An approach to reduce the number of skin samples in testing the transdermal permeation of drugs

Abstract

Although glyceryl trinitrate (GT) is a drug that easily permeates through skin, the variations in its transepidermal fluxes were high. The arithmetic mean of the GT flux (n = 31 skin samples from different individuals) was 16.5 micrograms cm-2 h-1 with a standard deviation of 42%. The extreme values were 4.1 and 36.9 micrograms cm-2 h-1, i.e. they differed by a factor of 9. Wide variations were also found for ephedrine, frusemide, caffeine, ethacrynic and benzoic acids and especially trospium chloride. All these fluxes were determined in an in-vitro permeation model at 32 degrees C using human epidermis. With the aim of standardizing epidermal preparations on their permeability, the extent to which the in-vitro GT fluxes through a human epidermal preparation correlate with those of other compounds was evaluated. The resulting standardization procedure consisted of two interactive parts: the correlation of the flux of a test-substance with that of GT using epidermal samples from three donors and estimating the minimum, mean and maximum flux of the test compound and quantitation of the transepidermal permeation of the test compound with those standardized epidermal preparations by calculating the GT standard coefficient defined by the slope of the line derived from the relation between GT flux units and the corresponding flux from the test compound.

In Vitro–In Vivo Correlation in Man of a Topically Applied Local Anesthetic Agent Using Numerical Convolution and Deconvolution

“…This difference could be a result of the large variability between the skin samples obtained from different subjects 19–23. The permeation results are obviously more sensitive to this variability when the skin is the rate‐controlling step rather than the formulation, which is the case here.…”