左旋氨氯地平溶析结晶工艺的研究

Study on Solventing-out Crystallization Process of Levoamlodipine

关键词:  左旋氨氯地平  溶析结晶  纯度  收率

Key words:  levoamlodipine  solventing-out crystallization  purity  yield

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。

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-heptane’s 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 is more, it is opening up good prospects for preparation of the single amlodipine enantiomer of a variety of formulation.