A comparison of the physical stability of amorphous felodipine and nifedipine systems
A comparison of the physical stability of amorphous felodipine and nifedipine systems
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DOI：
10.1007/s11095-006-9047-9
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发表时间：
2006-10-01
影响因子：
3.7
通讯作者：
Taylor, Lynne S.
中科院分区：
文献类型：
--
作者：
Marsac, Patrick J.;Konno, Hajime;Taylor, Lynne S.
目的。本研究的目的是研究导致两种结构相关的钙通道阻滞剂硝苯地平和非洛地平的等温成核率差异的热力学和动力学因素，无论是单独使用还是在聚（乙烯基吡咯烷酮）（PVP）存在下。材料和方法。将无定形系统的薄膜浇铸到载玻片上，并使用光学显微镜测定成核率。使用差示扫描量热法 (DSC) 测量纯化合物的结晶焓、熵和自由能。使用 DSC 表征每个非晶体系的分子迁移率和玻璃化转变温度，并使用红外光谱分析氢键模式。使用弗洛里-哈金斯晶格理论估计了聚合物存在下无定形药物热力学活性的组成依赖性。结果。硝苯地平比非洛地平更容易从亚稳态无定形形式结晶，无论是单独使用还是在 PVP 存在下，尽管具有相似的玻璃化转变温度和分子迁移率。硝苯地平具有较大的结晶驱动力和较低的成核活化能。结论。亚稳态形式本身的性质并不能解释硝苯地平结晶的更大倾向。当考虑非晶态系统的物理稳定性时，重要的是还要考虑晶态对应物的性质。
Purpose. The objective of this study was to investigate thermodynamic and kinetic factors contributing to differences in the isothermal nucleation rates of two structurally related calcium channel blockers, nifedipine and felodipine, both alone and in the presence of poly(vinylpyrrolidone) (PVP).Materials and Methods. Thin films of amorphous systems were cast onto glass slides and the nucleation rate was determined using optical microscopy. Enthalpy, entropy, and free energy of crystallization of the pure compounds were measured using differential scanning calorimetery (DSC). Molecular mobility and glass transition temperature of each amorphous system were characterized using DSC and hydrogen bonding patterns were analyzed with infrared spectroscopy. The composition dependence of the thermodynamic activity of the amorphous drug in the presence of the polymer was estimated using Flory-Huggins lattice theory.Results. Nifedipine crystallized more readily than felodipine from the metastable amorphous form both alone and in the presence of PVP despite having a similar glass transition temperature and molecular mobility. Nifedipine was found to have a larger enthalpic driving force for crystallization and a lower activation energy for nucleation.Conclusions. The properties of the metastable form alone did not explain the greater propensity for nifedipine crystallization. When considering the physical stability of amorphous systems, it is important to also consider the properties of the crystalline counterpart.