Correlation between the stability constant and pH for β-cyclodextrin complexes

Lisa Samuelsen, René Holm, Audrey Lathuile, Jens Christian Sidney Schönbeck

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

In drug formulations, cyclodextrins are used to increase aqueous solubility and chemical stability of drugs via formation of inclusion complexes. For ionizable drug molecules, the complexation strength depends on pH. Increased ionization leads to a more soluble drug, but also results in destabilization of cyclodextrin complexes. Therefore, formulation scientists aim to find a balance between increased drug solubility and high complexation strength. In this work, a theoretical expression for the dependency between the stability constant and pH is presented, allowing the accurate prediction of the stability constant at any pH. The theoretical expression requires three out of four input parameters; the pKa of the free guest molecule, the pKa of the complex, and the stability constants for the neutral and fully ionized complex. Stability constants for β-cyclodextrin and ibuprofen complexes were determined by isothermal titration calorimetry at seven pH values (2.5–5.5) and four temperatures (15–55 °C). All these measured stability constants complied with the theoretical expression. Ten additional data sets from the literature comprising eight different drug molecules and three different cyclodextrins confirmed the ability of the theoretical expression to account for the observed pH-dependence of stability constants.
Original languageEnglish
Article number118523
JournalInternational Journal of Pharmaceutics
Volume2019
Issue number568
ISSN0378-5173
DOIs
Publication statusPublished - 2019

Keywords

  • pH-dependency
  • Equilibrium constant
  • Guest molecule
  • Hydrophobic interactions
  • Ionization
  • Drug formulation

Activities

  • 1 Organisation and participation in conference

European Cyclodextrin Conference

Lisa Samuelsen (Participant)

2 Oct 20194 Oct 2019

Activity: Participating in or organising an eventOrganisation and participation in conference

Cite this