Glass-forming ability of compounds in marketed amorphous drug products
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Authors
Wyttenbach, Nicole
Author (Corporation)
Publication date
03/2017
Typ of student thesis
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Type
01A - Journal article
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Parent work
European Journal of Pharmaceutics and Biopharmaceutics
Special issue
DOI of the original publication
Link
Series
Series number
Volume
112
Issue / Number
Pages / Duration
204-208
Patent number
Publisher / Publishing institution
Elsevier
Place of publication / Event location
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Abstract
This note is about the glass-forming ability (GFA) of drugs marketed as amorphous solid dispersions or as pure amorphous compounds. A thermoanalytical method was complemented with an in silico study, which made use of molecular properties that were identified earlier as being relevant for GFA. Thus, molar volume together with effective numbers of torsional bonds and hydrogen bonding were used to map drugs that are as amorphous products on the market either as solid dispersion of without co-processed carrier as amorphous drug in a solid dosage form. Differential scanning calorimetry experiments showed that most compounds were stable glass formers (GFs) (class III) followed by so-called unstable GFs (class II) and finally, only vemurafenib was found in class I with increased crystallization propensity. The in silico results, however showed that all drugs were either clearly in the chemical space expected for GFs or they were borderline to the region that holds for high crystallization tendency. Interestingly, the pure amorphous compounds scattered in a very confined region of the molecular predictors. These findings can guide amorphous product development of future drug candidates. Based on the compound location in the given chemical space, amorphous formulation opportunities can be balanced against the risks of physical instability upon storage.
Keywords
Amorphous drug, Solid dispersion, Glass-forming ability, Molecular prediction
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ISBN
ISSN
0939-6411
1873-3441
1873-3441
Language
English
Created during FHNW affiliation
Yes
Strategic action fields FHNW
Publication status
Published
Review
Peer review of the complete publication
Open access category
License
Citation
Wyttenbach, N., & Kuentz, M. (2017). Glass-forming ability of compounds in marketed amorphous drug products. European Journal of Pharmaceutics and Biopharmaceutics, 112, 204–208. https://doi.org/10.1016/j.ejpb.2016.11.031