Alun Bowen Industrial Lectures.

This keynote lecture is a cornerstone of Industrial Group Meetings and has played an important part of both Spring and Autumn offerings.

The lectures were started in 1997 as a lasting tribute to Professor Alun Bowen's contribution to Industrial Crystallography, which is documented in his obituary on this site and in the Times. His widow and surviving daughter collected the posthumous Industrial Group Award at the November meeting 1996.

He served on the Industrial Group committee from 1984 and retired as Chairman in 1992. He continued his service as a BCA Council member giving that important industrial perspective. He was a once in a lifetime industrial crystallographer, at the fore front of the science, an acknowledged expert in texture and stress analysis - a model to his peers.

Lectures detailed on this page are:

• 2006 Ulrich Griesser, University of Innsbruck STRUCTURAL RELEVANCE AND ANALYSIS OF POLYMORPHISM IN DRUG DEVELOPMENT.
• 2003 Alexander M. Korsunsky STRUCTURAL ENGINEERING STUDIES USING HIGH ENERGY X-RAY DIFFRACTION.
• 2001 Colin Small CRYSTALLOGRAPHY IN THE AEROSPACE INDUSTRY
• 2000 S. R. BYRN CRYSTALLIZATION OF PHARMACEUTICALS
• 1999 David Rendle FORENSIC APPLICATIONS OF X-RAYS
• 1998 Robert Snyder THE DEVELOPMENT OF X-RAY ANALYSIS
• 1997 Paul Barnes CINE-CRYSTALLOGRAPHY PLUS.....

1997 Alun Bowen Industrial Lecture

CINE-CRYSTALLOGRAPHY PLUS.....

Professor Paul Barnes

Industrial Materials Group. Department of Crystallography, Birkbeck College, Malet Street, London WCIB 7HX, U.K.

Cine-cystallography implies (primarily) a time-dependent element to observation, whereas the plus refers to the use, simultaneous or otherwise, of more than one structural probe. These aspects complement the themes of this year's Industrial Group sessions. In this lecture I will indicate how certain techniques (e.g. synchrotron/neutron diffraction/scattering, EXAFS, computer-simulation) can be combined in this way, particularly with the view of reproducing specimen conditions that mimic real conditions in the synthesis and in-service performance of functional materials. I will give examples of application in the following three areas:

1. synthesis of ceramics.
   
   
2. zeolite ion-exchange and dehydration.
   
   
3. hydration of cements.
   
   

1998 Alun Bowen Industrial Lecture

THE DEVELOPMENT OF X-RAY ANALYSIS

Professor Robert L Snyder

Department of Materials Science and Engineering,

The Ohio State University, 2041 College Rd., Columbus OH 43210 USA.

The discovery of X-ray radiation by Roentgen in 1895 lit the fuse, which resulted in a sequential series of explosions, which blew away the shroud of ignorance surrounding the atomic nature of matter. Each explosion produced a new method for probing atomic secrets collectively known today as X-ray Analysis. From today's perspective the rapidity of these events is breathtaking: Diffraction - von Laue, 1912; Fluorescence - Moseley, 1913; Crystal Structure Analysis - Braggs 1913; Amorphous Scattering - Debye, 1915; Powder Diffraction - Debye & Scherrer, 1916; Crystallite Size Analysis - Scherrer, 1918; Indexing - Hull & Davey, 1921; Absorption Spectroscopy - Glocker & Frohnmeyer. 1923; Preferred Orientation Analysis - Wever, 1924; Residual Stress Analysis - Lester & Aborn, 1925; Quantitative Analysis, Navias, 1925; X-ray Reflection - Kiessig, 1931; Small Angle Scattering - Warren, 1937; Qualitative Analysis, Hanawalt, Rinn & Frevel - 1938.

Within about fifteen years of the discovery most of the principal tools of X-ray analysis were in place and ready to grow to the powerful methods we know today. The modern applications of X-ray powder diffraction: qualitative and quantitative analysis, size-strain analysis, indexing, preferred orientation and structure analysis, have produced solutions to problems that could not have been imagined by the fathers of the method.

The development of synchrotron sources has catalysed a new explosion of techniques in characterisation. Wavelength tunability allows diffraction analysis on each side of absorption edges, EXAFS and XANES analysis of poorly crystalline and amorphous materials, and 3D non-destructive tomographic analysis. High resolution X-ray and neutron instruments have permitted structure analysis to such level of detail that the fundamentals of high temperature superconductivity can be revealed. Other techniques such as total reflection diffraction, and fluorescence, and reflectometry have opened the world of thin film structure and properties to close examination.

