Enrofloxacin Gelatin Microcapsule Excipients, Impurities, Stability And Non-clinical Pharmacokinetics

Enrofloxacin?ENR?is a broad-spectrum antibacterial agent for animals.In order to improve the palatability of ENR,the laboratory prepared enrofloxacin gelatin microcapsules?EMS?by single coacervation.In order to further improve the preparation process of EMS and provide pharmacokinetic parameters for clinical use,the excipient types,impurity content,stability and non-clinical pharmacokinetic studies of EMS were studied.The results showed that:?1?EMS were prepared with medical grade bone gelatin and skin gelatin,the yield,encapsulation efficiency,drug loading,particle size,sudden release rate,comprehensive score and bitterness grade of the microcapsules prepared with two kinds of gelatin were not significantly different?P > 0.05?;there were no significant differences in yield,encapsulation efficiency,drug loading,particle size,sudden release rate,comprehensive score and bitterness grade?P > 0.05?between EMS prepared with medical grade raw materials?skin gelatin,tween 80,sodium sulfate,glutaraldehyde?and EMS prepared with reagent grade raw materials?gelatin,AEO-9,sodium sulfate,glutaraldehyde?;EMS prepared by 0.04% Tween80 group had higher encapsulation efficiency,microencapsulation dispersion and comprehensive score than those prepared by 0.02% and 0.03% Tween 80 group?P<0.05?,there were no significant difference in the yield,drug loading,particle size and burst release rate of EMS prepared by three concentration Tween 80 wetting agent groups?P>0.05?.Indicate that there was no significant difference between EMS prepared with pharmaceutical Tween 80?0.04%?,gelatin?skin gelatin or bone gelatin?,glutaraldehyde,sodium sulfate and EMS prepared with analytical pure excipients.?2?The average content of SO₄^2-in EMS determined by ion chromatography was7.94±0.67%;The content of glutaraldehyde in EMS determined by hplc method was0.03±0.01%,lower than 0.5%.Indicate that the contents of glutaraldehyde and total sulfateion in EMS were in accordance with the requirements.?3?After 24 months at room temperature,the properties of EMS remained unchanged,and the drug loading and release of EMS did not change significantly?P > 0.05?.Indicate that EMS could be stored at room temperature for at least 24 months.?4?The rats were given EMS and ENR at a single oral dose of 11.25 mg/kg and 45 mg/kg body weight,the t1/2ka and t1/2 of EMS were prolonged by 119.10%,113.46% and 99.94%,99.27% respectively;the relative bioavailability of EMS was 166.20% and 196.41%respectively.Indicate that EMS could achieve sustained release effect,improve the bioavailability of ENR and slow down the release rate of ENR in vivo.