| Enrofloxacin is a synthetic third-generation quinolone antibacterial drug approved by the FDA on October 4,1996, for livestock and aquatic quinolones. Oral absorption is good, plasma concentration is high and stable, widely distributed in the organization, and its metabolite is ciprofloxacin, and ciprofloxacin on a variety of livestock and poultry pathogens antibacterial activity is stronger than enrofloxacin, so it shows significant antibacterial drug effect (PAE).However, enrofloxacin is bitter, the animals often refuse to eat when directly dosing. Stearic acid follower solid fatty acids, plant oils and fats obtained, often used as a carrier of a solid dispersion, having a taste masking, sustained release effect. Sodium alginate and chitosan are biocompatible, biodegradable natural polymer materials, as microcapsule wall material used for taste masking and sustained release of the drug also received good results. In order to mask the bitter taste of enrofloxacin and improve its sustained-release effect, the experiment uses enrofloxacin as raw materials, emulsion solvent diffusion method is first prepared stearic acid the enrofloxacin solid dispersion the (ENRO-SD); pharmacokinetics of sodium alginate and chitosan capsule material to the external gel method were prepared chitosan alginate ENRO-SD the microcapsule (MS), and the nature of the microcapsules and in rabbits The kinetic properties were studied.In this study, prepared different concentrations of enrofloxacin solution to pigs drank, measured the bitterness threshold of pigs to enrofloxacin is 2μg/mL. Though the indicators between bitterness threshold and entrapment efficiency, we use single factor experiment and orthogonal design to optimize the preparation process of enrofloxacin microcapsules, the best available technology for 1:1 mass ratio of enrofloxacin and stearic acid dissolved in dichloromethane, so the concentration of the drug-containing of 0.15g/mL organic solution; then at room temperature, the solution was injected into a volume ratio of 1:10, a temperature of 25℃. The water-containing PVA20g/L; finally warmed to 40℃. methylene chloride, stirring was continued after the volatilization, i.e. a suspension of solid dispersion obtained enrofloxacin. In the quantity of 15g/L containing enrofloxacin solid dispersion was added to a suspension of sodium alginate, and a 10 gauge needle with a rate 8ml/min dropwise to containing CaCl2 concentration of 100g/L chitosan solution, and cured for 10min, after drying a double that was spherical and spherical enrofloxacin microencapsulated drug loading was 20.3%, the encapsulation efficiency was 89.8%.By detecting the particle size of the microcapsules, the in vitro dissolution in different dissolution media and its stability, the results showed that the average particle diameter of the microcapsules was 273.67μm;the 30s release in the simulated oral liquid Smaller 2μg/mL, the cumulative release of 2h in pH1.2 solution of hydrochloric acid is 8.1%, the cumulative release in pH6.8 phosphate buffer for 48h is 91%;after put in high light, high temperature for 10 days and in high humidity for 5 days, the oral release are less than 2μg/mL and have stability quality. Enrofloxacin drug substance and enrofloxacin microcapsules were mixed feeding to pigs, and then we count the collection of pigs. The results showed that the collection amount of the microcapsules group and the normal feed intake of the pigs are considerable, and significantly higher than the the ENRO Drug Substance group, which means it has good taste-masking effect. All the results show that enrofloxacin taste-masking microcapsules has good taste-masking,enteric-coated, sustained-release performance, and has the good stability.Of enrofloxacin and enrofloxacin microcapsules rabbits fed pharmacokinetic experiments. The results show that the group of enrofloxacin Ka (1.144±0.539) 1/h,t1/2α(5.552±1.736) h,t1/2β(5.587±1.594) h, AUC (0-∞) (11.242±2.968) mg/L*h, Tmax (0.5±0.118) h, Cmax (1.651±0.941) mg/L, fitting equation:C (ENRO) = 1.226e-0.125t+0.002 e-0.124+1.228 e-1.144; the enrofloxacin microcapsules group Ka (0.576±0.148) 1/h, t1/2α (2.344±1.004) h, t1/2β (30.104±1.802) h, AUC (0-∞) (32.767±3.362) mg/L*h, Tmax (2±0.198) h,Cmax (1.462±0.177) mg/L,its fitting equation:C (MS)= 4.576e-0.296+0.62 e-0.023+5.196 e-0.576. The group of enrofloxacin microcapsules than its bulk drugs has obvious characteristics of sustained-release and higher bioavailability.This experiment successfully prepared microcapsules of enrofloxacin, this method is simple and reliable, and the quality can be well controlled. Drug quality evaluation and the pharmacokinetics experiments show that the microcapsules do well in taste masking and sustained release, as well as increased stability, increased efficacy and convenient dosing, which provides it with a good prospect of application. |
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