Response Surface Methodology-Guided Development of Hot-Melt-Extruded Cannabidiol Solid Self-Emulsifying Drug Delivery Systems for Enhanced Drug Release and Stability

Background/Objectives: Cannabidiol (CBD) is a non-psychoactive phytocannabinoid, with numerous therapeutic applications. It can be used to treat pain, inflammation, anxiety, and schizophrenia and it is also used to treat severe forms of infant epilepsy. CBD is a highly lipophilic compound with low oral bioavailability due to poor aqueous solubility and extensive first-pass metabolism. Self-emulsifying drug delivery systems (SEDDSs) offer a promising approach to enhancing the solubility and stability of lipophilic compounds like CBD. This study aimed to design and optimize CBD-loaded solid SEDDSs (S-SEDDSs) using Response Surface Methodology (RSM) to identify the optimal formulation parameters for improved drug release and stability. Methods: Excipients were selected through qualitative screening studies, considering their functional properties in SEDDS development. A Central Composite Design (CCD) was employed for response surface optimization to evaluate the effect of independent variables on formulation performance, including oil concentration and the surfactant–co-surfactant ratio. Formulations were processed using hot-melt extrusion (HME). The lead formulation was tested for drug content, in vitro drug release and stability studies. Results: The solid SEDDS formulation showed a drug content of 98.15 ± 1.94% and achieved 76.6 ± 0.6% drug release within three hours during in vitro dissolution testing, compared to 28 ± 0.9% for pure CBD. During stability testing, the lead formulation showed minimal change at both 25 °C and 40 °C. Conclusions: Overall, the study demonstrated that RSM-guided formulation development combined with HME processing can produce CBD S-SEDDSs and improve in vitro drug release compared to pure CBD.