Proceedings of the Eighth International Symposium on Cyclodextrins

The cover illustration displays a-cyclodextrin with its MOLCAD program-generated contact
surface, onto which the molecular lipophilicity patterns (MLPs) are projected in a color code
ranging from blue (hydrophilic regions) to yellow (hydrophobic areas). The a-CO-donuts (top
entries) are viewed through the larger opening of the conically shaped molecule (left), thereby
exposing the intensely hydrophilic (blue) secondary hydroxyl face, or alternately, through the
smaller cone opening (right) revealing the surface areas above the six 6-CH20H groups to be
distinctly hydrophobic (yellow). The side view MLPs (lower entries), in closed fonn and bisected
with a ball- and stick-model insert, are oriented with the 2-0H/3-0H side (larger opening of the
torus) pointing upward; they clearly expose the distribution of hydrophillic (blue) and hydrophobic
(yellow) surface regions outside and inside the cavity. For further comments see F. W. Lichtenthaler and S. Immel, J. lnei. Phenom. Mol. Recogn. 25, 3-16 (1996), and pp. 3-16 of this volume.

Proceedings of the
Eighth International Symposium
on Cyclodextrins
Budapest, Hungary, March 31-Apri12, 1996

Edited by

J. SZEJTLI and L. SZENTE

CyC/olab, Cyc/odextrin Research and Development Laboratory Ltd.,
Budapest, Hungary

Partly reprinted from Journal of Inclusion Phenomena, Vol. 25, Nos. 1-3, 1996

KLUWER ACADEMIC PUBLISHERS

DORDRECHT / BOSTON / LONDON

A C.I.P. Catalogue record for this book is available from the Library of Congress

ISBN 0-7923-4029-9

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CONTENTS

Preface: Welcome (again) to Budapest ............................................................................... xvii

Sponsors ........................................................................................................................... xix
1. CYCLODEXTRINS & DERIVATIVES

Structures, Physical-Chemical Properties ................................................................. 1

1.1.

'"

Lichtenthaler, F. W., Immel, S.

The Lipophilicity Patterns ofCyclodextrins and of Non-Glucose
Cyc1ooligosaccharides ........................................................................................ '" " 3

'"

Veda, H., Endo, T., Nagase, H., Kobayashi, S., Nagai, T.

Isolation, Purification, and Characterization ofCyclomaltodecaose (&-CD) ............ 17

de Brauer, C., Claudy, P., Diot, M., Germain, P., LetotTe, J.M., Serpelloni, M.
Calorimetric Investigations of ~-Cyclodextrin Hydration Thermodynamic
Consequences of Water Exchange in Inclusion Reactions ...................................... 21

'"

Moreira da Silva, A.M.G., Steiner, Th., Saenger, W., Empis, J.M.A.,

Teixeira-Dias, J.J.c.
Hydration and Dehydration Processes of ~-Cyclodextrin: a Raman Spectroscopic
Study .................................................................................................................... 25

Bettinetti, G.P., Novak, c., Rillosi, M., Giordano, F., Mura, P.

Thermal Properties of a-Cyclodextrin Crystal Forms ............................................. 29

Nakanishi, H., Kanazawa, K., Yamagaki, T., Ishizuka Y., Tagaki., W.

NMR Study about the Structure and Behavior ofN-Peralkylamino-Cyc1odextrins
in Aqueous and Non-Aqueous Solvents ................................................................. 33

Witte, F., HotTmann, H.

Aggregation Behavior of Hydrophobically Modified ~-Cyclodextrins in Aqueous
Solutions ............................................................................................................... 37

Bako, I., Jicsinszky, L.

Comparison of Semiempirical and Molecular Mechanics Optimized Geometries
of Cyclodextrins ................................................. ' .................................................. 41
1.2.

Production of CDs

Flaschel, E., Andriamboavonjy E.R., Renken, A.

Transfer and Disproportionation Reaction of the Cyclodextrin Glucanotransferase
from Klebsiella Pneumoniae .................................................................................. 45

Lima, H.O.S., Zanin, G.M., de Moraes, F.F.

Enhanced Cyc10dextrin Production by Fermentation .............................................. 51

Matioli, G., Zan in, G.M., Guimaraes, de Moraes, F.F.

Screening for y-CGTase ........................................................................................ 55
Papers marked with an asterisk have also appeared in the Journal of Inclusion Phenomena, volume 25/\-3.

vi

Watanabe, N., Yamamoto, K., Tsuzuki, W., Oya, T., Kobayashi, S.

Effective Method for Producing Branched-a.-Cyclodextrins by Pullulanase and
Glucoamylase ........................................................................................................ 59
Glickstein, D., Bar, R.
Isolation and Characterization of a B. Circulans Strain and its CGTase .................. 63
Nakagawa, T., Ueno, K., Fujii, M., Koga, Y.
The Preparation of a Novel Cyclodextrin Homologue with D.P. Five [5lCD .......... 67

Chemical Modification of CDs

1.3.

