The automated, accurate and reproducible determination of steady-state permeation parameters from percutaneous permeation data.
Procedures for the in vitro determination of percutaneous permeation with Franz diffusion cells are widely accepted. However, the calculation of relevant endpoints, such as the steady-state flux (J) and the permeation coefficient (P(app)), still depends on visual data inspection or an approximation of the steady-state flux as the maximum observed absorption rate. As both these approaches must be considered inappropriate, an automated and reproducible algorithm to analyse permeation data is presented. The method detects both lag-times and non-linear data resulting from substance accumulation in the acceptor compartment of static diffusion cells. It was evaluated by using simulated data, and data from experiments with caffeine and testosterone on bovine udder skin and human reconstituted epidermis (SkinEthic), which represent model barriers with high and low barrier strengths, respectively. It was shown that the algorithm is a suitable method for the identification of steady-state ranges in permeation data. If used on data generated with appropriate experimental approaches, it is a reproducible and time-saving alternative to the visual analysis of diffusion data.
Niedorf
Frank
F
Institute for Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover Foundation, Hannover, Germany. frank.niedorf@tiho-hannover.de
Schmidt
Elisabeth
E
Kietzmann
Manfred
M
D000818:Animals; D001331:Automation; D002110:Caffeine / Q000494:pharmacology; D002417:Cattle; D004058:Diffusion; D008321:Mammary Glands, Animal; D008954:Models, Biological; D010539:Permeability; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012867:Skin / Q000187:drug effects*; D012879:Skin Physiological Phenomena; D013739:Testosterone / Q000494:pharmacology
D002110:Caffeine; D013739:Testosterone