Seeded Batch Cooling Crystallization with Temperature Cycling for the Control of Size Uniformity and Polymorphic Purity of Sulfathiazole Crystals
Seeded Batch Cooling Crystallization with Temperature Cycling for the Control of Size Uniformity and Polymorphic Purity of Sulfathiazole Crystals
复制标题
DOI：
10.1021/op900174b
复制
发表时间：
2009-11-01
影响因子：
3.4
通讯作者：
Rielly, Chris D.
中科院分区：
文献类型：
--
作者：
Abu Bakar, Mohd R.;Nagy, Zoltan K.;Rielly, Chris D.
用温度循环的方法对种子间歇冷却结晶法进行了实验研究，以获得较窄的晶粒度分布和生长出所需的多晶型的磺胺噻唑晶体。这项研究使用聚焦光束反射率测量(FBRM)和衰减全反射紫外/可见光(ATR-UV/VIS)光谱对过程进行现场监测和控制，基于FBRM读数，使用反馈控制方法驱动该过程，该方法采用加热和冷却阶段的交替循环，以保持与种子颗粒数量相对应的计数数量，同时增加平方加权弦长分布，表明系统中种子生长的动态过程。实验结果表明，温度循环法促进了产品的Ostwald成熟，促进了产品的生长，提高了产品的尺寸均匀性。该方法在控制多态纯度方面也有很好的应用前景，可以分别从正丙醇和水中培育出第一形态种子和第二形态种子。在新形成的晶体生长之前，水中的第一种种子首先转化为第二种形式和/或被第二种形式的核淹没。然而，在正丙醇中，第二形态和第三形态的种子根本不能生长。这项研究证实了磺胺噻唑晶体的成核和生长是由溶剂介导的，并且通过现场监测工具很好地捕捉到了对这些现象的洞察。
An experimental study has been conducted to evaluate the capability of a seeded batch cooling crystallization with a temperature cycling method to produce a narrow crystal size distribution and grow a desired polymorphic form of sulfathiazole crystals. The study used focused beam reflectance measurement (FBRM), and attenuated total reflectance ultraviolet/visible (ATR-UV/vis) spectroscopy for the in situ monitoring and control of the process, Based on the FBRM readings, the process was driven using a feedback control approach that employs alternating cycles of heating and cooling phases so that the number of counts, corresponding to the number of seed particles, is maintained, whilst the square-weighted chord length distribution, indicating the dynamic progress of the growth of the seeds in the system, is increased. Results of the experiments show that the temperature cycling method promoted Ostwald ripening, which helped in accelerating the growth and enhancing the size uniformity of the product. The method also has a good prospect to be implemented for the control of polymorphic purity, Seeds of Form I and Form II could be grown from n-propanol and water, respectively. Form I seeds in water were first transformed into Form II and/or swamped by nuclei of Form II, before the growth of the newly formed crystals took place. Seeds of Form II and Form III in n-propanol, however, were not able to grow at all. This study confirmed that the nucleation and growth of sulfathiazole crystals are solvent-mediated, and the insight into these phenomena was captured very well by the in situ monitoring tools.