Oscillatory Mixing for Crystallization of High Crystal Perfection Pharmaceuticals
Oscillatory Mixing for Crystallization of High Crystal Perfection Pharmaceuticals
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用于结晶高晶体完美度药物的振荡混合
DOI：
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发表时间：
2007
期刊：
影响因子：
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通讯作者：
R. Ristic
中科院分区：
文献类型：
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作者：
R. Ristic
原位原子力显微镜和激光光学显微镜对固定单晶生长的研究表明，溶液方向的变化及其相对于生长晶体表面的相对速度是最小化界面不稳定性的关键参数，从而影响晶体的结构质量。这些发现在振荡挡板间歇结晶器（OBBC）沉淀实验中得到了应用和验证，在该实验中，除流体力学外，所有外部条件如初始过饱和、结晶温度和功率密度都保持不变。采用激光散射、扫描电镜（SEM）和粉末x射线衍射分别表征了析出物的物理性质（尺寸分布、表面特征、微应变含量）。对所得结果的分析清楚地表明，OBBC中沉淀的颗粒质量明显高于叶轮驱动间歇式结晶器（IDBC）中常规混合产生的颗粒质量。使用计算流体动力学（CFD）软件包Fluent 5对IDBC和OBBC中的动态流体模式进行建模。该模型有助于更好地了解OBBC比IDBC能够沉淀出更高完美度的颗粒。此外，它还解释了粒子在OBBC中生长时与流动方向可互换的固定晶体相比所经历的水动力条件的高度等效性。
In-situ Atomic Force Microscopy and Laser Optical Microscopy studies on a fixed single crystal growth, showed that the change of the direction of solution and its relative velocity with respect to the faces of growing crystal, are critical parameters for the minimization of the interfacial instabilities and, in turn, to the structural quality of a crystal. These findings were applied and tested in oscillatory baffled batch crystallizer (OBBC) precipitation experiments, in which, apart from hydrodynamics, all external conditions such as initial supersaturation, crystallization temperature and power density were kept constant. The physical properties (size distribution, surface characteristics, micro-strain content) of the precipitates were characterized by laser light scattering, scanning electron microscopy (SEM), and powder X-ray diffraction, respectively. The analysis of obtained results shows clearly that particles precipitated in OBBC are of significantly higher quality than those produced in conventional mixing using impeller driven batch crystallizer (IDBC). A computational fluid dynamics (CFD) software package, Fluent 5, was used to model dynamical fluid patterns in IDBC and OBBC. The modelling helped to get better appreciation for being able to precipitate particles of considerably higher perfection in OBBC than in IDBC. Also, it accounts for a high degree of equivalency of hydrodynamic conditions that a particle experiences when it grows in OBBC compared to those of a fixed crystal with interchangeable flow direction.