Skip to main content
SpringerLink
Log in

Comparison between 2-hydroxypropyl-β-cyclodextrin and 2-hydroxypropyl-γ-cyclodextrin for inclusion complex formation with danazol

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

Abstract

Complexation in solution between danazol and two different cyclodextrins [2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and 2-hydroxypropyl-γ-cyclodextrin (HP-γ-CD)] was studied using phase solubility analysis, and one- and two-dimensional 1H-NMR. The increase of danazol solubility in the aqueous cyclodextrin solutions showed a linear relationship (AL profile). The apparent stability constant, K 1:1, of each complex was calculated and found to be 51.7 × 103 and 7.3 × 103 M−1 for danazol–HP-β-CD and danazol–HP-γ-CD, respectively. 1H-NMR spectroscopic analysis of varying ratios of danazol and the different cyclodextrins in a mixture of EtOD–D2O confirmed the 1:1 stoichiometry. Cross-peaks, from 2D ROESY 1H-NMR spectra, between protons of danazol and H3′ and H5′of cyclodextrins, which stay inside the cyclodextrin cavity, proved the formation of an inclusion complex between danazol and the cyclodextrins. For HP-β-CD, the inclusion complex is formed by entrance of the isooxazole and the A rings of danazol in the cyclodextrin cavity. For HP-γ-CD, two different inclusion structures may exist simultaneously in solution: one with the isooxazole and A ring in the cavity and the other with the C and D ring inside the cavity. DLS showed that self-aggregation of the CD’s was absent in the danazol HP-β-CD system up to a CD concentration of 10% and in the danazol HP-γ-CD system up to a CD concentration of 5%.

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

Similar content being viewed by others

References

  1. Vercellini, P., Somigliana, E., Vigano, P., Abbiati, A., Barbara, G., Crosignani, P.G.: Endometriosis: current therapies and new pharmacological developments. Drugs 69, 649–675 (2009)

    Article  CAS  Google Scholar 

  2. Maia, H., Casoy, J., Valente, J.: Is aromatase expression in the endometrium the cause of endometriosis and related infertility? Gynecol. Endocrinol. 25, 253–257 (2009)

    Article  CAS  Google Scholar 

  3. Devalia, H.L., Layer, G.T.: Current concepts in gynaecomastia. Surgeon 7(2), 114–119 (2009)

    Article  CAS  Google Scholar 

  4. Frank, M.M.: Hereditary angioedema. J. Allergy Clin. Immunol. 121, S398–S401 (2008)

    Article  CAS  Google Scholar 

  5. Araujo, A., Lima, M.A., Syvia, M.T.T.: Human T-lymphotropic virus 1 neurologic disease. Curr. Treat. Options Neurol. 10, 193–200 (2008)

    Article  Google Scholar 

  6. Daou, S., Federici, L., Zimmer, J., Maloisel, F., Serraj, K., Andrès, E.: Idiopathic thrombocytopenic purpura in elderly patients: a study of 47 cases from a single reference center. Eur. J. Intern. Med. 19, 447–451 (2008)

    Article  Google Scholar 

  7. Chen, X., Vaughn, J.M., Yacaman, M.J., Williams III, R.O., Johnston, K.P.: Rapid dissolution of high-potency danazol particles produced by evaporative precipitation into aqueous solution. Pharm. Sci. 93, 1867–1878 (2004)

    Article  CAS  Google Scholar 

  8. Badawy, S., Ghorab, M., Adeyeye, C.: Characterization and bioavailability of danazol-hydroxypropyl-β-cyclodextrin coprecipitates. Int. J. Pharm. 128, 45–54 (1996)

    Article  CAS  Google Scholar 

  9. Brewster, M., Loftsson, T.: Cyclodextrins as pharmaceutical solubilizers. Adv. Drug Del. Rev. 59, 645–666 (2007)

    Article  CAS  Google Scholar 

  10. Szejtli, J.: Introduction and general overview of cyclodextrin chemistry. Chem. Rev. 98, 1743–1754 (1998)

    Article  CAS  Google Scholar 

  11. Mosher, G.L., Thompson, D.O.: Complexation cyclodextrin. In: Swarbrick, J. (ed.) Encyclopedia of Pharmaceutical Technology, pp. 671–696. Marcel Dekker, New York (2007)

    Google Scholar 

  12. Carrier, R.L., Miller, L.A., Ahmed, I.: The utility of cyclodextrin for enhancing oral bioavailability. J. Control. Release 123, 78–99 (2007)

    Article  CAS  Google Scholar 

  13. Jadhav, G.S., Vavia, P.R.: Physicochemical, insilico and in vivo evaluation of danazol-β-cyclodextrin complex. Int. J. Pharm. 352, 5–16 (2007)

    Article  Google Scholar 

  14. Djedäine, F., Lin, S.Z., Perly, B., Wouessidjewe, D.: High-field nuclear magnetic resonance techniques for the investigation of a β-cyclodextrin: indomethacin inclusion complex. J. Pharm. Sci. 79, 643–646 (1990)

    Article  Google Scholar 

  15. Salvatierra, D., Jaime, C., Virgili, A., Sánchez-Ferrando, F.: Determination of the inclusion geometry for the β-cyclodextrin/benzoic acid complex by NMR and molecular modeling. J. Org. Chem. 61, 9578–9581 (1996)

