Pharmaceutical Research and Technology Laboratories, Astellas Pharma Inc., 180 Ozumi, Yaizu, Shizuoka, 425-0072, Japan.
Pharm Res. 2013 Feb;30(2):502-11. doi: 10.1007/s11095-012-0896-0. Epub 2012 Oct 27.
To investigate crystallization behavior on the surface of amorphous solid dispersion powder using inverse gas chromatography (IGC) and to predict the physical stability at temperatures below the glass transition temperature (T (g)).
Amorphous solid dispersion powder was prepared by melt-quenching of a mixture of crystalline nifedipine and polyvinylpyrrolidon (PVP) K-30. IGC was conducted by injecting undecane (probe gas) and methane (reference gas) repeatedly to the solid dispersion at temperatures below T (g). Surface crystallization was evaluated by the retention volume change of undecane based on the observation that the surface of the solid dispersion with crystallized nifedipine gives an increased retention volume.
On applying the retention volume change to the Hancock-Sharp equation, surface crystallization was found to follow a two-dimensional growth of nuclei mechanism. Estimation of the crystallization rates at temperatures far below T (g) using the Avrami-Erofeev equation and Arrhenius equation showed that, to maintain its quality for at least three years, the solid dispersion should be stored at -20°C (T (g) - 65°C).
IGC can be used to evaluate crystallization behavior on the surface of a solid dispersion powder, and, unlike traditional techniques, can also predict the stability of the solid dispersion based on the surface crystallization behavior.
使用反气相色谱法（IGC）研究无定形固体分散体粉末表面的结晶行为，并预测低于玻璃化转变温度（T（g））时的物理稳定性。
通过将结晶硝苯地平与聚乙烯吡咯烷酮（PVP）K-30 的混合物熔融淬火制备无定形固体分散体粉末。在低于 T（g）的温度下，通过反复将十一烷（探针气体）和甲烷（参比气体）注入固体分散体来进行 IGC。通过观察到具有结晶硝苯地平的固体分散体的表面给出增加的保留体积，基于十一烷的保留体积变化来评估表面结晶。
将保留体积变化应用于汉考克-夏普方程，发现表面结晶遵循核的二维生长机制。使用阿弗拉米-埃罗菲耶夫方程和阿雷尼乌斯方程在远低于 T（g）的温度下估算结晶速率表明，为了使其质量至少保持三年，固体分散体应储存在-20°C（T（g）-65°C）。
IGC 可用于评估固体分散体粉末表面的结晶行为，并且与传统技术不同，还可以根据表面结晶行为预测固体分散体的稳定性。
