Tim Fawcett Cyrus Crowder Fangling Needham Executive Director Principal Scientist Senior Scientist ICDD ICDD ICDD

Transcription

1 Tim Fawcett Cyrus Crowder Fangling Needham Executive Director Principal Scientist Senior Scientist ICDD ICDD ICDD

2 This document was presented at PPXRD - Pharmaceutical Powder X-ray Diffraction Symposium Sponsored by The International Centre for Diffraction Data This presentation is provided by the International Centre for Diffraction Data in cooperation with the authors and presenters of the PPXRD symposia for the express purpose of educating the scientific community. All copyrights for the presentation are retained by the original authors. The ICDD has received permission from the authors to post this material on our website and make the material available for viewing. Usage is restricted for the purposes of education and scientific research. PPXRD Website ICDD Website -

3 Introduction to PDF databases Material Identification Formulation Analysis Polymorph Analysis Crystallite Size Quantitative Analysis Nanomaterials Structure Analysis Cluster Analyses Crystallinity Integral Index

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5 1941 Joint Committee for Powder Diffraction Standards 2006 General member and customer survey 2007 PDF 4/Organics customer survey Annual input by member technical committees of the ICDD Phase Identification (95%) 20 30% Quantitative Analysis Several Methods Crystallinity Crystallite Size Polymorph Screening Powder Structure Analysis

6 PDF-2 PDF-4+ Inorganic Material Identification Identification and Quantitation PDF4/Organics Pharmaceutical Identification and Quantitation PDF4/Minerals Mineral Identification and Quantitation

7 ICSD PDF-4+ LPF PDF-2 NIST Powder Diffraction File ICDD Grants and Contributes CSD PDF-4/Organics

8 Release 2009 PDF 674,139 Unique Entries For Release 2009, Published 48,658 New Entries CCDC LPF NIST ICDD ICSD

9 Science 1998 ICSD RDB Development Strategic Alliances 2002 Full RDB 2003 Calc. Digital 2005 Patterns 2001 NIST M&A 2002 CSD Sybase 2005 LPF 2006 JAVA Interface 2006 ED EBSD 2007 Crystallite Size 2007 Statistics Pgm 2008 Exp 2007 Integral Index Patterns 2008 Sybase Upgrade 2009 Publication Software Developers Subfile Reorg 2005 Calc. Pat. Quality Analysis 2006 Auto Dup. Review Software Dev Integration 2007 Auto Subfiles 2006 Atom Wgt % 2007 Auto Cross Ref Fully automated RIR, Rietveld And LeBail Fitting 2008 Quality Exp. Pat.

10 Densities >3000 Zeolites

11 Launched in fall 2007 Database Tutorials (35) Launched in April, 2009 Knowledge Center links DXC, ICDD, AIP, PPXRD Tools PDF 4/Organics Searches on ~ 2400 articles and abstracts, including PPXRD

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13 1938 Hanawalt, Rinn and Frevel

14 1941 Card 1, 1941 PDF 978 Entries Hanawalt

15 Experimental pattern Positions and Intensities Reduced data d, I pairs Hanawalt, Frevel & Rinn 1938 Total Pattern Analysis Rietveld 1967 Pawley 1981 Toraya 1986 LeBail 1988

16 7. (1) 198,402 out of 370,844 (1.11 Million d spacings) 7.2 (0.1) A 27, (0.01) A 2, (0.001) A (0.0001) A ( ) A 1

17 Phase Identification works because of the precision and accuracy in measuring d spacings Both in the experiment and for reference patterns No calibration With standard calibration 1 10 parts per thousand parts per million Quality with Time 205,774 S Entries

18 Required of the user Good specimen preparation (particle statistics, preferred orientation) Appropriate particle size for good counting statistics Standardize and calibrate the instrument (Certified Standards) Internal standard for the most important work Use instrument settings appropriate for what your trying to measure Done by the ICDD Effective database Data are standardized Reference quality is measured and evaluated A range of tools are available for supplemental analytical observations (searches, indexes, physical properties, structural classifications) Done by the vendor Rigorous validated methods of Search/Match Batch processing for high speed, cluster tools for looking at large data sets Availability of high resolution optics and highly efficient detectors Tools for assisting in calibration and instrument standardization