Moser, J.G., Ruebner, A., Vervoorts, A., Wagner, B.

Cyclodextrin Dimers Used to Prevent Side Effects of Photochemotherapy and
General Tumor Chemotherapy .............................................................................. 71

Ruebner, A., Moser, J.G., Kirsch, D., Spengler, B., Andrees, S., Roehrs, S.
Synthesis of J3-Cyclodextrin Dimers as Carrier Systems for Photodynamic
Therapy of Cancer ................................................................................................ 77

Cucinotta, v., Grasso, G., Pedotti, S., Rizzarelli, E., Vecchio, G.

Three-Dimensional Cyclodextrin: a New Class of Hosts by Trehalose Capping
of J3-Cyclodextrin .................................................................................................. 81

Ahem, C., Darcy, R., O'KeetTe, F., Schwinte, P.

6-Hydroxyalkylamino-6-Deoxy-Cyclodextrins: Towards Dendrimeric HostMolecules ............................................................................................................. 85

Nepogodiev, S.A., Gattuso, G., Stoddart, J.F.

Synthesis and Properties of a New Family of Cyclodextrin Analogues ................... 89

Kovacs, J., Sallas, FL, Pinter, I., Marsura, A., Jicsinszky, L

New Type of Bridged Monoamino-J3-Cyc1odextrins .............................................. 95

Nogami, Y., Fujita, K., Ohta, K., Nasu, K., Shimada, H., Shinohara, c.,
Koga, T.
A New Synthetic Strategy ofCyclooligosaccharides. Cyclodextrin-Derived
Cycloaltrins Made up from a.(l ~4)-Linked Altropyranoses .................................... 99
Fujita, K., Mizuochi, M., Koga, K., Ohta, K.
Selective One-Point Cleavage of Capped J3-Cyclodextrin by Taka-Amylase A
Two-Step Synthesis ofGlycophane from J3-Cyclodextrin ..................................... 103

Amiel, c., Sebille, B.

New Associating Polymer Systems Involving Water Soluble J3-Cyclodextrin
Polymers ............................................................................................................. 107
Renard, E., Barnathan, G., Deratani, A., Sebille, B.
Characterization and Structure ofCyclodextrin-Epichiorohydrin PolymersEffects of Synthesis Parameters ........................................................................... 115

Hattori, K., Imata, H., Kubota, K., Matsuda, K., Aoyagi, M., Yamamoto, K.,
Jindoh, Ch., Yamanoi, T., Inazu, T.
The Synthesis of Oligosaccharide-Branched Cyclodextrins and their Interaction
with Concanavalin A ........................................................................................... 121

vii

Topchieva, LN., Elezkaya, S.Y., Polyakov, Y.A., Karezin, K.I.

Conjugates Based on Cyclodextrins and Poly(ethylene oxide) as Complexation
and Transport Agents .......................................................................................... 125
Topchieva, I.N., Panova, I.G., Gerasimov, Y.I.
Structural Aspects of Complexation between CDs and Poly(alkylene oxides) ...... 129
Luna, E.A., Bornancini, E.R., Thompson, D.O., Rajewski, R.A., SteUa, Y.J.
Characterization of Sulfobutyl Ether ~-Cyclodextrin Mixtures ............................. 133
de Kock, S.S., Penkier, L.J.
Development of a Sensitive and Accurate Method for the Qualitative Analysis
of Encapsin HPB ..................................................................... c...............

.137

Ortiz MeUett, C., Garcia Fernandez, J.M., Maciejewski, S., Defaye, J.

Synthesis, Water Solubility, and Inclusion Properties ofThioureido
~-Cyclodextrins .................................................................................................. 141
Defaye, J., Garcia Fernandez, J.M.
One Step Synthesis of Branched Cyclodextrins .................................................... 145
1.4.

Biological Properties
Antlsperger, G., Schmid, G.
Toxicological Comparison of Cyclodextrins ........................................................ 149
Shizuka, F., Hara, K., Hashimoto, H.
Dietary Fiber-Like Effects of Orally Administered Cyclodextrins in the Rat ."

. 157

2. CYCLODEXTRIN INCLUSION COMPLEXES ......................................................... 161

2.1.

Interaction with Specific Guests

Russell, N.R., McNamara, M.
Metallo-Cyclodextrins ......................................................................................... 163
Andersson, T., Westman, G., Stenhagen, G., Wennerstrom, O.
Enhanced Mass Spectrum ofthe 2: 1 a-CD-C 6o complex ..................................... 171

Berg, U., Berglund, M., B1adh, N., Svensson, A., Stodeman, M.

Structure and Dynamic Stability ofCyclodextrin Inclusion Complexes with
1,4-Disubstituted Bicyclo[2.2.2]Octanes .

