July 1996 Newsletter

Contents

1. Editorial
2. Chairman's Message
3. Chairman's Report 1995-6
4. X-Ray reflectivity workshop 17 Sept 1996 Advance Notice
5. IG Autumn Meeting 7 Nov 1996 Advance Notice
6. Pharmaceutical & Organic Compounds early 1997 Advance Notice
7. BCA Spring Meeting - Leeds 14 - 17 April 1997 Advance Notice
8. Non ambient workshop 4 Jun 1997 Advance Notice
9. World Wide Web BCA Site report
10. 1996 BCA Spring Meeting Structure and Data Report
11. 1996 BCA Spring Meeting Prefered Orientation Report
12. 1996 BCA Spring Meeting Crystallography Course Report
13. Pharmaceutical meeting 18 Mar 1996 Report
14. Quantitative meeting part II 14 Feb 1996 Report
15. IG Charter What's in it for me?
16. Committee members 1996

Editorial

The recent Spring Meeting of the BCA, held at Cambridge, proved to be not only highly successful technically, but also resulted in a series of changes to the constitution of the BCA itself (reported in Cr ystallography News). The success of the meeting has been, however, overshadowed by the untimely death of Alun Bowen just a few short weeks after presenting a paper in his usual exemplary manner. He will be sadly missed. A fuller obituary will be published in Crystallography News, but a short appreciation is included below.

The Industrial Group suffered change, our Chairman, Dave Dyson, relinquished his post, having ably steered the Group to its present strong position and his report, printe d below, details the successes. Dave Taylor has now taken over the reins, with Steve Norval being elected Vice Chairman, Keith Rogers elected to the committee and Philip Lake co-opted to provide expertise on the pharmaceutical side of industry. Both Keith and Philip were welcomed onto the committee. Jamshad Anwar, elected ICDD representative for the BCA, has become an ex-officio member of the Industrial Group.

A very successful IG innovation at the meeting was the course on crystallography , run by Jeremy Cockroft, which was well received by the participants. The technical presentations are reported below, and the quality and breadth of interest speak for themselves. There was a slightly better response to the call for posters, but we still seem to suffer from a lack of interest, whether industrial pressures these days preclude such exercises, or that the proprietary nature of the workplace places a restriction on people's ability to present is not clear. It is however a pity that thi s mode of presentation is not more widely utilised.

Forthcoming events include a Workshop scheduled for late September on practical X-Ray and neutron reflectivity, and is aimed at X-Ray Industrial Users who wish to understand and implement more fully this interesting technique. In early November the Autumn Meeting will discuss Crystallography in Industry, and next year will see an early meeting on pharmaceutical and organic materials, with the Spring Meeting in Leeds already being planned with two themes - diffraction with simultaneous methods and process and production methods. In addition, Ron Jenkins will be leading an Instrument Sensitivity Clinic. Later in the year a non-ambient workshop will be held.

Alun Wynne Lloyd Bowen

Alun Bowen died on 7 May 1996 after a long struggle against cancer. The funeral took place on 15 May. Alun was closely involved in setting up the BCA and the Industrial Group and had served as Group Chairman. He will be remembered by many of us as "Dr Texture". A fuller appreciation will appear in due course in Crystallography News. The Industrial Group has made a donation in his memory to the Appeal Fund of the Royal Marsden Hospital. Anyone wishing to be associated with this donation may do so by sending a contribution to Eric Kelly (payable to BCA-IG) or direct to the Appeal Fund at the Royal Marsden Hospital, Downs Road, Sutton, Surrey.

Chairman's Message

I would like to thank you for your confidence in me and look forward to serving you in my term of office helped by an able and experienced team of committee members. I am grateful to the retiring chairman David Dyson for his commitment to the Industrial Group in his seven years on the committee. I am sure he will still maintain an interest and involvement in our activities. I also express my thanks Trevor Carter for his work on the committee over the last four years, especially in producing our Newsletter, and the support over the last year as he handed over compilation and distribution to Bruce Fox.

In my term of office I would like to see a meeting programme with enough interest and variety to ensure that every Industrial practitioner of crystallographic techniques attends at least one of our meetings. I know that this is a tall order and it cannot be achieved without your help on two fronts. The first is ensuring that all industrial practitioners are aware of our activities. The second is making known your views on what topics should be covered or even volunteering a paper or better still a poster at one of our meetings.Membership and the Newsletter distribution are the key to making people aware. You only need to attend one of our meetings to become a member or renew existing membership of the BCA.

