Polymorphism engineering of mefenamic acid for enhanced pharmacokinetic performance.

Mefenamic acid, a BCS Class II drug, continues to face the longstanding challenges related to its suboptimal solubility and variable absorption, which necessitates frequent dosing of the drug resulting in ulcerogenicity. Guided by its polymorphic forms, the co-crystallization of mefenamic acid offers a unique advantage over the other advanced formulation strategies, including hydrotropy, nanosizing, and complexation for improving the drug bioavailability. However, the contemporary research limited only to the proof-of-concept studies fails to provide a clinical evidence or translational insights, which necessitates the rational design of synthons and engineering of the solid-state landscape of the drug for developing the co-crystallization formulation of mefenamic acid. This commentary provides critical insights into the polymorphism-driven co-crystal design of mefenamic acid aimed at filling the critical gaps in scalability and clinical translation.