Detection of pharmaceutical drug crystallites in solid dispersions by transmission electron microscopy

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


We explored the use of transmission electron microscopy (TEM) to evaluate the crystallinity of griseofulvin (GF)/hydroxypropyl methylcellulose acetate succinate (HPMCAS) solid dispersions. TEM, which provides both real-space images and electron diffraction patterns, was used to unambiguously identify GF crystals in spray dried GF. Using TEM, we were also able to detect GF crystals in a physical mixture of spray dried GF particles and spray dried HPMCAS particles with an overall crystallinity of ∼3 vol %, below the practical lower limit of detection for laboratory-scale wide-angle X-ray scattering (WAXS). Using TEM and WAXS, we did not find crystals in GF/HPMCAS solid dispersions with GF loadings of 5, 10, and 50 wt %. However, we detected GF crystals in annealed 5 wt % GF solid dispersion using TEM, whereas we did not detect crystals using in situ WAXS and modulated differential scanning calorimetry, thereby establishing the superior crystal detection sensitivity of TEM. We also performed TEM analysis of the in situ growth of GF crystals in a TEM sample of 50 wt % GF solid dispersion. Based on this study, TEM has significant potential for characterizing even small degrees of crystallinity in solid dispersions. (Figure Presented).

Original languageEnglish (US)
Pages (from-to)983-990
Number of pages8
JournalMolecular pharmaceutics
Issue number3
StatePublished - Mar 2 2015

Bibliographical note

Publisher Copyright:
© 2015 American Chemical Society.


  • crystal detection
  • solid dispersions
  • transmission electron microscopy

MRSEC Support

  • Shared

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't


Dive into the research topics of 'Detection of pharmaceutical drug crystallites in solid dispersions by transmission electron microscopy'. Together they form a unique fingerprint.

Cite this