Methods for in vitro percutaneous absorption studies. VI: Preparation of the barrier layer.

The skin membrane for in vitro percutaneous absorption studies was prepared so that it was similar in thickness to the in vivo barrier layer. A dermatome section from the skin surface produced a layer of skin that included the epidermis and papillary dermis (location of capillary loops) but without most of the dermal tissue. Improved absorption measurements were then obtained with hydrophobic compounds with the use of a polyethylene glycol 20 oleyl ether (PEG-20 oleyl ether) receptor fluid. With the haired rat, preparing a skin section 300-micron thick (and pretesting for damage to the barrier with H3-water) resulted in a membrane that gave values in good agreement with in vivo results for 3-phenyl-2-propenyl 2-aminobenzoate (cinnamyl anthranilate) (1) and benzo(a)pyrene absorption. When sparsely haired fuzzy rat skin was used, a section of skin 200-micron thick could be prepared without the need for pretesting for damage. Good agreement was obtained between in vivo and in vitro values for 1-(3-ethyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)etha none (acetyl ethyl tetramethyl tetralin) (2) and DDT with 0.5% PEG-20 oleyl ether in water as the receptor fluid. The skin of the fuzzy rat seemed more similar in permeability to human skin than did the skin of the hairless mouse when the absorption of six compounds was compared.