Monitoring of highly absorbing species in viscous and corrosive melts with inline visNIR spectroscop

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Monitoring of highly absorbing species in viscous
and corrosive melts with in-line vis-NIR
spectroscopy

• Ewan Polwart
• Process Analysis Team
• Process Technology

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(No Transcript)
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The formation and History of Avecia
INTEGRATED BIOSCIENCE BUSINESS
PHARMACEUTICALS (Merger April 1999)
Merger of Novartis Zeneca Agri
Businesses December 1999
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Avecias Core products

• Pharmaceutical Intermediates and Actives
• Biotechnology - Advanced Medicines
• Ink Jet Printing Materials
• Electronic Display Materials
• Metal Extraction chemicals
• Water-borne Resins
• Non Chlorine Pool Spa products

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Chemistry

• Reaction modifies physio-chemical properties of
  CuPc
• Only very slight change in shade
• Reaction gives controlled mixture of compounds
• These combined have desired properties

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Analysis Options

• Off-line analysis
• ? Sample collected and take to laboratory
• ? Expert analyst
• Analysis turn around time 1-2 h
• Requires manual handling of sample

• On-line analysis
• ? Automated analysis in reactor
• Rapid and frequent results
• No manual sampling
• ? Technically very demanding

• At-line analysis
• ? Sample analysed in local laboratory by process
  operators
• ? More rapid results turnaround
• Limited local analytical expertise
• Requires manual sampling

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Collecting Spectra Probing the Reaction

• Attenuated total reflectance
• Evanesant wave interacts with sample
• Only very short path length in sample
• Ideal for strongly absorbing samples
• Light absorption measured as characteristic of
  wavelength
• Zeiss MCS522 Spectrometer coupled to probe by
  fibre optics
• Ceramic bodied immersion probe with sapphire ATR
  crystal
• Chemically resistant

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Off-line/Reference Measurements

• Parameter 1 numerical scale describing the
  total level of substitution of CuPc (assesses
  total number of groups P Q).
• Parameter 2 numerical scale describing the
  number of Q groups attached to the CuPc molecule.
  
• Complex sample preparation
• Time consuming analysis

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Process Development Data
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Univariate Data AnalysisParameter 1

• Correlation between Parameter 1 and maximum
  absorbance in range 400 to 500 nm.
• R2 0.914 SEC/critical range 0.31

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Univariate Data Analysis Parameter 2

• Correlation between Parameter 2 and absorbance _at_
  781 nm.
• R20.988 SEC/Critical range 0.041

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Multivariate Data Analysis Single batch

• Parameter 1
• SG 2nd deriv, 11 pt/quad
• 3 latent variables
• SEC/Critical range 0.14

• Parameter 2
• SG 2nd deriv, 11 pt/quad
• 1 latent variables
• SEC/Critical range 0.13

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Multivariate vs. Univariate
Parameter 2
Parameter 1
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Multivariate vs. Univariate
Parameter 1
Parameter 2
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Multivariate Data Analysis Multi-batch

• Partial Least Squares (PLS) regression applied to
  data set
• Samples from 6 batches
• 14 for calibration
• 20 for testing model
• Preprocessing
• 2nd derivative (Savitzky-Golay, 11 pt, quadratic)
• Normalisation
• Mean centred
• Merit Stats
• Calibration
• LV 3
• SEC/Critical range 0.20
• R2 0.954
• Test
• SEP/Critical range 0.14

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Reactor
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Collecting Spectra Probing the Reaction
optical fibres to/from spectrometer

• One bounce ATR probe employed
• Probe installed in sampling baffle
• Probe only sees sample when sampler is open
• Should increase lifetime of probe
• Allows washing of probe, even during reaction

sample collected or rinse to waste
air driven sample delivery or wash
ATR probe
Sample delivery system
pneumatically actuated plate allows sample to
enter system
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Collecting Spectra Probing the Reaction

• Only collect spectra when the sampler is open
• Therefore only a limited quantity of data per
  batch, i.e. no longer continuous like development
  batches

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Plant Data
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Multivariate Data Analysis

• PLS
• Samples
• 11 samples from 2 batches
• 5 used for calibration
• 6 used to test model
• Pre-processing
• Apply same as for development batches
• 2nd deriv (SG, 11 pt, quad)
• Normalisation
• Mean centring
• Merit Stats
• Calibration
• LV 2
• SEC/Critical range 0.0033
• R2 0.999
• Test
• SEP/Critical range 0.21

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Future Work

• Obtain more data over coming manufacturing
  campaigns
• Incorporate data processing in to spectrometer
  software to allow reporting of Parameters 1 2
• Side-by side validation with current off-line
  methods
• Implement of on-line analyser in to control regime

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Conclusions

• Successfully used ATR-vis-NIR spectroscopy in the
  development lab to predict the desired end point
  for reaction
• Have successfully transferred the lab-based
  methodology to plant reactor as a permanent
  installation
• Have begun process of obtaining useful
  information from the plant data using chemometric
  methodologies developed using the lab data

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Acknowledgements

• Ian Wells, Steve Gilligan and Karen Johnston
• Stevie Gavin and Fiona Keenan
• All on 22 Workstation on P1 plant, Grangemouth
• In particular Brian Morrison