Department of Pharmaceutics, School of Pharmaceutical Science, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
Eur J Pharm Sci. 2012 Aug 15;46(5):446-54. doi: 10.1016/j.ejps.2012.03.008. Epub 2012 Mar 29.
The amorphous-to-crystalline transformation of nitrendipine was investigated using Raman spectroscopy and X-ray powder diffraction (XRPD). The nucleation and growth rate of crystalline nitrendipine in a medium containing poly (vinyl alcohol) (PVA) and polyethylene glycol (PEG 200) were quantitatively determined using image analysis based on polarized light microscopy. The findings from the image analysis revealed that the transformation process occurred through the dissolution of amorphous drug precipitate followed by the nucleation and growth of the crystalline phase with the amorphous precipitate acting as a reservoir for maintaining the supersaturation. The rates of nucleation and crystal growth of nitrendipine decreased with an increase in PEG 200 concentration in organic phase from 0% to 75% (v/v). Increasing the PVA concentration in water phase from 0.1% to 1.0% (w/w) also decreased the rates of nucleation and crystal growth, however, an increase in PVA concentration from 1.0% to 2.0% (w/w) did not result in a further decrease in the rates of nucleation and crystal growth. An increase in drug concentrations in the organic phase from 10 mg/ml to 30 mg/ml led to faster nucleation rates. However, a further increase in drug concentration to 100mg/ml decelerated the growth of nitrendipine crystals. Combining image analysis of polarized light micrographs together with Raman spectroscopy and XRPD provided an in-depth insight into solid state transformations in amorphous nitrendipine suspensions.
采用拉曼光谱和 X 射线粉末衍射（XRPD）研究了硝苯地平的无定形-晶型转变。使用基于偏光显微镜的图像分析定量测定了含有聚乙烯醇（PVA）和聚乙二醇（PEG 200）的介质中结晶硝苯地平的成核和生长速率。图像分析的结果表明，转化过程是通过无定形药物沉淀物的溶解，然后是晶相的成核和生长进行的，无定形沉淀物作为维持过饱和度的储库。随着有机相中 PEG 200 浓度从 0%增加到 75%（v/v），硝苯地平的成核和晶体生长速率降低。增加水相中的 PVA 浓度从 0.1%增加到 1.0%（w/w）也降低了成核和晶体生长速率，但是 PVA 浓度从 1.0%增加到 2.0%（w/w）不会导致成核和晶体生长速率进一步降低。有机相中药浓度从 10mg/ml 增加到 30mg/ml 导致更快的成核速率。然而，进一步将药物浓度增加到 100mg/ml 会减缓硝苯地平晶体的生长。将偏光显微镜图像的图像分析与拉曼光谱和 XRPD 相结合，深入了解了无定形硝苯地平悬浮液中的固态转变。
