132
In 1983, Professor Szejtli proposed to use DIMEB as parenteral drug carrier
(Szejtli 1983b, 1984a). The results were explained by the molecular encapsulation
concept. The complexation of a drug with DIMEB allowed a considerable increase
in the molecular mass of the guest, without establishing covalent bond. The consequence was a reduced diffusion rate. This behavior was interesting for specific
applications such as intramuscular or subcutaneous drug injections in rats (Szejtli
1983b, 1984a), e.g., on the action of lidocaine, a local anesthetic drug was nearly
doubled injecting the drug dissolved in aqueous DIMEB solution. The solubility of
lidocaine increased in presence of DIMEB. An increase of 2 mol in DIMEB concentration resulted in an increase of 1 mol in the concentration of dissolved lidocaine base. Chemical stability and duration of the biological effects of drug were
enhanced. Diffusion and biological elimination were also decreased on interaction
with DIMEB. NMR and circular dichroic spectra clearly showed the formation of
inclusion complexes as illustrated in Fig. 2.21. The same techniques were previously used to demonstrate the formation of an inclusion complex between DIMEB
and vitamin D3 (Szejtli et al. 1980f, g) or vitamin K3 (Szejtli et al. 1982a).
Solutions of soluble cyclodextrin polymers were also able to enhance the solubility of substances, e.g., drugs, vitamins, pollutants, etc., that were sparingly soluble
or practically insoluble in water (Szejtli 1984a; Szemán et al. 1987a, b), e.g., in a
10 g/100 mL β-cyclodextrin-epichlorohydrin polymer solution, 16 g cholic acid or
0.4 g benzene can be dissolved at room temperature; the solubility enhancement
factors were more than 50 and 6, respectively. These results were also explained by
molecular encapsulation (Szejtli 1984a).
In 1994, Professors Frömming and Szejtli wrote a famous monograph on the role
of cyclodextrins in pharmacy, which is still considered as a reference book in the
cyclodextrin community (Frömming and Szejtli 1994).
2.5.4 Applications of Cyclodextrins in Chromatography
Inclusion complexation of lipophilic guest molecules by soluble α- and
β-cyclodextrin polymers, prepared by cross-linking cyclodextrins using epichlorohydrin, showed to be useful in reversed phase thin-layer chromatography, e.g., for
separation of prostaglandins (Szejtli 1978, 1984b, 1985a; Cserháti et al. 1983a,
1984, 1988). The method was also used for the determination of cyclodextrin inclusion complex stability (Cserháti et al. 1983a, 1990a).
An interesting field of applications of insoluble β-cyclodextrin polymers (Zsadon
et al. 1979b; Szejtli 1980), also prepared by cross-linking cyclodextrins using epichlorohydrin, was in gel-inclusion chromatography for amino acids (Zsadon et al.
1979a), alkaloids (Zsadon et al. 1981, 1983), and proteins separation (Ujházy et al.
1988, 1989) and in gas chromatography or in liquid chromatography as packings
(Cserháti et al. 1983b; Szejtli 1985a). The separation was based either on selective
inclusion or on specific affinity. Preparative chromatography was also interesting
for separation of racemic mixtures. Figure 2.22 shows the resolution of 500 mg
G. Crini et al.
In 1983, Professor Szejtli proposed to use DIMEB as parenteral drug carrier
(Szejtli 1983b, 1984a). The results were explained by the molecular encapsulation
concept. The complexation of a drug with DIMEB allowed a considerable increase
in the molecular mass of the guest, without establishing covalent bond. The consequence was a reduced diffusion rate. This behavior was interesting for specific
applications such as intramuscular or subcutaneous drug injections in rats (Szejtli
1983b, 1984a), e.g., on the action of lidocaine, a local anesthetic drug was nearly
doubled injecting the drug dissolved in aqueous DIMEB solution. The solubility of
lidocaine increased in presence of DIMEB. An increase of 2 mol in DIMEB concentration resulted in an increase of 1 mol in the concentration of dissolved lidocaine base. Chemical stability and duration of the biological effects of drug were
enhanced. Diffusion and biological elimination were also decreased on interaction
with DIMEB. NMR and circular dichroic spectra clearly showed the formation of
inclusion complexes as illustrated in Fig. 2.21. The same techniques were previously used to demonstrate the formation of an inclusion complex between DIMEB
and vitamin D3 (Szejtli et al. 1980f, g) or vitamin K3 (Szejtli et al. 1982a).
Solutions of soluble cyclodextrin polymers were also able to enhance the solubility of substances, e.g., drugs, vitamins, pollutants, etc., that were sparingly soluble
or practically insoluble in water (Szejtli 1984a; Szemán et al. 1987a, b), e.g., in a
10 g/100 mL β-cyclodextrin-epichlorohydrin polymer solution, 16 g cholic acid or
0.4 g benzene can be dissolved at room temperature; the solubility enhancement
factors were more than 50 and 6, respectively. These results were also explained by
molecular encapsulation (Szejtli 1984a).
In 1994, Professors Frömming and Szejtli wrote a famous monograph on the role
of cyclodextrins in pharmacy, which is still considered as a reference book in the
cyclodextrin community (Frömming and Szejtli 1994).
2.5.4 Applications of Cyclodextrins in Chromatography
Inclusion complexation of lipophilic guest molecules by soluble α- and
β-cyclodextrin polymers, prepared by cross-linking cyclodextrins using epichlorohydrin, showed to be useful in reversed phase thin-layer chromatography, e.g., for
separation of prostaglandins (Szejtli 1978, 1984b, 1985a; Cserháti et al. 1983a,
1984, 1988). The method was also used for the determination of cyclodextrin inclusion complex stability (Cserháti et al. 1983a, 1990a).
An interesting field of applications of insoluble β-cyclodextrin polymers (Zsadon
et al. 1979b; Szejtli 1980), also prepared by cross-linking cyclodextrins using epichlorohydrin, was in gel-inclusion chromatography for amino acids (Zsadon et al.
1979a), alkaloids (Zsadon et al. 1981, 1983), and proteins separation (Ujházy et al.
1988, 1989) and in gas chromatography or in liquid chromatography as packings
(Cserháti et al. 1983b; Szejtli 1985a). The separation was based either on selective
inclusion or on specific affinity. Preparative chromatography was also interesting
for separation of racemic mixtures. Figure 2.22 shows the resolution of 500 mg
G. Crini et al.