Comparative Study on Cannabidiol‐Loaded Solubilizing Systems for Improvement of Oral Bioavailability: Liposome and Cyclodextrin‐Based Formulations

This study aimed to develop a CBD-loaded liposomal formulation (LIP/CBD) to improve its physicochemical properties and oral bioavailability (BA). LIP/CBD was prepared by the conventional solvent injection method. The physicochemical and pharmacokinetic properties of CBD were evaluated to clarify the possible improvement in the biopharmaceutical properties of CBD by the application of a liposomal system. For comparison, a cyclodextrin-based CBD formulation (CD/CBD) was prepared as a conventional solubilization system. Uniform spherical liposomes of LIP/CBD were observed by transmission electron microscopy, and the mean particle size was calculated to be approximately 120 nm with a polydispersity index of 0.13 and a zeta potential of -68 mV. The amount of CBD dissolved from crystalline CBD was very low under simulated intestinal pH condition (pH 6.8) due to its poor solubility and dispersibility. In contrast, LIP/CBD significantly enhanced the dissolution of CBD, as evidenced by 8-fold higher dissolution amount than that of crystalline CBD. Oral absorption of CBD from crystalline CBD was very poor owing to its low water solubility and severe first-pass metabolism. Orally administered LIP/CBD and CD/CBD exhibited significant improvements of oral absorption with 22- and 5.3-fold higher systemic exposure, respectively. The T_max of LIP/CBD was longer than that of CD/CBD, possibly due to the contribution of lymphatic absorption enhanced by lipidic components. The application of a liposomal system to CBD could be a viable option to enhance the physicochemical properties and oral BA of CBD.