Supercritical fluid assisted atomization introduced by an enhanced mixer for micronization of lysozyme: Particle morphology, size and protein stability
Supercritical fluid assisted atomization introduced by an enhanced mixer for micronization of lysozyme: Particle morphology, size and protein stability
复制标题
通过增强型混合器引入超临界流体辅助雾化，用于溶菌酶微粉化：颗粒形态、尺寸和蛋白质稳定性
DOI：
10.1016/j.ijpharm.2011.10.002
复制
发表时间：
2011-12-15
影响因子：
5.8
通讯作者：
Zhu, Zi-Qiang
中科院分区：
文献类型：
--
作者：
Du, Zhe;Guan, Yi-Xin;Zhu, Zi-Qiang
采用水力空化混合器（SAA-HCM）引入的超临界流体辅助雾化来生产溶菌酶微粒，其粒径分布受控在气雾剂药物输送范围内。该过程基于二氧化碳的雾化效应。一定量的二氧化碳在溶液中的增溶起着关键作用，HCM可以大大强化二氧化碳与液体原料之间的传质。使用水作为溶剂来溶解溶菌酶，因此没有检测到有机残留。研究了工艺参数对颗粒形成的影响，包括沉淀器中的温度、混合器中的压力和温度、溶液浓度以及CO(2)/溶液的进料比。这些颗粒的特征在于其形态和粒径：在最佳操作条件下始终可以生产出直径范围在 0.2 至 5 μm 之间的明确的球形和分离颗粒。生物活性测定表明，溶菌酶的活性通常保持在85%以上。进一步进行固态表征以研究溶菌酶在此过程中的变化。傅里叶变换红外光谱表明加工后的溶菌酶二级结构没有发生变化。 X射线衍射分析表明，所生产的溶菌酶颗粒仍保持与原料类似的无定形状态。差示扫描量热法和热重分析表明，水缔合性没有显着差异，但随着加工后含水量的增加而变化。 (C) 2011 Elsevier B.V. 保留所有权利。
Supercritical fluid assisted atomization introduced by hydrodynamic cavitation mixer (SAA-HCM) was used to produce lysozyme microparticles with controlled particle size distribution in the range for aerosol drug delivery. The process is based on the atomization effect of carbon dioxide. The solubilization of certain amount of carbon dioxide in the solution plays the key role and the HCM can intensify mass transfer between carbon dioxide and liquid feedstock greatly. Water was used as the solvent to solubilize lysozyme and thus no organic residual was detected. The influences of process parameters on particle formation were investigated including temperature in the precipitator, pressure and temperature in the mixer, concentration of the solution and feed ratio CO(2)/solution. The particles were characterized with respect to their morphologies and particle size: well defined, spherical and separated particles with diameters ranging between 0.2 and 5 mu m could be always produced at optimum operating conditions. Bio-activity assay showed that good activity maintenance of higher than 85% for lysozyme was usually achieved. Solid state characterizations were further performed to investigate the changes of lysozyme in the process. Fourier transform infrared spectroscopy indicated that no change in secondary structure had occurred for processed lysozyme. X-ray diffraction analysis showed that the lysozyme particles produced remained similarly amorphous as the raw material. Differential scanning calorimetry and thermogravimetry analysis revealed that there was no significant difference in water association but with the increase of water content after processing. (C) 2011 Elsevier B.V. All rights reserved.