Formulation and Evaluation of Solid Self-Nanoemulsifying Drug Delivery System of Cannabidiol for Enhanced Solubility and Bioavailability

<b>Background/Objectives:</b> This study aims to develop a solid self-nanoemulsifying drug delivery system (SNEDDS) to enhance the solubility and oral bioavailability of cannabidiol (CBD). <b>Methods:</b> According to the solubility of CBD and pseudo-ternary phase diagrams of the different ingredients, an oil (medium-chain triglyceride, MCT), mixed surfactants (Labrasol, Tween 80), and a co-surfactant (Transcutol) were selected for the SNEDDS. CBD-loaded SNEDDS formulations were prepared and characterized. The optimal SNEDDS was converted into solid SNEDDS powders via solid carrier adsorption and spray drying techniques. Various evaluations including flowability, drug release, self-emulsifying capacity, X-ray diffraction (XRD), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), morphology, and pharmacokinetic characteristics were conducted. Subsequently, the solid powders with fillers, disintegrants, and lubricants were added to the capsules for accelerated stability testing. <b>Results:</b> The investigations showed that the two S-SNEDDS formulations improved the CBD's solubility and in vitro drug release, with good storage stability. The pharmacokinetic data of Sprague Dawley rats indicated that a single oral dose of L-SNEDDS and spray drying SNEDDS led to a quicker absorption and a higher Cmax of CBD compared to the two oil-based controls (CBD-sesame oil (similar to Epidiolex^®) and CBD-MCT), which is favorable for the application of CBD products. <b>Conclusions:</b> SNEDDS is a prospective strategy for enhancing the solubility and oral bioavailability of CBD, and solid SNEDDS offers flexibility for developing more CBD-loaded solid formulations. Moreover, SNEDDS provides new concepts and methods for other poorly water-soluble drugs.