**1.1 Structure and properties of cyclodextrin**

In terms of structure, CDs have basket or truncated cone-like structure in which diameter of the inner cavity is a function of the glucopyranose units as shown in **Figure 2** [8]. The spherical arrangement of glucose units with secondary OH groups on wider end of the rim and primary OH groups on narrower end of the rim imparts it basket-like shape since the ability of primary OH groups to freely rotate decreases the diameter of the cavity at one end. Moreover, H-atoms bonded to CH group as well as OH groups form the external and hydrophilic exterior surface. In comparison to rims, internal cavity presents the hydrophobic microenvironment as it is surrounded with carbon and ether oxygen [9].

As cited earlier, there are three kinds of cyclodextrin, that is, Alpha α, Beta β, and Gamma γ also known as first or parent generation CDs. Due to the presence of sugar backbone in their framework, they can also be identified as cycloamyloses or dextrins [10, 11]. As far as the physicochemical properties are concerned, all the cyclodextrin molecules are large, hydrophilic, stable in basic media, hydrolyzable in acidic media,

**Figure 2.** *Schematic diagram of shape and dimensions of parent cyclodextrin [6, 7].*

*Cyclodextrins: An Overview of Fundamentals, Types, and Applications DOI: http://dx.doi.org/10.5772/intechopen.108078*


**Table 1.**

*Important characteristics of parent cyclodextrin [7].*

and similar in their ability to modify the physical, chemical, and biological features of drugs by yielding inclusion complexes (**Table 1**) [12].

The aqueous solubility of natural CDs and their complexes are known to be restricted, especially in case of *β*-CD, despite the fact that they are hydrophilic. This is owed to comparatively strong molecular bonding in CDs in their crystal state. Furthermore, significant number of intermolecular hydrogen bonds between secondary OH groups in the *β*-CD structure makes it stiff and inhibits the overall hydration. Interestingly, substituting any OH-group even by, for example, methyoxy group, can dramatically enhance the solubility. Nonetheless being less bulky, parent cyclodextrins exhibit lower molecular weight relative to their derivatives [13].

## **1.2 Derivatives of the CDs**

Given the lower aqueous solubility, numerous scientists tried to prepare and evaluated a variety of derivatives of the CDs of medicinal interest. The CDs derivatives can be produced by polymerizing or substituting the methyl, carboxymethyl, ethyl, hydroxyethyl, sulfabutyl, or even saccharides. Bonding various functional groups causes chemical alterations into the main and secondary OH groups of the parent CD molecules [13, 14]. These derivatizations are carried out to achieve the following goals:


Remarkably, till date, a myriad of CD derivatives have successfully been produced and analyzed, yet only a small number including methylated, hydroxy alkylated, and ether substituted derivatives have been employed in studies involving novel pharmaceutical applications [15].

1.Methylated derivatives can be prepared by randomly methylating any secondary OH group in C2, C3, or C6 locations or by selectively methylating all secondary OH groups of C2 position and primary OH groups of C6. In relation to the natural CDs, methylated ones exhibit altered physical, chemical, and structural characteristics. Solubility of methylated CD is also substantially greater;

however, the solubility is inversely proportional to the temperature as it diminishes when temperature rises.

