TITLE:
Optimizing Vitamin B12 Delivery in Solid Pharmaceutical Formats: The Role of Gelatin in Stability and Formulation Performance
AUTHORS:
Garima Chauhan, Tarun Goel, Pankaj Attarde, Heather Rodebush, Jiazhen Wang, Timothy Laughlin, Lijuan Li, John T. Stickney, Yan Li
KEYWORDS:
Vitamin B12, Gelatin Encapsulation, Gastric Stability, Caco-2, Passive Absorption
JOURNAL NAME:
Journal of Biomedical Science and Engineering,
Vol.19 No.7,
July
27,
2026
ABSTRACT: 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 - 3 h). Caco-2 monolayers presented 3-fold higher intracellular/basolateral vitamin B12 with gelatinised than with non-gelatinised vitamin B12, without TEER disruption. Conclusion: Gelatin encapsulation confers superior gastric stability and epithelial uptake, supporting progression to pharmacokinetic studies for improved therapeutic vitamin B12 delivery in absorption-compromised populations.