Formulation of inhalable lipid-based salbutamol sulfate microparticles by spray drying technique
Formulation of inhalable lipid-based salbutamol sulfate microparticles by spray drying technique
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DOI：
10.1186/2008-2231-22-50
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发表时间：
2014-06-11
影响因子：
3.6
通讯作者：
Barghi, Mohammad Ali
中科院分区：
文献类型：
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作者：
Daman, Zahra;Gilani, Kambiz;Barghi, Mohammad Ali
背景：这项工作的目的是借助由生物相容性磷脂或胆固醇组成的固体脂质微粒（SLmP）开发硫酸沙丁胺醇（SS）的干粉吸入器（DPI）制剂。方法：在喷雾干燥中使用两种不同的溶剂系统（乙醇和水-乙醇）和脂质载体（二棕榈酰磷脂酰胆碱（DPPC）和胆固醇）（含/不含L-亮氨酸）制备SLmP过程。将喷雾干燥的微粒与粗乳糖一水合物进行物理混合，以制成最终的 DPI 制剂，并对其物理特性以及体外药物释放曲线和雾化行为进行研究。结果：我们观察到制剂之间在尺寸、形态和体外肺部沉积方面的显着差异。特别是，用 DPPC 和 L-亮氨酸的水-乙醇（30：70 v/v）溶液制备的含 SS 的 SLmP，然后与粗乳糖（1：9 w/w）混合，在制剂中表现出最高的排放剂量（87.9％）和细颗粒分数（42.7％）。体外药物释放研究表明，尽管胆固醇和基于 DPPC 的微粒具有显着的初始爆发释放，但剩余药物的释放速度比纯药物慢。 结论：这项研究证明了在 SS 的 DPI 制剂中使用脂质载体和 L-亮氨酸的潜力，可以改善其雾化行为并延缓药物的释放曲线。
Background: The aim of this work was to develop dry powder inhaler (DPI) formulations of salbutamol sulfate (SS) by the aid of solid lipid microparticles (SLmPs), composed of biocompatible phospholipids or cholesterol.Methods: The SLmPs were prepared by using two different solvent systems (ethanol and water-ethanol) and lipid carriers (dipalmitoylphosphatidylcholine (DPPC) and cholesterol) with/without L-leucine in the spray drying process. The spray-dried microparticles were physically-mixed with coarse lactose monohydrate in order to make our final DPI formulations and were investigated in terms of physical characteristics as well as in vitro drug release profile and aerosolization behavior.Results: We observed significant differences in the sizes, morphologies, and in vitro pulmonary depositions between the formulations. In particular, the SS-containing SLmPs prepared with water-ethanol (30: 70 v/v) solution of DPPC and L-leucine which had then been blended with coarse lactose (1: 9 w/w) exhibited the highest emitted dose (87.9%) and fine particle fraction (42.7%) among the formulations. In vitro drug release study indicated that despite of having a significant initial burst release for both cholesterol and DPPC-based microparticles, the remained drug released more slowly than the pure drug.Conclusion: This study demonstrated the potential of using lipid carriers as well as L-leucine in DPI formulations of SS to improve its aerosolization behavior and retard the release profile of the drug.