In-vitro bioequivalence study of Tiotropium bromide inhaled drug emitted from Spiriva and Tiova formulations

Introduction: Asthma and other pulmonary diseases are currently treated in millions of people over the world with orally inhaled drugs (OIDs). The traditional pharmacokinetic approaches (AUC and Cmax determination) are currently not accepted by the FDA for evaluating the Inhalations drugs equivalence. The goal of the FDA solicitation (Solicitation Number: 10-223-SOL-00277, part 4) is that pharmacokinetic studies provide an indications and information’s about deposition of inhaled drugs at different regional of the lung. for slowly dissolving drugs (e.g fluticasone propionate) a smaller AUC and Cmax will be observed, if the drug is deposited more centrally, as the mucociliary clearance present in the central parts of the lung will remove a larger portion of the more centrally deposited dose, thus leading to a reduction in absorbed dose, AUC and Cmax. Moreover, fast dissolving drugs or drugs in solution differences in Cmax will indicate differences in the c/p ratio.