Physiological Pharmaceutics

240 Physiological PharmaceuticsFigure 10.10 Dependence of deposition of particulates on particle sizeimpact in the upper airways and are rapidly removed by mucociliary clearance. Smallerdroplets which escape impaction in the upper airways, in the range 0.5 to 5 µm, aresufficiently large to deposit by sedimentation, while those below 0.5 µ m are too small tosediment efficiently and migrate to the vessel walls by Brownian motion. The optimumdiameter for pulmonary penetration has been determined by studies of the deposition ofmonodisperse aerosols to be 2 to 3 µm 26 . Smaller particles are exhaled before sedimentationcan occur, although breath-holding can improve deposition in these cases. Extremely smallaerosols, below 0.1 µm, appear to deposit very efficiently through Brownian diffusion to thevessel walls, but such fine aerosols are extremely difficult to produce.Often the particle size does not remain constant as an aerosol moves from the deliverysystem into the respiratory tract. Volatile aerosols may become smaller through evaporationwhereas hygroscopic aerosols may grow dramatically. The exact relative humidity withinairways is not known, but particles produced from dry atmospheric aerosols have beenfound to double in diameter when the relative humidity is increased to 98%. Particle growthdue to absorption of moisture does not appear to affect total drug deposition in therespiratory tract 27 .Air in the deep branches of the lung has been estimated to contain around 40 gwater per cubic metre. Most aerosol particles will absorb moisture to a degree thatdepends on temperature, relative humidity and the nature of the aerosol particle. Thedegree of saturation is also device dependent since aerosols formed by jet nebulizers mayhave a very low humidity, while ultrasonic nebulizers produce an aerosol with a muchhigher humidity.Thermophoresis of particles has been reported to occur in the lung. This is amovement of droplets towards the cooler areas due to the more rapid Brownian motionin the warm areas. It is thought that this effect is small and short-lived in the lung, sincethe air in the deeper airways is rapidly brought to thermal equilibrium. Finally,electrostatic effects, in which the droplets are attracted to the vessel walls by virtue of asurface charge interaction, are thought to be unimportant in pulmonary delivery, due tothe high humidity.