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Preparation of Enrofloxacin Sustained-release Preparations and Its Pharmacokinetics

Author: LianMingXiang
Tutor: DuXiangDang
School: Henan Agricultural University
Course: Basic Veterinary Science
Keywords: Enrofloxacin PLA-mPEG Polymeric micelles Pharmacokinetics
CLC: R96
Type: Master's thesis
Year: 2011
Downloads: 18
Quote: 0
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Abstract


Enrofloxacin is an antibacterial drug indicated exclusively for veterinary use, which has a broad spectrum of activity. So, it is widely used in clinic. The enrofloxacin-polymeric micelles can improve their treatment effect by modifying their pharmacokinetic characteristics. The enrofloxacin-polymeric micelles were prepared in this study by a modified spontaneous emulsification solvent diffusion method. The preparation method of the enrofloxacin-polymeric micelles was further optimized by comparing with three different proportionality of D, L-lactide and mPEG. Then, their properties and release behavior in vitro was investigated. The method of examining the single factor was used to optimize the preparation procedure. The drug loading and encapsulation were determined by HPLC. The mean diameter and distribution of the particle size were also assayed. The formulation of drug loading micelles was confirmed by IR. To further study pharmacokinetic parameters of ENR-PM, the determination of enrofloxacin in serum was established,and its distribution and pharmacokinetics were explored in the healthy rats.The final preparation condition of the micelles was established by employing the polymer with the proportion of PLA16000- mPEG2000 as carrier, acetone as organic solvent. The mean diameter was (117.2±8.2) nm, and drug loading as well as the encapsulation efficiency were (3.3±0.17) % and (32.3±1.7) %, respectively. Enrofloxacin was found to be encapsulated in the micelles by IR. In vitro, enrofloxacin could be released sustainably from the micelles.ENR in serum was determined by HPLC-FLD. The standard curves for ENR were linear in a range of 50-5000ng·mL-1.Recoveries were more than 70% for ENR in 50-4000 ng·mL-1 fortified samples. The coefficients of variation were less than 6% and the results have a good reproductivity. In pharmacokinetic study, a single dose of ENR injection and ENR-PM injection were adminstrated to 26 rats by intravenous administration separately.Pharmacokinetic analyses were carried out by a computer soft ware 3P97. The results revealed that elimination half-life (tl/2β) lengthened from 5.107±0.742 h to 12.32±4.676 h;CL reduced from 0.869±0.164 mg·kg-1·h-1 to 0.448±0.098 mg·kg-1·h-1 ; AUC also increased significantly from 5.896±0.935μg·h·mL-1 to 11.691±3.161μg·h·mL-1, which indicated that ENR-PM had the sustained release properties. The kinetics of the ENR and ENR-PM after intravenous injection both complied with two-compartment open model.

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