. .. 175

Werner, T.C., Iannacone, J.L., Amoo, M.N.

The Binding of Pyrene and Other Probes to CD-Polymers .................................. 179

Hofler, Th., Wenz, G.

Determination of Binding Energies between Cyclodextrins and Aromatic Guest
Molecules by Microcalorimetry ......................................................................... 183
Buvari-Barcza, A., Rak, E., Meszaros, A., Barcza, L.
Complex Formation ofHydroxypropyl-~-Cyclodextrins with p-Nitropheno1... ..... 187

Cooper, A., Lovatt, M., Nutley, M.A.

Energetics ofProtein-Cyclodextrin Interactions ........................................ .

.... 189

viii

Giordano, F., Rillosi, M., Bettinetti, G.P., Gazzaniga, A., Majewski, W.,
Perrot, M.
Interaction of Supercritical Fluids with Drug/Cyclodextrin Inclusion Compounds
and Physical Mixtures ......................................................................................... 193
Mondik, P., Sopkova, A., Viernstein, H., Legendre, B.
Cyclodextrins in the Role of Host and Simultaneously Guest Component ............ 197

Kildemark, N., Larsen, K.L., Zimmermann, W.

Complex Formation of Unsaturated Cyclodextrin Solutions with Various
Polymers ............................................................................................................. 201

Krauter, L, Herrmann, W., Wenz, G.

Self Organization of Fluorescent Molecular Necklaces in Aqueous Solutions ....... 205

2.2.

Structural Studies

Bodor N., Huang, M.-J., Watt, J.D.

Theoretical AMI Studies of Inclusion Complexes of a- and ~-Cyclodextrins with
Methylated Benzoic Acids and Phenol, and a-Cyclodextrin with
Buckminsterfullerene........................................................................................... 209

Kohler, G., Grabner, G., Klein, e. Th., Marconi, G., Mayer, B., Monti, S.,
Rechthaler, K., Rotkiewicz, K., Viemstein, H., Wolschann, P.
Structure and Spectroscopic Properties of Cyclodextrin Inclusion Complexes ..... 215

Wouessidjewe, D., Lemesle-Lamache, v., Duchene, D., Perly, B.

Influence of Degree and Patterns of Substitution on the Inclusion Properties of
Ethylated ~-Cyclodextrins ................................................................................... 221

Cotta Ramusino, M., Bartolomei, M., Rufini, L.

IH NMR and UV Spectroscopic Study ofInclusion Complex Formation between
Pyridoxine and ~- and y-Cyclodextrins ................................................................ 225

Prokai, L., Ramanathan, R., Nawrocki, J., Eyler, J.

Electrospray Ionization Mass Spectrometry ofCyclodextrin Complexes of Amino
Acids and Peptides .............................................................................................. 229
Ikeda, T., Takahashi, T., Mori, M., Yoshida, K., Ueno, A., Toda, F.,
Schneider, H-J.
Chemically Switched DNA Intercalators Using Modified Cyclodextrin
Complexes .......................................................................................................... 233

Yamamoto, K., Nakao, T., Yonemochi, E., Oguchi, T.

Time Resolved Fluorescent Analysis for Sealed Heating ofDimethyl-~-Cyclodextrin
and Naphthalene System ..................................................................................... 237

Butkus, E., Martins, J.e., Berg, U.

IH NMR Study on the Inclusion ofBicyclo[3.3.1 ]Nonanes in Cyclodextrins ........ 241
Buvari-Barcza, A., Kajtlir, J., Barcza, L.
Hydroxypropyl Cyclodextrin Complexes: Relationships between the Substitution
Pattern, Stability Constants and Circular Dichroism Spectra ................................ 245
Ueno, A., Suzuki, T., Ikeda, H.
Fluorescent Cyclodextrins for Molecule Sensing .................................................. 251

ix

Biczok, L., Jicsinszky, L., Linschitz, H.

Hydrogen Bonding Interactions with Cyclodextrins: Utilization of Fluorenone
as a New Probe ................................................................................................... 255

Zia, V., Bomancini, E.R., Luna, E.A., Rajewski, R.A., Stella, v.J.
Effect of Alkyl Chain Length and Degree of Substitution on Complexation of
Sulfoalkyl ~-Cyclodextrins with Testosterone and Progesterone .......................... 259

Jicsinszky, L., Hashimoto, H., Mikuni, K., BakO, I., Szente, L.

Molecular Mechanics Studies on Cyclodextrin Complexes: Interaction of
Crocetin with Cyclodextrins ................................................................................ 263
2.3.

Enzyme-modeling

Seltzman, H.H., Szulc, Z.M.

Chemically Modified Cyclodextrins as Catalytic Enzyme Mimics ......................... 267

Martel, B., Morcellet, M., Crini, G.

