title: Influence of molecular mobility on the physical stability of amorphous pharmaceuticals in the supercooled and glassy States.
abstract: We investigated the correlation between molecular mobility and physical stability in three model systems, including griseofulvin, nifedipine, and nifedipine-polyvinylpyrrolidone dispersion, and identified the specific mobility mode responsible for instability. The molecular mobility in the glassy as well as the supercooled liquid states of the model systems were comprehensively characterized using dynamic dielectric spectroscopy. Crystallization kinetics was monitored by powder X-ray diffractometry using either a laboratory (in the supercooled state) or a synchrotron (glassy) X-ray source. Structural (α-) relaxation appeared to be the mobility responsible for the observed physical instability at temperatures above Tg. Although the direct measurement of the structural relaxation time below Tg was not experimentally feasible, dielectric measurements in the supercooled state were used to provide an estimate of the α-relaxation times as a function of temperature in glassy pharmaceuticals. Again, there was a strong correlation between the α-relaxation and physical instability (crystallization) in the glassy state but not with any secondary relaxations. These results suggest that structural relaxation is a major contributor to physical instability both above and below Tg in these model systems.
authors.affiliation: Department of Pharmaceutics, University of Minnesota , 308 Harvard Street SE, Minneapolis, Minnesota 55455, United States.
authors.forename: Khushboo
authors.initials: K
authors.lastname: Kothari
authors.forename: Vishard
authors.initials: V
authors.lastname: Ragoonanan
authors.forename: Raj
authors.initials: R
authors.lastname: Suryanarayanan
mesh_terms: D003460:Crystallization / Q000379:methods; D058266:Dielectric Spectroscopy; D004355:Drug Stability; D005898:Glass / Q000737:chemistry*; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D013696:Temperature; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D004364:Pharmaceutical Preparations