BCA IG Autumn Meeting Report
5th November 2009, World of Glass, St Helens.
Welcome – Anne Kavanagh, Chair, BCA Industrial Group
Anne provided the welcome for the day from the Industrial Group of the BCA for this first meeting incorporating a session of talks from the Young Crystallographer Group. This was also a break from tradition by holding an Autumn meeting at a commercial meeting venue in a switch from the original plan of a meeting at Pilkington.
Morning Session- Young Crystallographers.
Speakers: From left to right: John Kaniuka, David Berry Ludovic Renou, Suzanne Buttar, Min Zhao, Moataz Attallah.
Chair, Morning Session
John Kaniuka, Young Crystallographers
Introduction to Pilkington
John Kaniuka, Pilkington Group Limited.
John gave an overview of the company from its origins as a bottle maker on this site in St Helens in 1826 through the invention of the float process and the resultant expansion of the company leading to the privatisation of the original family firm and the takeover and assimilation into the NSG group in 2006. The group is divided by product lines into three groups, building products, automotive and speciality products with product lines ranging from window glass enhanced with coatings to keep it clean, retain internal heat, solar control, or decorative, noise insulation structural and fire protection properties. Questions revolved around some keen interest in a glass concept car.
Growth of functional pharmaceutical co-crystals via phase space manipulation.
David Berry, AstraZeneca
David began, with the aid of Zaworotko’s definition, by explaining what a co-crystal actually is and three reasons why they are important to the pharmaceutical industry; offer a route to novel pharmaceutical materials, altered physical properties (solubility, stability and bioavailability), can be designed because of Hydrogen bonding and synthon engineering. Various screening methods are now employed for co-crystals including, robot solution screening, solvent drop grinding/dry grinding, Thermal screen differential scanning calorimetry (DSC), hot stage microscopy (HSM) and nuclear magnetic resonance (NMR). He used four active pharmaceutical ingredients (API’s) for study; Carbamazepine, ibuprofen, piracetam, paracetamol and divided the co-crystal formers into 5 basic groups; Mono-carboxylated acids, Di-carboxylated acids, Benzoic acid derivatives, Sugars and Nitrogenous heterocycles. He presented a table of screening results for the 4 API’s and over 20 different formers, with only 5 showing positive results. The ibuprofen, nicotinamide, water co-crystal system phase diagram was presented and the advantages of this system explored.
Formulation and characterization of a fully amorphous solid dispersion for a low Tg (Glass Transition Temperature) drug.
Min Zhao, School of Pharmacy, University of East Anglia.
Min explained that more than 40% of drugs had little or no water solubility and 95% of drugs approved since 1995 have poor solubility, poor permeability or both and that making amorphous forms would improve efficacy but with the possible disadvantage of low stability. Paracetamol with a Tg (glass transition temperature) of ~25°C was chosen in this trial with a spray drying technique. It was necessary to use a polymer stabiliser. Polymers HPMC Methocel K4M, HPMC Methocel E4M, HPMC Methocel 5cp, HPMC Methocel15cp and HPMC Methocel 50cp, PVP Kollidort 17PF, and PVP Kollidon 90F and co-polymer Plasdone S-630 and Kollidon VA 64 were tested with drug loadings of 10 to 100%. They were prepared with an inlet temperature of 110°C and 5ml/min pump rate. The resulting samples were characterised with a number of techniques including calorimetry, XRPD and SEM and results were presented. It was found that Plasdone S-630 is the best polymer for inhibiting the crystallization of paracetamol and that fully amorphous paracetamol was produced in solid dispersion with Plasdone S-630 and a 30% drug loading. Tests at various temperatures and humidity showed that this material showed excellent long term stability.
Use of Cocrystals in the Pharmaceutical and Agrochemical Industry
Suzanne Buttar , Pharmorphix® Solid State Services.
Suzanne introduced her talk with a definition of a cocrystal (“a crystal containing two or more components together” – Dunitz) and the proton transfer relationship between the cocrystal and salt. She went on to describe the modification in functional properties that cocrystallisation can impart, such as; morphology, structure “apparent” solubility, dissolution rate and colour with improvements in chemical stability, mechanical stability, bulk density and hygroscopicity. Identifying a suitable set of conformers is an important part of design and preparation. Preparation techniques generally fall into three categories, thermal methods (DSC, Kofler), solvent interaction(slurrying, slow evaporation) and energy input (sonication, grinding, microwaves). Initial high throughput reaction screening analysis techniques are XRPD, 1HNMR or ion chromatography and DSC. With scaled up preparation if all three indicate co-crystal formation and a full spectrum of analytical techniques including single crystal XRD. The following examples of cocrystal formers were discussed: caffeine, carbamazepine, gabapentin lactam, succinic acid, oxalic acid and benzoic acid.
