Introducing the Morphologi G3 ID The future of particle characterization

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1 Introducing the Morphologi G3 ID The future of particle characterization Dr Anne Virden, Product technical specialist diffraction and analytical imaging

2 What is the Morphologi G3-ID? Advanced R&D particle characterization tool Combines automated imaging and Raman spectroscopy in one integrated platform

3 What is the Morphologi G3-ID? Measures 3 key particle properties Particle size Particle shape Chemical identity

4 Morphologi G3-ID hardware Morphologi G3 and Kaiser RamanRxn1 TM Fully integrated control Optical fibre coupled Imaging specifications Full capabilities of Morphologi G3 Dry powder dispersion option Raman specifications 785nm laser 3µm dia. spot size with 50x objective Spectral range 150cm cm -1 4cm -1 resolution

5 Why you may need Morphologi G3-ID Need to know the chemical identity of a class of particles e.g. presence of certain minerals in cement Need to measure the particle size/shape of ingredients in a blend e.g. drug in nasal spray or dry powder inhaler Size and shape characterization still does not solve your problem e.g. manufacturing troubleshooting Manual targeting of particles for Raman measurements takes too long

6 Morphologi G3-ID sample types Dry powders Morphologi G3S-ID includes integrated dry powder sample dispersion Wet suspensions High purity quartz microscope slides with coverslip Analyse dry by evaporation onto microscope slide Morphologi G3 wet cell not compatible Filter membranes Depends upon suitability of filter substrate and particle size/shape (>> 20µm and regular shaped particles)

7 HOW THE MORPHOLOGI G3-ID WORKS

8 What is automated image analysis Sample presentation Image capture Results generation Image processing

9 Automated image analysis: Results Size Parameters Circular equivalent diameter 134μm Length 290μm Width 67μm

10 How the Morphologi G3-ID works Sample presentation Automated for dry powders and granules Raman compatible wet dispersion Morphological measurement Automated imaging Automated particle size and shape Automated size and shape classification Chemical measurement Automated Raman spectroscopy Automated chemical ID Automated chemical classification

11 Chemical measurement particle selection Manual user selection Select images and right click Automatic particle selection Classes based upon size and/or shape

12 Morphologi G3-ID - chemical measurement Automatically collect spectrum from centre of each selected particle

13 Morphologi G3-ID - chemical correlation Measures strength of association between particle spectra and reference library spectra Correlation scores range from means no correlation 1 means strong correlation Particle spectrum High correlation to Active Low correlation to Excipient

14 Morphologi G3-ID - chemical classification Automatically classify using correlation scores Classify individual particles according to: Absolute e.g. Score ingredient >0.7 Relative e.g. Score ingredient 1 > score ingredient 2 Highest score in library Can combine with morphological parameters E.g. Size > 10um and score ingredient 3 >0.5

15 Morphologi G3-ID PSD of API in nasal spray Particle Size Distribution of one chemical entity

16 MORPHOLOGI G3-ID - APPLICATION EXAMPLES

17 PSD of API in nasal spray Regulatory requirement to measure particle size distribution (PSD) in generic nasal spray formulations to prove bioequivalence (BE) Prescribed methods based upon manual microscopy several limitations Subjective visual classification No verification of accuracy of method Regulatory push to use Raman spectroscopy to validate classification of the smallest particles Morphologi G3-ID provides an automated route to achieve this

18 PSD of API in nasal spray Sample dispersed between slide and coverslip Morphologi results scattergram of circularity vs. elongation Regions of high particle density separate API and Excipient particles. Excipient API

19 Application Example: Nasal spray Class particles based on Chemistry Scattergram shows relationship between different chemical components based on score

20 Application Example: Nasal spray Compare size distribution of components with CE Diam. (vol) for Mixture, API(32.15%) and Excipient (67.85%) Volume transformation: CE Diameter (µm) smoothed over 66 points % CE Diameter (µm)

21 Application Example: Nasal spray Further size class API particles in terms of Particle count classification (%) Classification API >10µm FP >10um % API 7-10µm FP 7-10um 3.617% API FP 3-7µm 3-7um 19.06% MCC 77.22% Unclassified 0% Percentage count to total included

22 PSD of API in nasal spray Based on initial Raman analysis compare morphological distributions of chemically identified components Identify parameter(s) that morphologically distinguish particles as excipient and filter in analysis SOP Future analyses - collect Raman spectra only on remaining particles Particles with Elongation>0.4 are not API

23 Cement Used in many building applications Composition and size is important to properties such as strength and workability of cement Compare PSD of components within 1 sample Compare PSD of certain components in different batches Samples dispersed by evaporative technique Sample 1 Sample 2

24 Cement scan area composite Sample 1 Sample 2

25 Example spectra of some pure known materials TiO2 Anatase Calcium Carbonate Calcite Clinker

26 Example spectra of other unknown materials also found in cement Cement 6 Cement 9 Cement 10 Cement 20

27 Compare PSD of different components within 1 sample

28 Compare PSD of different components within 1 sample

29 Compare PSD of same component in different samples

30 Proportion of each component by volume or number percentage Useful for Reverse Engineer or to check final composition

31 Contaminant particles in mixture Spherical particles identified within a powder What are the spheres made of?

32 Collect spectra of suspicious particles Compare with user generated library or export to 3 rd party format Can choose text (*.csv) or industry standard *.spc

33 Contaminant identification external database Upload exported spectrum to 3 rd party database Choose a suitable search algorithm Spectrum identified as polystyrene from 20,000+ candidates

34 Morphologi G3-ID - Summary Integrates particle size, shape and chemical identity in one platform Fully automated Raman chemical classification of 1000s of particulates Simple SOP driven operation, from sample dispersion through to size, shape and chemical analysis Suitable for dry powders, suspensions and membrane filters

35 Video of the Morphologi G3-ID in action