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J Pharm Sci. 2007 Feb;96(2):312-9.

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

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Department of Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland.


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.

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