X-ray powder diffraction - A powerful tool in the pharma industry
Dr Michael Caves, Malvern Aimil Instruments Pvt. Ltd.
Describes this tool, its current & futuristic applications through this Q&A.
Why is X-ray powder diffraction (XRPD) so important to the pharmaceutical industry?
XRPD is a powerful tool in the pharma industry because of its capability to help researchers identify crystalline structure of materials, identify phases that are present, distinguish between polymorphs, and even elucidate structure in amorphous materials. Proving that a new chemical entity (NCE) is indeed a novel structure is critical to patent positioning. Additionally, powder diffraction measurements can be made under non-ambient conditions (temperature, humidity, etc) such that material stability can be tested under extreme conditions. And most applications of XRPD are non-destructive in nature, leaving the sample intact for further investigation by other techniques.
What advances in XRPD in recent times have been most significant for pharmaceutical analysis?
In the past five years, new optics, stages and detectors have allowed more application capability to be added to a multi-purpose diffraction system, as well as improved the performance for even routine types of measurements. For example, new XRPD optics, such as PANalytical’s BraggBrentanoHD optic delivers 40% improved sensitivity for ultra low-level polymorph screening. New applications possible on an XRPD system include small angle X-ray scattering (SAXS) for nano-sized materials, which can determine size distribution and shape of materials including micelles, proteins, and nano-particles for drug delivery; with new detector technology and easy conversion of an XRPD system to hard radiation (such as Silver X-ray tube an- odes), pair distribution function (PDF) for investigating the structure of nano- and amorphous materials has brought this traditionally synchrotron beam-line application to a laboratory system; and these same advanced detectors for hard radiation lend themselves nicely to computed tomography (CT)on an XRPD system, to analyze non-destructively the inner structures of coatings on tablets, evaluate porosity and distribution of components within tablets, and even investigate tablets within packaging.
What are the recent trends in XRPD that you have seen from the pharmaceutical industry?
We are seeing a trend toward centralized research labs when mergers have occurred. This in turn has caused an increased interest in XRPD systems that can be used for multiple applications versus dedicated
systems for a specific application. So systems combining combinatorial screening, environmental chambers (heat and humidity), SAXS, and transmission capability are routinely being supplied to this industry.
What other techniques complement XRPD?
XRPD analysis for polymorph identification, structural analysis, and nano-particle size and shape is complementary to many techniques available in today’s analytical laboratories, not only for the information provided but also because it is non-destructive. Solid state NMR, spectroscopies such as near infrared(NIR) and Raman, and single crystal diffraction all provide molecular and crystalline structure information that compliments XRPD data. X-rayFluorescence (XRF) spectroscopy determines elemental composition, and data can be used in an automated fashion within XRPD phase analysis to restrict the search to only phases chemically possible.
How can a powder x-ray diffraction system assist researchers doing protein crystallography?
The two main applications that come to mind are powder diffraction for screening samples that will be taken to a beam line for structure determination, and SAXS of proteins for size and shape determination. Screening samples headed for a beamline can show the quality of the sample, whether it is a single phase, and can also allow indexing to determine lattice type and lattice parameters of the material. The advent of evacuated beampath SAXS chambers has also allowed for bioSAXS experiments on a multipurpose XRPD platform, to study for example the overall size, compactness and aggregation behavior of protein molecules in the irnative state (crystallization not required), and even to determine the 3D envelope structure at a resolution of 1-2 nm. And a very new addition to capabilities on an XRPD system is in situ protein crystallization with our new computer-controlled transmission humidity chamber.
What are up and coming XRPD techniques or applications that would be of interest to pharma?
One application that we see significant interest from pharmaceutical researchers is pair distribution function (PDF) analysis, which can be used to discriminate between different amorphous or crystalline pharmaceutical structures. Protein screening and indexing for researchers in the area of protein crystallography, which is typically done on single crystal instruments or at beam lines, is another area we see as a growth area for XRPD.
Finally, we have advanced software capability now, which includes using a method known as partial least squares regression (PLSR) to analyze XRPD data for things like % crystallinity without the use of an internal standard, keeping the method non-destructive. More developments are in the works, and it is through close collaboration with pharmaceutical companies that we are able to make many advances in XRPD to address the needs of the industry.
For more details, please contact:
Malvern Aimil Instruments Pvt. Ltd. Naimex House, A-8 Mohan Co-operative Industrial Estate, Mathura Road, New Delhi – 110044
Tel : 011-30810244 Fax : 011-26950011
Email : firstname.lastname@example.org
BioSAXS data confirming the tetramer structure glucose isomerase
The crystallization speed of salbutamol sulfate as a function of relative humidity at 25oC