Precipitation Complexation Method Produces Cannabidiol/β-Cyclodextrin Inclusion Complex Suitable for Sublingual Administration of Cannabidiol

In the present study, the precipitation complexation method was used to prepare a complex of cannabidiol (CBD) with β-CD. The effect of β-CD-complexation on the sublingual absorption of CBD was studied in rabbits. A solid CBD/β-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 µg/kg dose of CBD in all formulations) after sublingual administration of solid CBD/β-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/β-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 ng × min/mL; mean ± SD; n = 4) > sublingual solid CBD/β-CD complex (270 ± 120 ng × min/mL) > oral ethanolic CBD solution (concentrations in plasma below the quantitation limit). The results demonstrate that sublingual administration of a solid CBD/β-CD complex enhances the absorption of CBD in rabbits when compared to oral administration of ethanolic CBD. Furthermore, the solid CBD/β-CD complex may provide an alternative formulation for sublingual administration of CBD. ©2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96:312-319, 2007