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

Area of Science:

• Pharmaceutical Sciences
• Biomedical Engineering
• Respiratory Medicine

Background:

• Regional deposition of inhaled medicines is crucial for efficacy and influenced by inertial impaction.
• Current methods often convert impaction parameter cutoffs to size cutoffs at fixed flow rates, potentially causing interpretation errors.
• Reliance on size metrics like mass median aerodynamic diameter (MMAD) can lead to misconceptions in understanding drug deposition.

Purpose of the Study:

• To propose and validate the use of impaction parameter cutoffs (MMIP) over size cutoffs for analyzing respiratory drug deposition.
• To demonstrate how MMIP metrics improve the prediction of in vivo deposition across various conditions.
• To advocate for realistic flow profiles and anatomical models in in vitro testing for better in vitro-in vivo correlations.

Main Methods:

• Utilized impaction parameter cutoffs (MMIP and FPF_S3-F) instead of traditional size cutoffs (MMAD and FPF_<5µm).
• Employed realistic inspiratory flow profiles rather than fixed flow rates.
• Incorporated more anatomically relevant throat models for impactor testing.

Main Results:

• Metrics based on impaction parameter cutoffs (MMIP) provide a more accurate prediction of in vivo deposition trends compared to size-based metrics.
• Using MMIP eliminates the need for fixed flow rates, enabling the use of realistic inspiratory flow profiles.
• Improved in vitro-in vivo correlations were achieved by integrating MMIP metrics and realistic testing conditions.

Conclusions:

• Shifting from size-based to impaction parameter-based metrics enhances the interpretation of respiratory drug delivery device performance.
• The proposed methodology supports Quality by Design principles by enabling better early-stage formulation and device development.
• Accurate in vitro-in vivo correlations derived from MMIP metrics are essential for optimizing inhaled medicine delivery.