A Novel Self-Emulsifying Drug Delivery System (SEDDS) Based on VESIsorb® Formulation Technology Improving the Oral Bioavailability of Cannabidiol in Healthy Subjects.

ABSTRACT

Cannabidiol (CBD), a phytocannabinoid compound of Cannabis sativa, shows limited oral bioavailability due to its lipophilicity and extensive first-pass metabolism. CBD is also known for its high intra- and inter-subject absorption variability in humans. To overcome these limitations a novel self-emulsifying drug delivery system (SEDDS) based on VESIsorb® formulation technology incorporating CBD, as Hemp-Extract, was developed (SEDDS-CBD). The study objective was to evaluate the pharmacokinetic profile of SEDDS-CBD in a randomized, double-blind, cross-over design in 16 healthy volunteers under fasted conditions. As reference formulation, the same Hemp-Extract diluted with medium-chain triglycerides (MCT-CBD) was used. CBD dose was standardized to 25 mg. Pharmacokinetic parameters were analyzed from individual concentration-time curves. Single oral administration of SEDDS-CBD led to a 4.4-fold higher Cmax and a 2.85-/1.70-fold higher AUC0-8h/AUC0-24h compared to the reference formulation. Tmax was substantially shorter for SEDDS-CBD (1.0 h) compared to MCT-CBD (3.0 h). Subgroup analysis demonstrated a higher bioavailability in women compared to men. This difference was seen for MCT-CBD while SEDDS-CBD mitigated this gender effect. Overall, SEDDS-CBD showed a significant improvement for all determined pharmacokinetic parameters increased CBD plasma values (Cmax), favorably enhanced bioavailability (AUC) and fast absorption (Tmax). No safety concerns were noted following either administration.