地榆皂苷自乳化药物传递系统的制备及质量评价
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摘要
目的建立地榆皂苷自乳化药物传递系统的制备方法并对其进行质量评价。方法通过溶解度试验、辅料配伍、三元相图中形成乳剂区域面积的大小和D-最优混料实验设计来筛选地榆皂苷自乳化药物传递系统的处方组成和比例,以载药量、粒径和多分散系数为评价指标,对油相、表面活性剂和助表面活性剂的用量进行考察。最后以成乳的外观形态、粒径、多分散系数、Zeta电位和体外溶出度为评价指标,评价其质量。结果得到地榆皂苷自乳化药物传递系统最优处方为Obleique CC497-聚山梨酯20-Transcutol P(0.25∶0.45∶0.30),载药量23.93 mg/g,平均粒径为(207.92±2.13)nm,Zeta电位为(38.84±0.18)m V。体外释放结果表明,地榆皂苷自乳化药物传递系统的释药速率极显著地高于地榆皂苷原料药。结论首次建立了地榆皂苷自乳化药物传递系统,工艺合理可行,质量稳定。
Objective To optimize the formulation of the self-emulsifying drug delivery system of total saponins of Sanguisorba officinalis and evaluate its characteristics. Methods The formulation and its proportion of the self-emulsifying drug delivery system of total saponins of S. officinalis were optimized based on the solubility tests, formula compatibility, microemulsion area in the ternary phase diagram and D-optimal mixing experiment design. The dosage of oil phase, surfactant and co-surfactant were investigated by drug loading, particle size, and polydispersity index. The appearance, particle size, polydispersity index, Zeta potential, and in vitrorelease of preparation were finally evaluated. Results The ratio of oil phase, surfactant, and co-surfactant was 0.25∶ 0.45∶0.30. The drug loading was 23.93 mg/g, the average particle size was(207.92 ± 2.13) nm and the zeta potential was(38.84 ± 0.18) m V. The release of SEDDS was superior to the bulk drug apparently. Conclusion The self-emulsifying drug delivery system of total saponins of S. officinalis was established. The technology was feasible and the quality was stable.
Objective To optimize the formulation of the self-emulsifying drug delivery system of total saponins of Sanguisorba officinalis and evaluate its characteristics. Methods The formulation and its proportion of the self-emulsifying drug delivery system of total saponins of S. officinalis were optimized based on the solubility tests, formula compatibility, microemulsion area in the ternary phase diagram and D-optimal mixing experiment design. The dosage of oil phase, surfactant and co-surfactant were investigated by drug loading, particle size, and polydispersity index. The appearance, particle size, polydispersity index, Zeta potential, and in vitrorelease of preparation were finally evaluated. Results The ratio of oil phase, surfactant, and co-surfactant was 0.25∶ 0.45∶0.30. The drug loading was 23.93 mg/g, the average particle size was(207.92 ± 2.13) nm and the zeta potential was(38.84 ± 0.18) m V. The release of SEDDS was superior to the bulk drug apparently. Conclusion The self-emulsifying drug delivery system of total saponins of S. officinalis was established. The technology was feasible and the quality was stable.
引文
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[19]周维,李小芳,李平,等.基于液固压缩技术黄芩苷固体自微乳化释药系统的制备研究[J].中药与临床,2016,7(1):23-26.
[20]Lee D R,Ho M J,Jung H J,et al.Enhanced dissolution and oral absorption of tacrolimus by supersaturable self-emulsifying drug delivery system[J].Int J Nanomed,2016,11(7):1109-1117.
[21]童廷德,黄蕊,孙逊,等.丹酚酸B磷脂复合物自乳化药物传递系统的制备及质量评价[J].四川大学学报:医学版,2013,44(2):303-307.
[22]杨志欣,张文君,刘明玉,等.三叶豆紫檀苷磷脂复合物自微乳研制及跨膜转运研究[J].中草药,2016,47(4):573-579.
[2]代良敏,熊永爱,范奎,等.酸水解地榆总皂苷制备地榆皂苷元的工艺优选[J].中草药,2016,47(14):2454-2459.
