Study On The Model Of Solid Liquid Equilibrium And The Preparation Of Uitra-Fine Florfenicol Powder

Florfenicol is a broad spectrum antibiotic that is effective against many organisms. But the relatively low solubility of florfenicol in water limits its use in medicated drinking water systems for treatment of disease of swine and poultry. Increasing the solubility of florfenicol has important significance for enhancing its bioavailability. In this paper, florfenicol ultra-fine powder was prepared by dilution crystallization method, so that we can significantly increase its water-solubility in medicated drinking water systems. To choose appropriate solvent and anti-solvent and optimizate the crystallization process, solid-liquid equilibrium was firstly researched about florfenicol's dilution crystallization thermodynamics. In view of this, the solubilities of florfenicol in Propanone, Tetrahydrofuran, Methanol, Ethanol,1-propanol, Water and in binary Water+Ethanol and Water+Acetone solvent mixtures were measured by the light extinction measurement. It was studied about the effects of temperature and solvent ratio on the solubility. For solubility data of florfenicol in binary Water+Ethanol solvent mixtures, A hybrid model that combines solid-liquid equilibrium equation with combined nearly ideal binary solvent (CNIBS)/Redlich-Kister model is proposed to correlate the solubility of pharmaceutical compounds with both temperature and initial composition of binary solvent mixtures. Hybrid model parameters were obtained by multiple linear regression, then the better model choosed based on analysis and comparison the average relative error and single maximum relative error. According to p-values as the significant criterion of equation parameter, stepwise regression method was used to simplify the hybrid model, Integer Programming was implemented through the Genetic Algorithm in MATLAB to obtain the optimized parameter values with a fixed number of decimals. Some other solubility data calculated by this model were listed and compared with experimental results. This paper is not only providing useful models and data in the relative research but also putting forward a feasible process route for simplifing and optimizing models about mixed solvent systems. On the basis of thermodynamics, this paper has preliminarily studied this solvent crystallization process, by scanning electron microscopy investigated the impact of crystallization temperature, stirring speed and the ratio of solvent and antisolvent on the crystal form and crystal size type. The results show that at the low-temperature, high stirring speed and proper ratio of solvent and antisolvent, the average size of solvent crystallization product is about 10μm and it can meet the purpose.