硫酸沙丁胺醇/四氟乙烷气雾剂的处方筛选和大鼠呼吸道吸收研究

丁立; 张钧寿

硫酸沙丁胺醇/四氟乙烷气雾剂的处方筛选和大鼠呼吸道吸收研究

丁立,
张钧寿

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

摘要

摘要: 目的：研究以四氟乙烷（HFA-134a）为抛射剂的硫酸沙丁胺醇定量吸入气雾剂（MDI）的处方组成和大鼠吸入后呼吸道的吸收情况。方法：通过溶解度的测定和正交实验设计筛选气雾剂处方；采用大鼠鼻腔插管吸入法给予气雾剂；以荧光HPLC检测血药浓度，并对实验数据进行药代动力学研究。结果：筛选出稳定、均匀的非氟里昂MDI处方；建立了硫酸沙丁胺醇MDI的体内分析法；大鼠吸入硫酸沙丁胺醇/HFA-134a MDI后，对国外对照品和氟里昂处方零阶矩比值分别为109.86%和 135.54%。结论：初步认定HFA-134a可作为氟里昂MDI的替代抛射剂，大鼠吸入吸收效果优于氟里昂处方，与国外市售HFA-134a产品相当。

Abstract: 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.

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