X-Ray Powder Diffraction (XRPD) is considered an indispensable technique to pharmaceutical development activities. Can you review some current and emerging developments of XRPD?
There has been continuous development in high efficiency, energy selective detectors over the past decade. These new detectors have been combined with improved optics and miniature sources, which has enabled dramatic improvements in the quality of data, spatial resolution, portability of equipment, and significant reduction in data collection times. This has led to fundamental changes in lower detection limits for phase identification and quantitative analysis; the ability to study and understand both the coherent and incoherent scatter from the solid state (amorphous and nanomaterials); and with many new techniques to determine structures from powder data. In the last decade, there has been outstanding progress in method development and tools for the study and characterization of amorphous materials.
How has XRD instrumentation and software improved solid form screening?
High speed, high efficiency detectors have enabled XRD as a practical screening tool in combinatorial analysis. Spatial resolution and focusing of sources enable users to map a tablet in both elemental composition (XRF) and phase composition (XRD) leading to improved manufacturing processes. The improvements in speed (detector and source) enable dynamic in-situ solid state measurements for polymorph stability and product shelf life studies under variable temperature and humidity conditions.
On the software side, the Powder Diffraction File™ is a quality-reviewed compilation of powder, crystallographic and physical property data in a searchable relational database format that results in significant data mining capability for material identification and quantitative analysis. Total pattern analysis methods, such as Rietveld refinement and cluster analysis techniques, enable us to understand and control complex chemistries. Cluster analysis tools are invaluable for screening methods, as they can be used to select which specimens should be targeted for additional analysis.
The 2013 Powder Diffraction File™ contains 778,883 unique material sets. Can you review a few key attributes to the file?
The Powder Diffraction File™ is singularly designed to identify and characterize materials. This has many consequences in how we review, standardize, edit and categorize data for publication. Our review techniques are all based on quality in regards to the ability to identify materials. We specifically target certain classes of commercial materials for reference acquisition that might be analyzed in analytical, law enforcement, and pharmaceutical laboratories. We add inorganic materials to the PDF- 4/Organics database and organic materials to the PDF-4+ database that are common commercial materials. For example, in PDF-4/Organics we add inorganic excipients, pigments and buffers that might be in a tablet composition and we add polymers and common inorganics that might be used in pharmaceutical packing. For several decades, we have used grants to world leading laboratories to collect target materials that are not in the public domain via publications. The Powder Diffraction File™ combines powder and single crystal data, and more recently non-crystalline reference powder data. This results in the world largest collection of solid state materials in the targeted areas of pharmaceuticals, excipients, forensics and pigments for PDF-4/Organics and minerals, ceramics, metals and alloys for PDF-4+.
Can you explain the identification and quantitative analysis properties of the database?
Identification is fundamentally based on the accuracy and precision of d-spacing measurements made with modern powder diffraction equipment. Since most materials have multiple characteristic d-spacings, this provides a “fingerprint” for identification. The database contains hundreds of millions of characteristic d-spacings for solid state materials. These are placed in several types of indexed tables for rapid automated identification when compared to an unknown.
The database contains multiple tools for quantitative analysis; some of which use the intensity characteristics of the diffraction pattern, while others use the physical property characteristics of the materials (i.e., elemental composition). In the Powder Diffraction File™, we include all the various parameters needed for quantitative analysis. These parameters include atomic coordinates, unit cells, I/Ic values, and full digital patterns so that methods, such as the Reference Intensity Ratio, Rietveld, LeBail, and pattern fitting methods can be applied.
Dr. Timothy Fawcett received his B.S. in Chemistry at the University of Massachusetts and his Ph.D. in Inorganic Chemistry at Rutgers University. Tim worked for The Dow Chemical Company for 22 years, starting in the diffraction laboratory of Analytical Sciences and eventually managing several new product development groups within Corporate R&D. He became an ICDD fellow in 2000 and joined the ICDD as Executive Director in 2001.