以甘草酸为稳定剂制备黄芩苷固体纳米晶体
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摘要
目的制备以甘草酸为稳定剂的黄芩苷固体纳米晶体(baicalin solid nanocrystal,BCN-SN),并考察其体外释放特性。方法采用高速剪切-高压均质法制备黄芩苷纳米混悬剂,并进一步冷冻干燥得BCN-SN,以平均粒径及多分散指数(PDI)为指标采用单因素实验优化处方及工艺参数,对所得BCN-SN进行理化性质表征,并测定其体外溶出度。结果以甘草酸为稳定剂,甘露醇-甘草酸为冻干保护剂制备的BCN-SN平均粒径为(478.0±6.5)nm,PDI为0.230±0.015。扫描电镜显示BCN-SN呈不规则球形,大小较均匀;差式扫描量热法表明黄芩苷制备成固体纳米晶体后,以无定形状态存在;体外释放结果表明BCN-SN的溶出速率和溶解度显著高于物理混合物。结论以甘草酸作为天然稳定剂的固体纳米晶体制备方法简便,能显著改善难溶性药物的溶解性,具有广阔的应有前景。
Objective To prepare baicalin solid nanocrystal(BCN-SN) stabilized by glycyrrhizic acid(GA) and determine its in vitro release characteristics. Methods The high-speed shearing-high pressure homogenization technology was adopted in the preparation of BCN nanosuspension, and then BCN nanosuspension was solidified into BCN-SN by freeze-drying. The formula and process of BCN-SN were optimized by the single factor experiment with average particle size and polydispersity index(PDI) as indicator.BCN-SN were prepared under the optimal conditions and characterized for crystal-linity and particle size. In vitro release of BCN-SN was also determined. Results The particle size of BCN-SN stabilized by GA and protected by mannitol-GA was(478.0 ± 6.5) nm, and the polydispersity index(PDI) was 0.230 ± 0.015, respectively. The results of SEM showed that BCN-SN was irregular spherical and DSC showed that BCN-SN was amorphous after being prepared into solid nanocrystal. In the in vitro dissolution test, BCN-SN showed a significantly increased dissolution. Conclusion The method employed to prepare the BCN-SN stabilized by GA is simple and low-cost. BCN-SN can significantly improve the dissolution of BCN, which has a broad application.
Objective To prepare baicalin solid nanocrystal(BCN-SN) stabilized by glycyrrhizic acid(GA) and determine its in vitro release characteristics. Methods The high-speed shearing-high pressure homogenization technology was adopted in the preparation of BCN nanosuspension, and then BCN nanosuspension was solidified into BCN-SN by freeze-drying. The formula and process of BCN-SN were optimized by the single factor experiment with average particle size and polydispersity index(PDI) as indicator.BCN-SN were prepared under the optimal conditions and characterized for crystal-linity and particle size. In vitro release of BCN-SN was also determined. Results The particle size of BCN-SN stabilized by GA and protected by mannitol-GA was(478.0 ± 6.5) nm, and the polydispersity index(PDI) was 0.230 ± 0.015, respectively. The results of SEM showed that BCN-SN was irregular spherical and DSC showed that BCN-SN was amorphous after being prepared into solid nanocrystal. In the in vitro dissolution test, BCN-SN showed a significantly increased dissolution. Conclusion The method employed to prepare the BCN-SN stabilized by GA is simple and low-cost. BCN-SN can significantly improve the dissolution of BCN, which has a broad application.
引文
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[2]雷奇林,黄雅兰,钟茜,等.基于网络药理学的黄芩抗炎作用机制研究[J].中草药,2018,49(15):3523-3530.
[3]朱水兰,黎宇,严奉东,等.油酸诱导胰岛素抵抗Hep G2细胞模型优化及小檗碱、黄芩苷、葛根素和甘草苷的体外降糖作用研究[J].药物评价研究,2017,40(10):1402-1407.
[4]刘仁伟,刘冰.黄芩苷胶囊联合胸腺法新治疗慢性乙型肝炎的临床研究[J].现代药物与临床,2018,33(12):3312-3316.
