Physicochemical Factors Governing Lung Deposition

A number of physicochemical properties are associated with aerosol droplets of particles, which impact on their characteristics as aerosols. The most important of these may be related to the aerodynamic properties of aerosols (6).

The size of any particle may be related to a characteristic dimension (7). As examples, visual examination allows determination of projected area diameter, surface area measurement allows determination of equivalent surface diameter, and volume displacement allows determination of equivalent volume diameter. A full discussion of particle size measurement is beyond the scope of this chapter. It is sufficient to acknowledge that the method of describing particle size most relevant to describing aerosol particles is based on the aerodynamic behavior of the particle being studied. The size may then be described in terms of the equivalent diameter of a unit-density sphere with the same terminal settling velocity as the particle being studied. The terms of an expression relating different particle diameters in terms of terminal settling velocity take the following form (8):

^ pvgD2eC(De) PogDlC(Dae) kp18T7 KolSrj where kp and k0 are the shape factors for the particle (>1) and an equivalent sphere (1), respectively; pp and p0 are the densities of the particle and a unit-density (1 g/cm3) sphere, respectively; C(De) and C{D^) are the slip correction factors for an equivalent volume and an aerodynamically equivalent sphere, respectively; De and D.^, are the equivalent volume diameter and aerodynamically equivalent (aerodynamic) diameter, respectively; and g is the acceleration due to gravity.

Equation (1) points to a number of important particle properties. Clearly, the particle diameter, by any definition, plays a role in the behavior of the particle. The particle properties of density and shape are also of significance in aerosol behavior. The shape becomes important if particles deviate significantly from sphericity. The majority of pharmaceutical aerosol particles exhibit a high level of rotational symmetry and consequently do not deviate substantially from spherical behavior. The notable exception is that of elongated particles, fibers, or needles, which exhibit shape factor Kp substantially greater than 1. Density will frequently deviate from unity and must be considered in comparing aerodynamic and equivalent volume diameters.

The slip correction factors are important for particles smaller than 1 |im in diameter, which is rarely the case for pharmaceutical aerosols. Slip correction is required for the Stokes' equation to remain predictive of particle behavior for these small particles. Therefore, assuming the absence of shape effects for particles in the Stokes' regime of flow, equation (1) collapses into the following expression:

The capacity for aerosols to take on moisture by hygroscopicity gives rise to a kinetic phenomenon of change in particle size as a function of residence time at a particular ambient relative humidity (RH). This phenomenon can best be described in terms of the relationship between saturation ratio and particle size according to the following expression (9):

\Mspnd*

where p and ps are the partial and saturation vapor pressures of water in the atmosphere, respectively; Ms and Mw are the molecular weights of the solute and water, respectively; p and y are the density and surface tension of the solution, respectively; i is the number of ions into which the solute dissociates; and dp is the particle diameter. This phenomenon is of significance, since a change in the size of particles in transit through the high-humidity environment of the lungs (99.5% RH at 37°C) will give rise to altered deposition characteristics (10,11).

Pleural cavity

Left bronchus

Masai cavity

Oral cavity

Left lung

Trachea

Larynx

Pleural cavity

Left bronchus

Masai cavity

Oral cavity

Left lung

Trachea

Larynx

Right lung

Right bronchus

Figure 1 The anatomy of the lungs showing the major airway subdivisions.

Terminal bronchioles

Right lung

Right bronchus

Figure 1 The anatomy of the lungs showing the major airway subdivisions.

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