Stability testing aerosols

Thermal stability testing showed that the reaction mixture could decompose exothermically with self heating occurring on the plant scale from 145°C (the boiling point of the mixture is about 160°C). Decomposition of the reactant mass would lead to a runaway reaction with the generation of a toxic and irritant gas. This would be vented safely, as far as protecting the reactor from overpressure is concerned, by the emergency relief vent, but would cause a serious toxic and corrosive aerosol emission. 

Kohler (207) discusses problems with reproducibility of an inhaled dose with a Pari Provocation test Device 1 nebulizer as an example. The author eon-cludes that up to 50% of the volume loss in a nebulizer is due to vapor losses and, from this, it is clear that the intrabronchial dose cannot be caleulated aeeording to the weight loss of the nebulizer. It is also clear that evaporation of the nebulized solution leads to an increase in the eoncentration of the test substance, especially toward the end of the evaporation proeess. Kohler also concludes that, for the Pari inhalation device, a slower inhalation maneuver gives better reproducibihty, and that reservoirs that store the aerosol before inhalation increase reproducibility, for they stabilize the aerosol by vapor saturation. 

The Britter and McQuaid10 model was developed by performing a dimensional analysis and correlating existing data on dense cloud dispersion. The model is best suited for instantaneous or continuous ground-level releases of dense gases. The release is assumed to occur at ambient temperature and without aerosol or liquid droplet formation. Atmospheric stability was found to have little effect on the results and is not a part of the model. Most of the data came from dispersion tests in remote rural areas on mostly flat terrain. Thus the results are not applicable to areas where terrain effects are significant. 

The inclusion of the a routine microbial limit test in a marketed product stability protocol depends on the pharmaceutical dosage form. Typically, the test would be used only for nonsterile products, especially oral liquids, nasal sprays, and topical liquids, lotions, and creams that have sufficient water activity to support the growth of microorganisms. In contrast, tablets, powder- and liquid-filled capsules, topical ointments, vaginal and rectal suppositories, nonaqueous liquids and inhalation aerosols with a water activity too low to allow for the product to support the growth of microorganisms would not be routinely tested. 

Lowenthal, D. H., K. R. Wunschel, and K. A. Rahn, Tests of Regional Elemental Tracers of Pollution Aerosols. 1. Distinctness of Regional Signatures, Stability during Transport, and Empirical Validation, Environ. Sci. Techno ., 22, 413-420 (1988). 

The Mitex filters are also made of Teflon, but have no backing material. A 5 ym pore size Mitex filter was used because it is the smallest pore size available. Each of these is available in 37mm diameter disks and can be used in convenient, 3-piece polystyrene filter holders (Millipore Aerosol Monitors). Extracts of samples collected on these filters were tested for stability by conducting the following experiments. 

End-use stability and performance are the net result of good design and colorant selection. In the case of colorants, end-use stability and performance most often refer to ability to resist attack by chemicals, solvents, heat, weather, and gases and aerosols found in the product environment. The resistance of a plastic product to attack by any of these in a laboratory can produce definitive results. In combination, these elements are difficult to quantify not only in the laboratory but also in actual exposure to them. Thus, testing throughout a project from start to finish is vital to the technical and commercial success of that plastic product. In this chapter the focus is on the role the colorants play in the success. 

Specimen tubes should be centrifuged with stoppers in place. Closure reduces evaporation, which occurs rapidly in a warm centrifuge with the air currents set up by centrifugation. Stoppers also prevent aerosolization of infectious particles. Specimen tubes containing volatiles, such as ethanol, must be stoppered while they are spun. Centrifuging specimens with the stopper in place maintains anaerobic conditions, which are important in the measurement of carbon dioxide and ionized calcium. Removal of the stopper before centrifugation allows loss of carbon dioxide and an increase in blood pH. Control of pH is especially important for the enzymatic measurement of acid phosphatase, which is labile under alkaline conditions engendered by CO2 loss. Indeed, once the serum is separated for acid phosphatase tests, a tablet of disodium citrate should be added to stabilize the pH at about 6.2. 

In practice, perfumery companies test all products at 0-4 °C, 20 or 25 °C and 37 °C (or 40 °C) for 12 weeks as a minimum standard. In addition, tests at 45 or 50 °C may be used (except for aerosols, which could explode) if quick results are required, or if it is likely that the product will experience these sort of conditions during its life-cycle. Stability for 4 weeks at 50 °C is considered acceptable in many instances, but signs of instability should be taken as precautionary only, particularly if the samples still appear satisfactory at 37 or 40 °C. This is because certain chemical reactions could occur at these high temperatures that could not happen at ambient temperatures or even at 37 °C. Note that 37 °C has become an accepted standard because many cosmetic chemists believe there is a temperature barrier , corresponding to the heat of the human body, above which chemical reactions are accelerated beyond that predicted by the Arrhenius equation. 

Allergen inhalation tests are primarily a research tool. For this reason, the principles of standardization have been developed to try and assure the best possible intraindividual reproducibility. The principles of standardization outlined below are based on both scientific and empirical concepts. Standardization encompasses technical aspects (aerosol generation, inhalation, measurement of response) and nontechnical or subject-related aspects, the latter designed to assure patient stability. 

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