Fast-Disintegrating Sublingual Epinephrine Tablets: Effect of Tablet Dimensions on Tablet Characteristics

ABSTRACT

The purpose of this study was to evaluate the effect of changing dimensions on the hardness (H), disintegration time (DT), and wetting time (WT) of fast-disintegrating epinephrine tablets for sublingual administration as potential first aid treatment for anaphylaxis. Tablet formulations I and II, containing 0% and 10% epinephrine bitartrate, respectively, and weighing 150 mg were prepared by direct compression. Formulations were compressed at a range of forces using an 8/32″ die with concave punches (CP); a 10/32″ and an 11/32″ die with CP and flat punches (FP). Tablet weight variation, content uniformity, thickness, H, DT, and WT were measured. The 8/32″, 10/32″, and 11/32″ dies resulted in tablet thickness of ranges 0.25–0.19″, 0.17–0.1″, and 0.16–0.08″, respectively. The DT and WT using the 8/32″ die were ≤10 and ≤30 sec, respectively, at H ≤5.4 ± 0.2 kg for formulation I, and H ≤5.4 ± 0.3 kg for formulation II. The DT and WT were ≤10 and ≤30 sec, respectively, using 10/32″ die/CP, 10/32″ die/FP, 11/32″ die/CP, and 11/32″ die/FP at H ≤6.2 ± 0.6 kg, ≤6.8 ± 0.4 kg, ≤4.9 ± 0.1 kg, and ≤7.2 ± 0.3 kg, respectively, for formulation I. For formulation II, the DT and WT were ≤10 sec and ≤30 sec, respectively, when H < 4 kg. No difference in DT and WT was observed between concave and flat tablets. The 11/32″ and 10/32″ dies resulted in more ideal tablet dimensions for sublingual administration, but H must be maintained <4 kg to ensure rapid DT and WT.