Skip to main content
SpringerLink
Log in

Phase solubility and FTIR-ATR studies of idebenone/sulfobutyl ether β-cyclodextrin inclusion complex

  • Original Article
  • Published:
Journal of Inclusion Phenomena and Macrocyclic Chemistry Aims and scope Submit manuscript

Abstract

The favourable accessibility offered by sulfobutyl ether β-cyclodextrin (SBE-β-CD) for the complexation with idebenone (IDE) has been probed, as a function of temperature, in liquid state, by phase solubility study, and, in solid state, by FTIR-ATR technique. The phase solubility results indicated the formation of a IDE/SBE-β-CD inclusion complex with 1:1 molar ratio (AL type diagram), whose apparent stability constants at T = 300, 310, and 320 K have been estimated according to the Higuchi–Connors method. The formation of the inclusion complex has been confirmed on a freeze-dried and a co-precipitated product by FTIR-ATR spectroscopy, monitoring the changes induced by complexation on some characteristic vibrational bands of IDE. Quantitative studies, performed in a wide T range, from T = 250 K to T = 340 K, allowed us to extract information on the effect of temperature on the different hydrogen-bonded environments involving host, guest, and crystallization water molecules. Again, complexation is proved to enhance the stability of the guest, at least in the explored T range.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Degli Esposti, M., Ngo, A., Ghelli, A., Benelli, B., Carelli, V., McLennan, H., Linnane, A.W.: The interaction of Q analogs, particularly hydroxydecyl benzoquinone (idebenone), with the respiratory complexes of heart mitochondria. Arch. Biochem. Biophys. 330, 395–400 (1996)

    Article  CAS  Google Scholar 

  2. Geromel, V., Darin, N., Chrétien, D., Bénit, P., DeLonlay, P., Rötig, A., Munnich, A., Rustin, P.: Coenzyme Q(10) and idebenone in the therapy of respiratory chain diseases: rationale and comparative benefits. Genet. Metab. 77, 21–30 (2002)

    Article  CAS  Google Scholar 

  3. Gutzmann, H., Hadler, D.: Sustained efficacy and safety of idebenone in the treatment of Alzheimer’s disease: update on a 2-year double-blind multicentre study. J. Neural Transm. Suppl. 54, 301–310 (1998)

    CAS  Google Scholar 

  4. Thal, L.J., Grundman, M., Berg, J., Ernstrom, K., Margolin, R., Pfeiffer, E., Weiner, M.F., Zamrini, E., Thomas, R.G.: Idebenone treatment fails to slow cognitive decline in Alzheimer’s disease. Neurology 61, 1498–1502 (2003)

    Article  CAS  Google Scholar 

  5. Schols, L., Meyer, C.h., Schmid, G., Wilhelms, I., Przuntek, H.: Therapeutic strategies in Friedreich’s ataxia. J. Neural Transm. Suppl. 68, 135–145 (2004)

    Article  Google Scholar 

  6. Genova, M.L., Pich, M.M., Biondi, A., Bernacchia, A., Falasca, A., Bovina, C., Formiggini, G., Parenti Castelli, G., Lesnaz, G.: Mitochondrial production of oxygen radical species and the role of coenzyme Q as an antioxidant. Exp. Biol. Med. 228, 506–513 (2003)

    CAS  Google Scholar 

  7. Gillis, J.C., Benefield, P., McTavish, D.: Idebenone. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in age-related cognitive disorders. Drugs Aging 5, 133–152 (1994)

    Article  CAS  Google Scholar 

  8. Loftsson, T., Jarho, P., Masson, M., Jarvinen, T.: Cyclodextrins in drug delivery. Expert. Opin. Drug Deliv. 2, 335–351 (2005)

    Article  CAS  Google Scholar 

  9. Frank, D.W., Gray, J.E., Weaver, R.N.: Cyclodextrin nephrosis in the rat. Am. J. Pathol. 83, 367–382 (1976)

    CAS  Google Scholar 

  10. Irie, T., Uekama, K.: Pharmaceutical application of cyclodextrins. III. Toxicological issues and safety evaluation. J. Pharm. Sci. 86, 147–162 (1997)

    Article  CAS  Google Scholar 

  11. Rajewski, R.A., Traiger, G., Bresnahan, J., Jaberaboansari, P., Stella, V.J., Thompson, D.O.: Preliminary safety evaluation of parenterally administered sulfoalkyl ether β-cyclodextrin derivatives. J. Pharm. Sci. 84, 927–932 (1995)

    Article  CAS  Google Scholar 

  12. Stella, V.J., Rajewski, R.A.: Cyclodextrins: their future in drug formulation and delivery. Pharm. Res. 14, 556–567 (1997)

    Article  CAS  Google Scholar 

  13. Luna, E., Vander Velde, D.G., Tait, R.J., Thompson, D.O., Rajewski, R.A., Stella, V.J.: Isolation and characterization by NMR spectroscopy of three monosubstituted 4-sulfobutyl ether derivatives of cyclomaltoheptaose (β-cyclodextrin). Carbohydr. Res. 299, 111–118 (1997)

    Article  CAS  Google Scholar 

  14. Holvoet, C., Heyden, Y.V., Plaizier-Vercammen, J.: Inclusion complexation of diazepam with different cyclodextrins in formulations for parenteral use. Pharmazie 60, 598–603 (2005)

    CAS  Google Scholar 

  15. Järvinen, T., Järvinen, K., Urtti, A., Thompson, D., Stella, V.J.: Sulfobuthyl ether beta-cyclodextrin (SBE-beta-CD) in eyedrops improves the tolerability of a topically applied pilocarpine prodrug in rabbits. J. Ocul. Pharmacol. Ther. 11, 95–106 (1995)

