Development of a Novel Nanoemulsion Formulation to Improve Intestinal Absorption of Cannabidiol

Abstract

<b><i>Background:</i></b> Cannabidiol (CBD) is highly lipophilic, and its oral bioavailability is known to be very low in humans. In this study, we developed a novel nanoemulsion preparation of CBD (CBD-NE) to improve the poor solubility and absorption of CBD. The pharmacokinetic profiles of CBD in rats were evaluated after oral administrations of CBD oil and CBD-NE, and the effect of bile secretion on CBD absorption was also evaluated. <b><i>Methods:</i></b> The CBD-NE formulation developed in this study consisted of vitamin E acetate, ethanol, Tween-20, and distilled water (1.7/3.8/70/24.5, w/w%). A CBD oil formulation (CBD oil, control) 100 mg/kg or CBD-NE 50 mg/kg was orally administered to rats, and the blood samples were collected over time. Moreover, the CBD oil or CBD-NE was orally administered to bile-fistulated rats, and the pharmacokinetic profiles of CBD were also evaluated. CBD concentrations in plasma were measured using LC-MS/MS. <b><i>Results:</i></b> The particle size of CBD-NE was 35.3 ± 11.8 nm. Mean T<sub>max</sub> of CBD-NE was shortened significantly by the factor of 3 (from 8.00 to 2.40 h, <i>p</i> < 0.001) and AUC<sub>0–</sub><sub>∞</sub>/dose increased by 65% (from 0.272 ± 0.045 to 0.448 ± 0.087 h L/kg) compared with CBD oil. AUC<sub>0–</sub><sub>∞</sub>/dose and C<sub>max</sub>/dose after oral administration of CBD oil were significantly reduced by the factor of 27 and 23 (<i>p</i> < 0.05 and <i>p</i> < 0.01), respectively, in bile-fistulated rats compared with the untreated rats. In contrast, all pharmacokinetic parameters after oral administration of CBD-NE were not significantly different between the untreated and bile-fistulated rats. Therefore, these results demonstrated that conventional CBD oil formulation but not CBD-NE requires bile-mediated micelle formation. <b><i>Conclusions:</i></b> The novel NE formulation developed in this study successfully improved the absorption of CBD regardless of bile secretion. The newly developed oral CBD-NE preparation could be useful to achieve a more stable and quicker onset of action by CBD.