Skip to main content
Log in

Dipyridamole/β-cyclodextrin complexation: effect of buffer species, thermodynamics, and guest–host interactions probed by 1H-NMR and molecular modeling studies

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

Abstract

The complexation parameters of dipyridamole (Dipy) with β-cyclodextrin (β-CD) were investigated by using several techniques including phase solubility diagrams (PSD), proton nuclear magnetic resonance (1H-NMR), x-ray powder diffractometry (XRPD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and molecular mechanical modeling (MM+). From the pH-solubility profiles, two basic pK as at 6.4 and 2.7 were estimated. The linear correlation of the free energy of Dipy/β-CD complex formation (ΔG 11) with the corresponding free energy of inherent Dipy aqueous solubility (ΔG So), obtained from the linear variation of ln K 11 with that of the inherent Dipy solubility (ln S o) at different pHs and ionic strengths, was used to measure the contribution of the hydrophobic character of Dipy to include into the hydrophobic β-CD cavity. Complex formation of Dipy was driven by favorable enthalpy (ΔH° = −14.8 kJ/mol) and entropy (ΔS° = 31.9 J/mol K) factors. 1H-NMR and molecular mechanical modeling studies indicate the formation of different isomeric 1:1 and 1:2 complexes, where both the piperidine and diethanolamine moieties get separately included into the β-CD cavity. Molecular mechanical modeling computations indicate that the dominant driving force for complexation is Van der Waals with lower contribution from electrostatic interactions. 1H-NMR and XRPD, DSC, SEM studies of isolated solid complexes indicate the formation of inclusion complexes in aqueous solution.

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
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. AHFS drug information: Dipyridamole monograph. www.ashp.Org/mngrphs/ahfs/a382830.htm

  2. Drug bank: Dipyridamole monograph. http://www.drugbank.ca/drugs/DB00975

  3. Khalil, A., Belal, F., Al-Badr, A.A.: Dipyridamole comprehensive profile. In: Brittain, H.G. (ed.) Profiles of Drug Substances, Excipients, and Related Methodology, vol. 31, pp. 215–280. Elsevier Academic Press Inc., CA/USA (2005)

  4. Stella, V.J., Rajewski, R.A.: Cyclodextrins: their future in drug formulation and delivery. Pharm. Res 14, 556–567 (1997). doi:10.1023/A:1012136608249

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  6. Loftsson, T., Ducheˆne, D.: Cyclodextrins and their therapeutic applications. Int. J. Pharm. 329, 1–11 (2007). doi:10.1016/j.ijpharm.2006.10.044

    Article  CAS  Google Scholar 

  7. Torri, G., Naggi, A., Fregnan, G.B., Trebbi, A.: Dipyridamole-β-cyclodextrin complex: preparation and characterization. Pharmazie 45, 193–195 (1990)

    CAS  Google Scholar 

  8. Al Omari, M.M., Zughul, M.B., Davies, J.E.D., Badwan, A.A.: Sildenafil/cyclodextrin complexation: stability constants, thermodynamics, and guest-host interactions probed by 1H-NMR and molecular modeling studies. J. Pharm. Biomed. Anal 41, 857–865 (2006). doi:10.1016/j.jpba.2006.01.055

    Article  CAS  Google Scholar 

  9. Al Omari, M.M., Zughul, M.B., Davies, J.E.D., Badwan, A.A.: Effect of buffer species on the complexation of basic drug terfenadine with β-cyclodextrin. J. Incl. Phenom. Macrocycl. Chem 58, 227–235 (2007). doi:10.1007/s10847-006-9147-5

    Article  CAS  Google Scholar 

  10. Higuchi, T., Connors, K.A.: In: Reilley, C.N. (ed.) Advances in Analytical Chemistry Instrumentation, pp. 117–212. Wiley-Interscience, New York (1965)

  11. Zughul, M.B., Badwan, A.A.: SL2 type phase solubility diagrams, complex formation and chemical speciation of soluble species. J. Incl. Phenom. Macrocycl. Chem 31, 243–264 (1998). doi:10.1023/A:1007965424219

    Article  CAS  Google Scholar 

  12. Al Omari, M.M., Zughul, M.B., Davies, J.E.D., Badwan, A.A.: Effect of buffer species on the inclusion complexation of acidic drug celecoxib with cyclodextrin in solution. J. Incl. Phenom. Macrocycl. Chem 55, 247–254 (2006). doi:10.1007/s10847-005-9041-6

    Article  Google Scholar 

  13. Taraszewska, J., Migut, K., Kozbiat, M.: Complexation of flutamide by native and modified cyclodextrins. J. Phys. Org. Chem 16, 121–126 (2003). doi:10.1002/poc.582

    Article  CAS  Google Scholar 

  14. Avdeef, A., Bendels, S., Tsinman, O., Tsinman, K., Kansy, M.: Solubility-excipient classification gradient maps. Pharm. Res 24, 530–545 (2007). doi:10.1007/s11095-006-9169-0

    Article  CAS  Google Scholar 

  15. Al Omari, M.M., Zughul, M.B., Davies, J.E.D., Badwan, A.A.: Cisapride/β-cyclodextrin complexation: stability constants, thermodynamics, and guest-host interactions probed by 1H-NMR and molecular modeling studies. J. Incl. Phenom. Macrocycl. Chem 57, 511–517 (2007). doi:10.1007/s10847-006-9242-7

    Article  CAS  Google Scholar 

  16. Al Omari, M.M., El-Barghouthi, M.I., Zughul, M.B., Davies, J.E.D., Badwan, A.A.: Comparative study of the inclusion complexation of pizotifen and ketotifen with native and modified cyclodextrins. J. Solut. Chem 37, 249–264 (2008). doi:10.1007/s10953-007-9234-2

    Article  CAS  Google Scholar 

  17. Al Omari, M.M., Zughul, M.B., Davies, J.E.D., Badwan, A.A.: Astemizole/cyclodextrin inclusion complexes: phase solubility, physicochemical characterization and molecular modeling studies. J. Solut. Chem 37, 875–893 (2008). doi:10.1007/s10953-008-9277-z

    Article  CAS  Google Scholar 

  18. Ventura, C.A., Giannone, I., Paolino, D., Pistara, V., Corsaro, A., Puglisi, G.: Preparation of celecoxib-dimethy-β-cyclodextrin inclusion complex: characterization and in vitro permeation study. Eur. J. Med. Chem 40, 624–631 (2005). doi:10.1016/j.ejmech.2005.03.001

    Article  CAS  Google Scholar 

  19. Saichek, R.E., Reddy, K.R.: Electrokinetically enhanced remediation of hydrophobic organic compounds in soils: a review. Crit. Rev. Environ. Sci. Technol 35, 115–192 (2005). doi:10.1080/10643380590900237

    Article  CAS  Google Scholar 

  20. Connors, K.A.: The stability of cyclodextrin complexes in solution. Chem. Rev 97, 1325–1358 (1997). doi:10.1021/cr960371r

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mahmoud M. Al Omari.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Al Omari, M.M., El-Barghouthi, M.I., Zughul, M.B. et al. Dipyridamole/β-cyclodextrin complexation: effect of buffer species, thermodynamics, and guest–host interactions probed by 1H-NMR and molecular modeling studies. J Incl Phenom Macrocycl Chem 64, 305–315 (2009). https://doi.org/10.1007/s10847-009-9569-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10847-009-9569-y

Keywords

Navigation