{"title":"Development of a Novel Nano-emulsion Formulation to Improve Intestinal Absorption of Cannabidiol.","authors":"Yukako Nakano, Masataka Tajima, Erika Sugiyama, Vilasinee Hirunpanich Sato, Hitoshi Sato","doi":"10.1159/000497361","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":"2 1","pages":"35-42"},"PeriodicalIF":0.0000,"publicationDate":"2019-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000497361","citationCount":"50","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Medical Cannabis and Cannabinoids","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1159/000497361","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2019/9/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 50
Abstract
Background: 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.
Methods: 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.
Results: The particle size of CBD-NE was 35.3 ± 11.8 nm. Mean Tmax of CBD-NE was shortened significantly by the factor of 3 (from 8.00 to 2.40 h, p < 0.001) and AUC0-∞/dose increased by 65% (from 0.272 ± 0.045 to 0.448 ± 0.087 h L/kg) compared with CBD oil. AUC0-∞/dose and Cmax/dose after oral administration of CBD oil were significantly reduced by the factor of 27 and 23 (p < 0.05 and p < 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.
Conclusions: 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.
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