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

Drug Dev Ind Pharm. 2009 Dec;35(12):1452-9. doi: 10.3109/03639040903002151.

Abstract

Objective: The aim of this study was to prepare the inclusion complex of genipin (GP) and beta-cyclodextrin (beta-CD) with improved stability, solubility, and bioavailability and to study the pharmacokinetics of beta-CD inclusion complex in mice.

Methods: Lyophilization was employed in the preparation of the inclusion complex of GP-beta-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-beta-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-beta-CD exhibited the dissimilar pharmacokinetics from that of free GP after intravenous administration. The inclusion complex of GP-beta-CD displayed longer MRT(0-infinity) and higher AUC(0-infinity) than free GP did.

Conclusions: The relative bioavailability of the inclusion complex of GP-beta-CD to free GP was 305.3%, which demonstrated that GP formulations containing beta-CD significantly increased the bioavailability.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics*
  • Biological Availability
  • Calorimetry, Differential Scanning
  • Drug Carriers / chemistry*
  • Drug Carriers / pharmacokinetics*
  • Drug Stability
  • Freeze Drying
  • Half-Life
  • Iridoid Glycosides
  • Iridoids / blood
  • Iridoids / chemistry
  • Iridoids / pharmacokinetics*
  • Male
  • Mice
  • Powder Diffraction
  • Random Allocation
  • Solubility
  • Spectrophotometry, Ultraviolet
  • Spectroscopy, Fourier Transform Infrared
  • beta-Cyclodextrins / chemistry*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Drug Carriers
  • Iridoid Glycosides
  • Iridoids
  • beta-Cyclodextrins
  • genipin