Transmucosal delivery of the medical Cannabis oil via a nanoemulsion formulation

Nowadays, oral oil extracts of Cannabis represent the most relevant galenic plant-derived formulations employed in clinics. Nevertheless, the low and variable Delta 9-tetrahydrocannabinol (THC) oral bioavailability due to hepatic first-pass metabolism and low solubility in biological fluids makes Cannabis pharmacological response highly unpredictable. In this scenario, new formulation strategies appear crucial to improve cannabinoids bioavail-ability and stability, administration comfort and patient compliance. Here, we present a nanoemulsion (NE) for the buccal administration of olive oil extract from a Cannabis sativa L. variety (Bedrocan (R)). A preliminary study was carried out on olive oil-based NE to identify the optimal formulation conditions to achieve a stable system. The Bedrocan (R)-loaded NE were then prepared and characterized for size, polydispersity index, stability upon delivery by the common buccal nebulizers.THC content and release in simulated buccal fluids and permeation studies across porcine buccal mucosa. The Bedrocan (R) NEs ensured THC stability and solubility in the buccal medium as compared with the Cannabis oil extract. Furthermore, the nanoemulsification process led to a THC diffusion and absorption on buccal mucosa 20-folds and 2-folds higher than olive oil extract, respectively. Overall, the results suggest that Bedrocan (R) NE represents a novel formulation strategy for the buccal administration of Cannabis extracts that can overcome the limits associated with conventional oily formulations.