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

Mehak Mehta | Zendy; Khushboo Kothari | Zendy; Vishard Ragoonanan | Zendy; Raj Suryanarayanan | Zendy

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

Author(s) -

Mehak Mehta,

Khushboo Kothari,

Vishard Ragoonanan,

Raj Suryanarayanan

Publication year - 2016

Publication title -

molecular pharmaceutics

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.13

H-Index - 127

eISSN - 1543-8392

pISSN - 1543-8384

DOI - 10.1021/acs.molpharmaceut.5b00950

Subject(s) - crystallization , supercooling , amorphous solid , fragility , plasticizer , relaxation (psychology) , materials science , thermodynamics , chemical engineering , water content , water of crystallization , dispersion (optics) , chemistry , chemical physics , crystallography , organic chemistry , psychology , social psychology , physics , geotechnical engineering , optics , engineering

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.

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