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16 October 2016 : Animal Research  

Characterization and Bioavailability of Wogonin by Different Administration Routes in Beagles

Na ZhuACE, Jian-chun LiBCF, Jin-xiu ZhuACD, Xiu WangCFG, Jin ZhangBDG

DOI: 10.12659/MSM.897621

Med Sci Monit 2016; 22:3737-3745

Abstract

BACKGROUND: With the gradually accumulating research on pharmacological activity of wogonin, the in vitro analysis research on wogonin has become more and more popular, but there are very few reports about in vivo detection, and there are no solid dispersions (SDs) of Wogonin. The aim of this study was to explore the formation of solid dispersions (SDs) of wogonin. The reasons for the low bioavailability were studied through different routes of administration.

MATERIAL AND METHODS: SDs was formulated using the solvent evaporation method via polyvinylpyrrolidone K30 (PVP). The characterization of the drug and its carrier was detected by X-ray diffraction (XRD) and differential scanning calorimetry (DSC). The serum concentrations of Wogonin were detected using the LC-MS/MS method. Six beagles were fed 3 different formulations of wogonin in 3 cycles.

RESULTS: The SDs of wogonin had a higher solubility than the physical mixtures. Based on XRD and DSC, wogonin was transformed from a crystalline morphology to an amorphous structure. The main pharmacokinetic parameters of i.g. administration (crude material and SD) and i.v. route were as follows: Cmax (2.5±1.1), (7.9±3.3), and (6838.7±1322.1) μg/L, tmax (0.7±0.3) and (0.3±0.2) h for the former, AUC0-t (7.1±2.0), (21.0±3.2) and (629.7±111.8) μg·h/L. The absolute bioavailability of native wogonin and wogonin arginine solution were (0.59±0.35)% and (3.65± 2.60)%. Further research showed that the low bioavailability of wogonin might be associated with low solubility and rapid combination with glucuronic acid in vivo.

CONCLUSIONS: The significantly increased solubility of SDs and the further preparation of arginine solution could significantly increase the bioavailability of wogonin.

Keywords: Biological Availability, Arginine - pharmacokinetics, Chemistry, Pharmaceutical, Dogs, Drug Carriers - pharmacokinetics, Flavanones - pharmacokinetics, Random Allocation, Solubility, tandem mass spectrometry, X-Ray Diffraction

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750