[3]代良敏,熊永爱,杨桂燕,等.地榆皂苷类成分对环磷酰胺致小鼠骨髓抑制的保护作用研究[J].天然产物研究与开发,2016,28(6):852-859.
[4]苏柘僮,刘英,徐佳丽,等.应用Box-Behnken设计优化地榆皂苷的闪式提取工艺研究[J].中草药,2012,43(3):501-504.
[5]高小平,吴建明,邹文俊,等.地榆促造血作用的有效部位筛选[J].中国天然药物,2006,4(2):137-140.
[6]邹文俊,刘芳,吴建明,等.地榆总皂苷促造血细胞增殖效应研究[J].中草药,2012,43(5):929-933.
[7]代燕平,高小平,吴建明,等.地榆总皂苷对巨核祖细胞增殖分化及相关受体表达的影响[J].中国中药杂志,2014,39(9):1685-1689.
[8]Wang Y,Probin V,Zhou D.Cancer therapy-induced residual bone marrow injury-mechanisms of induction and implication for therapy[J].Curr Cancer TherapyRev,2006,2(3):271-279.
[9]吴朝花,严俊丽,王益,等.艳山姜挥发油自乳化释药系统的优化及评价[J].中草药,2017,48(19):3970-3976.
[10]Pouton C W.Lipid formulations for oral administration of drugs:Non-emulsifying,self-emulsifying and‘selfmicro-emulsifying’drug delivery systems[J].Eur J Pharm Sci,2000,11(2Suppl):S93-S98.
[11]柯秀梅,刘频健,余文敏,等.丹参酮类组分自乳化释药系统的肠吸收特征研究[J].中草药,2017,48(13):2697-2703.
[12]Valicherla G R,Dave K M,Syed A A,et al.Formulation optimization of docetaxel loaded self-emulsifying drug delivery system to enhance bioavailability and anti-tumor activity[J].Sci Rep,2016,doi:10.1038/srep26895.
[13]柯秀梅,杨荣平,郭响香,等.自乳化释药系统(SEDDS)对姜黄素类组分增溶作用的研究[J].中草药,2014,45(7):935-941.
[14]代良敏,熊永爱,杨明,等.三步碱沉法制备地榆总皂苷的工艺优选[J].中国实验方剂学杂志,2016,22(18):9-12.
[15]苏柘僮,刘英,徐佳丽,等.应用Box-Behnken设计优化地榆皂苷的闪式提取工艺研究[J].中草药,2012,43(3):501-504.
[16]邵兵,唐景玲,纪宏宇,等.五仁醇自乳化释药系统的制备及体外特性评价[J].中国药房,2012,23(43):4059-4062.
[17]Spósito Pá,Mazzeti A L,De O F C,et al.Ravuconazole self-emulsifying delivery system:In vitro activity against trypanosoma cruziamastigotes and in vivo toxicity[J].Int J Nanomed,2017,12(17):3785-3799.
[18]Salimi A,Zadeh B S M,Hemati A A,et al.Design and evaluation of self-emulsifying drug delivery system(SEDDS)of carvedilol to improve the oral absorption[J].Jundishapur J Nat Pharm Prod,2014,9(3):e16125.
[19]周维,李小芳,李平,等.基于液固压缩技术黄芩苷固体自微乳化释药系统的制备研究[J].中药与临床,2016,7(1):23-26.
[20]Lee D R,Ho M J,Jung H J,et al.Enhanced dissolution and oral absorption of tacrolimus by supersaturable self-emulsifying drug delivery system[J].Int J Nanomed,2016,11(7):1109-1117.
[21]童廷德,黄蕊,孙逊,等.丹酚酸B磷脂复合物自乳化药物传递系统的制备及质量评价[J].四川大学学报:医学版,2013,44(2):303-307.
[22]杨志欣,张文君,刘明玉,等.三叶豆紫檀苷磷脂复合物自微乳研制及跨膜转运研究[J].中草药,2016,47(4):573-579.