Preparation of Crystalline Cefquinome Free Acid via Reverse Anti-Solvent Crystallization: Physicochemical Characterization and Pharmacokinetics in Chickens

<b>Background</b>: The therapeutic efficiency of cefquinome is currently limited by the low solubility and short half-life of its commercial sulfate form (SCFQ). This study aimed to improve these properties by preparing a novel crystalline cefquinome free acid (CFQ) via a reverse anti-solvent crystallization method. <b>Methods</b>: The optimal crystallization conditions were determined through a single factor test. And the product was characterized using X-ray powder diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy. Meanwhile, in vitro and in vivo pharmaceutical evaluation were conducted. <b>Results</b>: CFQ was sucessfully obtained and the optimal crystallization conditions were determined. Comparative in vitro studies showed that CFQ exhibited improved water solubility and dissolution rates compared to SCFQ. In vivo pharmacokinetic evaluations in chickens demonstrated that CFQ significantly prolonged the elimination half-life and increased the area under the concentration-time curve, achieving a relative bioavailability of 139.92%. <b>Conclusions</b>: The novel CFQ crystal effectively overcomes the crystallization difficulties of cefquinome and offers a promising alternative formulation with enhanced bioavailability and sustained drug action.