PROCEEDINGS OF THE NINTH INTERNATIONAL SYMPOSIUM ON CYCLODEXTRINS

Proceedings of the Ninth International Symposium on Cyclodextrins

Santiago de Compostela, Spain, May 31-June 3, 1998

Edited by

J.J. Torres Labandeira

and

J.L. Vila-Jato Department of Pharmacy and Pharmaceutical Technology, University ofSantiago de Compostela, Spain

SPRINGER-SCIENCE+BUSINESS MEDIA, B.V.

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

ISBN 978-94-010-5971-8 ISBN 978-94-011-4681-4 (eBook) DOI 10.1007/978-94-011-4681-4

Printed an acid-free paper

The cover illustration displays the solid-state conformation of !X-cycJoaltrin (!X-CA) in different forms: the molecule adopts a conformation of 3-fold rotational symmetry with a unique alternating sequence of 4C, and 'C4 altropyranose chair geometries (upper left model, space group P63), resul­ting in banana-shaped disaccharide units, of which one is represented as a space-filling CPK-type model (lower left entry). In the crystaI lattice the compact molecules are stacked in transposed lay­ers (upper right, water molecules left off for clarity). Each !X-CA molecule is embedded into a matri x of 21 water molecules (Iower right, view along the hexagonal c-axis). The space filling models reveal !X-CA to be devoid of a central 'through-going' cavity. The graphics were generated using Brickmann's MOLCAD molecular modeling program; for further information see the web­pages at 'http://caramel.oc.chemie.tudarmstadt.de/immellmolcadlGalIery.html'or oS. Immel, G.E. Schmitt, and F.W. Lichtenthaler: !X-CycJoaltrin: Conformation and Properties in the Solid-State and Aqueous Solution.' , pp. 41-48 of this volume.

AlI Rights Reserved © 1999 Springer Science+Business Media Dordrecht Originally published by Kluwer Academic Publishers in 1999 Softcover reprint ofthe hardcover Ist edition 1999 No part of the material protected by this copyright notice may be reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording or by any information storage and retrieval system, without written permission from the copyright owner.

Dedicated to

Dr. Tsuneji Nagai and Dr. Josef Szejtli

on their 65th Birthday

Contents

Preface: Welcome to Santiago de Compostela ............................................ xvii Acknowledgements and Sponsors ..................................................... xviii

1. SEPARATION AND CHARACTERIZATION

J.Y. Carbonell and J. Ma Sendra. Development of a fluorimetric-FIA method to monitor cyclodextrin production from starch and the formation of inclusion complexes ................. .3

C. Cn!minon, F. Djedaini-Pilard, C. Pean, R. Vienet, B. Perly, J. Grassi and P. Pradelles. Development of enzyme immunoassays specific for naturalll- and y-cyclodextrins and synthetic derivatives. Pharmacokinetic analysis of cyclodextrins in rat ......................... 7

C.Amiel, B. Sebille, E. Renard, S. Picavet, R. Geref. The role of host guest interaction in thickening and phase separation of Il-cyclodextrin polymer and polymers bearing cyclic hydrophobic side groups .......................................................... 11

H. Imata and K. Takahashi. Specific binding and precipitation of y- cydodextrin with monosaccharide in an aqueous solution .............................................. .15

N. Rabearimonjy, S. Ounnar, M. Righezza and M. Dreux. Analysis of hydroxypropyl cyclodextrins by liquid chromatography and evaporative light scattering detection ............... 19

I. Caron, P. Chaimbault, C. Elfakir and M. Dreux. LC-ELSD or (and) LC-MS: a well suited technique for characterization of the differences in the commercially available DM-Il-CDS ........ 23

F. Trotta, Y. Morone, M. Zanetti and G. Camino. Thermal degradation of cyclodextrins ......... 27

2. CYCLODEXTRIN DERIVATIVES

A.R. Khan, P. Forgo, K.J. Stine and Y.T. D'Souza. Selective modifications of cyclodextrins ..... .33

J. Pitha. Cyclodextrin derivatives with enhanced solubilizing power and lower toxicity .......... .37

S. Immel, G. E. Schmitt and F.W. Lichtenthaler. a-Cycloaltrin: conformation and properties in the solid state and aqueous solution ................................................. .41

J. Kovacs, I. Pinter, L. Jicsinszky, N. Roos andA. Marsura. Symmetrical and non-symmetrical urea derivatives of B-cyclodextrin and piperazine: application in capillary electrophoresis ........ .49

A. Morva, E. Fenyvesi, N. Roos, B. Zsadon and J. Szejtli. Sulfated cydodextrin derivatives ..... .53

S. Immel, G.E. Schmitt and F.W. Lichtenthaler. The molecular geometries of cyclofructins ...... 57

H. Gohlke, S. Immel, F.W. Lichtenthaler and G.E. Schmitt. Molecular geometries offuranoid /3 (1-43) and /3 (1-46 )-linked cyclogalactins ............................................ 63

