Effect of Water on Molecular Mobility and Physical Stability of Amorphous Pharmaceuticals

Mehak Mehta, Khushboo Kothari, Vishard Ragoonanan, Raj Suryanarayanan

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63 Scopus citations


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 (Tg/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 Tg/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 Tg.

Original languageEnglish (US)
Pages (from-to)1339-1346
Number of pages8
JournalMolecular Pharmaceutics
Issue number4
StatePublished - Apr 4 2016


  • amorphous
  • crystallization
  • dielectric
  • molecular mobility
  • water


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