Investigation of L-leucine in reducing the moisture-induced deterioration of spray-dried salbutamol sulfate power for inhalation
Investigation of L-leucine in reducing the moisture-induced deterioration of spray-dried salbutamol sulfate power for inhalation
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DOI：
10.1016/j.ijpharm.2017.07.033
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发表时间：
2017-09-15
影响因子：
5.8
通讯作者：
Chan, Hak-Kim
中科院分区：
文献类型：
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作者：
Li, Liang;Leung, Sharon Shui Yee;Chan, Hak-Kim
本研究的目的是调查L-亮氨酸（LL）在防止水分引起的喷雾干燥（SD）硫酸沙丁胺醇（SS）的体外雾化性能恶化的能力。采用喷雾干燥法制备了不同质量分数（5-80%）的LL和SS，并采用激光衍射、X射线粉末衍射（XRD）和动态水蒸气吸附（DVS）等方法对粉末的理化性质进行了表征。此外，通过扫描电子显微镜（SEM）和X射线光电子能谱（XPS）分析了细颗粒的表面形貌和化学组成。采用新一代冲击式雾化器（NGI）对不同相对湿度（RH）条件下保存的粉末进行体外雾化性能评价。SD SS粉末是适度吸湿性和无定形的，其中在储存时吸收水分导致雾化性能下降。结果表明，在60%RH下，40%（w/w）LL足以消除水分对雾化性能的影响。含有40%（w/w）LL的制剂还使SD SS粉末（储存在干燥器中）的雾化性能最大化，其中发射分数为90.0 +/-1.8%，并且基于回收剂量（FPFrecovered）和发射剂量（FPFemitted）的细颗粒分数分别为78.0 +/-3.7%和86.6 +/-2.9%。其基本机理是结晶LL增加了颗粒表面的粗糙度，降低了颗粒的融合性和内聚性，有利于分散。然而，要防止由于SD SS的重结晶而导致75%RH下水分引起的雾化性能恶化，仍然存在很大的挑战。总之，LL是一种潜在的赋形剂，用于减少水分引起的SD无定形粉末的雾化性能恶化，但在防止重结晶引起的恶化方面仍然存在缺点。(C)2017爱思唯尔B. V.保留所有权利。
The aim of this study was to investigate the ability of L-leucine (LL) in preventing moisture-induced deterioration in the in vitro aerosolization performance of spray-dried (SD) salbutamol sulfate (SS). Increasing mass fraction of LL (5-80%) were co-spray dried with SS, and the physicochemical properties of the powders were characterized by laser diffraction, X-ray powder diffraction (XRD) and dynamic vapour sorption (DVS). Furthermore, the surface morphology and chemistry of fine particles was analyzed by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). The in vitro aerosolization performance of powders stored at different relative humidity (RH) was evaluated by a next generation impactor (NGI). The SD SS powders were moderately hygroscopic and amorphous, of which the uptake of moisture upon storage caused a drop in the aerosolization performance. The results showed that 40% (w/w) LL was sufficient to eliminate the effect of moisture on the aerosolization performance at 60% RH. The formulation containing 40% (w/w) LL also maximized the aerosolization performance of SD SS powders (stored in desiccator) with the emitted fraction being 90.0 +/- 1.8%, and the fine particle fraction based on the recovered dose (FPFrecovered) and emitted dose (FPFemitted) being 78.0 +/- 3.7% and 86.6 +/- 2.9%, respectively. The underlying mechanisms were that the crystalline LL increased the degree of particle surface corrugation, and reduced particle fusion and cohesiveness to facilitate dispersion. However, there is still a great challenge to prevent the moisture-induced deterioration in the aerosolization performance at 75% RH due to the recrystallization of SD SS. In conclusion, LL is a potential excipient for reducing moisture-induced deterioration in the aerosolization performance of SD amorphous powders, but still has drawbacks in preventing the recrystallization-induced deterioration. (C) 2017 Elsevier B.V. All rights reserved.