Pulmonary drug delivery clearance

The pharmacokinetic/dynamic parameters involved in pulmonary drug delivery of glucocorticoids have been reviewed. Among these, low oral bioavailability, high pulmonary deposition, pronounced clearance, and sustained pulmonary release are the most important parameters to be considered. 

Drug delivery to the respiratory tract has been characterized in the past decade by an increase in knowledge of drug droplet or particle manufacture, behavior, aerosol dispersion, lung deposition and clearance. The number of diseases for which aerosol therapy may be applicable has increased dramatically. The pharmaceutical scientist is no longer limited to pulmonary diseases as therapeutic targets. Substantial progress has been made in every area of pharmaceutical aerosol science, and it is anticipated that this will ultimately lead to many new therapies. 

Another issue is reproducibility. The formulation may work perfectly in an in vitro test system, but the dosage form requires aerosolization, and lung deposition is a function of the characteristics of the aerosol (dose, mass concentration, droplet/particle size, etc.) and the nature of the inspiratory maneuver, a factor that the patient has control over. These factors can influence performance to a far greater extent than can be built into a particle, and thus the term controlled does not seem a defensible objective for pulmonary delivery. The vagaries of the deposition profile and of the amount that will deposit also imply that sustaining a certain drug concentration is a difficult proposition, but the loosest definition extended release, seems an acceptable goal within the boundaries set by the clearance mechanisms. 

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