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The world leader in serving scienceProprietary & Confidential
Utilizing Novel technologies in Material Sciences.
Let us help you in your R&D, processing and analyzing workflow.
Our systems enable you to increase your efficient to deliver
sustainable and cost-effective processes and products
Iain Mayer
North UK Sales Manager
Molecular Spectroscopy and Material Characterization
2 Proprietary & Confidential
• $17 billion in revenues
• $700 million spent on R&D
• 50,000 employees
• 50 countries
• 5 premier brands
The World Leader in Serving Science
3 Proprietary & Confidential
Clinical Oncology
Next Gen Sequencing
Analytical Instruments Life Science Solutions
Laboratory Products
and Services
Specialty Diagnostics
25%
19%
19%
37%
$17B
Revenue
Mass
Spectrometry
Q-Exactive HF
mass spectrometer
Chromatography
Vanquish
Ultra HPLC
Chemical and
Environmental Analysis
Gemini handheld
analyzer
Clinical
Diagnostics
Oral-Eze Oral Fluid
Collection System
Transplant
Diagnostics
NXType High
Resolution Genotyping
ImmunoDiagnostics
ImmunoCAP Allergy
and Asthma Tests
Microbiology
Antimicrobial Susceptibility
Testing Solutions
QuantStudio
Dx R qPCR
Genetic
Sciences
Sorvall WX+
Ultracentrifuge
Lab Equipment
Lab
Consumables
E1 ClipTip
Pipette
system
Distribution and
BioPharma
Services
Chemicals
BioProduction
Cell Culture
Reagents
Enterprise and
Instrument
Services
Biosciences
Life Science
Reagents
Pathology
Rotary
Microtome
Our Business Segments
Human
Identification
GlobalFiler
PCR Amplification Kit
The world leader in serving scienceProprietary & Confidential
Material Science Solutions
Our solutions are used to deliver innovative, high-value products in a globally competitive
market.
5 Proprietary & Confidential
Product selection Molecular Spectroscopy
Nicolet iS5 FT-IR Nicolet iS50 FT-IR Nicolet iN10 IR-Microscope Antaris NIR
DXR2xi Raman microscope PicoSpin45&80 NMR Evolution UV NanoDrop One
6 Proprietary & Confidential
Product selection Material Characterization
HAAKE MiniJet HAAKE PolyLab OS HAAKE PharmaLab 16
HAAKE ViscoTester 2 HAAKE VT-iQ HAAKE MARS Rheometer with FT-IR
The world leader in serving scienceProprietary & Confidential
Material Science Products
Our unique knowledge in the market
8 Proprietary & Confidential
Our unique knowledge in the market
Processing your materials
Laboratory Extruders/-Mixers/-Compounders
Analyzing your
incomming materials
FTIR, NIR, and Raman Spectroscopy
Physical testing of your materials
Viscometers, Rheometers and Hybrid Techniques
Analyzing your
final products
FTIR, NIR, and Raman Spectroscopy
Traditional routing
Failure of test, not matching the
expectations.
What when went wrong and during
which step  when?
9 Proprietary & Confidential
Our unique knowledge in the market
Processing your materials
Laboratory Extruders/-Mixers/-Compounders
Analyzing your
incomming materials
FTIR, NIR, and Raman Spectroscopy
Physical testing of your materials
Viscometers, Rheometers and Hybrid Techniques
Analyzing your
final products
FTIR, NIR, and Raman Spectroscopy
- With the correct equipment
- By understanding the applications
We able you to make the cross correlations simultaneous
Continuous control and information gathering during your processes.
Prevent failure, Better understanding of processes, Save time and
Money
10 Proprietary & Confidential
Rheology with FT-IR
 With a rheometer we study the steady state and time
dependent viscoelastic properties of a material as a
function of stress and/or strain
 The viscoelastic properties of a material depend on
the structure and especially the structural changes of the
material on the molecular level
 What happens inside the sample on the molecular level?
