Phase Diagrams of Praziquantel and Vanillic Acid Cocrystals: Racemic Compound and Conglomerate System,Crystal Growth & Design

当前位置： X-MOL 学术 › Cryst. Growth Des. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Phase Diagrams of Praziquantel and Vanillic Acid Cocrystals: Racemic Compound and Conglomerate System
Crystal Growth & Design ( IF 3.2 ) Pub Date : 2024-04-03 , DOI: 10.1021/acs.cgd.4c00114
Charline J. J. Gerard ₁ , Clément Pinetre ₁ , Hugo Cercel ₁ , Maxime D. Charpentier ₂ , Morgane Sanselme ₁ , Nicolas Couvrat ₁ , Clément Brandel ₁ , Yohann Cartigny ₁ , Valérie Dupray ₁ , Joop H. ter Horst _{1,

3}

Affiliation

Praziquantel (PZQ) is widely used to treat schistosomiasis. However, this chiral active pharmaceutical ingredient (API) is still produced as a racemic compound while only the (R)-enantiomer is active. A possible way to control the solid properties of chiral APIs and herewith to separate the enantiomers is their cocrystallization with a coformer to form a conglomerate cocrystal. Vanillic acid (VA) has been previously identified as a coformer able to form two different cocrystal forms with PZQ. While the first one has been characterized and identified as an equimolar racemic cocrystal (i.e., a 1:1 (±)PZQ:VA racemic cocrystal), the properties of the second cocrystal remain unknown. In this paper, a variety of analytical methods (XRPD, DSC, and SHG) have been used to characterize the second cocrystal form. The results show that this second cocrystal form is a 1:2 (+)/(−)PZQ:2VA cocrystal, which crystallizes as a conglomerate, opening routes toward the separation of PZQ enantiomers through preferential crystallization. This study shows the importance of testing several stoichiometries in a screening context, as the desired form or properties, such as a conglomerate cocrystal, could be found in a nonequimolar cocrystal.

中文翻译：

吡喹酮和香草酸共晶的相图：外消旋化合物和聚集体系

吡喹酮（PZQ）广泛用于治疗血吸虫病。然而，这种手性活性药物成分 (API) 仍然以外消旋化合物的形式生产，而只有 ( R )-对映体具有活性。控制手性 API 的固体性质并由此分离对映体的一种可能方法是它们与共形成体共结晶以形成聚集体共晶。香草酸 (VA) 先前已被鉴定为能够与 PZQ 形成两种不同共晶形式的共形成剂。虽然第一个共晶已被表征并鉴定为等摩尔外消旋共晶（即 1:1 (±)PZQ:VA 外消旋共晶），但第二个共晶的性质仍然未知。在本文中，使用了多种分析方法（XRPD、DSC 和 SHG）来表征第二种共晶形式。结果表明，第二种共晶形式是 1:2 (+)/(-)PZQ:2VA 共晶，其结晶为团聚体，开辟了通过优先结晶分离 PZQ 对映体的途径。这项研究表明了在筛选背景下测试几种化学计量的重要性，因为可以在非等摩尔共晶中找到所需的形式或特性，例如团聚共晶。

更新日期：2024-04-03

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南