Use of lipid disperse systems in transdermal drug delivery: Comparative study of flufenamic acid permeation among rat abdominal skin, silicon rubber membrane and stratum corneum sheet isolated from hamster cheek pouch

The characteristics of in vitro permeation of flufenamic acid (FA) from lipid disperse systems composed of phosphatidylcholine (PC) and glycosylceramide (GC) were compared among rat abdominal skin, a silicon rubber membrane (Silastic^®) and a stratum corneum (SC) sheet isolated from hamster cheek pouch. When a PC dispersion (PCD) containing 20 μmol PC/ml was applied, the permeation of FA through rat skin was enhanced approx. 2.2-fold compared with that from the lipid-free suspension (LFS). Further, a nearly 2-fold enhancement was observed when a GC-containing PCD (10% GC-PCD) was examined. A similar pattern of enhancement could be reproduced when cheek pouch SC was used instead of, rat skin, whereas it was not observed in Silastic^®. The enhanced permeation in the skin could not be explained on the basis of the incremental increase in the apparent solubilities. A significant correlation was observed between skin permeation and epidermal tissue uptake of FA from LFS and PCDs, although the nearly 2-fold increase found in 10% GC-PCD might be due to mechanisms other than the increase in epidermal tissue uptake. The usefulness of an SC sheet isolated from hamster cheek pouch, a new model membrane without appendages, in studying the direct action of either permeation enhancers or dosage forms designed to enhance the percutaneous permeation of drugs on the SC is discussed.