    Article  Google Scholar 

  16. Puglisi, G., Ventura, C.A., Fresta, M., Vandelli, M.A., Cavallaro, G., Zappalà, M.: Preparation and physico-chemical study of inclusion complexes between idebenone and modified β-cyclodextrin. J. Incl. Phenom. 24, 193–210 (1996)

    Article  CAS  Google Scholar 

  17. Higuchi, T., Connors, K.A.: Phase solubility techniques. Adv. Anal. Chem. Instr. 4, 117–212 (1965)

    CAS  Google Scholar 

  18. Gibaud, S., Zirar, S.B., Mutzenhardt, P., Fries, I., Astier, A.: Melarsoprol-cyclodextrins inclusion complexes. Int. J. Pharm. 306, 107–121 (2005)

    Article  CAS  Google Scholar 

  19. Maréchal, Y.: Observing the water molecule in macromolecules and aqueous media using infrared spectrometry. J. Mol. Struct. 648, 27–47 (2003)

    Article  Google Scholar 

  20. Szejtli, J.: Cyclodextrins and their inclusion compounds. Akademiai Kiado, Budapest (1982)

    Google Scholar 

  21. Dotsikas, Y., Kontopanou, E., Allagiannis, C., Loukas, Y.L.: Interaction of 6-p-toluidinylnaphthalene-2-sulphonate with β-cyclodextrin. J. Pharm. Biomed. Anal. 23, 997–1003 (2000)

    Article  CAS  Google Scholar 

  22. Jara, F., Dominquez, M., Rezende, M.C.: The interaction of solvatochromic pyridiniophenolates with cyclodextrins. Tetrahedron 62, 7817–7823 (2006)

    Article  CAS  Google Scholar 

  23. Aramă, C., Nicolescu, C., Nedelcu, A., Monciu, C.M.: Synthesis and characterization of the inclusion complex between repaglinide and sulfobutylether-β-cyclodextrin (Captisol®). J. Incl. Phenom. Macrocycl. Chem. 70, 421–428 (2011)

    Article  Google Scholar 

  24. Crupi, V., Guella, G., Majolino, D., Mancini, I., Rossi, B., Stancanelli, R., Venuti, V., Verrocchio, P., Viliani, G.: T-dependence of the vibrational dynamics of IBP/diME-β-CD in solid state: a FT-IR spectral and quantum chemical study. J. Mol. Struct. 972, 75–80 (2010)

    Article  CAS  Google Scholar 

  25. Crupi, V., Majolino, D., Venuti, V., Guella, G., Mancini, I., Rossi, B., Verrocchio, P., Viliani, G., Stancanelli, R.: Temperature effect on the vibrational dynamics of cyclodextrin inclusion complexes: investigation by FTIR-ATR spectroscopy and numerical simulation. J. Phys. Chem. A 114, 6811–6817 (2010)

    Article  CAS  Google Scholar 

  26. Gavira, J.M., Hernanz, A., Bratu, I.: Dehydration of β-cyclodextrin: an IR ν(OH) band profile analysis. Vib. Spectrosc. 32, 137–146 (2003)

    Article  CAS  Google Scholar 

  27. Crupi, V., Ficarra, R., Guardo, M., Majolino, D., Stancanelli, R., Venuti, V.: UV–vis and FTIR-ATR spectroscopic techniques to study the inclusion complexes of genistein with β-cyclodextrins. J. Pharm. Biomed. Anal. 44, 110–117 (2007)

    Article  CAS  Google Scholar 

  28. Stancanelli, R., Ficarra, R., Cannavà, C., Guardo, M., Calabrò, M.L., Ficarra, P., Ottanà, R., Maccari, R., Crupi, V., Majolino, D., Venuti, V.: UV–vis and FTIR-ATR characterization of 9-fluorenon-2-carboxyester/(2-hydroxypropyl)-β-cyclodextrin inclusion complex. J. Pharm. Biomed. Anal. 47, 704–709 (2008)

    Article  CAS  Google Scholar 

  29. Cannavà, C., Crupi, V., Ficarra, P., Guardo, M., Majolino, D., Stancanelli, R., Venuti, V.: Physicochemical characterization of coumestrol/β-cyclodextrins inclusion complexes by UV–vis and FTIR-ATR spectroscopies. Vib. Spectrosc. 48, 172–178 (2008)

    Article  Google Scholar 

  30. Bratu, I., Veiga, F., Fernandes, C., Hernanz, A., Gavira, J.M.: Infrared spectroscopic study of triacetyl-β-cyclodextrin and its inclusion complex with nicapiridine. Spectroscopy 18, 459–467 (2004)

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dipartimento Farmaco-Chimico, Facoltà di Farmacia, Università di Messina, Viale Annunziata, 98168, Messina, Italy

    C. Cannavà, M. Guardo, R. Stancanelli, S. Tommasini & C. A. Ventura

  2. Dipartimento di Fisica, Facoltà di Scienze MM. FF. NN., Università di Messina, Viale Ferdinando Stagno D’Alcontres 31, Messina, Italy

    V. Crupi, D. Majolino & V. Venuti

Authors
  1. C. Cannavà
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. V. Crupi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Guardo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. Majolino
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R. Stancanelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S. Tommasini
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C. A. Ventura
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. V. Venuti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C. Cannavà.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cannavà, C., Crupi, V., Guardo, M. et al. Phase solubility and FTIR-ATR studies of idebenone/sulfobutyl ether β-cyclodextrin inclusion complex. J Incl Phenom Macrocycl Chem 75, 255–262 (2013). https://doi.org/10.1007/s10847-012-0110-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10847-012-0110-3

Keywords

Search

Navigation