Jia Lihong, Yin Qiuxiang, Zhou Lina, Zhang Xia, Wang Chang, Du Wei, Zhou Ling
School of Chemical Engineering and Technology, State Key Laboratory of Chemical Engineering, Tianjin University Tianjin 300072 People's Republic of China
Collaborative Innovation Center of Chemical Science and Chemical Engineering Tianjin 300072 People's Republic of China.
RSC Adv. 2018 Mar 7;8(18):9697-9706. doi: 10.1039/c7ra13094e. eCollection 2018 Mar 5.
The concomitant crystallization of spironolactone form II and its ethanol solvate was investigated in ethanol by means of process analytical techniques, such as particle vision and measurement (PVM), focused beam reflectance measurement (FBRM) and Raman spectroscopy. The concomitant crystals were characterized by optical microscopy, powder X-ray diffraction, differential scanning calorimetry and thermogravimetric analysis. Analysis results of primary nucleation kinetics based on the experimental data of the induction time show that the ethanol solvate is the kinetically favored form with a lower interfacial energy, a higher nucleation rate and a smaller radius of the critical nucleus, compared with form II. At a high supersaturation, the crystallization process is dominated by kinetic factors and only the ethanol solvate is obtained. Whereas, at a low supersaturation, only form II crystallizes out owing to its thermodynamic priority. At a moderate supersaturation, concomitant crystals are found as a result of their nearly equal nucleation rates. In summary, the real cause for concomitant crystallization of form II and ethanol solvate of spironolactone is their simultaneous nucleation.
通过过程分析技术，如颗粒视觉与测量（PVM）、聚焦光束反射测量（FBRM）和拉曼光谱，在乙醇中研究了螺内酯II型及其乙醇溶剂化物的同时结晶。通过光学显微镜、粉末X射线衍射、差示扫描量热法和热重分析对同时晶体进行了表征。基于诱导时间的实验数据的初级成核动力学分析结果表明，与II型相比，乙醇溶剂化物是动力学上更有利的晶型，具有更低的界面能、更高的成核速率和更小的临界核半径。在高过饱和度下，结晶过程受动力学因素主导，仅得到乙醇溶剂化物。而在低过饱和度下，由于II型的热力学优先性，只有II型结晶析出。在中等过饱和度下，由于它们的成核速率几乎相等，发现了同时晶体。总之，螺内酯II型和乙醇溶剂化物同时结晶的真正原因是它们的同时成核。
