Development and Characterization of Cannabidiol Self-Emulsifying Drug Delivery System: In Vitro and In Vivo Evaluation

Cannabidiol (CBD) is a non-psychoactive phyto-cannabinoid with numerous pharmacological potentials. CBD is a lipophilic drug with poor and varied bioavailability due to its low water solubility and extensive first-pass metabolism, and it is highly affected by the presence of food. A self-emulsifying drug delivery system (SEDDS) was developed to improve the aqueous solubility and oral bioavailability of CBD. The formulation strategy involved incorporating excipients that maintain drug solubility under both fasted and fed conditions, while potentially mitigating first-pass metabolism to enhance overall bioavailability and dose proportionality. Caproyl^® 90, Tween^® 20, and Transcutol^® HP were selected as the oil phase, surfactant, and cosolvent, respectively, for formulation preparation and screening. CBD SEDDS formulations containing Caproyl^® 90 ≤20% <i>w</i>/<i>w</i> and Tween^® 20 above 40% <i>w</i>/<i>w</i> yield particles below 200 nm. CBD SEDDS with Tween^® 20 65% <i>w</i>/<i>w</i> or higher showed in vitro release of more than 90%. After in vitro digestion, CTT1, CTT4, and CTT8 remained stable under gastrointestinal conditions and maintained CBD solubility of at least 50%. The most promising formulations, CTT4 and CTT8, were used for in vivo evaluations. Both formulations showed similar in vitro results; however, in vivo, CTT4 demonstrated 2.4-fold higher bioavailability than CTT8. Overall, optimizing the level of inhibitory surfactant appears to be a promising strategy for improving CBD bioavailability.