槲皮素磷脂复合物固体分散体和固体分散体的制备及评价

doi:10.5246/jcps.2019.12.082

中国药学(英文版) ›› 2019, Vol. 28 ›› Issue (12): 868-877.DOI: 10.5246/jcps.2019.12.082

槲皮素磷脂复合物固体分散体和固体分散体的制备及评价

刘蒸生¹, 郝海军², 范明松^2*

1. 湖南省长沙市珂信肿瘤医院, 湖南长沙 410000
2. 上海雷允上药业有限公司技术中心, 上海 201401

收稿日期:2019-08-18 修回日期:2019-10-12 出版日期:2019-12-28 发布日期:2019-11-05
通讯作者: Tel.: +86-21-67103277, E-mail: fanms@shiys.com
基金资助:
National Science and Technology Major Projects “Major New Drugs Innovation and Development” (Grant No. 2018ZX09201019-002-009).

Quercetin-phospholipids complex solid dispersion and quercetin solid dispersion: preparation and evaluation

Zhengsheng Liu¹, Haijun Hao², Mingsong Fan^2*

1. Changsha Kexin cancer hospital, Changsha 410000, China
2. Technique Center, Shanghai Leiyunshang Pharmaceutical Co., Ltd., Shanghai 201401, China

Received:2019-08-18 Revised:2019-10-12 Online:2019-12-28 Published:2019-11-05
Contact: Tel.: +86-21-67103277, E-mail: fanms@shiys.com
Supported by:
National Science and Technology Major Projects “Major New Drugs Innovation and Development” (Grant No. 2018ZX09201019-002-009).

摘要/Abstract

摘要：

槲皮素在体外具有很多生物活性和药理作用, 但是由于溶解度较差导致口服吸收生物利用度很低, 极大地限制了在临床上的应用。本研究分别采用溶剂挥发法制备槲皮素固体分散体和槲皮素磷脂复合物固体分散体来改善槲皮素的体内吸收。XRD结果显示, 槲皮素以无定型或分子状态高度分散于固体分散体和磷脂复合物固体分散体中, 有助于提高其溶解度和溶出度。槲皮素固体分散体和磷脂复合物固体分散体分别将槲皮素的溶解度由(4.03±0.02) μg/mL提高至(26.91±0.06) μg/mL和(30.65±0.06) μg/mL, 其中槲皮素在磷脂复合物固体分散体溶解度高于在固体分散体中的溶解度。体外溶出试验结果显示, 固体分散体和磷脂复合物固体分散体的最大溶出度由9.57%分别提高至93.81%和94.16%。药动学研究结果显示, 固体分散体和磷脂复合物固体分散体均可提高槲皮素的口服吸收生物利用度, 生物利用度分别提高至149.49% 和198.32%。重要的是槲皮素磷脂复合物固体分散体的生物利用度高于槲皮素固体分散体。因此, 对于水溶性和透膜性均较差的药物来讲, 磷脂复合物固体分散体更有效地促进药物吸收进而得到更高的生物利用度。

关键词: 槲皮素, 固体分散体, 磷脂复合物, 生物利用度

Abstract:

Quercetin (QUE) has many beneficial biological activities and pharmacological actions in vitro. However, its oral bioavailability in vivo was very poor due to poor solubility, and severely restricted its clinical applications. In this study, we preparedquercetin solid dispersion (QUE-SD) and quercetin phospholipids complex solid dispersion (QUE-PC-SD) by a solvent evaporationmethod to improve the absorption of QUE in vivo. The results of XRD of QUE-SD and QUE-PC-SD showed that QUE was dispersed homogeneously in an amorphous or molecular state in QUE-SD and QUE-PC-SD, which could contribute to improve the solubility and dissolution of QUE. The solubility of QUE-SD and QUE-PC-SD was enhanced from (4.03±0.02) μg/mL to (26.91±0.06) μg/mL and (30.65±0.06) μg/mL, respectively. The solubility of QUE-PC-SD was higher than that of QUE-SD. In vitro dissolution study, it was showed that the maximum dissolution of QUE (9.57%) from the QUE-SD and QUE-PC-SD was enhanced to 93.81% and 94.16%, respectively. The results of pharmacokinetic experiment indicated that the QUE-SD and QUE-PC-SD exhibited considerable enhancement in the oral bioavailability. The relative bioavailability of QUE-SD and QUE-PC-SD compared with QUE were 149.49% and 198.32%, respectively. In addition, the relative bioavailability of QUE-PC-SD was also higher than that of QUE-SD. Therefore, in regard to drugs with poor solubility and low permeation, an active constituent-PC-SD system could result to a better absorption and higher bioavailability.

Key words: Quercetin, Solid dispersion, Phospholipids complex, Bioavailability

中图分类号:

R944

Supporting:

刘蒸生, 郝海军, 范明松. 槲皮素磷脂复合物固体分散体和固体分散体的制备及评价[J]. 中国药学(英文版), 2019, 28(12): 868-877.

Zhengsheng Liu, Haijun Hao, Mingsong Fan. Quercetin-phospholipids complex solid dispersion and quercetin solid dispersion: preparation and evaluation[J]. Journal of Chinese Pharmaceutical Sciences, 2019, 28(12): 868-877.

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槲皮素磷脂复合物固体分散体和固体分散体的制备及评价

Quercetin-phospholipids complex solid dispersion and quercetin solid dispersion: preparation and evaluation

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