title: Effect of Water on Molecular Mobility and Physical Stability of Amorphous Pharmaceuticals.
abstract: 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.
authors.affiliation: Department of Pharmaceutics, University of Minnesota , Minneapolis, Minnesota 55455, United States.
authors.forename: Mehak
authors.initials: M
authors.lastname: Mehta
authors.affiliation: Department of Pharmaceutics, University of Minnesota , Minneapolis, Minnesota 55455, United States.
authors.forename: Khushboo
authors.initials: K
authors.lastname: Kothari
authors.affiliation: Department of Pharmaceutics, University of Minnesota , Minneapolis, Minnesota 55455, United States.
authors.forename: Vishard
authors.initials: V
authors.lastname: Ragoonanan
authors.affiliation: Department of Pharmaceutics, University of Minnesota , Minneapolis, Minnesota 55455, United States.
authors.forename: Raj
authors.initials: R
authors.lastname: Suryanarayanan
mesh_terms: D003460:Crystallization; D011108:Polymers / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry; D013696:Temperature; D014753:Vinyl Compounds / Q000737:chemistry; D014867:Water; D014961:X-Ray Diffraction
chemical_list: D011108:Polymers; D014753:Vinyl Compounds; D014867:Water; D011205:Povidone; C011566:vinyl acetate
keywords: amorphous; crystallization; dielectric; molecular mobility; water