Physical Stability of Salbutamol Sulfate Suspensions in HFA-134a and HFO-1234ze(E)
Erik Boldt1, Gregory Smith1
1Honeywell International, 20 Peabody Street, Buffalo, NY 14210, USA
Summary
With the growing push to convert pressurized metered dose inhalers (pMDIs) to new low global warming potential (GWP) propellants, an understanding of the physical compatibility of active pharmaceutical ingredients (APIs) with the propellants is necessary for reformulation. Suspension formulations encounter several challenges that solution formulations do not, including destabilization through sedimentation, creaming, flocculation, and/or coalescence. Each of these can have negative effects on the formulation, causing performance issues. Therefore, a thorough understanding of the physical suspension is of the utmost importance.
This study examined the physical stability of salbutamol sulfate formulations in both a currently used propellant, hydrofluoroalkane (HFA)-134a, and an alternative low-GWP propellant hydrofluoroolefin (HFO)-1234ze(E) through use of static multiple light scattering (SMLS) methods. Salbutamol sulfate suspensions in HFO-1234ze(E) were more stable and had a lower sedimentation rate compared to HFA-134a, though flocculation was more persistent. The addition of ethanol reduced flocculation and sedimentation rate in HFO-1234ze(E), increasing the total stability over time.