Shape

The shape can have a profound effect on the aerodynamic behavior of particles. Perhaps the best-studied nonspherical shapes are those of elongated particles, because of the toxic effects of mineral fibers such as asbestos. It has been known that the aerodynamic diameters of particles with high axial ratios are almost independent of their length and equal to approximately two to three times the Dae of a sphere of the same density and diameter equal to the short dimension of the particle in question [22,24,25]. It is this peculiar behavior that enables even very long, thin fibers to deposit in alveoli [100, 101]. The deposition of these fibers in the peripheral lungs is enhanced by interception (see the earlier section on Interception as a mechanism of deposition); particles with compact shapes and the same Dae would be more likely to be exhaled under normal breathing conditions. It is possible to prepare drug particles with these types of shapes, for example, by control of the crystallization conditions. If the crystal growth takes place preferentially in the longitudinal direction so that the drug particles have similar thickness, then a powder with a narrow distribution of aerodynamic diameters should be obtained. This was, indeed, observed with two drugs engineered in the manner described previously [25,102,103]. Preparation of drug powders with elongated particles may, therefore, provide the means to achieve a more selective delivery, especially to the lung periphery. The modification of the shape is probably useful only for drugs that have a relatively slow dissolution rate in water. Otherwise, the original shape would change, ultimately into spherical droplets, on entry into the respiratory tract.

Traditionally, nonspherical particles have been avoided because of the potential problems with powder flow. This phenomenon has not been studied in depth, but some published work suggests that the respirable fraction of the drug obtained from a breath-driven dry powder inhaler may not depend very much on the particle shape [104].

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