Lyotropic, liquid crystalline nanostructures of aqueous dilutions of SMEDDS revealed by small-angle X-ray scattering: Impact on solubility and drug release

The present study was conducted to characterise the liquid crystalline phases that occur upon diluting a SMEDDS and to elucidate the role of these phases on drug solubilisation and release. Small-angle X-ray scattering (SAXS) was used to probe the structures in aqueous dilutions of 3 SMEDDS consisting of propylene glycol mono- and dicaprylate and mono- and dicaprate (PGDCDC) and d-α-tocopheryl polyethylene glycol succinate 1000 (TPGS 1000), polysorbate 80 (P80) or polyoxyl 40 hydrogenated castor oil (P40HC). The scattering patterns revealed the formation of either a random periodic or a lamellar phase when 10% (w/w) water was added. All formulations exhibited lamellar structures at 20% (w/w) aqueous dilution, of which the layer-to-layer distance increased upon further addition of water. At 40% (w/w) water, a hexagonal or lamellar phase was formed, depending on the geometry of the surfactant. Temperature did not alter the phases formed. Incorporation of the drug UC 781 only slightly enlarged the characteristic dimensions of the liquid crystalline phases. Drug solubility decreased upon aqueous dilution, although 10% (w/w) dilutions of PGDCDC-P80 SMEDDS and PGDCDC-TPGS 1000 SMEDDS revealed a highly increased solubility as compared to the pure formulations. Drug release data revealed that UC 781 release could not be linked to the solubilisation capacity of the SMEDDS, but could be associated with the solubility of UC 781 in the phases formed at water concentrations above 10% (w/w).