左旋氨氯地平溶析结晶工艺的研究.pdfVIP

·药物化学 · 左旋氨氯地平溶析结晶工艺的研究 卢定强 1,2 1 1 1 1 ，常亚军 ，凌岫泉 ，贾静 ，党安旺 (1.南京工业大学药学院，南京 210009 ；2.江苏省药物研究所，南京 210009) 摘要：目的 研究利用溶析结晶法提纯左旋氨氯地平的工艺。方法 采用差重法测定正庚烷-二氯甲烷混合溶剂的溶解度， 研究了左旋氨氯地平溶析结晶的温度、反溶剂的含量及导入方式、搅拌转速对左旋氨氯地平的纯度和收率的影响。结果 左旋氨氯地平在正庚烷-二氯甲烷溶液中的溶解度随着正庚烷浓度的升高而减小，确定了最佳结晶条件为温度：25 ℃；正 庚烷/二氯甲烷质量比为 1.5~1.75；搅拌速度：300 r·min1。结论 该结晶工艺得到的产品纯度和收率较高，其工艺具有 操作简易、易于工业化等特点，同时也为氨氯地平单一对映体制备成各种剂型开辟良好的前景。 关键词：左旋氨氯地平；溶析结晶；纯度；收率 中图分类号：R916.691 文献标志码：A 文章编号：1007-7693(2010)11-1006-04 Study on Solventing-out Crystallization Process of Levoamlodipine 1,2 1 1 1 1 LU Dingqiang , CHANG Yajun , LING Xiuquan , JIA Jing , DANG Anwang (1.School of Pharmacy, Nanjing University of Technology, Nanjing 210009, China; 2.Jiangsu Provincial Institute of Material Medica, Nanjing 210009, China) ABSTRACT: OBJECTIVE To study the solventing-out crystallization process of levoamlodipine. METHODS The gravimetric method was used to measure the solubility of levoamlodipine in the mixture of n-heptane and dichloromethane. It is studied the effect factors on the purity and the yield of levoamlodipine crystallization which included the temperature, the quantity of anti-solvent, the flow rate of n-heptane introduced into levoamlodipine dichloromethane solution and the rotary speed. RESULTS The solubility of levoamlodipine in the mixture increased remarkably during the reduction of the n-heptanes ratio at the fixed temperatures. The optimized condition was temperatures: 25 ℃ ; the mass ratio of n-heptane to dichloromethane: 1.51.75; rate of rotation: 300 r ·min1. CONCLUSION The product obtained from the crystallization process has the higher purity and yield. The technology has the advantages such as simple operation, easy-to-industrialization and so on. What i