Critical characteristics for corticosteroid solution metered dose inhaler bioequivalence

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Aerosol Science

Background:

• Determining bioequivalence for solution pressurized metered dose inhalers (pMDI) is challenging due to poorly defined critical product characteristics.
• Understanding non-aerodynamic properties of emitted aerosol particles is crucial for assessing biopharmaceutical differences.

Purpose of the Study:

• To elucidate the non-aerodynamic properties of aerosol particles from two solution pMDI products (QVAR and Sanasthmax).
• To characterize physicochemical and biopharmaceutical differences in beclomethasone dipropionate (BDP) particles.
• To evaluate the potential of novel particle analysis techniques for bioequivalence assessment.

Main Methods:

• Employed novel particle capture and analysis techniques.
• Characterized physicochemical properties (size, porosity, solid state) of BDP particles.
• Utilized a cell culture dissolution-absorption model to assess drug disposition and predict systemic absorption.

Main Results:

• Sanasthmax emitted BDP particles were larger, less porous, less crystalline, and dissolved 20-fold slower than QVAR.
• QVAR delivered approximately 50% more BDP across respiratory epithelial cell layers in 60 minutes compared to Sanasthmax.
• The cell culture model predicted human systemic absorption of BDP, highlighting formulation effects on drug disposition.

Conclusions:

• Significant differences in BDP particle properties exist between QVAR and Sanasthmax pMDIs.
• Novel particle characterization techniques can detect formulation-dependent performance differences.
• The developed model shows potential for assessing bioequivalence of aerosolized drug products.