Drug clearance, lung deposition

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. 

Newman, S.P. Newhouse, M.T. Effect of add-on devices for aerosol drug delivery deposition studies and clinical aspects. J. Aerosol Med Depositions, Clearance, and Effects in the Lung 1996, 9, 55-70. 

We have already discussed the impact of inspiratory flow rate on deposition the faster the subject inhales, the more material is deposited at bends and bifurcations in the upper and central airways, and the less material reaches the deep lung. Inspiratory flow rate may also affect the performance of inhalation systems this is particularly important in passive dry powder inhalers in which the energy of breathing is utilized to deagglomerate the formulation. Thus, for such systems, there is a contradictory requirement for the need to use high inspiratory flow rate to achieve fine particle size for deep lung delivery and yet to have sufficiently low inspiratory flow rate to avoid impaction before the drug entry to the absorptive surfaces devoid of mucociliary clearance. 

C, and sometimes referred to the elements of life, and these radioisotopes are particularly suitable for incorporating into the drug molecule, thus allowing not only the deposition of the drug, but also its absorption and clearance from the lungs to be studied. " ... 

A significant portion of drug delivered by metered-dose inhaler (MDI) or dry powder inhalation (50-90%) reaches the GI tract. The overall amount depends on how much drug is deposited in the oropharynx and swallowed and how much pulmonary deposited drug is removed from the lung by mucociliary clearance, ultimately reaching the GI tract. The oral bioavailability of the drug (F),... 

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