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Crystallization of Amorphous Nimesulide: The Relationship between Crystal Growth Kinetics and Liquid Dynamics
oleh: Qin Shi, Yanan Wang, Jianfei Kong
Format: | Article |
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Diterbitkan: | MDPI AG 2023-03-01 |
Deskripsi
Understanding crystallization and its correlations with liquid dynamics is relevant for developing robust amorphous pharmaceutical solids. Herein, nimesulide, a classical anti-inflammatory agent, was used as a model system for studying the correlations between crystallization kinetics and molecular dynamics. Kinetic parts of crystal growth (<i>u</i><sub>kin</sub>) of nimesulide exhibited a power law dependence upon the liquid viscosity (<i>η</i>) as <i>u</i><sub>kin</sub>~<i>η</i><sup>−0.61</sup>. Bulk molecular diffusivities (<i>D</i><sub>Bulk</sub>) of nimesulide were predicted by a force-level statistical–mechanical model from the α-relaxation times, which revealed the relationship as <i>u</i><sub>kin</sub>~<i>D</i><sub>bulk</sub><sup>0.65</sup>. Bulk crystal growth kinetics of nimesulide in deeply supercooled liquid exhibited a fragility-dependent decoupling from <i>τ</i><sub>α</sub>. The correlations between growth kinetics and α-relaxation times predicted by the Adam–Gibbs–Vogel equation in a glassy state were also explored, for both the freshly made and fully equilibrated glass. These findings are relevant for the in-depth understanding and prediction of the physical stability of amorphous pharmaceutical solids.