Lipid-based formulations to increase cannabidiol bioavailability: In vitro digestion tests, pre-clinical assessment and clinical trial

• Published in: International journal of pharmaceutics 2021-11, Vol.609, p.121159, Article 121159
• Main Authors: De Prá, Manuel A.A., Vardanega, Renata, Loss, Carla G.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Bioavailability; Biological Availability; Cannabidiol; Cross-Over Studies; Digestion; Drug Delivery Systems; Emulsions; Glyceryl monolinoleate; Humans; Lipids; Medium-chain triglycerides; Mice; SEDDS; Solubility
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2021.121159

[Display omitted] Herein, medium-chain triglycerides (MCT), glyceryl monolinoleate (GML), and a self-emulsifying drug delivery system (SEDDS) for cannabidiol (CBD) delivery were compared using in vitro and in vivo (mouse and human) studies. In vitro digestion tests showed that SEDDS yielded the highest CBD recovery in the aqueous phase (86 ± 2%), followed by GML (13 ± 2%) and MCT (5.6% ± 0.8%). In vivo tests (mouse) revealed that SEDDS promoted the highest CBD exposure, exhibiting an area under the plasma concentration-time curve (AUC0-6h) 1.48 times greater than GML and 3.97 times greater than that of the MCT formulation. A single-dose, open-label, crossover study performed in 11 volunteers showed that SEDDS increased CBD AUC0-12h by 1.12 and 1.48 times in relation to GML and MCT, respectively. The in vitro–in vivo correlation was r2 0.75 for mice and r2 0.66 for humans. The AUC correlation between mice and humans was 0.98. Collectively, these results indicate that the lipid profile substantially influences CBD delivery and highlights the potential of the SEDDS and GML formulations as candidate solutions for increasing CBD AUC and bioavailability.