Development and Pharmacokinetic Evaluation of a Self-Nanoemulsifying Drug Delivery System for the Oral Delivery of Cannabidiol

The number of lipophilic drug candidates in pharmaceutical discovery pipelines has increased in recent years. These drugs often possess physicochemical properties that result in poor oral bioavailability, and their clinical potential may be limited without adequate formulation strategies. Cannabidiol (CBD) is an excellent example of a highly lipophilic compound with poor oral bioavailability, due to low water solubility and extensive first-pass metabolism.

Highlights

CBD-SNEDDS formulations were developed using a digestion-resistant surfactant.

Digestion of the CBD-SNEDDS formulations resulted in minimal drug precipitation.

CBD-SNEDDS improved the in vivo exposure to CBD relative to a simple oil formulation.

CBD-SNEDDS were also compared in vivo with a sesame oil-based formulation of CBD.

An approach that may overcome these limitations is formulation of the drug in self-nanoemulsifying drug delivery systems (SNEDDS). Herein, CBD-SNEDDS formulations were prepared and evaluated in vitro. Promising formulations (F2, F4) were administered to healthy female Sprague-Dawley rats via oral gavage (20 mg/kg CBD). Resulting pharmacokinetic parameters of CBD were compared to those following administration of CBD in two oil-based formulations: a medium-chain triglyceride oil vehicle (MCT-CBD), and a sesame oil-based formulation similar in composition to an FDA-approved formulation of CBD, Epidiolex® (SO-CBD).

Compared to MCT-CBD, administration of the SNEDDS formulations led to more rapid absorption of CBD (median T_max values: 0.5 h (F2), 1 h (F4), 6 h (MCT-CBD)). Administration of F2 and F4 formulations also improved the systemic exposure to CBD by 2.2 and 2.8-fold compared to MCT-CBD; however, no improvement was found compared to SO-CBD.

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Materials: Brij® O10 (polyoxyethylene (10) oleyl ether), sesame oil, olive oil, Tween® 80 (polyoxyethylene sorbitan monooleate), ethyl 3-methyl-3-phenylglycidate, maleic acid and lipase from porcine pancreas (Type II) were purchased from Sigma Aldrich (Oakville, ON, Canada). Light mineral oil NF/FCC was obtained from Fisher Scientific (Waltham, MA, USA). Captex® 355 EP/NF (MCT oil) was a gift from Abitec Corporation (Janesville, WI, USA). Labrafac^TM CC (MCT oil) was a gift from Gattefossé (Saint-Priest, France). FaSSIF/FeSSIF/FaSSGF and FaSSIF-V2 powders were purchased from Biorelevant.com Ltd. Calcium chloride dihydrate, propylene glycol, sodium chloride and sodium hydroxide pellets were purchased from BioShop Canada Inc. (Burlington, ON, Canada). Hydrochloric acid (6 M) and sodium hydroxide (10 M) were obtained from VWR Chemicals (Radnor, PA, USA). CBD isolate (98%) was obtained from Toronto Research Chemicals.

Article information: Lie Yun Kok, Pauric Bannigan, Forugh Sanaee, James C. Evans, Michael Dunne, Maximilian Regenold, Lubabah Ahmed, David Dubins, Christine Allen, Development and Pharmacokinetic Evaluation of a Self-Nanoemulsifying Drug Delivery System for the Oral Delivery of Cannabidiol, European Journal of Pharmaceutical Sciences, 2021. https://doi.org/10.1016/j.ejps.2021.106058.

See also our editorial special on excipients for CBD: