Influence of human skin specimens consisting of different skin layers on the result of in vitro permeation experiments.
The literature exhibits high variation in results from drug permeation experiments across human skin. Our purpose was to investigate the influence of human skin specimens, consisting of different skin layers and resulting from different skin preparation techniques, on the in vitro permeation of a model drug, i.e. flufenamic acid (FFA). FFA permeation across human (1) trypsin-isolated stratum corneum, (2) heat-separated epidermis and (3) dermis, (4) dermatomized skin and (5) full-thickness skin (FTS) from either a hydrophilic or lipophilic donor was investigated in Franz-type diffusion cells. Cumulative permeated drug amounts were plotted versus time, and a fit to Fick's 2nd law of diffusion was performed. Since performing skin diffusion experiments in the laboratory is time consuming and expensive, especially when using FTS, we also investigated the possibility of calculating the resistances of composite skin layers from the diffusion resistances of the individual skin layers. Due to short lag time, practical handling and economic preparation, heat-separated epidermis appears to be superior in human skin in vitro permeation experiments compared to separated stratumcorneum sheets, dermatomized skin and FTS. Furthermore, we found a good correlation between calculated and experimental resistances which underlines that calculation of the total diffusion resistance of composed skin preparations from resistances of individual skin layers is legitimate and useful. Considering our findings, improved interpretation of literature data and more consistent results for future permeation experiments are possible.
Henning
A
A
Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbrucken, Germany.
Neumann
D
D
Kostka
K-H
KH
Lehr
C-M
CM
Schaefer
U F
UF
D000287:Administration, Topical; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D004058:Diffusion; D004817:Epidermis / Q000737:chemistry / Q000378:metabolism; D005260:Female; D005439:Flufenamic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D010539:Permeability; D014677:Pharmaceutical Vehicles; D012867:Skin / Q000737:chemistry / Q000378:metabolism*; D012995:Solubility; D013048:Specimen Handling / Q000379:methods*
D000893:Anti-Inflammatory Agents; D014677:Pharmaceutical Vehicles; D005439:Flufenamic Acid