Advancing nasal formulation characterization: Considerations toward a robust and precise method to determine the mass fraction below 10 μm in nasal products

The expanding role of the nasal route in drug administration for local and systemic treatments has prompted the need for precise delivery methods to ensure efficacy and patient safety. This study addresses the challenges of evaluating the mass fraction below 10 μm in nasal products, a crucial factor in assessing lung deposition of drugs of nasal formulations. Current regulatory guidelines advocate for this assessment, yet a standardized compendial methodology is lacking. To fill this gap, we comprehensively examined several methods to determine a robust approach for quantifying the mass fraction below 10 μm in nasal products. As model formulation, a commercial nasal product (aqueous solution of sodium cromoglycate) was utilized. The assessment of mass fractions below 10 μm necessitates considerations like general handling, precise assessment of delivered dose, robust recovery, and appropriate impactor size analysis techniques. The choice of impactor and of inlet for size analysis may significantly influence the generated results. In this regard, the study highlights the necessity for careful impactor and inlet selection to ensure accurate measurements. In the course of this, the Kiel Nasal Inlet (KNI) had been designed to optimize nasal product testing, addressing the shortcomings of existing inlets. The KNI performed well across different laboratories and reproducible between impactor types. For the determination of mass fraction below 10 μm, the Fast Screening Impactor is the preferred choice of the authors.