Transmucosal delivery of testosterone in rabbits using novel bi‐layer mucoadhesive wax‐film composite disks

Testosterone exhibits very low oral bioavailability because of its low aqueous solubility and extensive first‐pass metabolism. The purpose of this study was to develop a novel bi‐layer mucoadhesive wax‐film composite (WFC), and to test the relative bioavailability of testosterone via the buccal route in rabbits. The release rate of testosterone from optimal WFCs (3/8‐in. diameter) per unit surface area was 5.6 μg cm2 mL−1 min−1 and was zero‐order. Bi‐layer WFCs (average weight of 14 ± 2.6 mg and thickness of 186 ± 34 microns) containing 4 mg of testosterone were applied to the buccal pouch of anesthetized New Zealand white rabbits. Rabbits (n = 3) injected intravenously had Cmax and area under the curve values of 1200 ± 46 ng/mL, and 48,227 ± 12,995 ng*min/mL, respectively. Rabbits (n = 3) dosed via the buccal pouch had Cmax, Tmax, and area under the curve values of 127 ± 13 ng/mL, 200 ± 35 min, and 24,221 ± 1543 ng*min/mL. The relative bioavailability for rabbits treated with the WFC was 50.2 ± 3.2% with a coefficient of variation of 6.4%. It was concluded that these bi‐layer mucoadhesive WFCs disks could deliver physiologically relevant amounts of insoluble drugs such as testosterone across the buccal mucosa. © 2002 Wiley‐Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:2016-2025, 2002