Industrial Group of the BCA

Reports on Industrial Group Meetings in 1998

18 March 1998 Ph armacy meeting
Sessions at BCA 98 Annual Meeting in St Andrews
Workshop on Diffraction at Elevated Temperatures 3 June 98
Workshop on Residual Stress Measurement by X-ray Methods Open University, Milton Keynes
4 November 1998 Autumn meeting

Structural Elucidation of Organic and Pharmaceutical Materials by laboratory XRD

Roche Discovery, Welwyn, 18th March 1998.

The meeting, which was attended by 60 people, was the second to be held under the auspices of the Industrial Group of the British Crystallographic Association and follows successful meetings in the two previous years. The meeting was opened by Dr Mike Atwood of Roche Discovery who took the opportunity to explain the increasing importance of crystallographic techniques to the company and the success they were having in obtaining structural i nformation from X-ray powder data.

Prof. Daniel Louer of the University of Rennes then discussed his approach to structure analysis from powder data with laboratory X-rays. Since 1986 his group has been successful in solving from scratch thirty structures. They include cases with unit cell volumes as large as 7471A and up to 29 atoms in the asymmetric cell. He stresses the importance of precision in peak position which was attainable with correctly adjusted diffractometers, e.g. average discrepancies of 0.005deg two theta.

Dr Jeremy Cockcroft of Birkbeck College then spoke on the topic of sample preparation and data collection. This depended firstly on the purpose of the data collection and secondly on the possible means of obtaining the data. With these decided time should the be spent preparing a pure sample, preparing the sample, collecting high resolution and high quality data, plotting data and determining peak positions, indexing peaks and refining lattice parameters.

Dr. Mary Jane Tremayne of the University of St Andrews then explained the practical aspects of Rietveld Refinement. She explained the technique uses a least squares refinement of the whole pattern to generate best fit and that it makes no attempt to match intensities or to allow for overlap. Experience has shown that it is better to use restraints rather than constraints when optimising the data and examination of the residuals provides str ong clues as to the nature of any error in the fit.

Dr Steve Norval then updated the meeting on the progress that was being made towards introducing an European X-ray diffraction standard. The standard is required for the accreditation of laboratories and in the support of patents. The draft is expected by May 1999 and once adopted it is expected to become an International Standard.

Prof. Bill David & Dr Ken Shankland of the ISIS facility then related the considerable success they were having using their approach to Ab-Initio structure determination. They collect high quality data at angles beyond those usually used for indexing and then use the genetic algorithm and simulated annealing, which avoid false local minima on the response surface, to generate theoretical powder patterns which they then compare with the experimental data. Their approach can handle ionic structures and real molecules that are flexible and it has been used to so lve the structure of compounds from camphor to capsaicin.

Dr Chris Frampton then presented a paper on the isolation and crystallisation of the elusive orthorhombic polymorph of paracetomol. The work had been undertaken as part of a tripartite project between Roche, Pfizer and SKB and the Universities of Bradford, Surrey and Strathclyde. Early attempts at isolating Form II were unsuccessful but it was found that Form II was produced when the molten Form I was cooled. This ma terial was then used to seed saturated solutions of the drug. This procedure produced the required form provided the product was harvested within 30 minutes to prevent reversion to form I. Examination of Form II has revealed that it can, unlike Form I, be used for direct compression formulations.

The final presentation was by Dr Arndt Kern of Bruker AXS who presented information on the various powder X-ray equipment available. The meeting was closed by Mr David Taylor who thanked those who had contributed to making the day a success. The Industrial Group would like to thank Philips Analytical and Bruker AXS for subsidising the meeting.

Philip Lake

Report of Industrial Group Annual Spring Meeting, 1998, St Andrews

A full programme, set in delightful if wet St Andrews, resulted in good attendances at the Industrial Group presentations (and at the Sunday evening Ceilidh!).

Plen ary Lecture - Order and Disorder in Block Copolymer Systems.

Patrick Fairclough presented a paper on order and disorder in polymer systems. Using an extruder with a slit die he and his co-workers have investigated the crystallisation of homo and co-polymers on extrusion. By using synchrotron radiation and simultaneously measuring the wide (WAXS) and small angle X-Ray scattering (SAXS), they have concluded that homopolymers initially crystallise by spinodal decomposition an d not by nucleation, whilst copolymer behaviour depends upon block length. Results were presented for both SAXS/WAXS and grazing incidence SAXS/reflectivity.