Catalytic Esterolysis ofp-Nitrophenyl Acetate by ~-Cyclodextrin Associated
to Poly(Vinylamine) and a Benzylated Derivative ................................................ 273

Ikeda, H., Nishikawa, S., Takaoka, J., Akiike, T., Yamamoto, Y., Ueno, A.,
Toda, F.
Cyclodextrin Homo- and Hetero-Dimers as Enzyme Models ............................... 277

Sandeep Prabhu, K., Ramadoss, e.S.

Hydrolysis ofN-Benzoyl-L-Tyrosine Ethyl Ester Anchored in CD by
a.-Chymotrypsin and Subtilisin ............................................................................ 281
3. CYCLODEXTRINS IN PHARMACEUTICALS .......................................................... 285
3.1.

Drug/CD-Complexes

Glass, B.D., Worthington, M.S., Krallis, A., Stubbs, e.

Piroxicam Sodium: Effect ofInclusion Complexation with

~-Cyclodextrin

.......... 287

Puttipipatkbachom, S., Prasitpom, K.

Interaction ofPiroxicam Polymorphs with

~-Cyclodextrin

in Ground Mixtures .... 291

Piel, G., Pochet, L., Delattre, L., Delarge, J.

Study of the Influence of y-Cyclodextrin on the Mosidomine Photostability ......... 297

Antal L., Dombi, Gy., Novak, Cs., Kata, M.

Preparation and Investigation of Products Containing Tolperisone-HCI and
CDs .................................................................................................................... 301

Esclusa-Diaz, M.T., Perez-Marcos, M.B., Vila-Jato, J.L. TorresLabandeira, J.J.

Improvement in the Dissolution Properties ofKetoconazole through
Multicomponent ~-Cyclodextrin Complexation ................................................... 305

Moyano, J.R., Gines, J.M., Arias, M.J., Perez-Martinez, J.I., Bettinetti, G.,
Giordano, F.
Study of Complexation of Gliclazide with ~-Cyclodextrin in Solution by NMR
Techniques .......................................................................................................... 309

Caira, M.R., Griffith, v.J., Brown, G.R., Nassimbeni, L.R.

X-Ray Structures and Thermal Analyses of New CDlDrug Inclusion
Compounds ......................................................................................................... 313

Aigner, Z., Dombi, Gy., Kata, M.

Increasing the Solubility Characteristics ofD-Norgestrel with Cyclodextrins ....... 317

Bassani, V.L., Krieger, D., Duchene, D., Wouessidjewe, D.

Enhanced Water-Solubility of Albendazole by Hydroxypropyl-j3-Cyclodextrin
Complexation ...................................................................................................... 321
Mura, P., Bettinetti, G.P., Manderioli, A., Faucci, M.T., Bramanti, G.,
Setti, M.
Comparative Study of the Inclusion Properties of j3-Cyclodextrins for Ketoprofen
and Ibuprofen in Solution and in the Solid State .................................................. 325

Worthington, M.S., Glass, B.D., Penkler, L.J.

Phase Solubility Analysis in Studying the Interaction ofNifedipine with Selected
Cyclodextrins in Aqueous Solution ...................................................................... 329

Perrakis, A., Tsitsa, P., Hamodrakas, S.J., Antoniadou-Vyza, E.

Complexation of Active Antibacterial Adamantanol Derivatives with j3CD.
Structure Determination by X-Ray Crystallography and NMR ............................. 333

* . Antoniadou-Vyza, E., Thitsa P., Theodoropoulou, E., Mavromoustakos, T.

Complexation of New Active Antibacterial Adamantan Derivatives with j3CD:
Preparation and Characterization of Complexes. Study of the Thermotropic
Properties of Pure and Complex Form with Dipalmitoyl Phosphatidylcholine
Bilayers ............................................................................................................... 337
Kreaz, R.M., Dombi, Gy., Kata., M.
Increasing the Solubility of Furosemide with Cyclodextrins ................................. 341
Gyeresi, A., Tokes, B., Regdon, G., Kata, M., Nagy, G.
Study of the Solubility and Photostability ofNifedipine and its Derivatives
with CDs............................................................................................................. 345
Veiga, F., Sousa, A.
Effect of Temperature and Humidity on the Stability ofTolbutarnidelj3-Cyclodextrin
Inclusion Complexes ........................................................................................... 349

Hirayama, F., Usami, M., Kimura, K., Uekama, K.

Crystallization and Polymorphic Transition Behavior of Chloramphenicol Palmitate
in 2-Hydroxypropyl-j3-Cyclodextrin Matrix ......................................................... 353
Tokihiro, K., Irie., T., Uekama, K.
Differential Effects of Cyclodextrin Derivatives on Aggregation and Thermal
Behavior of Insulin .............................................................................................. 357

Lovatt, M., Cooper, A., Camilleri, P.

