title: Epinephrine for the treatment of anaphylaxis: do all 40 mg sublingual epinephrine tablet formulations with similar in vitro characteristics have the same bioavailability?
abstract: Epinephrine autoinjectors are underutilized in the first aid emergency treatment of anaphylaxis in the community; so non-invasive sublingual epinephrine administration is being proposed. In order to determine the effect of changing excipients on the bioavailability of sublingual epinephrine, four distinct fast-disintegrating epinephrine 40 mg tablet formulations, A, B, C and D, were manufactured using direct compression. All formulations were evaluated for tablet hardness (H), disintegration time (DT) and wetting time (WT). In a prospective 5-way crossover study, four sublingual formulations and epinephrine 0.3 mg i.m. as a control were tested sequentially in a validated rabbit model. Blood samples were collected before dosing and at intervals afterwards. Epinephrine plasma concentrations were measured using HPLC-EC. All tablet formulations met USP standards for weight variation and content uniformity, and resulted in similar mean H, DT and WT (n=6). The area under the curve (AUC), maximum concentration (C(max)) and time at which C(max) was achieved (T(max)) did not differ significantly after the sublingual administration of formulation A and epinephrine 0.3 mg i.m. The AUC after B, C and D were significantly lower (p<0.05) than after epinephrine 0.3 mg i.m. These results suggest that the selection of excipients used in these tablet formulations can affect the bioavailability of sublingually administered epinephrine.
authors.affiliation: Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Mutasem M
authors.initials: MM
authors.lastname: Rawas-Qalaji
authors.forename: F Estelle R
authors.initials: FE
authors.lastname: Simons
authors.forename: Keith J
authors.initials: KJ
authors.lastname: Simons
mesh_terms: D000286:Administration, Sublingual; D000707:Anaphylaxis / Q000188:drug therapy*; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D004837:Epinephrine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011817:Rabbits; D013607:Tablets
chemical_list: D013607:Tablets; D004837:Epinephrine