Reports on Industrial Group Meetings in 1999

• IG Forum Over view Royal Court Hotel, Coventry 12-13 April 1999
  • Dr David Rendle Industrial Group Award 1999
  • Diffraction & the Material Scientist IG Forum 12-13 April 1999
  • Pharmaceuticals Polymorphism: Supporting Techniques for Structure Determination IG Forum 12-13 April 1999
  • Pharmaceuticals Polymorphism: Case Histories IG Forum 12-13 April 1999
  • Workshop R ietveld Analysis IG Forum 12-13 April 1999
  • Assuring Quality of XRD measurements & Industrial Applications IG Forum 12-13 April 1999
  • Thin Films IG Forum 12-13 April 1999
• Autumn Meeting Birkbeck, 4 November 1999

BCA IG Forum

11-12 April 1999 Royal Court Hotel Coventry

Meeting Overview

The Industrial Crystall ography Forum, held at the Royal Court Hotel, Coventry, was a new venture for the BCA's Industrial Group. It was the first two-day meeting to be organized by the Group and parallel sessions were introduced for the first time, to cater for the growing number of members from the Pharmaceutical industry. The aim of the forum was not simply to present the latest developments in the field; as implied by the title, it was an opportunity for industrial crystallographers to meet and discuss matters of commo n interest.

After the welcome and introductions by Steve Norval, the Group's Chairman, parallel special-interest sessions were held during the morning of Monday, 12 April. One was devoted to various applications of diffraction methods in materials science, from residual stress measurement to the formidable problems associated with obtaining data from explosive materials. Complementary techniques for determining the structure of polymorphic pharmaceutical materials were covered in the other session.

A workshop on applications of the Rietveld method occupied the early part of the afternoon, followed by the Group's Annual General Meeting. The Chairman then presented the Industrial Group Award to Dr David Rendle of the Forensic Science Service. This is made from time to time in recognition of a sustained contribution to industrial crystallography and David Rendle is a worthy recipient of the award. He joined the Metropolitan Police Forensic Science Laboratory in 1975 and has sin ce developed equipment and a range of techniques for working with very small specimens. His work, involving a wide range of materials and using X-ray diffraction, fluorescence and radiography, has of necessity been carried out to the exacting standards required in the law courts. Appropriately, the award consisted of a mounted model of the heroin structure! David Rendle then gave the Alun Bowen Lecture, an annual event to commemorate a former Chairman of the Group, entitled 'Forensic Applications of X-rays'. This provided an interesting and entertaining insight into the work of the Forensic Science Service, such as the identification of paint flakes, glass fragments, hair, fibres and other 'contact traces', the analysis and quantification of drugs, often providing a means of ascertaining their source, and the use of radiography to detect fraud and forgery.

The morning session on Tuesday, 13 April, opened with contributions on the alignment and performance testing of diffractometers, of importance in ensuring the quality of XRD data, and this was followed by further papers on industrial applications. Parallel sessions during the afternoon were devoted to studies of thin films and to contributions from members in the pharmaceutical industry. The proceedings concluded with an open discussion.

The Organizing Committee are to be complimented on devising so balanced a programme, with about the right mix of plenary and parallel sessions and a diverse scientific content which reflected the range of crystallography practised in industrial laboratories. The forum was well supported, through sponsorship and active participation, by several firms which provide diffraction equipment or services. Indeed, it is questionable whether such an ambitious meeting could have been held without this support. That the forum attracted in the region of 85 participants demonstrates the value of such a meeting to the industrial crystallographic community.

Ian Lang ford

Industrial Group Award 1999

Dr David Rendle

David Rendle (Left in picture)was presented with an Industrial Group award during the Industrial Crystallography Forum held at Coventry. The award recognized David's long-term contributions to the application of crystallography in forensic science.

David studied at Loughborough Universit y of Technology, then in Canada at the Universities of Waterloo and Guelph. After a post doctoral period at the University of British Columbia he joined the Metropolitan Police Forensic Science Laboratory in 1975 where he has continued through changes in his role and the organisation's name. David has also had a long association with the BCA Industrial Group. He was a founder member and a member of the Committee from 1989-92.

David has a fine record of analytical work, largely within the d iscipline of forensic science. He has specialized in working with small samples in XRD. This has led to a range of published papers covering sample preparation, use of Debye-Scherrer cameras including back reflection, a simple Gandolfi attachment, paint pigment analysis, drugs and metabolite identification. Special mention has to be given to the automated Debye-Scherrer camera developed by David in the Police Forensic Laboratories. He has also been involved in developing the use of soft X-rays for d etecting forgeries, re-sealed envelopes and even serial numbers filed off engine blocks. All this work has, of necessity, been carried out to the exacting standards needed for a Court of Law.

To bring David's involvement with crystallography up to date and into the wider world, he is an active member of ICDD. He has championed the cause of organic phases in the Powder Diffraction File and currently chairs the Organic Materials sub-committee.

