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

doi:10.5246/jcps.2015.12.100

Abstract

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

CLC Number:

R944

Supporting:

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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