C. Pian, F. Djedai'ni-Pilard, C. Creminon, A. Wijkhuisen, J. Grassi, P. Guenot, Ph. Jehan and B. Perly. Synthesis and characterization of peptido-cyclodextrins dedicated to drug targeting ...... . . ... 69

viii

F. Djedaini-Pilard, M. Gosnat, S. Steinbruckner, J.P. Dalbiez, G. Crini, B. Perly andA. Gadelle. Mono-6-tosyl-13-cyclodextrin: preparation, hydrolysis and self-inclusion studies in aqueous solution ....................................................................... 73

e. Ortiz Mellet, J.M. Garcia Fernandez, J.M. Benito, H. Law, K. Chmurski and J. Defaye. Thiourea-bridged 13-cyclodextrin conjugates ............................................ 77

C. Amiel, L. Moine, W. Brown, E. Renard, P. Guerin and B. Sebille. Associations of amphiphilic degradable polymers with l3-cyclodextrin polymers: pH - dependant network ................... 81

N.M. Gosselet, F. Beucler and B. Sebille. Original associating system between hydrophobic ally modified N, N-dimethylacrylamide hydroxyethyl methacrylate copolymers and water soluble 13-cyclodextrins polymers .......................................................... 85

K.L. Larsen, L. Duedahl-Olesen, L.H. Pedersen and W. Zimmermann. Production of cyclomaltonaose (i5-cyclodextrin) by various cyclodextrin glycosyltransferases ................. 89

K.L. Larsen, T. Endo, H. Veda and W. Zimmermann. Capillary electrophoretic investigation of the inclusion complex forming properties oflarge cyc10dextrins .......................... 93

L. Janus, G. Crini. M. Morcellet, G. Torri,A. Cambiaghi,A. Naggi and C. Vecchio New sorbents containing 13-cyclodextrin: Synthesis, characterisation and, sorption properties ........... 97

T.N.T. Phan, M. Bacquet and M. Morcellet. Preparation and characterization of sorbents containing 13 CD derivatives coated or grafted onto silica gel ............................. .1 01

J.e. Debouzy, F. Fauvelle,A. Gadelle, V. Dabouis,A. Perrin, B. Brasme,A. Peinequin and B. Perly. Comparative cation chelating properties of per (3,6 anhydro), -and per (3,6 anhydro-2-0Me) a-cyclodextrins ............................................... .105

M. Masson, J. Pitha and T. Loftsson. Synthesis of cyc10dextrin glycerol ethers and investigation of their binding properties ....................................................... .1 09

K. Fujita, K. Ohta, Y. Nogami, K. Nasu, T. Shiratani, M. Sudo and T. Koga. Conformational eqUilibria of a-cycloaltrin in solutions .............................................. .113

T. Inazu, T. Yamanoi, K. Haneda, M. Mizuno, K. Matsuda, T. Yamazaki, M. Takeuchi, H. Tsurui and K. Hattori. The synthesis of oligosaccharide-branched cyclodextrins ............ 117

K. Suehiro, T. Sugino and M. Kuramori. Crystallization of partially O-alkylated 13-cyc1odextrins by including polymers .......................................................... .121

E. Memi~oglu, D. Charon, D. Duchene and A.A. Hincal. Synthesis of per (2,3-di-o-hexanoyl)-13-cyclodextrin and characterization of amphiphilic 13-cyclodextrin nanoparticles ................. 125

H. Ikeda, Y. Horimoto, M. Nakata and A. Veno. Thiamine-appended cyc10dextrin dimer as a ligase model ................................................................... 129

W-S. Lee, H. Mihara andA. Veno. Substituted cyclodextrins with amino acids as hydrolysis enzyme models ............................................................... .133

T. Aoyagi, H. Ikeda and A. Veno. Synthesis and molecular recognition abilities of modified '(-cyclodextrins bearing two pyrene moieties .......................................... 137

K. Takahashi, M. Kitsuta and K. (motani. Molecular "!ego" composed of monosubstituted cyclodextrins ................. . .............................................. 141

T. Yamagaki, Y. Ishizuka, S-I. Kawabata, H. Nakanishi. Structural analyses of sugar branched cyclodextrin derivatives by the post-source decay fragment method in MALDI-TOF mass spectrometry .....

Y. Ishizuka, T. Nemoto, M. Fujiwara, K-I. Fujita and H. Nakanishi. Three dimensional structure of branched u-cyclodextrins in solution ................ .

