The pulmonary administration landscape has rapidly advanced in recent years. Targeted design of particles by spray-drying for dry powder inhaler development offers an invaluable tool for engineering of new carriers. In this work, different formulation and process aspects of spray-drying were exploited to produce new lactose carriers. Using an integrated approach, lactose was spray-dried in the presence of polyethylene glycol 200 (PEG 200), and the in vitro performance of the resulting particles was compared with other grades of lactose with varying anomeric compositions and/or physical properties. The anomeric composition of lactose in lactose–PEG 200 feed solutions of variable compositions was analyzed via polarimetry at different temperatures. These results were correlated with the solid-state and anomeric composition of the resulting spray-dried particles using modulated differential scanning calorimetry and wide-angle X-ray scattering. The distinct selected grades of lactose were characterized in terms of their micromeritic properties using laser diffraction, helium pycnometry, and gas adsorption, and their particle surface morphologies were evaluated via scanning electron microscopy. Adhesive mixtures of the different lactose carriers with inhalable-sized salbutamol sulfate, as a model drug, were prepared in low doses and evaluated for their blend homogeneity and aerodynamic performance using a Next Generation Impactor. Characterization of the spray-dried particles revealed that predominantly crystalline (in an anomeric ratio 0.8:1 of α to β) spherical particles with a mean size of 50.9 ± 0.4 μm could be produced. Finally, it was apparent that micromeritic, in particular, the shape, and surface properties (inherent to solid-state and anomeric composition) of carrier particles dominantly control DPI delivery. This provided an insight into the relatively inferior performance of the adhesive blends containing the spherical spray-dried lactose–PEG 200 composites.

中文翻译：

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干粉吸入器载体设计的评估：各种端基组成和乳糖物理性质的比较案例研究

近年来，肺行政管理形势迅速发展。通过喷雾干燥对粉末进行有针对性的设计，以开发干粉吸入器，为新载体的工程设计提供了宝贵的工具。在这项工作中，利用喷雾干燥的不同配方和工艺方面来生产新的乳糖载体。使用集成方法，将乳糖在聚乙二醇200（PEG 200）存在下进行喷雾干燥，然后将所得颗粒的体外性能与具有不同端基异构体组成和/或物理性质的其他等级的乳糖进行比较。通过旋光法在不同温度下分析可变组成的乳糖–PEG 200进料溶液中乳糖的异头组成。这些结果与使用调制差示扫描量热法和广角X射线散射法得到的喷雾干燥颗粒的固态和异头组成相关。使用激光衍射，氦比重瓶法和气体吸附法对乳糖的不同等级进行了表征，并通过扫描电子显微镜对它们的颗粒表面形态进行了评估。以低剂量制备不同乳糖载体与可吸入大小的硫酸沙丁胺醇的粘合剂混合物，作为模型药物，并使用新一代Impactor评估其混合均匀性和空气动力学性能。喷雾干燥颗粒的表征表明主要为结晶（异头比为0.8：可以生产1个平均尺寸为50.9±0.4μm的α到β）球形颗粒。最后，很明显的是，载体颗粒的微粒，特别是形状和表面性质（固有于固态和异头组成）是控制DPI传递的主要因素。这为含有球形喷雾干燥乳糖–PEG 200复合材料的胶粘剂共混物的相对较差的性能提供了一个见解。