Switching to a Low Global Warming Potential Propellant in a Pressurized Metered-Dose Inhaler Does Not Affect the Pharmacokinetics of Combined Beclometasone Dipropionate/Formoterol Fumarate.

PURPOSE: Use of high global warming potential propellants (eg, 1,1,1,2-tetrafluoroethane [HFA-134a]) in pressurized metered-dose inhalers (pMDIs) is being phased down. Extrafine formulation of beclometasone dipropionate (BDP)/formoterol fumarate (FF), approved for the treatment of asthma or chronic obstructive pulmonary disease via HFA-134a propellant pMDI, is being reformulated using the low global warming potential propellant 1,1-difluoroethane (HFA-152a). Two studies compared BDP/FF pharmacokinetics delivered via pMDI using HFA-152a versus HFA-134a.

METHODS

Both studies (N = 90 in each) were single-dose (4 actuations), randomized, double-blind, 4-way crossover, in healthy volunteers. The first evaluated bioequivalence of BDP/FF 100/6 µg per actuation (ie, medium strength in terms of BDP), with and without a spacer; the second evaluated BDP/FF 200/6 µg per actuation (high-strength), with and without a spacer. The primary variables were AUC0-t, Cmax, and Tmax for BDP, beclometasone-17-monopropionate (active metabolite of BDP), and formoterol, as well as AUC between time 0 and 30 minutes after dose (AUC0-30 min) for formoterol. Bioequivalence was concluded for Cmax, AUC0-t, and formoterol AUC0-30 min if the 90% CI of the ratio of geometric means for the 2 formulations was contained between 80% and 125%.

FINDINGS: Bioequivalence of the 2 propellants was demonstrated in both studies for BDP, beclometasone-17-monopropionate, and formoterol Cmax and AUC0-t, as well as for formoterol AUC0-30 min, with and without the spacer, with no differences between formulations for Tmax.

IMPLICATIONS: Bioequivalence was formally demonstrated between the BDP/FF HFA-134a and HFA-152a formulations.