Solid state stabilisation of the orally delivered drugs atenolol, glibenclamide, memantine and paracetamol through their complexation with cucurbit[7]uril

F.J. McInnes, N.G. Anthony, Alan R. Kennedy, Nial J. Wheate

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

The inclusion of the cardiovascular -blocker drug atenolol, the antidiabetic drug glibenclamide, the Alzheimer's NMDA glutamate receptor drug memantine and the analgesic/antipyretic drug paracetamol by cucurbit[7]uril (CB[7]) has been studied by 1H nuclear magnetic resonance spectroscopy, electrospray ionisation mass spectrometry, molecular modelling, fluorescence displacement assays and differential scanning calorimetry. All four drugs form 1:1 host-guest complexes with CB[7], but the exchange kinetics and location of the binding is different for each drug. Atenolol is bound over the central phenyl ring with a binding constant of 4.2 × 104 M-1, whereas glibenclamide is bound over the terminal cyclohexyl group with a binding constant of 1.7 × 105 M-1, and memantine is totally bound within the CB[7] cavity. Paracetamol is bound in two locations, over the central phenyl ring and over the methyl group, with the CB[7] molecule shuttling quickly between the two sites. Inclusion by CB[7] was shown by differential scanning calorimetry to physically stabilise all four drugs, which has applications preventing drug degradation and improving drug processing and formulation.
Original languageEnglish
Pages (from-to)765-773
Number of pages8
JournalOrganic and Biomolecular Chemistry
Volume8
Issue number4
DOIs
Publication statusPublished - 2010

Keywords

  • solid state stabilisation
  • drugs
  • atenolol
  • glibenclamide
  • memantine
  • paracetamol
  • complexation
  • cucurbit[7]uril

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