Reports on Meetings in 1996

• 7 Nov 96 Crystallography in Industry
• Industrial Award for 96
• Sessions at BCA 96 Annual Meeting in Cambridge
• 17 September 96 Worksh op practical Reflectivity for Industry
• 18 Mar 96 X-RAY POWDER DIFFRACTlON in the PHARMACEUTlCAL INDUSTRY

X-RAY POWDER DIFFRACTION in the PHARMACEUTlCAL INDUSTRY.

a meeting held at Glaxo Wellcome, Stevenage, l8th March 1996

This meeting was attended by 45 people, mainly industrial users of powder crystallography in the pharmaceutical industry. There were also representatives from academia, agrochemi cals, dyestuffs, and forensic science who all have some interest in relatively small organic molecules as opposed to the inorganic applications pursued by most of the powder crystallographic community. In general, organics crystallise in large, 'soft' unit cells of low absorption with diffraction characterised over a relatively small range of 2 theta (typically ca. 0-35 degrees). Indexing as a proof of purity and quantitation of polymorphic mixtures are particularly important issues.

Dr St eve Tarling discussed the power of the technique for defending patent protection of polymorphs. The cost of XRPD equipment is insignificant compared to the legal costs of patent litigation!. The theme was continued by Dr Marek Zakrzewski (Philips;Holland) who discussed the factors influencing the nature of pharmaceutical products (habit, milling, desired polymorph), The role of single crystal data, theoretical powder patterns and molecular modelling was also considered.

Dr Marcus Winter (Si emens) spoke on optimising the configuration of powder diffractometers for pharmaceutical applications. Of particular interest was a means of looking at formulated tablets in-situ.

Dr Jamshed Anwar discussed pressure induced phase changes by experiment and simulation. These experiments give an an insight into the sensitivity and compressibility of formulated tablets.

The afternoon session started with three short talks by Bob Lancaster, Sue Staniforth, and Philip Lake (all Glaxo-W ellcome). They discussed the sensitivity of various drug molecules to relative humidity and temperature.

The final lecture of the day was given by Robin Shirley (University of Surrey), who demonstrated powder indexing software and discussed the importance of indexing in the characterisation of pharmaceutical polymorphs.

There followed a period of open discussion on a variety of subjects including indexing, calibration, regulatory issues, and how the instrument manufacturers can be more helpful to a minority group in the field of XRPD.

The future of a group specialising in organic/pharmaceuticals crystallography was aired. It was generally felt that the day was an unqualified success and given the response and interest in the meeting it was agreed that there should be more activity in the area. It was also agreed that further such meetings should be held under the auspices of the BCA.

Philip Lake

Indust rial Group

Report - Spring Meeting - Cambridge

April 1st - April 4th 1996

• I Structure and DataTim Hyde
• II Preferred orientation Craig Adam
• III Essential Crystallography Course Bruce Fox

I - Structure & Data

The first lect ure session, 'Structure and Data' complemented the Industrial Group organised 2-day intensive short course run at the Conference on "Essential Crystallography for Powder Diffraction Users" by Jeremy Cockroft, (Birkbeck College, London).

X-Ray Absorption Spectroscopy (XAFS), as a complementary technique to XRD was described by Neville Greaves, (CCLRC Daresbury). Due to its ability to look at local structure in liquids and amorphous materials in addition to crystalline solids, and its element specific nature of analysis (and low concentration levels detectable), XAFS is an ideal complementary tool for the diffractionist. An example of recrystallization of ion beam damaged silicon wafers was utilised to show its ability to look at impurity level concentrations of arsenic in silicon at the surface and in the bulk material. Cordierite glass ceramics was another ideal example described which illustrates the complementarity to XRD. Chromium oxide as a nucle ating agent in cordierite was studied by XAFS with X-Ray diffraction and X-Ray Small Angle Scattering in an in-situ experiment at temperatures to 1300 C. A pattern assigned to a magnesium chromium oxide-magnesium aluminate spinel was identified as the chromium intermediate.

An overview of the determination of a Single Crystal X-Ray Structure using modern techniques was provided by Marjorie Harding, (Liverpool University). Provided a suitable quality crystal is available, a full structural analysis using modern automated software and hardware, is likely within 1-3 days. Some 15,000 such 'small molecule' structures are published annually. New developments such as area detectors, rotating anode generators and routine cryostatic crystal cooling to 80K will speed throughput further, and allow problem structures' (disorder, twinning, large molecules, small crystals, etc.) to be further addressed.

An overview of modelling and display software for use in crystallogr aphy was provided by Robert Jackson, (Keele University). With today's computing facilities, PC based systems are often adequate whereas once only workstations were employed for these techniques. The talk was fully illustrated with molecular graphics output from a wide range of software sources. The differing structural refinement approaches centred on 'structural', or 'energy' based calculations were outlined. Interatomic potentials are necessary for energy based refinement, which i s often the "best" technique if close to the result. 'Structural' based refinement using average bond lengths and angles to predict structures shows some exciting possibilities. Trial random structures are generated and a goodness of fit factor calculated which takes into account penalties for variations from averaged structures. The best fits can now be 'bred' to generate better refined structures. Examples from the zeolite structures MAPO-36 and Na Zeolite Y, and lithium ruthenate were used.