K. Teranishi, S. Tanabe, A. Komoda, M. Hisamatsu and T. Yamada. Synthesis and enhanced chemiluminescence of new monocyclomaltooligosaccharide-bound

ix

.145

. .. 149

6-phenylimidazo[ I ,2-a ]pyrazin-3(7H)-ones .. . ................................. 153

G.P. Bettinetti, H. Veda, M. Sorrenti and A. Negri. Thermal behaviour and phase transitions of cyclomaltononaose(8-cyclodextrin) , ... , ................ , ...................... 157

J.-P. Moldenhauer and H. Reuscher. Textile finishing with MCT-13-cyclodextrin .. . ........ 161

H. Veda, T. Endo, H. Nagase, S. Kobayashi and T. Nagai. Isolation, purification, and characterization of cyclomaltooctadecaose (v-CD) and cyclomaltononadecaose (~-CD) ... 167

P. Schwinte, A. Holohan, R. Darcy and F. O'Keeffe. Supramolecular assembly of polycharged 13-cyclodextrin derivatives: Formation of heterodimers between a polyamino- and a polysulfonato-13-cyclodextrin .............. , . . . . . . . . .................... 171

S. Bertini, G. Crini, A.-M. Naggi, R. Suardi, G. Torri, C. Vecchi, L. Janus, B. Martel and M. Morcellet. Insoluble polymers with high amounts of 13 CD: characterization and adsorption capacity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . , .. 175

J. Carrazana Garcia, W.AI Soufi, M, Novo Rodriquez and J. Vazquez Tato. Influence of pH on the stability of the inclusion complex of methyl orange and 13-cyclodextrin .. 179

K. Chmurski and J. Defaye. An improved synthesis of perC 6-deoxyhalo) cycl odextrins nsing N-halo succinimides-triphenylphosphine in dimethylformamide . . .183

3. CYCLODEXTRINS IN PHARMACY AND BIOTECHNOLOGY

J. Leite Pinto and H.M. Cabral Marques. Anti-asthmatic-cyclodextrin inclusion complex for pulmonary delivery . . . . . . . . . . . . . . . , ... 189

P. Baldet-Dupy andA. Deratani. Cyclodextrin-containing membranes. Synthesis and separation properties in pertraction ... , .193

F.W.H.M. Merkus, P.H.M. Van der Kuy, E. Marttin, S.G. Romeijn and J.e. Verhoef. Efficacy and safety of cyclodextrins in nasal drug delivery .... 197

A.M. Reis, H.M. Cabral Marques and I. Kcllaway. A Preliminary study of a 13-cyclodextrinl salbutamol complex for possible use is a dry powder inhaler , .. , . , ...... ' ... 203

M.S. Linal'es, M. DE Bcrtorello and M. Longhi. Solubility of a isoxazolyl-naphtoquinone by complexation with hydropxypropyl-fl- cyclodextrin .. , .207

T. Van Hecs, B. Evrard, G. Piel and L. Dclattrc. A comparative study of the dissolution properties ofpiroxicam-l3-cyclodextrin inclusion complexes prepared by different methods, , .. , .. 2l1

G. Piel, T. Van Hecs, B. Eward and L. Dclattrc. A comparative pharmacokinetlc study of intravenous solutions of miconazole with or without cyclodextrins , , .. , . , . , .... , , , . , , , . , , . , .215

x

G. Piel, B. Evrard, T. Van Hees, C. Fernandez del Pozo and L. Delattre. Development of a sustained release dosage form containing a diclofenac-cyclodextrin inclusion complex .......... 219

B. Evrard, P. Chiap, G. Piel, T. Van Hees, F. Ghalmi, B. Losson and L. Delattre. Influence of cyclodextrins on the solubility and the pharmacokinetics of albendazole .................... .223

A.M. Kaukonen, H. Lennernas and J-P Mannermaa. Evaluation of spironolactone bioavailability from solutions of B-cyclodextrin derivatives in rats ......................... .227

A. Ueno, S. Matsumura, T. Kanai and H, Mihara. Chemosensors of modified cyclodextrins for detecting molecules ............................................................ .231

H.Asanuma, M. Shibata, T. Hishiya and M. Komiyama. Molecularly imprinted cyclodextrin polymers as artificial receptors - The requisites for remarkable imprinting .................... 235

D. Duchene, G. Ponchel and D. Wouessidjewe. New developments in improvement og drug solubility and availability by cyclodextrins ........................................... .239

F. Hirayama, K. Minami and K. Uekama. Design and evaluation of colon-specific drug delivery system based on cyclodextrin conjugates ............................................ .247

N. Bodor, W-MWu and J. Wu. The effect of2-hydroxypropyl-B-cyclodextrin on the solubility, stability and brain targeting of chemical delivery systems for neuropeptides .................. .257

T. Loftsson, M. Masson and J.F. Sigurjonsdottir. Enhanced complexation efficacy of cyclodextrins .257

J. Savolainen, K. Jarvinen, H. Taipale, P. Jarho, T. Loftsson and T. Jarvinen. Coadministration of a water-soluble polymer increases the usefulness of cyclodextrins in solid oral dosage forms ... .261

