Korhonen Ossi, Bhugra Chandan, Pikal Michael J
Department of Pharmaceutics, University of Kuopio, PO Box 1627, FI-70211 Kuopio, Finland.
J Pharm Sci. 2008 Sep;97(9):3830-41. doi: 10.1002/jps.21273.
The aim of the present study is to determine if the correlation between molecular mobility and crystallization growth rates exists over a broad temperature range from temperatures below the glass transition (T(g)) to temperatures above the glass transition. Phenobarbital and solid dispersions of phenobarbital with PVP and L-proline were studied in this research. Relaxation times below and above the T(g) were measured. Crystallization was followed in a hot-stage microscope and crystal growth rates were measured by observing radial growth of a single crystal. Arrhenius type temperature dependences were found both in relaxation times and crystal growth rates over studied temperature ranges, in all cases studied except in the case of pure phenobarbital, where a change of slope was observed for the crystal growth rate for the temperature range below T(g). For all cases, molecular mobility was correlated with crystal growth rate, for the temperature range studied, with a coupling coefficient of 0.38 for phenobarbital, and 0.23 and 0.28 for solid dispersions with PVP and proline respectively. By establishing the coupling between molecular mobility and crystal growth rate, predictive models can be created to estimate the stability of amorphous materials both, for pure form as well as for solid dispersions.
本研究的目的是确定在从低于玻璃化转变温度（T(g)）到高于玻璃化转变温度的宽温度范围内，分子迁移率与结晶生长速率之间是否存在相关性。本研究对苯巴比妥以及苯巴比妥与聚乙烯吡咯烷酮（PVP）和L-脯氨酸的固体分散体进行了研究。测量了T(g)以下和以上的弛豫时间。在热台显微镜下跟踪结晶过程，并通过观察单晶的径向生长来测量晶体生长速率。在所研究的温度范围内，除了纯苯巴比妥的情况外，在所有研究的案例中，弛豫时间和晶体生长速率均呈现出阿累尼乌斯型温度依赖性，在纯苯巴比妥的案例中，观察到T(g)以下温度范围内晶体生长速率的斜率发生了变化。对于所有案例，在所研究的温度范围内，分子迁移率与晶体生长速率相关，苯巴比妥的耦合系数为0.38，与PVP和脯氨酸的固体分散体的耦合系数分别为0.23和0.28。通过建立分子迁移率与晶体生长速率之间的耦合关系，可以创建预测模型，以估计纯形式以及固体分散体的无定形材料的稳定性。
