The ‘molecular encapsulation’ of many compounds can be performed with cyclodextrins. This operation often advantageously modifies the various physical and chemical properties of the encapsulated molecules. This method is simpler and cheaper than most other methods of encapsulation. The molecular structure of cyclodextrins renders them able to include other molecules, as a result of which powder-like crystalline inclusion complexes are formed.
The molecular dimensions of the three most significant cyclodextrins, α-, β- and γ-cyclodextrins, built up of 6, 7, and 8 glucopyranose units respectively are shown in Figure 3.6 (Zsadon et at., 1978, 1979). As a consequence of the C1 conformation of the glucopyranose units, all secondary -OH groups are located on one side of the torus-like cyclodextrin molecule, while all primary -OH groups are on the other side. The ‘lining’ of the internal cavity is formed by H-atoms and glycosidic oxygen bridge atoms, therefore this surface is slightly apolar. The structure of α-cyclodextrin is shown in Figure 3.7 (French, 1987). β-Cyclodextrin has a slightly sweet taste, is odorless, and is fairly stable against acid hydrolysis (Szejtli and Budai, 1976). In alkaline media, like other non-reducing oligo- and polysaccharides it is also rather stable.
Molecules, or functional groups of molecules, having molecular dimensions that correspond to the cyclodextrin cavity, being less hydrophilic than water, can be included in the cyclodextrin cavity if both components are dissolved in water. In solution, the slightly apolar cyclodextrin cavity is occupied by water molecules, which is energetically unfavorable (polarapolar interactions) and they are therefore readily substituted by appropriate ‘guest molecules’ which are less polar than water (Szejtli, 1969; Bergeron et al., 1977). The inclusion complexes thus formed are relatively stable, their water solubility compared to pure β-cyclodextrin is greatly reduced so they rapidly separate out in the crystalline form. The physical and chemical characteristics of the included molecules are significantly modified.
Since covalent bonds do not form between the components, under physiological conditions the complexes are easily dissociated. The simplest method is to stir or shake the aqueous solution (cold or warm, neutral or acidic) of cyclodextrin together with the guest molecule or its solution (Cramer and Henglein, 1956). After equilibrium has been attained water is eliminated by freeze drying, spray drying or by any other convenient method; the microcrystalline product often being separated by filtration.
The hydroxyl groups of the cyclodextrins show different reactivities. The primary hydroxyl groups react most easily whilst the C3-OH groups are most resistant to substitution. From cyclodextrins cross-linked polymers can be prepared in the form of fibrous (Szejtli et at., 1978), block (Solms and Egli, 1965), film (Wiedenhof, 1969) and bead (Wiedenhof et at., 1969) polymers. Such polymers make a variety of specific inclusion chromatographic separations possible.
In the pharmaceutical industry, cyclodextrin is utilized mainly as an auxiliary substance to improve the stability and absorption qualities of active ingredients in tablets. This makes the production and introduction of numerous active substances possible whose stability, compatibility or absorption features have so far prevented their use. In terms of the pharmaceutical industry the following effects can be achieved by cyclodextrin complexation:
- volatile compounds can be stabilized without losses through evaporation,
- liquid compounds can be transformed into crystalline, compressible forms,
- solubility in water as well as the rate of dissolution of poorly soluble substances can be increased,
- bad taste and smell can be masked by complex formation (Hamilton and Heady, 1970),
- cyclodextrin inclusion complexation offers almost full protection against atmospheric oxidation of easily oxidizable substances.
The application/potential application of cyclodextrin inclusion complexes in the food industry can be essentially divided into two categories. First, diminished storage losses (inhibition of volatility and decomposition induced by oxygen, light or heat) and secondly the elimination of disagreeable tastes and smells or other noxious components.
Essential oils extracted from well known spices (dill, tarragon, marjoram etc.) form stable crystalline complexes with cyclodextrins. These aromatics generally consist of a large group of components but by adequate technology an unaltered composition can be assured allowing the same taste sensation to be attained as with the corresponding fresh spice. The cyclodextrin complexes of volatile, readily oxidizable aroma-substances (flavorings) are stable to oxygen, light and heat, however, in aqueous media, e.g. in the mouth, they dissociate instantly and their flavoring action is readily experienced. Complexes of essential oils are utilizable in cosmetics, dairy products etc. More information on cyclodextrins can be found by reference to Szejtli (1988) and Nakamura and Hara (1993).