基于超临界流体技术的四环素超细微粒制备

Preparation of Tetracycline Microparticles Based on Supercritical Fluid Technique

吸入式给药既要求药物微粒有合适的平均粒径,又要求粒径分布在较小的范围内。利用近两年提出的超临界流体膨胀减压过程,以四环素-水+乙醇-二氧化碳系统为研究对象,成功制备了适于吸入式给药的四环素超细微粒,系统分析了混合器压力和温度、溶液浓度及进液速率对微粒形态,粒径和粒径分布的影响。结果表明:利用超临界膨胀减压过程,以水和乙醇的混合溶液为溶剂,可制备出粒径在1～3μm的四环素超细微粒,且大部分微粒形态呈完好的球形;各影响因素对微粒粒径及其分布均有不同程度的影响,其中混合器压力和溶液浓度对微粒粒径及其分布的影响最明显,进液速率和混合器温度的影响较小。在研究操作范围内,较为理想的操作条件为混合器压力12MPa、温度60℃,溶液浓度15mg·mL-1,进液速度5mL·min-1。

Inhalation administration requests the microparticles with appropriate average diameters and narrow diameter distribution.In this paper,the tetracycline microparticles suitable for inhalation administration were prepared successfully by supercritical fluid expansion depressurization process developed in recent years.The influences of the operation parameters including the pressure and temperature in the mixing vessel,the solution concentration and the solution feed rate on the particle morphology,diameter and diameter distribution were investigated in detail.The results show that the tetracycline microparticles with diameters between 1 and 3 μm can be obtained by using the mixture of water and ethanol as initial solvent.Most of the prepared particles are well-defined spherical in morphology.The different process parameters have different influences on particle size and particle size distributions.The pressure in the mixing vessel and the solution concentration are two most effective parameters,while the solution feed rate is the next and the temperature in the mixing vessel has little influence on the formation of microparticles.The optimal operation conditions for preparing tetracycline microparticles in the operation range of this work were found as follows：the pressure of 12 MPa and temperature of 60℃ in the mixing vessel,the solution concentration of 15 mg·mL-1 and the solution feed rate of 5 mL·min-1.