Kietzmann, M., M. Wolff, C. Arth, and P. Bonn. Obtaining Another Apparently Well Known Result. The Predictive Value of an In Vitro Study of Dermal Absorption: Absorption of Estradiol-17b in the Isolated Perfused Bovine Udder. 1998. Perspectives in Percutaneous Penetration. Vol. 6A, pg. 79.

Using the isolated perfused bovine udder as an in vitro model of transdermal absorption, the delivery and percutaneous absorption of estradiol-17b was studied. Udder perfusion with gassed Tyrodes solution was started within 30 minutes after cattle slaughtering. Thereafter, estradiol-17b was administered as an ingredient of two different transdermal delivery systems (TTS-A and TTS-B) which were fixed on the udder skin. Both transdermal delivery systems were matrix-type self-adhesive patches in which the active ingredient estradiol-17b is completely dissolved. The formulation TTS-A had a drug content of 4.5% estradiol-17b with an active release area of 8 cm². TTS-B was a commercially available product with a patch size of 16 cm² (containing 2.55% estradiol-17b , labelled in vivo release of 60 ug/day). Using an enzyme immunoassay, estradiol-17b was measured in adhesive tape strips of the horny layer as well as in microtome sections of the viable udder skin 3, 6 and 8 hr after administration of the patches. After topical treatment with TTS-A, the estradiol-17b concentration in the horny layer and in the viable skin was about 2-3 fold higher than after administration of TTS-B. This demonstrated that estradiol-17b delivery and flux via the skin were significantly influenced by the galenic formulation of the patches.

The results of the in vitro study were comparable with results of a bioavailability study. In an open, randomized, multiple dose, cross over study, both patches were compared in 8 healthy postmenopausal women. After administration of TTS-A, the maximum estradiol-17b plasma concentration was significantly higher than after administration of TTS-B.

In conclusion, the isolated perfused bovine udder is a useful in vitro model with significant predictive value for studies of dermal penetration and absorption of drug formulations.