Development and Characterization of a Microemulsion Containing a Cannabidiol Oil and a Hydrophilic Extract from Sambucus ebulus for Topical Administration

Abstract

Cannabidiol (CBD) is a safe and non-psychotropic phytocannabinoid with a wide range of potential therapeutic anti-inflamatory and antioxidant activities. Due to its lipophilicity, it is normally available dissolved in oily phases. The main aim of this work was to develop and characterize a new formulation of a microemulsion with potential anti-inflammatory and antioxidant activity for the topical treatment of inflammatory skin disorders. The microemulsion system was composed of a 20% CBD oil, which served as the hydrophobic phase; Labrasol/Plurol Oleique (1:1), which served as surfactant and cosurfactant (S/CoS), respectively; and an aqueous vegetal extract obtained from Sambucus ebulus L. (S. ebulus) ripe fruits, which has potential anti-oxidant and anti-inflammatory activity and which served as the aqueous phase. A pseudo-ternary phase diagram was generated, leading to the selection of an optimal proportion of 62% (S/CoS), 27% CBD oil and 11% water and, after its reproducibility was tested, the aqueous phases were replaced by the vegetal hydrophilic extract. The defined systems were characterized in terms of conductivity, droplet size (by laser scattering), compatibility of components (by differential scanning calorimetry) and rheological properties (using a rotational rheometer). The designed microemulsion showed good stability and slight pseudo-plastic behavior. The release properties of CBD from the oil phase and caffeic acid from the aqueous phase of the microemulsion were studied via in vitro diffusion experiments using flow-through diffusion cells and were compared to those of a CBD oil and a microemulsion containing only CBD as an active substance. It was found that the inclusion of the original oil in microemulsions did not result in a significant modification of the release of CBD, suggesting the possibility of including hydrophilic active compounds in the formulation and establishing an interesting strategy for the development of future formulations.

Keywords: cannabidiol; diffusion studies; microemulsion; phytocannabinoids; rheological properties; vegetal extract.

Figure 1

Pseudo-ternary phase diagram showing all the tested titration lines up to the limits of the microemulsion area (red dots). Green light area represents the estimated microemulsion area. Increasing the water proportion (to the left side of the diagram) led to the creation of an emulsion system.

Figure 2

Conductivity value vs. hydrophilic phase proportion added under continuous stirring. Milli-Q^® water (blue line) and aqueous extract of S. ebulus (green line).

Figure 3

Droplet-size distribution (nanometers) for the microemulsion–extract (green bars), microemulsion–water (blue bars) and an emulsion (orange bars) obtained during the titration processes.

Figure 4

Viscosity-vs.-shear rate profiles showing the mean viscosity value (A), and shear stress-vs.-shear rate upward and downward rheograms (B).

Figure 5

Differential scanning calorimetry (DSC) curves of pure CBD crystalline (green line), CBD oil (blue line) and the microemulsion containing the same commercial oil as the oily phase (pink line). Red curve denotes base lines.

Figure 6

Cumulative diffusion profile as a percentage for the three formulations (CBD oil—orange, microemulsion with water—blue, microemulsion with the extract—green). The cumulative diffusion profile of CAF from the microemulsion with the extract was also included for comparison (red). Right-side bar chart: release constant (h⁻¹) ± confidence interval (p < 0.05).