Enhanced Solubility of Poorly Soluble Compounds by Inclusion Complexes with Cyclodextrins

Abstract

Cyclodextrins (CDs) are cyclic oligosaccharides consisting of (α-1,4)-linked D-glucopyranose units. In aqueous solutions, CDs form water-soluble inclusion complexes with poorly soluble lipophilic compounds via uptake of some of the lipophilic moieties of the compounds into the central cavity. As lipophilic compounds form complexes with CDs through non-covalent intermolecular interactions, the formation of inclusion complexes between CDs and lipophilic compounds in solution is in an equilibrium state. Although CDs are widely used to solubilize poorly soluble drugs, they rarely penetrate biological membranes under physiological conditions, enabling only the drug released from the CD to be absorbed through the membrane. While the formation of strong inclusion complexes in aqueous solution promotes drug solubilization, the drug must be released from the CD for absorption into the body. Therefore, when using CDs for drug solubilization, it is important to consider the stability constant between the drug and the chosen CD. Even though recent advances in high-throughput technology have facilitated the development of many new and potentially useful compounds, a large proportion are poorly soluble in water. Maximizing the capabilities of CDs should thus enable the use of many new but poorly soluble compounds as pharmaceuticals or for other applications.

graphical abstract