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Salt Cocrystal and Salt of Marbofloxacin with Butenedioic Acid: Impact of cis–trans Isomerism of Coformer on the Conformation and Properties of Marbofloxacin
Crystal Growth & Design ( IF 3.2 ) Pub Date : 2024-01-10 , DOI: 10.1021/acs.cgd.3c01300 Yujiao Li 1 , Yunan Zhang 1 , Qi An 1 , Jingwen Shi 1 , Lixin Liu 1
Crystal Growth & Design ( IF 3.2 ) Pub Date : 2024-01-10 , DOI: 10.1021/acs.cgd.3c01300 Yujiao Li 1 , Yunan Zhang 1 , Qi An 1 , Jingwen Shi 1 , Lixin Liu 1
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Based on the study of the effect of positional isomerism of coformer functional groups on the cocrystallization and physicochemical properties of the active pharmaceutical ingredients, the impact of cis–trans isomeric butenedioic acid as coformers on the conformation, crystal structure, and its physicochemical properties of marbofloxacin was further explored. In this work, fumaric acid (FA) and maleic acid (MA) with different configurations were chosen as coformers to synthesize the pharmaceutical salt cocrystal (MBF-FA-H2FA) and salt (MBF-MA) of marbofloxacin (MBF), and their structures were fully characterized. Significant differences between the conformations of marbofloxacin in the salt cocrystal and in salt were found. In the salt cocrystal, the N atom of the piperazine group from marbofloxacin is coplanar with the pyridone ring, and the whole is straight like fumaric acid, whereas the marbofloxacin piperazine group in the salt is bent like the maleic acid configuration. Furthermore, the conformational variability of marbofloxacin in the salt cocrystal and the salt resulted in different crystal structures and opposite physicochemical properties. Notably, both multicomponent crystals have a surface hydrophilic intercalation structure. However, the salt cocrystal and salt exhibited different solubility and permeability. Specifically, the MBF-MA salt showed improved solubility and permeability, while the MBF-FA-H2FA salt cocrystal showed a decreased solubility and permeation rate compared to MBF. In addition, in vitro bacterial inhibitory activity assays indicated that the MBF-MA salt has stronger inhibitory activity against Gram-negative and Gram-positive bacterial strains than the MBF-FA-H2FA salt cocrystal and pure MBF.
中文翻译：
马波沙星与丁烯二酸的盐共晶和盐：共形成物顺反异构体对马波沙星构象和性质的影响
通过研究共聚体官能团位置异构对活性药物成分共结晶和理化性质的影响，探讨顺反异构体丁烯二酸作为共聚体对马波沙星构象、晶体结构及其理化性质的影响进行了进一步探讨。本工作选择不同构型的富马酸（FA）和马来酸（MA）作为共形成体，合成了马波沙星（MBF）药用盐共晶（MBF-FA-H 2 FA）和盐（MBF-MA），并且它们的结构得到了充分的表征。发现盐共晶中和盐中马波沙星的构象之间存在显着差异。在盐共晶中，马波沙星的哌嗪基团的N原子与吡啶酮环共面，整体像富马酸一样直，而盐中的马波沙星哌嗪基团像马来酸构型一样弯曲。此外，盐共晶和盐中马波沙星的构象变化导致不同的晶体结构和相反的理化性质。值得注意的是，两种多组分晶体都具有表面亲水性插层结构。然而，盐共晶和盐表现出不同的溶解度和渗透性。具体地，与MBF相比，MBF-MA盐显示出改善的溶解度和渗透率，而MBF-FA-H 2 FA盐共晶显示出降低的溶解度和渗透率。此外，体外细菌抑制活性测定表明MBF-MA盐对革兰氏阴性和革兰氏阳性菌株的抑制活性比MBF-FA-H 2 FA盐共晶和纯MBF更强。
更新日期：2024-01-10
中文翻译：
马波沙星与丁烯二酸的盐共晶和盐：共形成物顺反异构体对马波沙星构象和性质的影响
通过研究共聚体官能团位置异构对活性药物成分共结晶和理化性质的影响，探讨顺反异构体丁烯二酸作为共聚体对马波沙星构象、晶体结构及其理化性质的影响进行了进一步探讨。本工作选择不同构型的富马酸（FA）和马来酸（MA）作为共形成体，合成了马波沙星（MBF）药用盐共晶（MBF-FA-H 2 FA）和盐（MBF-MA），并且它们的结构得到了充分的表征。发现盐共晶中和盐中马波沙星的构象之间存在显着差异。在盐共晶中，马波沙星的哌嗪基团的N原子与吡啶酮环共面，整体像富马酸一样直，而盐中的马波沙星哌嗪基团像马来酸构型一样弯曲。此外，盐共晶和盐中马波沙星的构象变化导致不同的晶体结构和相反的理化性质。值得注意的是，两种多组分晶体都具有表面亲水性插层结构。然而，盐共晶和盐表现出不同的溶解度和渗透性。具体地，与MBF相比，MBF-MA盐显示出改善的溶解度和渗透率，而MBF-FA-H 2 FA盐共晶显示出降低的溶解度和渗透率。此外，体外细菌抑制活性测定表明MBF-MA盐对革兰氏阴性和革兰氏阳性菌株的抑制活性比MBF-FA-H 2 FA盐共晶和纯MBF更强。
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