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Nanometer-scale residual crystals in a hot melt extruded amorphous solid dispersion: characterization by transmission electron microscopy
Date
2018
Abstract
Common characterization techniques used to detect crystallinity in amorphous solid dispersions (ASD) typically have detection or quantification limits on the order of 1%. Herein, an amorphous solid dispersion of indomethacin and polyvinylpyrrolidone/vinyl acetate copolymer produced by hot melt extrusion was determined to be amorphous by powder X-ray diffraction and differential scanning calorimetry. However, through the use of transmission electron microscopy, residual crystals of two populations were identified: single crystals mid-dissolution (<100 nm) and nanocrystalline domains of 5â 10 nm in size. Both domain types were observed to contain a high defect density. Polarized light microscopy and scanning electron microscopy techniques supplement these findings by corroborating crystallinity. The use of high resolution analytical techniques to identify and characterize residual crystallinity is considered an important first step to understand the significance of these residual crystalline populations to ASD performance attributes.
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Description
peer-reviewed
Publisher
American Chemical Society
Citation
Crystal Growth and Design;18 (12), pp. 7633-7640
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Funding Information
U.S. Food and Drug Administration (FDA), National Institute for Pharmaceutical Technology and Education, National Science Foundation