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首页> 外文期刊>Crystal growth & design >Elusive Seed Formation via Electrical Confinement: Control of a Novel Cocrystal in Cooling Crystallization
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Elusive Seed Formation via Electrical Confinement: Control of a Novel Cocrystal in Cooling Crystallization

机译：通过电监禁难以使用的种子形成：控制冷却结晶中的新型CoCrystal

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摘要

Pharmaceutical cocrystals are multicomponent materials formed to enhance the properties of active pharmaceutical ingredients (APIs) and are commercially used to increase the number of drug candidates that successfully make it through the drug discovery pipeline. Nevertheless, the industrial production of cocrystals and other elusive solid forms remains a challenge. The main limitations are due to challenges related to the scale-up, solid-form control, and undesirable parameters needed for the preparation method. This study leverages the features of electrospray crystallization to generate elusive cocrystal forms that contain the API acetaminophen (paracetamol) and its regioisomer metacetamol. We report the formation of a new cocrystal, which is held together by van der Waals interactions, and the use of the newly electrosprayed cocrystals as seeds to tune the performance of cooling crystallization, allowing this commonly used crystallization method to produce the elusive cocrystal. The electrosprayed cocrystal displays a previously unseen sponge-like surface topology and a fourfold solubility enhancement over those found for single-component APIs. This new technology expands the accessibility to new solid forms that were previously inaccessible by other crystallization methods.
机译：药物共晶体是多组分材料，用于增强活性药物成分（API）的性能，并在商业上用于增加成功通过药物发现管道的候选药物数量。然而，共晶和其他难以捉摸的固体形式的工业生产仍然是一个挑战。主要的限制是由于与放大、固体形态控制和制备方法所需的不良参数有关的挑战。本研究利用电喷雾结晶的特点，生成难以捉摸的共晶形式，其中包含API醋氨酚（扑热息痛）及其区域异构体美他命。我们报告了一种新的共晶的形成，这种共晶通过范德华相互作用结合在一起，并使用新的电喷雾共晶作为种子来调节冷却结晶的性能，使这种常用的结晶方法能够产生难以捉摸的共晶。与单组分原料药相比，电喷雾共晶显示出以前未见过的海绵状表面拓扑结构和四倍的溶解度增强。这项新技术使人们能够接触到以前其他结晶方法无法接触到的新固体形式。

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