【摘要】 为了寻找一种高效的奥利司他结晶工艺,对溶剂种类、晶种、反溶剂加入量、待结晶溶液浓度、搅拌转速和降温速度等因素进行了研究。通过静态结晶实验,确立了甲醇/水为最佳的结晶体系及其比例,加入晶种能明显提高奥利司他的析晶温度,提高产品含量和纯度。在此基础上,经正交试验设计L9(34),通过50 L结晶罐动态考察了各因素对奥利司他结晶产品含量和收率的影响,并进一步优化了加水方式。结果表明:按照2℃/h速率降温,初始奥利司他质量浓度为30 g/L,反溶剂水的加量为25%(体积分数),分2次加入,析晶前加入产品质量0.1%的晶种,搅拌转速250 r/min条件下,所得奥利司他晶体含量和收率最高。经高效液相色谱(HPLC)检测,奥利司他含量可达98.6%,收率可达85.3%。更多还原

【Abstract】 The crystallization of orlistat was studied by the single factor test and the orthogonal experiment design. Factors influencing the orlistat crystallization,such as solvent types,seed,the amount of water,the concentration of the solution,stirring speed and cooling speed were investigated. By static crystallization experiments,the crystallization of methanol / water as the best system and its proportion were established. Also adding crystal seed can obviously improve the crystallization temperature of orlistat,as well as improving product purity and content. Based on single factor test,the orthogonal experiment design L9( 34) was carried out with all dynamic factors in 50 L crystallization reactor,as well as further optimization of water addition. Results show that the highest orlistat crystal content and recovery were obtained. Under the optimal conditions,the rate of the cooling temperature was 2 ℃ / h,the initial concentration of orlistat was 30 g / L,adding the amount of the solvent water was 25%( V / V),twice to add,the 0. 1% seed by weight of orlistat was added before crystallization,the condition of stirring speed was 250 r / min. By HPLC analysis,orlistat content was 98. 6%,and yield was 85. 3%.更多还原