Anti-convulsant efficacy of long-acting injectable cannabidiol formulation (IVL5005) in the pentylenetetrazol-induced convulsions, with pharmacokinetic characterization

Soyoung Youm¹Joo Young Cha²Slgirim Lee²Young Dai Seo²Kun Hee Park³Aeri Song³Hyun-Je Park³Woo-Chan Son^1*Juhee Kim^2*

• ¹Asan Medical Center, University of Ulsan, Ulsan, Republic of Korea
• ²Inventage Lab Inc, Seongnam-si, Republic of Korea
• ³Yuhan Care, YOUNGIN-SI, Republic of Korea

Cannabidiol (CBD) has demonstrated therapeutic potential in neurological disorders, particularly epilepsy. Epidiolex® , an FDA-approved oral CBD solution, is indicated for rare epileptic disorders such as Lennox–Gastaut syndrome and Dravet syndrome. However, its clinical utility is limited by rapid metabolism, short duration of action, and low oral bioavailability. To address these limitations, we developed a long-acting injectable (LAI) formulation of CBD (IVL5005) using IVL-DrugFluidic® technology to achieve sustained and controlled drug release. CBD-loaded microspheres were manufactured and characterized by physicochemical analyses and in vitro release profiling. In an in vivo pharmacokinetic study, all candidate formulations provided sustained systemic exposure for up to 4 weeks after a single subcutaneous injection. The optimized formulation, which exhibited prolonged release with minimal initial burst, was selected for efficacy evaluation in a pentylenetetrazole (PTZ)-induced convulsion model. In this model, IVL5005 demonstrated significant, durable anticonvulsant efficacy from a single dose, whereas the oral CBD solution produced only transient effect. IVL5005 also achieved a lower maximum plasma concentration compared with oral CBD solution, which may reduce the risk of peak concentration-related adverse effects and suggests a favorable safety profile. Furthermore, no hepatic toxicity was observed with IVL5005, while liver changes were detected in the oral CBD group, likely due to extensive first-pass metabolism. These results indicate that IVL5005 may overcome key limitations of oral CBD and support its further development as a long-acting therapeutic option for epilepsy.