Energetics ofCyclodextrin-Induced Dissociation of Insulin ................................. 361
Masson, M., Loftsson, T., Fridriksd6ttir, H., Seir Petersen, D., J6nsd6ttir, S.
Complexation of Drug Compounds with Ionic and Non-Ionic Cyclodextrins ....... 365

xi

Ugwu, S.O., Alcala, M.J., Bhardwaj, R., Blanchard, J.

The Application of Equilibrium Dialysis to the Determination ofDrug-Cyclodextrin
Stability Constants .............................................................................................. 369

Fridriksd6ttir, H., Loftsson, T.

Solubilization of f3-Cyclodextrin ......................................................................... 373

Whittaker, D. V., Penkler, L.J., Glintenkamp, L.A., Bosch van Oudtshoorn,

M.e., Wessels, Ph.L.
Diclofenac-f3-Cyclodextrin Inclusion in Solution Proton Magnetic Resonance
and Molecular Modelling Studies ........................................................................ 377

3.2.

Ocular. Nasal and Transdermal Delivery

Marttin, E., Verhoef, J.e., Romeijn, S.G., Merkus, F.W.H.M.

Cyclodextrins in Nasal Drug Delivery: Trends and Perspectives ........................... 381

Kondo, T., Nishimura, K., Hirata, M., Irie, T., Uekama, K.

Effects ofCyclodextrins on Nasal Absroption and Analgesic Activity ofOpioids
in Rats ................................................................................................................ 387

Stefansson, E., Th6risd6ttir, S., Gudmundsson, O.G., Loftsson, T.,

Fridriksd6ttir, H., Kristinsson, J.K.
2-Hydroxypropyl-f3-Cyclodextrin in Eye Drops. Evaluation of Artificial
Tear-Drops in Human Patients ............................................................................ 391

Jarho, P., Urtti, A., Pate, D.W., Suhonen, P., Jarvinen, T.

The Effects ofHP-f3-CD on Aqueous Solubility, Stability and in Vitro Corneal
Penetration of Anandamide ................................................................................. 395

Jarho, P., Jarvinen, K., Urtti, A., SteUa, v.J., Jarvinen, T.

The Effect of SBE-7-f3-CD with Viscous Vehicle on Ocular Delivery of
Pilocarpine Prodrug in Rabbit~ ............................................................................ 399

Loftsson, T., Sigurdard6ttir, A.M.

Cyclodextrins as Skin Penetration Enhancers ....................................................... 403

Loftsson, T., Stefansson, E., Fridriksd6ttir, H., Kristinsson, J.K.

Novel CD-Based Drug Delivery System .............................................................. 407
3.3.

Specific Formulations

Uekama, K., Hirayama, F., Irie, T.

New Functions ofPeracylated f3-Cyclodextrins as Sustained-Release Drug
Carriers ............................................................................................................... 413

Nakanishi, K., Masukawa, T., Nadai, T., Yoshii, K., Okada, S., Miyajima, K.
Prolonged Release of Drug from Triacetyl-f3CD Complex for Oral and Rectal
Administration .................................................................................................... 419

Duchene, D., Wouessidjewe, D.

Amphiphilic CycIodextrins and Targeting of Drugs .............................................. 423

Lemos-Senna, E., Wouessidjewe, D., Duchene, D.

Release Profiles of a Hydrophobic Drug Incorporated in Modified CycIodextrin
Nanospheres ....................................................................................................... 431

xii

Regdon, G. jr., Bacskay, I., Gergely, A.., Hodi, K., Regdon, G. sen., Kata, M.

Influence of Cyc10dextrins on the in Vitro Drug Liberation of Rectal

Suppositories Containing Benzodiazepine Derivates ............................................ 435

Minami, K., Hirayama, F., Uekama, K.

Preparation and Pharmaceutical Evaluation of Ester-Type Conjugates of
Biphenylyl Acetic Acid and Cyclodextrins as Colon-Targeting Prodrugs .............. 439

Fenyvesi, E., Ujhazi, A., Szejtli, J., Piitter, S., Gan, T.G.

Controlled Release of Drugs from CD Polymers Substituted with Ionic Groups ... 443

Tasic, Lj., Milic-Askrabic, J., Rajic, D.

Effect of Cyclodextrins on the Physical Properties and Dissolution Rate of
Carbamazepine Tablets ....................................................................................... 449

Tarimci, N., Kilinc, T., Ermis, D.

The Effect of2-Hydroxypropyl-f3-Cyclodextrin on Release ofNaproxen from
Pluronic F-127 Gel.. ............................................................................................ 453

Echezarreta-Lopez, M., Vila-.Jato, J.L., Torres-Labandeira, J.J.

The Effects ofCyclodextrins on the Incompatibility of Dexamethasone-Polymyxin
B in Solution ....................................................................................................... 457

Celebi, N., Giil, Z.I., Ocak, F., Yildiz, S., Acartiirk, F.

