A NOVEL APPROACH FOR ENHANCING THE SUBLINGUAL ABSORPTION OF EPINEPHRINE FROM RAPIDLY DISINTEGRATING TABLETS FOR THE POTENTIAL FIRST-AID TREATMENT OF ANAPHYLAXIS

Jonas Auditorium

Objective. Our objective was to evaluate the rate and extent of absorption of epinephrine microcrystals (Epi-MC) administered from rapidly disintegrating sublingual tablets (RDSTs). Background. For the treatment of anaphylaxis in community settings, an IM injection of Epi 0.3 mg in the thigh using an auto-injector is the drug of choice and the only available dosage form in the market. Previously, we showed that Epi 40 mg from RDSTs is bioequivalent to Epi 0.3 mg IM injection in our validated rabbit model. Methods. The rate and extent of Epi absorption from Epi 40 mg RDSTs and Epi-MC 20 mg RDSTs (n=5) were evaluated in rabbits using a randomized crossover study design. Epi 0.3 mg IM injections in the thigh and placebo RDSTs were used as positive and negative controls, respectively. Blood samples were collected at frequent intervals and Epi concentrations were measured using HPLC with electrochemical detection. Results. Mean (SD) AUC0-60 and Cmax from Epi-MC 20 mg RDSTs (942±244 ng/ml/min and 38±10 ng/ml) and Epi 40 mg RDSTs (678±149 ng/ml/min and 32±10 ng/ml) did not differ significantly (p > 0.05) from each other or from Epi 0.3 mg IM injections (592±122 ng/ml/min and 28±7 ng/ml), but these were all significantly higher (p < 0.05) than endogenous Epi from placebo RDSTs (220±78 ng/ml/min and 8±3 ng/ml). The mean±SD Tmax was not significantly different (p > 0.05) between all formulations. Conclusion. The Epi- MC RDSTs improved Epi absorption two-fold and reduced the required bioequivalent dose by 50%. These sublingual Epi tablets are suitable for Phase I human studies. Grants. This study was partially funded by Health Professions Division Grant and the President's Faculty Research & Development Grant, Nova Southeastern University