Chiral resolution at the solid state, Pharmophix's approach
Ludovic Renou , Pharmorphix® Solid State Services
Ludovic gave a definition of chirality as when two objects form a pair of enantiomers that are symmetrical about a mirror plane. He used Modafinil a psychostimulant used in the treatment of narcolepsy (and as a performance enhancing drug by athletes) as an example. The patented synthesis leads to a racemate containing 50% of each enantiomer and the object of the study was to produce a single enantiomer by crystallisation. He went on to explain the strategies for chiral resolution from the most common state of a racemic compound with no discrimination of the enatiomers in the solid state. The less common racemic conglomerate is the most suitable strategy for chiral resolution with preferential crystallisation or salt formation produced by AS3PC (Auto Seeded Programmed Polythermic Preferential Crystallization). XRPD, single crystal XRD and Raman were used to test the experimental products.
Comparative Quantitative Characterisation of Alloy Microstructures using X-ray Diffraction and Electron Microscopy Techniques
Moataz Attallah, Materials Science Centre, University of Manchester.
Moataz talk on the characterisation of alloy microstructures was aimed at highlighting the shortcomings of certain quantitative characterisation techniques when used without prior knowledge of the microstructure. The overall objective of quantitative characterisation is to establish the structure-property relations in metallic materials, by correlating the size/density of the microstructural features to the macro properties. In this work, electron microscopy (FE-SEM, TEM and EBSD) was compared with XRD (lab and high energy synchrotron) in performing quantitative phase analysis (QPA) of the alpha+beta titanium alloys. The work clarified that some techniques are incapable of performing QPA confidently, as they are limited by their resolution, sampling volume/area, surface or transmission, or quantitative errors (e.g. Rietveld refinement). It was found that the knowledge of the alloy microstructure using electron microscopy can be essential for a successful QPA using XRD as it can provide physically and chemically sensible fitting parameters for Rietveld refinement.
LUNCH BREAK.
An excellent buffet lunch was rounded off with a conducted tour of the cone building – part of the World of Glass heritage site. Delegates are pictured inside the Victorian building in the photograph below.
Afternoon Session: Crystallography in Industry
Chair, Afternoon Session
Mark Farnworth, Pilkington Group Limited.
Speakers, From left to right: Helen Blade, Graham Smith, Chris Staddon, David Beveridge, Mark Farnworth, Judith Shackleton.
Applications of Crystallography in the Glass Industry.
Mark Farnworth, Pilkington Group Limited
Mark ran through some examples of the XRPD work on refractories, thin films, reflectivity and the new micro XRD facility. The amount of glassy phase in refractory bricks used to build glass furnaces and float baths can affect service life. XRPD is used with a simple straight line calibration based on known mixtures of crystalline and amorphous quartz and the countrate obtained at a fixed goniometer angle. Coatings on the glass surface are important in enhancing glass performance and glancing angle XRD can provide useful insight into the character of the coating deposition. Columnar growth is often present and pole figures provide a useful tool to quantify the degree of crystal orientation. X-ray reflectivity (XRR) in a theta/ 2 theta scan at low angle (typically 0.2 to 5 degrees) provides information on coating thickness, density and both surface and interface roughness by refining a model of the coating structure. The new micro XRD capability is being used to identify tiny particles found from screening raw materials to see if they will be detrimental to glass making. Other applications are tiny faults in glass and coatings and typing the form of NiS inclusions.
Characterisation and Prediction of Physical Stability of Amorphous Materials during Pharmaceutical Development: Pair-Wise Distribution Function.
Helen Blade, AstraZeneca.
Amorphous drug formulations are becoming more common in addressing issues of bioavailability and stability. A comparative Pair Wise Distribution Function (PDF) is being used as a rapid screening method as a test for an amorphous product. A PDF can answer the questions: is the amorphous material stable, is it amorphous or nanocrystalline, is the formulation a true solid dispersion or is it phase separated? Conventional reflection XRPD scans are used to provide data for software PDFgetX2 software. It is important to reduce background scatter in the scan and low background substrates and vacuum or light gas paths to reduce air scatter are recommended. Helen went on to explain how AZ are using PDF in the drug development process with the help of some case studies showing that amorphous drugs were stable, that amorphous and nanocrystalline could be differentiated, and a Felodipine - Copovidone example to show that solid dispersion and phase separation could be discriminated. PDF can provide a ranking of physical stability at the point of preparation, negating the need for stability studies and helps to speed up the overall drug development process.
