吡喹酮与酚酸共晶的发现、表征和评价。

Cocrystals of Praziquantel with Phenolic Acids: Discovery, Characterization, and Evaluation.

机构信息

Beijing City Key Laboratory of Polymorphic Drugs, Center of Pharmaceutical Polymorphs, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

Beijing City Key Laboratory of Drug Target and Screening Research, National Center for Pharmaceutical Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

出版信息

Molecules. 2022 Mar 21;27(6):2022. doi: 10.3390/molecules27062022.

DOI:10.3390/molecules27062022

PMID:35335384

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8956121/

Abstract

Solvent-assisted grinding (SAG) and solution slow evaporation (SSE) methods are generally used for the preparation of cocrystals. However, even by using the same solvent, active pharmaceutical ingredient (API), and cocrystal coformer (CCF), the cocrystals prepared using the two methods above are sometimes inconsistent. In the present study, in the cocrystal synthesis of praziquantel (PRA) with polyhydroxy phenolic acid, including protocatechuic acid (PA), gallic acid (GA), and ferulic acid (FA), five different cocrystals were prepared using SAG and SSE. Three of the cocrystals prepared using the SAG method have the structural characteristics of carboxylic acid dimer, and two cocrystals prepared using the SSE method formed cocrystal solvates with the structural characteristics of carboxylic acid monomer. For phenolic acids containing only one phenolic hydroxyl group (ferulic acid), when preparing cocrystals with PRA by using SAG and SSE, the same product was obtained. In addition, the weak molecular interactions that were observed in the cocrystal are explained at the molecular level by using theoretical calculation methods. Finally, the in vitro solubility of cocrystals without crystal solvents and in vivo bioavailability of PRA-FA were evaluated to further understand the influence on the physicochemical properties of API for the introduction of CCF.

摘要

溶剂辅助研磨（SAG）和溶液缓慢蒸发（SSE）方法通常用于制备共晶。然而，即使使用相同的溶剂、活性药物成分（API）和共晶形成剂（CCF），通过上述两种方法制备的共晶有时也不一致。在本研究中，在吡喹酮（PRA）与多羟基酚酸（包括原儿茶酸（PA）、没食子酸（GA）和阿魏酸（FA））的共晶合成中，使用 SAG 和 SSE 制备了五种不同的共晶。使用 SAG 方法制备的三种共晶具有羧酸二聚体的结构特征，而使用 SSE 方法制备的两种共晶形成了具有羧酸单体结构特征的共晶溶剂化物。对于仅含有一个酚羟基的酚酸（阿魏酸），当使用 SAG 和 SSE 与 PRA 制备共晶时，得到了相同的产物。此外，通过理论计算方法，从分子水平上解释了共晶中观察到的弱分子相互作用。最后，评估了无晶溶剂的共晶的体外溶解度和 PRA-FA 的体内生物利用度，以进一步了解 CCF 的引入对 API 理化性质的影响。