Development and Characterization of an Ibuprofen-Salicylic Acid Co-crystal with Improved Solubility

Background

Ibuprofen is a widely used non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. However, its clinical efficacy is limited by poor solubility and bioavailability.

Objectives

This study aimed to: Select an appropriate co-former for ibuprofen using computational tools; synthesize and characterize an ibuprofen-salicylic acid co-crystal and evaluate its solubility and dissolution properties.

Methods

Computational tools, including Avogadro, AutoDock Vina, and MGL Tools, were used for molecular docking, employing the Lamarckian genetic algorithm to determine docking scores to search for the selection of a co-former. Salicylic acid showed the best interaction and was selected. Four different methods were used to make ibuprofen-salicylic acid co-crystals. The co-crystal was analyzed using X-ray diffraction (XRD), thermal analysis, and spectroscopic techniques to confirm its structure. The aqueous solubility and dissolution rate of the co-crystal were evaluated and compared with pure ibuprofen.

Results

The ibuprofen-salicylic acid co-crystals synthesized using solvent-assisted co-crystallization technique exhibited a distinct crystalline structure and thermal behavior compared to their individual components. Aqueous solubility was significantly enhanced in comparison to pure ibuprofen.

Conclusion

The ibuprofen-salicylic acid co-crystal demonstrated improved aqueous solubility and dissolution rate, suggesting its potential for enhancing the oral bioavailability of ibuprofen.