超临界辅助雾化法制备红霉素超细微粒

Preparation of Erythromycin Micro-Particles by Supercritical Assisted Atomization

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略技术，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1-3μm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10．5MPa，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。

Supereritical 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.