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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(0.2497±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)、(1.254 0±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(7437.03±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。
OBJECTIVE To determine the equilibrium solubility of niclosamide in different aqueous media, surfactants and organic solvents, to provide basis for the determination of niclosamide, pharmacokinetics and design of new formulations. Methods High performance liquid chromatography (HPLC) was used to determine the effects of niclosamide in different aqueous mediums such as physiological saline, 5% dextrose solution, PBS (pH7.4) at 25 ℃ and 37 ℃ And balanced solubility in deionized water. The effects of surfactant tween-80, sodium dodecyl sulfate (SDS) and span-80 on the equilibrium solubility of niclosamide were compared. Ether, tetrahydrofurane and other 15 kinds of common organic solvents in the equilibrium solubility. Results The equilibrium solubility of niclosamide in physiological saline, 5% dextrose solution, PBS (pH7.4) buffer solution and deionized water was low, followed by (0.2497 ± 0.005 3) and (0.232 ± 0.001 (0.313 2 ± 0.014 5), (0.253 3 ± 0.005 9), (1.254 ± 0.008 6) in the order of (0.552 2 ± 0.005 0) and (0.233 9 ± 0.000 6) μg / , (0.270 5 ± 0.001 9) μg / ml. The solubilities of niclosamide with different surfactants were tween-80> SDS> span-80. The equilibrium solubility of niclosamide in organic solvents was larger than that in aqueous medium, with the highest value of (7437.03 ± 94.40) μg / ml in tetrahydrofuran and the lowest (50.67 ± 0.66) μg / ml in petroleum ether. CONCLUSIONS The niclosamide is poorly water-soluble. The non-ionic surfactant tween-80 can significantly increase its dissolubility and its equilibrium solubility in some organic solvents such as tetrahydrofuran and acetone.