M. Masson and T. Loftsson. Evaluation of degradation studies performed in aqueous cyclodextrin solutions ..................................................................... .265

Lj. Tasie, J. Millie, M. Primorac, M. Stupar and S. Simovie. The effect of cellulose ethers on indomethacinlcyclodextrin complexation ............................................. 269

Th. Breul, J.C. Gautier, J.M. Herbert, R. Ghirlando, B. Perly, Ph. Saudemon. Physicochemical characterization and pharmacological properties of different cyclodextrin complexes of a platelet activating factor receptor antagonist: SR 27417 A ................................. 273

A. Gerloczy, M. Vikmon, J. SzejtIi, E. Redenti and P. Ventura. Mutual solubility enhancement by binary and multi component complexation of clomiphene and tamoxifen ................... 277

M. Vikmon, 1. Kolbe, J. Szejtli, E. Redenti and P. Ventura. Preparation and characterization of piroxicam alkali-salt-y-cyclodextrin complexes ........................................ 281

K. Okimoto, M. Miyake, O. Aoki, N. Ohnishi, T. Irie, K. Uekema, R.A. Rajewski and Y.J. Stella. Design and evaluation of a porosity-controlled osmotic pump tablet for chlorpromazine using (SBE) 7m-B-CD ................................................................ 285

E. Fenyvesi, J. Szejtli, F. Trotta, E. Redenti and P. Ventura. Comparison of the solubilizing effect of ethyl carbonate of y-cyclodextrin to other cyclodextrin derivatives . . . . . . . . . . . . . . . . .289

K. Miyake, T. Irie, F. Hirayama and K. Uekema. Improved solubility and oral bioavailability of cyclosporin a by hydrophilic cyclodextrin complexation. . . . . . . . . . . . . . . . . . . . . . .293

K. Kimura, F. Hirayam and K. Uekama. Effect of amorphous B-cyclodextrins on crystallization and polymorphic transition of tolbutamide in solid state . . . . . . . . . . . . . . . . . . . . . . . . . . . . .297

xi

N. Ono, F. Hirayama and K. Uekama. A new method for determination of stability constant of cyclodextrin complexes by membrane permeation technique ............................. .301

S. Tajiri, T. Tahara, K. Tokihiro, T. Irie and K. Uekama. Effects of hydrophilic cyclodextrins in aggregation of recombinant human growth hormone ................................. .305

S. Mieda, F. Hirayama and K. Uekama. Preparation and pharmaceutical evaluation ofheptakis (2,6-di-0-methyl-3-0-acetyl) -B-cyclodextrin ......................................... .309

Y. Okamoto, M. Hirano,A. Kondo, K. Miyake, T. Irie, F. Hirayama and K. Uekama. Characterization of itraconazole/2-hydroxypropyl-B-cyclodextrin inclusion complex in aqueous solution ................................................................ 313

K. Nakanishi, M. Nishi, T. Masukawa, T. Nadai and K. Miyajima. Sustained release and intestinal absorption of drug from the hydrophobic U-, B- and y-cyclodextrin complexes ........ .317

M.D. Veiga and F. Ahsan. Hydroxypropyl garnma-cyclodextrin as a solubiliser and dissolution enhancing agent: the case of tolbutamide-a poorly water-soluble drug ....................... 321

M.D. Veiga and F. Ahsan. Interactions of surfactants with tolbutamide-B-cyclodextrin inclusion compound: the consequence in drug dissolution ....................................... .325

M.D. Veiga, F. Ahsan and M. Merino. Differential scanning calorimetry as an analytical tool in determining the interaction between drug and cyclodextrin ............................... .329

K. KIokkers, E. Fenyvesi, L. Szente and J. Szejtli. Solubility enhancer decreases the dissolution of complexed drugs: effect of sodium-lauryl-sulfate on dissolution profile of complexed drugs ... .333

J. Jicsinszky and I. Kolbe. Interaction between ranitidine hydrochloride and B-cyclodextrin ..... .337

A. Buvari-Barcza and L. Barcza. Physical and chemical changes in the properties of B-cyclodextrin on inclusion complex formation ....................................... .341

S.M. Kbomutow, I.A. Sidorov, D.V. Dovbnya and M.V. Donova. A new nonlinear method on determination of the stability constant for the steroid-cyclodextrin complex .................. .343

J.I. Perez Martinez, M.J. Arias, J.R. Moyano, E. Morillo, A. Rabasco and J.M. Gines. 2,4-Dichlorophenoxyacetic acid u- and B CD inclusion complexes. A IH-nuclear magnetic resonance study ............................................................... .34 7

J.R. Moyano, M.J. Arias, M.e. Ortiz, M.A. Garrido, J.M. Gines and F. Giordano. Investigation of the inclusion complex and stoichiometry of omeprazole with B-CD by 1 H-NMR spectroscopy .. .351

