甘草酸超微粉体的反溶剂重结晶法制备、表征及中试放大工艺的研究
发布时间：2018-11-03 20:00
【摘要】：本文对反溶剂重结晶法制备甘草酸超微粉体进行了研究,在确定制备工艺时,采用响应面试验设计方法对影响甘草酸超微粉体质量优劣的系列影响因子进行筛选,通过制备温度从13℃到31。C,甘草酸无水乙醇溶液浓度从275 mg/ml到425 mg/ml,反溶剂与溶剂体积比从8：1到16：1,反应强度从1000 r/min到2000 r/min和反应时间从4.75mmin到8.25min的32个不同的多因素试验,结合各组实验产物的粒径,选出制备甘草酸超细微粒的最佳工艺条件。并且对得到的甘草酸超微粉体进行扫描电子显微镜(SEM)、X射线衍射(xRD)、傅立叶变换红外光谱(FT-IR)、差示量热(DSC)以及热重分析(TG)等检测,比较制备前后甘草酸在形貌,晶态,化学结构等方面的变化。通过体外溶出度试验,比较制备前后溶出度及生物利用度的差异。 此外,为了实现甘草酸超微粉体制备的工业化生产,在甘草酸反溶剂重结晶小试工艺成熟的基础上,运用实验室自主研发的新型设备-逆流负压反溶剂微粉制备装置对其进行了中试放大研究,以检测该路线的可行性,力争设计出在工业生产中有实用价值的切实可行、利于操作的工艺。 通过对实验进行验证得到了甘草酸微粉制备的最佳工艺条件：甘草酸浓度：275mg/mL,体积比：9.96,反应强度1105.98 r·min-1,温度：30.34℃,时间为5.52min在上述制备条件下得到的微粉粒径达到了203nm,与微粉化预测值220 nm相接近。制备后的甘草酸粒径变小、分布均匀,并且晶态,化学结构,组成成分等未发生变化,溶解度却增大并且生物利用度提高,对中试放大产品质量的检测结果表明,产品粒径稳定,为实现工业化生产奠定了坚实基础。
[Abstract]:In this paper, the preparation of ultrafine glycyrrhizic acid powder by anti-solvent recrystallization method was studied. When the preparation process was determined, a series of factors affecting the quality of ultrafine glycyrrhizic acid powder were selected by using the response surface test design method. The concentration of anhydrous ethanol solution of glycyrrhizic acid ranged from 275 mg/ml to 425 mg/ml, and the volume ratio of antisolvent to solvent was from 8:1 to 16: 1. The reaction intensity ranged from 1000 r/min to 2000 r/min and the reaction time was 32 different factors from 4.75mmin to 8.25min. The optimum preparation conditions of glycyrrhizic acid ultrafine particles were selected according to the particle size of each group. The ultrafine glycyrrhizic acid powder was detected by scanning electron microscope (SEM), (SEM), X ray diffraction (xRD),) Fourier transform infrared spectroscopy (FT-IR), differential calorimetry (DSC) and thermogravimetric analysis (TG). The morphology, crystal state and chemical structure of glycyrrhizic acid were compared before and after preparation. The dissolution and bioavailability before and after preparation were compared by in vitro dissolution test. In addition, in order to realize the industrial production of ultrafine glycyrrhizic acid powder, the anti-solvent recrystallization process of glycyrrhizic acid was developed. In order to test the feasibility of this route, a pilot scale up study was carried out by using a new equipment developed by the laboratory, the counter-current negative pressure anti-solvent micro-powder preparation device, in order to design a practical value in industrial production. An easy-to-operate process. The optimum conditions for the preparation of glycyrrhizic acid powder were obtained: glycyrrhizic acid concentration: 275 mg / mL, volume ratio: 9.96, reaction intensity: 1105.98 r min-1, temperature: 30.34 鈩，
本文编号：2308857
[Abstract]:In this paper, the preparation of ultrafine glycyrrhizic acid powder by anti-solvent recrystallization method was studied. When the preparation process was determined, a series of factors affecting the quality of ultrafine glycyrrhizic acid powder were selected by using the response surface test design method. The concentration of anhydrous ethanol solution of glycyrrhizic acid ranged from 275 mg/ml to 425 mg/ml, and the volume ratio of antisolvent to solvent was from 8:1 to 16: 1. The reaction intensity ranged from 1000 r/min to 2000 r/min and the reaction time was 32 different factors from 4.75mmin to 8.25min. The optimum preparation conditions of glycyrrhizic acid ultrafine particles were selected according to the particle size of each group. The ultrafine glycyrrhizic acid powder was detected by scanning electron microscope (SEM), (SEM), X ray diffraction (xRD),) Fourier transform infrared spectroscopy (FT-IR), differential calorimetry (DSC) and thermogravimetric analysis (TG). The morphology, crystal state and chemical structure of glycyrrhizic acid were compared before and after preparation. The dissolution and bioavailability before and after preparation were compared by in vitro dissolution test. In addition, in order to realize the industrial production of ultrafine glycyrrhizic acid powder, the anti-solvent recrystallization process of glycyrrhizic acid was developed. In order to test the feasibility of this route, a pilot scale up study was carried out by using a new equipment developed by the laboratory, the counter-current negative pressure anti-solvent micro-powder preparation device, in order to design a practical value in industrial production. An easy-to-operate process. The optimum conditions for the preparation of glycyrrhizic acid powder were obtained: glycyrrhizic acid concentration: 275 mg / mL, volume ratio: 9.96, reaction intensity: 1105.98 r min-1, temperature: 30.34 鈩，
本文编号：2308857
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