Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, Indiana 47907, USA.
J Pharm Sci. 2011 May;100(5):1793-804. doi: 10.1002/jps.22415. Epub 2010 Dec 16.
The goal of this study was to provide a better framework for understanding the bulk and surface disorder in milled crystalline materials. The surface and bulk properties of two model compounds, ketoconazole and griseofulvin, were characterized by inverse gas chromatography as a function of cryomilling time. Cryomilling was used to decrease the effect of temperature-induced changes, which commonly occur during milling. A reduction in crystallinity was observed for both compounds by powder X-ray diffraction and differential scanning calorimetry (DSC). Particle size analysis revealed a continued mode of attrition for griseofulvin, whereas attrition followed by growth was observed for ketoconazole. An increase in surface energy for both compounds was noticed upon initial milling, followed by a decrease as milling time continued. A determination and comparison of the surface phase transformations using chromatographic methods and DSC was carried out. Both ketoconazole and griseofulvin showed an earlier phase transformation relative to DSC. It is proposed that an intermediate metastable state for griseofulvin and a change in the surface structure of ketoconazole is the consequence of the cryomilling process.
本研究的目的是为理解研磨结晶材料的体相和表面无序提供更好的框架。通过反气相色谱法，研究了两种模型化合物酮康唑和灰黄霉素的表面和体相性质，作为冷冻研磨时间的函数。冷冻研磨用于减少在研磨过程中通常发生的温度诱导变化的影响。粉末 X 射线衍射和差示扫描量热法（DSC）都表明两种化合物的结晶度降低。粒度分析表明灰黄霉素的磨损模式持续，而酮康唑则是磨损后生长。在初始研磨时，两种化合物的表面能都有所增加，随着研磨时间的继续，表面能又有所下降。使用色谱法和 DSC 对表面相转变进行了测定和比较。酮康唑和灰黄霉素都表现出相对于 DSC 更早的相转变。据推测，灰黄霉素的中间亚稳状态和酮康唑表面结构的变化是冷冻研磨过程的结果。