Bruce Fox

The subject for the first Industrial Group Session was "Data Quality -Fit for the Purpose", with Mary Vickers (Cambridge University) chairing the session.

Ron Jenkins (ICDD) spoke first, on the problems of preparing an d identifying samples. The subjects covered ranged from how to mix samples, getting good counting statistics to the problems of data collection and the advantages and disadvantages of internal and external standards. He then went on to review developments in the Powder Diffraction File (PDF). These include the imminent inclusion of calculated patterns from the Karlsruhe Inorganic Crystal Structure Database ( taking the total number of patterns to about 110,000 ), and the development of the PDF third level full pattern version.

Jamshad Anwar (King's College London) then talked about the difficulties of analysing organic materials, with particular reference to pharmaceuticals. The complexities of polymorphs, hydrates, phase instabilities during grinding, low symmetry, low scattering and the presence of texture make these compounds particularly difficult to analyse. Profile fitting and Rietveld analysis were reviewed and the limitations of both techniques were discussed. Those of us in the audience who work on well behaved metallic crystalline materials were extremely grateful that our samples are not as difficult as this to work on!

Richard Todd ( University of Manchester ). showed how the old-established techniques of line broadening can be applied to new equipment on new materials to provide information that cannot be obtained in any other way. Richard is studying Al₂O₃/SiC ceramic composites for wear applications and has used peak shift and line broadening from neutron scattering data (collected on the HRPD in the ISIS facility) to obtain size and residual stress data for the different crystallites in his materials. He emphasised that one type of analysis is not sufficient to get the answer - you require several means of analysis to achieve the correct answer.

Kevin Knight (RAL) finished the session with a talk on the wide applications of neutron diffraction. He began by briefly d escribing time of flight neutron diffraction and then demonstrated the unique problem solving capabilities of the technique. Examples ranged from the structure of Russelite (showing light atom sensitivity) to octahedral cation site ordering in Olivine, and the structure of fast ion conductors in fuel cells.

The session provided a valuable insight into how various techniques can ( and possibly more importantly cannot ) be used , and showed that only by choosing the right combination of data collection and analysis can you hope to get "the right answer".

Colin Small

The Alun Bowen Industrial Lecture was presented by Prof. Bob Snyder of the Ohio State University. Titled "The Development of X-ray Analysis," Prof Snyder painted a broad tapestry of X-ray utilisation, starting with Roentgen in 1895 and finishing with the latest methods such as grazing incidence and EXAFS. Pointing out that, within 15 years of Roentgen's discovery most of the tools available today had been defined, each specific discovery was exemplified with slides of the original work followed by its development and the latest implementation of that idea. As examples of the modern scene, the arrival of synchrotron radiation with its wavelength tunability has led to EXAFS and XANES analysis of poorly crystalline materials. The precision of high resolution instruments has revealed fundamen tals of superconductivity, and grazing incidence has opened the door to thin film analysis. Time dependent studies are now readily achievable, allowing reactions to be followed together with, for example, phase transitions, kinetics, etc. A thoroughly fascinating review of our field, and a superb re-statement of the utility of X-rays.

Bruce Fox

Hardware and Software Developments.

Marcus Winter of Bruker AXS presented a range of hardware (for XRD, single crystal, area and Position Sensitive detectors) available from Bruker, concentrating on the new D8 diffractometer. With modular design, features of the goniometer were detailed as: accuracy and reproducibility 0.0001deg; an 11cm concentric hole on the goniometer axis for large samples; variable diameter measuring circles to take advantage of parallel beam geometry and focusing mirrors; a wide dynamic range scintillation counter. The capability of examining a wide range of samples was stressed, from engine crankshafts to capillaries and fibres. New, 32bit software completes the package. Finally, a new x,y,z translation stage for microdiffractometry (50m spot size) was detailed, for use with the GADDS area detector.

