Cyclodextrins in the Pharmaceutical Field

Abstract

Cyclodextrins (CyDs) are cyclic oligosaccharides, containing a minimum of six D-(+)-glycopyranose units attached by α-1, 4-linkages produced by the action of the cyclodextrin-trans-glycosidase enzyme on a medium containing starch. CyDs are somewhat cone-shaped. The outside of CyDs is hydrophilic and the inside of the cavity is hydrophobic in character. If a molecule fits entirely or at least partially into the cavity, an inclusion complex may be formed. In general, hydrophobic molecules, rather than hydrophilic ones, have a higher affinity to the CyD cavity in aqueous solutions. The CyD complexes thus formed are stabilized by various intermolecular forces, such as hydrophobic interaction, van der Waals forces, hydrogen bonding, release of high energy water molecules in complex formation and release of strain energy in the macromolecular CyD ring. Orally administered CyDs have shown to be harmless, because insignificant amounts are absorbed.

Parenterally administered natural CyDs may cause severe nephrotoxicity, particularly β-CyD, due to the formation of low solubility of β-CyD-cholesterol complexes which precipitate in the kidney. Parenterally administered natural CyDs may also cause shape changes and hemolysis of human erythrocytes. Hydroxyalkylated-β-CyDs appear to lack these toxic potentials.

Molecular encapsulation may occur both in the solid state and in solution. Physicochemical properties of the guest molecule may be changed by CyD inclusion complexation. These alterations provide methods to characterize and detect inclusion. There are methods to detect inclusion in solid state and in solution. Some of the methods used to detect inclusion in solution may also be used to determine the complex stability constant. The alteration of physicochemical properties of the guest molecule may be useful to enhance drug properties such as solubility, dissolution rate, bioavailability, stability or to reduce side effects.