Cyclodextrins in Modern Pharmaceutics: A Comprehensive Review of Structural Diversity, Host–Guest Complexation, and Evolving Applications as Pharmaceutical Excipients and Active Pharmaceutical Ingredients

ABSTRACT:Cyclodextrins (CDs) are cyclic oligosaccharides produced by enzymatic degradation of starch that have evolved,over more than a century of study, from laboratory curiosities into indispensable tools of pharmaceutical science.Their truncated-cone architecture, with a hydrophilic exterior and a relatively apolar internal cavity, allows thereversible, non-covalent encapsulation of a remarkably broad range of lipophilic guest molecules. This host–guestchemistry underlies their principal pharmaceutical roles: solubility and dissolution enhancement, chemical andphysical stabilization, taste- and odor-masking, and permeability modulation across mucosal barriers. Beyond theirclassical function as inert excipients, selected CD derivatives now act as active pharmaceutical ingredients in theirown right, most notably sugammadex,a modified γ-cyclodextrin used to reverse steroidal neuromuscular blockade.This review synthesizes current literature on CD structural chemistry and classification, the thermodynamics andanalytical characterization of inclusion complexation, excipient and API applications, regulatory and toxicologicalstatus by route of administration, marketed CD-containing formulations, and emerging frontiers including CD-basednanocarriers, biosensors, and oncology applications. Persistent challenges in scale-up, regulatory harmonization, andrational complex design are discussed alongside future directions for this versatile class of pharmaceutical materials.