Zhao Yongfeng, Fan Ying, Zhang Yan, Xu Hong, Li Min, Zhu Yunjie, Yang Zhao
College of Pharmacy, Qingdao University, Qingdao, 266071, China.
Pharmacy Department, Qingdao Special Servicemen Recuperation Center of CPLA Navy, Qingdao, 266071, China.
Heliyon. 2023 Jun 21;9(6):e17494. doi: 10.1016/j.heliyon.2023.e17494. eCollection 2023 Jun.
According to crystal engineering, the pharmaceutical intermediate -nitrobenzoic acid (MNBA), which contains a carboxylic acid group, was selected as a coformer (CCF) for drug cocrystallization with famotidine (FMT), and a new stable FMT salt cocrystal was synthesized. The salt cocrystals were characterized by scanning electron microscopy, differential scanning calorimetry, thermogravimetric analysis, infrared spectroscopy, powder X-ray diffraction and X-ray single crystal diffraction. A single crystal structure of FMT-MNBA (1:1) was successfully obtained, and then the solubility and permeability of the newly synthesized salt cocrystal were studied. The results showed that, compared with free FMT, the FMT from the FMT-MNBA cocrystal showed improved permeability. This study provides a synthetic method to improve the permeability of BCS III drugs, which will contribute to the development of low-permeability drugs.
根据晶体工程学原理，选择含有羧酸基团的医药中间体间硝基苯甲酸（MNBA）作为共形成物（CCF），与法莫替丁（FMT）进行药物共结晶，合成了一种新型稳定的FMT盐共晶体。通过扫描电子显微镜、差示扫描量热法、热重分析、红外光谱、粉末X射线衍射和X射线单晶衍射对盐共晶体进行了表征。成功获得了FMT-MNBA（1:1）的单晶结构，随后研究了新合成盐共晶体的溶解度和渗透性。结果表明，与游离FMT相比，FMT-MNBA共晶体中的FMT渗透性有所提高。本研究提供了一种提高BCS III类药物渗透性的合成方法，这将有助于低渗透性药物的开发。
