This study is an in-depth investigation into the performance of test dry powder inhaler (DPI) formulations of tiotropium developed for the Aptar Prohaler and the reference product Spiriva® HandiHaler®.
The research focuses on characterizing these products using realistic breathing profiles, which are then employed in an in-silico Regional Deposition Model (RDM) and physiologically-based pharmacokinetic simulation model (PK Simulation). The study aims to address the long-standing challenge in the pharmaceutical industry of determining bioequivalence (BE) for locally acting respiratory products.
The study uses a Prohaler device filled with blisters containing tiotropium bromide formulated with carrier lactose, and compares this test product with four different batches of Spiriva Handihaler®. The research employs the Nanopharm Inhalation Flow Profiling system to record the breath profiles from a healthy volunteer using the test and reference devices.
The study also includes regional deposition modelling (RDM) and simulated pharmacokinetic profiles for test and reference products. The results suggest that the extrathoracic (ET), tracheobronchial region (BB), and bronchiolar region (bb) deposition were similar between test and reference products.
The study concludes that conventional compendial APSD testing has limited utility to directly predict in vivo. It highlights significant batch to batch variability in the in vitro performance of the reference product Spiriva Handihaler. The study emphasizes the potential of in silico tools, once validated with actual PK data, in ascertaining in vitro and in vivo relationships for dry powder inhalers.
