摘要
5-单硝酸异山梨酯主要用于预防心绞痛、治疗冠心病、心肌梗死以及持续性心绞痛,适宜的结晶工艺是药物生产的关键。采用动态法测定了5-单硝酸异山梨酯在乙二醇中的溶解度,使用Apelblat model,Van’t Hoff model对溶解度数据进行了拟合,采用降温结晶法研究5-单硝酸异山梨酯在乙二醇中的结晶介稳区和诱导期,考察了初始浓度、搅拌速率、降温速率、终点温度和晶种加入量等因素对5-单硝酸异山梨酯降温结晶收率的影响,并进行了工艺条件优化。结果表明,适宜的操作条件为初始浓度1.797 mol/L,搅拌速率400 r/min,降温速率0.9 K/min,终点温度273 K,晶种加入量为溶质质量的0.5%,在该条件下收率为33.2%。该研究为5-单硝酸异山梨酯结晶新工艺的开发提供了依据。
5-mononitroisosorbide is mainly used to prevent angina and treat coronary heart disease.The appropriate crystallization process is the key to drug production.The solubility of 5-mononitroisosorbide in ethylene glycol was determined by dynamic method.The solubility was fitted by Apelblat model and Van’t Hoff model.The crystallization metastable zone and induction period of 5-mononitroisosorbide in ethylene glycol was studied by cooling crystallization method.The effects of initial concentration,stirring rate,cooling rate,terminal temperature,and seed addition on the cooling crystallization yield of 5-mononitroisosorbide were investigated.The process conditions were optimized.The results showed that,the optimum operating conditions are as follows:the initial concentration is 1.797 mol/L,the stirring rate is 400 r/min,the cooling rate is 0.9 K/min,the end temperature is 273 K,and the seed addition is 0.5%of the solute mass.Under these conditions,the yield is 33.2%.This study provides a basis for the development of a new crystallization process of 5-mononitroisosorbide.
作者
张峻炜
李琼
王佳琦
陈帅龙
ZHANG Junwei;LI Qiong;WANG Jiaqi;CHEN Shuailong(School of Chemical Engineering and Food Science,Zhengzhou University of Technology,Zhengzhou,Henan 450044,China)
出处
《中州大学学报》
2023年第6期119-123,共5页
Journal of Zhongzhou University
基金
河南省高等学校重点科研项目计划(21B530008)
河南省科技攻关项目(222102310480)。
关键词
5-单硝酸异山梨酯
冷却结晶
介稳区
诱导期
工艺优化
5-mononitroisosorbide
cooling crystallization
metastable zone
induction period
process optimization
