Preparation and evaluation of florfenicol/dimethyl-β-cyclodextrin inclusion compound
Objective To improve the solubility,dissolution rate and bioavailability of florfenicol(FF),a FF/dimethyl-β-cyclodextrin(DM-β-CD)inclusion complex(FF/DM-β-CD)was prepared and evaluated.Methods The binding free energies of FF with 6 cyclodextrins(CDs)were calculated by molecular docking,and then the phase solubility of FF in 4 cyclodextrin solutions was determined to screen for a proper CD.FF/DM-β-CD was prepared by stirring under the heating method and characterized by differential scanning calorimetry(DSC),powder X-ray diffractometry(PXRD),and Fourier transform infrared spectrometry(FT-IR).The solubility,solution stability,in vitro dissolution and in vivo pharmacokinetics of FF/DM-β-CD were investigated.Results The results of molecular docking and phase solubility determination showed that the docking model of FF with hydroxypropyl-β-cyclodextrin(HP-β-CD),DM-β-CD and sulfobutyl-β-cyclodextrin(SBE-β-CD)was stable,and DM-β-CD exhibited the best enhancing effect on the solubility of FF.Using DM-β-CD as inclusion material,FF/DM-β-CD was prepared successfully by stirring under the heating method.DSC,PXRD and FT-IR results confirmed the formation of FF/DM-β-CD.FF/DM-β-CD could significantly increase the solubility of FF in standard hard water,tap water,deionized water,and purified water,which were at least 55.0 times higher than that of FF.When stored at 25 ℃,the FF/DM-β-CD solution was still clear in tap water after 1 day,while a small amount of precipitate occurred in standard hard water,pure water and deionized water.The amount of precipitate gradually increased with time and was the least in tap water after 7 days.There were no significant differences between the in vitro dissolution of FF/DM-β-CD in standard hard water,tap water,deionized water and purified water.At 5 min,the cumulative dissolution percentage of FF/DM-β-CD reached 100％at 25 ℃,which was 17.09 times that of FF raw material.Compared with FF,the bioavailability of FF/DM-β-CD in chickens increased with F=165.24％.Conclusion FF/DM-β-CD prepared with DM-β-CD as inclusion material could significantly improve the solubility,dissolution and bioavailability of FF.
FlorfenicolDimethyl-β-cyclodextrinInclusion complexSolubilityIn vitro dissolutionIn vivo pharmacokinetics
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