In Vitro-In Vivo Correlations Observed With Indacaterol-Based Formulations Delivered with the Breezhaler®

Background: Establishing robust in vitro-in vivo correlations (IVIVC) between aerosol performance, pharmacokinetics, and clinical efficacy is critical in developing bioequivalent drug-device combination products. Recent studies have demonstrated that realistic throat models tested under realistic test conditions may provide good IVIVC with respect to total lung deposition. Methods: The Alberta idealized throat (AIT) model was utilized with mean peak inspiratory flow rates determined from patient breathing studies. Various formulations of indacaterol (e.g., lactose blends, fixed dose combinations, engineered PulmoSphere particles) were tested in the AIT model and in clinical pharmacokinetic studies. Results: Good IVIVC were observed with respect to total lung deposition, systemic delivery, and the contribution of oral absorption to systemic delivery, with percentage differences from the mean in vivo measurements <15%, with most comparisons <5%. Conclusions: Anatomical throat models represent an exciting tool to aid in formulation development of pharmaceutical aerosols.