Miyazaki Tamaki, Aso Yukio, Kawanishi Toru
Division of Drugs, National Institute of Health Sciences, Setagaya-ku, Tokyo 158-8501, Japan.
J Pharm Sci. 2011 Oct;100(10):4413-20. doi: 10.1002/jps.22603. Epub 2011 May 3.
Amorphous nifedipine (NFD), which has a smooth surface immediately after preparation, was shown to have structures resembling clusters of curling and branching fibers approximately 1 μm wide by atomic force microscopy (AFM) after storage at 25°C. The size of the cluster-like structures increased with storage over time, implying crystal growth. The average elongation rate of the fibers determined by AFM at ambient room temperature was 1.1 × 10(-9) m/s, and this agreed well with the crystal growth rate of 1.6 × 10(-9) m/s determined by polarized light microscopy. The crystal growth rate of NFD in solid dispersions with 5% polyethylene glycol (PEG) was found to be 5.0 × 10(-8) m/s by AFM. Although this value was approximately the same as that obtained by polarized light microscopy, three-dimensional information obtained by AFM for the crystallization of NFD in a solid dispersion with PEG revealed that the changes in topography were not a consequence of surface crystal growth, but rather attributable to the growth of crystals formed in the amorphous bulk. For solid dispersions with α,β-poly(N-5-hydroxypentyl)-l-aspartamide, acceleration of NFD crystallization by tapping with an AFM probe was observed. The present study has demonstrated the feasibility and application of AFM for interpretation of surface crystallization data.
无定形硝苯地平（NFD）在制备后表面光滑，在25°C储存后通过原子力显微镜（AFM）观察到其具有类似于宽度约为1μm的卷曲和分支纤维簇的结构。随着储存时间的延长，簇状结构的尺寸增大，这意味着晶体在生长。在室温下通过AFM测定的纤维平均伸长率为1.1×10^(-9) m/s，这与通过偏光显微镜测定的1.6×10^(-9) m/s的晶体生长速率非常吻合。通过AFM发现NFD在含有5%聚乙二醇（PEG）的固体分散体中的晶体生长速率为5.0×10^(-8) m/s。虽然该值与通过偏光显微镜获得的值大致相同，但AFM获得的关于NFD在与PEG的固体分散体中结晶的三维信息表明，形貌变化不是表面晶体生长的结果，而是归因于在无定形主体中形成的晶体的生长。对于含有α,β-聚（N-5-羟戊基）-L-天冬酰胺的固体分散体，观察到用AFM探针轻敲可加速NFD结晶。本研究证明了AFM在解释表面结晶数据方面的可行性和应用。
