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| Naji, M. |
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| Motta, Antonella |
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| Aletan, Dirar |
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| Mohamed, Tarek |
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| Ertürk, Emre |
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| Taccardi, Nicola |
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| Kononenko, Denys |
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| Petrov, R. H. | Madrid |
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| Alshaaer, Mazen | Brussels |
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| Bih, L. |
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| Casati, R. |
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| Muller, Hermance |
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| Kočí, Jan | Prague |
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| Šuljagić, Marija |
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| Kalteremidou, Kalliopi-Artemi | Brussels |
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| Azam, Siraj |
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| Ospanova, Alyiya |
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| Blanpain, Bart |
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| Ali, M. A. |
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| Popa, V. |
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| Rančić, M. |
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| Ollier, Nadège |
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| Azevedo, Nuno Monteiro |
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| Landes, Michael |
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| Rignanese, Gian-Marco |
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Cornett, Claus
University of Copenhagen
in Cooperation with on an Cooperation-Score of 37%
Topics
Publications (4/4 displayed)
- 2015Formation mechanism of coamorphous drug−amino acid mixturescitations
- 2013Interpreting the Disordered Crystal Structure of Sodium Naproxen Tetrahydratecitations
- 2013Exploring the solid-form landscape of pharmaceutical hydratescitations
- 2011Assessment of crystalline disorder in cryo-milled samples of indomethacin using atomic pair-wise distribution functionscitations
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article
Formation mechanism of coamorphous drug−amino acid mixtures
Abstract
Two coamorphous drug−amino acid systems, indomethacin−tryptophan (Ind−Trp) and furosemide−tryptophan Fur−Trp), were analyzed toward their ease of amorphization and mechanism of coamorphization during ball milling. The two mixtures were compared to the corresponding amorphization of the pure drug without amino acid. Powder blends at a 1:1 molar ratio were milled for varying times, and their physicochemical properties were investigated using XRPD, 13C solid state NMR (ssNMR), and DSC. Comilling the drug with the amino acid reduced the milling time required to obtain an amorphous powder from more than 90 min in the case of the pure drugs to 30 min for the coamorphous powders. Amorphization was observed as reductions in XRPD reflections and was additionally quantified based on normalized principal component analysis (PCA) scores of the ssNMR spectra. Furthermore, the evolution in the glass temperature (Tg) of the coamorphous systems over time indicated complete coamorphization after 30 min of milling. Based on the DSC data it was possible to identify the formation mechanism of the two coamorphous systems. The Tg position of the samples suggested that coamorphous Ind−Trp was formed by the amino acid being dissolved in the amorphous drug, whereas coamorphous Fur−Trp was formed by the drug being dissolved in the amorphous amino acid.