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Randomized Controlled Trial
. 2019 Aug 16;24(16):2967.
doi: 10.3390/molecules24162967.

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

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Free PMC article
Randomized Controlled Trial

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

Katharina Knaub et al. Molecules. .
Free PMC article

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.

Keywords: CBD; Cannabis sativa; SEDDS; bioavailability; cannabidiol; hemp extract; human; oral drug delivery system; pharmacokinetic.

Conflict of interest statement

C.S., K.K., R.W., T.D., T.S.: employees of contracted research organization. M.W. is independent statistician supporting with data analysis. The study was sponsored by Vesifact AG, Switzerland. The sponsors contributed to the discussion about the study design and selection of outcome measures prior to study start. Study realization, data analysis and report generating were independently undertaken by BioTeSys GmbH and M.W. The authors from BioTeSys GmbH and M.W. declare no conflict of interest regarding the publication of this paper.

Figures

Figure 1
Figure 1
Cannabidiol (CBD) plasma concentration time profile after ingestion of self-emulsifying drug delivery system-cannabidiol (SEDDS-CBD) (green) and medium-chain triglycerides-cannabidiol (MCT-CBD) (black) depicted as summary curves of mean values at single time points (mean ± 95% CI) for all subjects.
Figure 2
Figure 2
CBD plasma concentration time profile after ingestion of MCT-CBD (a) and SEDDS-CBD (b) depicted as summary curves of mean values at single time points (mean ± 95% CI) for women (red, dotted-line) and men (blue, solid line).
Figure 3
Figure 3
Study flow.

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