氧化苦参碱磷脂复合物固体脂质纳米粒冻干粉的制备与质量评价
|
摘要
目的:制备氧化苦参碱磷脂复合物固体脂质纳米粒(OMT-PC-SLN)冻干粉,并对其进行药剂学性质评价。方法:采用伪三元相图优选微乳处方;以包封率为指标,采用单因素试验优选OMT-PC-SLN冻干粉的处方工艺;利用透射电子显微镜(TEM)观察该制剂的外观形态,激光粒度仪测定粒径,并考察OMT-PC-SLN冻干粉的体外释药性能。结果:最佳处方工艺为大豆磷脂和15-羟基硬脂酸聚乙二醇酯(Kolliphor HS 15)为乳化剂,乙醇为助乳化剂,乳化剂与助乳化剂的比例(Km)=3∶2,油相∶(乳化剂+助乳化剂)=1∶9,氧化苦参碱磷脂复合物-硬脂酸-大豆磷脂-Kolliphor HS 15-乙醇(30∶100∶180∶360∶360);含4%甘露醇的水50 m L为外水相,1 000 r·min-1冰浴搅拌固化1 h,于-20℃预冻24 h,取出,干燥24 h。OMT-PC-SLN冻干粉外观呈类球形,包封率(38. 09±1. 24)%,平均粒径785. 5 nm,多分散系数(PDI) 0. 456,Zeta电位-24. 82 m V;体外释放结果表明OMT-PC-SLN冻干粉2 h时累积释放率72. 63%,12 h累积释放率98. 42%,原料药在2 h的累积释放率98. 60%。结论:优选的OMT-PC-SLN冻干粉处方工艺稳定、重复性好;与原料药相比,OMT-PC-SLN冻干粉体外释放较慢,具有一定的缓释效果。
Objective: To prepare oxymatrine phospholipid complex solid lipid nanoparticles( OMT-PCSLN) lyophilized powder and evaluate its pharmaceutical properties. Method: Pseudo-ternary phase diagram was employed to optimize the formula of microemulsion; single factor experiments were adopted to optimize the formulation process of OMT-PC-SLN lyophilized powder with encapsulation efficiency as index; the morphology of this preparation was observed by transmission electron microscope( TEM). The particle size was measured by particle size analyzer and the in vitro release performance of OMT-PC-SLN lyophilized powder was examined.Result: Optimal formulation process was as following: taking soybean phospholipid and polyethylene glycol 15-hydroxystearate( Kolliphor HS 15) as the emulsifier,ethanol as co-emulsifier,ratio of emulsifier to co-emulsifier( Km) = 3 ∶ 2,oil phase ∶( emulsifier + co-emulsifier) = 1 ∶ 9,oxymatrine phospholipid complex-stearic acidsoybean phospholipid-Kolliphor HS 15-ethanol( 30 ∶ 100 ∶ 180 ∶ 360 ∶ 360); taking 50 m L of 4% mannitol solution as the external aqueous phase,ice bath stirring at 1 000 r·min-1 and solidifying for 1 h,precooled at-20 ℃ for24 h, took out and dried for 24 h. OMT-PC-SLN lyophilized powder was spherical in appearance with encapsulation efficiency of( 38. 09 ± 1. 24) %, average particle size of 785. 5 nm, polydispersity coefficient( PDI) of 0. 456 and the Zeta potential of-24. 82 m V. The cumulative release rates of OMT-PC-SLN lyophilized powder were 72. 63% at 2 h and 98. 42% at 12 h; the cumulative release rate of oxymatrine( crude drug) was98. 60% at 2 h. Conclusion: This optimized formulation process of OMT-PC-SLN lyophilized powder is stable with good repeatability; compared with oxymatrine,OMT-PC-SLN lyophilized powder has a certain sustained-release effect.
