Effect of Encapsulating a Pseudo-Decapeptide Containing Arginine on PLGA: A Solid-State NMR Study

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Abstract

The effects of incorporating an amorphous decapeptide in PLGA on the cooperative and local motions of the polymer chains have been evaluated. Whereas assessment of the bulk properties is used traditionally for studies of host guest interactions, there are only rare examples where molecular-level understanding of such amorphous host guest systems has been sought. Moreover, addressing the mechanism of interactions and stabilisation of a drug in a polymeric network is a key factor for the achievement of reproducibility of the formulations and ultimately the preparation of composites able to deliver drugs with consistency. We present a methodology combining the study of the dynamics by solid-state NMR and the characterisation of the bulk properties to address and localise the presence of interactions in PLGA/guest omposites. The results (estimation of relaxation times, 2D wideline separation and T-g measurements) suggested (1) the existence of a drug polymer solid solution and (2) significant changes in the local dynamics of both the drug and the polymer in their composites depending on the loading level. The changes in the local dynamics as well as in the cooperative motions of the polymer chains in the composites were attributed to the formation of guest-polymer interactions. Differentiation of the affinity of glycolide or lactide units for interactions was also apparent. (C) 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:2681- 2696, 2010

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