Development And Evaluation Of New Solid Forms Of Florfenicol

Florfenicol is an antibiotic drug that can effectively deal with a variety of livestock diseases.It is widely used in aquaculture,veterinary clinics,and livestock infections.However,because of its poor solubility in water and insufficient absorption,florfenicol is difficult to be directly used in the antibacterial treatment of organisms.Therefore,developing a new solid form of florfenicol to increase its solubility in water is of great research interest.The crystalline thermodynamic properties of florfenicol was discussed firstly.The solubility of florfenicol in binary solvent mixtures of acetone +(methanol or ethanol or isopropanol)was experimentally measured at temperature ranging from 278.15 K to 318.15 K.The modified Apelblat equation,NRTL model,combined nearly ideal binary solvent/ Redlich–Kister(CNIBS/R-K)model,and Jouban-Acree model were used to fit the experimental solubility data,respectively.Moreover,thermodynamic properties of the investigated systems including entropy,enthalpy and Gibbs free energy of the solute were calculated to analyze the rule of dissolution.Then,the appropriate ligands for florfenicol co-crystal were screened by grinding method and solution suspension method.The method of preparing florfenicol-B cocrystal was developed by selecting suitable solvent,ratio of material and crystallization method.Co-crystals were characterized by DSC,PXRD,TGA,FTIR,Raman,microscopy,and ESP potential distributions in Gaussian simulations to validate the formation of co-crystal and how the hydrogen bonds are formed.Then,the process conditions of the florfenicol micro-nano technology was discussed including the crystallization method,solvent,cooling rate,stirring type and dispersant by crystal size,crystal habit and aggregation degree.Under the optimal conditions,florfenicol nano-particles with a particle size of ?200 nm×5 ?m were obtained.The new solids are smaller,more uniform and more dispersed than before.Based on the above studies,the solubility,dissolution rate and stability of florfenicol,florfenicol co-crystal and florfenicol nano-particles in water were measured.The results showed that solubility and dissolution rate of both florfenicol co-crystal and florfenicol nano-particles were greatly improved,and the stability was also satisfactory.