Abstract:

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) liq. cryst. structures composed of monoolein, tricaprylin, and water. The microstructural characteristics of these complex multi-component systems were elucidated by rheol., SAXS, and DSC measurements. Addn. of up to 20 wt% phosphatidylcholine improved significantly the elastic properties of the systems (lower values of tan $δ$ ) 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 physiol. temp. Rheol. 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 liq.-like behavior and resulting in very short relaxation times (0.04-0.1 s). Labrasol, solubilized at high concns. (up to 12 wt%) into the liq. 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. [on SciFinder(R)]