Data Requirements for the Reliable Use of Atomic Pair Distribution Functions in Amorphous Pharmaceutical Fingerprinting

Abstract

The ambiguities make data measured using low energy x-rays unsuitable for fingerprinting active pharmaceutical ingredients and small molecule systems, and, in general, copper anode diffractometers are undesirable for this purpose; however, laboratory x-ray sources with either Mo or Ag anodes are well suited for this application.

Toward Phase Quantification at the Nanoscale Using the Total Scattering Pair Distribution Function (TSPDF) Method: Recrystallization of Cryomilled Sulfamerazine

“…19 A recent investigation into the minimum energies necessary to study amorphous pharmaceutical compounds found that there is not enough information in data collected on CALS diffractometers for reliable fingerprinting analysis. 11 However, MALS and SALS diffractometers and synchrotrons are capable of producing sufficiently information-rich PDFs. 11 Sample Preparation and Characterization.…”

Interrelationships Between Structure and the Properties of Amorphous Solids of Pharmaceutical Interest

“…44,46,47 Strong evidence also exists, that to this picture must be added a second order parameter arising from a tendency of such homogeneous preferred arrangements to be altered by localized bond orientational order, particularly as the liquid is cooled below T m into the supercooled and glassy states. 23 Such localized orientational order can arise from preferred geometric packing arrangements as with fragile more nonpolar liquids, as well as from specific directional hydrogen bonding and tetrahedral covalent arrangements, as in strong liquids such as inorganic oxides, for example, SiO 2 .…”

Local structure studies using the pair distribution function

“…using CuK radiations) may be used [8], however the PDF obtained are relatively featureless and dominated by spurious effects from the Fourier transform or poor normalization, which can lead to misinterpretations of the data. It is thus more favorable to use shorter wavelength radiations for PDF analysis [9]. Note that the angular 01003-p. 5 EPJ Web of Conferences resolution of the diffractometer is less restrictive, though too low resolution in reciprocal space leads to a rapid decrease of the PDF intensity with distance in direct space.…”

“…Here, several peaks corresponding to well identified pairs of atoms can be observed, either because they are isolated (the first 3 peaks) or because they strongly dominate the PDF (the Pb-Pb peaks). Although they correspond to interatomic distances in a crystalline phase, these peaks clearly 01003-p. 9 EPJ Web of Conferences have a finite width. This width is due to the distribution of distances for the given atomic pair, due to thermal displacements and static disorder.…”