Formation and Release Enhancement of a Novel Small-Molecule Hydrogel Containing Sulindac and Meglumine

Up to now, most hydrogel-related studies have been devoted to the preparation of drug-containing macromolecular gels via the introduction of polymer matrices, together with the clarification of their assembly mechanisms and biomedical applications. In contrast, studies concerning the design of small-molecule gel systems remain relatively limited. As gel research progresses, drug small-molecule hydrogels have attracted growing interest for formulation development. This study investigated whether designing a small-molecule hydrogel could serve as an effective solubilization approach for sulindac (SUL)-a nonsteroidal anti-inflammatory drug clinically restricted by its poor aqueous solubility. Then, a SUL small-molecule hydrogel was prepared by straightforward mixing of SUL with biologically safe meglumine (MEG) in a minimal volume of deionized water, which exhibited a characteristic three-dimensional network structure and favorable viscoelastic properties. The characterization and simulation results indicated that the hydrogel formation was contingent upon the SUL-MEG miscibility, dissolution-aggregation equilibrium and intermolecular self-assembly. Consequently, the resulting SUL-MEG hydrogel exhibited 546 times higher solubility compared to the pure SUL. Meanwhile, the SUL-MEG hydrogel demonstrated superior release kinetics and supersaturation capacity, characterized by rapid attainment of peak concentrations and sustained supersaturated release. These enhanced performances were attributed to the high-energy state of the hydrogel itself and the molecular complexation between SUL and MEG. In conclusion, this study presents a feasible formulation strategy for overcoming the poor water solubility of insoluble drugs through the development of small-molecule hydrogel formulations.