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Debouzy JC, Crouzier D, Bourbon F, et al. Interaction Study of an Amorphous Solid Dispersion of Cyclosporin A in Poly-Alpha-Cyclodextrin with Model Membranes by (1)H-, (2)H-, (31)P-NMR and Electron Spin Resonance. J Drug Deliv. 2014;2014:575719doi: 10.1155/2014/575719.
Debouzy, J. C., Crouzier, D., Bourbon, F., Lahiani-Skiba, M., & Skiba, M. (2014). Interaction Study of an Amorphous Solid Dispersion of Cyclosporin A in Poly-Alpha-Cyclodextrin with Model Membranes by (1)H-, (2)H-, (31)P-NMR and Electron Spin Resonance. Journal of drug delivery, 2014575719. https://doi.org/10.1155/2014/575719
Debouzy, Jean-Claude, et al. "Interaction Study of an Amorphous Solid Dispersion of Cyclosporin A in Poly-Alpha-Cyclodextrin with Model Membranes by (1)H-, (2)H-, (31)P-NMR and Electron Spin Resonance." Journal of drug delivery vol. 2014 (2014): 575719. doi: https://doi.org/10.1155/2014/575719
Debouzy JC, Crouzier D, Bourbon F, Lahiani-Skiba M, Skiba M. Interaction Study of an Amorphous Solid Dispersion of Cyclosporin A in Poly-Alpha-Cyclodextrin with Model Membranes by (1)H-, (2)H-, (31)P-NMR and Electron Spin Resonance. J Drug Deliv. 2014;2014:575719. doi: 10.1155/2014/575719. Epub 2014 May 05. PMID: 24883210; PMCID: PMC4027026.
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J Drug Deliv. 2014;2014:575719. doi: 10.1155/2014/575719. Epub 2014 May 05.

Interaction Study of an Amorphous Solid Dispersion of Cyclosporin A in Poly-Alpha-Cyclodextrin with Model Membranes by (1)H-, (2)H-, (31)P-NMR and Electron Spin Resonance.

Journal of drug delivery

Jean-Claude Debouzy, David Crouzier, Fréderic Bourbon, Malika Lahiani-Skiba, Mohamed Skiba

Affiliations

  1. IRBA, RNI-Biophysics Laboratory, 24, avenue des Maquis du Grésivaudan, BP 82, 38702 La Tronche Cedex, France.
  2. Galenic Pharmaceutical Laboratory, LAGEP UMR CNRS 5007, UFR Medicine and Pharmacy, 22 boulevard Gambetta, 76183 Rouen, France.

PMID: 24883210 PMCID: PMC4027026 DOI: 10.1155/2014/575719

Abstract

The properties of an amorphous solid dispersion of cyclosporine A (ASD) prepared with the copolymer alpha cyclodextrin (POLYA) and cyclosporine A (CYSP) were investigated by (1)H-NMR in solution and its membrane interactions were studied by (1)H-NMR in small unilamellar vesicles and by (31)P (2)H NMR in phospholipidic dispersions of DMPC (dimyristoylphosphatidylcholine) in comparison with those of POLYA and CYSP alone. (1)H-NMR chemical shift variations showed that CYSP really interacts with POLYA, with possible adduct formation, dispersion in the solid matrix of the POLYA, and also complex formation. A coarse approach to the latter mechanism was tested using the continuous variations method, indicating an apparent 1 : 1 stoichiometry. Calculations gave an apparent association constant of log Ka = 4.5. A study of the interactions with phospholipidic dispersions of DMPC showed that only limited interactions occurred at the polar head group level ((31)P). Conversely, by comparison with the expected chain rigidification induced by CYSP, POLYA induced an increase in the fluidity of the layer while ASD formation led to these effects almost being overcome at 298 K. At higher temperature, while the effect of CYSP seems to vanish, a resulting global increase in chain fluidity was found in the presence of ASD.

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