Fine Particle Fraction: The Good and the Bad.

Abstract

Fine particle fraction (FPF) is defined in general terms as the fraction or percentage of the drug mass contained in an aerosol cloud that may be small enough to enter the lungs and exert a clinical effect. An aerodynamic diameter of 5 μm represents the approximate border between "fine" and "coarse" particles, but there is no universally agreed upon definition of FPF in terms of an aerodynamic particle size range. FPF alone does not adequately describe a heterodisperse aerodynamic particle size distribution, and it needs to be combined with another measure or measures indicating the width of the distribution. When determined using techniques specified in United States and European Pharmacopeias, FPF is measured by cascade impactors that have straight-sided ninety degree inlets through which air is drawn at a constant rate. It is not the purpose of in vitro tests to predict in vivo behavior, and FPF is primarily a measure of aerosol quality. Despite this, FPF broadly predicts the amount of drug from an inhaler device depositing in the lungs, but it systematically overestimates whole lung deposition and may not correctly predict the relative lung depositions for two inhalers of different types. The relationship between FPF and both drug pharmacokinetics and clinical response is incompletely understood at the present time, and more studies are needed to investigate these relationships. Modifications to impactor technologies, including inlets that mimic the human extrathoracic airways and the use of realistic breathing patterns, would be expected to improve the predictive power of in vitro tests for drug delivery in vivo.