【摘要】：本文對反溶劑重結(jié)晶法制備甘草酸超微粉體進行了研究,在確定制備工藝時,采用響應(yīng)面試驗設(shè)計方法對影響甘草酸超微粉體質(zhì)量優(yōu)劣的系列影響因子進行篩選,通過制備溫度從13℃到31。C,甘草酸無水乙醇溶液濃度從275 mg/ml到425 mg/ml,反溶劑與溶劑體積比從8：1到16：1,反應(yīng)強度從1000 r/min到2000 r/min和反應(yīng)時間從4.75mmin到8.25min的32個不同的多因素試驗,結(jié)合各組實驗產(chǎn)物的粒徑,選出制備甘草酸超細(xì)微粒的最佳工藝條件。并且對得到的甘草酸超微粉體進行掃描電子顯微鏡(SEM)、X射線衍射(xRD)、傅立葉變換紅外光譜(FT-IR)、差示量熱(DSC)以及熱重分析(TG)等檢測,比較制備前后甘草酸在形貌,晶態(tài),化學(xué)結(jié)構(gòu)等方面的變化。通過體外溶出度試驗,比較制備前后溶出度及生物利用度的差異。 此外,為了實現(xiàn)甘草酸超微粉體制備的工業(yè)化生產(chǎn),在甘草酸反溶劑重結(jié)晶小試工藝成熟的基礎(chǔ)上,運用實驗室自主研發(fā)的新型設(shè)備-逆流負(fù)壓反溶劑微粉制備裝置對其進行了中試放大研究,以檢測該路線的可行性,力爭設(shè)計出在工業(yè)生產(chǎn)中有實用價值的切實可行、利于操作的工藝。 通過對實驗進行驗證得到了甘草酸微粉制備的最佳工藝條件：甘草酸濃度：275mg/mL,體積比：9.96,反應(yīng)強度1105.98 r·min-1,溫度：30.34℃,時間為5.52min在上述制備條件下得到的微粉粒徑達到了203nm,與微粉化預(yù)測值220 nm相接近。制備后的甘草酸粒徑變小、分布均勻,并且晶態(tài),化學(xué)結(jié)構(gòu),組成成分等未發(fā)生變化,溶解度卻增大并且生物利用度提高,對中試放大產(chǎn)品質(zhì)量的檢測結(jié)果表明,產(chǎn)品粒徑穩(wěn)定,為實現(xiàn)工業(yè)化生產(chǎn)奠定了堅實基礎(chǔ)。
[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，

本文編號：2308857