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医药导报  2019, Vol. 38 Issue (6): 770-774    DOI: 10.3870/j.issn.1004-0781.2019.06.019
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新型载体罗汉果苷V对紫杉醇的增溶作用*
王杏利1(),王爽2,张雷3,罗玉琴1,韦铭旻1,吴春勇4,张峻颖1()
1.中国药科大学中药制药系,南京 211198
2.广东食品药品监督管理局认证审评中心,广州 510080
3.山东省食品药品检验研究院,济南 250101
4.中国药科大学药物分析系,南京 210009
Solubilization Effects of Novel Carrier Mogroside V on Paclitaxel
Xingli WANG1(),Shuang WANG2,Lei ZHANG3,Yuqing LUO1,Mingmin WEI1,Chunyong WU4,Junying ZHANG1()
1.Department of TCMs Pharmaceuticals, China Pharmaceutical University , Nanjing 211198, China
2.Center for Certification and Evaluation, Guangdong Food and Drug Administration, Guangzhou 510080,China
3.Shandong Institute for Food and Drug Control, Jinan 250101,China
4.Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009 ,China
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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。

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王杏利
王爽
张雷
罗玉琴
韦铭旻
吴春勇
张峻颖
关键词 罗汉果苷Ⅴ紫杉醇新型载体固体分散体溶出度    
Abstract

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.

Key wordsMogroside V    Paclitaxel    Novel carrier    Solid dispersion    Dissolution
收稿日期: 2018-09-30      出版日期: 2019-06-11
基金资助:*国家自然科学基金资助项目(81473357,81673681);中央高校基本科研业务费(2015PT062)
引用本文:   
王杏利,王爽,张雷,罗玉琴,韦铭旻,吴春勇,张峻颖. 新型载体罗汉果苷V对紫杉醇的增溶作用*[J]. 医药导报, 2019, 38(6): 770-774.
Xingli WANG,Shuang WANG,Lei ZHANG,Yuqing LUO,Mingmin WEI,Chunyong WU,Junying ZHANG. Solubilization Effects of Novel Carrier Mogroside V on Paclitaxel. Herald of Medicine, 2019, 38(6): 770-774.
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http://www.yydbzz.com/CN/10.3870/j.issn.1004-0781.2019.06.019      或      http://www.yydbzz.com/CN/Y2019/V38/I6/770
图1  4种溶液的HPLC图谱
A.空白溶剂;B.罗汉果苷V对照品溶液;C.紫杉醇对照品;D.紫杉醇-罗汉果苷V固体分散体溶液;1.罗汉果苷V;2.紫杉醇
浓度水平 加入量 测得量 回收率 平均回收率 RSD
mg %
12.04 12.12 100.7
12.02 12.20 101.5 101.2 0.46
12.01 12.19 101.5
10.01 10.07 100.6
10.02 10.04 100.2 100.4 0.21
10.01 10.06 100.5
8.03 8.04 100.1
8.02 7.85 97.9 99.2 1.16
8.01 7.98 99.6
表1  紫杉醇加样回收率实验结果
图2  紫杉醇/罗汉果苷Ⅴ物理混合物的增溶倍数变化曲线
图3  罗汉果苷V(A)、固体分散体(B)、物理混合物(C)、紫杉醇(D) DSC图谱
图4  紫杉醇、物理混合物和固体分散体的体外溶出曲线
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