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Analysis of a Nanocrystalline Polymer Dispersion of Ebselen Using Solid-State NMR, Raman Microscopy, and Powder X-ray Diffraction

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ABSTRACT

Purpose

Nanocrystalline drug-polymer dispersions are of significant interest in pharmaceutical delivery. The purpose of this work is to demonstrate the applicability of methods based on two-dimensional (2D) and multinuclear solid-state NMR (SSNMR) to a novel nanocrystalline pharmaceutical dispersion of ebselen with polyvinylpyrrolidone-vinyl acetate (PVP-VA), after initial characterization with other techniques.

Methods

A nanocrystalline dispersion of ebselen with PVP-VA was prepared and characterized by powder X-ray diffraction (PXRD), confocal Raman microscopy and mapping, and differential scanning calorimetry (DSC), and then subjected to detailed 1D and 2D SSNMR analysis involving 1H, 13C, and 77Se isotopes and 1H spin diffusion.

Results

PXRD was used to show that dispersion contains nanocrystalline ebselen in the 35–60 nm size range. Confocal Raman microscopy and spectral mapping were able to detect regions where short-range interactions may occur between ebselen and PVP-VA. Spin diffusion effects were analyzed using 2D SSNMR experiments and are able to directly detect interactions between ebselen and the surrounding PVP-VA.

Conclusions

The methods used here, particularly the 2D SSNMR methods based on spin diffusion, provided detailed structural information about a nanocrystalline polymer dispersion of ebselen, and should be useful in other studies of these types of materials.

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  1. Product Development, GlaxoSmithKline plc., 709 Swedeland Road, King of Prussia, Pennsylvania, 19406, USA

    Frederick G. Vogt & Glenn R. Williams

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  1. Frederick G. Vogt
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Correspondence to Frederick G. Vogt.

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Vogt, F.G., Williams, G.R. Analysis of a Nanocrystalline Polymer Dispersion of Ebselen Using Solid-State NMR, Raman Microscopy, and Powder X-ray Diffraction. Pharm Res 29, 1866–1881 (2012). https://doi.org/10.1007/s11095-012-0713-9

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