Formulation Development and Evaluation of Cannabidiol Hot-Melt Extruded Solid Self-Emulsifying Drug Delivery System for Oral Applications

Cannabidiol (CBD) is a highly lipophilic compound with poor oral bioavailability, due to poor aqueous solubility and extensive pre-systemic metabolism. The aim of this study was to explore the potential of employing Hot Melt Extrusion (HME) technology for the continuous production of Self Emulsifying Drug Delivery Systems (SEDDS) to improve the solubility and in vitro dissolution performance of CBD. Accordingly, different placebos were processed through HME in order to obtain a lead CBD loaded solid SEDDS.

Two SEDDS were prepared with sesame oil, Poloxamer 188, Gelucire^®59/14, PEO N80 and Soluplus^®. Moreover, Vitamin E was added as an antioxidant. The SEDDS formulations demonstrated emulsification times of 9.19 and 9.30 min for F1 and F2 respectively. The formed emulsions showed smaller droplet size ranging from 150–400 nm that could improve lymphatic uptake of CBD and reduce first pass metabolism.

Both formulations showed significantly faster in vitro dissolution rate (90% for F1 and 83% for F2) compared to 14% for the pure CBD within the first hour, giving an enhanced release profile. The formulations were tested for stability over a 60-day time period at 4°C, 25°C, and 40°C. Formulation F1 was stable over the 60-day time-period at 4°C. Therefore, the continuous HME technology could replace conventional methods for processing SEDDS and improve the oral delivery of CBD for better therapeutic outcomes.

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Materials

Cannabidiol (CBD) derived from hemp was used in this study and was a gift from ElSohly Laboratories, Inc. (Oxford, MS, USA). Sesame oil, Poloxamer 188 and PEG 6000 were purchased from Fisher Scientific (St. Louis, MO, USA).   Soluplus® and TPGS was obtained as a gift from BASF (Florham Park, NJ, USA). Gelucire 59/14 was gifted form Gattefossé (Paramus, New Jersey, USA) and PEO N80 was received as a gift from Colorcon Inc. (Harleysville, PA, USA). Solvents used for the analysis were of high-performance liquid chromatography (HPLC) grade and were pur-chased from Fischer Scientific (Fair Lawn, NJ, USA).

Sanil, K., Almotairy, A., Uttreja, P. et al. Formulation Development and Evaluation of Cannabidiol Hot-Melt Extruded Solid Self-Emulsifying Drug Delivery System for Oral Applications. AAPS PharmSciTech 25, 136 (2024). https://doi.org/10.1208/s12249-024-02857-z

Read also our introduction article on “Cannabidiol (CBD)“ here: