Dry powder inhalers (DPIs) are drug–device combination products where the complexity of the formulation, its interaction with the device, and input from users play important roles in the drug delivery. As the landscape of DPI products advances with new powder formulations and novel device designs, understanding how these advancements impact performance can aid in developing generics that are therapeutically equivalent to the reference listed drug (RLD) products. This review details the current understanding of the formulation and device related principles driving DPI performance, past and present research efforts to characterize these performance factors, and the implications that advances in formulation and device design may present for evaluating bioequivalence (BE) for generic development.

Purpose: Although in vitro studies recommended for establishing bioequivalence of locally acting nasal suspension products provide useful information regarding product performance, currently they are not designed to fully account for variability introduced by patient-specific factors such as administration technique and breathing patterns. This limitation, combined with ethical and practical challenges in conducting pediatric clinical trials, creates a knowledge gap in understanding age-related differences in nasal drug delivery. Methods: Anatomically realistic in vitro nasal models representing an average child and adult, in terms of total drug delivery to the sites of intended action posterior to nasal valve, were used to investigate the sensitivity of regional nasal drug deposition to variations in administration parameters and breathing conditions. Three breathing conditions were evaluated: breath hold, gentle sniffing, and vigorous sniffing. Administration parameters were varied using a Box-Behnken experimental design. Results: Results showed that for commercially available nasal sprays, breathing patterns did not significantly affect drug delivery in the adult model, but extreme conditions (no breathing vs. vigorous sniffing) caused significant differences in anterior deposition in the child model. Differences between gentle sniffing and the other conditions were not statistically significant. The sensitivity analysis revealed that in vitro drug deposition patterns differ between child and adult nasal cavities under identical user parameter variations, and variable importance differed across nasal cavity regions. Conclusions: This study demonstrates the potential for targeted drug delivery by enabling the identification of the optimal administration parameters to achieve desired outcomes, such as enhanced drug deposition in specific nasal regions.