Process Optimization And Evaluation Target Of Ceftiofur Hydrochloride Injection Study On Pharmacokinetics Of Animal

Ceftiofur as the first animal-specific third generation cephalosporins, is now widely used in veterinary clinical to treatment of respiratory bacterial infections and related diseases, due to its strong antibacterial activity and broad antibiotic spectrum. This dissertation aims to provide a theoretical foundation for the optimization of ceftiofur injection process and clinical rational drug using, by evaluation of the process optimization and the pharmacokinetics in target animal.This thesis tested and compared the viscosity, the analog injection effect, the sedimentation volume ratio and the dispersity of ceftiofur hydrochloride injection, which produced by Hunan Agricultural University Animal Pharmaceutical Co., Ltd. before and after the process optimization and other selling products on the market. After optimization, the viscosity reduced from 269.5±21.5 mPa s to 204.0±16.7 mPa s (P<0.05), and showed no significant difference with the products of Shandong Lukang Pharmaceutical Co., Ltd., and Qilu Animal Health Products Co., Ltd. (P> 0.05); the injection time were shorter (P<0.05); the subsidence showed no significant difference (P> 0.05). but both of them are larger than the sedimentation of Qilu Pharmaceutical’s product in 72h (P<0.05); all of the products after process optimization were no agglomeration, precipitation, and adhering slag phenomenon. The results showed that the viscosity, settlement ratio, needle through property and other aspects have been well improved after optimization.Selecting 18 healthy adult hybrid white pigs and divided into three groups randomly, and then intramuscular inject of ceftiofur hydrochloride suspension injection by 5 mg/kg body weight dose with the three kinds of products:products by Hunan Agricultural University Animal Pharmaceutical Co.. Ltd. after process optimization, products by Qilu Animal Health Products Co., Ltd., and products by Hunan Agricultural University Animal Pharmaceutical Co., Ltd. before process optimization. Take 3 mL blood from precava at 1,4, 8,11,24.48,72,96,120,144 h respectively, and detect the concentration of ceftiofur hydrochloride in plasma by HPLC. The results showed that intramuscular injection of products produced by Hunan Agricultural University Animal Pharmaceutical Co., Ltd. after or before process optimization can reach effective blood concentration in a short time. Among the 6 pigs injected old process products, two pigs can only maintain effective blood concentration for three days, the other four pigs’ can maintained for 5 days, while intramuscular injection of new process products,6 pigs capable of maintaining an effective blood concentration for four days, and four pigs can maintain effective blood concentration for five days. The results illustrate that both old and new process products can prolong the effective blood concentration of hydrochloric ceftiofur, and certificate the products after process optimization is better than the products with old process by drug effect.The process optimization and target animal pharmacokinetic studies of ceftiofur hydrochloride injection plays an important role in providing long-acting release, good stability ceftiofur for the clinic.