The interaction of nifedipine with selected cyclodextrins and the subsequent solubility-permeability trade-off

Avital Beig, Jonathan M. Miller, Arik Dahan

Research output: Contribution to journalArticlepeer-review


The purpose of this study was to investigate the interaction of 2-hydroxypropyl-β-cyclodextrin (HPβCD) and 2,6-dimethyl-β- cyclodextrin (DMβCD) with the lipophilic drug nifedipine and to investigate the subsequent solubility-permeability interplay. Solubility curves of nifedipine with HPβCD and DMβCD in MES buffer were evaluated using phase solubility methods. Then, the apparent permeability of nifedipine was investigated as a function of increasing HPβCD/DMβCD concentration in the hexadecane-based PAMPA model. The interaction with nifedipine was CD dependent; significantly higher stability constant was obtained for DMβCD in comparison with HPβCD. Moreover, nifedipine displays different type of interaction with these CDs; a 1:1 stoichiometric inclusion complex was apparent with HPβCD, while 1:2 stoichiometry was apparent for DMβCD. In all cases, decreased apparent intestinal permeability of nifedipine as a function of increasing CD level and nifedipine apparent solubility was obtained. A quasi-equilibrium mass transport analysis was developed to explain this solubility-permeability interplay; the model enabled excellent quantitative prediction of nifedipine's permeability as a function of CD concentrations. This work demonstrates that when using CDs in solubility-enabling formulations, a trade-off exists between solubility increase and permeability decrease that must not be overlooked. This trade-off was found to be independent of the type of CD-drug interaction. The transport model presented here can aid in striking the appropriate solubility-permeability balance in order to achieve optimal overall absorption.

Original languageAmerican English
Pages (from-to)1293-1299
Number of pages7
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Issue number3 PART B
StatePublished - 1 Jan 2013


  • Cyclodextrins
  • Intestinal permeability
  • Low-solubility drugs
  • Oral absorption
  • Solubility-enabling formulations
  • Solubility-permeability interplay

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Pharmaceutical Science


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