lipophilic film-formers, such as silicones, substantive amino-silicones, mineral oils and certain liquid oligopolymers. To the extent that they form impenetratable films across the transpirational zones, they produce effects ranging from heavy breathing to death by asphyxiation. Smokers, older people and those with respiratory problems are most vulnerable. In many cases hospitalized patients can be successfully treated with oxygenated air for a few days until the films fade away. The sustained inhalation of very finely divided silicone sprays has caused the death of workers in the U.S., Japan, Europe and probably other areas. In one well known example, dozens of people were employed in the rehabilitation of worn leather “bomber jackets,” working under essentially non-ventilated conditions. The sprays are thought to have contained about 95% propellant, capable of producing particles in the respirational range of about 1–8 micron diameters. The efficiency of the pulmonary protective system is recognized by pharmaceutical metered dose inhalant (MDI) marketers. In one recent study, the Salbuterol active ingredient was milled to a mean particle size of 2.73 microns and administered nasally using a formula that also contained a bit of excipient and about 96% HFC-134a propellant. The study showed that only about 8% to 11% of the drug actually impacted the final bronchioles and alveolar target areas. These were later confirmed using radioactive analysis. It is well known that Salbuterol (and many other MDI drug substances) very quickly absorb moisture from the virtually 100% humidity in the lungs. The particles then expand, but still remain under about seven microns in mean diameter, and thus in the alveolar penetrating range. Particle Size Considerations Most particle size analyses assume that diameters apply to essentially round spheres of constant dimensions. This can sometimes be misleading. By about 1940, the aerosol industry recognized that sprayed particles were emitted in a variety of diameters. For instance, a spray with a mean diameter of 30 microns would contain individual particles ranging from 15 to 45 microns, and with 1–2% of the weight consisting of particles from 10–15 and 45–50 microns. The first attempts to define particle size distributions came from M.L. Yoeman, about 1945. He sprayed various products downward onto petrolatum-filmed glass plates and measured the diameter of about 200 of the micro-craters they produced. These were then converted mathematically into particle size. This crude mode of analysis was greatly improved by scientists at the Battelle Memorial Institute with their Cascade Impactor, introduced in 1956. Sprayed particles were wafted at a fixed air speed through up to about 14 “catchplates,” each more restrictive than the previous one. The plates were then weighed to determine the percentage collected at each station. Evaporation, humidity, limited size range, shape, density and other factors have complicated the analysis, but the instrument is still used today in some laboratories. The modern standard for particle size determinations is the laser diffraction light scattering equipment provided by Malvern Instruments. Aerosols can be sprayed through a laser beam from typical distances of 7.9" (200mm) or 9.8" (250mm). At the usual initial velocities of about 26 ft/sec. (depending on particle size, pressure, etc.), the spray reaches the beam after about 0.035 sec. By this time, either most or nearly all of the (chilled) propellant will have evaporated, depending on the formulation. The solvents will evaporate more slowly. These factors have a small reducing effect on particle size. For example, if 50% of the particle weight is ethanol, which evaporates after a second or two, the particle diameter will only shrink to about 80% of the original. Aerosol valve suppliers generally have a Malvern instrument at one of their plants. A few contract fillers have one. Others are employed at such as Underwriter’s Laboratories (UL) and major marketers. Some provide data only on particles of 10 microns or larger. Others can count particles all the way down to about 0.01-micron (10 nanometers) and can be used for silicone lubricants, smoke detector testers and other aerosols with well over 90% propellant. Laser instruments give a “snap-shot” Small Particle of particle size distribution. Multiple readings are helpful if taken under various conditions—after spraying for various times, after shaking the dispenser, at different product temperatures, with several valves of the same specification and with the range of viscosities exhibited by the formulation. Flight time variations can be important in sizing work. Evaporation, deliquescence, bubble formation, spallation, change of shape, Partial and complete blockage of alveolar transpirational sites by a film-former. Schematic drawing to show the operation of the Battelle Cascade Impactor. Large Particle Large Jet Small Jet 24 Spray March 2016
Spray March 2016
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