Figure 1. The phase solubility diagram of CBD with b-CD. The phase solubility study was performed in duplicate.

Figure 1 shows that CBD forms B-type phase solubility diagram with b-CD. The CBD concentration first
increases from the level of the intrinsic solubility of CBD (S0 = 0.2 mM) to the maximum solubility of the complex
(3.1 mM). A further increase in CD concentration does not result in any further increase in the solubility of CBD
but leads to precipitation of the inclusion complex. Generally, B-type phase-solubility behavior is typical for
natural CDs since the drug/CD inclusion complex is more soluble than the free drug itself but the solubility limit
of the drug/CD complex is reached within the concentration range of the CD.

Figure 2. The dissolution profiles of CBD capsule formulations: CBD/b-CD complex (White) and plain CBD (Black)

The values of t50% for the dissolution of CBD were significantly (p < 0.05) smaller for CBD/b-CD complex
capsules (7.1 min; mean SD; n = 4) than for plain CBD in capsules (29.5 min).

CONCLUSIONS

The results demonstrate that the precipitation complexation method can be utilized in the
development of sublingual CD-formulations. Both the aqueous solubility and dissolution rate of CBD
were increased by b-CD-complexation. Furthermore, sublingual delivery of the CBD/b-CD complex increases
the bioavailability of CBD in comparison with oral dosage forms.