Skip to main content
Log in

“Surface water” and “strong-bonded water” in cyclodextrins: a Karl Fischer titration approach

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

Abstract

Cyclodextrins are some of the most used carriers for bioactive compounds (as host–guest complex) and many factors influence the association–dissociation of this complex, some of them being related to hydrophobicity. In the solid state, cyclodextrins contain two types of water molecules: “surface” water molecules (especially close to the crystal surface) and “strong-bonded” water molecules (especially from the cyclodextrin cavity), but the classification is hard to do, and the concentration of these water molecules are relatively difficult to estimate by simple methods.

In the present study we used the volumetric Karl Fischer titration to estimate these types of water molecules in cyclodextrins by means of the rate of water reaction (related to diffusion from cyclodextrin crystals). “Surface” water molecules are titrated with rates between 1.8–2.8 mM/s for α-cyclodextrin, while for β-cyclodextrin these rates are little bit higher (2.9–3.4 mM/s). The rates corresponding to “strong-bonded” water molecules are approximately tens fold lower (0.05–0.3 mM/s for α-cyclodextrin and 0.15–0.33 mM/s for β-cyclodextrin). The approximate ratio between “surface” and “strong-bonded” water molecules could also be estimated by this simple and rapid method.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

KFT:

Karl Fischer titration

aCD:

α-cyclodextrin

bCD:

β-cyclodextrin

References

  1. Challa, R., Ahuja, A., Ali, J., Khar, R.K.: Cyclodextrins in drug delivery: an updated review. AAPS PharmSciTech 6, E329–E357 (2005). doi:10.1208/pt060243

    Article  Google Scholar 

  2. Sliwa, W., Girek, T.: Noncovalently-bound cyclodextrin dimers and related compounds (review). Chem. Heterocycl. Compd. 41, 1343–1361 (2005). doi:10.1007/s10593-006-0001-x

    Article  CAS  Google Scholar 

  3. Martin Del Valle, E.M.: Cyclodextrins and their uses–a review. Proc. Biochem. 39, 1033–1046 (2004). doi:10.1016/S0032-9592(03)00258-9

    Article  Google Scholar 

  4. Cabral Marques, H.M.: A review on cyclodextrin encapsulation of essential oils and volatiles. Flavour Fragr. J. 25, 313–326 (2010). doi:10.1002/ffj.2019

    Article  CAS  Google Scholar 

  5. Szente, L., Szejtli, J.: Cyclodextrins as food ingredients. Trends Food Sci. Technol. 15, 137–142 (2004). doi:10.1016/j.tifs.2003.09.019

    Article  CAS  Google Scholar 

  6. Loftsson, T., Jarvinen, T.: Cyclodextrins in ophthalmic drug delivery. Adv. Drug Deliv. Rev. 36, 59–79 (1999). doi:10.1016/j.ijpharm.2006.10.044

    Article  Google Scholar 

  7. Szejtli, J.: Cyclodextrin Technology. Kluwer Academic Publishers, Dordrecht (1988)

    Google Scholar 

  8. Szejtli, J., Szente, L.: Elimination of bitter, disgusting tastes of drugs and foods by cyclodextrins. Eur. J. Pharm. Biopharm. 61, 115–125 (2005). doi:10.1016/j.ejpb.2005.05.006

    Article  CAS  Google Scholar 

  9. Lim, H.J., Cho, E.C., Shim, J., Kim, D.-H., An, E.J., Kim, J.: Polymer-associated liposomes as a novel delivery system for cyclodextrin-bound drugs. J. Colloid Interface Sci. 320, 460–468 (2008). doi:10.1016/j.jcis.2008.01.025

    Article  CAS  Google Scholar 

  10. Kurkov, S.V., Ukhatskaya, E.V., Loftsson, T.: Drug/cyclodextrin: beyond inclusion complexation. J. Incl. Phenom. Macrocycl. Chem. 69, 297–301 (2011). doi:10.1007/s10847-010-9756-x

