期刊
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
卷 49, 期 2, 页码 323-332出版社
ELSEVIER
DOI: 10.1016/j.ejps.2013.03.016
关键词
Glass-forming ability; Amorphous stability; Prediction; Molecular weight; Glass transition temperature; Crystallization temperature
资金
- Swedish Research Council [621-2008-3777, 621-2011-2445]
- Swedish Agency for Innovation Systems [2010-00966]
- Vinnova [2010-00966] Funding Source: Vinnova
- Swedish Research Council [2010-00966] Funding Source: Swedish Research Council
The purpose of this study was to investigate if rapidly measured physical properties can predict glass-forming ability and glass stability of drug compounds. A series of 50 structurally diverse drug molecules were studied with respect to glass-forming ability and, for glass-formers (n = 24), the physical stability upon 1 month of storage was determined. Spray-drying and melt-cooling were used to produce the amorphous material and the solid state was analysed by Differential Scanning Calorimetry (DSC) and Powder X-ray Diffraction. Thermal properties and molecular weight (Mw) were used to develop predictive models of (i) glass-forming ability and (ii) physical stability. In total, the glass-forming ability was correctly predicted for 90% of the drugs from their Mw alone. As a rule of thumb, drugs with Mw greater than 300 g/mole are expected to be transformed to its amorphous state by using standard process technology. Glass transition temperature and Mw predicted the physical stability upon storage correctly for 78% of the glass-forming compounds. A strong sigmoidal relationship (R-2 of 0.96) was identified between crystallization temperature and stability. These findings have the potential to rationalize decisions schemes for utilizing and developing amorphous formulations, through early predictions of glass-forming ability from Mw and physical stability from simple DSC characterization. (C) 2013 Elsevier B.V. All rights reserved.
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