Examination of 19F-NMR as a tool for investigation of drug-cyclodextrin complexes
| Autor: | J. F. Sigurjónsdóttir, Sigridur Jonsdottir, Már Másson, Thorsteinn Loftsson |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Magnetic Resonance Spectroscopy
Inorganic chemistry Pharmaceutical Science Fluorine-19 NMR Dexamethasone Excipients chemistry.chemical_compound Fluoxetine Drug Discovery Organic chemistry Solubility Chromatography High Pressure Liquid Pharmacology chemistry.chemical_classification Cyclodextrins Trifluoromethyl Cyclodextrin Chemical shift Organic Chemistry beta-Cyclodextrins Nuclear magnetic resonance spectroscopy Fluorine Diflunisal 2-Hydroxypropyl-beta-cyclodextrin Solvent chemistry Pharmaceutical Preparations Stability constants of complexes |
| Zdroj: | Drug development and industrial pharmacy. 29(1) |
| ISSN: | 0363-9045 |
| Popis: | Fluorine nuclear magnetic-resonance spectroscopy (19F-NMR) was used to measure complexation of three fluorine-containing drugs--dexamthasone, fluoxetine hydrochloride, and diflunisal sodium--with 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD). Poor aqueous solubility inhibited investigation of dexamethasone complexes with this method. Complexation caused separation of the fluorine peaks that could be assigned to the two enantiomers of fluoxetine hydrochloride. The trifluoromethyl group of the drug was not included, or only partially included, in the cyclodextrin cavity and the shift changes resulting from complexation were small (0.04 and -0.05 ppm). The NMR method, therefore, could not be used to determine complex stoichiometry and complex stability constants, as chemical-shift changes were influenced by changes in the composition of the solvent medium. The difluorophenyl group of diflunisal sodium was fully included in the cyclodextrin cavity and the chemical-shift changes were large, 2.0 and 1.4 ppm, for C2' and C4' fluorine atoms, respectively. Using the continuous variation method, a 1:1 stoichiometry was determined for the complex. The chemical shift changes could also be used to determine the stability constant (Kc) for complex formation. The value obtained for the fluorine that enters deeper into the cavity was 2000 M(-1). The data shows that, given that the drug has sufficient solubility, one-dimensional 19F-NMR can be a fast and convenient method to investigate drug-cyclodextrin complexes. However, when the results are interpreted it must be taken into account that the solvent medium can affect the chemical shifts of the fluorine peaks. |
| Databáze: | OpenAIRE |
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