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Avoiding pits on the energy landscape – alternative strategies for stabilizing nateglinide co-amorphous systems.
- Source :
- CrystEngComm; 7/21/2024, Vol. 26 Issue 27, p3653-3664, 12p
- Publication Year :
- 2024
-
Abstract
- Amorphous solid phases can be represented by shallow basins in the potential energy hypersurface. Glasses formed by substances with prolific crystal polymorphism, such as nateglinide, an anti-diabetes drug, are susceptible to greater kinetical instability. Their energy landscape is characterized by deep pits in an accessible range, into which the supramolecular configuration can fall, when the amorphous solid relaxes to some crystalline polymorph. Alternative co-amorphization strategies are explored in this work to overcome the crystallization of nateglinide amorphous phases, namely by comparing two synthetic approaches, cryo-milling and quench-cooling, for a dual-drug system in combination with ranolazine. An alternative co-former, the essential amino-acid tryptophan, was also used for the synthesis of a cryo-milled nateglinide co-amorphous system. Enhanced kinetical stability for up to 8 months is achieved with both multicomponent systems. Their physico-chemical characterization in 3 molar ratios is accompanied by the study of their relaxation processes by broadband dielectric spectroscopy. Despite the higher glass transition temperatures obtained for the cryo-milled co-amorphous system with tryptophan, the co-amorphous salt system with ranolazine was found to have higher kinetical stability upon heating or ageing. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14668033
- Volume :
- 26
- Issue :
- 27
- Database :
- Complementary Index
- Journal :
- CrystEngComm
- Publication Type :
- Academic Journal
- Accession number :
- 178299498
- Full Text :
- https://doi.org/10.1039/d4ce00195h