期刊
MOLECULAR PHARMACEUTICS
卷 13, 期 4, 页码 1339-1346出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.5b00950
关键词
amorphous; crystallization; water; molecular mobility; dielectric
资金
- William and Mildred Peters endowment fund
- Center for Pharmaceutical Processing and Research
- NSF through the MRSEC program
- DOE Office of Science [DE-AC02-06CH11357]
We investigated the influence of sorbed water concentration on the molecular mobility and crystallization behavior in a model amorphous drug and a solid dispersion. The temperature scaling (T-g/T) allowed us to simultaneously evaluate the effects of water content and temperature on the relaxation time. In the supercooled dispersions, once scaled, the relaxation times of the systems with different water content overlapped. Thus, the observed increase in mobility could be explained by the plasticization effect of water. This effect also explained the decrease in crystallization onset temperature brought about by water. That is, plasticization is the underlying mechanism governing the observed increase in mobility and physical instability in the supercooled state. Similar results were observed in the glassy drug substance. A single linear relationship was observed between crystallization time (time for 0.5% crystallization) and T-g/T in both dry and water containing systems. Since fragility is unaffected by modest amounts of water, much like crystallization time, the mobility in the glass is expected to scale with T-g.
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