Preparation, characterization, and pharmacokinetics of the inclusion complex of genipin-β-cyclodextrin

Abstract

Objective: The aim of this study was to prepare the inclusion complex of genipin (GP) and β-cyclodextrin (β-CD) with improved stability, solubility, and bioavailability and to study the pharmacokinetics of β-CD inclusion complex in mice. Methods: Lyophilization was employed in the preparation of the inclusion complex of GP–β-CD, whose formation was confirmed by infrared, ultraviolet, differential scanning calorimetry, X-ray diffraction, and phase solubility method. Comparative studies on the in vitro solubility and stability and in vivo evaluation of GP in mice were investigated. Liquid–liquid extraction was used for the isolation of GP in the assay of its concentration. After injection in the caudal vein at equal doses of the inclusion complex of free GP, the drug concentration in mice plasma at fixed time after administration was determined by high-performance liquid chromatography method. Results: The results demonstrated that GP–β-CD solid powders showed improved stability and solubility in aqueous solution, when comparing with free GP. The results of the in vivo study showed that the inclusion complex of GP–β-CD exhibited the dissimilar pharmacokinetics from that of free GP after intravenous administration. The inclusion complex of GP–β-CD displayed longer MRT_0–∞ and higher AUC_0–∞ than free GP did. Conclusions: The relative bioavailability of the inclusion complex of GP–β-CD to free GP was 305.3%, which demonstrated that GP formulations containing β-CD significantly increased the bioavailability.

Keywords:

• β-Cyclodextrin
• genipin
• inclusion complex
• pharmacokinetics
• solubility
• stability

Acknowledgments

This study was supported by National Natural Science Foundation of China (grant no. 30500667) and Shanghai Science and Technology Committee (grant no. 05QMX1449).

Declaration of interest: The authors report no conflicts of interest.