基于ATR-UV实时浓度检测的扑热息痛冷却结晶过程研究

Cooling crystallization of paracetamol in ethanol solution based on real-time ATR-UV measurement

以无水乙醇-扑热息痛为模型物体系,对基于衰减全反射紫外光谱(ATR-UV)分析的结晶过程实时浓度检测进行了研究。采用偏最小二乘法进行结晶过程浓度关联,建立了ATR-UV实时浓度检测模型,该模型实时分析结果与重量法测量结果一致,均方根平均偏差为0.0075。通过ATR-UV实时浓度分析关联结晶过程的过饱和度变化,并结合聚焦光束反射测量技术分析了不同降温方式对结晶产品的影响。结果表明:相对于自然冷却和线性冷却温度控制方式,受控冷却过程能获得尺寸更大、分布更均一的晶体产品。

Real-time concentration determination is critical in process analytical technology for advance quality control of crystallization. A novel approach is presented to correlate in-situ concentration of paracetamol in ethanol solution with the attenuated total reflection/ultraviolet （ATR-UV） spectrum by using the partial least squares method. The correlated concentrations are well consistent with the measurement of gravimetric method and the root-mean-square derivation is found to be 0.0075. Supersaturation correlation based on the developed ATR-UV in-situ concentration measurement, coupled with focused beam reflection measurement for monitoring the nucleation and growth during crystallization procedure, is utilized to investigate the effect of three cooling policies on cooling crystallization, i.e., natural cooling policy （NCP）, linear cooling policy （LCP） and control cooling policy （CCP）. The results show that the CCP has advantages over NCP and LCP in producing more crystals with the large and well-distributed crystal sizes.