Physicochemical Effects on Lung Disposition of Pharmaceutical Aerosols

The physical control of drug release in the airways (formulation control) and the chemical manipulation of lung disposition and longevity (by prodrug and analogue design) are both discussed as means of providing improved therapeutics for aerosol delivery. Control of drug release by physical entrapment suffers from two major disadvantages: dilution of the active with inert ingredients requires larger total doses to be delivered; and adverse immunologic reactions due to particulate insolubility may be increased by some formulation approaches. Molecular modification, to form prodrugs, analogues, or macromolecular drugs with altered airway affinities and bioavailabilities seems to offer greater promise for future therapeutic aerosols. We should be able to target inhaled drugs, temporally and spatially, by careful control of molecular characteristics.