Request Copyright Permission

Translational In Vitro Screening Approach to Support the Development of Dry Powder Inhalation Products by Predicting Clinical Bioavailability

Gamelas B, Mestre M, Costa C, Morais D, Ribeiro R, Ferreira B, Viegas C, Pereira D, Marques L, Valente P, Chaves R, Ribeiro A, Ferreira F.

Respiratory Drug Delivery 2026. Volume 1, 2026: 8-0.

Abstract:

Clinical failure in respiratory drug development is often driven by inadequate or non-selective exposure to the target tissue, resulting in a lack of efficacy or off-target toxicity. Inhalation development remains heavily dependent on aerodynamic characterization, which reflects the impact of particle engineering and device design in drug delivery efficiency, but does not capture additional drug absorption and clearance mechanisms in the respiratory tract. This work presents a translational, tiered in vitro screening approach to better predict the clinical bioavailability of dry powder inhalation products. This integrated approach combines methods to assess dissolution, epithelial permeability, and macrophage response under physiologically relevant conditions, monitored by defined quality parameters. These methods were developed to generate mechanistic data on key drug delivery processes with potential relevance for integration into physiologically based pharmacokinetic (PBPK) models. By linking drug and formulation attributes to biological performance and exposure-related mechanisms, the framework supports a transition from empirical and non-physiological characterization toward predictive, model-informed approaches across inhaled drug discovery and development.