The long-term objective of this application is to commercialize an effective topical formulation of dapsone for the treatment of dermatitis herpetiformis (DH). The specific aims of this research plan are: 1) Manufacture a 50Kg biobatch utilizing Good Manufacturing Practices (GMP's) in an FDA approved drug facility, 2) Complete process development of the 1% dapsone topical gel, 3) Complete the animal safety testing using product from this 50Kg biobatch, 4) Complete IND stability testing using product from this 50Kg biobatch, 5) Establish tentative expiry dating for the 1% dapsone gel, 6) File a patent application providing intellectual property protection for the dapsone product, 7) Prepare the IND for 1% Dapsone Topical Gel for treatment of DH, and, 8) Prepare an Orphan Drug grant application and a Phase II SBIR grant application. In-vitro skin diffusion studies have shown that this optimized dapsone formulation can maintain drug concentrations in the skin that are equivalent or slightly greater than the skin levels following oral dosing. Since oral treatment with dapsone results in significant red-blood cell hemolysis, complete blood counts are done weekly for the first month of therapy and then every 6-8 weeks. Deaths associated with the administration of oral dapsone have been reported from agranulocytosis, aplastic anemia, and other blood dyscrasias. Since topical dapsone will avoid the high systemic drug levels of oral dosing for DH, the 1% dapsone gel product will provide tremendous safety advantages. Manufacture of the biobatch will be completed by DPT Laboratories while product safety testing will be completed by North American Science Associates, Inc. ViroTex will establish tentative expiry dating, complete product stability and submit the IND application. Topical dapsone will be both safer and more convenient for the patient suffering from DH. This product will be a welcomed addition to the products dermatologists have available for topical therapy of skin disease. PROPOSED COMMERCIAL APPLICATION: The current annual market for treatment of inflammatory dermatoses with oral dapsone is estimated to be $1.5 million. The 1% dapsone gel will be the only topical product approved for DH and will have significant safety advantages compared with oral dapsone. This product will likely be used for steroid-sparring of many other inflammatory dermatosis
