Cyclodextrins as Modulators of Photostability and Photochemical Behavior: Mechanisms, Analytical Assessment, and Applications

Photostability is a critical determinant of the performance and safety of light-sensitive compounds, yet the effects of cyclodextrin (CD) complexation are often interpreted as uniformly protective. This review critically examines how native and modified CDs and CD-based supramolecular architectures influence photodegradation and other light-driven processes across pharmaceuticals, natural bioactives, vitamins, sunscreen filters, dyes, photosensitizers, and agrochemicals. Evidence from experimental studies is evaluated in relation to host–guest inclusion geometry, conformational restriction, aggregation, microenvironmental polarity, oxygen accessibility, and excited-state and radical pathways. Direct quantification of intact compounds by stability-indicating chromatography (e.g., HPLC/UPLC) is distinguished from indirect indicators such as spectral changes or retained functional activity. The literature reveals condition-dependent outcomes ranging from substantial photoprotection to negligible effects or accelerated photodegradation, potentially reflecting disruption of protective guest aggregates or differential shielding of hydrolysis- and photolysis-prone regions. We also discuss photoresponsive systems in which CD association is exploited to control, rather than suppress, photochemical reactions. Reliable assessment requires matched irradiation controls, characterized irradiation spectra and doses (using ICH Q1B benchmarks where applicable), and consideration of formulation effects. Overall, cyclodextrins emerge as context-dependent modulators of photochemical behavior, supporting a shift from empirical complexation toward mechanism-guided design of light-stable and photoactive systems.