Dr Steve Norval ( Rig ht in picture)

Diffraction & the Material Scientist

Judith Shackleton of Philips Analytical chaired the session. The first speaker was Mike Fitzpatrick from the Open University who talked about the complimentary use of neutrons and x-rays for residual stress measurement. He briefly explained the two techniques and highlighted the similarities and differences (particularly cost and penetration depth) between them. Mike emphasised t hat the major benefit of neutrons is that they can provide a validation method for models and for x-rays in the case of near surface measurements. He then showed some results on welds in a 27mm thick section plate. Mike finished by mentioning some future developments such as the new ENGINE X neutron instrument at ISIS and the growing use of synchrotron x-rays.

Arnold Vermeulen from Philips Analytical Holland, talked about techniques for line profile analysis. He showed that with val ues of integral breadth, FWHM and peak position from profile fitting, along with a spreadsheet program such as EXCEL, it was possible to determine size and strain broadening using plots created in EXCEL. Examples of instrument resolution functions, Williamson-Hall plots, and multiple line methods were shown.

Ian Brough from the Manchester Materials Science Centre talked about Electron BackScattered Diffraction. He briefly introduced the experimental technique and talked about its use for texture and grain size measurement/misorientation studies. The advances in PCs over the last few years has meant that fully automated data acquisition is now possible with up to 100000 patterns /hr being collected. This meant that data for pole figures could be collected in minutes compared to several hours for a conventional x-ray diffractometer. Ian finished off by talking about some of the applications of the technique such as crystallography of fracture and phase identification.

< b>Michael Cartwright from Cranfield University was next up talking about the hazards associated with x-ray diffraction of explosive materials. He gave an outline of the hazards (e.g. toxicity,spontaneous combustion in air), and the safety procedures employed. Mike spoke about several systems such as RDX, HMX TATP and Azides and explained how x-ray diffraction had been used to investigate the different polymorphs of these materials. Lastly, he described a piece of glass apparatus developed in-hou se to prepare samples under an inert atmosphere. He finished the talk with a list of factors to be considered when dealing with hazardous materials.

The last talk of the morning was by Colin Small of Rolls-Royce Derby who described how x-ray diffraction was used to solve a problem with ceramic cores used to manufacture high-pressure turbine blades. These operate at temperatures above the material's melting point and therefore require internal cooling channels Problems were encountere d with dimensional stability and flaking of surface layers. The cores are made from a mixture of amorphous silica, alumina and zircon. Phase analysis using x-ray diffraction showed that there were differences between the volume fractions of Cristobalite and amorphous silica between the surface and centre of the ceramic cores. The formation of Cristobalite with its associated 6% volume change, which offset the shrinkage on firing, resulted in improved dimensional stability of the cores.

Alt ogether a very varied and enjoyable morning!

Philip Holdway

Pharmaceuticals Polymorphism:

Supporting Techniques for Structure Determination

Although the theme of this meeting is industrial applications of X-ray powder diffraction, the pharmaceutical industry almost always uses this technique as part of a panel of analytical techniques for the characterisation of polymorphs and solvates. It is rare for a single technique to provide all the answers. This, combined with practical considerations such as limited amounts of sample or the requirement for robust methods at manufacturing sites, means that a team approach toward characterisation using a range of methods (usually in R&D) is required. The presentations in this session covered a range of techniques, highlighting their advantages and complimentarity to powder diffraction.

Norman Shankland (Univ. of Strathclyde) presented on "Struct ural Transformations Observed By Diffraction" and highlighted the advantages of neutron diffraction for structure solution using the HRPD (high resolution powder diffractometer at the ISIS spallation neutron source. Examples described included the transformations between pyrene II and pyrene I on heating and the reverse transition on cooling a single crystal. The use of neutron diffraction to determine the site occupancy of the water molecules in norfloxacin hydrates, which could not be determined u sing X-rays, was discussed.

"Polymorphism Studied by Solid-State NMR" was presented by Robin Harris (Univ. of Durham) describing the use of magic-angle spinning NMR for the recognition and quantification of polymorphs. The number of molecules in the asymmetric unit, intermolecular interactions and non-bonded interatomic distances can be determined to provide constraints for full structural analysis using powder diffraction. Solid-state NMR can also distinguish static and dynamic diso rder, be applied to amorphous systems and be used to characterise heterogeneous systems (e.g. tablets).

The usefulness of molecular modelling was described by Roger Davey (UMIST) using the 2 forms of 2, 6-dihydroxybenzoic acid to illustrate how crystal solvent interactions determine which form is isolated. Crystals of each form were grown and the molecular interactions at the fast-growing surface were determined. It is hoped that a more detailed understanding of these interactions c an be used to help the chemist design a more robust isolation procedure.

Ian Cooper (Roche Discovery) discussed "Thermal analysis and thermodynamics in the study of the solid state properties of drug discovery compounds". DSC, Modulated-temperature DSC (MTDSC), TGA and Hot-stage microscopy are powerful discriminatory techniques but can also be used to determine the relative stability of the known crystalline forms. Understanding these relationships is important in preventing convers ions during scale-up or storage. MTDSC is a relatively new approach that can offer useful insights into the properties of amorphous materials via measurement of the glass transition.

