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

Research output: Contribution to journalArticle

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Abstract

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
Volume12
Issue number3
DOIs
StatePublished - Mar 2 2015

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Keywords

  • crystal detection
  • solid dispersions
  • transmission electron microscopy

How much support was provided by MRSEC?

  • Shared

Reporting period for MRSEC

  • Period 1

PubMed: MeSH publication types

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

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