2004 ANNUAL SCIENTIFIC SEMINAR 507 and controlled disruption of the SC lipid barrier is a key aspect underlying most trans-dermal delivery technologies for the effective delivery of drugs. However, disruption of the SC lipid barrier can be an undesired consequence of components contained within topically applied consumer products, resulting in undesirable and consumer unacceptable skin irritation. Our laboratory has developed several ex v/vo and /n vitro experimental methods, based upon our long-term interest in understanding lipid structure and organization in the SC. We are utilizing this developing understanding, and the concomitant measurement capabilities, to probe the effect of formulation components on the structure of the SC lipid barrier. Changes in the fundamental physical behavior of SC lipids are being quantitatively related to biological consequences such as skin irritation. With this experimental approach we are developing the capability to describe and predict the potential of such molecules to compromise the skin barrier, and lead to irritation. Discussion The thermal transitions of lipids within intact isolated SC corneum and in vitro lipid models have been measured using both differential scanning calorimetry (DSC) and thermotropic Fourier transform infrared (FrJ:R) spectroscopy. Changes in the temperature at which lipid transitions are observed, both in the intermolecular packing of SC barrier lipids, as well as in the intramolecular chain melting, have been measured for SC exposed to a wide range of lipophilic molecules. Tnitial results clearly suggest that some components of topical skincare formulations, including pharmaceutical actives such as retinoic acid and some widely used cosmetic oils, can significantly damage lipid organization in the SC, potentially leading directly to skin irritation. This presentation will provide details on the molecular information gained from our DSC and FrJ:R studies of stratum corneum and in vitro stratum corneum lipid models, and describe the structural changes observed as a consequence of certain formulation ingredients. The fundamental biophysical data will then be related to skin irritation results to demonstrate the developing correlation between changes in barrier lipid behavior and observed skin irritation. The utility of exploiting this basic understanding of stratum corneum lipid biophysics to predict and screen for potential skin irritation, as well as design formulations with the minimum potential for causing irritation, will be highlighted in this presentation.