AAPS PharmSciTech

, Volume 15, Issue 4, pp 872–881 | Cite as

Experimental and Computational Studies of Physicochemical Properties Influence NSAID-Cyclodextrin Complexation

  • Linda A. Felton
  • Carmen Popescu
  • Cody Wiley
  • Emilio Xavier Esposito
  • Philippe Lefevre
  • Anton J. Hopfinger
Research Article


The objective of this research was to investigate physicochemical properties of an active pharmaceutical ingredient (API) that influence cyclodextrin complexation through experimental and computational studies. Native β-cyclodextrin (B-CD) and two hydroxypropyl derivatives were first evaluated by conventional phase solubility experiments for their ability to complex four poorly water-soluble nonsteroidal anti-inflammatory drugs (NSAIDs). Differential scanning calorimetry was used to confirm complexation. Secondly, molecular modeling was used to estimate Log P and aqueous solubility (S o) of the NSAIDs. Molecular dynamics simulations (MDS) were used to investigate the thermodynamics and geometry of drug-CD cavity docking. NSAID solubility increased linearly with increasing CD concentration for the two CD derivatives (displaying an AL profile), whereas increases in drug solubility were low and plateaued in the B-CD solutions (type B profile). The calculated Log P and S o of the NSAIDs were in good concordance with experimental values reported in the literature. Side chain substitutions on the B-CD moiety did not significantly influence complexation. Explicitly, complexation and the associated solubility increase were mainly dependent on the chemical structure of the NSAID. MDS indicated that each NSAID-CD complex had a distinct geometry. Moreover, complexing energy had a large, stabilizing, and fairly constant hydrophobic component for a given CD across the NSAIDs, while electrostatic and solvation interaction complex energies were quite variable but smaller in magnitude.


complexation cyclodextrin NSAID simulation modeling solubility 



Funding for this work was supported in part by Roquette Freres. Computational facilities from both Exe Research LLC and The Chem21 Group, Inc. were made available in order to perform the modeling and molecular dynamics simulation studies reported in this paper.


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Copyright information

© American Association of Pharmaceutical Scientists 2014

Authors and Affiliations

  • Linda A. Felton
    • 1
  • Carmen Popescu
    • 2
  • Cody Wiley
    • 1
  • Emilio Xavier Esposito
    • 3
    • 4
  • Philippe Lefevre
    • 5
  • Anton J. Hopfinger
    • 1
    • 3
  1. 1.College of Pharmacy, Department of Pharmaceutical SciencesUniversity of New MexicoAlbuquerqueUSA
  2. 2.Roquette America, Inc.GenevaUSA
  3. 3.The Chem21 Group, Inc.Lake ForestUSA
  4. 4.Exe Research LLCEast LansingUSA
  5. 5.Roquette FreresLestremFrance

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