Solubility, Release Behavior and Membrane Permeability of a Ibuprofen Hydrogel Co-Assembled with N-Methyl-D-Glucosamine

Small-molecule hydrogels have gradually become a research hotspot compared with polymeric hydrogels, but their practical advantages have not been fully realized in the development of pharmaceutical formulations. This study aimed to explore whether the N-methyl-D-glucosamine (GLU) could be introduced to form a ibuprofen (IBU) hydrogel for overcoming its water solubility defect and optimizing its pharmaceutical properties. Such an IBU-GLU hydrogel was prepared by simply mixing IBU with GLU in small-volume deionized water. The formed IBU-GLU hydrogel was characterized by SEM, rheology, DSC, PXRD and FTIR analyses. In addition, the solubility, in vitro release and permeability were also investigated to evaluate the solubilization and permeability-promoting effects. The resulting IBU-GLU hydrogel exhibited a typical 3D structure with excellent viscoelasticity, which relied on the equilibrium of aggregation and dissolution, as well as a good miscibility between IBU and GLU, and self-assembly driven by intermolecular interactions in an aqueous environment. Compared to pure IBU, the IBU solubility of the IBU-GLU hydrogel was significantly improved by 38.4-fold. Furthermore, IBU-GLU hydrogel demonstrated superior release rates and supersaturation ability, which was attributed to its high-energy state and internal molecular complexation. Additionally, compared with the commercially available IBU hydrogel, the prepared IBU-GLU hydrogel significantly accelerated IBU membrane permeation. Thus, this study highlighted that the designed IBU-GLU hydrogel could serve as a feasible approach to enhance the release and permeability of IBU for its druggability optimization.