摘要
目的 测定氯硝柳胺在不同水相介质、表面活性剂及有机溶剂中的平衡溶解度,为氯硝柳胺的含量测定、药代动力学的研究以及新剂型的设计等提供依据. 方法 采用高效液相色谱(high performance liquid chromatography,HPLC)法测定温度为25℃和37℃时氯硝柳胺在不同水相介质如生理盐水、5％葡萄糖溶液、PBS (pH7.4)缓冲液和去离子水中的平衡溶解度.比较表面活性剂聚山梨酯80 (tween-80)、十二烷基硫酸钠(SDS)和司盘80 (span-80)对氯硝柳胺平衡溶解度的影响,并测定氯硝柳胺在石油醚、四氢味喃等15种常见有机溶剂中的平衡溶解度. 结果 氯硝柳胺在生理盐水、5％葡萄糖溶液、PBS (pH7.4)缓冲液和去离子水中的平衡溶解度均较低,25℃下依次为(0.249 7±0.005 3)、(0.232 0±0.001 2)、(0.552 2±0.005 0)、(0.233 9±0.000 6) μg/ml,37℃下依次为(0.313 2±0.014 5)、(0.253 3±0.005 9)、(1.2540±0.008 6)、(0.270 5±0.001 9) μg/ml.不同表面活性剂对氯硝柳胺的增溶能力为tween-80＞SDS＞span-80.氯硝柳胺在有机溶剂中的平衡溶解度比水性介质大,其中在四氢呋喃中最大,为(743 7.03±94.40) μg/ml,在石油醚中最小,为(50.67 ±0.66)μg/ml. 结论 氯硝柳胺水溶性差,非离子型表面活性剂tween-80可显著增加其溶解能力,在某些有机溶剂如四氢呋喃和丙酮中的平衡溶解度较大.
Abstract
Objective To determine the equilibrium solubility of niclosamide in different aqueous mediums,surfactants and organic solvents,thus providing further basis for the content determination,pharmacodynamics study and the design of new dosage forms of the drug.Methods High performance liquid chromatography was used to detect the equilibrium solubility of niclosamide in different aqueous mediums such as saline,5％ glucose solution,pH7.4 phosphate buffer and deionized water at 25 ℃ and 37 ℃.The effect of different surfactants including polysorbate 80(tween-80),sodium dodecyl sulfate(SDS) and sorbitane monooleate (span-80) on the equilibrium solubility of niclosamide were studied at the same time,and the equilibrium solubilities of niclosamide in some common organic solvents,e.g.petroleun ether,tetrahydrofuran were determined.Results Niclosamide was poorly soluble in aqueous mediums.The equilibrium solubilities of niclosamide in saline,5％ glucose solution,pH7.4 phosphate buffer and deionized water were (0.249 7±0.005 3),(0.232 0±0.001 2),(0.552 2±0.005 0),(0.233 9±0.000 6) μg/ml at 25 ℃ and (0.313 2±0.014 5),(0.253 3± 0.005 9),(1.254 0±0.008 6),(0.270 5±0.001 9) μg/ml at 37 ℃,respectively.The solubilizing power of different surfactants were tween-80＞SDS＞span-80.The equilibrium solubility of niclosamide in organic solvents was greater than that in aqueous mediums.Among them,the equilibrium solubility was the highest in tetrahydrofuran and the lowest in petroleum ether,which was(743 7.03±94.40) μg/ml and (50.67±0.66) μg/ml,respectively.Conclusion Niclosamide is a hydrophobic drug.The non-ionic surfactant polysorbate 80 can significantly increase the solubility of the drug.The equilibrium solubility is higher in some organic solvents such as tetrahydrofuran and acetone.
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维普
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