Wheate, N.J. and Vora, V. and Anthony, N.G. and McInnes, F.J. (2010) Host-guest complexes of the antituberculosis drugs pyrazinamide and isoniazid with cucurbituril. Journal of Inclusion Phenomena and Macrocyclic Chemistry, 68 (3-4). pp. 359-367. ISSN 0923-0750Full text not available in this repository. (Request a copy from the Strathclyde author)
The potential use of cucurbituril (CB) as an excipient in oral formulations for improved drug physical stability or for improved drug delivery was examined with the antituberculosis drugs pyrazinamide (pyrazine-2-carboxamide) and isoniazid (isonicotinohydrazide). Both drugs form 1:1 host-guest complexes with CB as determined by H-1 nuclear magnetic resonance spectrometry, electrospray ionisation mass spectrometry and molecular modelling. Drug binding is stabilised by hydrophobic effects between the pyridine and pyrazine rings of isoniazid and pyrazinamide, respectively, to the inside cavity of the CB macrocycle as well as hydrogen bonds between the hydrazide and amide groups of each drug to the CB carbonyl portals. At pH 1.5, isoniazid binds CB with a binding constant of 5.6 x 10(5) M-1, whilst pyrazinamide binds CB at pH 7 with a much smaller binding constant (4.8 x 10(3) M-1). Finally, CB prevents drug melting through encapsulation. Where previously pyrazinamide displays a typical melting point of 189 A degrees C and isoniazid 171 A degrees C, by differential scanning calorimetry, no melting or degradation at temperatures up to 280 A degrees C is observed for either drug once bound by CB.
|Keywords:||tuberculosis, cucurbituril , pyrazinamide, isoniazid, Pharmacy and materia medica, Chemistry(all), Condensed Matter Physics|
|Subjects:||Medicine > Pharmacy and materia medica|
|Department:||Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences|
|Depositing user:||Strathprints Administrator|
|Date Deposited:||13 Jun 2011 14:05|
|Last modified:||22 Mar 2017 11:08|