This Newsletter and Crystallography News are the main means of advertising our meetings. Crystallography News is only sent to paid up BCA members. The Industrial group Newslette r is freely available to anyone (it is produced and distributed by committee members without cost). We have already extended our mailing list with the help of Philips and Siemens and I welcome new readers, but we must continue to update our list to ensure that we reach the widest possible audience.

You can help by informing me of changes within your organisation that mean the right people are not receiving the Newsletter and by circulating it to relevant colleagues. If you meet people new to the field please spread the word about the Industrial Group, and put them in contact with Eric Kelly our secretary.

Contact myself with changes of address or to have your name removed from the mailing list. The target is to get a copy of our newsletter onto the desk of every industrial scientist interested in applications of X-Ray Diffraction and related crystallographic techniques. Back issues of this Newsletter and Group information are available on the BCA World Wide Web site at:-www .cryst.bbk.ac.uk/BCA/index.htm. I hope that you will play an active part in our group activities.

Let us know your views and tell us the areas you want to see covered in the programme. Come to at least one of our meetings each year and your continued membership will be ensured. I hope to speak with most of you in the next three years but please take the initiative and give me a call or e-mail your ideas. With your help I am confident of an interesting and rewarding term of office.

Dave Taylor

BCA Industrial Group on the World Wide Web.

Surfing the Internet seems to be a somewhat over-hyped expression these days, but the quantity of information and relative ease of access would seem to make it a useful communications and learning tool. In Industry, however, wheels can turn slowly, due to a mixture of financial constraint and computer security restraint. The latter seems more important in terms of s afeguarding the firm's network, thus although I can already e-mail people and my company has its own Web page, I cannot, as yet, directly access the Web. So I took advantage of Kate Crennell's kind offer to visit the physical site of our Web page, at the Rutherford Appleton Laboratories to learn first-hand the intricacies of the system.

Kate is the editor of Crystallography News and our Web Master (Mistress?) who deals with the BCA Home Page which leads, amongst other things, to the Industr ial Group pages. You will find copies of our recent newsletters, the committee details and notice of forthcoming meetings. The ability to branch out from this starting point was a revelation, easily culling information on fibre diffraction, both facilities and software, in a matter of moments. In discussion with Kate, I suggested that the creation of a list of consultants and services would be useful for Industrial users, and this has now been put in place. If you offer a service, or you can suggest or recommend a facility or resource, please let Kate know.

The BCA Home Page can be accessed on: http://gordon.cryst.bbk.ac.uk/BCA/index.html

The IG page either from the above, or http://gordon.cryst.bbk.ac.uk/BCA/IG/ig.html

You can contact Kate Crennell at PO Box 64, Didcot, Oxon. OX11 0TH

e-mail: [email protected] tel 01235 834357

Bruce Fox

X-RAY POWDER DIFFRACTION in the PHA RMACEUTICAL INDUSTRY.

held at Glaxo Wellcome, Stevenage, 18th 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, agrochemicals, 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 crystall ise in large, 'soft' unit cells of low absorption with diffraction characterised over a relatively small range of 2 theta (typically ca. 0-55 degrees). Indexing as a proof of purity and quantitation of polymorphic mixtures are particularly important issues.

Dr Steve 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 Zakrz ewski (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 (Siemens) 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 induc ed phase changes by experiment and simulation. These experiments give 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 Wellcome). 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/pharmaceutical crystallography was aired. It was generally felt that the day was an unqualified success and given the respon se 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 Glaxo Wellcome

Quantitative Phase Analysis Using X-Ray Diffraction Techniques (QXRD Part II)

QXRD Part II, an Industrial Group Workshop focusing on accuracy, precision of measurement and the requirements for accreditation of q uantitative methods, was held at the Philips Research Laboratories, Redhill, Surrey on the 14 February 1996. Quantitative X-Ray Diffraction (QXRD) is perhaps best explained by Robert Reynolds, Jr: "QXRD contains many pitfalls whose deleterious effects on the data are not obvious from an examination of the final results. Precision is easy, but as R.L. Snyder (a colleague) has remarked, accuracy comes from God". Over recent years however, major advancements have been achieved with the aid of improveme nts in computing technology, that has changed the current feeling in QXRD. Although, as was re-enforced in QXRD Part I on 7 June 1995 "User beware", with these advancements in instrumentation it is easy to believe that precision is in fact true accuracy and ignores the myriad of factors that make many laboratories' results so inaccurate. Judging by the 38 participants from 25 laboratories, QXRD is a difficult but important application of X-Ray diffraction (XRD).

