Utilizing glycerol as a plasticizer, an accelerated physical stability testing method of amorphous solid dispersions (ASDs) was developed. The influence of glycerol concentration on the glass transition temperature and α-relaxation time (a measure of molecular mobility) of amorphous ketoconazole, celecoxib, and the solid dispersions of each prepared with polyvinylpyrrolidone was investigated. By temperature scaling (Tg/T), the effects of glycerol concentration and temperature on the relaxation time were simultaneously evaluated. Glycerol, in a concentration dependent manner, accelerated crystallization in all of the systems without affecting the fragility. In celecoxib-PVP ASDs, the drug crystallization was well coupled to molecular mobility and was essentially unaltered at glycerol concentrations up to 2% w/w. The acceleration in crystallization brought about by glycerol expedited the determination of the coupling between molecular mobility and crystallization. As a result, we were able to predict the physical stability of the unplasticized ASD. This approach is especially useful for ASDs with high polymer content where drug crystallization is extremely slow at the relevant storage temperature.
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