摘要
通过生物显微镜、X射线粉末衍射(XRD)、马尔文粒度分析仪,差热分析(DSC)及在线聚焦反射测量仪(FBRM)和粒子成像测量仪(PVM)研究了在卡马西平结晶过程中各种操作参数对产品质量特别是晶型的影响,具体考察了溶剂、晶种、结晶方式、干燥、温度、搅拌速率及冷却速率对晶体产品质量的影响。结果表明,不同溶剂中缓慢结晶,高介电常数溶剂(如醇类)中得到卡马西平晶型Ⅲ,乙醇-水混合物中当乙醇摩尔分数低于40%时结晶产物为二水物,四氢呋喃中结晶得到晶型Ⅱ,其他溶剂得到产品为混合晶型;对于醇类溶剂,蒸发结晶一般得到卡马西平晶型Ⅱ,而缓慢冷却得晶型Ⅲ;以正丙醇为溶剂,加大量颗粒较小的晶种可以得到粒度较均一的产品;晶型Ⅱ产品由于特殊的结构,易于有结晶用溶剂包藏在晶体中,加热到约140℃溶剂逸出;温度是影响晶型的重要因素,在较高温度区间(90~76℃)结晶得晶型Ⅱ,而在低温度区间(52~20℃)得晶型Ⅲ;搅拌速率在较低的温度下对晶型没有影响,搅拌速率大可以避免晶体的聚集,形成较均匀的颗粒;3种降温速率结果显示,产品均为卡马西平晶型Ⅲ,但先慢后快的降温速率可以得到更均匀的颗粒晶体。
Crystallization process of carbamazepine( CBZ) polymorphs was investigated using biomicroscope,X-ray powder diffraction( XRD),Malvin particle analysis,DSC and FBRM and PVM. The effect of different operation factors such as solvents,seeds,crystallization method,drying,temperature,agitation rate and cooling rate on the properties,especially the polymorph of carbamazepine were investigated. The results show that CBZ dihydrate can be recrystallization from ethanol-water mixture,CBZ form Ⅲ can be obtained through slow cooling in alcohol solvents,CBZ form Ⅱ is got by recrystallization in THF. The conformity of the particle can be obtained by adding large amount of fine seeds. The CBZ form Ⅱ is easy to include solvent because its special structure( the channel). The temperature play a mainly role for the polymorph of CBZ,it gives CBZ form Ⅲ a lower temperature range( 52 ~20 ℃),while gives CBZ formⅡa higher temperature range( 90 ~76 ℃). The mean particle size is easy to obtain when the stirring rate is higher. The cooling rate don't affect the polymorph of CBZ,all the products are CBZ form Ⅲ,but there is a difference in crystal size distribution( CSD).
出处
《精细化工》
EI
CAS
CSCD
北大核心
2015年第11期1248-1254,共7页
Fine Chemicals
基金
国家自然科学基金(21206032)
河南工业大学科技创新人才(2012CXRC08)~~
关键词
卡马西平
多晶型
结晶工艺
催化与分离提纯技术
carbamazepine
polymorph
crystallization process
catalysis
separation and purification technology