Journal of Bioequivalence & Bioavailability

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

6^th World Congress on Bioavailability & Bioequivalence: BA/BE Studies Summit

August 17-19, 2015 Chicago, USA

Salman Alfadhel

Posters-Accepted Abstracts: J Bioequiv Availab

Abstract:

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.
Methods: The in-vitro performance of delivering Tiotropium Bromide from Tiovaï?? were compared with results obtained from Spiriva
by using Next Generation Impactor (NGI) operated at different flow rate (30,40,50 and 60 L/min). The method described in the US
pharamacopoeia.
Results: The Emitted dose of Spiriva at flow rate of 30, 40, 50 and 60 L/min as percentage nominal dose (SD) were 100.4 (0.2), 100.4
(0.4), 100.2 (0.2) and 100.2 (0.2) respectively. In addition, the fine particle fraction of Spiriva at same flow rate (SD) were 50.3 (2.2),
55.6 (0.7), 60.4 (1.5) and 63.3 (6.7) respectively. The mass median aerodynamic diameter of Spiriva at flow rate of 30, 40, 50 and 60 L/
min were 3.3 (0.4), 2.9 (0.1), 2.4 (0.1) and 2.4 (0.1) respectively. In contrast, the Emitted dose of Tiova at flow rate of 30, 40, 50 and 60
L/min as percentage nominal dose (SD) were 100.4 (0.4), 100.2 (0.1), 100.1 (0.1) and 100.1 (0.1) respectively. The fine particle fraction
of Tiova at flow rate of 30, 40, 50 and 60 L/min (SD) were 44.9 (0.7), 49.2 (1.2), 52.2 (0.7) and 49.1 (2.7) respectively. In addition, the
mass median aerodynamic diameter of Spiriva at the same flow rate (SD) were 3.4 (0.1), 3.3 (0.1), 3.2 (0.1) and 3.5 (0.2) respectively.