Study On Preparation Of Florfenicol Ultrafine Powder By High Gravity Method

Florfenicol(FF),as a good alternative to methylsulfonamycin and chloramphenicol,can effectively inhibit Gram-negative,positive bacteria and other bacteria.It has the advantages of broad antibacterial spectrum,safe and efficient,etc.It is clinically used to treat diseases caused by bacterial infections in livestock and aquaculture animals.However,its inherent insolubility in water has limited the wide application of florfenicol.In this paper,we propose the preparation of florfenicol ultrafine powder by high-gravity method to improve its water solubility and thus its bioavailability.Firstly,this paper combined the high-gravity inverse solvent method with spray drying to prepare florfenicol solid dispersions,and the solubility of solid dispersions(SD)was improved by optimizing the solvent system,solution concentration,and carrier formulation.The morphology,structure and crystalline shape of SD were characterized,and the dissolution properties,dissolution properties and stability of the prepared SD were evaluated.The results showed that the particles of SD were mostly spherical particles with folded surface and the particle size was in the range of 1-2 μm;the FF were uniformly dispersed in the carrier by IR and differential scanning calorimetric analysis,and there was some interaction between FF and the carrier.It is not a simple physical mixing.XRD analysis showed that the SD was an amorphous powder.The dissolution experiment showed that the saturation solubility of FF in the prepared SD could reach 4.38 mg/m L,which was 3.0 times higher than that of the original FF,and the cumulative dissolution rate at 5 min was 3.5times higher compared with that of the original drug.The stability experiment showed that the SD can exist stably in high temperature and strong light environment,but moisture absorption will occur in high humidity environment,but the powder will not agglomerate,and the FF in SD will not recrystallize due to the water absorption of the powder.In general,the SD is more stable.Florfenicol’s water solubility was enhanced through the creation of florfenicol inclusion complexes utilizing both the cyclodextrin inclusion technique and the high-gravity inverse solvent method.Hydroxypropyl-β-cyclodextrin(HP-β-CD)was selected as the inclusion material and HPMC was used as the excipient.The inclusion complex FF-HP-β-CD-HPMC was prepared at 50℃ for 50 min.The results showed that the particles were mostly spherical particles with folded surface and the particle size was in the range of 1-2 μm.The HP-β-CD is wrapped in FF by IR and NMR analysis,and the inclusion is an amorphous powder by XRD analysis.The saturation solubility of FF in the package at 25 ℃ is 14.83mg/m L,and the inclusion can be dispersed in water at an API concentration of approximately 20.00 mg/m L and maintained for more than 6 h..The cumulative dissolution rate reached 89.4% in 5 min,which was 10.6 times higher than that of the original drug.In conclusion,this study has prepared an ultrafine powder of florfenicol with excellent water solubility as well as solubility,which provides a simple and effective strategy to improve the water solubility of florfenicol and also provides an idea for solubilization of other insoluble drugs.