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Title: Parts per Million Powder X-ray Diffraction

Here in this paper 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:
 [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [1]
  1. Purdue Univ., West Lafayette, IN (United States). Dept. of Chemistry
Publication Date:
OSTI Identifier:
1228102
Grant/Contract Number:
AC02-06CH11357; SC0000997; NIH-R01GM103401; NIH-R01GM103910
Type:
Accepted Manuscript
Journal Name:
Analytical Chemistry
Additional Journal Information:
Journal Volume: 87; Journal Issue: 21; Journal ID: ISSN 0003-2700
Publisher:
American Chemical Society (ACS)
Research Org:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org:
National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
Country of Publication:
United States
Language:
ENGLISH
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY