Molecular mobility of nifedipine-PVP and phenobarbital-PVP solid dispersions as measured by 13C-NMR spin-lattice relaxation time
Molecular mobility of nifedipine-PVP and phenobarbital-PVP solid dispersions as measured by 13C-NMR spin-lattice relaxation time
复制标题
DOI：
10.1002/jps.20545
复制
发表时间：
2006-02-01
影响因子：
3.8
通讯作者：
Yoshioka, S
中科院分区：
文献类型：
--
作者：
Aso, Y;Yoshioka, S
将PVP与硝苯地平或苯巴比妥的混合物熔融后快速冷却，制备了不同药物含量的硝苯地平-PVP和苯巴比妥-PVP无定形固体分散体。用C-13-CP/MAS核磁共振测定了PVP、硝苯地平和苯巴比妥碳的化学位移和自旋晶格驰豫时间(T-1)，以阐明药物与PVP的相互作用以及药物和PVP在固体分散体中的局部分子迁移性。随着药物含量的增加，PVP羰基碳的化学位移增大，当药物与PVP单体的摩尔比约为1：1时，化学位移达到平台值，这表明PVP羰基与药物之间存在氢键作用。固体分散体中PVP羰基碳的T-1随药物含量的增加而增大，表明PVP羰基碳通过氢键相互作用而迁移率降低。药物碳的T-1随PVP含量的增加而增加，当PVP单体单元与药物的摩尔比超过约1：1时，T-1的增加不明显。这些结果表明，PVP吡咯烷酮环与药物分子的局域运动是通过氢键作用减少的。局域迁移率的降低似乎是稳定药物无定形状态的因素之一。(C)2005年Wiley-Liss，Inc.和美国药剂师协会。
Amorphous nifedipine-PVP and phenobarbital-PVP solid dispersions with various drug contents were prepared by melting and subsequent rapid cooling of mixtures of PVP and nifedipine, or phenobarbital. Chemical shifts and spin-lattice relaxation times (T-1) of PVP, nifedipine, and phenobarbital carbons were determined by C-13-CP/MAS NMR to elucidate drug-PVP interactions and the localized molecular mobility of drug and PVP in the solid dispersions. The chemical shift of the PVP carbonyl carbon increased as the drug content increased, appearing to reach a plateau at a molar ratio of drug to PVP monomer unit of approximately 1:1, suggesting hydrogen bond interactions between the PVP carbonyl group and the drugs. T-1 of the PVP carbonyl carbon in the solid dispersions increased as the drug content increased, indicating that the mobility of the PVP carbonyl carbon was decreased by hydrogen bond interactions. T-1 of the drug carbons increased as the PVP content increased, and this increase in T-1 became less obvious when the molar ratio of PVP monomer unit to drug exceeded approximately 1:1. These results suggest that the localized motion of the PVP pyrrolidone ring and the drug molecules is reduced by hydrogen bond interactions. Decreases in localized mobility appear to be one of the factors that stabilize the amorphous state of drugs. (C) 2005 Wiley-Liss, Inc. and the American Pharmacists Association.