Objective: To prepare oxymatrine phospholipid complex solid lipid nanoparticles( OMT-PCSLN) lyophilized powder and evaluate its pharmaceutical properties. Method: Pseudo-ternary phase diagram was employed to optimize the formula of microemulsion; single factor experiments were adopted to optimize the formulation process of OMT-PC-SLN lyophilized powder with encapsulation efficiency as index; the morphology of this preparation was observed by transmission electron microscope( TEM). The particle size was measured by particle size analyzer and the in vitro release performance of OMT-PC-SLN lyophilized powder was examined.Result: Optimal formulation process was as following: taking soybean phospholipid and polyethylene glycol 15-hydroxystearate( Kolliphor HS 15) as the emulsifier,ethanol as co-emulsifier,ratio of emulsifier to co-emulsifier( Km) = 3 ∶ 2,oil phase ∶( emulsifier + co-emulsifier) = 1 ∶ 9,oxymatrine phospholipid complex-stearic acidsoybean phospholipid-Kolliphor HS 15-ethanol( 30 ∶ 100 ∶ 180 ∶ 360 ∶ 360); taking 50 m L of 4% mannitol solution as the external aqueous phase,ice bath stirring at 1 000 r·min-1 and solidifying for 1 h,precooled at-20 ℃ for24 h, took out and dried for 24 h. OMT-PC-SLN lyophilized powder was spherical in appearance with encapsulation efficiency of( 38. 09 ± 1. 24) %, average particle size of 785. 5 nm, polydispersity coefficient( PDI) of 0. 456 and the Zeta potential of-24. 82 m V. The cumulative release rates of OMT-PC-SLN lyophilized powder were 72. 63% at 2 h and 98. 42% at 12 h; the cumulative release rate of oxymatrine( crude drug) was98. 60% at 2 h. Conclusion: This optimized formulation process of OMT-PC-SLN lyophilized powder is stable with good repeatability; compared with oxymatrine,OMT-PC-SLN lyophilized powder has a certain sustained-release effect.
引文
[1] Rodenak-Kladniew B,Islan G A,de Bravo M G,et al.Design,characterization and in vitro evaluation of linalool-loaded solid lipid nanoparticles as potent tool in cancer therapy[J]. Colloids Surf B Biointerfaces,2017,154:123-132.
[2]夏爱晓,宋倩倩,孙渊.固体脂质纳米粒制备及应用研究进展[J].药学实践杂志,2012,30(5):331-333.
[3]朴林梅,金勇,崔艳琳,等.月见草油固体脂质纳米粒的制备及质量评价[J].中药材,2015,38(6):1290-1294.
[4]吕佳,刘冰,张振秋,等.苦参碱固体脂质纳米粒的制备[J].中国实验方剂学杂志,2013,19(19):61-63.
[5]石磊,史丽娟.中药单体-氧化苦参碱药理作用研究新进展[J].山西医药杂志,2015,44(2):123-126.
[6]史丽娟,王磊,宋光耀.氧化苦参碱肝脏药理作用的研究进展[J].世界科学技术—中医药现代化,2014,16(2):448-451.
[7] HUANG L H,ZHONG Y M,XIONG X H,et al. The disposition of oxymatrine in the vascularly perfused rat intestine-liver preparation and its metabolism in rat liver microsomes[J]. J Pharm Sci,2016,105(2):897-903.
[8]陈晓峡,向小庆,叶红,等.苦参碱及氧化苦参碱抗肿瘤作用的研究进展[J].中国实验方剂学杂志,2013,19(11):361-364.
[9]张彦燕,王羿,徐旖旎,等.氧化苦参碱对TGF-β1诱导心肌细胞损伤的保护作用[J].中国实验方剂学杂志,2017,23(17):149-153.
[10]付凌云,黄海烽,徐旖旎,等.氧化苦参碱抑制p38MAPK磷酸化改善醛固酮诱导心肌成纤维细胞增殖[J].中国实验方剂学杂志,2017,23(22):103-107.
[11]刘苏,秦晶,陆伟根,等.氧化苦参碱在大鼠体内药代动力学特征[J].中成药,2011,33(6):962-965.
[12]万发里,邓树海,苗彩云.氧化苦参碱缓释片的制备及其体外释药动力学研究[J].中国药学杂志,2005,39(13):1002-1003.
[13]游荣辉,王陆军,丛龙波,等.氧化苦参碱磷脂复合物的理化性质研究[J].解放军药学学报,2007,23(3):191-194.
[14]袁海龙,杨明,游荣辉,等.氧化苦参碱磷脂复合物的制备、评价及药代动力学研究(英文)[C]//世界中医药学会联合会.第二届中药现代化新剂型新技术国际学术会议论文集:2006年卷.北京:中国学术期刊(光盘版)电子杂志社,2006:288-298.
[15]张蕾,訾鹏,高洁,等.非离子型表面活性剂HS 15在药剂中的研究进展[J].药学进展,2015,39(5):370-375.
