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在超分子凝中选择性结晶的pyrazinamide多态:通过模仿凝器和溶剂的协同选择性

Qi Zhang¹, Yizhen Yan², Yisheng Xu³

¹State Key Laboratory of Chemical Engineering, East China University of Science and Technology, Shanghai 200237, China; Department of Chemistry, Durham University, Durham DH1 3LE, UK.

Journal of colloid and interface science

|February 20, 2025

概括

一种新型的凝器模仿了pyrazinamide (PZA) 结构,使得转移性PZA形式β和δ的选择性结晶成为可能. 这种超分子凝结晶提供了一条独特的途径,在室温下实现纯PZA形式β.

科学领域:

超分子化学超分子化学
结晶科学结晶科学
制药的多态化制药的多态化

背景情况:

皮拉津胺 (PZA) 是一种具有高度多态性的关键药物,不同的晶体形式可以影响疗效.
控制结晶以获得特定的PZA多态,特别是转移稳定的多态,仍然是制药制造业的一个重大挑战.

研究的目的:

合成一种模仿凝剂,能够复制pyrazinamide的化学结构.
调查超分子凝相结晶用于选择性PZA多态生成的使用.
建立一种可靠的方法,以在室温下获取纯元稳定PZA Form β.

主要方法:

一种设计以模仿pyrazinamide结构的 bis (尿素) 凝剂的合成.
在合成的凝器中,PZA在酸和DMSO中的超分子凝阶段结晶.
结晶结果与传统溶液结晶方法的比较.

主要成果:

模拟凝器成功促进了PZA的高分子凝阶段结晶.
纯转移性PZA形式β和δ分别在酸和DMSO中选择性获得.
这种方法提供了在室温下获得纯PZA形式β的唯一已知的途径,与产生混合多态的溶液结晶不同.

结论:

使用PZA模拟凝器进行超分子凝相结晶是控制PZA多态性的有效策略.
凝剂和溶剂的相互作用,特别是与PZA的碳基群的相互作用,影响核化,并使转化稳定形式的选择性结晶成为可能.
这种方法为特定药物多态的有针对性生产提供了一个有希望的途径,增强了制药发展.

关键词:

凝阶段结晶的结晶.模仿的冷机模仿的冷机制药的多形态物质.皮拉津胺的使用方法溶剂效应是一种溶剂效应.

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