The main structural databases available to crystallographers were described by Sharon Bellard, (Royal Society of Chemistry). The philosophy behind all of the main structural databases is similar. Comprehensive coverage of a well defined subject area containing accurate information which has been critically evaluated was stressed for all databases. The accessibility was also described for each database, as formats such as CD-ROM, on-line, and Internet enquiries are now available . The NRCC Metals Data File and the Inorganic Crystal Structure Database, (inorganics), Cambridge Structural Database (organic and organometallics) and ICDD-JCPDS (organics and inorganics) and the Protein Database ('PDB' - biological macromolecules) Databases were fully covered by the lecture. (Editor's note: you can get further information about any of these database from links in the BCA home page on the World Wide Web).

Finally, Jan Skakle, (Aberdeen University) , described the production of good quality XRD Data for submission to the ICDD. Through the ICDD Grant in Aid program approximately 30 diffraction patterns per year are submitted by Aberdeen University for inclusion in the JCPDS Database. All aspects from the reason for analysis (new phase, re-examination of previous data), through selection of standards (internal or external), to indexing and lattice refinement were covered, along with background information on JCPDS quality mark nomenclature and criteria. Tim Hyde, Johnson Matthey
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II - Preferred Orientation

The Industrial Group plenary lecture was chaired by David Dyson who introduced the speaker, Dr David Dingley (Bristol University). The technique of orientation imaging microscopy has been developed by Dr Dingley and his collaborators in the USA, over the past few years. Dr Dingley briefly reviewed its development and application before describing the technique in detail. The principle involves the collection of the diffraction pattern, produced from a sample in the SEM, which results from the, largely elastic, backscattered electrons. This clearly contains crystallite orientation information for each point on the surface of the material and the overall diffraction "image" describes the surface texture. The key to the success of the technique, as far as the materials scientist is concerned, arises from the sophisticated image processing which Dr Dingley described in his talk. The basis of this is a half-transformation of the diffraction image where a matrix is constructed, the elements of which correspond to the diffracted intensity at each pixel point. A sequence of look-up tables are used to identify symmetry axes and eventually phase identification. By setting thresholds, grain boundaries may be identified and textures highlighted; in exceptional cases with a resolution of 4nm. Dr Dingley then demonstrated the power of the technique by a range of metallurgical examples - Al and Ni based alloys, retained Austenite in steel and the partial crystallisation of Ferrite. He emphasised the quantitative nature of this approach; it can provide, instantly, colour-coded maps of grain-size distributions and orientation distributions across a metal surface. A consequence of this quantitative approach is that the metallurgist needs to specify clearly what is meant by a particular microstructural parameter.

The plenary was followed by a session of contributed papers on the theme of "Preferred Orientation". This session carried forward some of the materials characterisation issues raised during the plenary in the area of texture analysis, with an emphasis on X-Ray diffraction techniques. The session was chaired by Colin Small. The first two contributors focused on experimental aspects, in particular on methods of ensuring a good signal/noise ratio in pole figures and subsequent orientation distribution functions.

Erich Hovestreydt (Siemens Analytical) described the "Hi-STAR" area detector system and its advantages in texture analysis. This system is a compact, multiwire, 2-dimensional, position sensitive detector which offers good spatial resolution (100gm) and a high speed of data acquisition. He showed its benefits through a range of applications which included induced strain in polypropylene under stress, the textu re and molecular orientation in wool fibres and highly textured, deposited Cu layers.

This talk was followed by one from Dr A Kinneging (Philips, Almelo) on the use of oscillation methods in texture measurement. This approach aims to improve the data quality obtained in the conventional Schulz method of data acquisition, by oscillating the sample in order to increase the crystal statistics. Various modes of oscillation were described and evaluated. The optimum technique was concluded to be plane parallel oscillation perpendicular to the diffracting planes under linear X-Ray illumination. This maximises the surface area from which diffracted rays are collected. The technique was illustrated by an application to coarse grained aluminium.

It was the task of the next speaker, Dr David Dyson (British Steel) to cover the interpretation of X-Ray diffraction data, in the context of texture. The semi-quantitative pole figure approach examines the orie ntation of a particular set of (hkl) planes. Clustering of points indicates grains which are oriented in a similar fashion. There are a range of standard pole figures for the various classical textures found by the metallurgist. The rather more quantitative approach of calculating and using orientation distribution functions (o.d.f.) was then covered. This involves deducing the rigorous relationship between the distribution of crystallographic axes and the sample axes for the individual crystallite s in a material. The o.d.f. can be usefully employed in following changes in texture resulting from mechanically and thermally induced transformations in the material. Finally Dr Dyson included a mention of the use of microscopy in texture measurement and illustrated the power of this technique in showing how grain textures blend together.

The remaining presentations indicated the diverse range of materials exhibiting texture and texture-related properties.

Dr Alun Bowen (DRA Farnborough) covered a range of applications to engineering materials. He explained the crucial links between microstructure and the processing, properties and performance of a material. Dr Bowen explained the difficulties in linking microstructural analysis to the performance of structures of magnitude 102m. Such links could benefit from a two-stage approach which included consideration of the intermediate stage of fracture mechanics ( 10- 3m).Texture in a product may be a good or bad f actor; in particular the link between texture and the elastic modulus of metallic engineering materials is an important relationship. A useful monitor of texture in this context is the volume fraction of basal poles along the stress axis determined by X-Ray diffraction. This correlates well with elastic modulus in a variety of materials, including Ti alloys, and allows investigation of superplastic strain. A similar approach has been used successfully in the examination of vapour deposited Al alloys and in SiC composite Al alloys. The link between texture and fatigue life for Ti:Al alloys was illustrated. The talk concluded with a warning to beware the gremlin pole figure!