The overall objective of the project is to develop a transdermal dosage form of the H1-blocker carbinoxamine for 24-hour control of allergic rhinitis. In Phase I the feasibility of such dosage will be tested. In vitro transdermal penetration experiments with nude mouse skins, as well as in vivo tests on shaved rabbit skins will be used to determine percutaneous flux values. Formulations optimized for percutaneous transfer will be incorporated into BIOTEK's patented DermaPatch transdermal dosage system, for in vitro and in vivo tests of performance. Preliminary studies conducted in our laboratory are very promising and showed that about 1 mg/day of carbinoxamine diffused across nude mouse skin from a 5 square centimeter patch. The formulation proved non-irritating in a rabbit primary skin irritation study, and the drug appeared thermally stable in its free base form. Another objective of the project is to generate information necessary for the submission of a Drug Master File, and an Investigational New Drug Application to the FDA in Phase II of the project. In Phase II we propose to finalize the base formulation of the delivery system and to develop the complete DermaPatch system for that formulation. At that point, industrial support will be sought for commercialization.
