新型载体罗汉果苷V对紫杉醇的增溶作用
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摘要
目的考察罗汉果苷V作为新型载体对难溶性药物的增溶作用。方法以罗汉果苷V为载体,紫杉醇为模型药物,采用溶剂法制备紫杉醇-罗汉果苷V固体分散体。采用高效液相色谱(HPLC)法测定紫杉醇的含量,考察固体分散体中紫杉醇的饱和溶解度和体外溶出性能的变化。同时,用差示热扫描法(DSC)进行物相鉴别,评价药物在固体分散体中晶型变化。结果紫杉醇-罗汉果苷Ⅴ固体分散体的饱和溶解度比紫杉醇增加约375倍;与紫杉醇比较,固体分散体的体外溶出速率和累积溶出度明显提高;差示热扫描法结果表明,紫杉醇在固体分散体内以无定形存在。结论罗汉果苷V能明显增加难溶性药物的溶解度和体外溶出度,且该载体安全、无毒,有望成为难溶性药物增溶的新型载体。
Objective To investigate the solubilization effects of mogroside V as a novel carrier on the poorly soluble drugs. Methods Using mogroside V as a carrier and paclitaxel as a model drug, a solid dispersion of paclitaxel-mogroside V was prepared by the solvent method.The content of paclitaxel was determined by high performance liquid chromatography(HPLC). The saturated solubility and in vitro dissolution of paclitaxel were investigated.In addition, differential thermal scanning(DSC) was used for phase identification and evaluation of drug crystal changes in solid dispersion. Results Paclitaxel-mogroside V solid dispersion showed pronounced improvement in both dissolution rate and drug solubility, as evidenced by a 375-fold increase in solubility compared with paclitaxel.The results of DSC indicated that paclitaxel was in amorphous form in solid dispersion. Conclusion Mogroside V can improve the solubility and in vitro dissolution of the poorly soluble drug.Being safe and non-toxic, mogroside V was found to have suitable characteristics to be used as a pharmaceutical excipient.
Objective To investigate the solubilization effects of mogroside V as a novel carrier on the poorly soluble drugs. Methods Using mogroside V as a carrier and paclitaxel as a model drug, a solid dispersion of paclitaxel-mogroside V was prepared by the solvent method.The content of paclitaxel was determined by high performance liquid chromatography(HPLC). The saturated solubility and in vitro dissolution of paclitaxel were investigated.In addition, differential thermal scanning(DSC) was used for phase identification and evaluation of drug crystal changes in solid dispersion. Results Paclitaxel-mogroside V solid dispersion showed pronounced improvement in both dissolution rate and drug solubility, as evidenced by a 375-fold increase in solubility compared with paclitaxel.The results of DSC indicated that paclitaxel was in amorphous form in solid dispersion. Conclusion Mogroside V can improve the solubility and in vitro dissolution of the poorly soluble drug.Being safe and non-toxic, mogroside V was found to have suitable characteristics to be used as a pharmaceutical excipient.
引文
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[7] TOZUKA Y,HIGASHI K,MORITA T,et al.Transglycosy-lated rutin-specific non-surface-active nanostructure affects absorption enhancement of flurbiprofen[J].Eur J Pharm Biopharm,2012,82(1):120-126.
[8] JIA Z,YANG X.A minor,sweet cucurbitane glycoside from Siraitia grosvenorii[J].Nat Prod Commun,2009,4(6):769-772.
[9] 莫丽英,吴春勇,王杏利,等.基于糖基化修饰的靶向药物传递系统研究概况[J].中国实验方剂学杂志,2018,24(13):209-219.
[10] NICOLAOU K C,DAI W M,GUY M R K.Chemistry and biology of taxol[J].Angew Chem Int Edit,1994,33(1):15-44.
[11] JORDAN M A.Mechanism of action of antitumor drugs that interact with microtubules and tubulin[J].Curr Med Chem Anti Canc Agents,2002,2(1):1-17.
[12] 程丹,许幼发,傅志勤,等.靶向肿瘤微环境的紫杉醇前药研究进展[J].药学实践杂志,2018,36(1):1-8.
[13] BARDELMEIJER H A,OUWEHAND M,BUCKLE T,et al.Low systemic exposure of oral docetaxel in mice resulting from extensive first-pass metabolism is boosted by ritonavir [J].Cancer Res,2002,62(21):6158-6164.
[14] GELDERBLOM H,VERWEIJ J,NOOTER K,et al.Cremo-phor EL:the drawbacks and advantages of vehicle selection for drug formulation[J].Eur J Cancer,2001,37(13):1590-1598.
[15] 刘蒸生,郝海军,马进安.高乌甲素磷脂复合物及其固体分散体在大鼠体内的药动学[J].医药导报,2018,37(4):449-452.
[16] TOZUTA Y,IMONO M,UCHIYAMA H,et al.Dry powder formulation with α-glycosyltransferase -treated stevia for the effective absorption of hydrophobic bioactive compounds in crude drugs [J].Powder Technol,2013,240:2-6.