Descamps M, Willart J F, Dudognon E, Caron V
Laboratoire de Dynamique et Structure des Matériaux Moléculaires, UMR, CNRS 8024, University of LILLE1, Bat P5 - 59655 Villeneuve d'Ascq Cedex, France.
J Pharm Sci. 2007 May;96(5):1398-407. doi: 10.1002/jps.20939.
Milling is a usual process used in the course of drug formulation, which however may change the physical nature of the end product. The diversity of the transformations of organic compounds upon milling has been widely demonstrated in the pharmaceutical literature. However, no effort has still been devoted to study the correlation between the nature of the transformation and the milling conditions. Results clarifying such transformations are shortly reviewed with special attention paid to the temperature of milling. The importance of the position of the glass transition temperature compared with that of milling is demonstrated. It is shown that decreasing the milling temperature leads to an increase of the amorphization tendency whereas milling above T(g) can produce a crystal-to-crystal transformation between polymorphic varieties. These observations contradict the usual suggestion that milling transforms the physical state only by a heating effect which induces a local melting. Equilibrium thermodynamics does not seem appropriate for describing the process. The driven alloys concept offers a more rational framework to interpret the effect of the milling temperature. Other results are also presented, which demonstrate the possibility for milling to form low temperature solid-state alloys that offer new promising ways to stabilize amorphous molecular solids.
研磨是药物制剂过程中常用的一种工艺，然而它可能会改变最终产品的物理性质。药物文献中已广泛证明了有机化合物在研磨时转化的多样性。然而，仍未有人致力于研究转化性质与研磨条件之间的相关性。本文简要回顾了阐明此类转化的结果，并特别关注了研磨温度。文中展示了玻璃化转变温度与研磨温度相比的重要性。结果表明，降低研磨温度会导致非晶化趋势增加，而在玻璃化转变温度以上进行研磨会在多晶型变体之间产生晶型到晶型的转变。这些观察结果与通常的观点相矛盾，即研磨仅通过诱导局部熔化的热效应来改变物理状态。平衡热力学似乎并不适合描述这一过程。驱动合金概念为解释研磨温度的影响提供了一个更合理的框架。还展示了其他结果，这些结果证明了研磨形成低温固态合金的可能性，这为稳定无定形分子固体提供了新的有前景的方法。
