超临界CO_2抗溶剂法制备姜黄素-EC缓释复合微粒的工艺研究

Preparation of curcumin-EC sustained-release composite particles by supercritical CO_2 anti-solvent technology

采用超临界CO2抗溶剂法制备具有缓释效果的姜黄素-乙基纤维素(EC)复合微粒。以载药量和回收率为综合评价指标,在单因素的基础上采用正交试验设计优选姜黄素-EC缓释复合微粒的制备工艺,并对优选的工艺组合进行了载药量、回收率、粒径分布、扫描电镜(SEM)、红外光谱(IR)、差示扫描量热法(DSC)以及体外溶出等实验分析。正交试验得到的优选工艺为结晶温度45℃,结晶压力10 MPa,姜黄素质量浓度8 g·L-1,溶液体积流量0.9 m L·min-1,动态CO2流出速度4 L·min-1。此工艺条件下,制备的复合微粒的平均载药量和回收率分别为33.01%,83.97%,体积平均粒径为20.632μm;IR与DSC分析表明姜黄素与EC可能发生了相互作用;体外溶出实验表明姜黄素-EC复合微粒具有良好的缓释效果。超临界CO2抗溶剂法可制备具有缓释效果的姜黄素-EC复合微粒。

Curcumin-ethyl-cellulose （EC） sustained-release composite particles were prepared by using supercritical CO2 anti-sol- vent technology. With drug loading and yield of inclusion complex as evaluation indexes,on the basis of single factor tests, orthogonal experimental design was used to optimize the preparation process of curcumin-EC sustained-release composite particles. The experi- ments such as drug loading, yield, particle size distribution, electron microscope analysis （SEM）, infrared spectrum （IR）, differenti- al scanning calorimetry （DSC） and in vitro dissolution were used to analyze the optimal process combination. The orthogonal experi- mental optimization process conditions were set as follows： crystallization temperature 45 ℃, crystallization pressure 10 MPa, curcumin concentration 8 g · L^- 1, solvent flow rate 0. 9 mL · min^- 1, and CO2 velocity 4 L · min ^- 1. Under the optimal conditions, the average drug loading and yield of curcumin-EC sustained-release composite particles were 33.01% and 83.97% , and the average particle size of the particles was 20. 632 μm. IR and DSC analysis showed that curcumin might complex with EC. The experiments of in vitro disso- lution showed that curcumin-EC composite particles had good sustained-release effect. Curcumin-EC sustained-release composite parti- cles can be prepared by supercritical CO2 anti-solvent technology.