Formulation and in vitro evaluation of liposomal and self-microemulsifying drug delivery systems for oral delivery of cannabidiol

Cannabidiol (CBD) is a highly lipophilic molecule characterized by low oral bioavailability, primarily due to its limited solubility and extensive first-pass metabolism. This study aims to improve apparent solubility of cannabidiol through the development of liposomal and self-microemulsifying drug delivery systems (SMEDDS). Liposomes incorporating ω-3 fatty acids, and SMEDDS formulations were prepared and assessed regarding their hydrodynamic diameter, polydispersity index, and z-potential. Furthermore, tablets were developed from lyophilized powders and encapsulated into enteric-coated capsules to protect CBD from degradation in the acidic environment of the stomach, minimizing conversion to unwanted metabolites and ensuring greater stability. Both liposomes and SMEEDS formulations showed significantly faster dissolution rate (81 % for L1, 94 % for L2, 69 % for S1 and 66 % for S2) compared to 28 % of pure CBD tablet formulation within 720 min in simulated intestinal fluid conditions (pH = 6.8). Lyophilized formulations were evaluated by Scanning Electron Microscopy (SEM), and powder X-ray diffraction (XRPD) confirming the amorphous or molecularly dissolved state of CBD within the formulations. The overall antioxidant activity of CBD was retained after incorporation into liposomes and SMEDDS as measured by DPPH assay. Overall, these findings indicate that liposomes and SMEDDS are promising oral drug delivery systems for enhancing the solubility of CBD.