三元固体分散体提高利多卡因溶解度研究

doi:10.5246/jcps.2020.01.005

中国药学(英文版) ›› 2020, Vol. 29 ›› Issue (1): 55-65.DOI: 10.5246/jcps.2020.01.005

三元固体分散体提高利多卡因溶解度研究

樊文玲^1,2*, 徐艳^1,2, 张心怡^1,2, 狄留庆^1,2, 李磊³

1. 南京中医药大学药学院, 江苏南京 210023
2. 江苏省中药高效给药系统工程技术研究中心, 江苏南京 210023
3. 南京大学化学化工学院, 江苏南京 210023

收稿日期:2019-09-14 修回日期:2019-10-23 出版日期:2020-01-21 发布日期:2019-11-15
通讯作者: Tel.: +86-025-85811317, E-mail: fanwl.happy@163.com
基金资助:
National Natural Science Fund of China (Grant No. 30801552 & 81274095), the third key project funded by Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization (Grant No. 012092002006-10), the 55th postdoctoral project (Grant No. 021062001001).

Study on solubility improvement of lidocaine by ternary solid dispersion

Wenling Fan^1,2*, Yan Xu^1,2, Xinyi Zhang^1,2, Liuqing Di^1,2, Lei Li³

1. School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
2. Institute of Jiangsu Engineering Research Center for Efficient Delivery System of Traditional Chinese Medicine, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
3. Department of Chemical Engineering, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China

Received:2019-09-14 Revised:2019-10-23 Online:2020-01-21 Published:2019-11-15
Contact: Tel.: +86-025-85811317, E-mail: fanwl.happy@163.com
Supported by:
National Natural Science Fund of China (Grant No. 30801552 & 81274095), the third key project funded by Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization (Grant No. 012092002006-10), the 55th postdoctoral project (Grant No. 021062001001).

摘要/Abstract

摘要：

使用熔融法制备利多卡因-泊洛沙姆固体分散体以提高利多卡因的溶解度及溶出度。以利多卡因(LIC) 作为模型药物,分别使用泊洛沙姆188 (P188) 和泊洛沙姆407 (P407) 作为单一及混合载体,制备三元及二元固体分散体并进行比较。使用DSC、XRD、SEM及FTIR进行一系列表征,通过溶出度试验研究固体分散体的溶出特性,药物以晶体形式存在于载体中,药物溶出度及溶解度结果较原料药均有明显提高。相溶解度研究显示出药物与载体呈AL型曲线,有分子相互作用的存在。此外,还考察了固体分散体在不同相对湿度下的长期稳定性,稳定性测试结果表明三元及二元利多卡因-泊洛沙姆固体分散体在不同湿度下, 6个月内保持稳定。研究结果表明,混合泊洛沙姆三元固体分散体可以显著提高难溶性利多卡因的溶出度和溶解度。

关键词: 溶解度, 利多卡因, 泊洛沙姆, 固体分散体

Abstract:

In the present study, we aimed to probe the possibility of using mixed poloxamers as carriers to prepare ternary solid dispersion (SD) that facilitated solubility and dissolution rate of the poorly water soluble drug and compare with binary SD with single poloxamer. Lidocaine (LIC) was selected as a model drug, and poloxamer 188 (P188) and poloxamer 407 (P407) were utilized as single and mixed carriers. Depending on DSC and the dissolution testing, the appropriate ratio of SD prepared by melting method was optimized. Ternary and binary SD was characterized by DSC, XRD, SEM and FTIR. In vitro dissolution study, phase solubility study and saturated solubility study were performed to clarify solubilization from apparent phenomena and inherent reason. Moreover, stability study under different relative humidity (RH) was investigated. Physical characterizations of binary and ternary SD exhibited the formation of eutectic mixture and the presence of molecular interaction. Compared with the pure LIC, the dissolution rate and solubility of LIC in binary and ternary SDs were enhanced. The phase solubility study revealed an AL-type curve. Furthermore, the stability test indicated that ternary and binary SD was stable. The results of this study demonstrated that SD with mixed poloxamers could improve dissolution rate and solubility of poorly water-soluble drug.

Key words: Solubility, Lidocaine, Poloxamer, Solid dispersion

中图分类号:

R944

Supporting:

樊文玲, 徐艳, 张心怡, 狄留庆, 李磊. 三元固体分散体提高利多卡因溶解度研究[J]. 中国药学(英文版), 2020, 29(1): 55-65.

Wenling Fan, Yan Xu, Xinyi Zhang, Liuqing Di, Lei Li. Study on solubility improvement of lidocaine by ternary solid dispersion[J]. Journal of Chinese Pharmaceutical Sciences, 2020, 29(1): 55-65.

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三元固体分散体提高利多卡因溶解度研究

Study on solubility improvement of lidocaine by ternary solid dispersion

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