Abstract
A rabbit model for investigating sublingual drug absorption was established yielding results consistent with clinical data reported in the literature. Using propranolol as a model compound the effect of formulation and dosing variables was explored as a means to characterize the limiting parameters of this model. In addition, verapamil and captopril were selected as reference compounds to compare this model to sublingual absorption in humans. Rabbits were dosed sublingually and systemic absorption was measured over time. Sublingual absorption of propranolol was dependent on dosing solution pH and volume. Intra-oral spray device did not affect the overall exposure compared to instillation using a syringe. Despite species and dosing regimen differences the relative bioavailabilities of propranolol and verapamil were very similar in rabbits and humans. In contrast, captopril absorption from the sublingual cavity of rabbits was low and did not agree with that observed in man. Here we report a sublingual rabbit model of drug delivery and its potential utility in preclinical development of intra-oral dosage forms.
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