Formulating stable hexosome dispersions with a technical grade diglycerol-based surfactant

We report on the phase behavior of a technical grade and commercially available diglycerol monoisostearate, C41V, and its use for the preparation of nanostructured liquid crystal dispersions (hexosomes). C41V in water forms a reverse hexagonal liquid crystal at room temperature and in a wide range of concentrations (0.5-95 wt%); this hexagonal liquid crystal is stable up to 70 °C. A simple and effective method has been developed to disperse hexosomes with an encapsulated active molecule (Ketoprofen) that consists of (1) producing a nano-emulsion stabilized by an amphiphilic block copolymer (Pluronic F127) and containing ethyl acetate and C41V by using ultrasounds and (2) evaporating the solvent to produce hexosomes. The size of the hexosomes and ultrasound dispersion time is markedly reduced by using ethyl acetate as an auxiliary solvent with an optimal initial ratio of C41V:ethyl acetate of 50:50. Dynamic light scattering shows that the size of the hexosomes decreases as the concentration of stabilizer F127 or encapsulated Ketoprofen is increased. The lattice parameter in the hexagonal structure is calculated from small angle scattering data to be ca. 5.3  nm and is only slightly dependent on the amount of F127 and/or encapsulated Ketoprofen. Cryo electron microscopy reveals that the samples contain hexosomes and these coexist with spherical, likely F127 micelles. Lastly, hexosomes show a pH responsive release of Ketoprofen which could be useful for target delivery in the gastrointestinal tract.