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20 MgO and TiO2 Synchrotron Data 10 Phases Multiple Databases Quantitation of 8 Components

21 Celebrex Digital Pattern Comparison Stearate Celecoxib Alpha Lactose Monohydrate

22 Celecoxib New in 2009, data to 60 degrees 22,389,668 d spacings to 66,275,578 d spacings Alpha Lactose Monohydrate

23 Celebrex Match and Identification Process SIeve Goodness of Merit Comparison

24 13 Case Studies 10 Diffractometer 3 Synchrotron 10 Case Studies with the PDF 4/Organics

25 Subfiles Excipients Inorganic Salts! Merck Pharmacuetical Bioactivity Polymers Pigments Forensic Explosives 5,703 Inorganics 18,691 Entries In these 5 subfiles

26 Five groups of materials Four year study Pharmaceuticals Vitamins Supplements Fertilizers Alka Selzer Plus Centrum Performance Saw Palmetto MirAcid Tums EX (Extra Strength) Centrum St. John s Wort Miracle Grow Pepcid AC Centrum Silver Oyster Calcium Bone Meal Promethazine Hydrochloride Centrum Carb Smart Echanacea Goldenseal Rose Bloom Benadryl Vitapower Red* Melatonin Slow Release Kroger Decongestant VitapowerYellow* Lipoic Acid StarterFertilizer Alavert Vitapower Grey* Stick Robitussin Cough Drops Senior Vitae Weight Loss Garden Tone Claritin Childrens Chewable Stacker Celebrex Capsules Vitamin E with Fe TrimSpa Donnatal MegaMan CortiSlim Effexor MegaWoman FireStarter WomenUltra AnabolX One a Day Acclimate SunTheanine Materials from Kroger Supermarket, Happy Harry s, Ace Hardware, CVS Pharmacy Genaurdi s Supermarket, Argonne and Oak Ridge, GNC

27 TrimSpa Intensity on log scale TRIMSPA, reduced data d,i pairs Calcite Calcium HydroxyPhosphate Glucosamine Hydrochloride Caffeine The Food and Drug Administration (FDA) has notified Trimspa that it has not demonstrated that claims for their product are scientifically supportable.

28 USE SUBFILES!!!!! 1. Eliminates false positives particularly with complex patterns 2. Greatly assists in the statistics of trace/minor phase analysis

29 Tutorials 3 Case Studies Inorganic Materials

30 Major phases Celecoxib and Alpha Lactose Monohydrate Peaks at and A, Use the excipients subfile 2 Unknown peak locations match 2/3 of top 3 peaks of stearic acid with the 3 rd peak overlapping with Celecoxib

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32 Cellulose II Cellulose I beta

33 Tablet of Pepcid AC Same molecule, two different crystalline forms

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35 Use ICDD software Its designed for data mining Vendor software designed for high throughput identification Data mining is an effective tool for identifying polymorphs

36 Search Fields in PDF 4/Organics Molecular Symmetry Examine Crystal System, Space Group, Space Group Number, Pearson Symbols Molecular Volume Examine Author Cell, Crystal Cell and Reduced Cells, Cell Axis Ratio s, Cell Volumes Molecular Packing Examine Powder patterns for differences in interplanar spacing, examine strong lines (d1, d2, d3) and long lines (l1, l2, l3)

37 908 Glycine and glycine derivatives

38 Symmetry vs Volume with inserts of the diffraction patterns for the points in question

39 Plots two parameters (edge vs volume)

40 PDF PDF PDF Cell II Cell I beta Cell I alpha Via PDF-4+ Pepcid AC Scardi, Leoni Faber References for Form I alpha, Form I beta and Form II Simulation of microcrystalline states of cellulose

