| Enfloxacin(ENR)is a broad spectrum of animal-specific antimicrobials.The laboratory had prepared enrofloxacin gelatin microcapsule(EMS)that used packing materials with gelatin by single condensation method.In order to clarify the release characteristics in vitro,stability and animal transport characteristics in the body of EMS,through the EMS content determination method to establish and verify,the EMS release determination,the stability test of EMS in the rumen and the pharmacokinetic test of EMS,the determination in vitro of EMS content by UV spectrophotometry(UV)and HPLC was established;the release of EMS in acid and buffer was determined;the effects of high temperature,high humidity and strong light on the stability of EMS were investigated and their stability was measured;The stability of enrofloxacin gelatin microcapsules in rumen was investigated,pigs were selected as target animals,and pharmacokinetic studies were carried out in EMS target animals.The results showed that:(1)The specificity,linearity,precision and recovery rate of UV spectrophotometry method(Measured at 270 nm)and HPLC(Column:4.6*250 mm,5 ?m,C18 column;mobile phase:0.025 mol/L phosphoric acid:acetonitrile = 83:17;detection wavelength:278 nm;column temperature:25 ?)were all consistent with the request.The two method could be used for the quality control of EMS.(2)The ENR cumulative release of 2 h in acid reached 81.63%,while the EMS cumulative release rate of 2 h in acid was only 9.07%.After 2 h,the release rate was measured in buffer at pH 6,8,the ENR dissolved more than 90%at 0.5h,while the dissolution of EMS was 93.83%at 36h,showed that EMS was more stable than ENR in acid,and EMS has a significant sustained release effect in pH 6.8 buffer.The EMS release data were fitted with the first order equation and the Higuchi equation,the results showed that the release curve of EMS accorded with the first order equation,the release equation was ln(1-Mt/M?)=-0.0858t+4.819,r=0.970,t90 was 29.32h.(3)EMS was placed under high temperature(60?)conditions for 10 days,the drug content decreased by more than 5%;under the condition of 40? after 10 d,the EMS drug loadings reduced 0.8%<5%;Placed in the high humidity conditions(RH90%± 5%,75 ± 5%)10d.The moisture-absorption weight gain of EMS more than 5%;placed in strong light conditions for 10d,the EMS color from pale brown to light yellow,drug loading decreased by 0.684%<5%.The results show that EMS is sensitive to high temperature,high humidity and light,should be kept in a cool,dark,dry place.(4)After 6 months of accelerated and long-term trials,the appearance(microcapsule color,morphology)were not significantly changed,changes of drug loading in three batches of microcapsules(2.261%,1.911%,2.629%)and the release changes(0.657%,0.748%,0.286%)were lower than 5%.Predicted that the EMS is valid for 14 years according to the accelerated test(40±2?)results(5)The degradation rate of EMS was gradually increased with the prolongation of residence time in bovine rumen,and the degradation rate of 24h reached 60%,indicating that the stability of tilmicosin gelatin microcapsules in the bovine rumen was poor.(6)The HPLC method for ENR content determination in pig blood was established(Column:C18,5?m,4.6 mm × 250 mm;mobile phase:acetonitrile:0.1 mol/L phosphoric acid= 20:80;Flow rate:1.0 mL/min;column temperature:35 ?;injection volume:50 ?L).The ENR was extracted by acetonitrile.The specificity,linearity,detection limit and quantitative limit,precision and recovery rate of this method are in accordance with the test requirements and can be used for the determination of ENR in porcine plasma.(7)After giving oral administration to the pig,the half-life(t1/2ka)was 1.007±0.069h,the elimination half-life(t1/2?)was 4.975±0.252h,the peak time(tmax)was 3.034±0.162h,the area under the curve(AUC)was 25.860±11.039?g·h/mL,the bioavailability(F)was 99.75±0.108%,the peak concentration(Cmax)was 2.359±0.0248?g/mL,Compared with ENR(tl/2ka 0.432±0.069h,t1/2? 2.619±0.069h,tmax 1.354±0.125h,AUC 15.531 ±0.790?g·h/mL,F 97.155±2.404%,Cmax 2.823±0.096?g/mL),increased by 133.10%,89.96%,124.08%,66.51%,2.67%,and decreased by 16.44%,which indicated that EMS body absorption and elimination process in the pig significantly extended,can achieve sustained release effect,and improve the bioavailability. |
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