 Using IR-Spectroscopy (and/or Raman, X-ray, NMR, light
scattering etc.) we can clarify those time and/or
deformation dependent structural changes of a material
11 Proprietary & Confidential
Rheology with FT-IR
 Simultaneous data acquisition
 IR acquisition rate can be chosen to fit application
12 Proprietary & Confidential
Rheology with FT-IR
Spectrum taken after:
0 min
20 min
40 min
50 min
60 min
70 min
80 min
Auflösung: 4 cm-1 30/03/2010Technik: ATR - mit Rheo Anzahl Scans: 8
210021502200225023002350
Wavenumber cm-1
Auflösung: 4 cm-1 30Probe: Technik: ATR - mit Rheo Anzahl Scans: 8
14501500155016001650170017501800
Wavenumber cm-1
0.00.10.20.30.40.5
AbsorbanceUnits
Auflösung: 4 cm-1 30/03/2010Probe: Technik: ATR - mit Rheo Anzahl Scans: 8
500100015002000250030003500
Wavenumber cm-1
0.00.10.20.30.40.50.60.7
AbsorbanceUnits
≀≀
 NCO stretching decreasing
 C=O/ urethane (non-bonded) stable
 HNCO (Amide II) combined motion increasing
13 Proprietary & Confidential
Rheology with a Microscope
Rheological Data
Images
14 Proprietary & Confidential
Polylab OS extruder and rheology
Single Screw
Twin Screw
Mixer Testing
15 Proprietary & Confidential
Measurements with elongation diePolylab OS extruder and rheology
16 Proprietary & Confidential
Continuous Process Monitoring by NIR
• Advantages of HME + NIR Easy to implement in the HME
process
• No offline sampling
• No sample preparation
• No reagents or disposables
• Non-evasive, Non-destructive (sample and process are not
influenced by the measurement)
• Chemical and physical information from a single spectrum
• Answer in seconds / real-time information
• •Challenges of HME + NIR Calibration Model to be
developed
• Only reflectance mode not always enough
• Die design for transmission measurement
Antaris MX process analyzer provides simultaneous measurement
of up to 4 points and is also capable of continuous internal
referencing (backgrounds) during measurement
17 Proprietary & Confidential
Sampling Points on the Extruder
• Analysis by transmission or diffuse
reflection depending on the
application
• Probes can be customized to fit any
physical interface
• Multiple sites available for probe
integration
• Horizontal mounting in feeders
• Vertical mounting after screws
18 Proprietary & Confidential
Calibration Development
• PEG 2000
• 2.5 - 15%
• 10% Carbamazepine (CBZ) held constant
• Amplitude change at 5912 cm-1
• Carbamazepine (CBZ)
• 5 - 20%
• 10% PEG 2000 held constant
• Amplitude change at 5064 cm-1
19 Proprietary & Confidential
Real-time Monitoring by NIR Detects Process Changes
20 Proprietary & Confidential
Hot Melt Extrusion of Pharmaceuticals: Raman
• DXRxi Raman Imaging System
• Raman Imaging Applications
• Area and Confocal Images
• Raman Images @ > 600 spectra per second
• Image Centric Operation
• Point and Shoot Capabilities
• 455, 532, 633, 780HB nm Lasers
• Fiber Optics
Process / product optimisation
• Morphology, crystallinity and kinetics, polymorphism
Process monitoring / control (PAT, QbD)
Controlled release (solid dispersions)
• Rapid release
• Sustained release
• Co-crystal formation
21 Proprietary & Confidential
Morphology: Differentiating Polymorphs
• Very few techniques sensitive to crystalline structure differences
Yellow Polymorph
Orange Polymorph
Red Polymorph
three different polymorphs of a pharmaceutical compound.
22 Proprietary & Confidential
Analysis of Pharmaceuticals on a tablet, TSG
Acetaminophen Caffeine Titanium DioxideAspirin
11 x 11 mm surface area
5.4 million spectra!!!
0.5 mm pixel size
Acquisition (1.8 ms/spectrum)
~3 hour collect time!!
Component
Calculated %
(Surface Area)
Reported %
Aspirin 38.6 37
Acetaminophen 35.4 37
Caffeine 7.7 9.6
23 Proprietary & Confidential
Co-Extrusion Die, final product
Cross section of a co-extrudate with a clear defect of the outer shell
layer.
