超临界辅助雾化法制备红霉素超细微粒

2007 年 2 月 Journal of Chemical Engineering of Chinese Universities Feb. 2007 文章编号：1003-9015(2007)01-0043-05

超临界辅助雾化法制备红霉素超细微粒

李志义, 赵顺轩, 蒋静智, 刘学武, 孟庭宇

(大连理工大学流体与粉体工程研究设计所, 辽宁大连 116012)

摘要：超临界辅助雾化(SAA)过程是近两年才提出的一种制备纳、微米粉体微粒的新方法，是一种高效的超细粉体

制备技术，在药物超细化处理方面有广阔的应用前景。在自建的超临界辅助雾化过程实验装置上，以红霉素-乙醇-二

氧化碳系统为研究对象，分别研究了混合器压力和温度、溶液浓度及进液速率对微粒形态和粒径的影响。实验结果表

明：选用乙醇做溶剂可制备出粒径在1~3 µm的红霉素超细微粒，大部分微粒形态呈完整的球形；各影响因素对微粒

粒径及粒径分布均有不同程度的影响，其中混合器压力对微粒粒径及粒径分布的影响最明显，混合器温度的影响最小，微粒粒径及粒径分布可通过改变操作参数进行控制；在本研究范围内，最优操作条件为混合器压力10.5 MPa，混合器

温度70℃，溶液浓度15mg⋅min−1，进液速度9mL⋅min−1。实验制得的微粒适用于吸入式给药。

关键词：超临界辅助雾化过程；红霉素；超细微粒；吸入式给药

中图分类号：TQ028.672；TQ029.1；R978.15 文献标识码：A

Preparation of Erythromycin Micro-Particles by Supercritical Assisted Atomization

LI Zhi-yi, ZHAO Shun-xuan, JIANG Jing-zhi, LIU Xue-wu, MENG Ting-yu (Research & Design Institute of Fluid and Powder Engineering, School of Chemical Engineering, Dalian

University of Technology, Dalian 116012, China)

Abstract: Supercritical assisted atomization (SAA) is a new technique developed recently for producing nano- and micro-particles, and it has promising potentials in pharmaceutical micronization. An experimental apparatus for SAA process was set up, and the experiments for producing erythromycin micro-particles from erythromycin-ethanol-CO2 system by SAA process were conducted. The effects of process parameters, such as the pressure and the temperature of the saturator, the inlet flow rate and inlet solution concentration of the precipitator, on the particle size (PS) and particle size distributions (PSD) were examined. The experiments show that the PS and PSD of particles produced by SAA process can be controlled by adjusting process parameters, and among them, the pressure of the saturator used has the most effect on the PS and PSD, while the temperature of the saturator has the least effect. When using ethanol as solvent, the optimum operating conditions of using SAA process to produce erythromycin micro-particles from erythromycin-ethanol-CO2 system were found as follows. The pressure and temperature of the saturator are 10.5 MPa and 70℃, respectively, the inlet flow rate and the concentration of inlet solution of the precipitator are 9 mL·min−1 and 15 mg⋅mL−1, respectively. Using SAA process with above conditions, the erythromycin particles with diameters between 1~3 µm can be obtained, and which are suitable to be used for inhalation delivery system.

Key words: supercritical assisted atomization; erythromycin; micro-particles; inhalation delivery

1引言

红霉素是最早应用于临床的大环内酯类广谱抗生素[1]，对革兰氏阳性菌作用强，临床上主要用于呼

收稿日期：2005-07-10；修订日期：2005-12-06。

基金项目：国家自然科学基金资助项目(30400571)，辽宁省自然科学基金资助项目(20032123)。

作者简介：李志义(1959-)，男，甘肃天水人，大连理工大学教授，博士。通讯联系人：李志义，E-mail：lizy@