Cláudia Costa1, Mykaella Mestre1,2, Beatriz Gamelas1,2, Daniel Pereira1 & Alexandre Ribeiro1
1 Hovione FarmaCiência SA, R&D, Analytical Development, Lumiar, 1649-038, Portugal
2 Institute for Bioengineering and Biosciences (iBB), Lisboa, 1049-001, Portugal
Summary
Dissolution of orally inhaled dry powder products (OIDPs) plays a central role in determining the rate and extent of drug absorption within the respiratory tract. It is particularly critical for poorly water-soluble compounds, where dissolution can be the rate-limiting step for pulmonary absorption. Accurate characterization of dissolution behaviour is essential for optimizing formulation performance and ensuring therapeutic efficacy and consistency. Dissolution testing methodologies were employed to investigate the dissolution behaviour of the fine particle fraction of two inhaled Biopharmaceutics Classification System (iBCS) class Active Pharmaceutical Ingredients (APIs), fluticasone furoate (FF) and salmeterol (SA). A Fast-Screening Impactor (FSI) and Glass Twin Impinger (GTI) were used to collect fine particle fractions and dissolution profiling was performed using the Paddle Over Disk (POD) USP Apparatus II and the Transwell® system. The results demonstrate the impact of API solubility on dissolution performance. SA, a highly soluble drug, was fully dissolved in 5 minutes. In contrast, FF exhibited significantly lower solubility, reaching 92% after 12 hours. The POD system showed lower variability compared to Transwell®, likely due to amount of recovered API, media volume, and setup complexity. However, both methods met criteria and produced comparable dissolution profiles, nearly reaching FF’s maximum solubility (1 µg/mL) in 8 hours. This study demonstrated consistent dissolution profiles across two distinct apparatuses, confirming the method’s robustness and reliability by reflecting the formulation’s intrinsic dissolution behavior under defined conditions, independent of apparatus effects. Comparative studies as these are critical for moving toward regulatory acceptance of dissolution methods as drug development tools.