[5]Ping Y,Yu L,Hu Y Q,et al.Study on targeting and in vitro anti-oxidation of baicalin solid lipid nanoparticles[J].Chin Herb Med,2012,4(4):336-340.
[6]赵炎军,王建平,吴凡,等.黄芩苷PEG-PLGA纳米胶束的制备、表征及在急性心肌缺血模型大鼠体内的组织分布[J].中草药,2018,49(18):4269-4276.
[7]吴玉梅,李新悦,张谦,等.单克隆抗体OX26修饰的丹酚酸B/黄芩苷纳米结构脂质载体研究[J].中草药,2018,49(12):2801-2808.
[8]高彩芳,夏加璇,朱颖,等.纳米技术在改善中药有效成分成药性中的应用[J].中草药,2018,49(12):2754-2762.
[9]申宝德,连王权,沈成英,等.微型化介质研磨法制备难溶性黄酮类化合物纳米混悬剂[J].中草药,2017,48(21):4413-4418.
[10]徐浩,高艺璇,王向涛.槲皮素纳米混悬剂的制备、表征及抗乳腺癌研究[J].中草药,2019,50(1):42-51.
[11]武娜,张利红,程玲,等.金丝桃苷固体纳米晶体的制备及其体外释放研究[J].中草药,2015,46(12):1759-1763.
[12]靳世英,袁海龙,靳士晓,等.黄芩苷纳米晶体微丸的制备及其药代动力学初步研究[J].中国中药杂志,2013,38(8):1156-1159.
[13]Wu W,He W,Tan Y,et al.Food protein-stabilized nanoemulsions as potential delivery systems for poorly water-soluble drugs:preparation,in vitro characterization,and pharmacokinetics in rats[J].Int J Nanomed,2011,20(11):521-532.
[14]Hawkins M J.Protein nanoparticles as drug carriers in clinical medicine[J].Adv Drug Delivery Rev,2008,60(8):876-885.
[15]Gü?lü-üstünda??,Mazza G.Saponins:Properties,applications and processing[J].Crit Rev Food Sci,2007,47(3):231-258.
[16]Xie Y,Ma Y,Xu J,et al.Panax notoginseng saponins as a novel nature stabilizer for poorly soluble drug nanocrystals:A case study with baicalein[J].Molecules,2016,21(9):1149-1160.
[17]Chen Y,Liu Y,Xu J,et al.A natural triterpenoid saponin as multifunctional stabilizer for drug nanosuspension powder[J].AAPS Pharm Sci Tech,2017,18(7):1-10.
[18]Yue P F,Li Y,Wan J,et al.Study on formability of solid nanosuspensions during nanodispersion and solidification:I.Novel role of stabilizer/drug property[J].Int J Pharm,2013,454(1):269-277.
[19]Zong L L,Li X H,Wang H Y,et al.Formulation and characterization of biocompatible and stable IV.itraconazole nanosuspensions stabilized by a new stabilizer polyethylene glycol-poly(betabenzyl-laspartate)(PEG-PBLA)[J].Int J Pharm,2017,531(1):108-117.
[20]Xu Y,Liu X Y,Lian R Y,et al.Enhanced dissolution andoral bioavailability of aripiprazole nanosuspensions prepared bynanoprecipitation/homogenization based on acid-base neutralization[J].Int J Pharm,2012,438(12):287-295.
[21]汪小涵,钟芮娜,申宝德,等.落新妇苷无定型纳米混悬剂的制备及其体外评价[J].中国中药杂志,2018,43(8):1626-1632.
[22]杨璇.甘草对葛根、黄芩增溶作用和机理的研究[D].北京:北京中医药大学,2013.
[23]中国药典[S].一部.2015.
[24]He W,Lu Y,Qi J,et al.Food proteins as novel nanosuspension stabilizers for poorly water-soluble drugs[J].Int J Pharm,2013,441(12):269-278.
[25]韩宝来,刘伟芬,李禄辉.应用新型稳定剂制备紫杉醇纳米混悬剂及其稳定作用评价[J].国际药学研究杂志,2018,45(5):393-399.
[26]李涯松,杨洁红,樊守艳,等.甘草酸对雷公藤多甙治疗类风湿性关节炎增效减毒作用的实验研究[J].中国中医药科技,2008,15(4):293-294.