Bitter (Kaippu)-Coated Metformin Tablets: An Extra-Oral Bitter Taste Receptor (TAS2R) Pathway Hypothesis for Gunapaadam-Aligned Formulation Design

This article proposes a deliberately narrowed extension of the Suvai-coated sublingual delivery framework: rather than placing a bitter (Kaippu) taste coat on a sublingual tablet — where metformin's hydrophilic, high-dose, transporter-dependent absorption profile makes the sublingual route mechanistically unsuitable — the bitter coat is instead applied to a conventional, swallowed metformin tablet. Conventional swallowing preserves metformin's established oral pharmacokinetics, which depend on intestinal OCT1/PMAT transporters rather than passive sublingual diffusion. The therapeutic taste signal is then proposed to act not through the primary tongue-to-NTS gustatory pathway (which requires minutes of sublingual contact unavailable in a swallowed dosage form) but through a secondary, independently documented pathway: extra-oral bitter taste receptors (TAS2R family) expressed in the gastrointestinal tract itself. This reframes the Kaippu-Kabam Gunapaadam principle as a gutreceptor hypothesis rather than a sublingual-contact hypothesis, removing the metformin absorption conflict while preserving testability.