药学学报, 2019, 54(1): 41-47
引用本文:
沈佩亚, 窦海涛, 钱帅, 张建军, 高缘. 烟酰胺络合增溶布洛芬的机制研究[J]. 药学学报, 2019, 54(1): 41-47.
SHEN Pei-ya, DOU Hai-tao, QIAN Shuai, ZHANG Jian-jun, GAO Yuan. Mechanism studies on solubility enhancement of ibuprofen by complexation with nicotinamide[J]. Acta Pharmaceutica Sinica, 2019, 54(1): 41-47.

烟酰胺络合增溶布洛芬的机制研究
沈佩亚1, 窦海涛1, 钱帅1, 张建军2, 高缘1
1. 中国药科大学中药学院, 江苏 南京 211198;
2. 中国药科大学药学院, 江苏 南京 211198
摘要:
本文研究了烟酰胺(nicotinamide,NIC)对难溶性药物布洛芬(ibuprofen,IBU)的增溶作用,并通过络合模型,结合荧光淬灭、拉曼光谱等分析络合物的形成机制。结果表明,NIC可显著提高IBU的溶解度,且随着NIC浓度的增加,IBU的溶解度也随之增大,呈现Ap型络合曲线,其络合常数K1:1K1:2分别为0.24和4.00。荧光光谱表明,随着NIC浓度的增加,IBU所产生的荧光逐渐减弱,呈现明显的荧光淬灭现象,结合拉曼光谱分析可能是由于IBU分子中的苯环与NIC分子中吡啶环之间产生偶极-偶极作用力,形成水溶性络合物,使IBU溶解度显著增加。
关键词:    布洛芬      烟酰胺      络合物      溶解度      荧光     
Mechanism studies on solubility enhancement of ibuprofen by complexation with nicotinamide
SHEN Pei-ya1, DOU Hai-tao1, QIAN Shuai1, ZHANG Jian-jun2, GAO Yuan1
1. Department of Traditional Chinese Pharmaceutics, China Pharmaceutical University, Nanjing 211198, China;
2. Department of Pharmaceutics, China Pharmaceutical University, Nanjing 211198, China
Abstract:
The aim of this study is to investigate the effect of nicotinamide (NIC) on the solubility/dissolution of a poorly soluble drug ibuprofen (IBU), and to explore the mechanism of the formed soluble complex by complexation model, fluorescence quenching and Raman spectroscope. The results showed that NIC could significantly improve the solubility of IBU, and exhibited an Ap type complexation profile. The calculated complexation constants of K1:1 and K1:2 were 0.24 and 4.00, respectively. In the solution, the fluorescent intensity of IBU gradually decreased with the increase of NIC, exhibiting the typical fluorescence-quenching phenomenon. The Raman spectrum showed stretching vibrations, bending vibrations, and rocking vibrations ascribed to benzene ring of IBU and pyridine ring of NIC disappeared or significantly shifted, suggested that the soluble complex was formed by dipole-dipole interaction force between the benzene group on IBU and pyridine group on NIC, resulting in the aqueous solubility enhancement of IBU. In comparison to IBU alone, the physical mixture of IBU and NIC showed significantly higher dissolution rate (1.6-fold) and extent.
Key words:    ibuprofen    nicotinamide    complex    solubility    fluorescence   
收稿日期: 2018-08-27
DOI: 10.16438/j.0513-4870.2018-0786
基金项目: 国家自然科学基金资助项目(81703712,81773675,81873012);江苏省自然科学基金资助项目(BK20150703,BK20151438);江苏省"双创计划"(2015);中国药科大学"双一流"建设(CPU2018GY11,CPU2018GY27).
通讯作者: 高缘,Tel/Fax:86-25-83379418,E-mail:newgaoyuan@163.com
Email: newgaoyuan@163.com
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