A research team from the University of Florence has published a study in the International Journal of Pharmaceutics, detailing a new self-microemulsifying drug delivery system (SMEDDS) designed to improve the oral delivery of cannabidiol (CBD).

The team constructed a pseudoternary phase diagram to identify optimal components, ultimately formulating a system using Capryol 90 and isopropyl myristate as the oil phase, with Kolliphor HS 15 and Transcutol HP as surfactant and co-surfactant. The SMEDDS formulation, containing 2% CBD, showed nearly complete drug recovery (99.86%) and remained stable during one month of storage.

When diluted in water and simulated gastric and intestinal fluids, the system produced microemulsions with droplet sizes under 30 nanometers and high uniformity. Unlike unformulated CBD, which showed significant degradation under these conditions, the SMEDDS maintained stability even in enzyme-containing media. Permeability testing demonstrated strong CBD recovery (99.50%) compared to unformulated CBD, which displayed high membrane retention.

Caco-2 cell studies found that both SMEDDS-formulated CBD and free (unformulated) CBD permeated intestinal cell layers at similar rates, though SMEDDS maintained stability over time while free CBD degraded more rapidly. Importantly, free CBD at high concentrations nearly eliminated the expression of the Tight Junction Protein 1 (TJP1) gene, critical for maintaining cellular barriers. In contrast, CBD delivered via the SMEDDS microemulsion only partially reduced TJP1 expression, suggesting a protective effect.

Researchers conclude the study by saying “In conclusion, our results evidenced that SMEDDS can be unconventional effective formulations of CBD for oral administration, able to increase the oral bioaccessibility due to an enhanced solubility and stability, facilitating a more consistent CBD absorption. Finally, SMEDDS can be manufactured using simple and economical equipment, making large-scale production feasible.

The full text of the study can be found by clicking here.