Investigating Miscibility and Molecular Mobility of Nifedipine-PVP Amorphous Solid Dispersions Using Solid-State NMR Spectroscopy

被引:139
作者
Yuan, Xiaoda [1 ]
Sperger, Diana [1 ]
Munson, Eric J. [1 ]
机构
[1] Univ Kentucky, Coll Pharm, Dept Pharmaceut Sci, Lexington, KY 40536 USA
基金
美国国家科学基金会;
关键词
solid-state NMR; amorphous; solid dispersion; miscibility; relaxation time; nifedipine; PVP; PHYSICAL STABILITY; ENTHALPY RELAXATION; INDOMETHACIN; CRYSTALLIZATION; TRANSITION; MIXTURES; POLYVINYLPYRROLIDONE; COMPATIBILITY; TEMPERATURE; BLENDS;
D O I
10.1021/mp400498n
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Solid-state NMR (SSNMR) H-1 T-1 and T-1p relaxation times were used to evaluate the miscibility of amorphous solid dispersions of nifedipine (NIF) and polyvinylpyrrolidone (PVP) prepared by three different methods: melt quenching in the typical lab setting, spray drying and melt quenching in the NMR rotor while spinning. Of the five compositions prepared by melt quenching in the lab setting, the 95:5 and 90:10 NIF:PVP (w:w) amorphous solid dispersions were not miscible while 75:25, 60:40, and 50:50 NIF:PVP dispersions were miscible by the H-1 T-1p measurements. domain size of the miscible systems was estimated to be less 4.5 nm. Amorphous solid dispersions with composition of 90:10 NIF:PVP prepared by spray drying and melt.. quenching in the NMR rotor showed miscibility by H-1 T-1p values. Variable-temperature SSNMR H-1 T-1p relaxation measurements revealed a change in relaxation time at approximately 20 degrees C below T-g, suggesting increased molecular mobility above that temperature.
引用
收藏
页码:329 / 337
页数:9
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