2015
DOI: 10.1021/mp500682x
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Detection of Pharmaceutical Drug Crystallites in Solid Dispersions by Transmission Electron Microscopy

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… Show more

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Cited by 40 publications
(45 citation statements)
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“…Therefore, the recorded induction time was approximated to be the induction time to nucleation without a considerable delay due to slow growth rates, obviating the need to detect nanometer sized nuclei and their associated difficulties. 19,20…”
Section: Methodsmentioning
confidence: 99%
“…Therefore, the recorded induction time was approximated to be the induction time to nucleation without a considerable delay due to slow growth rates, obviating the need to detect nanometer sized nuclei and their associated difficulties. 19,20…”
Section: Methodsmentioning
confidence: 99%
“…The use of TEM in the pharmaceutical industry has begun to become more prominent because it can provide information at length scales not normally accessible to other techniques, identify the presence of low-levels of crystalline material and be used in the routine structural determination of small organic crystals [46,47,48,49,50]. The results here show that using the SMF method real-space lattice information can be obtained indirectly in STEM at lower magnifications than is required for direct lattice imaging, reducing the total electron fluence and damage applied to the sample.…”
Section: Discussionmentioning
confidence: 99%
“…Furthermore, Transmission Electron Microscopy (TEM) with substantially higher resolution can also be used to further enhance the detectability of phase separation. One of the numerous possibilities with TEM is also the measurement of Selected Area Electron Diffraction (SAED) pattern, which enables crystallinity measurements of areas less than 1 µm in size [ 88 ]. Atomic Force Microscopy (AFM) is a resource intensive technique but can detect crystallized material in the ASD film with a resolution of up to 1 nm [ 60 ].…”
Section: Product Development Strategymentioning
confidence: 99%