Paul Pennartz of Nonius BV detailed the use of the 120deg curved plate detector, pointing out the advantages of this arrangement for time resolved studies. The goniometer is provid ed with a central hole capable of taking a range of fitments. An example of clay mineral analysis was presented: using a micro-well holder, 1.75mm x 0.03mm, similar results were obtained to using normal holders. As an example of time resolution, the intercalation of montmorillonite by water was shown at 5 second intervals.

Celeste Reiss of Philips next presented the Xpert MRD goniometer. The leading innovation here was claimed to be the introduction of "plug-in" optical mod ules. Tube orientation from spot to line focus can be achieved by simple rotation of the tube holder, and 2 plug in modules can be accommodated after the tube. The various modules are: graded mirror giving high resolution and up to 10x increased count rate; monocapillary giving a 130micron spot size with only 0.3deg divergence; and a polycapillary which gives "quasi parallel" beam of 5 to 10mm diameter with again low axial divergence (useful for stress and texture). A full suite of 32bit software wh ich includes texture software capable of Orientational Distribution Function (ODF), inverse pole figures and real 3D plots is available.

Graham Fraser of Bede Scientific Instruments Ltd. next detailed a revolutionary X-ray source. Using electromagnetic focusing of the electron beam in the tube together with a close coupled specularily reflecting mirror, spot sizes from 25 to 8micron are achievable, but with an X-ray brightness equivalent to 5kW rotating anode generators, a lbeit with less than 50W input power! Although the stated aim is to provide a source suitable for protein crystallography, its application to diffraction problems in general seems certain. Examples of phase gradient contrast radiography were presented, with comments on the wide potential that this technique offered in non destructive analysis of a wide range of samples.

Marc Wisemann of Stoe & Cie. next detailed the STADI MP goniometer, where considerable thought has l ed to a unique system where three geometries are obtained on one optical bench. A monochromator remains attached to the tube, giving a beam profile which initially converges to a point focus and the diverges. By choosing sampling positions in the three zones, transmission data of high resolution can be obtained (convergent beam area); texture and residual stress are effected at the point focus; Bragg Brentano geometry is achievable if the divergent beam area. Thus, by simply moving to one of three p re-set positions, a wide range of experiments may be effected on one goniometer, with no re-alignment required.

Alex Renshaw of Oxford Cryosystems finished this session with a demonstration of the utility and flexibility of the crystallographica software package which runs on a PC.

Bruce Fox

INDUSTRIAL GROUP MEETING REPORT

Workshop on Diffraction at Elevated Temperatures.
I.C.I. Technology, Wilton, 3rd June 1998.
The day began with a tour of the laboratories at Wilton followed by a formal welcome from Steve Fletcher. Dave Taylor and Steve Norval continued the days events with a Round Table Discussion covering:

Instrumentation

Temperature control and calibration

Calibration of the goniometer

Data quality

Gaseous environments etc.

David Taylor gave an account on the progress of H igh Temperature Diffraction over the last 30+ years at Pilkington Glass, Lathom. The first instrument used there was a Rikagu Denki obtained in 1963 - the latest being a GTP Chamber (1990). The factors influencing the development of the technique such as - more powerful x-ray sources, solid state electronics, computer automation, detectors and x-ray optics were described. Such developments have enabled in-situ studies of dynamic processes to be made such as reactions, phase transitions and grain gro wth. Such reaction studies at Pilkington involve devitrification processes and following the phase transitions of quartz through to crystobalite and tridymite. David pointed out that care must be taken when studying reactive species as the associated enthalpy can lead to very large changes in the temperature of the specimen. A number of other complementary techniques are employed such as DSC, TGA, TMA, MS (EGA) and optical which identify temperatures where changes occur without necessarily identifyi ng the phase. Tips were given on how to maximise intensity and gain optimal resolution by slit choice. Time was spent on discussing the furnace requirements and some special features where corrosive atmospheres and high pressures are involved as well as the different methods of heating and controlling the furnace temperature and temperature calibration. A list of useful materials for temperature calibration purposes was provided.

MATERIAL TEMPERATURE°C TRANSITION in dium 156 melt tin 232 melt potassium chlorate 300 ortho > cubic lead 327 melt zinc 420 melt potassium sulphate 583 ortho > hex

After lunch Jamshed Anwar (Computational Pharmaceutical Sciences) gave a presentation on Quantitation and Reaction Kinetics. He described a method for in-situ analysis using the transformation of b to g sul fanilamide as a model process. This transformation takes place at 132°C in under 4 minutes. Consequently a rapid means of collecting data is necessary.

