The factors influencing particle and droplet deposition in the lung are summarized as a preliminary to considering aerosol generation and administration.
The deposition characteristics and efficacy of an aerosol depend largely on the particle or droplet size [11-13]. The purpose for which the product will be used will dictate the most suitable particle size. Large droplets of significant mass may achieve high velocities as a result of spraying. Their momentum will carry them directly to the selected surface, for example, to the skin, where they will deposit, coalesce, and coat or coat on wiping. Smaller droplets would not have great enough momentum to pass directly to the surface and would hang in the atmosphere until, under the influence of gravity, they would deposit on any available surface. Very small particles might remain in the atmosphere for an extended period of time and present an inhalation hazard. In 1966, the Task Group on Lung Dynamics, concerned mainly with the hazards of inhalation of environmental pollutants, collated experimental and theoretical models from the literature and proposed a model for deposition and clearance of particles from the lung .
The aim was to identify the influence of particle size on deposition in different regions of the lung. In contrast to the approach of investigators in the fields of environmental health and industrial hygiene, the inhalation aerosol formulator wants the particles or droplets to be small enough to deposit in the lung [8,9]. The particles or droplets should be in a size range that allows them, suspended in air, to pass beyond the first surfaces they encounter on inspiration, those of the mouth, throat, and upper airways, and to pass to the lower airways.
The Task Group model suggested that particles larger than 10 mm in diameter are most likely to deposit in the mouth and throat. Between the sizes of 5 and 10 mm, a transition from mouth to airway deposition occurs. Particles smaller than 5-mm diameter deposit more frequently in the lower airways and, thus, would be appropriate for pharmaceutical inhalation aerosols. The Task Group model, based on nose breathing, illustrates the general principles of the relationship between particle size and lung deposition. However, it may overestimate the total deposition and the fraction of particles depositing in the alveoli by ignoring mouth breathing . Deposition in the lung is the subject of continued speculation, but it is generally accepted that the formulator should target the 1- to 5-mm range as desirable for airway deposition.
Figure 1 shows graphically the Task Group on Lung Dynamics model for lung deposition. This figure is shown to illustrate a commonly held misconception about aerosol deposition. Three regions of deposition are shown: the nasopharyngeal, tracheobronchial, and pulmonary regions. Particles or droplets smaller than 1 mm deposit predominantly in the tracheobronchial and pulmonary regions. Little or none of the aerosol in this size range deposits in the nasopharynx.
This often leads to the potentially erroneous conclusion that submicrometer aerosols would generally be most appropriate for lower airway deposition of pharmacologically active agents to achieve the desired therapeutic effect.
The mass of material reaching the site of action is related directly to the therapeutic effect. Small individual particles carry very little mass. These are difficult to generate in high concentrations and are subject to a varying degree, depending on particle size, to exhalation. The fraction deposited at the site of action is only of value when the total mass is equal to or exceeds the therapeutic
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