An HII liquid crystal-based delivery system for cyclosporin A: Physical characterization

In the present study we demonstrate that large quantities of cyclosporin A and three dermal penetration enhancers (phosphatidylcholine, ethanol, or Labrasol) can be solubilized into reverse hexagonal (HII) liquid crystalline structures composed of monoolein, tricaprylin, and water. The microstructural characteristics of these complex multi-component systems were elucidated by rheological, SAXS, and DSC measurements. Addition of up to 20 wt% phosphatidylcholine improved significantly the elastic properties of the systems (lower values of tanδtanδ) and increased the thermal stability of the mesophases enabling us to solubilize up to 6 wt% cyclosporin A and two other enhancers (Labrasol and ethanol) to obtain stable mesophases at physiological temperature. Rheological measurements revealed that solubilization of cyclosporin A alone has a destabilizing effect on the reverse hexagonal phases: it caused a deterioration in the elastic properties of the systems, leading to more liquid-like behavior and resulting in very short relaxation times (0.04–0.1 s). Labrasol, solubilized at high concentrations (up to 12 wt%) into the liquid crystals, also demonstrated a destabilizing effect on the HII structure: the decreasing elasticity of the system was attributed to Labrasol's presumed locus at the interface and its ability to bind water, as shown by DSC measurements. Ethanol had a destabilizing effect similar to that of Labrasol, yet the effect appeared to be more pronounced, probably due to its higher water-binding capability.

Graphical abstractIn this study we solubilized large quantities of cyclosporin A and three dermal penetration enhancers (phosphatidylcholine, ethanol, and Labrasol) into HII liquid crystalline structures. Using rheological, SAXS and DSC measurements, we have characterized microstructural properties of these systems.Figure optionsDownload full-size imageDownload as PowerPoint slide