Methods for In Vitro Percutaneous Absorption Studies III: Hydrophobic Compounds

• Published in: Journal of pharmaceutical sciences 1984-09, Vol.73 (9), p.1255-1258
• Main Authors: Bronaugh, Robert L., Stewart, Raymond F.
• Format: Article
• Language: English
• Subjects: Absorption-percutaneous; Absorption—percutaneous, in vitro, hydrophobic compounds; Animals; Biological and medical sciences; Chemistry, Pharmaceutical; Cortisone - metabolism; Diffusion; Female; hydrophobic compounds; Hydrophobic compounds-in vitro percutaneous absorption; in vitro; Medical sciences; Naphthalenes - metabolism; ortho-Aminobenzoates - metabolism; Pharmaceutical Preparations - metabolism; Pharmaceutical Vehicles; Pharmacology. Drug treatments; Plant Oils; Polyethylene Glycols - metabolism; Rats; Skin Absorption; Skin, nail, hair, dermoskeleton; Solubility; Solvents; Surface-Active Agents; Testosterone - metabolism; Tetrahydronaphthalenes - metabolism; Urea - metabolism
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.2600730916

The absorption of two hydrophobic compounds through rat skin was measured by in vivo and in vitro techniques. The permeation of the fragrance ingredients 3-phenyl-2-propenyl 2-aminobenzoate (I) and 1-(3-ethyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)ethanone (II) was measured from a petrolatum and an acetone vehicle. Increases in permeation of 8-fold (I) and 95-fold (II) were observed when the compounds were tested in vivo under conditions similar to in vitro procedures. The apparent inability of the compounds to freely enter the diffusion cell receptor fluid was partially reversed by replacing normal saline with other fluids: rabbit serum, 3% bovine serum albumin, organic solvents, and dilutions of four nonionic surfactants. The effect of the receptor fluids on the integrity of the skin barrier was assessed by measuring the permeability of control compounds (cortisone, urea, and water). A 6% solution of polyethylene glycol 20 oleyl ether was the receptor fluid of choice. Without apparent damage to the skin, 61% (petrolatum vehicle) or 73% (acetone vehicle) of the in vivo absorption of I was obtained. With II, only 32% of the in vivo absorption was achieved (petrolatum vehicle). Even when the surfactant solution is used, significant differences may still remain between in vivo and in vitro results.