AN X-RAY-DIFFRACTION STUDY OF SOME MODEL STRATUM-CORNEUM LIPIDS CONTAINING AZONE AND DODECYL-L-PYROGLUTAMATE

The effects of the lipophilic permeation enhancers Azone and dodecyl-L-pyroglutamate (dlp) on some model stratum corneum lipids have been examined using small angle X-ray diffraction and differential scanning calorimetry. A matrix composed only of six fatty acids showed an endothermic transition at 43-degrees-C, below which a diffraction pattern characteristic of a mixed hexagonal and lamellar structure was seen. Combining the fatty acids with cholesterol and ceramides shifted the endothermic transition up to 54-degrees-C. The diffraction pattern now indicated a lamellar structure below this temperature, with a primary reflection at 6.5 nm. The addition of up to 30% w/w Azone or dlp strongly attenuated the mainly hexagonal periodicity of the fatty acid matrix, although the d-spacing was only altered (decreased) with dlp. The lamellar periodicity of the fatty acid/cholesterol/ceramide matrix was attenuated much less by the enhancers. In this case, an initial small decrease in d-spacing with Azone could also be detected. The temperature and enthalpy of the fatty acid matrix's endothermic transition were continually reduced with increasing enhancer concentrations, whereas those for the fatty acid/cholesterol/ceramide system were hardly altered. Higher concentrations of enhancer dispersed completely the hexagonal diffraction pattern of the fatty acid matrix. leaving only lamellar periodicity. It was evident that both Azone and dlp were intercolated into the lipid structures and induced lateral swelling. These findings could be explained on the basis of the shapes of the enhancer molecules, which have large interfacial areas and head groups compared with their alkyl chain volumes.