羟基喜树碱磷脂复合物固体分散体和油制剂生物利用度的比较

doi:10.5246/jcps.2015.12.100

中国药学(英文版) ›› 2015, Vol. 24 ›› Issue (12): 780-788.DOI: 10.5246/jcps.2015.12.100

羟基喜树碱磷脂复合物固体分散体和油制剂生物利用度的比较

吴先闯¹, 郝海军², 刘瑜新¹, 宋晓勇^1*, 张永州¹, 张红芹³

1. 河南大学淮河医院药学部, 河南开封 475000
2. 上海医药工业研究院, 上海 200437
3. 上海艾韦特医药科技有限公司, 上海 201203

收稿日期:2015-07-07 修回日期:2015-09-01 出版日期:2015-12-22 发布日期:2015-09-30
通讯作者: Tel.: 0371-23906970, E-mail: sxyyjk@sina.com
基金资助:
Science and Technology Department of Henan province Fund Project (Grant No. 144300510019).

Bioavailability of 10-hydroxycamptothecin-phospholipid complex loaded by solid dispersion and lipid-based formulations

Xianchuang Wu¹, Haijun Hao², Yuxin Liu¹, Xiaoyong Song^1*, Yongzhou Zhang¹, Hongqin Zhang³

1. Department of Pharmacy, Huai He Hospital of Henan University, Kaifeng 475000, China
2. Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China
3. Shanghai Advanced Vehicle Technology Pharmaceutical L.T.D. Co, Shanghai 201203, China

Received:2015-07-07 Revised:2015-09-01 Online:2015-12-22 Published:2015-09-30
Contact: Tel.: 0371-23906970, E-mail: sxyyjk@sina.com
Supported by:
Science and Technology Department of Henan province Fund Project (Grant No. 144300510019).

摘要/Abstract

摘要：

羟基喜树碱在体外具有确切的药理作用, 但是由于自身的各种原因导致其体内生物利用度很低, 限制了在临床上的应用。本文采用磷脂复合物技术改善其溶解性能并提高生物利用度。X-衍射实验确定了羟基喜树碱磷脂复合物(HCPT-PC)的形成。但是磷脂复合物粘性较大, 影响了药物的溶出进而不利于药物的吸收。为了改善磷脂复合物粘性较大的问题, 通过简单的制备工艺制备了HCPT-PC固体分散体(HCPT-PC-SD)和油制剂(HCPT-PC-lipid-based formulations)。结果显示, 固体分散体技术大大改善了HCPT-PC中药物的溶出速率, 在45 min内溶出度达到91.73%。药动学研究结果显示, 与HCPT-PC相比, HCPT-PC-SD 和油制剂的AUC₀_–_t得到进一步提高。因此, 固体分散体和油制剂是进一步提高HCPT-PC生物利用度的有研究前景的给药系统。HCPT-PC油制剂生物利用度与HCPT-PC-SD相比, 提高效果更为明显。而且由于HCPT-PC油制剂的制备工艺简单, 有利于实现工业化生产。

关键词: 羟基喜树碱, 磷脂复合物, 固体分散体, 油制剂, 生物利用度

Abstract:

Previous study has shown that 10-hydroxycamptothecin (HCPT) has well-established pharmacological effectsin vitro. However, its in vivo bioavailability is very poor due to various problems, which severely restricts its clinical applications. In the present study, phospholipid complex (PC) technology was employed to improve the solubility and bioavailability of HCPT. XRD data confirmed the formation of HCPT-PC. However, our previously prepared HCPT-PC is too sticky, which may result in the slow dissolution rate and negative effects on its absorption. Therefore, we prepared HCPT-PC-solid dispersion (HCPT-PC-SD) and lipid-based formulations of HCPT-PC through simple preparation process. The results showed that the dissolution rate of HCPT-PC was effectively improved by solid dispersion technology, which reached 91.73% in 45 min. Pharmacokinetic study revealed that the AUC₀_–_tof HCPT-PC-SD and HCPT-PC lipid-based formulations was effectively further increased compared with HCPT-PC. Moreover, we found that the combination of SD technology and lipid-base formulations could be a promising drug-delivery system to improve the oral bioavailability of HCPT-PC. In addition, we showed that the bioavailability of HCPT-PC lipid-base formulations was even greater than that of HCPT-PC-SD. In particular, lipid-base formulations could be prepared just by a simple method, suggesting its feasibility of industrialization.

Key words: 10-Hydroxycamptothecin, Phospholipid complex, Solid dispersion, Lipid-based formulations, Bioavailability

中图分类号:

R944

Supporting:

吴先闯, 郝海军, 刘瑜新, 宋晓勇, 张永州, 张红芹. 羟基喜树碱磷脂复合物固体分散体和油制剂生物利用度的比较[J]. 中国药学(英文版), 2015, 24(12): 780-788.

Xianchuang Wu, Haijun Hao, Yuxin Liu, Xiaoyong Song, Yongzhou Zhang, Hongqin Zhang. Bioavailability of 10-hydroxycamptothecin-phospholipid complex loaded by solid dispersion and lipid-based formulations[J]. Journal of Chinese Pharmaceutical Sciences, 2015, 24(12): 780-788.

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羟基喜树碱磷脂复合物固体分散体和油制剂生物利用度的比较

Bioavailability of 10-hydroxycamptothecin-phospholipid complex loaded by solid dispersion and lipid-based formulations

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