Buccal delivery of small molecules and biologics: of mucoadhesive polymers, films, and nanoparticles

- The buccal route has been exploited for selected potent small molecules.
- Research to achieve buccal insulin delivery is based on avoiding the GIT.
- Buccal insulin clinical trials have led to variable results with no FDA approvals.
- There is a rationale for buccal delivery of glucagon-like peptide 1 analogues.
- Development of printed films is timely and offer an opportunity for complex systems.

Buccal delivery of macromolecules (biologics) sets a great challenge for researchers. Although several niche small molecule products have been approved as simple sprays, tablets and oral films, it is not simply a case of adapting existing technologies to biologics. Buccal delivery of insulin has reached clinical trials with two approaches: oromucosal sprays of the peptide with permeation enhancers, and embedded gold nanoparticles in a dissolvable film. However, neither of these approaches have led to FDA approvals likely due to poor efficacy, submaximal peptide loading in the dosage form, and to wide intra-subject variability in pharmacokinetics and pharmacodynamics. It is likely however that printed film designs with lower molecular weight stable biotech payloads including lipophilic glucagon-like 1 (GLP-1) agonists and macrocycles with long half-lives will generate greater efficacy than was achieved to date for insulin.

152