Buccal Insulin Delivery Systems: Formulation Approaches, Stability Constraints, and Translational Prospects.

Insulin delivery via the buccal route has shown long-standing promise for diabetes therapy, but clinical translation remains limited. Most systems address only part of the delivery problem, whereas a viable product must simultaneously provide adequate insulin residence time, effective mucus and epithelial permeation, stability, dose consistency, safety, and manufacturability. This review examines the biological and formulation barriers limiting buccal insulin delivery and compares major platform types, including mucoadhesive films and patches, nanocarrier-based systems, deformable vesicles, chemistry-led permeation approaches, and device-enabled strategies. Stability, alongside limited permeability, is considered a key barrier, while aggregation and excipient-related instability remain insufficiently addressed. This review also discusses why promising preclinical findings often fail to translate, exhibiting low bioavailability, variability, safety concerns, and scale-up challenges recurring across platforms. Overall, further progress in buccal insulin delivery will depend on formulation strategies that better integrate permeation enhancement, stability preservation, and translational feasibility.