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.

Comparison of Five Oral Cannabidiol Preparations in Adult Humans: Pharmacokinetics, Body Composition, and Heart Rate Variability

“…The high degree of variability in CBD absorption and the resulting pharmacokinetic parameters following CBD ingestion have been previously described [4,12,[18][19][20]. Potential explanations for variable, and often poor, CBD absorption have pertained to properties of the CBD itself (e.g., poor water solubility) and also variability brought about by the significant first pass metabolism it must endure following oral ingestion.…”

“…Potential explanations for variable, and often poor, CBD absorption have pertained to properties of the CBD itself (e.g., poor water solubility) and also variability brought about by the significant first pass metabolism it must endure following oral ingestion. To counter these potential absorption hurdles, CBD preparations have been modified, with mixed success, in a variety of ways, including generation of synthetic CBD [20], creation of water-soluble CBD powders [12], development of self-emulsifying delivery systems [18,20], and encapsulation of CBD within gelatin matrix pellets [21] and liposomes [22]. One important consideration when evaluating CBD formulations is the pharmacokinetic goal and intended use of the CBD.…”

Towards Better Delivery of Cannabidiol (CBD)

“…Intrinsic problematic issues, such as polymorphism, low aqueous solubility and poor bioavailability, hinder the effective clinical development of CBD as an oral drug in the solid-state. SEDDS offer a way to increase bioavailability by increasing the solubilisation of CBD in the aqueous environment of the GI tract, allowing more CBD to cross the unstirred water layer of the GI tract and move into lymphatic or blood circulation [ 51 ]. However, SEDDS can cause chemical instabilities of drugs and high surfactant concentrations have the potential to irritate the GI tract.…”

“…Methods to increase oral CBD bioavailability have included self-emulsifying drug delivery systems (SEDDS). These involve mixtures of oils, surfactants, and solvents that produce nano or micro sized droplets when they come into contact with an aqueous solution such as in the gut [ 51 ]. The small nature of the droplets increases the surface area available for drugs to be dissolved and absorbed.…”

“…This formulation has been proven safe and effective in a paediatric population with treatment-resistant epilepsy [ 1 ]. Another group recently reported a 4.4-fold increase in C max , enhanced bioavailability, and shorter T max with a SEDDS-CBD formulation based on VESIsorb ® technology compared to a control CBD oil [ 51 ]. VESIsorb ® is a novel lipid-based delivery system which self-assembles on contact with an aqueous phase into a colloidal delivery system, which solubilises the drug and improves diffusion and absorption and thus bioavailability [ 55 ].…”