    Article  CAS  Google Scholar 

  11. Germain, P., de Brauer, C., Diot, M., Letoffe, J.M.: Influence of the water content on the thermal behaviour of β-cyclodextrin at low and very low temperature. J. Incl. Phenom. Macrocycl. Chem. 31, 205–212 (1998). doi:10.1023/A:1007961306473

    Article  CAS  Google Scholar 

  12. Giordano, F., Gazzaniga, A., Bettinetti, G.P., Manna, A.L.: The influence of water content on the binding capacity of β-cyclodextrin. Int. J. Pharm. 62, 153–156 (1990). doi:10.1016/0378-5173(90)90229-W

    Article  CAS  Google Scholar 

  13. García-Río, L., Mejuto, J.C., Rodríguez-Dafonte, P., Hall, R.W.: The role of water release from the cyclodextrin cavity in the complexation of benzoyl chlorides by dimethyl-β-cyclodextrin. Tetrahedron 66, 2529–2537 (2010). doi:10.1016/j.tet.2009.12.005

    Article  Google Scholar 

  14. Hădărugă, D.I., Hădărugă, N.G., Merkh, G., Isengard, H.-D.: Water content of fatty acid/cyclodextrin nanoparticles. J. Agroaliment. Proc. Technol. 16, 230–235 (2010)

    Google Scholar 

  15. Hădărugă, D.I., Hădărugă, N.G., Bandur, G.N., Isengard, H.-D.: Water content of flavonoid/cyclodextrin nanoparticles: Relationship with the structural descriptors of biologically active compounds. Food Chem. 132, 1651–1659 (2012). doi:10.1016/j.foodchem.2011.06.004

    Article  Google Scholar 

  16. Ponce Cevallos, P.A., Buera, M.P., Elizalde, B.E.: Encapsulation of cinnamon and thyme essential oils components (cinnamaldehyde and thymol) in β-cyclodextrin: effect of interactions with water on complex stability. Food Eng. 99, 70–75 (2010). doi:10.1016/j.jfoodeng.2010.01.039

    Article  Google Scholar 

  17. Brewster, M.E., Loftsson, T.: Cyclodextrins as pharmaceutical solubilizers. Adv. Drug Deliv. Rev. 59, 645–666 (2007). doi:10.1016/j.addr.2007.05.012

    Article  CAS  Google Scholar 

  18. Hădărugă, D.I., Hădărugă, N.G., Butnaru, G., Tatu, C., Gruia, A.: Bioactive microparticles (10): thermal and oxidative stability of nicotine and its complex with β-cyclodextrin. J. Incl. Phenom. Macrocycl. Chem. 68, 155–164 (2010). doi:10.1007/s10847-010-9761-0

    Article  Google Scholar 

  19. Hădărugă, N.G., Hădărugă, D.I., Păunescu, V., Tatu, C., Ordodi, V.L., Bandur, G., Lupea, A.X.: Bioactive nanoparticles (6). Thermal stability of linoleic acid/α- and β-cyclodextrin complexes. Food Chem. 99, 500–508 (2006). doi:10.1016/j.foodchem.2005.08.012

    Article  Google Scholar 

  20. Hansch, C., Leo, A., Koekman, D.: Exploring QSAR. Hydrophobic, electronic, and steric constants. American Chemical Society, Washington (1995)

Download references

Acknowledgments

This work was supported by Ministry of Education, Research, Youth, and Sports from Romania, PN2_62072/2008.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Daniel Ioan Hădărugă.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hădărugă, N.G., Hădărugă, D.I. & Isengard, HD. “Surface water” and “strong-bonded water” in cyclodextrins: a Karl Fischer titration approach. J Incl Phenom Macrocycl Chem 75, 297–302 (2013). https://doi.org/10.1007/s10847-012-0143-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10847-012-0143-7

Keywords

Navigation