    Article  CAS  Google Scholar 

  16. Higuchi, T., Connors, K.A.: Phase solubility technique. Adv. Anal. Chem. Inst. 4, 212–217 (1965)

    Google Scholar 

  17. Keller, R.: The Computer Aided Resonance Assignment Tutorial, 1st edn. CANTINA Verlag, Goldau (2004)

    Google Scholar 

  18. Loftsson, T., Brewster, M.: Pharmaceutical applications of cyclodextrins. J. Pharm. Sci. 85, 1017–1025 (1996)

    Article  CAS  Google Scholar 

  19. Uekama, K., Fujinaga, T., Otagiri, M., Yamasaki, M.: Inclusion complexations of steroid hormones with cyclodextrins in water and in solid phase. Int. J. Pharm. 10, 1–15 (1982)

    Article  CAS  Google Scholar 

  20. Larsen, K.L., Acchmann, F.L., Wimmer, R., Stella, V.J., Kjølner, U.M.: Phase solubility and structure of the inclusion complexes of prednisolone and 6α-methylprednisolone with various cyclodextrin. J. Pharm. Sci. 94, 507–515 (2005)

    Article  CAS  Google Scholar 

  21. Martin, A.: Complexation and protein binding. In: Martin, A. (ed.) Physical Pharmacy, 4th edn, pp. 251–283. Lippincott Williams and Wilkins, Baltimore (1993)

    Google Scholar 

  22. C Fernandes, C.M., Carhalvo, R.A., da Costa, S.P., Veiga, F.: Multimodal molecular encapsulation of nicardipine hydrochloride by β-cyclodextrin, hydroxypropyl-β-cyclodextrin and triacetyl-β-cyclodextrin in solution. Structural studies by 1H NMR and ROESY experiments. Eur. J. Pharm. Sci. 18, 285–296 (2003)

    Article  Google Scholar 

  23. Ganza-Gonzalez, A., Vila-Jato, J.L., Anguiano-Igea, S., Otero-Espinar, F.J., Blanco-Méndez, J.: A proton nuclear magnetic resonance study of the inclusion complex of naproxen with β-cyclodextrin. Int. J. Pharm. 106, 179–185 (1994)

    Article  CAS  Google Scholar 

  24. Másson, M., Loftsson, T., Jónsdóttir, S., Fridriksdóttir, H., Peterson, D.S.: Stabilisation of ionic drugs through complexation with non-ionic and ionic cyclodextrins. Int. J. Pharm. 164, 45–55 (1998)

    Article  Google Scholar 

  25. Do, T.T., Nauwelaerts, K., Froeyen, M., Baudemprez, L., Van Speybroeck, M., Augustijns, P., Annaert, P., Martens, J., Van Humbeeck, J., Van den Mooter, G.: Comparison of the complexation between methylprednisolone and different cyclodextrins in solution by 1H-NMR and molecular modeling studies. J. Pharm. Sci. 99(9), 3863–3873 (2010)

    Google Scholar 

  26. Chankvetadze, B., Lomsadze, K., Burjanadze, N., Breitkeutz, J., Pinto, G., Chesse, M., Berganthal, K., Blaschke, G.: Comparative enantioseparations with native beta-cyclodextrin, randomly acetylated beta-cyclodextrin and heptakis-(2, 3-di-O-acetyl)-beta-cyclodextrin in capillary electrophoresis. Electrophoresis 24, 1083–1091 (2003)

    Article  CAS  Google Scholar 

  27. Messner, M., Kurkov, S.V., Jansook, P., Loftsson, T.: Self-assembled cyclodextrin aggregates and nanoparticles. Int. J. Pharm. 387, 199–208 (2010)

    Article  CAS  Google Scholar 

Download references

Acknowledgments

A K.U. Leuven Industrial Research Fund (IOF) provided financial support for this study. MVS acknowledges the Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT-Vlaanderen) for a PhD grant.

Author information

Authors and Affiliations

  1. Laboratory for Pharmacotechnology and Biopharmacy, KU Leuven, Herestraat 49, 3000, Leuven, Belgium

    Thao Do Thi, Michiel Van Speybroeck, Patrick Augustijns, Pieter Annaert & Guy Van den Mooter

  2. Laboratory for Medicinal Chemistry, KU Leuven, Leuven, Belgium

    Koen Nauwelaerts & Luc Baudemprez

  3. Department of Chemical Engineering, KU Leuven, Leuven, Belgium

    Jan Vermant

  4. Centre for Surface Chemistry and Catalysis, KU Leuven, Leuven, Belgium

    Johan Martens

  5. Department of Metallurgy and Materials Engineering, KU Leuven, Leuven, Belgium

    Jan Van Humbeeck

Authors
  1. Thao Do Thi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Koen Nauwelaerts
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Luc Baudemprez
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michiel Van Speybroeck
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jan Vermant
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Patrick Augustijns
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Pieter Annaert
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Johan Martens
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jan Van Humbeeck
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Guy Van den Mooter
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Guy Van den Mooter.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Thi, T.D., Nauwelaerts, K., Baudemprez, L. et al. Comparison between 2-hydroxypropyl-β-cyclodextrin and 2-hydroxypropyl-γ-cyclodextrin for inclusion complex formation with danazol. J Incl Phenom Macrocycl Chem 71, 137–147 (2011). https://doi.org/10.1007/s10847-010-9917-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10847-010-9917-y

Keywords

Search

Navigation