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Beta-Cyclodextrin Bead Polymer
Cyclodextrin polymers can be obtained in the form of beads when the reaction of
cyclodextrin with polyfunctional compounds is carried out in aqueous phase dispersed in a non-polar solvent (Wiedenhof et al. 1971).
An independent procedure was developed for the preparation of cyclodextrin
bead polymer in the second half of the 1970s in the Chinoin Biochemical Research
Laboratory in cooperation with the Eötvös University Faculty of Sciences. The
invention was based on applying polyvinyl alcohol, polyvinyl acetate, or polyvinyl
alcohol-acetate copolymer as a protecting colloid in emulsion polymerization of
cyclodextrin using a polyfunctional coupling reactant such as epichlorohydrin and/
or other diepoxy compounds. The cross-linking reaction was performed in two
steps: first a water-soluble pre-polymer was formed with epichlorohydrin in a
homogeneous phase, and then a diepoxy compound under less alkaline conditions
was used for further cross-linking in a heterogeneous phase applying toluene as
water-immiscible solvent. The development started in 1976 by optimizing the reaction conditions in a laboratory scale (Fenyvesi et al. 1979). A patent was applied in
1978 and then granted in 1981 both in Hungary and in the USA (Szejtli et al. 1981).
The aim was a wound healing formulation for veterinary application in the form of
spherical beads of 100–300 μm diameter. The healing effect was based on the high
swelling of beads which sucked up the wound exudate, thus ensuring clean wound
surface and fast healing of otherwise slowly healing, oozing wounds. Utilizing
cyclodextrin functioning as a drug carrier, various antiseptic agents such as iodine
were added to the formulation (Fenyvesi 1988; Szejtli et al. 1988c). These antiseptic
agents were released into the wound in a sustained manner.
Application of the cyclodextrin polymer beads as column packing in gel chromatography was also foreseen. In addition to the analytical applications (Zsadon et al.
1979b, 1981, 1983, 1986, 1987; Cserháti et al. 1983; Szilasi et al. 1985; Ujházi et al.
1989), the use in preparative chromatography was worked out, too. A method was
developed for the selective removal of phenylalanine from protein hydrolysate
aimed for nourishing patients in phenylketonuria by simply eluting the protein
hydrolysate through a cyclodextrin bead polymer column (Szente et al. 1981).
Another application was foreseen for the removal of bitter components such as naringin from citrus juices (Ujházi and Szejtli 1989). Based on the similarity to crosslinked dextran polymer of Pharmacia (Sweden) named Sephadex-25, this
cyclodextrin polymer was named CDP-25.
The first scaling up was performed at Eötvös University Faculty of Sciences in
1981. The most important step was replacing toluene to less toxic paraffin oil. The
resulting 1600 g bead polymers were of the desired size (0.09–0.31 mm), spherical
shape and swelling (4.7 mL/g), and cyclodextrin content measured by iodometric
titration after acidic hydrolysis (55–60%). The methods for characterization were
standardized and documented (Kálóy 1980). The flow chart of preparation and the
scanning electron microscopic photo are illustrated in Fig. 4.15 and Fig. 4.16,
respectively.
É. Fenyvesi et al.
Beta-Cyclodextrin Bead Polymer
Cyclodextrin polymers can be obtained in the form of beads when the reaction of
cyclodextrin with polyfunctional compounds is carried out in aqueous phase dispersed in a non-polar solvent (Wiedenhof et al. 1971).
An independent procedure was developed for the preparation of cyclodextrin
bead polymer in the second half of the 1970s in the Chinoin Biochemical Research
Laboratory in cooperation with the Eötvös University Faculty of Sciences. The
invention was based on applying polyvinyl alcohol, polyvinyl acetate, or polyvinyl
alcohol-acetate copolymer as a protecting colloid in emulsion polymerization of
cyclodextrin using a polyfunctional coupling reactant such as epichlorohydrin and/
or other diepoxy compounds. The cross-linking reaction was performed in two
steps: first a water-soluble pre-polymer was formed with epichlorohydrin in a
homogeneous phase, and then a diepoxy compound under less alkaline conditions
was used for further cross-linking in a heterogeneous phase applying toluene as
water-immiscible solvent. The development started in 1976 by optimizing the reaction conditions in a laboratory scale (Fenyvesi et al. 1979). A patent was applied in
1978 and then granted in 1981 both in Hungary and in the USA (Szejtli et al. 1981).
The aim was a wound healing formulation for veterinary application in the form of
spherical beads of 100–300 μm diameter. The healing effect was based on the high
swelling of beads which sucked up the wound exudate, thus ensuring clean wound
surface and fast healing of otherwise slowly healing, oozing wounds. Utilizing
cyclodextrin functioning as a drug carrier, various antiseptic agents such as iodine
were added to the formulation (Fenyvesi 1988; Szejtli et al. 1988c). These antiseptic
agents were released into the wound in a sustained manner.
Application of the cyclodextrin polymer beads as column packing in gel chromatography was also foreseen. In addition to the analytical applications (Zsadon et al.
1979b, 1981, 1983, 1986, 1987; Cserháti et al. 1983; Szilasi et al. 1985; Ujházi et al.
1989), the use in preparative chromatography was worked out, too. A method was
developed for the selective removal of phenylalanine from protein hydrolysate
aimed for nourishing patients in phenylketonuria by simply eluting the protein
hydrolysate through a cyclodextrin bead polymer column (Szente et al. 1981).
Another application was foreseen for the removal of bitter components such as naringin from citrus juices (Ujházi and Szejtli 1989). Based on the similarity to crosslinked dextran polymer of Pharmacia (Sweden) named Sephadex-25, this
cyclodextrin polymer was named CDP-25.
The first scaling up was performed at Eötvös University Faculty of Sciences in
1981. The most important step was replacing toluene to less toxic paraffin oil. The
resulting 1600 g bead polymers were of the desired size (0.09–0.31 mm), spherical
shape and swelling (4.7 mL/g), and cyclodextrin content measured by iodometric
titration after acidic hydrolysis (55–60%). The methods for characterization were
standardized and documented (Kálóy 1980). The flow chart of preparation and the
scanning electron microscopic photo are illustrated in Fig. 4.15 and Fig. 4.16,
respectively.
É. Fenyvesi et al.