Design of Dry Powder Inhalers: 1. Does Size Matter?

Regional deposition of inhaled medicines in the respiratory tract is heavily influenced by inertial impaction. Despite this, the current convention is to convert impaction parameter cutoffs on stages in impactors to size cutoffs by operating the impactor at a fixed flow rate. While such a practice has utility when using impactors as a quality control tool, a focus on size metrics (e.g., mass median aerodynamic diameter [MMAD] and fine particle fraction [FPF_<5µm]) may lead to misconceptions in the interpretation of impactor data. In contrast, using metrics based on impaction parameter cutoffs (MMIP and FPF_S3-F) enables a more accurate prediction of trends in in vivo deposition with variations in device resistance, flow rate, airway size, and other dependent variables. Using impaction parameter cutoffs also eliminates the need to run the impactor at a fixed flow rate, thereby allowing realistic inspiratory flow profiles to be utilized. This, combined with the use of more realistic anatomical throats and impaction parameter metrics, enables improved in vitro-in vivo correlations to guide early formulation and device development in the spirit of Quality by Design principles.