Development of a transmucosal oral gum (TOG) delivery system is proposed for diphenhydramine, a first-line antiemetic for treatment of nausea, including patients with HIV disease. Although many antiemetics are available for use, nearly all are administered by oral ingestion with slow onset of effects. A buffered TOG delivery system will provide advantages over existing medications including: a) rapid delivery of diphenhydramine into the bloodstream followed by sustained release, providing early and lasting nausea relief; b) avoidance of first-pass effects; c) improved bioavailability; d) user control over dosing; and e) convenience of use. Transmucosal systems invented by this research team with demonstrated efficacy will be adapted for diphenhydramine. Standardized, in vitro, mechanical gum chewing methodology and a validated HPLC assay will be used in dissolution studies to optimize performance. Gum prototypes targeted for medication release necessary for rapid and sustained nausea relief will be developed. Optimization of a diphenhydramine TOG delivery system will allow for future assessment in humans and subsequent commercialization. A safe and effective TOG medication, available over-the-counter, with a rapid onset and sustained action will improve nausea treatment significantly. PROPOSED COMMERCIAL APPLICATION: The need for medication delivery systems capable of rapid relief of nausea is considerable. For people with HIV disease, nausea and vomiting are often side effects of medications or symptoms of an underlying illness. Although many antiemetics are available for use, nearly all ere administered by oral ingestion with slow onset of effects. The proposed oral transmucosal delivery of diphenhydramine by a buffered gum would provide an innovative means of rapid and sustained, safe, and effective over-the-counter treatment of nausea. A large commercial market exists for treatment of nausea in adults, especially for those suffering with HIV disease.