Etude de la diffusion dans les hydrogels polymeres par spectroscopie et imagerie RMN.

摘要

Much attention is devoted to the study of diffusion in polymer systems because of its fundamental importance and its application in various fields such as controlled drug delivery in pharmaceutical sciences. A better understanding of the factors controlling the diffusion process could lead to a more effective design of controlled release systems. This work has focused on both, the analysis of the diffusing process in model hydrogel systems, and the study of water uptake in crosslinked high amylose starch tablets.;Pulsed-field NMR spectroscopy was used to study the diffusion of three dendrimers with carboxylic acid end groups in aqueous solutions and in gels of neutral poly(vinyl alcohol) and cationic poly(allylamine). The effects of the size of the diffusing probe, the polymer concentration and the temperature on the self-diffusion of the dendrimers were analyzed. It is shown that the ionic nature of the polymer matrix affects the diffusion of the dendrimers. Ionic interactions between the diffusing probes and the cationic poly(allylamine) gel resulted in a more complex diffusive behavior, lower self-diffusion coefficients and a higher activation energy.;NMR imaging, a non-invasive and non-destructive technique, was used to study water uptake and diffusion in crosslinked high amylose starch tablets. Crosslinked high amylose starch is an innovative excipient used by pharmaceutical industry for the sustained release of drugs. The water uptake and the swelling of crosslinked starch tablets are prerequisites to the drug release. The diffusion of water in the starch tablets was studied at different temperatures and the influence of drug loading on the diffusion processes was also investigated. The results demonstrate, in every case, that tablet swelling was anisotropic while diffusion was almost isotropic. The effect of temperature on both swelling and water uptake was significant. The diffusive behavior of water changed from Fickian to case II when temperature was raised. In drug-loaded tablets, the water uptake was faster than in plain tablets, whereas the swelling of the tablet was practically unaffected. Finally, the comparison of NMR imaging water uptake data and drug release data shows that drug release from starch based tablet is diffusion controlled.;In order to analyze the differences caused by the hydration of the starch excipient on both the structure and the dynamic of the starch chains, starch excipients prepared by two different crosslinking methods, were compared by cross-polarization 13C NMR spectroscopy with variable contact times. The tablets made of two types of crosslinked starch were shown to have different starch chain organizations when analyzed by CP-MAS 13C NMR spectroscopy.;Keywords. Diffusion, self-diffusion, pulsed-field NMR spectroscopy, NMR imaging, hydrogels, starch, drug release, pharmaceutical tablets, crosslinked high amylose starch.