Lobo Jennifer M, Schiavone Helena, Palakodaty Srinivas, York Peter, Clark Andy, Tzannis Stelios T
Nektar Therapeutics, 150 Industrial Road, San Carlos, California 94070, USA.
J Pharm Sci. 2005 Oct;94(10):2276-88. doi: 10.1002/jps.20305.
The objective of this study was to develop SEDS-engineered budesonide particles suitable for dry powder inhalation delivery and to evaluate their aerosol performance across a range of passive dry powder inhalers (DPI). SEDS budesonide powders were manufactured in Nektar's SCF manufacturing plant and compared to the micronized drug and commercial powder (Pulmicort Turbuhaler, AstraZeneca). Aerosol performance was evaluated by determining emitted dose (ED) by a variation of the USP method and fine particle fraction (FPF) using Andersen cascade impaction. The SCF powder dispersed best in the Turbospin and Eclipse devices, exhibiting high EDs (70%-80%) and relatively low variability (RSD 8%-13%). Regardless of the device, the SEDS material outperformed both the micronized drug and the commercial powder, while exhibiting good batch-to-batch reproducibility (RSD <5%). All powders exhibited flow rate-dependent ED, albeit for the SEDS material it was minimized at reduced fill weights. This was attributed to inadequate and variable powder clearance from the capsules at low inspiratory flow rates, which was more pronounced in the Eclipse and Cyclohaler. The results demonstrate that SEDS is an attractive particle-engineering process that may enhance pulmonary performance of budesonide and possibly facilitate development of other small molecule pulmonary products in passive DPI.
本研究的目的是开发适用于干粉吸入给药的超临界流体工程化布地奈德颗粒，并评估其在一系列被动干粉吸入器（DPI）中的气溶胶性能。超临界流体法布地奈德粉末在Nektar的超临界流体制造工厂生产，并与微粉化药物和市售粉末（普米克都保，阿斯利康）进行比较。通过采用美国药典方法的变体测定发射剂量（ED）以及使用安德森级联撞击器测定细颗粒分数（FPF）来评估气溶胶性能。超临界流体法粉末在Turbospin和Eclipse装置中分散性最佳，表现出高发射剂量（70%-80%）和相对较低的变异性（相对标准偏差8%-13%）。无论使用何种装置，超临界流体法材料均优于微粉化药物和市售粉末，同时表现出良好的批次间重现性（相对标准偏差<5%）。所有粉末的发射剂量均表现出与流速相关，尽管对于超临界流体法材料，在减少填充重量时这种相关性最小化。这归因于在低吸气流量下胶囊内粉末清除不足且变化不定，在Eclipse和Cyclohaler中更为明显。结果表明，超临界流体法是一种有吸引力的颗粒工程工艺，可增强布地奈德的肺部性能，并可能促进其他小分子肺部产品在被动干粉吸入器中的开发。
