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

摘要

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 multinudear 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 ID and 2D SSNMR analysis involving ~1H, ~(13)C, and ~(77)Se isotopes and 'H 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.