Continuous Crystallization and Polymorph Dynamics in the L-Glutamic Acid System
Continuous Crystallization and Polymorph Dynamics in the L-Glutamic Acid System
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DOI：
10.1021/op500171n
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发表时间：
2014-11-01
影响因子：
3.4
通讯作者：
Myerson, Allan S.
中科院分区：
文献类型：
--
作者：
Lai, Tsai-Ta C.;Ferguson, Steven;Myerson, Allan S.
研究了在连续混合悬浮液混合产物去除（MSMPR）结晶过程中，L-谷氨酸的多晶型动力学随停留时间和温度的变化。结果表明，它是可能的，选择性地生产亚稳或稳定的多晶型物，通过在MSMPR结晶器中的动力学控制的结晶，通过操纵结晶器温度和停留时间。此外，在实验和建模研究的基础上，发现接种不一定足以在给定的稳态下改变多晶型，表明这种传统的多晶型控制策略可能不适用于MSMPR系统。亚稳态α形式和稳定β形式的成核和生长动力学之间的竞争是在特定稳态条件下确定多晶型结果的主要因素。在25 ° C和120分钟停留时间下实验获得具有稳定β多晶型群体的亚稳态，其中来自α形式的小扰动可诱导稳态多晶型的变化。与传统的溶剂介导的转化不同，这种多晶型转化是动力学驱动力相互作用的结果。此外，我们的动态模拟表明，当在25 ℃的温度下操作时，需要长的停留时间（>17.4 h）才能获得稳定的β形式的稳态。我们的研究表明，设计MSMPR结晶的一个挑战是在产生所需产率和多晶型物的条件下各种形式的生长和成核动力学的相互作用。
Polymorph dynamics of l-glutamic acid were examined during continuous mixed suspension mixed product removal (MSMPR) crystallization as a function of residence time and temperature. Results indicate that it is possible to selectively produce metastable or stable polymorphs via a kinetically controlled crystallization in an MSMPR crystallizer by manipulating the crystallizer temperature and residence time. Additionally, on the basis of experimental and modeling studies, it was found that seeding is not necessarily sufficient to alter polymorphism at a given steady state, indicating that this traditional polymorph control strategy may not be applicable in MSMPR systems. The competition between nucleation and growth kinetics of the metastable alpha form and the stable beta form is the major factor in determining the polymorphic outcome at particular steady state conditions. A metastable steady state with a population of the stable beta polymorphic was experimentally obtained at 25 degrees C and 120 min residence time where a small perturbation from the alpha form could induce a change in the steady state polymorphism. This polymorphic transformation, unlike the traditional solvent-mediated transformation, is a result of the interplay of kinetic driving forces. In addition, our dynamic simulation suggests that long residence times (>17.4 h) are required to obtain a steady state of the stable beta form when operating at temperatures of 25 degrees C. Our studies indicate one challenge for designing a MSMPR crystallization will be the interplay of growth and nucleation kinetics of the various forms at conditions which produce the desired yield and polymorph.