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Physiologic lipid mixture, or barrier cream, represents a topical formulation made with the major stratum corneum (SC) intercellular lipid constituents, ceramide, free fatty acid, cholesterol and / or cholesterol sulfate, with a specific mixing ratio. While there have been a lot of experimental and clinical reports for its beneficial effects on skin barrier function, little has been studied for its potential effects on topical drug delivery system, when used as a vehicle. As a physiologic lipid mixture, multi-lamellar emulsion (MLE) is composed with pseudoceramide (PC-9S), free fatty acids and cholesterol. Moreover, MLE expresses lamellar structure, which is similar to that of human skin`s stratum corneum (SC) intercellular lipids. Previously, we have shown that MLE has beneficial effects on skin barrier functions, including permeability barrier and hydration barrier. In this study, the vehicle effects MLE was studied using hydrocortisone (HC) as a model compound. 1% of HC was incorporated into MLE (MLE/HC) and commercially available HC cream product was used as a comparator. Permeation and penetration of HC through and within the excised human skin were measured and dissolution and partitioning of HC from the formulations were also measured using synthetic membranes. While permeation of HC through the excised human skin, which was assessed by measuring the HC concentration in receptor solution of Franz cell, was lower in MLE/HC, penetration of HC within the human skin, assessed by the concentration of HC in SC, epidermis, and dermis, showed that concentration of HC is quite higher in MLE/HC formulation in SC. These results suggested that higher retention of HC in the skin, especially in SC, occurred with MLE/HC. Franz cell experiments with synthetic membrane (Strat-M, EMD Millipore Corporation, Billerica, MA) showed higher partitioning of HC into the Strat-M membrane from the MLE/HC formulation than comparator. However, higher dissolution rate of HC was observed in the comparator product. From these results, it can be hypothesized that MLE, with its structural similarity to SC intercellular lipid, can facilitate the partitioning of active ingredients into the skin, and has a significant vehicle effects for topical formulation.
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