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The unexpected increase of clotrimazole apparent solubility using randomly methylated β‐cyclodextrin
Author(s) -
Pradines Bénédicte,
Gallard JeanFrançois,
Iorga Bogdan I.,
Gueutin Claire,
Ponchel Gilles,
Loiseau Philippe M.,
Bouchemal Kawthar
Publication year - 2015
Publication title -
journal of molecular recognition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.401
H-Index - 79
eISSN - 1099-1352
pISSN - 0952-3499
DOI - 10.1002/jmr.2432
Subject(s) - solubility , chemistry , clotrimazole , cyclodextrin , nuclear overhauser effect , nuclear chemistry , two dimensional nuclear magnetic resonance spectroscopy , proton nmr , chromatography , stereochemistry , nuclear magnetic resonance spectroscopy , organic chemistry , antifungal , medicine , dermatology
Clotrimazole (CTZ) and cyclodextrin (CD) inclusion complexes having improved apparent water solubility were obtained from phase solubility diagrams. β‐CD (1.5% w/w ) and hydroxypropyl‐β‐CD (40% w/w ) offered poor CTZ solubility enhancements (12 and 384 times, respectively). Unexpectedly, the apparent solubility of CTZ was 9980 times increased from 0.4 µg.mL −1 (1.42 μM) without CD to 4.89 mg.mL −1 (14.9 mM) using randomly‐methylated β‐CD (Me‐β‐CD) (40% w/w ). This is the highest apparent CTZ solubility improvement ever reported in the literature using conventional CDs. Quantitative nuclear magnetic resonance ( 1 H‐NMR) coupled with two‐dimensional nuclear Overhauser effect (NOESY) experiments and molecular docking calculations showed that the highest interactions with Me‐β‐CD were reported for CTZ two phenyl groups. A lower interaction was reported for chlorophenyl, while imidazole had the weakest interaction with Me‐β‐CD. Copyright © 2015 John Wiley & Sons, Ltd.