Issue 12, 2015

Hydrotrope accumulation around the drug: the driving force for solubilization and minimum hydrotrope concentration for nicotinamide and urea

Abstract

Nicotinamide is an effective non-micellar hydrotrope (solubilizer) for drugs with low aqueous solubility. To clarify the molecular basis of nicotinamide’s hydrotropic effectiveness, we present here a rigorous statistical thermodynamic theory, based on the Kirkwood–Buff theory of solutions, and our recent application of it to hydrotropy. We have shown that (i) nicotinamide self-association reduces solubilization efficiency, contrary to the previous hypothesis which claimed that self-association drives solubilization and (ii) the minimum hydrotrope concentration (MHC), namely, the threshold concentration above which solubility suddenly increases, is caused not by the bulk-phase self-association of nicotinamides as has been postulated previously, but by the enhancement of nicotinamide–nicotinamide interaction around the drug molecules. We have thus established a new view of hydrotropy – it is nicotinamide’s non-stoichiometric accumulation around the drug that is the basis of solubility increase above MHC.

Graphical abstract: Hydrotrope accumulation around the drug: the driving force for solubilization and minimum hydrotrope concentration for nicotinamide and urea

Article information

Article type
Paper
Submitted
20 Nov 2014
Accepted
12 Feb 2015
First published
27 Feb 2015

Phys. Chem. Chem. Phys., 2015,17, 8028-8037

Hydrotrope accumulation around the drug: the driving force for solubilization and minimum hydrotrope concentration for nicotinamide and urea

J. J. Booth, M. Omar, S. Abbott and S. Shimizu, Phys. Chem. Chem. Phys., 2015, 17, 8028 DOI: 10.1039/C4CP05414H

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements