Parts per Million Powder X-ray Diffraction

Abstract

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.

Properties of Cu-Based Shape-Memory Alloys Prepared by Selective Laser Melting

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Probing molecule-like isolated octahedra via phase stabilization of zero-dimensional cesium lead halide nanocrystals

“…1g). Though the phase stabilization of Cs 4 PbX 6 were concluded based on XRD results, this technique has its own limitation of insensitivity to detect any minor crystalline phase below 5% 34 . Henceforth, to further support the phase stabilization, optical characterization was exploited owing to its high sensitivity to detect even trace of fluorescent CsPbX 3 impurity.…”

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“…Novel analytical tools such as optical coherence tomography and interferometry can provide fast and non-invasive analysis of printed layer thickness, surface roughness/deformation created via solvent evaporation, the degree of adherence of printed drops with the substrate as well as spatial distributions . Newman and colleagues recently employed Second Harmonic Generation (SHG) microscopy-guided synchrotron powder X-ray diffraction to detect 100 ppm crystalline ritonavir in a hydroxypropyl methylcellulose (HPMC) matrix (Newman et al, 2015), while SHG microscopy-coupled confocal Raman spectroscopy enabled analysis of trace crystallites of paclitaxel in lyophilized Abraxane powder . Such analyses on printed films probably offer solid-state distribution in printed dots and their homogeneity (Chowdhury et al, 2014).…”