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

64 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.
LanguageEnglish
Pages765-773
Number of pages8
JournalOrganic and Biomolecular Chemistry
Volume8
Issue number4
DOIs
Publication statusPublished - 2010

Fingerprint

Memantine
Atenolol
Glyburide
Acetaminophen
Complexation
drugs
Stabilization
stabilization
solid state
Pharmaceutical Preparations
Differential Scanning Calorimetry
Cardiovascular Agents
Antipyretics
Drug Compounding
Electrospray Ionization Mass Spectrometry
Glutamate Receptors
Differential scanning calorimetry
N-Methyl-D-Aspartate Receptors
Hypoglycemic Agents
Analgesics

Keywords

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

Cite this

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Solid state stabilisation of the orally delivered drugs atenolol, glibenclamide, memantine and paracetamol through their complexation with cucurbit[7]uril. / McInnes, F.J.; Anthony, N.G.; Kennedy, Alan R.; Wheate, Nial J.

In: Organic and Biomolecular Chemistry, Vol. 8, No. 4, 2010, p. 765-773.

Research output: Contribution to journalArticle

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