响应面设计法优化反溶剂重结晶制备甘草酸微粉

以乙醇为溶剂,乙酸乙酯作为反溶剂制备甘草酸微粉,采用响应面—中心组合设计法,对甘草酸微粉颗粒大小和形貌的主要影响因子（溶剂与反溶剂体积比、温度、反应强度、反应时间、溶液浓度）进行考察,并得到最佳工艺条件。实验分别利用扫描电镜（SEM）、X射线衍射（XRD）、红外光谱（FT-IR）、热重分析（TG）、差示扫描（DSC）和激光粒度等分析方法对原粉及微粉的性质进行了表征。研究结果表明：粒径与体系温度、反应时间成正比,并随反溶剂与溶剂体积比的增加呈现先减小后增大的趋势。验证实验结果表明：甘草酸浓度：275mg/mL,体积比：9.96,反应强度为1105.98 r/min,温度为30.34℃,时间为5.52min的条件下测得微粉粒径达到了203nm,与微粉化预测值220nm相接近,此外,表征参数显示微粉的化学性质较原药并无明显改变,最终制得较原粉形态规则且分布均匀的小颗粒。

Optimization of Anti-solvent Recrystallization of Glycyrrhizin Acid Powder Using Response Surface Methodology

Taking ethanol as solvent,glycyrrhizic acid powder was prepared by ethylacetate as the anti-solvent.Response surface central composite design was used to inspect the major factors（volume ratio of solvent and anti-solvent,temperature,intensity of reaction,reaction time,solution concentration）affecting the size and morphology of Glycyrrhizic acid powder.In order to characterize the untreated Glycyrrhizic acid and Glycyrrhizic acid power,experiments were conducted using scanning electron microscope（SEM）,X-ray diffraction（XRD）,infrared spectroscopy（FT-IR）,thermogravimetric analysis（TG）,differential scanning calorimetry（DSC）and the average particle size analysis.Results show that the particle size has a positive relationship with system temperature and reaction time,but presents a trend of decreasing first and then increasing as the volume ratio of anti-solvent and solvent increases.The result of verification experiment indicates that the measured powder particle size reaches 203nm when the concentration is 275mg/ml;volume ratio is 9.96;reaction intensity is 1105.98r/min;temperature is 30.34℃ and reaction time is 5.52min,which is close to the forecast powder of 220nm.In addition,characterization parameters show that the physical and chemical properties of the powder do not significantly change when compared with the original drug.Finally,particle with regular shape and uniform distribution is obtained.