Precipitation complexation method produces cannabidiol/beta-cyclodextrin inclusion complex suitable for sublingual administration of cannabidiol

J Pharm Sci. 2007 Feb;96(2):312-9. doi: 10.1002/jps.20766.

Abstract

In the present study, the precipitation complexation method was used to prepare a complex of cannabidiol (CBD) with beta-CD. The effect of beta-CD-complexation on the sublingual absorption of CBD was studied in rabbits. A solid CBD/beta-CD inclusion complex was prepared by precipitation and the effect of complex formation on the dissolution rate of CBD was studied. The absorption of CBD (a 250 microg/kg dose of CBD in all formulations) after sublingual administration of solid CBD/beta-CD complex and ethanolic CBD solution, and after oral administration of ethanolic CBD solution, was studied in vivo in rabbits. The dissolution rate of solid CBD/beta-CD complex in vitro was significantly (p<0.05) higher than that of plain CBD. The absorption of CBD (AUC0-300 min) decreased in the following order: sublingual ethanolic CBD solution (420+/-120 ngxmin/mL; mean+/-SD; n=4)>sublingual solid CBD/beta-CD complex (270+/-120 ngxmin/mL)>oral ethanolic CBD solution (concentrations in plasma below the quantitation limit). The results demonstrate that sublingual administration of a solid CBD/beta-CD complex enhances the absorption of CBD in rabbits when compared to oral administration of ethanolic CBD. Furthermore, the solid CBD/beta-CD complex may provide an alternative formulation for sublingual administration of CBD.

MeSH terms

  • Absorption
  • Administration, Oral
  • Administration, Sublingual
  • Animals
  • Biological Availability
  • Cannabidiol / administration & dosage
  • Cannabidiol / chemistry*
  • Cannabidiol / pharmacokinetics*
  • Chemical Precipitation
  • Drug Compounding
  • Ethanol / chemistry
  • Female
  • Male
  • Rabbits
  • Solubility
  • beta-Cyclodextrins / administration & dosage
  • beta-Cyclodextrins / chemistry*

Substances

  • beta-Cyclodextrins
  • Cannabidiol
  • Ethanol
  • betadex