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

Mehta, Mehak; Kothari, Khushboo; Ragoonanan, Vishard; Suryanarayanan, Raj

doi:10.1021/acs.molpharmaceut.5b00950

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

Journal Article · Tue Mar 08 00:00:00 EST 2016 · Molecular Pharmaceutics

DOI:https://doi.org/10.1021/acs.molpharmaceut.5b00950· OSTI ID:1259882

Mehta, Mehak ^[1]; Kothari, Khushboo ^[1]; Ragoonanan, Vishard ^[1]; Suryanarayanan, Raj ^[1]

Univ. of Minnesota, Minneapolis, MN (United States)

In this work, 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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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC); William and Mildred Peters; Center for Pharmaceutical Processing and Research; National Science Foundation (NSF)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1259882

Journal Information:: Molecular Pharmaceutics, Vol. 13, Issue 4; ISSN 1543-8384

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 66 works

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