Transformation of a liposomal dispersion containing ibuprofen lysinate and phospholipids into mixed micelles - physico-chemical characterization and influence on drug permeation through excised human stratum corneum.

Our study is meant as a contribution to the investigation of molecular association of phospholipids and amphiphilic substances like, e.g. non-steroidal anti-inflammatory drugs. Our research focused on physico-chemical characterization of ternary systems containing ibuprofen lysinate, lecithin and water. The influence of the resulting microstructures on drug release and permeation through excised human stratum corneum was also investigated. Depending on the mixing ratio different physical states (lamellar and hexagonal liquid crystals, micellar solutions, liposomal dispersions and biphasic systems) were determined by gross, polarizing microscopic and small angle-X-ray analysis. A special emphasis was laid upon the storage-induced transformation of liposomal dispersions into mixed micellar solutions and its influence on drug release and permeation. A model for the transformation process is presented. Drug release of the liposomal dispersion (Da=1.1x10-5 cm2/s) and of the identically composed mixed micellar solution (Da=2.9x10-5 cm2/s) was delayed compared with the data of the aqueous drug solution (Da=4.7x10-5 cm2/s). Because of the association of ibuprofen lysinate molecules with phospholipid molecules within the liposomal and the mixed micellar system the share of free ibuprofen lysinate monomers, which can pass through the dialysis membrane in the release experiment, is markedly reduced. The results of permeation experiments of these systems, however, did not correspond to the release data. The permeability of the mixed micellar solution rose after 6 weeks of storage (P=4.2x10-8 cm/s), and almost reached the permeation of the aqueous solution (P=3.9x10-8 cm/s), whereas the permeation of the liposomal dispersion was very slow (P=1.5x10-8 cm/s). The different colloidal microstructures of the formulations obviously resulted in divergent interactions with the permeation barrier - the stratum corneum - and subsequently in different permeation behavior. Copyright 1998 Elsevier Science B.V.