Purpose

This study aims to understand the impact of spray drying nozzles on particle surface composition and aerosol stability.

Methods

The combination formulations of colistin and azithromycin were formulated by 2-fluid nozzle (2 N) or 3-fluid (3 N) spray drying in a molar ratio of 1:1. A 3-factor, 2-level (2³) factorial design was selected to investigate effects of flow rate, inlet temperature and feed concentration on yield of spray drying and the performance of the spray dried formulations for the 3 N.

Results

FPF values for the 2 N formulation (72.9 ± 1.9% for azithromycin & 73.4 ± 0.8% for colistin) were higher than those for the 3 N formulation (56.5 ± 3.8% for azithromycin & 55.1 ± 1.6% for colistin) when stored at 20% RH for 1 day, which could be attributed to smaller physical size for the 2 N. There was no change in FPF for both drugs in the 2 N formulation after storage at 75% RH for 90 days; however, there was a slight increase in FPF for colistin in the 3 N formulation at the same storage conditions. Surface enrichment of hydrophobic azithromycin was measured by X-ray photoelectron spectroscopy for both 2 N and 3 N formulations and interactions were studied using FTIR.

Conclusions

The 3-fluid nozzle provides flexibility in choosing different solvents and has the capability to spray dry at higher feed solid concentrations. This study highlights the impact of hydrophobic azithromycin enrichment on particle surface irrespective of the nozzle type, on the prevention of moisture-induced deterioration of FPF for hygroscopic colistin.

中文翻译：

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使用三流体喷嘴喷雾干燥的可吸入组合粉末制剂的表面组成和雾化稳定性

目的

本研究旨在了解喷雾干燥喷嘴对颗粒表面成分和气溶胶稳定性的影响。

方法

多粘菌素和阿奇霉素的组合制剂通过2流体喷嘴（2 N）或3流体（3 N）喷雾干燥以1:1的摩尔比配制。选择3 因子、2 水平 (2 ³ ) 析因设计来研究流速、入口温度和进料浓度对喷雾干燥产率和喷雾干燥配方对 3 N 性能的影响。

结果

在 20 ℃保存时，2 N 制剂的 FPF 值（阿奇霉素 72.9 ± 1.9% 和多粘菌素 73.4 ± 0.8%）高于 3 N 制剂的值（阿奇霉素 56.5 ± 3.8% 和多粘菌素 55.1 ± 1.6%） % RH 保存 1 天，这可归因于 2 N 的较小物理尺寸。在 75% RH 下储存 90 天后，2 N 制剂中两种药物的 FPF 没有变化；然而，在相同的储存条件下，3 N 制剂中多粘菌素的 FPF 略有增加。疏水性阿奇霉素的表面富集通过 X 射线光电子能谱测量 2 N 和 3 N 制剂，并使用 FTIR 研究相互作用。

结论

三流体喷嘴提供了选择不同溶剂的灵活性，并且能够在较高的进料固体浓度下进行喷雾干燥。该研究强调了疏水性阿奇霉素富集对颗粒表面的影响，无论喷嘴类型如何，都可以防止吸湿性粘菌素的 FPF 因水分引起的变质。