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 microg x cm(2) x mL(-1) x 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 C(max) and area under the curve values of 1200 +/- 46 ng/mL, and 48,227 +/- 12,995 ng x min/mL, respectively. Rabbits (n = 3) dosed via the buccal pouch had C(max), T(max), and area under the curve values of 127 +/- 13 ng/mL, 200 +/- 35 min, and 24,221 +/- 1543 ng x 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.
Jay
Steven
S
Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 907 Rose Street, Lexington, Kentucky 40536-0082, USA.
Fountain
William
W
Cui
Zhengrong
Z
Mumper
Russell J
RJ
D000180:Acrylic Resins; D000269:Adhesives; D000278:Administration, Buccal; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D009061:Mouth Mucosa / Q000378:metabolism; D011817:Rabbits; D013696:Temperature; D013739:Testosterone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013997:Time Factors; D014885:Waxes
D000180:Acrylic Resins; D000269:Adhesives; D004337:Drug Carriers; D014885:Waxes; D013739:Testosterone; C030312:calcium polycarbophil