A high-strength dense supramolecular gellan gel - metal-phenolic network gel: Application in the control of crystallization behavior of Active Pharmaceutical Ingredients.

The size, morphology, and polymorphism of active pharmaceutical ingredients (APIs) are key determinants of pharmaceutical formulation performance. These properties are a focus of recent studies on supramolecular gels for drug crystallization. Unlike conventional gels composed solely of biological macromolecules, a supramolecular gel system (TA-FeIII-GG) was constructed using gellan gum (GG) as the base framework and incorporating a TA-FeIII coordination complex, enhancing the intermolecular interactions within the gel network. The crystallization of two model APIs, carbamazepine (CBZ) and vinpocetine (VIN), was investigated to evaluate the effect of spatial confinement on crystal morphology. Compared to GG alone, the TA-FeIII-GG gel exhibited a denser network structure and higher mechanical strength. Consequently, the APIs crystals formed within this system displayed markedly altered morphologies, appearing as well-defined polyhedral block-shaped structures. As a result, CBZ crystals formed in the TA-FeIII-GG gel exhibited a significantly slower release rate, with a complete release time approximately 1.8-fold longer than needle-like crystals. However, needle-like crystals are more easily obtained under conventional crystallization conditions, whereas block-like CBZ crystals are more advantageous in oral pharmaceutical applications. Therefore, this method proposes a new approach for controlling the morphology of API crystals, which can be used in sustained-release formulations.