Investigation of the Effect off3CD on in Vitro Release ofKetaconazole from
Different Gel Bases ............................................................................................. 461

Loukas, Y.L., Vraka, V., Gregoriadis, G.

Drugs in Cyclodextrins in Liposomes: A Novel Approach to Drug Stability
Against Photochemical Oxidation ........................................................................ 465
3.4.

Bioavailability and Biomedical Effects

Stella, V.J.
SBE7-I3-CD, a New, Novel and Safe Polyanionic I3-Cyclodextrin Derivative:
Characterization and Biomedical Applications ..................................................... 471

Baumann, R., Rys. P., Uhlschmid, G.K., Wu, Z.

Selective Synthesis of Negatively Charged Derivatives of I3-Cyclodextrin and
their Biological Effects ........................................................................................ 477

Penkler, L.J., Whittaker, D.V., Glintenkamp, L.A., Bosch van

Oudtshoorn, M.e.,
Enhanced Pharmacokinetic Properties of Oral and Parenteral DiclofenacCyclodextrin Delivery Systems ........................................................................... 481

Piel, G., Delneuville, I., Delattre, L.

In Vitro and in Vivo Studies on Sodium Nimesulide-f3-Cyclodextrin Inclusion
Complex ............................................................................................................. 487
Felmeray, I., Fenyvesi, E., Neumark, T., Takacs, J., Gerloczy, A., Szejtli J.
Effect of Cyclodextrin Bead Polymer on Wound Healing .................................... .491

Everest-Todd, M.
Topical Application of Cyclodextrin Ethers in the Control of Pain ....................... 495

xiii

Brewster, M.E., Anderson, W.R., Webb, A., Bodor, N., Pop, E.

Anesthetic Activity and Pharmacokinetics of the Neurosteroid Alfaxalone
Fonnulated in 2-Hydroxypropyl-f3-Cyclodextrin in the Rat .................................. 499
Brewster, M.E., Murakami, T., Anderson, W.R., Bodor, N., Pop, E.
Improved Oral Bioavailability of the Brain-Targeting Estrogen, E2-CDs,
through the Use ofCarboxymethylethyl-f3-CycIodextrin ..................................... 503
Brewster, M.E., Howes, J., Griffith, W., Garty, N., Bodor, N., Anderson, W.R.,
Pop,E.
Intravenous and Buccal2-Hydroxypropyl-I3-Cyclodextrin Fonnulations of
E2-CDs-Phase I Clinical Trials ...................................................... , ..................... 507
Brewster, M.E., Anderson, W.R., Loftsson, T., Bodor, N., Pop, E.
Effect of 2-Hydroxypropyl-f3-Cyclodextrin Complexes of the Neurosteroids,
Alfaxalone, Pregnanolone and Pregnenolone, on Various Convulsant Stimuli
and the Mouse .................................................................................................... 511
Gerloczy, A., Szeman, J., Csabai, K., Kolbe, L, Jicsinszky, L., Acerbi, D.,
Ventura, P., Redenti, E., Szejtli, J.
Pharmacokinetic Study of Orally Administered Ketoconazole and its
Multicomponent Complex on Rabbits ofNonnal and Low Gastric Acidity .......... 515

4. INDUSTRIAL APPLICATIONS OF CYCLODEXTRINS ............................................ 519

4.1.

Biotechnology

Bar, R.
Application ofCyclodextrins in Biotechnology .................................................... 521
Donova, M.V., Dovbnya, D.V. Koschcheyenko, K.A.
Modified CDs-Mediated Enhancement of Microbial Sterol Sidechain
Degradation ........................................................................................................ 527
Kolossvary, G.J., Kolossvary, I., Banky-Elod, E.
In Vitro Study and Computational Simulation of Cyclodextrin Inclusion
Complexes in Enzymatic Lipid Hydrolysis ........................................................... 531
Ishaque, M., Sticht-Groh, V.
Degradation ofFattyacid-Cyclodextrin Complexes by Mycobacteria .................... 535
4.2.

Textile Industry

Trinh, T.
Cyclodextrins in Fabric Care Consumer Products ................................................ 541
Buschmann, H.-J.
CD Dye Complexes and their Use in Dyeing Processes ........................................ 547

Reuscher, H. Hirsenkorn, R.
Beta W7 MCT - New Ways in Surface Modification ........................................... 553

Denter, D., Schollmeyer, E.

Surface Modification of Synthetic and Natural Fibres by Fixation ofCycIodextrin
Derivatives .......................................................................................................... 559

xiv

Remi, E., Fenyvesi, E., Rusznak, I., Vag, A.

The Action of Lipophilic UV Absorbers - Solubilized by Cyclodextrin - on
Photofading of Aqueous Solution of Azoreactived Dyes ...................................... 565

Shao, Y., Martel, B., Morcellet, M., Weltrowski, M., Crini, G.

