Structural Elucidation and Release Enhancement of the Florfenicol/β-Cyclodextrin Inclusion Complex

The limited aqueous solubility and dissolution rate of Florfenicol (FLO) constrain its therapeutic efficacy. In this study, we enhance these properties by forming an inclusion complex with β-cyclodextrin (β-CD). Employing a cooling-based solution method, the FLO/β-CD complex was synthesized, which was verified to have a stoichiometry of 1:2 through combined nuclear magnetic resonance proton spectra and single-crystal structural analysis. A ternary phase diagram guided our development of a green synthesis route for the pure complex, leveraging slow solvent evaporation and cooling techniques. Significantly, we demonstrate that at temperatures of 10, 25, and 35 °C, the complex markedly improves FLO's solubility and dissolution rate. This work not only offers a valuable strategy to overcome the challenges associated with FLO's bioavailability but also provides insightful guidance for the industrial-scale production of high-purity FLO/β-CD complexes, presenting an advancement in the formulation of poorly soluble pharmaceutical compounds.