The objective of this study was to evaluate the gum from Hakea gibbosa (hakea) as a sustained-release and mucoadhesive component in buccal tablets for a model peptide, namely, salmon calcitonin. Flat-faced core tablets containing either 12 or 32 mg of hakea and 40 microg (200 IU) of salmon calcitonin (sCT) per tablet were formulated using a direct compression technique and were coated with Cutina on all but one face. The in vitro release profiles were sigmoidal in nature and according to a mathematical model indicated super Case II transport as the primary mechanism of release. The resulting plasma sCT and calcium concentrations were determined following both intravenous administration and buccal application of mucoadhesive tablets in rabbits. Following intravenous administration, the mean values determined for t(1/2) (alpha), t(1/2) (beta), V(d), and CL for sCT were 0.76 +/- 0.06 min, 67 +/- 18 min, 1484 +/- 454 mL/kg, and 19 +/- 2 mL/min.kg, respectively. Following the application of the mucoadhesive buccal tablets which contained 40 microg of sCT and either 12 or 32 mg of hakea, the calculated apparent bioavailability (F) and clearance (CL) were 37 +/- 6% and 19 +/- 3.3 mL/min.kg and 16 +/- 8% and 18 +/- 0.4 mL/min. kg, respectively. Serum calcium concentrations indicated that biologically active sCT was delivered across the rabbit buccal mucosa. The strength of mucoadhesion of the tablets was also quantitated in terms of the force of detachment as a function of time. The force of detachment for the mucoadhesive buccal tablets containing either 12 or 32 mg of hakea and 40 microg of sCT increased from 4.47 +/- 0.68 to 8.41 +/- 1.0 N and 8.23 +/- 1.62 to 14.98 +/- 1.63 N, respectively, from 5 to 90 min following application to excised rabbit intestinal mucosa. These results demonstrate that the novel, natural gum from Hakea gibbosa may be used to sustain the release of sCT from a unidirectional-release buccal tablet. The mechanism of in vitro release is likely to involve peptide diffusion/polymer dissolution. The mucoadhesive strength, as measured by the force of detachment, can be modulated by altering the amount of hakea in the tablet. The mucoadhesive buccal tablets described in this paper represent an improved transbuccal delivery system for therapeutic polypeptides.