Gary Nichols (Pfizer Central Research) spoke provocatively on "Polarised Light Microscopy - probably the most versatile crystal polymorph probe in the world !" Polarised light microscopy is more than a century old and there is a danger that its capabilities are neglected in favour of the more "high-tech" approaches. Different polymorphs can be distinguished by their optical properties under polarised light. A hot-stage can be used to detect solvated crystals and to study conversions between crystal forms. Polarised light microscopy can also be used to identify the crystal system.

Finally, Bob Lancaster (Glaxo Wellcome) spoke on "Vibrational Spectroscopy - Does it still have a role now we all have powder diffraction capability ?" He answered this in the affirmative by describing the recent advances in these techniques, particularly FT-Raman spectroscopy and Raman microscopy. Raman is particularly well-suited to the characterisation of drug substance in formulations because of the reduced overlap (c.f. IR) from the excipient signals. IR is particularly sensitive to hydrogen bonding and hydration.

David Lee

Pharmaceutical Special Interest - Polymorphism:

Case Histories

The second pha rmaceutical session was based upon case histories of polymorphism. There were six presentations given from representatives of the pharmaceutical industry. The presentations focussed on how different analytical techniques were utilised in conjunction with X-ray crystallography to solve real problems in solid state chemistry.

Workshop - Rietveld Analysis

Jamshed Anwar (Kings College London) started the workshop by introducing the princi ples of the Rietveld method. The technique uses least squares to minimise the difference between observed and calculated points to give the best fit over the full powder profile. He stressed the importance of a high ratio of observations to parameters and that simultaneous refinement of multiple data sets or rigid body constraints can be used to obtain this.

A number of applications of the Rietveld method were then discussed. Martin Vickers (Birkbeck College) showed that Ri etveld is not only used for structural refinement but that profile fitting can be used for quantitative phase analysis provided that the structure and pattern of the analyte is known. He demonstrated (after receiving numerous samples!) how X-ray powder diffraction data can be used to quantitatively determine the ratio of amorphous to crystalline content in chocolate.

As a least squares analysis, Rietveld needs an approximately correct structural model to enable successful s tructure refinement. This was demonstrated by Bill David (Rutherford Appleton Lab) in a talk that focused on the structure determination of pharmaceutical compounds from powder diffraction data. It is clear that although traditional direct methods can be used for initial structure solution as in the case of chlorothiazide, the use of global optimisation methods employing molecular connectivity represents the most promising route for the structure solution of more complex molecular materials from pow der diffraction data.

Ian Langford (Birmingham University) talked about the application of the Rietveld method to modelling sample imperfections by line profile analysis. He explained that although line breadths and shapes have recently been modelled as a function of hkl for anisotropic effects, it is difficult for Rietveld programs to make provision for all possible cases of sample-induced modifications to instrumental line profiles.

In the f inal presentation, Arnt Kern (Bruker-AXS) introduced the new fundamental parameters approach to profile analysis. Instrument and sample contributions are calculated from first principles both reducing the number of parameters to be refined and giving refinable parameters that have real physical significance. The use of this approach along with improved refinement algorithms was demonstrated by a fully automated refinement that achieves convergence significantly faster than conventional Rietveld prog rams, and is capable of ab initio structure solution from powder data as part of the refinement process.

Maryjane Tremayne

Assuring Quality of XRD measurements

Performance Testing of XRPD Instruments - Burkhard Peplinksi, from the Federal Institute for Materials Research and Testing discussed how the recent advances in computer system and instrumentation now allow whole pattern Rietveld techniques to be used to determine the precision of X-ray powder diffraction systems.

Whole pattern methods have allowed a much more rigorous assessment of the influence of our choice of, for example fixed or automatic divergence slits. There were some surprising conclusions regarding the best choice of slits for Rietveld and other applications. Ordinary, commercially available, calcium fluoride was used as a standard as well as a pure, synthetic Cordierite for low 2 theta calibration, always a problem! Si_{3< /sub>N4 was also described as a useful standard. A round robin is also being organised using a silicon nitride, powder standard, contact [email protected] for further details.}

Diffractometer Alignment- Dave Taylor, a well-known consultant in the XRD field, outlined the importance of regular tests to insure that your diffractometer is in good working order. Many of us treat instruments as " black boxes" to the detriment of our results! You can use all or part of the procedures in the BCA Round Robin on Diffractometer Performance. The tests are available on a floppy. Even just a measure of peak position and the FWHM, at high and low 2 theta will give insight into potential problems. Dave talked about the influence of various aberrations (axial divergence, etc) and how to minimise them. The procedure for aligning a diffractometer was also described together with the pros and cons for the various NIST standards. It appears that the famous silicon standard may ind eed be too transparent for precise alignment tests on modern machines.

A lively discussion followed about the various types of standards. Also, NIST are preparing a new low angle standard, silver behenate, the largest d spacing is about 19.5Å.

Determination of Crystallinity and Unit Cell Size of Faujasites - Faujasites are zeolites and are used as catalysts in the chemical industry. The crystallinity and unit cell size is important to their performance. Jan van Mechelen Shell International, Amsterdam described a new program, which has been developed to determine these properties quickly, easily and at reasonable cost. Jan also discussed the influence of humidity control, background fitting and the choice of reflections.