J.F. Sigurjonsdottir, M.Masson and T. Loftsson. Influence of cyclodextrins on the chemical stability of salmon calcitonin in aqueous solution ...................................... .355

T. Loftsson and M. Masson. Complexation propierties of B-cyclodextrin sulfobutylether sodium salt. . . . . . . . . . . . . . . . ..................................................... 359

T. Masson, T. Loftsson and E. Stefansson. How do cyclodextrins enhance drug permeability through biological membranes? ................................................... .363

G.P. Bettinetti, M. Sorrenti,A. Negri, P. MUJ"a, M.T. Faueci and M. Setti. Differential scanning calorimetry analysis of crystallinity changes of naproxen in ground mixtures with maltohexaose. the non cyclic analog of alpha-cyclodextrin .................. . . . . . . . . . . . . .. .367

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G.P.Bettinetti, M. Sorenti,A. Negri, P. Mura and M.T. Faucci. Dissolution rate and thennal properties of naproxen in mixtures with amorphous or crystalline dimethylB-cyclodextrin ....... .371

P. Mura, G. Franchi, M.T. Faucci, A. Manderioli and G. Bramanti. Improvement of econazole solubility in multicomponent systems with cyclodextrins and acids ........................ .375

F. Melani, P. Mura and B. Tracuzzi. Phase-solubility analysis and moleCUlar modeling in the study of naproxen-cyclodextrin interaction ........................................... .379

E. Antoniadou-Vyza, E. Xitiroglou, A. Papadopoulos and T. Mayromoustakos. Potency modification of antibacterial adamantane derivatives by compexation with B-CD and HP-B-CD. Study of their thennotropic properties in dipalmitoyl phosphatidylcholine bilayers containing cholesterol and l3C NMR study of their structures ..................................... .383

C. Pean, A. Wijkhuisen, F. Djedai'ni-Pilard, C. Creminion, J. Grassi and B.Perly. Pharmacological investigations of new peptido-cyclodextrins ............................. .387

M.R. Caira and V.J. Griffith. Characterization of cyclodextrin complexes of (S)-naproxen by X-ray and thennal methods of analysis ............................................... 391

D.V. Dovbnya, S.M. Khomutov, V.M. Nikolayeva and M.V. Donova. CD-medium control of microbial sterol sidechain cleavage ................................................. .395

A. Munoz-Ruiz and P. Paronen. Compressional properties of cyclodextrins ................. .399

C. Pean, J. Fischer, S. Doly,A. Wijkhuisen, F Djedaini- Pilard, R. Shigemoto, e. Creminon, B. Perly and M. Conrath. In vitro and in vivo investigations of the specific binding of substance P-y-cyclodextrin adducts to rat brain NKI receptors .................................... .403

T. Wimmer, M. Regiert and J.P. Moldenhauer. Stabilization of retinol with y-cyclodectrin ..... .407

L. Nieto-Reyes, M.E. Villar-Lopez, J.A. Castro Hermida, E. Ares-Mazas, F. Otero-Espinar and J. Blanco-Mendez. Inclusion study in B-cyc1odextrin and dimetyl-B-cyclodextrin of antiparasitaries in solution and in th" solid state ....................................... .411

M.E. Villar-Lopez, L. Nieto-Reyes, F. Otero-Espinar and J. Blanco-Mendez. Study of inclusion compound of triamcinolone acetonide .............................................. .415

P. Ramos, E. Alvarez Parrilla, F. Meijide, J.A. Seijas, E. Rodriguez Nunez and J. Vazquez Toto. Complexation of bile salts by B-cyclodextrin and derivatives ............................. .419

D. Wouessidjewe and C. Rosselli. lHNMR contribution to prove the fonnation of inclusion complex between nimesulide and B-cyc1odextrin and its hydrophilic derivatives ............... .423

N.R. Russell, N. Van Hoof and M. McNamara. Complexation of amino acids by 6A.. (hydroxyethylamino )-6A-deoxy-B-cyclodextrin (B-CDea) and the Metallo-derivatives in Aqueous Solution ..................................................................... .427

M.e. Pineiro Marinez,A. Carro Martinez, P. De Labra Pinon, M.B. Perez Marcos, J.L. Vila Jato and J.J. Torres Labandeira. Effect of the complexation of ciprofloxacin and norfloxacin with cyclodextrin derivatives on its dissolution characteristics ................... .433

