Exploring Tyramine's Role in the Formation of Supramolecular Adducts with Nonsteroidal Anti-Inflammatory Drugs

Abstract

In pharmaceutical crystal engineering, salification and co-crystallization are well-established strategies to enhance the physicochemical properties of nonsteroidal anti-inflammatory drugs (NSAIDs), which typically exhibit low aqueous solubility. This study introduces three new multicomponent crystalline systems of NSAIDs (S-naproxen, flurbiprofen, and ketoprofen) with the co-former tyramine, designed using knowledge-based methods. Additionally, a new polymorph of the diflunisal–tyramine system, synthesized via mechanochemical techniques, is reported. The new multicomponent systems were thoroughly characterized using solid-state NMR and single-crystal X-ray diffraction. Aqueous solubility tests conducted through solution ¹H NMR experiments revealed increased equilibrium solubility for all samples, highlighting the efficacy of crystal engineering in modulating the physicochemical properties of drugs.