Cyclodextrin inclusion as a pharmaceutical reaction field: kinetic, pathway and structural control beyond equilibrium

Cyclodextrins (CDs) are widely used pharmaceutical excipients typically evaluated within equilibrium thermodynamic frameworks. However, many degradation processes, including radical-driven oxidation, photochemical reactions, and tautomerism-coupled instability, proceed under nonequilibrium conditions that cannot be fully explained by binding constants alone. This review presents CDs as molecular-scale reaction fields that modulate kinetic accessibility, pathway competition, and structural population distributions. Using three representative systems, we illustrate distinct modes of control: kinetic suppression of radical encounters in edaravone oxidation, pathway reorganization in ketoprofen photochemistry revealed by singular value decomposition (SVD), and structural equilibrium bias in avobenzone. By integrating kinetic analysis, time-resolved spectroscopy, and multivariate approaches, we present evidence that CDs can regulate reaction behavior beyond equilibrium complexation. This framework provides a basis for understanding formulation-dependent stability and offers design principles for CD-enabled stabilization strategies under nonequilibrium conditions.