M. Echcrzarreta-Lopez, T. Esclusa-Diaz, J.L. Vila-Jato and J.J. Torres-Labandeira. Effect of hydroxypropyl-Il-cyclodextrin on the stability of pilocarpine in solution. Influence of the complex preparation . . . . . . . . . . . . . . . . . . .. .437

xiii

B. Pose Vilarnovo, L. Santana Penin, M.B. Perez-Marcos, J.L.Vila-Jato and J.J. Torres-Labandeira. Dissolution behaviour of diclofenac sodium-l3- and hydroxypropyl-l3-cyclodextrin inclusion complexes ............ . . . . . . . . . . . . . . . . . . . . . . . . . . .441

E.A. Zannou, S. Shiraishi, Y.M. Rao and Y.J. Stella. Effect of (SBEhm-l3-CD on methylprednisolone transport across ethylcellulose microporous membranes .............. .445

M. Skiba, S. Shawky-Tous, D. Wouessidjewe and D. Duchene. Optimization of entrapment of metronidazole in amphiphilic 13-cyclodextrin nanospheres .............. . .............. .449

P.B. Weisz, M.M. Joullie, P. Portonovo, E.1. Marx, J.M. Tarbell, H. Kaji, R.L. Wilensky and E. Macarak. Cyclodextrin polysulfates in cell biology and therapeutic pharmacology . . . .453

Y. Stella, K. Uekama, T. Irie, Y.M. Rao, E.A. Zannou, R.A. Rajewski, S. Shiraishi and K. Okimoto. The use of (SBEhm-l3-CD (CAPISTOLTM) as a solubilizing and osmotic agent for controlled and complete oral delivery of poorly water soluble drugs ........................ .459

H.O.S. Lima, A.M. Moraes and M.H.A. Santana, F.F. De Moraes and G.M. Zanin. Preparation and characterization of inclusion complexes of cyc10dextrins and tuberculosis primary treatment drugs . . . . . . . . . . . .......... .463

B. Cappello, M. Iervolino, M.1. La Rotonda and A. Miro. Influence of different cyclodextrins on physico-chemical and pharmacological properties of etodolac . . . . . . . . . .. .467

M.S. Worthington, B.D. Glass and L.J. Penkler. Solid-state nifedipine-cyclodextrin photostability studi es ........... .471

P.R. Vavia and N.A.Adhage. Inclusion complexation ofnimesulide with l3-cyclodextrins and its formulation into tablets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .475

P.R. Vavia and N.A.Adhage. Inclusion complexation oftolfenamic acid with l3-cyclodextrins and its formulation into tablets . . . . . . . . . . . . . . . . . . . . . . . .. .479

M.E. Villar-Lopez, F. Otero-Espinar and J. Blanco-Mendez. Preparation by extrusion! spheronization of triamcinolone 13-cyclodextrin pellets as a fast release dosage form ...... .483

4. CYCLODEXTRINS IN CHEMISTRY

B. Andi and R. Yazdanparast. Renaturation of SDS- and thermally denaturated cellulase system by a-cyclodextrin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .489

I. Uemasu, S. Kushiyama and R. Aizawa. Absorption and recovery of volatile chlorinated hydrocarbons by use of aqueous solutions of branched cyclodextrins . .493

E. Nunez Delicado, M. Sojo,A. Sanchez Ferrer and F. Garcia Ca.-mona. Oxidation of hydrophobic o-diphenols by lipoxygenase in the presence of cyclodextrins .. . ... .497

Y. Cucinotta, G. Grasso, G. Maccarrone,A. Mazzaglia and G. Vecchio. Inclusion properties, metal ion coordination ability and analytical applications of trehalose capped cyclodextrins . . .. 501

LN. Topchicva. Covalent and non-covalent adducts based on cyclodextrins and poly (ethyleneoxide) .. . .... 50S

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F. Trotta and D. Cantamessa. The effect of cyclodextrins on the hydrolysis of benzyl halides. .509

J. Jicsinsky. Regioselective substitution of cyclodextrins without using protecting groups ....... .513

T. Tanabe and A. Veno. Molecular imprinting system using cyclodextrin ................. 517

M. Tamura, De Gao,A. Veno. Energy transfer in naphthalene-containing rotaxane and polyrotaxane . . . . . . . . . . . . . . .............. 521

J.M. Lopez-Nicolas, R. Bru, J.M. Lopez-Roca and F. Garcia Carmona. Kinetic study of the oxidation of linoleic acid by soybean Iipoxygenase in presence of 13-cyclodextrin ............... 525

C. Marie, L. Leclercq, M. Morcellet and B. Martel. Esterolysis reaction catalysed by 13-cyclodextrin: influence of the tacticity of water-soluble polymers ............ . ....... 529

C. Roselli, B. Perly, S. Cassel, P. Rollin, R. lori, L, Manici, S. Palmieri. Cyclodextrin assistance in the enzymatic degradation of the moringa glucosinolate . . . . .533

A. Fragoso, R. CAo and Y. Rodriguez. Kinetic effects on the dismutation of superoxide radical by copper (II) complexes of cyclodextrin-based SOD models . . . . . . . . . . . . . . . . .537

