Improved Aerosolization Stability of Inhalable Tobramycin Powder Formulation by Co-Spray Drying with Colistin,Pharmaceutical Research

当前位置： X-MOL 学术 › Pharm. Res. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Improved Aerosolization Stability of Inhalable Tobramycin Powder Formulation by Co-Spray Drying with Colistin
Pharmaceutical Research ( IF 3.5 ) Pub Date : 2022-08-02 , DOI: 10.1007/s11095-022-03344-5
Vaibhav Pathak ₁ , Heejun Park ₁ , Dmitry Zemlyanov ₂ , Sonal V Bhujbal ₁ , Maizbha Uddin Ahmed ₁ , Mohammad A K Azad ₃ , Jian Li ₃ , Qi Tony Zhou ₁

Affiliation

Purpose

Tobramycin shows synergistic antibacterial activity with colistin and can reduce the toxic effects of colistin. The purpose of this study is to prepare pulmonary powder formulations containing both colistin and tobramycin and to assess their in vitro aerosol performance and storage stability.

Methods

The dry powder formulations were manufactured using a lab-scale spray dryer. In vitro aerosol performance was measured using a Next Generation Impactor. The storage stability of the dry powder formulations was measured at 22°C and two relative humidity levels – 20 and 55%. Colistin composition on the particle surface was measured using X-ray photoelectron spectroscopy.

Results

Two combination formulations, with 1:1 and 1:5 molar ratios of colistin and tobramycin, showed fine particle fractions (FPF) of 85%, which was significantly higher than that of the spray dried tobramycin (45%). FPF of the tobramycin formulation increased significantly when stored for four weeks at both 20% and 55% RH. In contrast, FPF values of both combination formulations and spray dried colistin remained stable at both humidity levels. Particle surface of each combination was significantly enriched in colistin molecules; 1:5 combination showed 77% by wt. colistin.

Conclusions

The superior aerosol performance and aerosolization stability of 1:1 and 1:5 combination formulations of colistin and tobramycin could be attributed to enrichment of colistin on the co-spray dried particle surface. The observed powder properties may be the result of a surfactant-like assembly of these colistin molecules during spray drying, thus forming a hydrophobic particle surface.

中文翻译：

通过与粘菌素共喷雾干燥提高可吸入妥布霉素粉末制剂的雾化稳定性

目的

Tobramycin 与粘菌素具有协同抗菌活性，可降低粘菌素的毒性作用。本研究的目的是制备同时含有粘菌素和妥布霉素的肺部粉末制剂，并评估其体外气雾剂性能和储存稳定性。

方法

干粉制剂是使用实验室规模的喷雾干燥器制造的。使用下一代冲击器测量体外气溶胶性能。干粉制剂的储存稳定性是在 22°C 和两个相对湿度水平（20% 和 55%）下测量的。使用 X 射线光电子能谱测量颗粒表面上的粘菌素组成。

结果

粘菌素和妥布霉素的摩尔比为 1:1 和 1:5 的两种组合制剂显示出 85% 的细颗粒分数 (FPF)，显着高于喷雾干燥的妥布霉素 (45%)。当在 20% 和 55% RH 下储存 4 周时，妥布霉素制剂的 FPF 显着增加。相反，组合制剂和喷雾干燥粘菌素的 FPF 值在两种湿度水平下均保持稳定。每种组合的颗粒表面均显着富集粘菌素分子；1:5 组合显示 77%（重量）。粘菌素。