Cannabidiol-Loaded Microemulsion: Pharmaceutical Development and Preliminary Hemocompatibility Assessment

Sócrates Egito
Federal University of Rio Grande do Norte

Co-authors: Lucas Gabriel da Silva Oliveira¹, Ícaro Chaves Girão¹, Fabia Julliana Jorge de Souza¹, Wógenes Nunes de Oliveira², Eryvaldo Sócrates Tabosa do Egito^1
1Federal University of Rio Grande do Norte, ²State University of Paraíba

Cannabidiol (CBD) has substantial therapeutic potential, but its pharmaceutical development remains challenged by its poor aqueous solubility and variable biopharmaceutical performance. Oil-in-water microemulsions offer a versatile approach to increase the apparent aqueous dispersibility of highly lipophilic compounds while enabling dilution and incorporation into different pharmaceutical dosage forms. This study developed a CBD-loaded microemulsion (CBD-ME), characterized its physicochemical properties, and performed a preliminary safety assessment based on in vitro hemolytic activity in human erythrocytes. CBD-ME was composed of Lipoid® S100 (6.3% w/w), Tween® 80 (14.7% w/w), Miglyol® 812N (11% w/w), purified water (68% w/w), and CBD (15 mg/mL). A high-energy sonication procedure was employed to facilitate preparation of the phospholipid-containing system while avoiding heating and organic solvents. Physicochemical characterization included droplet size (DS), polydispersity index (PdI), pH, conductivity, and entrapment efficiency (EE). Hemolytic activity was evaluated using a 5% suspension of human erythrocytes exposed to CBD-ME at CBD concentrations of 25, 50, and 75 μg/mL and to corresponding amounts of blank ME for 1 h at 37 ± 2 °C. Hemolytic activity was evaluated using a 5% suspension of human erythrocytes exposed to blank microemulsion (blank ME) and CBD-loaded microemulsion (CBD-ME) at CBD-equivalent concentrations of 25, 50, and 75 μg/mL for 1 h at 37 ± 2 °C. Hemoglobin release was quantified spectrophotometrically at 540 nm using Triton X-100 and 0.9% saline as positive and negative controls, respectively. CBD-ME exhibited a DS of 27.69 ± 0.05 nm, PdI of 0.261 ± 0.017, conductivity of 132.47 ± 0.23 μS/cm, pH of 6.10 ± 0.06, and EE of 97.3 ± 0.7%. The formulation combined a nanometric droplet size with a CBD payload of 15 mg/mL in a water-rich oil-in-water system containing only 11% oil. Both blank ME and CBD-ME produced less than 1% hemolysis at all evaluated concentrations, indicating negligible erythrocyte membrane damage under the tested conditions. These findings provide preliminary evidence of the favorable blood compatibility of CBD-ME and support its further investigation as a flexible pharmaceutical platform for CBD delivery. Its aqueous continuous phase, nanometric organization, and ability to maintain CBD dispersed at 15 mg/mL may facilitate dilution and incorporation into route-specific dosage forms. Additional hemocompatibility and safety studies tailored to the intended route of administration are warranted.