We combined high-energy wet media milling and spray drying to engineer dry powders for inhalation consisting of geometrically large, low-density particles with superior aerodynamic properties and fast dissolution. Peclet number proved to be a useful instrument to guide choice of the additives and process conditions for generating low-density powders by spray drying. Composite dry powders consisted of milled and stabilized budesonide nanoparticles, leucine or albumin as matrix formers, and ammonium carbonate as a pore former. Powders of different composition showed fairly large and comparable geometric particle sizes (de,50 > 4.4 µm) with effective densities strongly depending on the present matrix former. Powders with lowest density reached an aerosol performance of up to 60%, which is well above most commercial, carrier-based products. It was also demonstrated that the nanomilling step was indispensable to yield such good aerosol performance. Dissolution of aerodynamically classified particle fractions showed a very fast onset and was largely completed within 30 min irrespective of the formulation and the impactor stage. Mathematical kinetic modeling was used to deduce the API dissolution rate coefficient from the results obtained using a modified USP 2 apparatus. Dissolution rate was found to be determined by the properties of the API nanoparticles rather than those of the composite particles. The employment of industrially established, solely water-based processes allows introducing the presented approach as a platform technology for the development of well-performing pulmonary formulations.

中文翻译：

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生产快速溶解的低密度粉末，以通过纳米悬浮液的喷雾干燥来改善肺部沉积。

我们将高能湿介质研磨和喷雾干燥相结合，设计出用于吸入的干粉，这些干粉由几何形状大的低密度颗粒组成，具有出色的空气动力学特性和快速溶解性。经证明，Peclet号是指导添加剂选择和通过喷雾干燥产生低密度粉末的工艺条件的有用工具。复合干粉由研磨和稳定的布地奈德纳米颗粒，亮氨酸或白蛋白作为基质形成剂，碳酸铵作为成孔剂组成。不同组成的粉末显示出相当大且相当的几何粒度（de，50> 4.4 µm），有效密度强烈取决于本基质形成剂。密度最低的粉末的气溶胶性能高达60％，远高于大多数商业，基于载体的产品。还证明了纳米研磨步骤对于产生如此好的气溶胶性能是必不可少的。空气动力学分类的颗粒级分的溶解显示出非常快的起效，并且在30分钟内基本完成，而与制剂和撞击阶段无关。使用数学动力学模型从使用改进的USP 2仪器获得的结果推导出API溶出速率系数。发现溶解速率由API纳米颗粒的性质而不是由复合颗粒的性质决定。采用工业上建立的，完全基于水的工艺，可以将所介绍的方法引入平台，以开发性能良好的肺部制剂。