Department of Pharmaceutics, School of Pharmaceutical Science, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
Pharm Res. 2012 Jan;29(1):158-69. doi: 10.1007/s11095-011-0522-6. Epub 2011 Jul 12.
To investigate anti-solvent crystallization and growth mechanism of nitrendipine spherical crystals in an aqueous solution containing polymeric additives.
Size and shape of crystals were investigated using laser diffractometry, optical microscopy and scanning electron microscopy (SEM). Crystalline form was determined by X-ray powder diffractometer (XRPD). During crystal growth, morphological changes at different time points were observed using SEM.
Morphology of nitrendipine crystals was affected by polymers and temperature. Monodispersed micro-spherical crystals were obtained when polyvinyl alcohol (PVA) and PEG 200 were present in crystallization medium at 2°C. During crystallization, large number of amorphous nanoparticles was first observed, followed by aggregation into a core for spherical crystals. Once crystalline state was achieved, rapid growth on core surface was observed with amorphous particles acting as a reservoir allowing formation of star-like particles with needle-like subunits. Spherical crystals were formed by filling the gap between needle-like distinct crystalline units of star-like templates with molecules from dissolved amorphous particles.
Monodispersed nitrendipine spherical crystals were obtained using carefully controlled conditions. A mechanism for the nitrendipine spherical crystal growth is suggested. These findings provide a new insight into spherulitic crystallization of active pharmaceutical ingredients.
研究含有高分子添加剂的水溶液中硝苯地平球形晶体的抗溶剂结晶和生长机制。
采用激光衍射法、光学显微镜和扫描电子显微镜（SEM）研究晶体的大小和形状。通过 X 射线粉末衍射仪（XRPD）确定晶体形式。在晶体生长过程中，使用 SEM 观察不同时间点的形貌变化。
聚合物和温度对硝苯地平晶体的形态有影响。当聚乙烯醇（PVA）和聚乙二醇 200 存在于 2°C 的结晶介质中时，可得到单分散的微球形晶体。在结晶过程中，首先观察到大量无定形纳米颗粒，然后聚集形成球形晶体的核心。一旦达到结晶状态，就会在核心表面快速生长，无定形颗粒作为储库，允许形成具有针状亚基的星形颗粒。通过从溶解的无定形颗粒中填充星形模板的针状明显结晶单元之间的间隙，形成球形晶体。
通过精心控制条件，得到了单分散的硝苯地平球形晶体。提出了硝苯地平球形晶体生长的机制。这些发现为活性药物成分的球晶结晶提供了新的见解。
