Evaluation of Hakea gibbosa as a sustained-release and mucoadhesive component of buccal tablets

Oral administration of peptides and proteins results in poor bioavailability. Parenteral route, on the other hand, needs frequent administration because of short elimination half-life. Sustained buccal delivery represents an attractive alternative mode of delivery. The overall objective of this research project was to evaluate the mucoadhesive and sustained-release properties of the water-soluble gum obtained from Hakea gibbosa (Hakea) in buccal tablets, both in vitro and in vivo, using chlorpheniramine maleate and salmon calcitonin as model therapeutic agents.; Dissolution studies indicated that the direct compression technique was more efficient in sustaining the release of chlorpheniramine maleate than the wet granulation technique. The mechanism of sustained release was more likely due to hindered diffusion of chlorpheniramine maleate through the hydrated Hakea, rather than chemical interaction. The in vitro calcitonin release profiles were sigmoidal in nature and indicated super case-II transport as the primary mechanism of release. Following the application of the mucoadhesive chlorpheniramine maleate and calcitonin buccal tablets, not only were the peak plasma concentrations achieved rapidly, but were also maintained throughout the period of application showing the in vivo efficacy of the Hakea gum to sustain the release of incorporated model drugs. Serum calcium concentrations indicated that biologically active calcitonin was delivered across the rabbit buccal mucosa. The strength of mucoadhesion of the tablets in terms of the force of detachment indicated the excellent mucoadhesive properties of the gum and suggested that the mucoadhesive strength can be modulated by altering either the amount of Hakea per tablet or the force used to apply the tablet. The effect of the Hakea gum on the activity of a model protease enzyme pyroglutamate aminopeptidase was investigated by performing enzyme kinetic studies. The mechanism for the inhibition of the enzyme by Hakea appeared to be a mixed-linear type (non-competitive inhibition).; Thus, the natural gum may be a promising additive not only for its sustained-release and mucoadhesive properties, but also for its ability to retard the enzymatic degradation of therapeutic polypeptides incorporated in dosage forms. The mucoadhesive buccal tablets evaluated represent an improved transbuccal delivery system for both conventional drug substances and peptides.