ABSTRACT
Conventional in vitro tests to assess the aerodynamic particle size distribution (APSD) from inhaler devices use simple right-angle inlets ("mouth-throats", MTs) to cascade impactors, and air is drawn through the system at a fixed flow for a fixed time. Since this arrangement differs substantially from both human oropharyngeal airway anatomy and the patterns of air flow when patients use inhalers, the ability of in vitro tests to predict in vivo deposition of pharmaceutical aerosols has been limited. MTs that mimic the human anatomy, coupled with simulated breathing patterns, have yielded estimates of lung dose from in vitro data that closely match those from in vivo gamma scintigraphic or pharmacokinetic studies. However, different models of MTs do not always yield identical data, and selection of an anatomical MT and representative inhalation profiles remains challenging. Improved in vitro - in vivo correlations (IVIVCs) for inhaled drug products could permit increased reliance on in vitro data when developing new inhaled drug products, and could ultimately result in accelerated drug product development, together with reduced research and development spending.