Particulate samples were collected in situ on membrane filters and in University of Washington MKIII and MKV cascade impactors. The MKV impactor, operated at reduced pressure and with a cyclone preseparator, provided 13 discrete particle-size fractions with median diameters ranging from 0,07 to 20 pm with up to 6 of the fractions in the highly respirable submicron particle range. The concentrations of up to 35 elements and estimates of the size distributions of particles in each of the fly-ash fractions were determined by instrumental neutron activation analysis and by electron microscopy, respectively. Mechanisms of fine-particle formation and chemical enrichment in the flue-gas desulfurization system are discussed. 

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