HFA-134a driven salbutamol sulfate metered-dose inhaler：formulation screening and respiratory tract absorption in rats

Aim ：To study the hydrofluoroalkane-driven(HFA-134a) salbutamol sulfate(SS) MDI formulation compositions and the respiratory tract absorption in rats. Methods ：Solubility determination and orthogonal design were used to aid the screening of non-CFC SS MDI formulations.Rats were exposed to SS MDI via intubation inhalation.Fluorescent HPLC detection was developed to determine plasma SS concentration in rats given the selected SS MDI formulations.Analysis of the plasma drug level-time profiles was performed by the statistical moment approach. Results ：Stable and homogeneous non-CFC SS MDI formulations were obtained.The developed HPLC method was validated and used to assay SS levels in the rats after inhalation of the MDI.AUC ratios of the SS/HFA-134a-driven MDI formulation to the reference SS MDI and CFC SS MDI formulation were 109.86% and 135.54%，respectively. Conclusion ：It is proven that the absorption of the HFA-134a SS MDI formulation in rats is equivalent to the simulant formulation commercially available oversea and better than CFC formulation.