Abstract: A new formulation of sarafloxacin/β-cyclodextrin (SAR/β-CD) inclusion complex microcapsules was prepared and characterized, and its solubilization ratio and entrapment efficiency were determined. The dissolution and pharmacokinetics of SAR/β-CD inclusion complex microcapsules were studied in vitro and in vivo. The inclusion complex microcapsules were prepared by the stirring method. The characterization was carried out by transmission electron microscope (TEM), scanning electron microscope (SEM) and powder X-ray diffraction (PXRD). The solubilization ratio and entrapment efficiency of SAR/β-CD inclusion complex microcapsules were determined by liquid chromatography, and the release of SAR/β-CD cyclodextrin inclusion complex microcapsules in phosphate buffer (pH6.8) was studied by dissolution experiment. Finally, the pharmacokinetics of inclusion complex microcapsules was evaluated in chicken with oral administration. Physical and chemical characterization showed that the drug entered the β-cyclodextrin cavity and SAR/β-CD inclusion complex microcapsules were successfully obtained. The average solubilization ratio and entrapment efficiency of the three batches of SAR/β-CD inclusion complex microcapsules were 25.3 times and 90.3%, respectively. The dissolution rate of SAR/β-CD inclusion complex microcapsules in phosphate buffer (pH6.8) was 95.6%, while that of common powder was only 72.2%. The solubility and dissolution of the preparation were significantly improved after the inclusion reaction. In pharmacokinetic experiments, the standard curve of pharmacokinetic determination of plasma concentration was y=1.563 2x-0.189 6, R²=0.999 3, which showed a good linear relationship in the range of 0.25 -10.00 μg·mL^-1. The precision RSD of the analytical method is less than 10%, and the accuracy of the analytical method is more than 90% and less than 110%. The recovery experiments showed that the recovery rates of low concentration (0.50 μg·mL^-1), medium concentration (1.00 μg·mL^-1) and high concentration (2.50 μg·mL^-1) were 90.55%±3.81%, 93.85%±3.14% and 98.19%±5.41%, respectively. The freeze-thaw experiment shows that the freeze-thaw stability (n=3) accords with the regulations of China Veterinary Pharmacopoeia (2015 edition). The pharmacokinetic tests showed that the AUC (mg·h^-1·L^-1), T_max(h) and C_max (μg·mL^-1) of SAR/β-CD inclusion complex microcapsules and sarafloxacin powder were 43.59±0.50, 2.18±0.09, 5.99±0.30 and 17.27±0.30, 0.98±0.07, 1.19±0.10, respectively. A new dosage form of SAR/β-cyclodextrin inclusion complex microcapsule was obtained, which can significantly improve the drug dissolution rate and bioavailability. It is of great significance to the popularization and application of quinolones.

Key words: sarafloxacin, microcapsule, preparation, characterization, pharmacokinetic