title: 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.
authors.affiliation: Department of Chemistry, Purdue University , West Lafayette, Indiana, United States.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Newman
authors.affiliation: Department of Chemistry, Purdue University , West Lafayette, Indiana, United States.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Schmitt
authors.affiliation: Department of Chemistry, Purdue University , West Lafayette, Indiana, United States.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Toth
authors.affiliation: Department of Chemistry, Purdue University , West Lafayette, Indiana, United States.
authors.forename: Fengyuan
authors.initials: F
authors.lastname: Deng
authors.affiliation: Department of Chemistry, Purdue University , West Lafayette, Indiana, United States.
authors.forename: Shijie
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, Purdue University , West Lafayette, Indiana, United States.
authors.forename: Garth J
authors.initials: GJ
authors.lastname: Simpson
mesh_terms: D057230:Limit of Detection; D033362:Powder Diffraction / Q000379:methods*