After a warm welcome, the on e day workshop began in earnest at 10:40 with Judith Shackelton (Philips Analytical X-Ray) giving an informative introduction and overview into many methods of quantification. The quantitative methods discussed highlighted many problems resulting from the nature of the samples themselves, and the way they affect the approach of workers in various fields. Judith, advised everyone to check their results for reproducibility, spread of data and to running test samples.

Nick Elton (ECC Internat ional) warned about the errors of particle statistics. He explained that particle statistics errors may be significant when low levels of analyte are quantified. The magnitude of this error also depends on diffractometer geometry as well as low numbers of analyte. Particle statistics can be improved by use of wide collimating slits, broad focus X-Ray tubes and by rocking or spinning the sample. As a rule, it is best to maximise the number of particles analysed and this can only be achieved by keepin g the particles small. However, over milling can damage the crystal structure so, a compromise often has to be struck between good particle statistics and errors associated with line broadening and production of amorphous material.

Glyn Carter (Geochem Group) explained in detail the Chung Method of matrix flushing. He began with an introduction into the work of Frank Chung and went on to use three simple derivations of the well-established intensity equation for a single hkl reflection to prove that the relationship between integrated intensity and abundance follows a linear relationship always passing through the origin. Provided that an internal reference material can be used to calibrate diffractometer geometry and sample multiplicity factors, this relationship shows that XRD is quantitative under ideal conditions. Using this theoretical relationship, it was demonstrated that by stringent analytical procedures and the employment of good calibration techniques that it is possible t o achieve acceptable and accurate results experimentally, provided you can obtain a set of pure standard phases or emulate by mathematical models the diffracting behaviour of each phase present in the mixture. Glyn also put forward the suggestion that Rietveld, may help with understanding this diffracting behaviour.

Don Williams (Sietronics & Siemens) introduced a practical application of Rietveld to calculate full profile patterns and intensity scale factors. As a means of matching cal culated intensity for each point in a step scan and its difference from the observed intensity at that point. He went on to explain, that the refinement of Rietveld scale factors are a function of the concentration of each phase in a mixture and with the aid of a computing package you can achieve quite accurate phase concentrations. I feel that Rietveld may prove to be the only way to help overcome the may problems associated with correctly determining true intensity values and Rietveld scale factor s are a step forward.

The afternoon session began promptly at 14:30 Walter Gutteridge (British Cement Association) was the first speaker of the afternoon session, and maintained a captive audience with his enthusiastic approach to his talk about practical application of QXRD within the Cement Industry. After a brief introduction about the British Standard for Portland Cement. he went through a step by step approach to its analysis and explained that many of the problems associated with QXR D can be overcome with a methodical analytical method.

Jim Chisholm (Health and Safety Executive) gave a insight into thin samples - airborne dust on filters. He explained that, ideally thin samples can be used to determine the mass of a crystalline phase in any thin polycrystalline film. QXRD is achieved by the use of a calibration standard matched to the samples being analysed and the basic principle of the external standard method. He explained that QXRD gives reasonable precision and d etection limits even in an application such as airborne dusts which take the technique close to its limits; but accuracy is another question.

David Dyson (British Steel) was the last speaker of the day and presented an informative talk on the requirements of quantitative methods for accreditation. He explained that accreditation provides for a sensible approach to proving the worth of results. It ensures that all equipment really performs to an acceptable standard throughout its lifetime. T he benefits are three fold: instrumentation is functioning properly, that the user's training is affirmed and equipment is validated. It confirms that you are "doing things right" rather than "doing the right thing". David, gave the closing statement for the meeting where he commented that QXRD has may problems to overcome but these meetings have gone a way towards answering many of them. He suggested another forum to answer many points raised at this meeting. He reiterated that good basic principle s are the only true bases for QXRD: adequately trained staff, traceable standards, reliable and well-maintained instrument, documentation and control systems, a professional approach to compliance with the standard and an understanding of the sample. Results are worthless unless they quote the level of error or confidence. In conclusion, QXRD is foreseeable as an industrial tool, however, more research is needed before the general User can reap its benefits. Only through the efforts of manufactures can this be achieved.

I would like to acknowledge the efforts of Jo Jutson (BICC Cables) and Sally Smith (Philips) for their organisational skills in arranging seven relatively complex talks promptly. I would also like to thank Philips Research Laboratories for their warm hospitality.

Glyn Carter,Geochem Group