Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907, USA.
Int J Pharm. 2011 Nov 25;420(1):68-75. doi: 10.1016/j.ijpharm.2011.08.022. Epub 2011 Aug 19.
Mechanical activation of pharmaceutical materials presents an important but poorly understood phenomenon of milled molecular crystals. In this work, a strategy was followed in an effort to understand this phenomenon, cryo-milled of both crystalline and amorphous counterpart of bile acids materials were characterized by X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC). The XRPD results for the 30-min milled crystalline powders displayed a characteristic amorphous halo patterns for all compounds tested. The DSC thermograms exhibited the typical glass transition temperatures (T(g)) associated with amorphous but only for two materials. For the remaining four milled compounds, a rather interesting behavior was manifested through a characteristic exothermal bimodal peak. The findings seemed to suggest that the occurrence of this event was not related to the (T(g)), but likely to the melting temperature (T(m)). The DSC results for the melt-quenched (amorphous) ursodeoxycholic acid after cryo-milling revealed that the material crystallized after the influence of the mechanical stress, and a bimodal peak was also observed similar to that of the cryo-milled crystalline material. It is contemplated that the response of the physical instability of the disordered phase could be explained either by the result of surface crystallization kinetics which is different from that of the bulk crystallization, or by the creation of supersaturated dislocated crystal prior to amorphization.
药物材料的机械活化呈现出一个重要但尚未被充分理解的现象，即被研磨的分子晶体。在这项工作中，我们遵循了一种策略，试图理解这一现象，对胆汁酸材料的结晶态和非晶态的对照物进行了低温研磨，并通过 X 射线粉末衍射（XRPD）和差示扫描量热法（DSC）进行了表征。30 分钟研磨的结晶粉末的 XRPD 结果显示，所有测试化合物都呈现出特征性的非晶晕带图案。DSC 热谱图显示出与非晶态相关的典型玻璃化转变温度（T(g)），但仅适用于两种材料。对于其余四种研磨化合物，表现出一种相当有趣的行为，即呈现出特征的放热双峰峰。研究结果似乎表明，这种现象的发生与（T(g)）无关，而可能与熔融温度（T(m)）有关。低温研磨后的熔融淬火（非晶态）熊去氧胆酸的 DSC 结果表明，在机械应力的影响下，该材料在结晶后结晶，也观察到双峰峰，类似于低温研磨的结晶材料。可以认为，无序相物理不稳定性的响应可以通过表面结晶动力学的结果来解释，该结果与体结晶动力学不同，或者通过在非晶化之前形成过饱和位错晶体来解释。
