Analysis of Powder X-ray Diffraction Data

Powder X-ray diffraction offers insight into key aspects of solidified pharmaceutical compounds and excipients. These can range from simple form identification tasks over analyses of purity, composition and degree of crystallinity to sophisticated structure solution efforts. Due to the complexity of the data, computational analysis is crucial to access the information content contained in the diffraction data.

Accelrys offers a comprehensive set of advanced tools to cover any aspect of powder X-ray data analysis, together with platform capabilities for automation and web-enablement of these tools.

Form Identification

Form identification tasks can be accomplished using various techniques. Indexing tasks performed by Materials Studio modules Reflex and X-Cell allow determining unit cell parameters based on peak positions. Reference structures (either known from previous indexing or structural database such as the CSD) together with the Reflex module can accurately assign experimental patterns to the correct structures. For routine analyses, these refinement tasks can be automated either within Materials Studio’s scripting API or as a Web Port application within Pipeline Pilot’s data-pipelining environment.

Related Case Studies
Crystalline component identification from simulated powder X-ray diffraction patterns
X-Cell - a novel and robust indexing program for medium- to high-quality powder diffraction data

Form Quantification

Quantification of polymorphic mixtures, hydrate to anhydrate transitions, impurity phases, or sample compositions are key tasks not only during early development, but also during scale-up studies. The Reflex QPA module provides a flexible solution to this challenge as it allows using both diffraction patterns and crystal structures as reference phases. Furthermore, this application can be automated either via scripting or as a Web Port application within Pipeline Pilot’s data-pipelining environment.

Related Case Study
Formation of isomorphic desolvates

Amorphous Content Characterization

Monitoring the degree of crystallinity is crucial not only for controlled dissolution behavior of the solid form, but can also critically affect the shelf life of a pharmaceutical product as the amorphous content can crystallize over time. The Reflex module allows estimating the degree of crystallinity based on powder X-ray data, avoiding costly dissolution experiments. Materials Studio’s Amorphous Cell and Forcite modules can be used to simulate the diffraction pattern of 100% amorphous samples – a distinct advantage as purely amorphous samples are often difficult to prepare experimentally.

Structure Determination

In pharmaceutical applications it often proves difficult to grow crystallites large enough to perform single crystal X-ray diffraction experiments. In these cases structure solution from powder data might be attempted. The Materials Studio module Reflex Plus offers a complete package for the determination of crystal structures from medium- to high-quality powder diffraction data. Complementary Materials Studio modules such as Forcite or DMol³ can help be used to verify the proposed structure by performing total energy calculations.

Related Case Studies
Crystal structure determination from experimental powder data
Crystal structure determination from conventional powder diffraction data: Application to hydrates, hydrochloride salts, and metastable polymorphs
Crystal structure solution of a metastable polymorph from powder X-Ray diffraction data

Related Software and Services

• Materials Studio Amorphous Cell - Provides a versatile technique used to develop an understanding of molecular properties and behavior, especially for liquids and amorphous polymers
• Materials Studio Forcite - Performs energy calculation and geometry optimization of molecules and periodic systems
• Materials Studio DMol³ - Combines computational speed with the accuracy of quantum mechanical methods to predict materials properties both reliably and quickly
• Materials Studio Reflex - Aids the determination of crystal structure and assists the interpretation of diffraction data
• Materials Studio Reflex QPA - Allows the determination of the relative proportion of different phases in a mixture based on powder diffraction data
• Materials Studio Reflex Plus - Assists in the determination of crystal structures from medium- to high-quality powder diffraction data
• Materials Studio X-Cell - Provides an indexing algorithm for medium- to high-quality powder diffraction data
• SciTegic Pipeline Pilot Web Port - Allows protocol based applications to be presented through a web interface that is intuitive and easy to use for the chemist, but still takes full advantage of the high-speed processing and automation that Pipeline Pilot provides.
• Contract Research & Scientific Consulting Services - through access to our full suite of software, the experienced computational scientists at Accelrys can collaborate with you on your projects.