阿莫西林成核与生长动力学

Nucleation and growth kinetics of amoxicillin

阿莫西林现有结晶工艺获得的晶体粒度过小,直接影响到后续的过滤、干燥以及包装运输,研究其结晶动力学参数以指导结晶工艺,控制结晶过程中晶体的成核速度与生长速度,对提高晶体粒度有着重要意义。文章分别采用激光法和显微摄像的方法对阿莫西林结晶过程中初级成核、二次成核和单晶体生长速度进行了测定,计算出动力学相关数据。通过实验确定阿莫西林初级成核中均相成核与非均相成核的分界过饱和度S=4.5以及各自对应的成核自由能与成核半径,确定了二次成核发生时间与过饱和度间的关系以及阿莫西林晶体的生长速率与过饱和度的关系,并由生长指数m=1.995 5推出阿莫西林的生长机制为螺旋错位生长。通过阿莫西林结晶动力学研究为改进和优化结晶过程提供了理论基础。

The size of amoxicillin crystals is so small that may directly affect the downstream unit operations such as filtering, drying, packing and shipping by using existing crystallization process. It is of significance for increasing the crystal size by controlling nucleation rate and growth rate of the crystallization process based on the kinetics study. The laser method and video microscopy were used to measure the primary nucleation, secondary nucleation and growth of amoxieillin, and the classical theory of primary nucleation was used to quantify the nucleation process. When supersaturation ratio S 〉 4. 5, homogeneous nucleation occurred; when S 〈 4. 5, heterogeneous nucleation occurred. The relationship among critical free energy of nucleation, critical radius of nucleation and supersaturation was calculated. By measuring the occurring time of secondary nucleation in different supersaturation, the relationship between the secondary nucleation and supersaturation was obtained. The growth rate is related to the supersaturation ratio of amoxicillin and the growth index m = 1. 995 5 means that the growth mechanism of amoxicillin is spiral growth. All of these can be used as basic data to improve and optimize the crystallization process.