Optimizing vitamin B12 delivery in solid pharmaceutical formats: The Role of Gelatin in Stability and Formulation Performance

Background Cyanocobalamin delivery in solid oral formulations is limited by gastric acid instability and the dependence on impaired haptocorrin/ intrinsic factor/ pathways in groups at high-risk of vitamin B12 deficiency such as metformin-treated diabetic patients (14–41% vitamin B12 deficiency) and older adults (10–40%). Gelatin encapsulation may enhance vitamin B12 delivery at therapeutic doses via acid protection and mucoadhesion. Methods In vitro studies compared 1% w/w gelatinised cyanocobalamin with non-gelatinised vitamin B12 using simulated gastric fluid (SGF, pH 1.2; HPLC stability 0–3 h) and differentiated Caco-2 monolayers (24 h apical uptake ± SGF/SIF preexposure; LC17 MS/MS; TEER). Results Gelatinised vitamin B12 retained 97.1% to 98.3% whereas non-gelatinised vitamin B12 retained 90.0% to 93.7% of the total vitamin B12 content in SGF (3-fold less degradation, 1-3h). Caco-2 monolayers presented 3˜-fold higher intracellular/basolateral vitamin B12 with gelatinised than with non-gelatinised vitamin B12, without TEER disruption. Conclusions Gelatin encapsulation confers superior gastric stability and epithelial uptake, supporting progression to pharmacokinetic studies for improved therapeutic vitamin B12 delivery in absorption-compromised populations.