超临界CO_2抗溶剂法制备芹菜素微粒的工艺研究

Preparation process of apigenin particles by supercritical CO_2 anti-solvent method

目的采用超临界CO2抗溶剂法制备芹菜素微粒,以微粒的平均粒径为评价指标,在单因素试验的基础上设计正交试验优选芹菜素微粒的制备工艺,并考察其体外溶出速率。方法对微粒进行粒度分布、扫描电镜(SEM)分析、傅里叶红外吸收光谱(FTIR)检测及差示扫描量热(DSC)法以验证优选的最佳工艺;进行芹菜素原料与芹菜素优选工艺微粒的体外溶出测试。结果正交试验得出的优选工艺条件:丙酮及二甲基亚砜共溶剂比例为24∶1,结晶温度40℃,结晶压力10 MPa,溶液体积流量2.0 mL/min,芹菜素质量浓度8 mg/mL;在此条件下可制备得到粒径明显小于芹菜素原料的芹菜素微粒,SEM显示芹菜素微粒呈不规则状;FTIR与DSC观察结果表明芹菜素微粒未发生化学结构的改变;体外溶出测试显示芹菜素优选工艺微粒的溶出速率明显高于原料药的溶出速率。结论超临界CO2抗溶剂法可用于制备芹菜素微粒,且可推测经处理后的芹菜素生物利用度提高,为制备超细微粒提供参考。

Objective To prepare the apigenin particles by supercritical CO2 anti-solvent technology,to optimize the preparation process of apigenin particles on the basis of single factor experiments using the average particle size as evaluation index through orthogonal test design,and to investigate the in vitro dissolution rate.Methods The particle size distribution,scanning electromicroscope（SEM） analysis,infrared spectrum（IR）,and differential scanning calorimetry（DSC） were used to validate the selected process.The external dissolution rates of apigenin ingredient and apigenin particles of the optimal process were tested to speculate the bioavailability of apigenin.Results The optimal process conditions by orthogonal test were set as follows：The proportion of acetone and dimethyl sulfoxide（DMSO） was 24∶1,temperature was 40 ℃,pressure was 10 MPa,solution volumetric flow rate was 2.0 mL/min,and mass concentration of apigenin was 8 mg/mL.Under the optimal conditions,the volume average particle size was obviously smaller than that of ingredient.And the shapes of apigenin were irregular.FTIR and DSC analyses showed that the chemical structure did not change.The results showed that the in vitro dissolution rate of apigenin particles of the optimal process was significantly larger than that of apigenin ingredient.Conclusion The supercritical CO2 anti-solvent technology is feasible to prepare apigenin particles and promote its bioavailability,and it provides a reference basis for preparing ultrafine particles.