Development of an in vivo animal model for skin penetration in hairless rats assessed by mass balance.
The aim of the study was to develop an in vivo animal model for studies of the penetration of topically applied drugs into the skin of hairless rats. Protective appliances were designed for non-occluded and finite-dose application of topical formulations. The design allowed 2 test sites for each rat and free mobility throughout the test period. By consecutive tape stripping, monitored by measurements of transepidermal water loss and confirmed by histological examination of skin biopsies, 10 tape strippings were found to remove the stratum corneum completely. For assessment of the model, (14)C-salicylic acid and (14)C-butyl salicylate were topically applied. Rapid and differentiated percutaneous absorption of both compounds were shown by urinary excretion data. For (14)C-salicylic acid the amount on the skin surface, in the stratum corneum and in the viable skin was determined. Total mass balance on the applied radioactivity was performed and a recovery of 90 +/- 2% was achieved. The radioactivity found in the protective appliances (<10%) was explained by lateral skin diffusion of the model compounds into the dressings.
Simonsen
Lene
L
Pharmaceutical Formulation, Leo Pharmaceutical Products, 55 Industriparken, DK-2750 Ballerup, Denmark. lene.simonsen@leo-pharma.com
Petersen
Mads B
MB
Benfeldt
Eva
E
Serup
Jørgen
J
D000287:Administration, Topical; D000818:Animals; D002250:Carbon Radioisotopes / Q000032:analysis; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation / Q000379:methods*; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism; D005260:Female; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D020156:Salicylic Acid / Q000032:analysis / Q000493:pharmacokinetics; D012588:Scintillation Counting / Q000295:instrumentation / Q000379:methods; D012869:Skin Absorption / Q000187:drug effects / Q000502:physiology*
D002250:Carbon Radioisotopes; D020156:Salicylic Acid