Faculty of Chemistry, University of Lodz, Pomorska 163/165, 90-236, Lodz, Poland.
University of Lodz Doctoral School of Exact and Natural Sciences, Narutowicza 68, 901-136, Lodz, Poland.
Sci Rep. 2024 Nov 26;14(1):29317. doi: 10.1038/s41598-024-80665-y.
Enrofloxacin (EFX) is a third-generation synthetic fluoroquinolone with a broad spectrum of antibacterial activity but suffers from low water solubility, affecting its bioavailability. This study attempts to enhance the physicochemical and biological properties of enrofloxacin by converting it into multicomponent forms using crystal engineering concepts. Cocrystallization of enrofloxacin with isomeric pyridine-2,n-dicarboxylic acids (n = 3,4,5,6) resulted in four new crystalline salts (1:1): EFX·Py2,3DCA, EFX·Py2,4DCA, EFX·Py2,5DCA·HO and EFX·Py2,6DCA·HO; two of these are monohydrates. The protonation of the nitrogen atom of the piperazine moiety and the presence of crystallization water molecules were confirmed by single-crystal X-ray diffraction and Fourier transform infrared spectroscopy. Thermogravimetric analysis provided information on the thermal behaviour of multicomponent forms. The biological studies showed that the obtained salts are characterized by high antibacterial activity against Gram-positive and Gram-negative bacteria, and their haemolytic activity is low. The new salts demonstrate significantly greater solubility in water compared to the parent drug, along with enhanced antibacterial activity; hence, pyridinedicarboxylic acids appear to be efficient cocrystallizing agents for improving the efficacy of pharmaceutical ingredients.
恩诺沙星（EFX）是一种具有广谱抗菌活性的第三代合成氟喹诺酮类药物，但水溶性低，影响其生物利用度。本研究试图通过晶体工程概念将其转化为多组分形式来提高恩诺沙星的物理化学和生物学性质。用晶体工程概念将恩诺沙星与异构体吡啶-2,3-二羧酸（n=3,4,5,6）共晶化得到四个新的结晶盐（1:1）：EFX·Py2,3DCA、EFX·Py2,4DCA、EFX·Py2,5DCA·HO 和 EFX·Py2,6DCA·HO；其中两种为一水合物。氮原子的质子化和结晶水分子的存在通过单晶 X 射线衍射和傅里叶变换红外光谱得到证实。热重分析提供了多组分形式热行为的信息。生物研究表明，所得到的盐对革兰氏阳性菌和革兰氏阴性菌具有高抗菌活性，且溶血活性低。与母体药物相比，新盐在水中的溶解度显著提高，同时抗菌活性增强；因此，吡啶二羧酸似乎是提高药物成分疗效的有效共晶化剂。
