ABSORPTION OF TASTE-MASKED RAPIDLY-DISINTEGRATING SUBLINGUAL EPINEPHRINE TABLETS FOR PEDIATRIC USE FOR THE TREATMENT OF ANAPHYLAXIS

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Objective. to evaluate the sublingual (SL) bioavailability of E 30mg as a potential pediatric dose from RDSTs in comparison with IM E 0.15 mg from the EpiPen Jr. Background. Epinephrine (E) is life-saving treatment for anaphylaxis in community settings and E auto-injector (E-autos) are routinely prescribed. We developed rapidlydisintegrating sublingual tablets (RDST) of E as a potential alternative dosage form. Methods. RDSTs containing E 30mg were manufactured by direct compression. Dissolution was evaluated in vitro using our validated apparatus and method (AAPS PharmSciTech 2011;12(2):544-52). We studied the rate and extent of E absorption from the RDSTs in our validated rabbit model (n=5) using a parallel-dose design. The positive control was IM E 0.15mg from an EpiPen Jr. The negative control was a placebo RDST. Blood samples were collected at frequent intervals and E concentrations were measured using HPLC with electrochemical detection. Results. RDSTs resulted in total in vitro release of E within 60sec. The mean±SEM maximum plasma concentration (Cmax) of 16.7±1.9ng/mL at a peak time (Tmax) of 21min after SL E 30mg did not differ significantly (p > 0.05) from the Cmax of 18.8±1.9ng/mL at a Tmax of 36min after IM E 0.15mg in the thigh. The Cmax of both doses was significantly higher than the Cmax of 7.5±1.7ng/mL of endogenous E after placebo. Area under the curves (AUC) after SL E 30mg RDST, placebo RDST, and EpiPen Jr were significantly different. Conclusion. These taste-masked RDSTs containing E 30 mg dose are suitable for Phase I studies in humans. Grants. No financial or in-kind support for this study was provided by any corporate sponsor.