Guerain Mathieu, Willart Jean-François
Université de Lille, CNRS, INRA, ENSCL, UMR8207, UMET, Unité Matériaux et Transformations, F-59650 Villeneuve d'Ascq, France.
Pharmaceutics. 2025 Jul 21;17(7):946. doi: 10.3390/pharmaceutics17070946.
A review of the literature on polymorphic transformations by milling on pharmaceutical materials was carried out. The available information on 18 pharmaceutical materials was compiled. In particular, when data are available, the starting and final crystalline forms, their enantiotropic or monotropic relationship, the glass transition temperature of the compound and its melting temperature, the experimental observation of a transient or partial amorphization of compounds, and the transformation kinetics make it possible to suggest a two-step transformation mechanism. First, an amorphization occurs under milling of the starting polymorphic form. Secondly, a recrystallization of the amorphous form occurs towards the final form. The observed transformation kinetics are due to the fact that the recrystallization of the amorphous material towards the final form depends on the accidental formation of a cluster of this form during milling. Moreover, the observation of the transient amorphous form depends on the relative position of the glass transition temperature of the material with respect to the milling temperature. This mechanism seems to be independent of the enantiotropic or monotropic character of the polymorphic forms involved in the transformation.
对通过研磨实现药物材料多晶型转变的文献进行了综述。收集了18种药物材料的现有信息。特别是，当有数据可用时，起始和最终晶型、它们的互变异构或单向性、化合物的玻璃化转变温度及其熔点、化合物瞬态或部分非晶化的实验观察结果以及转变动力学使得有可能提出一种两步转变机制。首先，在起始多晶型物研磨过程中发生非晶化。其次，无定形形式向最终形式发生重结晶。观察到的转变动力学是由于无定形材料向最终形式的重结晶取决于研磨过程中这种形式的聚集体的偶然形成。此外，瞬态无定形形式的观察取决于材料的玻璃化转变温度相对于研磨温度的相对位置。这种机制似乎与转变中涉及的多晶型物的互变异构或单向性特征无关。
