204
solvent was removed by steam distillation. Pure alpha-cyclodextrin was obtained by
crystallization upon cooling. The solid chloroform complexes of beta-cyclodextrin
and gamma-cyclodextrin were suspended in water, and chloroform was removed by
distillation. Cyclohexane was added in order to precipitate beta-cyclodextrin. The
precipitate was re-suspended in water and cyclohexane removed by distillation.
Then the pure beta-cyclodextrin was obtained by crystallization upon cooling. To
obtain pure gamma-cyclodextrin, the filtrate was concentrated, and cyclohexane
removed by distillation followed by crystallization. The resulting alpha- cyclodextrin,
beta-cyclodextrin, and gamma-cyclodextrin products were of high purity (99.3%,
99.9%, and 99.8%, respectively). This new technology was brought into effect at the
Chinoin plant CH-IV, in 1985. Overall 85.5 kg gamma-cyclodextrin was produced
in four 1500 L volume conversion batches; neither alpha- nor beta-cyclodextrin was
prepared by this way.
In the scaling up of alpha-cyclodextrin production based on developments of
Chinoin Biotechnology Department (Seres’s team), decanol was used as precipitant
to convert 25 v/v % corn starch into alpha-cyclodextrin as main component. The
technology transfer and optimization were finished with success at the pilot plant at
Győr Distillery in the first half of 1988. During this optimization series of experiments, the achieved typical alpha-cyclodextrin content was 7–13 v/v % of conversion mixture. The average yield was 9.6 kg alpha-cyclodextrin/100 kg corn starch.
Because of political and economic changeover, industrial alpha-cyclodextrin processing efforts at Győr Distillery were interrupted.
4.2.4 Determination of the Individual Cyclodextrins
in the Product
At the beginning, analyses of the cyclodextrins were only semi-quantitative. Thinlayer chromatography was a sufficient mode to separate individual cyclodextrins
from process samples. A unique new reverse phase thin-layer chromatography
method was developed for this purpose by researchers of Chinoin Biotechnology
Development. The applied mobile phase on Kieselgel layer was a dioxane/ammonium hydroxide 10/7 v/v mixture. It was a preliminary implementation of the later
discovered hydrophilic interaction chromatography mode in the early 1970s and has
been shown to work in this case. Later overpressured layer chromatography was
also used for analysis of high number of samples.
Based on Cramer’s early work on phenolphthalein cyclodextrin-induced decolorization, special quantitative analytical methods were developed by Cyclodextrin
Research Laboratory team (Szejtli et al. 1978; Vikmon 1982) based on cyclodextrin
complexation of various acid-base indicator dyes. The intensity of transmitted light
due to the shift in absorption maxima in presence of cyclodextrin was measured
spectrophotometrically. It was discussed later that appropriate dyes as methyl
orange and Congo red also gave stable 1:1 complexes with cyclodextrin (Barcza and
Buvari-Barcza 1989). These dyes having no any selectivity were able to detect only
É. Fenyvesi et al.
solvent was removed by steam distillation. Pure alpha-cyclodextrin was obtained by
crystallization upon cooling. The solid chloroform complexes of beta-cyclodextrin
and gamma-cyclodextrin were suspended in water, and chloroform was removed by
distillation. Cyclohexane was added in order to precipitate beta-cyclodextrin. The
precipitate was re-suspended in water and cyclohexane removed by distillation.
Then the pure beta-cyclodextrin was obtained by crystallization upon cooling. To
obtain pure gamma-cyclodextrin, the filtrate was concentrated, and cyclohexane
removed by distillation followed by crystallization. The resulting alpha- cyclodextrin,
beta-cyclodextrin, and gamma-cyclodextrin products were of high purity (99.3%,
99.9%, and 99.8%, respectively). This new technology was brought into effect at the
Chinoin plant CH-IV, in 1985. Overall 85.5 kg gamma-cyclodextrin was produced
in four 1500 L volume conversion batches; neither alpha- nor beta-cyclodextrin was
prepared by this way.
In the scaling up of alpha-cyclodextrin production based on developments of
Chinoin Biotechnology Department (Seres’s team), decanol was used as precipitant
to convert 25 v/v % corn starch into alpha-cyclodextrin as main component. The
technology transfer and optimization were finished with success at the pilot plant at
Győr Distillery in the first half of 1988. During this optimization series of experiments, the achieved typical alpha-cyclodextrin content was 7–13 v/v % of conversion mixture. The average yield was 9.6 kg alpha-cyclodextrin/100 kg corn starch.
Because of political and economic changeover, industrial alpha-cyclodextrin processing efforts at Győr Distillery were interrupted.
4.2.4 Determination of the Individual Cyclodextrins
in the Product
At the beginning, analyses of the cyclodextrins were only semi-quantitative. Thinlayer chromatography was a sufficient mode to separate individual cyclodextrins
from process samples. A unique new reverse phase thin-layer chromatography
method was developed for this purpose by researchers of Chinoin Biotechnology
Development. The applied mobile phase on Kieselgel layer was a dioxane/ammonium hydroxide 10/7 v/v mixture. It was a preliminary implementation of the later
discovered hydrophilic interaction chromatography mode in the early 1970s and has
been shown to work in this case. Later overpressured layer chromatography was
also used for analysis of high number of samples.
Based on Cramer’s early work on phenolphthalein cyclodextrin-induced decolorization, special quantitative analytical methods were developed by Cyclodextrin
Research Laboratory team (Szejtli et al. 1978; Vikmon 1982) based on cyclodextrin
complexation of various acid-base indicator dyes. The intensity of transmitted light
due to the shift in absorption maxima in presence of cyclodextrin was measured
spectrophotometrically. It was discussed later that appropriate dyes as methyl
orange and Congo red also gave stable 1:1 complexes with cyclodextrin (Barcza and
Buvari-Barcza 1989). These dyes having no any selectivity were able to detect only
É. Fenyvesi et al.