The final session of the afternoon dealt with some user applications. Mark Farnworth of Pilkington Technology described in detail a number of features outlined earlier by David Taylor placing particular emphasis on the design and operation of heater control equipment whilst Ian Rigby of Zeneca Specialties described the 'screening' process employing several techniques at Blackley in polymorphic characterisation for new research compounds and details regarding the design and performance of an in-house constructed X-ray hot stage unit.

Useful Reference Books and Papers
This list has been added to the list of high-temperature equipment

Doug Bray

Workshop on Residual Stress Measurement by X-ray Metho ds

The Open University, Milton Keynes,24th September 1998

Twenty-seven people attended the meeting held under the Auspices of the Industrial Group of the British Crystallographic Association. The delegates were welcomed by Dr. Mike Fitzpatrick who explained the structure of the Open University and the importance of residual stress measurements within his Materials Department.

Kath Clay of Hexmat Materials Consultancy gave the first presentation. This was a concise and clear explanation of the technique and its limitations. She stressed that it is a surface technique and that depth profiling meant removal of material, which may in itself modify any residual stress in the underlying matrix. The difference between Elastic and Plastic strain was also clearly explained.

The next presentation was given by Colin Small of Rolls-Royce. He encouraged users of the technique to explore the use of different radiations and (hkl) reflections to get as high a 2q angle of diffraction as possible. This could reward the user with better quality data, accuracy and respectability. He than gave examples of analysis of some vital components in Rolls-Royce Aeroengines.

Phil Holdway, DERA, Farnborough, then outlined the various techniques for pinpointing the peak positions. This provoked a lively discussion which involved Ka ₂ peak stripping, peak profile fitting, use of peak centroid, use of peak t ip only, cross correlation technique, number of counting positions over a peak, etc. Delegate participation cunningly led by the presenter made this a very informative session.

Colin Small then gave a presentation based around material removal and corrections, and best practice. This was to have been presented by Neil Fox of Rolls-Royce who could not be present because his wife decided it would be a good day to give birth to a bouncing 9lb 10oz baby boy - Congratulations to Neil and his wi fe.

Finally Brian Shore of Newcastle University demonstrated how residual stress measurements could be performed on difficult samples like gear wheels. However if Brian's ingenious sample presentation failed it became necessary to cut up the sample. How to do this without altering the original stresses in the gear provoked a final flurry of suggestions and ideas.

The meeting was closed by Kath Clay who thanked those who had contributed to the successful meeting. The Industrial Grou p would like to thank Kent Engineering and Stresstech for subsidising the Meeting.

Derrick Hart

Autumn Meeting of the Industrial Group

4 November 1998, Zeneca Specialities, Runcorn, Manchester

The meeting was opened by Dr Steve Norval, chairman of the Industrial Group, and we then watched a site safety video. Dr Graham McPherson, our host and local organiser, gave an introduction to Zeneca which is often considered as purely a pharmaceutical company. However, it is best considered as a life science company as in addition to the pharmaceuticals, there are two other main businesses: agrochemicals and specialities. The latter includes various food companies, bioscience and life science, resins and industrial colour (inkjet colours).

DARTS (Daresbury Analytical Research and Technology Service) was set up to make it easier for industrialists to obtain access to the synchrotron source at Daresbur y. Dr Chris Frampton (Roche) outlined two excellent examples of the application of Darts to pharmaceutical problem solving. In the first instance Roche had a 64 atom structure (33 non H atoms) from which they could only obtain powder data but really wanted to know the connectivity. Chris indexed the data and guessed a space group using in-house powder data. Two data sets were then obtained on station 9.1: the first was used to confirm the space group and the second one (collected wi th increasing dwell times at higher angles) was used for structure determination. The structure was solved by Prof Bill David and Dr Ken Shanklin using a simulated annealing approach. This is currently the largest structure solved from powder data and the information has been used in a patent. Chris's second example was solving structures from single crystals that were too small (in one dimension) to give useable in-house data. The material of interest,C₂₂H₃₅N₃O₅S₁, gave 9 solid forms two of which were solved, for regulatory purposes, using data obtained by DARTS.

