ToolFusion Chemical
ToolFusion Chemical
📋 Case Study

Pharmaceutical API Purification via Crystallization

Residual solvent (isopropanol) >500 ppm violating ICH Q3C guidelines

🏗️ Project Overview

Manufacture of high-purity ibuprofen API at FDA-compliant facility

🎯 Challenge

Residual solvent (isopropanol) >500 ppm violating ICH Q3C guidelines

🔧 Design Approach

Anti-solvent crystallization with controlled supersaturation profile and residence time optimization in draft-tube MSMPR crystallizer

📐 Design Diagram

Pharmaceutical API Purification via Crystallization Challenge: Residual IPA >500 ppm (ICH Q3C violation) API + IPA Anti-solvent Purified crystals + mother liquor S = C/C* = 1.8 τ = residence time MCS = k·G⁻⁰·⁴⁵·τ⁰·⁵ = 120 μm Key: Crystallizer Process stream

AI-generated project design illustration

📐 Key Calculations

Supersaturation Ratio (S)

C/C*
Result: 1.8
Drives nucleation rate

Mean Crystal Size (MCS)

k·G⁻⁰·⁴⁵·τ⁰·⁵
Result: 120 μm
Impacts filtration rate & drying time

📊 Results

Solvent reduced to <50 ppm; yield increased 7%; cycle time decreased by 22%

💡 Lessons Learned

  • •Seeding strategy critical for polymorph control
  • •In-line PAT (FBRM + Raman) enabled real-time supersaturation control

✅ Key Takeaways

  • 1Seeding strategy critical for polymorph control
  • 2In-line PAT (FBRM + Raman) enabled real-time supersaturation control