伊曲茶碱溶析结晶工艺

Dilution Crystallization Process of Istradefylline

药物结晶工艺是药物工业生产流程中至关重要的环节。通过单因素实验,以伊曲茶碱晶体收率、粒度分布作为评价标准,考察结晶液初始浓度、溶析剂用量、结晶温度、陈化时间、溶析剂滴加速率等因素的影响。通过分析各种影响因素,得到伊曲茶碱较佳结晶条件:结晶液初始浓度12 mg/mL,水和N,N-二甲基甲酰胺(DMF)体积分数比3∶1,滴加速率2 mL/min,结晶温度20℃、陈化时间60 min。通过该方案获得伊曲茶碱晶体呈短针状,收率、平均粒径、变异系数分别为93.7%、12.6μm、4.25,为工业上制备高质量的伊曲茶碱产品提供基础依据和参考。

The drug crystallization process is a very important part in drug industry production process. Single factor experiment was conducted to evaluate the crystal yield and particle size distribution of istradefylline. The effects of initial concentration of crystallization solution, amount of anti-solvent, crystallization temperature, aging time and dripping speed of anti-solvent were investigated. By analyzing various influencing factors, the optimal crystallization conditions of istradefylline were obtained. The initial conc-entration of crystallization solution was 12 mg/mL, the volume fraction ratio of water to DMF was 3∶1, the dripping speed was 2 mL/min, the crystallization temperature was 20 ℃, and the aging time was 60 min. The crystal of istradefylline was short needle shape with yield, mean grain size and coefficient of variation of 93.7%, 12.6 μm and 4.25, respectively, which provided basic basis and reference for preparing high-quality products of istradefylline in industry.