Sorption of Textile Dyes on J3-Cyclodextrin-Epichlorhydrin Gels ......................... 571

4.3.

Food and Cosmetics

Regiert, M.,Wimmer, T., Moldenhauer, J.-P.

Application ofy-Cyclodextrin for the Stabilization and/or Dispersion of Vegetable
Oils Containing Triglycerides of Polyunsaturated Acids ....................................... 575

Yoshii, B., Furuta, T., Yasunishi, A., Linko, Y.-Y., Linko, P.

Oxidation Stability ofEicosapentaenoic and Docosahexaenoic Acid Included in
Cyclodextrins ...................................................................................................... 579
Furuta, T., Yoshii, B., Fujimoto, T., Yasunishi, A., Linko, Y.-Y., Linko, P.
A Short-Cut Method for Estimating I-Menthol Retention Included in
Cyclodextrin During Drying a Single Drop .......................................................... 583
Giordano, R, Pierin, C., Rillosi, M., Bettinetti, G.P., Gazzaniga, A.,
Cursano, R., Fossati, E.
Interaction ofCyclodextrins and their Polymeric Derivatives with Spearmint Oil:
Preparation of Durable Flavors for Chewing-Gums ............................................. 587
Matsuda, B., Tanaka, M., Arima, B., Uekama, K.
Effect of2-Hydroxypropyl-Cyclodextrins on Percutaneous Absorption ofpHydroxybenzoic Acid .......................................................................................... 591
Environment Protection and Chemical Technologies

4.4.

Uemasu, I., Kushiyama, S., Aizawa, R.

Capture of Volatile Chlorinated Hydrocarbons by Aqueous Solutions of
Branched Cyclodextrins ...................................................................................... 597

Trotta, F., Ferrari, R.P., Laurenti, E., Moraglio, G., Trossi, A.

Removal of Phenols from Aqueous Solutions in the Presence of Horseradish
Peroxidase and Cyclodextrin Derivatives ............................................................. 601

*
*

Fenyvesi, E., Szeman, J., Szejtli, J.

Extraction ofPAHS and Pesticides fun Contaminated Soils with Aqueous CD
Solutions ............................................................................................................. 605
Gruiz, K., Fenyvesi, E., Kriston, E., Molnar, M., Horvath, B.
Potential Use of Cyclodextrins in Soil Bioremediation ......................................... 609
Pagliero, C., Natoli, M., Trotta, F., Drioli, E.
Preparation and Characterization ofPeek-WC/J3-Cyclodextrin Carbonate
Membranes ......................................................................................................... 613
Marzona, M., Carpignano, R., Girelli, S., Dolci, M.
J3-Cyclodextrin Complex of the Insecticide Azinpohos-Methyl... .......................... 619
Perez-Martinez, J.L, Gines, J.M., Arias, M.J., Moyano, J.R., Morillo, E.,
Ruiz-Conde, A., Sanchez-Soto, P.J., Novak, Cs.
Preparation and Characterization of2,4-D Complexes with a-Cyclodextrin ........ 623

xv

Kohler, G., Viernstein, B., Woischann, P.

Molecular Calculations and Thermodynamical Considerations on the Solubility
Enhancement ofTriflurnizole by Cyclodextrin Complexation ............................... 627

5. ANALYTICAL SEPARATIONS BY CYCLODEX1RINS ............................................ 633

Fanali, S.
Use ofCyclodextrins or their Derivatives in Capillary Electrophoresis and High
Performance Liquid Chromatography .................................................................. 635
Schurig, V.
Unified Enantioselective Chromatography Involving a Permethylated
~-Cyclodextrin Bonded to a Dimethylpolysiloxane (Chirasil-Dex) ....................... 641
Juvancz, Z., Merkides, K.E., Jicsinszky, L.
Perspectives of Chiral Capillary Electrophoresis Using Phosphated Cyclodextrins
as Additives ........................................................................................................ 649
Trotta, F., Zerbinati, 0., Giovannoli, c., Baggiani, c., Giraudi, G.,
Moraglio, G.
Enantiomeric Separation ofDichioroprop by Capillary Electrophoresis Using
~-Cyclodextrin Derivatives as Chiral Resolving Agents ....................................... 653

Kano, K., Kitae, T., Takashima, B.

Use of Electrostatic Interaction for Chiral Recognition. Enantioselective
Complexation of Anionic Binaphthyls with Protonated Amino-f3-Cyc1odextrin .... 657
Smith, I.D., Simpson, c.F.
Investigations into the GC Separation ofEnantiomers on 3-Trifluoroacetyl2,6-Dipentyl-y-Cyclodextrin ............................................................................... 663
Crini, G., Martel, B., Torri, G., Morcellet, M.
HPLC of Structural Isomers Using Cyclodextrin-Poly(Alkylamine) Systems
Coated on Silica Beads ........................................................................................ 667

*
*

Renard, E., Deratani, A., Djedaini-Pilard, F., Perly, B.

