DIFFUSIVITY AND STRUCTURAL POLYMORPHISM IN SOME MODEL STRATUM-CORNEUMLIPID SYSTEMS

Mixtures of model stratum corneum lipids were prepared in water from c holesterol, six fatty acids and ceramides. The influence of compositio n on the polymorphism of these mixtures and also on the diffusivity of a model drug within them, D(lip), was determined. The former was obta ined from X-ray diffraction and Fourier transform infrared spectrometr y, and the latter from a diffusional release model. An L(beta) structu re was formed for the composition approximating that of the extracellu lar lipids in intact human abdominal stratum corneum. D(lip) was indep endent of water content in the range 20-40% w/w, with the bilayers sho wing one dimensional swelling without lateral expansion. Although remo val of the ceramides did not result in a significant alteration in D(l ip), crystalline cholesterol now appeared. The ceramides were, therefo re, necessary for solubilization within the fatty acid bilayers of the large proportion of cholesterol present in the lipid fraction of inta ct SC. They were also responsible for a thermal L(alpha)-H(II) transit ion observed at approx. 68-degrees. At the concentration in which it e xists in intact SC, cholesterol also had only a minimal effect on D(li p), but was necessary to suppress H(II) phase formation within the fat ty acids and ensure an L(beta) structure. All lipid mixtures that had an L(beta) structure presented a diffusional barrier approx. 1 order o f magnitude greater than that of an unstructured, isotropic lipid mixt ure. H(II) structures formed at cholesterol/fatty acid proportions les s than approx 8:92 mol% and appeared more permeable than L(beta) ones. All the results indicate that the diffusional barrier within the mode l lipid mixtures is guaranteed essentially by the presence of an L(bet a) phase. Although the ceramides and cholesterol exert no intrinsic in fluence on the magnitude of D(lip), their presence in necessary for th e existence of an L(beta) phase at 33-degrees that is free of both cry stalline cholesterol and H(II) character.