Pharmaceutical Applications of Cyclodextrins and Their Derivatives

Kaneto Uekama, Fumitoshi Hirayama, and Hidetoshi Arima 

Cydodextrins and Their Complexes. Edited by Helena Dodziuk Copyright 2006 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 3-527-31280-3 

DMA-/ -CyD (4) Soluble in water, Low hemolytic Parenteral, oral, mucosal 

---

I 14 Pharmaceutical Applications of Cyclodextrins and Their Derivatives Table 14.1. Pharmaceutically Useful CyDs... 

With capillary electrophoresis (CE), another modern primarily analytically oriented separation methodology has recently found its way into routine and research laboratories of the pharmaceutical industries. As the most beneficial characteristics over HPLC separations the extremely high efficiency leading to enhanced peak capacities and often better detectability of minor impurities, complementary selectivity profiles to HPLC due to a different separation mechanism as well as the capability to perform separations faster than by HPLC are frequently encountered as the most prominent advantages. On the negative side, there have to be mentioned detection sensitivity limitations due to the short path length of on-capillary UV detection, less robust methods, and occasionally problems with run-to-run repeatability. Nevertheless, CE assays have now been adopted by industrial labs as well and this holds in particular for enantiomer separations of chiral pharmaceuticals. While native cyclodextrins and their derivatives, respectively, are commonly employed as chiral additives to the BGEs to create mobility differences for the distinct enantiomers in the electric field, it could be demonstrated that cinchona alkaloids [128-130] and in particular their derivatives are applicable selectors for CE enantiomer separation of chiral acids [19,66,119,131-136]. 

Pharmaceutical applications of cyclodextrins have been studied the most extensively. The identified roles of cyclodextrins are primarily to increase solubility, stability, and the bio availability of drugs with limited water solubility, to reduce the side effects and toxicity of drugs, and to alter their physical properties such as smell and taste. There have been many excellent reviews on the pharmaceutical utilization of cyclo dextrin and its derivatives by Loftsson and Brewster [45],Rajewski and Stella [46], and Irie et al. [47]. 

A wide area of supramolecular chemistry focuses on host-guest interactions between two or more molecules that are not covalently bonded (1). A special part of this chemistry deals with cyclodextrins and their derivatives (2). It is well known that cyclodextrins tend to include several types of hydrophobic guest molecules into their cavity. Accordingly, a large number of applications have been found in many areas, eg, in food chemistry as well as in the pharmaceutical (3) and cosmetic industries. Furthermore, cyclodextrins may be used in organic chemistry and also in polymer chemistry. 

Most industrial uses of cyclodextrins are based on their ability to form supramolecular inclusion complexes with diverse guests [4]. They are used as solubilizers or drug transporters for pharmaceutical applications [5], as stabilizers and taste protectors in food and cosmetic industries [6], and as static phase in chromatography [7] for the separation of chiral entities. The required properties of cyclodextrin derivatives vary depending on the desired application, such as enantioselectivity for the separation of enantiomers or stability of the inclusion complex for encapsulation of drugs. Native cyclodextrins rarely match perfectly to the application so their modification is necessary to fine-tune their properties. In that context, efficient and selective methodologies have to be developed to access new derivatives that could be adapted to the desired application. Cyclodextrins are a particular class of complex carbohydrate derivatives, as they are easily produced... 

---