Budesonide nanoparticle agglomerates as dry powder aerosols with rapid dissolution.
Budesonide nanoparticle agglomerates as dry powder aerosols with rapid dissolution.
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DOI：
10.1002/jps.21630
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发表时间：
2009-08
影响因子：
3.8
通讯作者：
Berkland C
中科院分区：
文献类型：
--
作者：
El-Gendy N;Gorman EM;Munson EJ;Berkland C
纳米颗粒技术代表了配制水溶性差的肺部药物的一种有吸引力的方法。不幸的是，雾化器或定量吸入器中使用的纳米颗粒悬浮液经常遭受物理不稳定性，表现为不受控制的团聚或奥斯特瓦尔德熟化。此外，将这种悬浮液加工成干粉可以产生宽的粒度分布。为了解决这些问题，开发了一种受控纳米颗粒絮凝工艺。通过将药物溶解在含有表面活性剂的有机溶剂中，然后在水中快速溶剂萃取，制备了难溶于水的药物布地奈德的纳米混悬剂。采用不同的表面活性剂来控制沉淀纳米颗粒的尺寸和表面电荷。使用亮氨酸絮凝纳米悬浮液并冻干。选定的布地奈德纳米颗粒悬浮液平均粒径范围为~160-230 nm，产率高，药物含量高。絮凝的纳米悬浮液产生微米尺寸的附聚物。冷冻干燥纳米颗粒团聚物产生具有吸入治疗所需空气动力学特性的干粉。此外，干燥的纳米颗粒附聚物制剂的溶出速率明显快于布地奈德原料。这项研究的结果表明，纳米颗粒团聚物具有肺部沉积所需的微观结构和促进难溶于水的药物快速溶解的纳米结构。
Nanoparticle technology represents an attractive approach for formulating poorly water soluble pulmonary medicines. Unfortunately, nanoparticle suspensions used in nebulizers or metered dose inhalers often suffer from physical instability in the form of uncontrolled agglomeration or Ostwald ripening. In addition, processing such suspensions into dry powders can yield broad particle size distributions. To address these encumbrances, a controlled nanoparticle flocculation process has been developed. Nanosuspensions of the poorly water soluble drug budesonide were prepared by dissolving the drug in organic solvent containing surfactants followed by rapid solvent extraction in water. Different surfactants were employed to control the size and surface charge of the precipitated nanoparticles. Nanosuspensions were flocculated using leucine and lyophilized. Selected budesonide nanoparticle suspensions exhibited an average particle size ranging from ~160–230 nm, high yield and high drug content. Flocculated nanosuspensions produced micron-sized agglomerates. Freeze-drying the nanoparticle agglomerates yielded dry powders with desirable aerodynamic properties for inhalation therapy. In addition, the dissolution rates of dried nanoparticle agglomerate formulations were significantly faster than that of stock budesonide. The results of this study suggest that nanoparticle agglomerates possess the microstructure desired for lung deposition and the nanostructure to facilitate rapid dissolution of poorly water soluble drugs.