The development of very efficient Position Sensitive Detectors (PSD) have opened powder diffraction methods to a wide range of time dependent studies. The most dramatic application of these "dynamic techniques" is to materials studies in real time monitoring of reactions, phase transitions, kinetics, stress development and sintering of crystallites, by taking rapid "snap shot" patterns of a material while heating it on a hot stage.

This paper will trace the origins of the applications of X-ray powder diffraction through to the modern era showing examples at the state of the art.

1999 Alun Bowen Industrial Lecture

Forensic Applications of X-rays

David Rendle

Metropolitan Laboratory, Forensic Science Service,
109 Lambeth Road, LONDON SE1 7LP, United Kingdom

Forensic science is the science behind expert evidence, and its strict definition is simply that science which is used in the law courts. X-ray techniques, just as many other analytical methods, have been used in forensic science for several decades. The main applications of X-rays are in X-ray powder diffraction (XRD), X-ray fluorescence (XRF) and X-radiography.

The need for non-destructive methods of analysis in order to preserve evidence can be of great importance, although this requirement may vary from country to country depending upon the prevailing criminal justice system. Most courts understand, and accept, that chemical analysis can result in destruction of a specimen, but in certain instances, Counsel may insist on seeing the specimen that was analysed, and having that same specimen re-analysed by their own scientists. In view of this, it is wise to use non-destructive analytical methods, where possible, as a matter of course. XRD, XRF and Radiography meet this requirement admirably.

The complementary techniques of XRD and XRF are used mainly in contact trace analysis. So-called contact traces (paint flakes, glass fragments, hair and fibres (natural and man-made), slivers of metal, soils, building materials, stains of any description, corrosion products and loose powdered materials) appear in the traditional areas of forensic science, where the identification and comparison of trace quantities of material can help in the conviction or exoneration of a person suspected of involvement in a crime. X-radiography has a role in the examination of a wide variety of objects, from light, low density objects such as documents using soft X-rays, to more dense objects using harder X-rays and electronography.

There is now, as never before, a perceived need to provide the investigating officer with as much useful scientific information as possible at the crime scene. The time saved by providing pertinent scientific information to the officer at the scene may be crucial to the way he/she directs the investigation. Development of instrumentation, particularly X-ray sources and detectors, with a view to miniaturization and hence portability of equipment, will be of paramount importance. Software requirements will mean Lap-top or Palm-top computers of sufficient power to process spectroscopic/diffraction data quickly, and the ability to accommodate a database and a search/match routine with an option for quantitative analysis.

2000 Alun Bowen Industrial Lecture

CRYSTALLIZATION OF PHARMACEUTICALS

S. R. BYRN, J. G. STOWELL, X. HE, G. STEPHENSON, AND U. GRIESSER,

PURDUE UNIVERSITY, WEST LAFAYETTE, IN

Crystallization of pharmaceuticals is a critical step in drug development. Crystallization allows control of the form as well as purification. Crystallization results in a drug substance (API) with controlled properties. The crystal form and the process for preparing it represents intellectual property and is sometimes protected by patents or trade secrets or both. Approaches to crystallization will be introduced. Three nonsolvated systems will be reviewed, ROY, 4'-methylROY, and WAY. In each case, crystallization of the forms will be reviewed and an energy temperature diagram will be constructed. This diagram will be used to explain how a crystallization strategy for each form of 4'-methylROY was developed. The crystal structure will also be used to explain how additives were used to stabilize unstable polymorphs of WAY. The crystal structures of the "tunnel" hydrates caffeine, theophylline, thiamine, and orotic acid will be also be reviewed. In these cases the use of the crystal structure to explain stability will be highlighted. Throughout the discussions, the powerful combination of crystal structure with other analytical techniques will be illustrated. This research was supported, in part, by the Purdue-Wisconsin Program on the Physical and Chemical Stability of Pharmaceutical Solids.

2001 Alun Bowen Industrial Lecture

CRYSTALLOGRAPHY IN THE AEROSPACE INDUSTRY.

Colin Small, Rolls-Royce plc, P.O.Box 31, Derby, DE24 8BJ, UK

Crystallography in the aerospace industry? Well if you were to go and ask my managers what they think about this subject you would be met with nearly blank stares. It is not that they do not know about the subject, most of them have scientific degrees that contain some physics. It is just that they are unaware that Rolls-Royce has a crystallography facility and that it is used to help solve development and service problems on gas turbine engines. The reason this happens is that telling a field service engineer that his engine (which at this point is usually not working) is full of Fe2O3 and CaSO4 (together with their associated lattice parameters) is not a useful answer. Similarly if you put a pole figure up in front of them and say ' this is why your material does not behave they way you think it does', they run away shouting 'I don't understand'. This is not to say that they are Philistines, its just that the answer in this form is not useful to them. Thus the job of the crystallographer in this industry is to apply the physics and technology, get the crystallography based answer and then turn it into information that engineers what and are willing to use. A couple of examples will illustrate this point:

(1) Gas turbines are wonderful vacuum cleaners- they swallow large amounts of grit and dust along with the air they need to operate. The dust reacts in the combustion chamber and on the hot turbine components. The reacted products can be very aggressive and cause premature failure of the components. Crystallography is needed to identify what is coming in, what is reacting, and how the reaction products affect the engine components. In reality, the questions being asked and answered are; what is it? Where does it come from? What can be done to stop it? You very quickly find yourself becoming a detective looking at not just crystallography, but also geology, chemistry and even phase equilibria to solve this sort of problem. However, the initial clues come from the crystallography.