Applications of Crystallography in the Aerospace Industry
Judith Shackleton, Materials Science Centre, University of Manchester
Judith highlighted the uses of XRD at Manchester but concentrated on their specialty, the measurement of residual stress in aerospace components for this talk with precise and accurate measurements being essential for quality control and necessary to certification. Typical applications are routine quality control, validating changes to manufacturing processes, manufacturing problems and, very rarely failures! The well documented sin2y method is used to calculate the residual stress from small shifts in the position of high angle diffraction peaks. The great advantage of this method is that a stress free d-spacing is not required. Problems are encountered with large samples which usually have irregular geometries, with few flat surfaces. These can be overcome by careful positioning and limiting the irradiated area. Laboratory based systems are typically restricted to 10 to 20 micron beam penetration. For increased penetration, especially for large components, synchrotron or neutron radiation is employed. In this case a stress free d-spacing is required and their measurement using Hauk’s method was discussed.
XRD N' Chips - What Makes Good Semiconductor Devices.
Chris Staddon, University of Nottingham
Advanced electronic devices based on semiconductors are a focus of research work at Nottingham. Molecular beam epitaxy and metal organic chemical vapor deposition are used to produce high quality semiconductor films based on GaAs or GaN for LED and solid state lasers etc. The structure and growth of these films are studied using XRD, TEM and photoluminescence. Chris highlighted three examples of the measurements; determining doping concentration, the cubic content of a hexagonal film and in plane orientation and size. Doping concentration of Mn in GaMnAs films was measured through the expansion of the lattice constant and simulation. For cubic / hexagonal ratio in GaN on sapphire a pole plot was used. The example for in plane orientation and size was GaN nano-rods.
Powder X-ray Diffraction for Process and Product Support in Shell Global Solutions.
Graham C. Smith, Shell Global Solutions UK
Graham started his presentation with an overview of the organisation and the migration from film and first generation automated systems to the modern equipment in use today. XRPD supports customer groups from within Shell (Fuels, Lubricant, Engine/Vehicle Testing, Refineries, Failure Diagnosis) and some work for external customers and went on to discuss some examples of their work. SEM-EDX was used to provide elemental composition (including the important light elements) for a boiler deposit which was a complex mix of iron sulphates and Haggite (Vanadium oxide hydroxide). A Plant deposit turned up a mix of FeF2, Fe2F5.7H2O and FeF2.4H2O. Some contamination from a fuel filter contained Cu, Fe3O4, graphite and CuO. A new area of work is on engine valve deposits using capillary optics directly on the valve. Asphaltenes in crude oils cause pipe blockage and XRD work on liquid crude oils and asphaltene extracts is helping further the understanding of this problem.
XRD in the Imaging Industry.
David Beveridge, Harman Technology
Historically the silver halides were the cornerstone of the imaging industry with AgCl (Fm3m), AgBr (Fm3m), AgI (beta P63mc) and (gamma F43m) playing the major roles. For films AgBr is used at typically 5 - 10 mole % and size around 0.75 µm, often core-shell structured with the core about 30 mole% and the shell about 5 mole %. For papers Ag(Cl, Br) is used typically near 50 mole % of each and around 0.3 µm size. The effect of the Iodide concentration on emulsion growth was shown in a series of images and diffraction scans. Three example of materials recovered from a photochemicals building were then shown with the presence of hydroquinone a possibility. Some brown material with white lumps turned out to be dust and oxidised sodium sulphite from XRF and XRD evaluation and the white lumps partly oxidised sodium sulphite. The brown material didn’t show the presence of hydroquinone by UV-Vis on a solution, but material from a laminar flow booth did. A second sample from the laminar flow booth showed Hydroquinone + KBr + various grots by XRD and XRF.
Anne Kavanagh closed the meeting by thanking all the speakers for the work that went into their presentations. She also thanked the staff at the venue for helping to make the meeting a success and an excellent lunch. She closed the meeting by thanking the delegates for sparing valuable time to attend and gave a reminder of the next meeting at Warwick in April 2010.
Dave Taylor, ICDD.
