Nicol, Thomas W. J., Matubayasi, Nobuyuki and Shimizu, Seishi orcid.org/0000-0002-7853-1683 (2016) Origin of nonlinearity in phase solubility:Solubilisation by cyclodextrin beyond stoichiometric complexation. Physical Chemistry Chemical Physics. pp. 15205-15217. ISSN 1463-9084
Abstract
Low solubility of drugs, which poses a serious problem in drug development, can in part be overcome by the use of cyclodextrins (CD) and their derivatives. Here, the key to solubilisation is identified as the formation of inclusion complexes with the drug molecule. If inclusion complexation were the only contribution to drug solubility, it would increase linearly with CD concentration (as per the Higuchi-Connors model); this is because inclusion complexation is a 1:1 stoichiometric process. However, solubility curves often deviate from this linearity, whose mechanism is yet to be understood. Here we aim to clarify the origin of such non-linearity, based upon the Kirkwood-Buff and the McMillan-Mayer theories of solutions. The rigorous statistical thermodynamic theory shows that solubilisation non-linearity can be rationalised by two contributions: CD-drug interaction and the drug-induced change of CD-CD interaction.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © the Owner Societies, 2016. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) |
Depositing User: | Pure (York) |
Date Deposited: | 26 May 2016 08:40 |
Last Modified: | 16 Oct 2024 12:59 |
Published Version: | https://doi.org/10.1039/c6cp01582d |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1039/c6cp01582d |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:100193 |