(2) Texture has a direct influence on the mechanical properties of thin, rolled metal sheet. Yet, it is the one property that the process engineers usually ignore because 'you cannot see it'. They will look at chemistry, microstructure, rolling schedules, infact just about anything before they even consider it. However, if you put a highly textured material into service unexpected failures can be linked directly to the development and control of the underlying crystallographic distribution. In this case the crystallographer has to find a way of communicating highly abstract concepts in a way that are interesting, useful and that can be used by non-specialists. They also have to introduce new analytical techniques and ways of representing the data while keeping the working understanding that the engineering fraternity has developed and is comfortable with. This is a challenge but a highly satisfying one when you realise how far texture is now an accepted, used and controlled part of our manufacturing processes.

(3) Through this talk I will expand and illustrate these points and show you that crystallography in the aerospace industry is an essential analytical tool - even if no one in the industry knows about it.

2003 Alun Bowen Industrial Lecture

STRUCTURAL ENGINEERING STUDIES USING HIGH ENERGY X-RAY DIFFRACTION.

Alexander M. Korsunsky, Department of Engineering Science, University of Oxford, Parks Road, Oxford OX1 3PJ, U.K.

At the Forum 2 meeting - 14th November 2003, Birkbeck College, London.

The availability of high flux, high energy X-ray instruments suitable for structural engineering research at SRS, Daresbury and ESRF, Grenoble has seen major improvements in the last decade. This led to systematic advances in various uses of high energy X-ray beams for non-destructive engineering analysis. Some of the recent achievements will be illustrated that are likely to determine avenues for further development.

The future will be strongly affected by the advent of new facilities, notably the dedicated engineering instrument JEEP and accompanying support facilities on DIAMOND, alongside the existing ENGIN-X neutron scanner. Although past may be a poor indicator of the future, it is all we have to go on in our attempts to provide the best engineering facility for years to come. I shall try to discuss the strategy for engineering instrumentation development in the light of industrially motivated research driving it.

2006 Alun Bowen Industrial Lecture

STRUCTURAL RELEVANCE AND ANALYSIS OF POLYMORPHISM IN DRUG DEVELOPMENT.

Ulrich Griesser, Institute of Pharmacy, University of Innsbruck, Innrain 52, 6020 Innsbruck, Austria.

At the 2006 Spring Meeting, Lancaster.

The fact that most of the active drug ingredients can exist in different crystal forms has attracted strong attention in pharmaceutical industry within the last decade. Interestingly, this interest was triggered by patent litigations and economic reasons rather than the awareness of the scientific challenge of this solid state phenomenon. The main push for the increasing research on solid state properties of new drug entities still comes from the regulatory requirements as well as issues related to patents of specific crystal forms. One result of all these activities is doubtless a more rational based drug development and manufacturing compared to the decades where polymorphism was largely ignored in industry. The second is the benefit and stimulus for various fields of basic and applied science such as structural and supramolecular chemistry, crystal engineering or theoretical and computational chemistry. Furthermore, the often subtle differences between polymorphs, order-disorder phenomena, low stability etc. offer many challenging tasks for all kinds of solid state analytical techniques and force us to improve the state of the art and to overcome existing analytical boundaries.

In order to understand the basic principles of the interplay of molecular recognition, thermodynamics, and kinetics it is clear that a variety of analytical techniques are required. Single crystal structure analysis, powder diffraction methods and spectroscopic techniques provide evidence about molecular assemblies and interactions in the solid state, other techniques such as thermal analysis, calorimetry and solubility studies give access to the thermodynamic features of polymorphs.

This lecture tries to outline some of the basic principles and problems of polymorphism in pharmaceuticals. By means of representative examples the nature of polymorphs including structural features, phase transition behavior and kinetic stability will be illustrated. Furthermore the importance of different analytical techniques will be addressed. Some emphasis will be placed on one of the pioneer techniques namely hot stage microscopy in order to highlight the value of this rather simple analytical tool for characterizing polymorphs, understanding solid state transformation phenonema and its usefulness for crystallographers solving problems related to crystal polymorphism.