Self Association and Cyclodextrin Solubilization of NSAIDs

  • Audur Magnusdottir
  • Már Másson
  • Thorsteinn Loftsson
Article

DOI: 10.1023/A:1023079322024

Cite this article as:
Magnusdottir, A., Másson, M. & Loftsson, T. Journal of Inclusion Phenomena (2002) 44: 213. doi:10.1023/A:1023079322024

Abstract

The phase solubility profiles with HPβCD of thesodium salt of the NSAIDs(non-steriodal anti-inflammatory drugs) ibuprofen anddiflunisal were studied. Theslopes of the phase solubility diagrams were determinedfor the sodium salt of ibuprofenat pH 6.1, 6.3 and 6.7, and for the sodium salt ofdiflunisal at pH 6.1 and 8.4. In allcases the slope of the phase solubility diagram wasgreater than unity. These resultssuggested that the stoichiometry of the complex formedwas greater than unity withrespect to the drug. However molecular modeling, NMRand UV studies clearlyshowed that the complex stoichiometry was 1:1. Theseconflicting results can beexplained by applying the theory developed for micellarforming compounds. Thusthe solubilization of the drugs is due partially frominclusion complex formation andpartially from solubilization by aggregation. Wehave therefore demonstrated that thesolubility of drugs in a cyclodextrin solution isexplained not only by inclusioncomplex formation but also by non-inclusion associationof the uncomplexed drugwith the complex.

diflunisal ibuprofen phase solubility diagrams self-association stoichiometry 

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Audur Magnusdottir
    • 1
  • Már Másson
    • 2
  • Thorsteinn Loftsson
    • 2
  1. 1.deCode GeneticsReykjavikIceland
  2. 2.Faculty of PharmacyUniversity of IcelandReykjavikIceland