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Journal of Drug Delivery
Volume 2014 (2014), Article ID 575719, 10 pages
http://dx.doi.org/10.1155/2014/575719
Research Article

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

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

Received 4 December 2013; Revised 21 March 2014; Accepted 31 March 2014; Published 5 May 2014

Academic Editor: Juan M. Irache

Copyright © 2014 Jean-Claude Debouzy et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 1H-NMR in solution and its membrane interactions were studied by 1H-NMR in small unilamellar vesicles and by 31P 2H NMR in phospholipidic dispersions of DMPC (dimyristoylphosphatidylcholine) in comparison with those of POLYA and CYSP alone. 1H-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 (31P). 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.