Pharmaceutics · 5 authors, 2 centres
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This review describes how cyclodextrin inclusion complexes improve drug bioavailability by enhancing solubility, stability, and controlled release. It covers synthetic methods for modified cyclodextrins and polymers, and analytical techniques to characterize true inclusion complexes. The clinical significance lies in enabling more effective oral, pediatric, ophthalmic, and targeted drug delivery.
**Background:** Many active pharmaceutical ingredients have low oral bioavailability due to poor solubility, chemical instability, or poor permeability. Cyclodextrins (CDs) are cyclic oligosaccharides with a hydrophobic cavity that can form inclusion complexes with drugs, improving their solubility, stability, and bioavailability. This review covers the use of natural and modified CDs, CD-based polymers, nanosponges, and nanofibers to enhance drug delivery, along with synthetic and analytical aspects.
**Methods:** The authors conducted a narrative review of the literature, summarizing key examples of CD inclusion complexes for improved bioavailability, stability, and formulation. They discuss synthetic strategies for functionalizing CDs (e.g., selective modification at primary and secondary rims, polymerization via ATRP, RAFT, ROP, and CuAAC) and analytical techniques for characterizing inclusion complexes in solid state (X-ray diffraction, DSC, TGA, SEM, FT-IR, Raman) and in solution (UV-Vis, fluorescence, NMR, HPLC, CE, MS, ITC, DLS).
**Key Results:** The review presents numerous examples: Gallic acid solubility increased >100-fold with HPβ-CD. Camptothecin lactone hydrolysis reduced from 40% to 3.4% with β-CD and to 6.7% with HPβ-CD. Pediatric griseofulvin bioavailability improved 4- to 6-fold with β-CD nanosponges. Ocular terconazole concentration increased 5- to 7-fold with DMβ-CD. Paclitaxel plasma concentrations were 4 times higher with HPβ-CD vs. aminoβ-CD. Curcumin plasma concentration doubled with HPβ-CD. Naringenin solubility increased hundreds of times and Caco-2 permeability increased 11-fold with HPβ-CD. Nanofibers of sulfisoxazole/HPβ-CD showed sustained release. The review also details synthetic routes for mono- and persubstituted CDs, CD-based polymers, and nanosponges, and compares analytical techniques for confirming inclusion complex formation.
**Clinical Implications:** Cyclodextrin inclusion complexes offer a versatile platform to overcome bioavailability challenges for BCS class IV drugs, labile compounds, and nutraceuticals. They enable improved oral, pediatric, ophthalmic, and targeted delivery, with potential for sustained release and reduced side effects. The combination of synthetic modifications and robust analytical characterization supports the development of more effective pharmaceutical formulations.