Ester Hydrolysis Reactor

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Ester Hydrolysis Reactor

• Emily Brennan
• Justin Hewitt
• Fiona Rask

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Purpose of Unit

• Takes output from anion exchanger
• Converts insulin ester into pure insulin
• Output to HPLC for final purification steps

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Hydrolysis Reaction

• Cleaves a methyl group from insulin precursor
  using acid catalyst (HCl)
• Allows folding into active conformation

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Neutralization Reaction

• Residual sodium hydroxide from anion exchanger is
  neutralized
• Use hydrochloric acid
• NaOH HCl ? H2O NaCl

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Reactor Selection

• Continuous reactor selected
• Operated in lots to ensure quality assurance
  requirements are met
• Higher productivity than batch
• Smaller volume required for same conversion

VS
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Reactor Configuration

• 3 reactors in parallel
• One reactor running continually to process an
  upstream lot
• Other reactors cleaned/maintained during
  operation

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Design Assumptions

• 96 reaction extent for hydrolysis
• 100 reaction extent for neutralization
• Operation time 330 days/year
• Production of insulin crystal 4065 kg/year

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Design Specifications

• Acid inlet 15.8 L/h
• Upstream process inlet 19.7 L/h
• Residence time estimate 2 hours
• Volume required 71 L
• Volume with 10 head space 80 L
• Well mixed reactor
• Material Stainless Steel

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Additional Process Considerations

• Product sensitive to reactor conditions
• Reaction is exothermic and high temperatures can
  denature insulin
• HCl input into reactor and pH extremes can also
  denature insulin

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Control Schemes
T set point 40oC
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Cost Estimate

• Reactor Suppliers
• Perry Videx
• Walker Engineered Products
• New Brunswick Scientific
• Controller supplier
• Aspen Technology Inc.

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Cost of Process

• Capital Cost 240,000
• Reactors (3)
• Controllers
• Operating Cost 4000/yr
• HCl (72 per ton)
• Utilities (0.06 per kWh)

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• Thank you