Cubosome dispersions as delivery systems for percutaneous administration of indomethacin

Purpose. The present study concerns the production and characterisation of cubosome dispersions as drug delivery systems for indomethacin, taken as model antiinflammatory drug. Methods. Dispersions were produced by emulsification of monoolein and poloxamer in water and by subsequent homogenization. Morphology and dimensional distribution of the disperse phase have been respectively characterized by cryo-transmission electron microscopy and Photon Correlation Spectroscopy. X-ray diffraction has been performed to determine the structural organization of the disperse phase. An in vitro diffusion study was conducted by Franz cell associated to SCE membrane on cubosome dispersions viscosized by carbomer. In vivo studies were performed to better investigate the performance of cubosome as indomethacin delivery system, in particular both skin reflectance spectrophotometry and tape stripping have been employed supported by HPLC analyses. Results. Microscopy studies showed the coexistence of vesicles and particles characterised by a cubic organisation, mean diameters of cubosomes were around 200 nm. X-ray diffraction revealed the presence of a bicontinuous cubic phase of spatial simmetry Im3m (Q229). Indomethacin incorporated in viscosized cubosomal dispersions exhibited a lower flux with respect to the analogue formulation containing the free drug in the aqueous phase and to the control formulation based on carbomer gel. Reflectance Spectroscopy enabled to demonstrate that indomethacin can be released in a prolonged fashion when incorporated into cubosomes. Tape stripping experiments corroborated this finding. Conclusions. Cubosomes can be proposed as nanoparticulate systems able to control the percutaneous absorption of indomethacin