Understanding penetration index measurements and regional lung targeting

Radiolabeling of pharmaceutical inhalation aerosols began in the late 1970s. Since then, well over 100 studies have been published. These studies have documented lung deposition for all inhalation dosage forms; pressurized metered dose inhalers (pMDIs), dry powder inhalers (DPIs), soft mist inhalers (SMIs), and nebulizers. They have provided valuable insight into the factors that influence total and regional lung deposition. Taken globally, this collection of data has recently been used to elucidate the influence of intersubject variability in head geometry on total lung deposition, showing good correspondence between theory and experiment. The analysis reported here is an attempt to take this data set one step "deeper" into the airways and understand the relationship between P/C ratio, derived from 2D imaging, and a more anatomically relevant biological distribution within the lung, 24-h clearance. Intersubject variability in regional deposition is also analyzed, although due to the sparse nature of the reported individual data only tentative conclusions can be drawn. Many different techniques for derivation and analysis of scintigraphic data have been reported in the literature, and this leads to some difficulties when performing the "meta-analyses" reported below. In this regard it is recommended that standardization of scintigraphy techniques should be a future goal.