Having had such a positive introduction the benefits of radiation synchrotron, Professor Bob Cernick assured us that the situation should improve and not deteriorate. The synchrotron source at Daresbury was the first such facility and is now showing signs of age. However, updates are planned over the next few years and when the new facility, Diamond, is ready these new stations will be placed on it. Both the government and Welcome Trust have agreed to provide funding and the new synchrotron source should be built in about 2004 or 2005 at a site still to be agreed.

Returning to pharmaceutical matters, Elaine Smith (Heriot Watt University) talked about her modelling work which seeks to predict polymorphs. Experimental evidence suggests that both phenazine and perylene have at least two polymeric forms but in each case only one structure has been well determined. Using the reported cells for both solved and unsolved structures she searched for potential packing arrangements and then ranked them using calculated energies. The work postulates two structures for which there is currently no reliable experimental determination.

In the 1998 release, the ICCD (International Centre for Diffraction Data) powder diffraction data base will grow by a step jump; 40000 additional patterns of which 8000 are new entries. Th ese have been calculated from the structural data in ICSD (Inorganic Chemistry Structural Database) and it is anticipated that ICCD will soon do the same for organic structures. The data have now grown so large that it is hard to bind books that contain all the entries. Thus ICDD are bringing out new software, PCSIWIN, which can be used to provide the functionality of the Hanawalt and Fink search manuals. PCPDFWIN software has also been upgraded and the new CD-ROM data needs the new search software. David Taylor demonstrated both these products. The only negative response was disappointment that it appears one must type the d/I file into PCSIWIN and cannot just copy and paste it in.

After lunch David Taylor kept us awake by wearing an American cap and telling us about the delights of Denver. Most of us have only glanced though the reports in Advances in X-ray Analysis (now available on a searchable CD-ROM). The event is a very large conference coverin g both XRD and XRF with many sessions running in parallel. In addition there are several workshops and teaching sessions.

Electron backscattered diffraction (EBSD) is becoming established as a technique that provides texture information which is often complementary to that provided by classic X-ray diffraction techniques. Being a scanning technique, information on grain size and misorientation can be obtained as well as a full pole figure or ODF. Dr Ian Brough (Manchester Materials Science Centre, UMIST) outlined the principles, advantages and limitations of the technique. As a metallurgist, he gave examples of its use to investigate texture in 3%SiFe for transformers and Al for cans where electrical and mechanical properties are influenced by texture. He also mentioned that in studying non-conducting samples difficulties can arise and sometimes these can be solved by a thin coating of C.

When glancing at glossy magazines one does not immediately think that the paper is covered in kaolinite. Dr Nick Elton (English China Clays) gave us a glimpse of the many factors that have to be considered when coating relatively rough paper to give a glossy finish and a good printability. X-ray data (peak ratios, rocking curves and/or pole figures) are used to quantify the in-plane alignment of the kaolinite and this correlates with an industrial measure of gloss. He showed how X-ray data have been used to help optimise conditions for calendering by investigating the effect of changing the temperature, pressure and number of cycles.

Dr Jim Chisholm (Health and Safety Laboratory) described some of the work that has been going on as part of the revision of the Method for Determination of Hazardous Substances for crystalline silica. The health hazard arises from quartz particles below a certain size and is measured by collecting airborne particles on filter paper in a small personal dosemeter. It has been known for over 40 years that quartz particles have a surface layer of amorphous material. The smaller particles have a larger proportion of amorphous material and hence a lower diffracted intensity (and the largest particles may give an intensity that is too low because of extinction). The general view is that size distribution does matter and as far as possible the standard should be a good match to samples. However, both the UK and US regulations require determination of crystalline silica and so long as areas a re used for quantification the size might not be important. Recent work has shown that the relationship between the US and UK standards depends on the method of comparison; in particular size distribution depends on flow rate. This re-emphasises the importance of matching samples and standards and having as much information as possible about standards.

About 35 people attended this meeting. Graham McPherson and Philip Lake did a good job of organising an interesting meeting, which covered a wide variety of topics.

Mary Vickers

Last updated 26 August 2002