41 Tutorials Tools Comprehensive Database with common polymorphs (Key polymorph data on cellulose added 2006) Calculated Digital Patterns (Added in 2003) Crystallite Size Simulation (Added in 2007)

42 48 Searches 66 Field Display Graphics Interface Point and Click JAVA interface Use multiple measurements of symmetry, molecular size, molecular volume, packing and molecular orientation to discover and identify polymorphism

43 Use of the database for multi component mixtures

44 Identification link to correct phase (especially for polymorphs) Round Robin example: Acetaminophen, Mannitol, Silicon

45 Silicon Cubic a= Fd 3m(227) Z=8 V= β D Mannitol Orthorhombic a= (70) b= (80) c= (60) P (19) Z= 4.00 V= Acetaminophen Polymorph Form I Monoclinic a= (60) b=9.2500(40) c=7.0820(20) β =115.52(3) P21/a (14) Z= 4.00 V= Choices 15 Choices

46 Quality Marks, Status, I/Ic, R factors (lack of electron density, (i.e. H s lowers quality mark!) β D Mannitol

47 Digital Pattern Calculation and Export Pattern Fitting (Cluster Analyses) Step 1: Phase Identification 2) I/Ic = 0.51 By RIR 3) Cross Reference to CSD Reference Code DMANT07 Rietveld

48 ICDD Databases Simulated Electron Pattern Electron Backscattering Pattern Calculated Diffraction Pattern PD3 full digital experimental data overlaid on historic stick pattern Bond Distances/Angles 3D Structure

49 Material Identification Formulation Analysis Polymorph Analysis Quantitative Analysis Structure Refinement Case Histories Tools for Analysis Links to Tutorials Links to More Case Histories Database, Tools, Methods

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52 Polymorph Analyses 6 Drug Examples Cellulose, Tegafur Bone, Teeth Nanomaterials PPXRD2-PPXRD8 Phase Identification Formulation Analysis Health Supplements Pharmacueticals Crystallinity Celullose Cluster Analysis 4 Case Studies Rietveld Analysis

53 Note: The low temperature form has a molecular configuration change from room temperature forms Low Temp Form Subtle polymorphism Molecular visualization (CSD) shows 2 similar configurations that vary in methyl group rotation and close contacts 2 Room Temp Forms

54 MegaMen Vitamin Application PDF-4/Organics Identification and Quantitation By Reference Intensity Ratio using PDF-4/Organics Minerals, Vitamins and Amino acids 9 Phase solution used data from 3 different databases ICDD-powder, ICSD single crystal, CCDC- single crystal Note: Scale of 240,000 counts for this data set, 119 peaks

55 Quantitation by Reference Intensity Ratio Centrum Performance Listed Comp* Five compounds are 46.5 wt % of tablet Normalized to 100%

56 Quantitation by Reference Intensity Ratio Centrum Silver MultiVitamin

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58 Advanced Techniques % Crystallinity Crystallite Size Polymorph Analysis Using Pattern Fitting Techniques Digital Library of Crystalline Polymorphs with varied crystallite size and amorphous cellulose Key Reference Pattern Amorphous Cellulose Not currently in the PDF Use digital Library to analyze polymorphs and crystallinity

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60 All calcium phosphate polytypes AZT Carbamazepine Celluloses SRM 640 SRM 660 SRM 676 and SRM 1776 Used all reference materials, used combined experimental and reference data, used all experimental data mix and match

61 Human dental enamel, 1999 OH rich, Ca 9.87, J.C. Elliot Apatites Mineral, R. Young, 1964 Another OCP??, 1957 An OCP derivative with 16 waters Watanabe et al 1998 OCP, Brown et. al, 1962

62 Low resolution data Deleted by editors Synthetics, some D, Na, CO3 doped (B types) Naturally occuring tooth enamels Ca 8 Ca 9 Synthetics and Mineral OCP Ca 8 Ca 9 calcium deficient