C.J. Easton, J.B. Harper and S.F. Lincoln. Cyclodextrins as molecular templates .541

M.G. Bakker, M.N. Lehmann and C. Chin. Cyclodextrin radicals produced by photochemical hydrogen abstraction by ketones and nitrogen heterocycles . . . . . . . . . . . . . . . . . . . . . . .. .545

K. Mikuni, K. Hara, W. Qiong, K. Hara and H. Hashimoto. Oxidative stability of docosa hexaenoic acid oil (triglyceride form) included in cyclodextrins . . . . . . . . . . . . . . . . . . . . . . . . .549

E. Almirall, A. Fragoso and R. Cao. Molecular recognition of a self-assembled monolayer of a polydithiocarbamate derivative of 13-cyclodextrin on silver ............................... .553

M. Sueiro, R. Vazquez Picos, E. Alvarez Parrilla, F. Meijide, P. Ramos, E. Rodriquez Nunez and J. Vazquez Tato. Inhibition by cyclodextrins of nitro sat ion reactions ................... .557

E.1. Popova, I. N. Karpov, I. N. Topchieva and O. I. Mikhalev. Molecular necklaces containing reporter molecules . . . . . . . . . . . . . . . . . . .................... .563

J. Pozuelo, F. Mendicuti and E. Saiz. Molecular dynamics simulations of polyrotaxanes formed by poly( oxytrimethylene) and a-cyclodextrins .............. .567

A. Gordano, F. Trotta, C. Manferti, E. Tocci and E. Drioli. Kinetic behaviour of ll-cyclodextrins immobilized in PEEK-WC membranes. . . . . . . . . . . . . . ................. 571

5. CYCLODEXTRINS IN ENVIRONMENT SCIENCES

L. Szente, E. Fenyvesi and J. Szejtli. Application of cyclodextrins in nuclear waste management .. 577

M. Marzona and R. Carpignano. Optimization of fuel oil desulfuration by fl-cyclodextrin ...... 583

K. Hattori and S. Murai. Inclusion of environmental contaminants with fl-cyciodextrin, and adsorption and removal by fl-cyclodextrin polymer.

S.P. Vila I'\o"a. J.E.C. Da Silva. S. Alves .11' .• H.C.I'\ Batista. J.D.F. Dc Sousa. G.F. De Sa and

.587

O.M.L. I\Ialta. Luminescent beha\lOr of Eu(ntah dipy complex in the presence of fl-cyclodextrins ... 59 I

xv

E. Morillo, R. Fernandez-Urrusuno, M.J.Arias, J.I. Perez-Martinez and J.M. Gines. Study of complexation between the pesticide chlorpyrifos and B- and HP-B-cyclodextrins ............. 595

M. Molnar, E. Fenyvesi, K. Gruiz and J. Szejtli. Application of randomly methylated B-cyclodextrin for bioremediation of contaminated soil .................................. 599

6. CYCLODEXTRINS AS CHIRAL SELECTORS

A. Mosandl, F. Podebrad, D. Bartschat, A. Kaunzinger, S. Reichert and M. Wiist. Modified cyclodextrins as versatile chiral stationary phases in flavour chemistry and life sciences ......... 605

A.G. Meyer, C.J. Easton, S.F. Lincoln and G.W. Simpson. B-cyclodextrins as molecular scaffolds to reverse the regioselectivity of nitrile oxide cycloadditions ....................... 609

A. Salvador, E. Varesio, J.L Veutbey and M. Dreux. Analysis and characterisation of commercial DM-B-CD. Influence of mixture composition in chiral separation in capillary electrophoresis and supercritical fluid chromatography ............................................... 613

I. Caron, C. Elfakir, M. Dreux, H. Leveque and R. Duval. Pure monopentenylated B-cyclodextrin as chiral agent: purity check by LC-ELSD and LC-MS .................................. 617

Z. Juvancz and G. SzejtIi. Cyclodextrins dominate the chiral chromography ................. 621

F. Djedaini-Pilard, M. Gosnat, V. Brucato-Mauclaire, C. Creminon, J.P. Dalbiez, S. Pilard, W, Luijten and B. Perly. New asymmetric B-cyclodextrin derivatives designed for chiral recognition .................................................................... 625

7. CYCLODEXTRIN COMPLEXES AND ITS CHARACTERIZATION

F.e. Machado, V.M. De Bellis and R.D. Sinisterra. Study of the formation of the inclusion compound between rhodium (II)3-chlorocinnamate and B-cyclodextrin ...................... 631

H. Yoshii, T. Kometani, T. Furuta, Y. Watanabe, V-V. Linko and P. Linko. Formation of inclusion complex of cyclodextrin in organic solvents and alcohols under anhydrous conditions ........... 635