This causes malfunction of the drug.

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Iain Mayer

  • 1. The world leader in serving scienceProprietary & Confidential Utilizing Novel technologies in Material Sciences. Let us help you in your R&D, processing and analyzing workflow. Our systems enable you to increase your efficient to deliver sustainable and cost-effective processes and products Iain Mayer North UK Sales Manager Molecular Spectroscopy and Material Characterization
  • 2. 2 Proprietary & Confidential • $17 billion in revenues • $700 million spent on R&D • 50,000 employees • 50 countries • 5 premier brands The World Leader in Serving Science
  • 3. 3 Proprietary & Confidential Clinical Oncology Next Gen Sequencing Analytical Instruments Life Science Solutions Laboratory Products and Services Specialty Diagnostics 25% 19% 19% 37% $17B Revenue Mass Spectrometry Q-Exactive HF mass spectrometer Chromatography Vanquish Ultra HPLC Chemical and Environmental Analysis Gemini handheld analyzer Clinical Diagnostics Oral-Eze Oral Fluid Collection System Transplant Diagnostics NXType High Resolution Genotyping ImmunoDiagnostics ImmunoCAP Allergy and Asthma Tests Microbiology Antimicrobial Susceptibility Testing Solutions QuantStudio Dx R qPCR Genetic Sciences Sorvall WX+ Ultracentrifuge Lab Equipment Lab Consumables E1 ClipTip Pipette system Distribution and BioPharma Services Chemicals BioProduction Cell Culture Reagents Enterprise and Instrument Services Biosciences Life Science Reagents Pathology Rotary Microtome Our Business Segments Human Identification GlobalFiler PCR Amplification Kit
  • 4. The world leader in serving scienceProprietary & Confidential Material Science Solutions Our solutions are used to deliver innovative, high-value products in a globally competitive market.
  • 5. 5 Proprietary & Confidential Product selection Molecular Spectroscopy Nicolet iS5 FT-IR Nicolet iS50 FT-IR Nicolet iN10 IR-Microscope Antaris NIR DXR2xi Raman microscope PicoSpin45&80 NMR Evolution UV NanoDrop One
  • 6. 6 Proprietary & Confidential Product selection Material Characterization HAAKE MiniJet HAAKE PolyLab OS HAAKE PharmaLab 16 HAAKE ViscoTester 2 HAAKE VT-iQ HAAKE MARS Rheometer with FT-IR
  • 7. The world leader in serving scienceProprietary & Confidential Material Science Products Our unique knowledge in the market
  • 8. 8 Proprietary & Confidential Our unique knowledge in the market Processing your materials Laboratory Extruders/-Mixers/-Compounders Analyzing your incomming materials FTIR, NIR, and Raman Spectroscopy Physical testing of your materials Viscometers, Rheometers and Hybrid Techniques Analyzing your final products FTIR, NIR, and Raman Spectroscopy Traditional routing Failure of test, not matching the expectations. What when went wrong and during which step  when?
