Aerosols physical stability

The droplet size of topical aerosol sprays does not need to be carefully controlled, and the dose usually is not metered as in inhalers. The spray may be used to apply the drug to the skin (topical aerosol) or mouth (lingual aerosol) and the functionality of the sprayer should be addressed. The drug product has no contact with the cap and short-term contact with the nozzle. A topical aerosol may be sterile or may conform to acceptance criteria for microbial limits. However, the physical stability of aerosols can lead to changes in total drug delivered per dose and total number of doses that may be obtained from the container. 

Elhissi, A. M. A., Faizi, M., Naji, W. F., Gill, H. S., and Taylor, K. M. G. 2007. Physical stability and aerosol properties of liposomes delivered using an air-jet nebulizer and a novel micropump device with large mesh apertures, Int. J. Pharm. 334 62-70. 

Most product information leaflets for nebulised medicine formulations discourage mixing of marketed formulations but in practice different formulations are frequently mixed to increase patient comfort. Particularly CF patients tend to combine medicines in order to save time as well as to overcome adverse effects (e.g. bronchoconstriction) of one active substance (antibiotic) by another (salbutamol). They also tend to refill their nebuliser with a new medicine without emptying and cleaning the nebuliser between the administrations. Relatively little has been reported in the literature about the compatibility of medicine mixtures, however, and interactions may be expected with respect to chemical and physical stability, droplet size distribution of the aerosol, nebuliser output rate and therapeutic effect. From a survey of studies on chemical stability, it is known that particularly domase alpha (Pulmozyme ) is incompatible with many other nebulised medicine formulations due to inactivation of the protein [63]. Additives, like stabilisers that work well in some medicine formulations, may be incompatible with other preparations and induce cloudiness... 

R ardless of the chemistry, there are some physical constraints on aerosol-gas interactions. Particles must be close to or at equilibrium with respect to the surrounding vapor to exist in air for any substantial period. Thus, the partial pressure of condensed species on particles must be less than or equal to the saturation vapor pressure at atmospheric temperature for stability. As shown later in this chapter, the requirement of low vapor pressure is particularly important to the stability of organic aerosols. 

Just as with organic combustion aerosols, the chemical and physical nature of inorganic solid substrates can have a dramatic impact on the photoreactivity of adsorbed PAH. In 1980, Korfmacher and co-workers reported that BaP, pyrene, and anthracene all pho-tolyzed efficiently in liquid solution but were resistant to photodegradation when adsorbed on coal fly ash. Subsequent studies confirmed this observation and revealed that the carbon content of the ash (and the associated darkening of color) is a key factor in establishing the photostability of these PAHs. Indeed, they were stabilized at relatively small percentages of carbon, e.g., 5% or less (Behymer and Hites, 1985, 1988 Yokley et al., 1986 Dunstan et al., 1989 Miller et al., 1990). 

For nebulizer and other aqueous aerosol products that use suspension systems, excipients are used to influence particle physical and chemical stability (e.g., microcrystalline cellulose for nasal sprays). The suitability of the physicochemical properties of these critical excipients should be thoroughly investigated and documented (12). Far more excipients have been included in formulations designed for nasal administration (Table 4). 

Another concern to formulators is the ingress of moisture into HFA-formulated MDIs [143], HFA propellants have a higher moisture affinity compared to the CFC propellants, especially HFA 134a. In addition, the inclusion of ethanol in some formulations increases its hydrophilicity. Moisture entering the canister can have several effects it may alter the physical or chemical stability of the formulation and aerosolization performance of HFA MDIs. Due to its lower volatility compared to... 

A simple physical relationship does not exist between synoptic measurements of wind speed and sea-salt aerosol concentrations in the marine atmosphere because of advection, hysteresis, condensation processes, and the varying stability of the marine boundary layer. In the region of the South Atlantic Ocean discussed in this chapter, the low correlation between the time series for sea-salt aerosol concentration and local wind speed is attributed to the high variability of the effects just mentioned. Removing the temporal constraint by ordering both data sets results in an extremely high (r = 0.99) correlation coefficient. This result provides promise for the... 

As it becomes increasingly probable that delivery of drugs as aerosols can be achieved readily, the focus can shift to the nature of the therapeutic agent and its physical and chemical stability in the required dosage forms. New chemical entities can be considered for delivery to the lungs to facilitate the control of pulmonary diseases or diseases that may be treated by pulmonary drug delivery. 

The former approach, attempting to measure the droplets in their fully hydrated state, has enjoyed more widespread use. Experimentally, this has been accomplished in a number of ways. The use of low-flow impactors that entrain minimal quantities of ambient air and hence maintain the quasiequilibrium humidity exiting the nebulizer is one approach (30). Adding humidified dilution air, rather than ambient air, to a high-volume cascade impactor is another. Cooling the impactor to the same temperature as the nebulizer cloud (reservoir) has also been shown to be an effective way of providing sufficient stabilization for aerosol measurement purposes (31). However, a technique that has been used extensively in conjunction with a large number of deposition studies is laser diffraction (3). As described above, this technique measures the physical diameter... 

Although many factors such as film thickness and adsorption behaviour have to be taken into account, the ability of a surfactant to reduce surface tension and contribute to surface elasticity is among the most important features of foam stabilization (see Section 5.4.3). The relation between Marangoni surface elasticity and foam stability [40-43] partially explains why some surfactants will act to promote foaming while others reduce foam stability (foam breakers or defoamers), and still others prevent foam formation in the first place (foam preventatives, foam inhibitors). Continued research into the dynamic physical properties of thin liquid films and bubble surfaces is necessary to more fully understand foaming behaviour. Schramm et /. [44] discuss some of the factors that must be considered in the selection of practical foam-forming surfactants for industrial processes. Sanders [45] provides a number of surfactant choices and formulation approached for the preparation of non-aqueous foam and non-aqueous aerosol foams. 

Polymer Degradation and Stability 33, 397-410 Kulmala, M., T. Vesala and A. Laaksonen (2000) Physical chemistry of aerosol formation. In Aerosol chemical processes in the environment (Ed. S. Spumy), Lewis Publ. Boca Raton, London, New York, Washington, pp. 23-46... 

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