The physicochemical parameters of marker compounds and vehicles for use in in vitro percutaneous absorption studies.
In order to prepare for a validation study to compare percutaneous absorption through reconstructed human epidermis with ex vivo skin absorption through human and animal skin, nine test compounds, covering a wide range of physicochemical properties were selected, namely: benzoic acid; caffeine; clotrimazole; digoxin; flufenamic acid; ivermectin; mannitol; nicotine; and testosterone. The donor and receptor media for the test substances, the addition of a solubiliser for the lipophilic compounds, as well as the stability and solubility of the test substances in the vehicles, were systematically analysed. Hydrophilic molecules, being freely soluble in water, were applied in buffered saline solutions. In order to overcome solubility restrictions for lipophilic compounds, the non-ionic surfactant, Igepal CA-630, was added to the donor vehicle, and, in the case of clotrimazole and ivermectin, also to the receptor fluid. The model molecules showed a suitable solubility and stability in the selected donor and receptor media throughout the whole duration of the test.
Across Barriers GmbH, Saarbrücken, Germany.
Monika
M
Kaca
Udo
U
Bock
Mohamed
M
Tawfik Jalal
Meike
M
Harms
Christine
C
Hoffmann
Christel
C
Müller-Goymann
Frank
F
Netzlaff
Ulrich
U
Schäfer
Claus-Michael
CM
Lehr
Eleonore
E
Haltner-Ukomadu
D000826:Animal Testing Alternatives; D000818:Animals; D019817:Benzoic Acid / Q000494:pharmacology; D002021:Buffers; D002110:Caffeine / Q000494:pharmacology; D003022:Clotrimazole / Q000494:pharmacology; D003470:Culture Media; D004077:Digoxin / Q000494:pharmacology; D004817:Epidermis / Q000187:drug effects / Q000502:physiology*; D005439:Flufenamic Acid / Q000494:pharmacology; D005858:Germany; D006801:Humans; D008823:Micelles; D011092:Polyethylene Glycols; D012869:Skin Absorption / Q000187:drug effects / Q000502:physiology*
D002021:Buffers; D003470:Culture Media; D008823:Micelles; D002110:Caffeine; D011092:Polyethylene Glycols; D005439:Flufenamic Acid; D004077:Digoxin; D019817:Benzoic Acid; D003022:Clotrimazole