Methods to enhance the complexation efficiency of cyclodextrins

In general, the complexation efficiency of cyclodextrins is rather low, and thus relatively large amounts of cyclodextrins are needed to complex small amounts of a drug. In addition, various pharmaceutical additives decrease the efficiency even further. Meanwhile, due to toxicological considerations, formulation bulk and production cost, it is important to use as little cyclodextrin as possible in pharmaceutical preparations. Several different methods, which can be applied in order to enhance the complexation efficiency of cyclodextrins, were evaluated. A sugaring-in effect could not be observed in aqueous cyclodextrin solutions. Polymers, and other rheological agents, increase the complexation efficiency by increasing the apparent stability constant of the drug/cyclodextrin complex. Ionization of a drug molecule sometimes increases the complexation efficiency by increasing the intrinsic solubility of the drug. Finally, enhanced complexation efficacy can be obtained by forming a more water-soluble drug derivative of a water- insoluble drug (i.e. prodrug with higher intrinsic solubility than the parent drug).