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

• Published in: Molecules (Basel, Switzerland) Vol. 24; no. 16; p. 2967
• Main Authors: Knaub, Katharina, Sartorius, Tina, Dharsono, Tanita, Wacker, Roland, Wilhelm, Manfred, Schön, Christiane
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 16.08.2019; MDPI
• Subjects: Administration, Oral; Adult; Analgesics - blood; Analgesics - pharmacokinetics; Anti-Anxiety Agents - blood; Anti-Anxiety Agents - pharmacokinetics; Area Under Curve; Bioavailability; Biological Availability; Cannabidiol; Cannabidiol - blood; Cannabidiol - pharmacokinetics; Cannabis sativa; CBD; Cross-Over Studies; Double-Blind Method; Drug delivery systems; Drug Delivery Systems - methods; Drug dosages; Emulsifying Agents - administration & dosage; Emulsifying Agents - chemistry; Fasting; Female; Food; Gender; Healthy Volunteers; Hemp; hemp extract; human; Humans; Male; Marijuana; Metabolism; oral drug delivery system; pharmacokinetic; Pharmacokinetics; Plasma; SEDDS; Sex Factors; Tetrahydrocannabinol; THC; Vegetarianism; Women; cannabidiol; Cannabis sativa; hemp extract; SEDDS; CBD; bioavailability; oral drug delivery system; pharmacokinetic; human
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24162967

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.