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| Naji, M. |
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| Motta, Antonella |
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| Mohamed, Tarek |
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| Ertürk, Emre |
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| Taccardi, Nicola |
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| Petrov, R. H. | Madrid |
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| Azam, Siraj |
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| Ali, M. A. |
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| Rančić, M. |
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| Azevedo, Nuno Monteiro |
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| Landes, Michael |
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| Rignanese, Gian-Marco |
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Larsen, Flemming Hofmann
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Topics
Publications (5/5 displayed)
- 2018Characterization of free radicals by electron spin resonance spectroscopy in biochars from pyrolysis at high heating rates and at high temperaturescitations
- 2016Influence of variation in molar ratio on co-amorphous drug-amino acid systemscitations
- 2016Characterization of free radicals by electron spin resonance spectroscopy in biochars from pyrolysis at high heating rates and at high temperaturescitations
- 2015Formation mechanism of coamorphous drug−amino acid mixturescitations
- 2011Metal Ion Controlled Polymorphism of a Peptide
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article
Influence of variation in molar ratio on co-amorphous drug-amino acid systems
Abstract
<p>Molecular interactions were investigated within four different co-amorphous drug-amino acid systems, namely indomethacin-tryptophan (Ind-Trp), furosemide-tryptophan (Fur-Trp), indomethacin-arginine (Ind-Arg) and furosemide-arginine (Fur-Arg). The co-amorphous systems were prepared by ball milling for 90min at different molar ratios and analyzed by XRPD and DSC. Interactions within the co-amorphous samples were evaluated based on the deviation between the actual glass transition temperature (Tg) and the theoretical Tg calculated by the Gordon-Taylor equation. The strongest interactions were observed in the 50mol% drug (1:1M ratio) mixtures, with the exception of co-amorphous Ind-Arg where the interactions within the 40mol% drug samples appear equally strong. A particularly large deviation between the theoretical and actual Tgs was observed within co-amorphous Ind-Arg and Fur-Arg systems. Further analysis of these co-amorphous systems by (13)C solid-state NMR (ssNMR) and FTIR confirmed that Ind and Fur formed a co-amorphous salt together with Arg. A modified approach of using the Gordon-Taylor equation was applied, using the equimolar co-amorphous mixture as one component, to describe the evolution of the Tgs with varying molar ratio between the drug and the amino acid. The actual Tgs for co-amorphous Ind-Trp, Fur-Trp and Fur-Arg were correctly described by this equation, confirming the assumption that the excess component was amorphous forming a homogeneous single component within the co-amorphous mixture without additional interactions. The modified equation described the Tgs of the co-amorphous Ind-Arg with excess Arg less well indicating possible further interactions; however, the FTIR and ssNMR data did not support the presence of additional intermolecular drug-amino acid interactions.</p>