Aerosol Administration Biological Factors

Factors that also govern the therapeutic effect are the anatomy and physiology of the individual and diseases of the lung. These are uncontrollable variables that are important to be aware of. The lung divides dichotomously over 23 generations until it reaches the alveolar sacs. There are 300 million of these covering more than 140 m2. The conducting airways are covered with smooth muscle and are innervated. Specialized cells produce mucus, and others carry cilia that transport the mucus to the trachea, where it exits and is swallowed. The purpose of these features of the lung is to prevent the entry of particulates and to maintain conditions suitable for gaseous exchange. This ensures that blood gases are maintained within prescribed limits. Thus, the pharmaceutical formulator is trying to overcome the natural housekeeping of the lung. It has been shown that the slow breathing in conjunction with a 10-sec breath hold gives improved deposition [218,219]. Why is this the case? Breathing slowly subjects particles to lower speeds, and, thus, they have less inertia. The likelihood that these particles will encounter a surface and impact in the mouth, throat, and upper airways is reduced, increasing their potential to deposit in the lower airways. At least one report suggests that the speed of inhalation may not be a significant factor [220]. Deep breathing in conjunction with breath holding has been correlated with increased aerosol persistence in the lung [219]. The breath hold allows a number of things to occur: Those particles that escape inertial impaction will be subject to sedimentation, failing under gravity, or to diffusion, random motion as a function of collisions with gas molecules. Each of these phenomena can transport the particles to a surface, where they will deposit. Thus, breath holding allows further deposition of aerosol particles that might otherwise be exhaled.

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