NMR Study of the Association of Propofol with Nonionic Surfactants

Momot, Konstantin I., Kuchel, Philip W., Chapman, Bogdan E., Deo, Peter, & Whittaker, Darryl (2003) NMR Study of the Association of Propofol with Nonionic Surfactants. Langmuir, 19(6), pp. 2088-2095.

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The general anesthetic 2,6-diisopropylphenol (propofol) is very poorly soluble in water and is normally administered in the form of an emulsion. We demonstrated that several commercially available nonionic surfactants (Tween 80, Cremophor EL, Poloxamer 188, Poloxamer 407, Solutol HS15, and Vitamin E TPGS)render propofol soluble with a specific solubilization capacity of at least 0.1 g/g. The room-temperature stability of the solutions appeared to be limited only by the chemical stability of the compounds involved. Theassociation between propofolandthe surfactantswasinvestigated by various NMR approaches, including measurements of diffusion coefficients, 1H longitudinal relaxation times, and the magnitude of intermolecular nuclear Overhauser effects. The results were consistent with the micellar solubilization mechanism of propofol by the surfactants (unimer solubilization in the case of Poloxamer 188). The 1H longitudinal relaxation and diffusion behavior of propofol were monoexponential in each case. Solubilization caused a considerable shortening of propofol’s proton T1’s. The values of the diffusion coefficient of propofol were several percent higher than those of surfactants. This was explained by the partitioning of propofol between swollen micelles and the aqueous solution. Diffusion measurements also revealed the presence of a rapidly diffusing ethylene oxide population in surfactant solutions, which is consistent with free poly(ethylene oxide) (PEO) known to be present in commercially produced surfactants. The free PEO blocks exhibited molecular association with the extramicellar propofol.

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ID Code: 2674
Item Type: Journal Article
Refereed: Yes
Additional Information: This article is freely available from the American Chemical Society website 12 months after the publication date. See links to publisher website in this record.
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Keywords: nuclear magnetic resonance, PGSE NMR diffusion measurements, micellar nonionic surfactants, propofol, drug delivery
DOI: 10.1021/la026722g
ISSN: 0743-7463
Divisions: Past > QUT Faculties & Divisions > Faculty of Science and Technology
Copyright Owner: Copyright 2003 American Chemical Society
Copyright Statement: The contents of this journal can be freely accessed online via the ACS web page 12 months after publication. See hypertext link.
Deposited On: 15 Sep 2006 00:00
Last Modified: 29 Feb 2012 13:20

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