E. Fenyvesy, L Jicsinszky, J. Szjetli and R. Schwarzenbach. Inclusion complexes ofUV filters in solution and in solid state ....................................................... 639

A. Nakamura, J.-H. Fuhrhop. Encapsulation of porphyrins by y-cycIodextrin ................ 645

S. Yasuda, Y. Goto, K. Miyake, K. Hata, J. Sumaoka, A. Harada, M. Komiyama and H. Skigekawa. Guest-dependent ordering of the self-assembled cyclodextrin inclusion complexes studied by scanning tunneling microscopy .................................... 649

M. Manabe, H. Kawamura, H. Katuura and M. Shiomi. The application of differential conductivity method to the determination of binding constant of B-cyclodextrin with sodium perfiuorooctanoate .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .... 653

A. Buvari-Barcza and L. Barcza. Influence of the guest, the type and degree of substitution on inclusion complex formation of sustituted B-cyclodextrins . . ......................... 657

e. Pean, F. Djedalni-PiJard, B. Perly. Reliable NMR experiments for the determination of the structure of cyclodextrin inclusion complexes in solution . . . .. ............... .659

xvi

D. Landy, S. Fourmentin, F. Elhoujhaji and G. Surpateanu. IH-NMR Circular dichroism and UV-visible spectroscopic study of inclusion complexes formation between 0-, m- and p-hydroxyphenol and B-cyclodextrin ................................................. 663

G. Gonzlilez Gaitano, T. Sanz, R. Gabarro, J.A. Rodriquez Cheda, M.e. Saez and G. Tardajos. Molar partial properties in host-guest systems: application to the inclusion complexes between B-cyclodextrin and sodium alkanoates ............................................... 667

T.C. Werner, J. Larose and J.S. Anderson. The binding of 2-naphthamides to B-cyclodextrin .... 671

E. Benes and G. SzjetIi. Publications - new products, is there any correlation? ................ 675

8. CYCLODEXTRINS IN FOOD AND COSMETICS

M. Bacquet, T.N.T. Phan, G. Crini, B. Martel and M. Morcellet. Preliminary study of dye sorption by various kinds of insoluble sorbents containing B-cyclodextrin .................... 681

T. Furuta, H. Yoshii, I. Hashimoto, Y. Katayama, X. Liu, V-V. Linko and P. Linko. Release characteristics of hydrophobic flavor encapsulated in cyclodextrins ......................... 685

A. Moreira da Silva, J.M.A. Empis and JJ.C. Teixeira-Dias.A IH-NMR study of inclusion compounds of model food flavours in B-cyclodextrin .................................... 689

L. Mentik. B-cyclodextrin emulsion: mecanism of emulsification and application to the preparation of green metalworking fluids ............................................. 693

Subject index ................................................................. 697

Dear Colleagues and Friends,

Welcome to this small and wonderful town in the Westcorner of Spain. After the discovery of the tomb of the Apostle St. James, the city has become the goal of thousands of pilgrims who came from all over Europe to venerate the Apostle and looking for a renew of their soul and life. This has not changed nowadays, but Santiago has become a place for cultural and scientific pilgrimage. It's University celebrated its SOoth anniversary in 1995, and Santiago became a scientific mee­tingpoint for the thousands of researchers that participated in the Conferences and Meetings.

This is the 9th International Symposium on Cyclodextrins. Previous Cyclodextrin Meetings were very successful and we wish you all the best for this one. Cyc10dextrin technology has grown up a lot since the discovery of these substances at the beginning of the Century. Many people from all over the world have contri­buted to this development, looking for its characterization and for new applications. This is not the end of the way and our participation in this Symposium proves it. We have here the opportunity to continue the trail, renew our knowledge and share with our friends the scientific uneasiness.

Have a nice stage in Santiago de Compostela and we look forward to being able to welcome you again some other time in future!

ACKNOWLEDGEMENTS The generous financial support of the following sponsors made it possible to organize this Symposium:

UNIVERSITY OF SANTIAGO DE COMPOSTELA. (Spain)

Secretaria de Estado de Universidades e Investigacion (Spain)

XUNTA DE GALICIA. Direccion Xeral de Investigacion (Spain)

The Nagai Foundation (Japan)

CYCLOLAB Ltd. (Hungary)

Cyclodextrin Technology Development Inc. CTD Inc. (USA)

CyDex, L.C. (USA)

Wacker-Chemie GmbH (Germany)

Asahi Foods Corporation (Japan)

Nihon Shokuhin Kako Co., Ltd (Japan)

Mercian Corporation (Japan)

Ensuiko (Bio Research Corp. of Yokohama. Japan)

Cyclodextrin Society of Japan

GlaxoWelicome, SA(Spain)

Chiesi Farmaceutici S.pA (Italy)

Kluwer Academic Publishers (The Netherlands)

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Special thanks to Mr. Carlos M. Varela ~lla, your help made it possible.