Improved photostability, solubility, hygroscopic stability and antimicrobial activity of fleroxacin by synthesis of fleroxacin-D-tartaric acid pharmaceutical salt

IF 4.4 2区 医学 Q1 PHARMACOLOGY & PHARMACY
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Abstract

To improve the solubility of the fluoroquinolone drug fleroxacin (FL), based on the previous experience of our research group in synthesizing co-crystals/salts of quinolone drugs to improve the physicochemical properties of drugs, Fleroxacin-D-tartaric acid dihydrate salt (FL-D-TT, C17H19F3N3O3·C4H5O6·2(H2O)), was synthesized for the first time using fleroxacin and D/L-tartaric acid (D/L-TT). Structural characterization of FL-D-TT was carried out using single-crystal X-ray diffraction, infrared spectral analysis (FT-IR) and powder X-ray diffraction (PXRD). Molecular electrostatic potential analysis showed that D-tartaric acid interacted more readily with FL than L-tartaric acid. The solubility of FL-D-TT (9.71 mg/mL, 1.82 mg/mL) was significantly higher compared to FL (0.39 mg/mL, 0.71 mg/mL) in water and buffer solution at pH 7.4. This may be attributed to the formation of charge-assisted hydrogen bonds (CAHBs) between FL and D-TT that facilitates the dissociation of FL cations in the dissolution medium, leading to an increase in FL solubility. This also led to some improvement in the in vitro antimicrobial activity of FL-D-TT against E. coli, S. typhi, and S. aureus. In addition, the hygroscopic stability of FL has been improved. Surprisingly, FL-D-TT had better photostability than FL, which could be attributed to the introduction of D-TT to make the photosensitizing moiety of FL more stable, which led to the improvement of the photostability of FL.

Abstract Image

通过合成氟罗沙星-D-酒石酸药用盐改善氟罗沙星的光稳定性、溶解性、吸湿稳定性和抗菌活性。
为了提高氟喹诺酮类药物氟罗沙星(Fleroxacin,FL)的溶解度,根据本课题组以往合成喹诺酮类药物共晶体/盐以改善药物理化性质的经验,首次合成了氟罗沙星-酒石酸二水盐(FL-D-TT,C17H19F3N3O3-C4H5O6-2(H2O))、首次利用氟罗沙星和 D/L 酒石酸(D/L-TT)合成了氟罗沙星-D-酒石酸二水盐(FL-D-TT,C17H19F3N3O3-C4H5O6-2(H2O))。利用单晶 X 射线衍射、红外光谱分析(FT-IR)和粉末 X 射线衍射(PXRD)对 FL-D-TT 进行了结构表征。分子静电位分析表明,D-酒石酸比 L-酒石酸更容易与 FL 发生相互作用。在水和 pH 值为 7.4 的缓冲溶液中,FL-D-TT 的溶解度(9.71 毫克/毫升,1.82 毫克/毫升)明显高于 FL(0.39 毫克/毫升,0.71 毫克/毫升)。这可能是由于 FL 和 D-TT 之间形成了电荷辅助氢键(CAHBs),促进了 FL 阳离子在溶解介质中的解离,从而提高了 FL 的溶解度。这也在一定程度上提高了 FL-D-TT 对大肠杆菌、伤寒杆菌和金黄色葡萄球菌的体外抗菌活性。此外,FL 的吸湿稳定性也得到了改善。令人惊讶的是,FL-D-TT 比 FL 具有更好的光稳定性,这可能是由于 D-TT 的引入使 FL 的光敏分子更加稳定,从而改善了 FL 的光稳定性。
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来源期刊
CiteScore
8.80
自引率
4.10%
发文量
211
审稿时长
36 days
期刊介绍: The European Journal of Pharmaceutics and Biopharmaceutics provides a medium for the publication of novel, innovative and hypothesis-driven research from the areas of Pharmaceutics and Biopharmaceutics. Topics covered include for example: Design and development of drug delivery systems for pharmaceuticals and biopharmaceuticals (small molecules, proteins, nucleic acids) Aspects of manufacturing process design Biomedical aspects of drug product design Strategies and formulations for controlled drug transport across biological barriers Physicochemical aspects of drug product development Novel excipients for drug product design Drug delivery and controlled release systems for systemic and local applications Nanomaterials for therapeutic and diagnostic purposes Advanced therapy medicinal products Medical devices supporting a distinct pharmacological effect.
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