Modification ofthe Face Selectivity in Asymmetric Induction by Cyclodextrins
through the Formation of Three-Component Inclusion Compounds ..................... 671
Gyimesi, J., Szokii, E., Magyar, K., Barcza, L.
Determination ofDrug-Cyciodextrin Binding Constants by Capillary Zone
Electrophoresis ................................................................................................... 675

SUBJECT INDEX ............................................................................................................ 679

WELCOME (again) TO BUDAPEST!

In 1980 the cyclodextrins had been known for a long time, and during the
preceding 30 months 239 CD-related abstracts had been publi~Jted by the
Chemical Abstracts, i.e. the number of CD-related publications grew to
8/month. Several laboratories, companies, prepared CDs, but almost
exclusively for research purposes. A group of scientists, scattered worldwide in various laboratories, however, suspected that the CDs were more,
much more than only challenging curiosities, some of these people dreamed
about or even prognosticated the production of thousands of tons of CDs, to
be used in hundreds or thousands of products and technologies. At any rate,
in 1980 the time seemed to be adequate for an international CDSymposium.
I have sent letters to about 100 colleagues, working on cyclodextrins in
the preceding years asking for their opinion: is it timely to organize a small
CD-Symposium? The answers were unanimously YES. So we began to
organize a CD-Symposium. I expected 25-30 participants outside Hungary,
and in best case - including the presentations of Hungarian colleagues about 35-40 lectures. The fIrst surprise was that on 30th of September 1982,
the fIrst day of the Symposium from 17 countries more than 180
participants arrived and the submitted manuscripts fIlled a 544 page volume
(Proceedings of the 1st International Cyclodextrin Symposium, Akademiai
Kiad6, Budapest and Reidel, Pub!. Co., Dordrecht, 1982).
The second surprise on the last day of this Symposium was a question
from a group of Japanese colleagues: "Do you intend to organize the second
International Cyclodextrin Symposium, as well?" That was the very
moment when the Budapest International Cyclodextrin Symposium was
named by the serial number 1. The second CD Symposium was organized
by Professor Nagai in 1984 in Tokyo, and since that time every second year
the CD-Symposia have regularly been organized: Lancaster 1986
(Dr.Davies), Munich 1988 (Dr.Huber), Paris 1990 (Prof.Duchene), Chicago
1992 (Dr. Hedges), Tokyo 1994 (Prof.Nagai) and again Budapest in 1996.
By now, the production of CDs worldwide has reached the several
thousand ton per year level and is dynamically growing. Not only the a-, /3and yCDs are produced industrially, but also some derivatives, like randomxvii

xviii

methylated, hydroxypropylated (3CD and branched (3CD. CD-containing

drugs, food and cosmetic products are approved, produced and marketed.
The number of CD-related publications is more than 12700 (March 1996).
This year (in average) every day four new papers are published somewhere
in the world, patent applications, conference abstracts which are dedicated
to some aspect of the cyclodextrins. It is a magnificent feeling to see, that
the many efforts have not been wasted without rewards! the recent
enormous development on CD-technology is reflected in the parameters of
this symposium: more than 230 participants from 32 countries, about 170
lectures and posters represent a new record in the successful series of CDSymposia. No doubt, that many new results which will be presented in this
Symposium - will soon be realised: new, even parenterally administrable
CD-derivatives, CD-complexed drugs with significantly improved
biopharmaceutical properties, the use of CDs in environmental protection,
in biotechnology, in food, cosmetics, chromatography, diagnostics, etc. will
need continuously growing amounts of CDs and new CD-derivatives and
complexes. I wish similar feeling of success to every mono-maniac
scientists, who dedicate years or decades to some well-selected project.
Please note, only the first 20 years are difficult, just those have to be
survived!
Budapest, March 1996
Prof.J. Szejtli

The generous financial support of the following

sponsors made possible to organize this Symposium

American Maize Product Co.

Chiesi Farmaceutici S.p.A.

Hammond,
IndianalUSA
Parma, Italy

Chinoin-Sanofi Pharm. Chem. Co. Budapest, Hungary

Ciba-Vision A G

Hettlingen, Switzerland

Cyclodextrin Tech. Dev. Inc.

Gaineswille,
FloridalUSA
Budapest, Hungary

Cyclolab Ltd.
CyDex,L.C
Ensuiko Sugar Co.

Overland Park,
Kansas/USA
Yokohama, Japan

Janssen Biotech N. V.

Beerse, Belgium

Kluwer Academic Publishers

Nagai Foundation

Dordrecht,
The Netherlands
Le Bar-sur-Loup,
France
Tokyo, Japan

Nat. Committee for Tech. Dev.

Budapest, Hungary

Wacker-Chemie GmbH

Munich, Germany

Mane Fils Prod. Aromatiques