Learoyd Tristan P, Burrows Jane L, French Eddie, Seville Peter C
School of Life and Health Sciences, Aston University, Birmingham, UK.
Eur J Pharm Biopharm. 2008 Feb;68(2):224-34. doi: 10.1016/j.ejpb.2007.04.017. Epub 2007 May 5.
In this study, we describe the preparation of highly dispersible dry powders for pulmonary drug delivery that display sustained drug release characteristics. Powders were prepared by spray-drying 30% v/v aqueous ethanol formulations containing terbutaline sulfate as a model drug, chitosan as a drug release modifier and leucine as an aerosolisation enhancer. The influence of chitosan molecular weight on the drug release profile was investigated by using low, medium and high molecular weight chitosan or combinations thereof. Following spray-drying, resultant powders were characterised using scanning electron microscopy, laser diffraction, tapped density analysis, differential scanning calorimetry and thermogravitational analysis. The in vitro aerosolisation performance and drug release profile were investigated using Multi-Stage Liquid Impinger analysis and modified USP II dissolution apparatus, respectively. The powders generated were of a suitable aerodynamic size for inhalation, had low moisture content and were amorphous in nature. The powders were highly dispersible, with emitted doses of over 90% and fine particle fractions of up to 82% of the total loaded dose, and mass median aerodynamic diameters of less than 2.5microm. A sustained drug release profile was observed during dissolution testing; increasing the molecular weight of the chitosan in the formulation increased the duration of drug release.
在本研究中，我们描述了用于肺部药物递送的具有持续药物释放特性的高度分散性干粉的制备。通过喷雾干燥含有硫酸特布他林作为模型药物、壳聚糖作为药物释放调节剂和亮氨酸作为雾化增强剂的30% v/v乙醇水溶液制剂来制备粉末。使用低、中、高分子量壳聚糖或其组合研究壳聚糖分子量对药物释放曲线的影响。喷雾干燥后，使用扫描电子显微镜、激光衍射、振实密度分析、差示扫描量热法和热重分析对所得粉末进行表征。分别使用多级液体冲击器分析和改良的美国药典II溶出装置研究体外雾化性能和药物释放曲线。所产生的粉末具有适合吸入的空气动力学尺寸，水分含量低且本质上为无定形。这些粉末具有高度分散性，发射剂量超过90%，细颗粒分数高达总装载剂量的82%，质量中值空气动力学直径小于2.5微米。在溶出测试中观察到持续的药物释放曲线；增加制剂中壳聚糖的分子量会延长药物释放持续时间。
