Issue 4, 2010
From the journal:

Organic & Biomolecular Chemistry

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

Fiona J. McInnes,a   Nahoum G. Anthony,a   Alan R. Kennedyb  and  Nial J. Wheate*a  

* Corresponding authors

a Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, John Arbuthnott Building, 27 Taylor Street, Glasgow, United Kingdom
E-mail: nial.wheate@strath.ac.uk
Fax: +44 141 552 2562
Tel: +44 141 548 4962

b Department of Pure and Applied Chemistry, University of Strathclyde, Royal College Building, 204 George Street, Glasgow, United Kingdom

Abstract

The inclusion of the cardiovascular β-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.

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

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Article information

DOI
https://doi.org/10.1039/B918372H
Article type
Paper
Submitted
08 Sep 2009
Accepted
20 Nov 2009
First published
04 Jan 2010

Org. Biomol. Chem., 2010,8, 765-773

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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, A. R. Kennedy and N. J. Wheate, Org. Biomol. Chem., 2010, 8, 765 DOI: 10.1039/B918372H

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