Development and pharmacokinetic evaluation of a self-nanoemulsifying drug delivery system for the oral delivery of cannabidiol

• Published in: European journal of pharmaceutical sciences 2022-01, Vol.168, p.106058-106058, Article 106058
• Main Authors: Kok, Lie Yun, Bannigan, Pauric, Sanaee, Forugh, Evans, James C., Dunne, Michael, Regenold, Maximilian, Ahmed, Lubabah, Dubins, David, Allen, Christine
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Bioavailability; Biological Availability; Cannabidiol; Drug Delivery Systems; Emulsions; Female; Lipophilic drugs; Nanoparticles; Oral delivery; Particle Size; Pharmacokinetics; Rats; Rats, Sprague-Dawley; Self-nanoemulsifying drug delivery systems; Solubility
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2021.106058

•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. 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. 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 obtained 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 Tmax 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. [Display omitted]