Formulation challenges of powders for the delivery of small molecular weight molecules as aerosols

Abstract

Those interested in the treatment of asthma have championed the use of dry powder inhalers (DPI) to deliver small molecular weight drug substances. One advantage of a DPI is that, unlike a pressurized metered dosed inhaler (pMDI), therapeutic administration requires minimal patient coordination to achieve inhaler actuation and drug delivery. Second, the use of a spacer is unnecessary with DPI delivery systems. Additionally, the propellant aftertaste that patients often detect following pMDI inhalation is not present with DPI systems. The major therapeutic categories of compound delivered in this manner have been ?2-adrenergic agonists, corticosteroids, and other anti-inflammatories (mast cell stabilizers and leukotriene analogs) (1). The general structures of the major therapeutic categories of drug are shown in Figure 1 (2). Most of these drugs have molecular weights less than 1?kDa. Macromolecular drug delivery to the lungs has been defined to include molecules >5?kDa, with a window of opportunity for transport through the lung between 5 and 20?kDa (3). The transition from small molecular weight to large molecular weight may arbitrarily be designated to occur between 1 and 5?kDa.