Different formulation techniques have been investigated to prepare highly aerosolizable dry powders to deliver a high dose of antibiotics to the lung for treating local infections. In this study, we investigated the influence of the co-amorphization of a model drug, kanamycin, with selected amino acids (valine, methionine, phenylalanine, and tryptophan) by co-spray drying on its aerosolization. The co-amorphicity was confirmed by thermal technique. The physical stability was monitored using low-frequency Raman spectroscopy coupled with principal component analysis. Except for the kanamycin-valine formulation, all the formulations offered improved fine particle fraction (FPF) with the highest FPF of 84% achieved for the kanamycin-methionine formulation. All the co-amorphous formulations were physically stable for 28 days at low relative humidity (25 °C/<15% RH) and exhibited stable aerosolization. At higher RH (53%), even though methionine transformed into its crystalline counterpart, the kanamycin-methionine formulation offered the best aerosolization stability without any decrease in FPF. While further studies are warranted to reveal the underlying mechanism, this study reports that the co-amorphization of kanamycin with amino acids, especially with methionine, has the potential to be developed as a high dose kanamycin dry powder formulation.

中文翻译：

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卡那霉素与氨基酸的共非晶化可改善雾化作用。

已经研究了不同的配制技术来制备高度可雾化的干粉，以将高剂量的抗生素输送到肺部以治疗局部感染。在这项研究中，我们研究了通过共喷雾干燥将模型药物卡那霉素与选定的氨基酸（缬氨酸，蛋氨酸，苯丙氨酸和色氨酸）共非晶化对其雾化的影响。通过热技术确认了共非晶性。使用低频拉曼光谱结合主成分分析监测物理稳定性。除卡那霉素-缬氨酸制剂外，所有制剂均提供了改进的细颗粒级分（FPF），卡那霉素-蛋氨酸制剂的最高FPF为84％。所有共非晶制剂在低相对湿度（25°C / <15％RH）下物理稳定28天，并表现出稳定的雾化作用。在较高的相对湿度（53％）下，即使将蛋氨酸转化为其结晶对应物，卡那霉素-蛋氨酸制剂仍可提供最佳的雾化稳定性，而FPF不会降低。尽管有必要进行进一步的研究以揭示其潜在机制，但该研究报告指出，卡那霉素与氨基酸（尤其是蛋氨酸）的共非晶化有可能发展为高剂量卡那霉素干粉制剂。