Combined anti-solvent and cooling method of manufacturing indomethacin-saccharin (IMC-SAC) co-crystal powders
Combined anti-solvent and cooling method of manufacturing indomethacin-saccharin (IMC-SAC) co-crystal powders
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DOI：
10.1016/j.jcrysgro.2014.07.057
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发表时间：
2014-12-15
影响因子：
1.8
通讯作者：
Choi, Guang J.
中科院分区：
文献类型：
--
作者：
Chun, Nan-Hee;Lee, Min-Jeong;Choi, Guang J.
反溶剂法已被证明是一种潜在的工业方法，以生产高纯度的药物共晶粉末。在本研究中，我们将反溶剂法与冷却相结合，以最大化吲哚美辛（IMC）和糖精（SAC）之间的溶液基共结晶的产率。冷却开始时间是关键工艺参数，其他参数根据前期工作结果确定。通过该组合方法制备了高纯度的IMC-SAC共晶粉末，而不考虑冷却开始石灰，并且产率显著提高。然而，一些材料性质，例如结晶度和粒度，受到冷却开始时间的影响;即，冷却是在成核之前开始（成核前冷却）还是在成核之后开始（成核后冷却）。当应用预成核冷却时，更大程度的过饱和导致alpha-IMC和IMC-SAC一起成核。亚稳态的α-IMC最终转变为稳定的IMC-SAC共晶颗粒，然后进行晶体生长。当应用后成核冷却时，在整个过程期间未检测到瞬态α-IMC。(C)2014爱思唯尔有限公司版权所有。
The anti-solvent approach has been demonstrated as one potential industrial method to produce pharmaceutical co-crystal powders with high purity. In this study, we combined the anti-solvent method with cooling to maximize the yield of the solution-based co-crystallization between indomethacin (IMC) and saccharin (SAC). The cooling start time was the key process parameter; other parameters were fixed based on results of preliminary work. Highly pure IMC-SAC co-crystal powders were produced via the combined method, regardless of the cooling start Lime, and the yield was substantially enhanced. However, some material properties, such as crystallinity and particle size, were affected by the cooling start time; i.e., whether cooling was started before nucleation (pre-nucleation cooling) or after nucleation (post-nucleation cooling). When pre-nucleation cooling was applied, a greater degree of supersaturation led to nucleation of alpha-IMC and IMC-SAC together. The metastable alpha-IMC eventually transitioned to stable IMC-SAC co-crystal particles, followed by crystal growth. When post-nucleation cooling was applied, the transient alpha-IMC was not detected during the entire process. (C) 2014 Elsevier B.V. All rights reserved.