药用辅料级枸橼酸三乙酯工艺研究

Study on Technology of High Purity Pharmaceutical Excipient Triethyl Citrate

目的:开发一种高纯度药用枸橼酸三乙酯制备方法。方法:以枸橼酸和乙醇为原料,在亚磷酸和对甲苯磺酸作用下,对原料配比、酯化时间、催化剂等因素进行充分研究,并提出一种简单有效的后处理方法。结果:成功制备出高纯度药用枸橼酸三乙酯,产品质量符合《中国药典》2020版四部、《美国药典》USP43-NF38、《欧洲药典》EP10.0等标准质量要求,最终产品的收率在85%以上,最大单一杂质≤0.1%。结论:该工艺采用常见的酯化催化剂,在保护促进剂作用下,经特定的后处理方式,即得高纯级枸橼酸三乙酯。此工艺简单,收率高,产品质量高,可实现连续化大生产。

Objective:In order to develop a prepration method for high-purity medicinal triethyl citrate.Methods:Using citric acid and ethanol as raw materials,the researchers fully studied the raw material ratio,esterification time,catalyst and other factors under the action of phosphite and p-toluenesulfonic acid,and put forward a simple and effective post-treatment method.Results:The high-purity medicinal triethyl citrate was prepared,and the quality of the product was in line with the fourth part of“Chinese Pharmacopoeia”2020 edition,“American Pharmacopoeia”USP43-NF38 and“European Pharmacopoeia”EP10.0 and other standard quality requirements,the yield of the final product was more than 85%,maximum single impurity≤0.1%.Conclusion:In this process,common esterification catalysts are used.Under the action of protective accelerators,high-purity triethyl citrate is obtained through specific post-treatment.This process is simple,high yield and high product quality.It can realize continuous large-scale production.