Anaphylaxis may follow the exposure of susceptible persons to an antigen such as food and medication. Prompt intramuscular injection of epinephrine in the thigh is the treatment of choice. Most anaphylactic reactions occur unexpectedly and the failure to administer epinephrine promptly may result in the death of patients. Epinephrine for self-administration, e.g. EpiPen autoinjectors, is available but underutilized. Therefore, alternative methods of administering epinephrine are being explored. Previously, we were able to develop and evaluate rapidly-disintegrating sublingual epinephrine tablets. Our studies showed that sublingually administered epinephrine is absorbed in both animals and humans, however, the relative bioavailability is very low, 0.6%. Dipivefrin is an epinephrine prodrug that is approved for the treatment of glaucoma as an eye drop (Propine, 0.1%).Dipivefrin has better biopharmaceutical properties than epinephrine and hence better bioavailability. Our objectives are to formulate dipivefrin into rapidly-disintegrating sublingual tablets and test their diffusion in vitro and ex vivo using dialysis and excised sublingual mucosal membranes, respectively. Dipivefrin sublingual tablets will be formulated using our previously patented formulation. Tablets will be evaluated for weight variation, content uniformity, friability, dimension, hardness, and disintegration time using the harmonized USP methods and criteria. The diffusion of 10, 20, and 40 mg dipivefrin (n=6) will be evaluated using a Franz Cells Diffusion System. Dipivefrin 10 mg solution and 40 mg epinephrine tablets will be used as controls. The mean±SDcumulative diffused dipivefrin and percentage, influx (J), permeability, and lag time will be calculated. The area under the curve (JAUC0-90), the maximum diffusion (Jmax), and the time to reach Jmax (Tmax) will be calculated and statistically compared by one-way ANOVA. Studies will be designed with a power of ≥80 and α<0.05.Dipivefrin sublingual tablets will offer efficient, non-invasive, and patient-friendly delivery system with fewer side effects than epinephrine injection for the treatment of anaphylaxis.