This podcast episode is about the key application of cyclodextrins: solubility enhancement.

Cyclodextrins (CDs) are important functional excipients in pharmaceuticals, primarily recognized for their ability to solubilize poorly water-soluble drugs. They are cyclic oligosaccharides derived from starch, shaped like a truncated cone or torus. The exterior of the cone is hydrophilic, while its central cavity is relatively lipophilic, allowing it to interact with hydrophobic guest molecules.

Here's an overview of their solubilization properties:

• Mechanism of Solubilization: The most prominent mechanism involves the formation of non-covalent, dynamic inclusion complexes in solution, where a drug molecule (guest) enters the lipophilic cavity of the cyclodextrin (host). Beyond this, CDs can also contribute to solubilization through the formation of non-inclusion based complexes, the creation of aggregates and related domains, and their capacity to form and stabilize supersaturated drug solutions.
• Impact on Drug Properties:
• Types of Cyclodextrins Used: The most commonly used cyclodextrins for pharmaceutical applications are α-cyclodextrin (αCD), β-cyclodextrin (βCD), and γ-cyclodextrin (γCD), along with some of their derivatives. Derivatives like hydroxypropyl-β-cyclodextrin (HPβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) are particularly well-studied and have advanced to market.
• Complex Stoichiometry and Challenges: While a 1:1 drug/cyclodextrin complex (one drug molecule with one CD molecule) is the most common stoichiometry, it has become clear that solubilizing effects often involve the formation of multiple inclusion and non-inclusion complexes. For natural cyclodextrins, a tendency to coprecipitate with the drug can limit their use, although using combinations of different cyclodextrins can help overcome this issue, sometimes showing additive or even synergistic solubilizing effects.

These properties make cyclodextrins valuable tools in addressing the challenges of poorly water-soluble drug candidates in pharmaceutical development.