Dry powder formulation of kanamycin with enhanced aerosolization efficiency for drug-resistant tuberculosis
Dry powder formulation of kanamycin with enhanced aerosolization efficiency for drug-resistant tuberculosis
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DOI：
10.1016/j.ijpharm.2017.06.004
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发表时间：
2017-08-07
影响因子：
5.8
通讯作者：
Das, Shyamal C.
中科院分区：
文献类型：
--
作者：
Momin, Mohammad A. M.;Sinha, Shubhra;Das, Shyamal C.
背景：卡那霉素是一种注射剂，目前用于治疗耐药结核病（TB）。非肠道卡那霉素引起高的全身毒性，这可以通过直接输送到肺部来避免。方法：采用Buchi B-290微型喷雾干燥机，以L-亮氨酸为原料，制备不同浓度（0、5、10、15和20%w/w）的吸湿性卡那霉素干粉。通过下一代撞击器（NGI）、激光衍射、扫描电子显微镜、X射线衍射、XPS、ATR-FTIR和热重分析对粉末的体外雾化效率、粒度、形态、结晶度、表面组成、药物-赋形剂相互作用和含水量进行表征。在25 +/-2 ℃/15%RH和25 +/-2 ℃/75%RH下储存一个月后，研究了粉末的物理化学和雾化稳定性。采用MTT法检测卡那霉素粉末对Calu-3和A549细胞的细胞毒性。
Background: Kanamycin, an injectable agent, is currently used to treat drug-resistant tuberculosis (TB). Parenteral kanamycin causes high systemic toxicity which could be avoided by direct delivery to the lungs. This study focused on producing a highly aerosolizable dry-powder of hygroscopic kanamycin by spray-drying with L-leucine.Methods: Kanamycin powders were prepared with different concentrations (0, 5,10,15 and 20% w/w) of L-leucine using the Buchi B-290 Mini Spray-Dryer. In vitro aerosolization efficiency, particle size, morphology, crystallinity, surface composition, drug-excipient interaction and moisture content of the powders were characterized by a Next Generation Impactor (NGI), laser diffraction, scanning electron microscopy, X-ray diffractometry, XPS, ATR-FTIR and thermogravimetric analysis. The physicochemical and aerosolization stability of the powders were investigated after one-month storage at 25 +/- 2 degrees C/15% RH and 25 +/- 2 degrees C/75% RH. The cytotoxicity on Calu-3 and A549 cells of the kanamycin powders was evaluated by MTT assay.Results: The spray-dried powder particles were in the inhalable size range (