[16]蒋楠,李晔,陈钢,等.鸦胆子油自微乳的制备及溶出度考察[J].中国实验方剂学杂志,2013,19(9):45-48.
[17]李楠,李锡晶,王倩.微乳法制备姜黄素固体脂质纳米粒[J].中国药房,2015,26(19):2698-2702.
[18]梁健钦,刘华钢.白藜芦醇固体脂质纳米粒制备工艺及形态学研究[J].中国实验方剂学杂志,2010,16(14):28-30.
[19]殷润婷,杨阳,张婕,等.固体脂质纳米粒的制备及在治疗中的应用研究[J].现代生物医学进展,2014,14(36):7182-7185.
[20]陆云华,曹丽萍,李茜,等.乌索酸固体脂质纳米粒的制备及其抗肿瘤活性考察[J].中国实验方剂学杂志,2014,20(19):1-5.
[2]夏爱晓,宋倩倩,孙渊.固体脂质纳米粒制备及应用研究进展[J].药学实践杂志,2012,30(5):331-333.
[3]朴林梅,金勇,崔艳琳,等.月见草油固体脂质纳米粒的制备及质量评价[J].中药材,2015,38(6):1290-1294.
[4]吕佳,刘冰,张振秋,等.苦参碱固体脂质纳米粒的制备[J].中国实验方剂学杂志,2013,19(19):61-63.
[5]石磊,史丽娟.中药单体-氧化苦参碱药理作用研究新进展[J].山西医药杂志,2015,44(2):123-126.
[6]史丽娟,王磊,宋光耀.氧化苦参碱肝脏药理作用的研究进展[J].世界科学技术—中医药现代化,2014,16(2):448-451.
[7] HUANG L H,ZHONG Y M,XIONG X H,et al. The disposition of oxymatrine in the vascularly perfused rat intestine-liver preparation and its metabolism in rat liver microsomes[J]. J Pharm Sci,2016,105(2):897-903.
[8]陈晓峡,向小庆,叶红,等.苦参碱及氧化苦参碱抗肿瘤作用的研究进展[J].中国实验方剂学杂志,2013,19(11):361-364.
[9]张彦燕,王羿,徐旖旎,等.氧化苦参碱对TGF-β1诱导心肌细胞损伤的保护作用[J].中国实验方剂学杂志,2017,23(17):149-153.
[10]付凌云,黄海烽,徐旖旎,等.氧化苦参碱抑制p38MAPK磷酸化改善醛固酮诱导心肌成纤维细胞增殖[J].中国实验方剂学杂志,2017,23(22):103-107.
[11]刘苏,秦晶,陆伟根,等.氧化苦参碱在大鼠体内药代动力学特征[J].中成药,2011,33(6):962-965.
[12]万发里,邓树海,苗彩云.氧化苦参碱缓释片的制备及其体外释药动力学研究[J].中国药学杂志,2005,39(13):1002-1003.
[13]游荣辉,王陆军,丛龙波,等.氧化苦参碱磷脂复合物的理化性质研究[J].解放军药学学报,2007,23(3):191-194.
[14]袁海龙,杨明,游荣辉,等.氧化苦参碱磷脂复合物的制备、评价及药代动力学研究(英文)[C]//世界中医药学会联合会.第二届中药现代化新剂型新技术国际学术会议论文集:2006年卷.北京:中国学术期刊(光盘版)电子杂志社,2006:288-298.
[15]张蕾,訾鹏,高洁,等.非离子型表面活性剂HS 15在药剂中的研究进展[J].药学进展,2015,39(5):370-375.
[16]蒋楠,李晔,陈钢,等.鸦胆子油自微乳的制备及溶出度考察[J].中国实验方剂学杂志,2013,19(9):45-48.
[17]李楠,李锡晶,王倩.微乳法制备姜黄素固体脂质纳米粒[J].中国药房,2015,26(19):2698-2702.
[18]梁健钦,刘华钢.白藜芦醇固体脂质纳米粒制备工艺及形态学研究[J].中国实验方剂学杂志,2010,16(14):28-30.
[19]殷润婷,杨阳,张婕,等.固体脂质纳米粒的制备及在治疗中的应用研究[J].现代生物医学进展,2014,14(36):7182-7185.
[20]陆云华,曹丽萍,李茜,等.乌索酸固体脂质纳米粒的制备及其抗肿瘤活性考察[J].中国实验方剂学杂志,2014,20(19):1-5.