Influence of lipophilicity on drug-cyclodextrin interactions: A calorimetric study

Laura J. Waters, Susan Bedford, Gareth M.B. Parkes, J. C. Mitchell

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

This study presents a systematic investigation of the interaction of three functionally related drugs, ibuprofen, ketoprofen and flurbiprofen, with two distinct forms of cyclodextrin at three specific temperatures, 298, 303 and 310 K using isothermal titration calorimetry (ITC). Although all three pharmaceutical compounds have similar pKa values, they exhibit widely differing lipophilicities. While previous authors have presented data regarding the binding of flurbiprofen and ibuprofen with β-cyclodextrin, this is the first report of the interaction of all three drug substances with β-cyclodextrin and 2-(hydroxypropyl)-β-cyclodextrin at controlled pH and temperature. For all scenarios, the associated changes in Gibbs free energy, enthalpy and entropy are presented alongside the stoichiometry and binding constants concerned. In all cases the binding was found to occur at a 1:1 ratio with an associated negative enthalpy and Gibbs free energy with the formation of the complex enthalpically, rather than entropically driven. The data further demonstrates a clear relationship between the thermodynamic behaviour and log P of the drug molecules. This work confirms the suitability of ITC to determine thermodynamic data for drug-cyclodextrin complex formations and provides an insight into the selection of appropriate cyclodextrins for bespoke pharmaceutical formulations.

LanguageEnglish
Pages102-106
Number of pages5
JournalThermochimica Acta
Volume511
Issue number1-2
Early online date6 Aug 2010
DOIs
Publication statusPublished - 20 Nov 2010

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Cyclodextrins
drugs
Gibbs free energy
titration
Pharmaceutical Preparations
Flurbiprofen
heat measurement
Ibuprofen
enthalpy
interactions
Calorimetry
Titration
Drug products
thermodynamics
Enthalpy
Thermodynamics
Ketoprofen
stoichiometry
entropy
formulations

Cite this

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title = "Influence of lipophilicity on drug-cyclodextrin interactions: A calorimetric study",
abstract = "This study presents a systematic investigation of the interaction of three functionally related drugs, ibuprofen, ketoprofen and flurbiprofen, with two distinct forms of cyclodextrin at three specific temperatures, 298, 303 and 310 K using isothermal titration calorimetry (ITC). Although all three pharmaceutical compounds have similar pKa values, they exhibit widely differing lipophilicities. While previous authors have presented data regarding the binding of flurbiprofen and ibuprofen with β-cyclodextrin, this is the first report of the interaction of all three drug substances with β-cyclodextrin and 2-(hydroxypropyl)-β-cyclodextrin at controlled pH and temperature. For all scenarios, the associated changes in Gibbs free energy, enthalpy and entropy are presented alongside the stoichiometry and binding constants concerned. In all cases the binding was found to occur at a 1:1 ratio with an associated negative enthalpy and Gibbs free energy with the formation of the complex enthalpically, rather than entropically driven. The data further demonstrates a clear relationship between the thermodynamic behaviour and log P of the drug molecules. This work confirms the suitability of ITC to determine thermodynamic data for drug-cyclodextrin complex formations and provides an insight into the selection of appropriate cyclodextrins for bespoke pharmaceutical formulations.",
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Influence of lipophilicity on drug-cyclodextrin interactions : A calorimetric study. / Waters, Laura J.; Bedford, Susan; Parkes, Gareth M.B.; Mitchell, J. C.

In: Thermochimica Acta, Vol. 511, No. 1-2, 20.11.2010, p. 102-106.

Research output: Contribution to journalArticle

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