  • 9. 9 Proprietary & Confidential Our unique knowledge in the market Processing your materials Laboratory Extruders/-Mixers/-Compounders Analyzing your incomming materials FTIR, NIR, and Raman Spectroscopy Physical testing of your materials Viscometers, Rheometers and Hybrid Techniques Analyzing your final products FTIR, NIR, and Raman Spectroscopy - With the correct equipment - By understanding the applications We able you to make the cross correlations simultaneous Continuous control and information gathering during your processes. Prevent failure, Better understanding of processes, Save time and Money
  • 10. 10 Proprietary & Confidential Rheology with FT-IR  With a rheometer we study the steady state and time dependent viscoelastic properties of a material as a function of stress and/or strain  The viscoelastic properties of a material depend on the structure and especially the structural changes of the material on the molecular level  What happens inside the sample on the molecular level?  Using IR-Spectroscopy (and/or Raman, X-ray, NMR, light scattering etc.) we can clarify those time and/or deformation dependent structural changes of a material
  • 11. 11 Proprietary & Confidential Rheology with FT-IR  Simultaneous data acquisition  IR acquisition rate can be chosen to fit application
  • 12. 12 Proprietary & Confidential Rheology with FT-IR Spectrum taken after: 0 min 20 min 40 min 50 min 60 min 70 min 80 min Auflösung: 4 cm-1 30/03/2010Technik: ATR - mit Rheo Anzahl Scans: 8 210021502200225023002350 Wavenumber cm-1 Auflösung: 4 cm-1 30Probe: Technik: ATR - mit Rheo Anzahl Scans: 8 14501500155016001650170017501800 Wavenumber cm-1 0.00.10.20.30.40.5 AbsorbanceUnits Auflösung: 4 cm-1 30/03/2010Probe: Technik: ATR - mit Rheo Anzahl Scans: 8 500100015002000250030003500 Wavenumber cm-1 0.00.10.20.30.40.50.60.7 AbsorbanceUnits ≀≀  NCO stretching decreasing  C=O/ urethane (non-bonded) stable  HNCO (Amide II) combined motion increasing
  • 13. 13 Proprietary & Confidential Rheology with a Microscope Rheological Data Images
  • 14. 14 Proprietary & Confidential Polylab OS extruder and rheology Single Screw Twin Screw Mixer Testing
  • 15. 15 Proprietary & Confidential Measurements with elongation diePolylab OS extruder and rheology
  • 16. 16 Proprietary & Confidential Continuous Process Monitoring by NIR • Advantages of HME + NIR Easy to implement in the HME process • No offline sampling • No sample preparation • No reagents or disposables • Non-evasive, Non-destructive (sample and process are not influenced by the measurement) • Chemical and physical information from a single spectrum • Answer in seconds / real-time information • •Challenges of HME + NIR Calibration Model to be developed • Only reflectance mode not always enough • Die design for transmission measurement Antaris MX process analyzer provides simultaneous measurement of up to 4 points and is also capable of continuous internal referencing (backgrounds) during measurement
  • 17. 17 Proprietary & Confidential Sampling Points on the Extruder • Analysis by transmission or diffuse reflection depending on the application • Probes can be customized to fit any physical interface • Multiple sites available for probe integration • Horizontal mounting in feeders • Vertical mounting after screws
  • 18. 18 Proprietary & Confidential Calibration Development • PEG 2000 • 2.5 - 15% • 10% Carbamazepine (CBZ) held constant • Amplitude change at 5912 cm-1 • Carbamazepine (CBZ) • 5 - 20% • 10% PEG 2000 held constant • Amplitude change at 5064 cm-1
  • 19. 19 Proprietary & Confidential Real-time Monitoring by NIR Detects Process Changes
  • 20. 20 Proprietary & Confidential Hot Melt Extrusion of Pharmaceuticals: Raman • DXRxi Raman Imaging System • Raman Imaging Applications • Area and Confocal Images • Raman Images @ > 600 spectra per second • Image Centric Operation • Point and Shoot Capabilities • 455, 532, 633, 780HB nm Lasers • Fiber Optics Process / product optimisation • Morphology, crystallinity and kinetics, polymorphism Process monitoring / control (PAT, QbD) Controlled release (solid dispersions) • Rapid release • Sustained release • Co-crystal formation
  • 21. 21 Proprietary & Confidential Morphology: Differentiating Polymorphs • Very few techniques sensitive to crystalline structure differences Yellow Polymorph Orange Polymorph Red Polymorph three different polymorphs of a pharmaceutical compound.
  • 22. 22 Proprietary & Confidential Analysis of Pharmaceuticals on a tablet, TSG Acetaminophen Caffeine Titanium DioxideAspirin 11 x 11 mm surface area 5.4 million spectra!!! 0.5 mm pixel size Acquisition (1.8 ms/spectrum) ~3 hour collect time!! Component Calculated % (Surface Area) Reported % Aspirin 38.6 37 Acetaminophen 35.4 37 Caffeine 7.7 9.6
  • 23. 23 Proprietary & Confidential Co-Extrusion Die, final product Cross section of a co-extrudate with a clear defect of the outer shell layer. This causes malfunction of the drug.