Cao Wenjin, Bates Simon, Peck Garnet E, Wildfong Peter L D, Qiu Zhihui, Morris Kenneth R
Department of Industrial and Physical Pharmacy, School of Pharmacy, 1336 Robert E. Heine Pharmacy Building, Purdue University, 47907-1336, West Lafayette, IN, USA.
J Pharm Biomed Anal. 2002 Nov 7;30(4):1111-9. doi: 10.1016/s0731-7085(02)00419-3.
This paper details the development of a method using parallel-beam X-ray powder diffractometry as a novel means of determining polymorphic composition in intact compacts. Two polymorphic systems, chlorpropamide and glycine, were selected. The polymorphic components were weighed, mixed, and compressed using a Carver press with 3/8-in. concave tooling. The compacts were then analyzed using parallel-beam X-ray powder diffractometry in transmission geometry. The data were processed using the profile-fitting module in the Shimadzu XRD-6000 software V 4.1 (for NT 4.0/98). The integrated intensity ratio of a selected peak for each crystal form was used for quantitation of each polymorph. Excellent linear correlation was observed for both polymorphic systems. The convex shape of the compact surface had no effect on the XRD patterns. Since parallel-beam X-ray diffractometry is not sensitive to the shape of the sample surface, it provides a simple method for quantifying polymorphs in intact compacts. Further work to extend this to formulated tablets is ongoing. The relatively larger variation in one of the peaks in the chlorpropamide study was found to be consistent with the computational analysis of the slip behavior of the stable polymorph. This method provides the first reported non-invasive X-ray diffraction pattern quantitation of crystal forms in intact compacts.
本文详细介绍了一种使用平行束X射线粉末衍射法作为测定完整压片中多晶型物组成的新方法的开发过程。选择了两个多晶型体系，即氯磺丙脲和甘氨酸。将多晶型组分称重、混合，并使用带有3/8英寸凹形模具的卡弗压力机进行压制。然后使用平行束X射线粉末衍射法在透射几何条件下对压片进行分析。数据使用岛津XRD - 6000软件V 4.1（适用于NT 4.0/98）中的轮廓拟合模块进行处理。每种晶型选定峰的积分强度比用于定量每种多晶型物。在两个多晶型体系中均观察到了良好的线性相关性。压片表面的凸形对XRD图谱没有影响。由于平行束X射线衍射法对样品表面形状不敏感，它为定量完整压片中的多晶型物提供了一种简单的方法。将此方法扩展到制剂片剂的进一步工作正在进行中。在氯磺丙脲研究中发现其中一个峰的相对较大变化与稳定多晶型物滑移行为的计算分析一致。该方法首次报道了对完整压片中晶型的非侵入性X射线衍射图谱定量。
