Preparation And Evaluation Of Sarafloxacin ?-Cyclodextrin Inclusion Complex

Sarafloxacin is a commonly used antibacterial drug in veterinary clinic.its common dosage form is water-soluble powder and is administered through drinking water.Due to its low solubility and unstable chemical properties,it has great limitations in clinical application.In this paper,a new dosage form of sarafloxacin was prepared with?-cyclodextrin,which aims to improve the solubility and bioavailability of sarafloxacin,and is of great significance for the clinical use of sarafloxacin.Sarafloxacin inclusion complex was prepared with?-cyclodextrin,and the preparation process of microcapsules was optimized by response surface method.The optimized preparation conditions are stirring temperature 50?,stirring time 4 h and stirring speed 300 r/min.The optimized spray drying conditions are as follows:air inlet temperature 160C,peristaltic pump speed 6.3r/min.The entrapment efficiency and solubilization ratio of the inclusion complex were 90.33%and 25.33 times,respectively.The inclusion complex microcapsules were characterized by powder X-ray diffraction,differential scanning quantity and thermogravimetry,scanning electron microscope,transmission electron microscope and nuclear magnetic resonance.There were rod-like sarafloxacin crystals in the vesicles of the inclusion complex microcapsules.The inclusion complex microcapsule was a dense and uniform massive structure.The longitudinal coordinate peak of the inclusion complex microcapsule was less than 5000,the peak shape became wider,and the diffraction pattern was halo-shaped,which changed the orientation of sarafloxacin molecules to some extent.The inclusion complex microcapsules began to decompose at 230.7?,accompanied by weight loss.The method for the determination of inclusion complex microcapsules by high performance liquid chromatography?HPLC?was established.The liquid chromatographic condition for content determination was Agilent ZORBAX SB-C18?4.6×150mm 5-Micron?column,the column temperature was 30?,the mobile phase was acetonitrile-2%tetrabutylammonium bromide system?13?87,v/v?,the detection wavelength was 280 nm,and the injection volume was 5?L.In the range of 9.94-99.40?g/mL,the regression equation of sarafloxacin was Y=34.66 X-15.867,and the correlation coefficient?R²?was 0.9999.The complexation behavior of sarafloxacin with?-cyclodextrin in solution was studied by Job's plot analysis,nuclear magnetic resonance and solubility method.The sarafloxacin entered the cavity from the wide mouth of?-cyclodextrin,piperazine and some quinoline rings were wrapped in the cavity.The stoichiometric ratio of microcapsules of the inclusion complex is 1:1.The inclusion and mechanism of the inclusion complex microcapsules were analyzed by molecular docking experiments.The distance between Hmur-3 of?-cyclodextrin and sarafloxacin piperazinyl and quinoline was 0.35nm,including multiple hydrogen bonds.Sarafloxacin can stably exist in the cavity of?-cyclodextrin.The drug release in vitro was studied by dissolution experiment.The cumulative dissolution of inclusion complex microcapsules reached 97%after 60 min.The cumulative dissolution of the physical mixture reached 63%after 60 min.The cumulative dissolution of sarafloxacin powder reached 74.4%after 60 min.CCK8 method was used to evaluate the cytotoxicity of inclusion complex microcapsules.The cytotoxicity of inclusion complex microcapsules was significantly lower than that of sarafloxacin.The IC₅₀=505.6?moL/L of IC₅₀=287.0?moL/L,inclusion complex microcapsules of sarafloxacin was calculated.The internal standard method was used to study the pharmacokinetics of chicken in vivo.The AUC values of inclusion complex microcapsules and sarafloxacin powder were 43.59±0.5 mg/h/L and 17.27±0.3 mg/h/L,respectively.The CL-F was 0.23±0.05 L/h/kg and 0.58±0.06 L/h/kg respectively.The Tmax of inclusion complex microcapsule and SAR powder were 2.18±0.09 h and0.98±0.07 h,respectively.The Cmax of microcapsule and sarafloxacin powder were 5.99±0.3?g/m L and 1.19±0.1?g/mL,respectively.The stability of the preparation was evaluated,the concentration changes of physical mixture and inclusion complex microcapsules were similar within 48 hours at pH1.5.At 120 h,the concentration of free drugs in the physical mixture decreased by 46%,while the concentration of inclusion complex microcapsules decreased by only 17%.The results show that the preparation process of inclusion complex microcapsules is stable and feasible,and the new inclusion complex microcapsules have good physical,chemical and biological properties,which is of positive significance for the development and clinical application of new dosage forms.