Physico-Chemical Properties, Aerosolization and Dissolution of Co-Spray Dried Azithromycin Particles with L-Leucine for Inhalation.
Physico-Chemical Properties, Aerosolization and Dissolution of Co-Spray Dried Azithromycin Particles with L-Leucine for Inhalation.
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DOI：
10.1007/s11095-017-2334-9
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发表时间：
2018-01-08
影响因子：
3.7
通讯作者：
Zhou QT
中科院分区：
文献类型：
--
作者：
Mangal S;Nie H;Xu R;Guo R;Cavallaro A;Zemlyanov D;Zhou QT
吸入疗法是治疗下呼吸道感染的常用方法。阿奇霉素对一些引起呼吸道感染的细菌有效；但其水溶性较差，可能限制其作为吸入治疗的疗效。本研究通过与l -亮氨酸共喷雾干燥阿奇霉素，开发了干粉吸入剂配方，以提高其溶出度。对所制备的粉末配方进行了粒径、形貌、表面组成和体外雾化性能的表征。考察了l -亮氨酸对阿奇霉素溶解度和体外溶出度的影响。单用阿奇霉素喷雾干燥制剂具有良好的雾化性能，其细颗粒分数（FPF）为62.5±4.1%。在配方中加入l -亮氨酸后，颗粒形貌和FPF没有明显变化，这可能是由于复合颗粒表面富集了阿奇霉素。重要的是，与单独喷雾干燥的无定形阿奇霉素粉末相比，阿奇霉素和l -亮氨酸共喷雾干燥粉末制剂的体外溶出率大大提高。阿奇霉素溶出增强的原因可能是复合体系的形成和酸性l -亮氨酸在共喷干粉中的溶出形成了阿奇霉素分子周围的酸性微环境。傅里叶变换红外光谱数据显示了阿奇霉素和l -亮氨酸在共喷雾干燥配方中的分子间相互作用。我们通过与氨基酸l -亮氨酸共同喷雾干燥，开发了具有令人满意的气溶胶性能和增强溶解性的干粉配方，用于水溶性弱碱阿奇霉素。
Inhalation therapy is popular to treat lower respiratory tract infections. Azithromycin is effective against some bacteria that cause respiratory tract infections; but it has poor water solubility that may limit its efficacy when administrated as inhalation therapy. In this study, dry powder inhaler formulations were developed by co-spray drying azithromycin with L-leucine with a purpose to improve dissolution. The produced powder formulations were characterized regarding particle size, morphology, surface composition and in-vitro aerosolization performance. Effects of L-leucine on the solubility and in-vitro dissolution of azithromycin were also evaluated. The spray dried azithromycin alone formulation exhibited a satisfactory aerosol performance with a fine particle fraction (FPF) of 62.5 ± 4.1%. Addition of L-leucine in the formulation resulted in no significant change in particle morphology and FPF, which can be attributed to enrichment of azithromycin on the surfaces of composite particles. Importantly, compared with the spray-dried amorphous azithromycin alone powder, the co-spray dried powder formulations of azithromycin and L-leucine demonstrated a substantially enhanced in-vitro dissolution rate. Such enhanced dissolution of azithromycin could be attributed to the formation of composite system and the acidic microenvironment around azithromycin molecules created by the dissolution of acidic L-leucine in the co-spray dried powder. Fourier transform infrared spectroscopic data showed intermolecular interactions between azithromycin and L-leucine in the co-spray dried formulations. We developed the dry powder formulations with satisfactory aerosol performance and enhanced dissolution for a poorly water soluble weak base, azithromycin, by co-spray drying with an amino acid, L-leucine.
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影响因子：
5.2
作者：
Favre-Bonté, S;Köhler, T;Van Delden, C
通讯作者：
Van Delden, C
影响因子：
5.8
作者：
Duret, Christophe;Wauthoz, Nathalie;Amighi, Karim
通讯作者：
Amighi, Karim
影响因子：
4.6
作者：
Gandhi, R;Pillai, O;Panchagnula, R
通讯作者：
Panchagnula, R
影响因子：
4.9
作者：
Jensen, Katrine Tarp;Larsen, Flemming Hofmann;Rades, Thomas
通讯作者：
Rades, Thomas
影响因子：
5.9
作者：
HOPKINS, S
通讯作者：
HOPKINS, S