Study On Process Optimization And In Vivo And In Vitro Evaluation Of Florfenicol Premix

Florfenicol,a mono-fluoro derivative of thiophene,is a new broad-spectrum amido alcohol antibiotic for veterinary use only.Florfenicol is mechanism of action is combining with the 50S subunit of the bacterial 70S ribosome to affect bacterial protein synthesis to kill the against Gram-positive and Gram-negative bacteria.However,florfenicol has poor water solubility and poor bioavailability,which limits the application.In order to improve the bioavailability of florfenicol in vivo,we carried out the study for optimize the formula and craft of florfenicol premix.And we also did research for the dissolution consistency,acute toxicity and pharmacokinetic of florfenicol premix.The formula and craft of florfenicol premix was optimized using solid dispersion technology.Based on the product particle size,water content and yield,the prescription and process of florfenicol premix were optimized by single factor test and orthogonal test,and the yield was 98.2%.The product has good dissolution in water and good stability,suitable for pilot production.A dissolution consistency study of florfenicol premix was performed in vitro.The Nuflor was used as the reference preparation.The florfenicol premix was used as the test preparation.The similarity of the two preparations was evaluated using the?2 factor method.The dissolution curves of florfenicol premix at 50 rpm and 37°C in artificial gastric juice,intestinal juice and water were similar to Nuflor.The florfenicol premix is consistent with the in vitro dissolution of Nuflor.The oral acute toxicity of florfenicol premix to Wistar rats was evaluated by Up-and-down procedure.The adverse effects of the florfenicol premix on the biological system and main organs of Wistar rats under acute exposure were determined by weight gain,organ coefficient,hematology,clinical chemistry and histopathology.The oral lethal dose(LD₅₀)of florfenicol premix is bigger than2000 mg/kg?low toxicity?,and liver may be the acute toxic target organ.An HPLC method was established for the determination of florfenicol concentration in swine plasma,and a comparative pharmacokinetic study of florfenicol in swine plasma was completed.The non-compartmental model was used to calculate the change in the plasma concentration of pigs after oral administration of two florfenicol preparations.The dosage and frequency of the two florfenicol dosage forms recommended by the clinic should be consistent and can be replaced with each other.In summary,this study established and optimized the formulation and process parameters of florfenicol premix.The consistency of the dissolution of florfenicol premix and Nuflor was evaluated.The oral acute toxicity of florfenicol premix was evaluated,too.we had completed the comparative pharmacokinetic study of florfenicol premix and Nuflor in pigs.It has guiding significance for the production and use rational of florfenicol premix.