Newman Justin A, Schmitt Paul D, Toth Scott J, Deng Fengyuan, Zhang Shijie, Simpson Garth J
Department of Chemistry, Purdue University , West Lafayette, Indiana, United States.
Anal Chem. 2015 Nov 3;87(21):10950-5. doi: 10.1021/acs.analchem.5b02758. Epub 2015 Oct 22.
Here we demonstrate the use of second harmonic generation (SHG) microscopy-guided synchrotron powder X-ray diffraction (PXRD) for the detection of trace crystalline active pharmaceutical ingredients in a common polymer blend. The combined instrument is capable of detecting 100 ppm crystalline ritonavir in an amorphous hydroxypropyl methylcellulose matrix with a high signal-to-noise ratio (>5000). The high spatial resolution afforded by SHG microscopy allows for the use of a minibeam collimator to reduce the total volume of material probed by synchrotron PXRD. The reduction in probed volume results in reduced background from amorphous material. The ability to detect low crystalline loading has the potential to improve measurements in the formulation pipeline for pharmaceutical solid dispersions, for which even trace quantities of crystalline active ingredients can negatively impact the stability and bioavailability of the final drug product.
在此，我们展示了利用二次谐波产生（SHG）显微镜引导的同步加速器粉末X射线衍射（PXRD）来检测常见聚合物共混物中的痕量结晶活性药物成分。该组合仪器能够在无定形羟丙基甲基纤维素基质中检测出百万分之一百浓度的结晶利托那韦，且具有高信噪比（>5000）。SHG显微镜提供的高空间分辨率使得能够使用微束准直器来减少同步加速器PXRD探测的材料总体积。探测体积的减少导致无定形材料背景的降低。检测低结晶负载量的能力有可能改善药物固体分散体制剂流程中的测量，因为即使痕量的结晶活性成分也可能对最终药品的稳定性和生物利用度产生负面影响。
