📋 Case Study

Pharmaceutical API Purification via Crystallization

Polymorphic instability and residual solvent > ICH Q3C limits (e.g., acetone > 5000 ppm)

🏗️ Project Overview

Active pharmaceutical ingredient (API) manufacturing in Singapore

🎯 Challenge

Polymorphic instability and residual solvent > ICH Q3C limits (e.g., acetone > 5000 ppm)

🔧 Design Approach

Anti-solvent crystallization with controlled supersaturation profile and vacuum drying under nitrogen purge

📐 Design Diagram

AI-generated project design illustration

📐 Key Calculations

Supersaturation Ratio (S)

C_actual / C_sat

Result: 1.8

Controls nucleation rate and crystal size distribution

Residual Solvent Prediction

ln(C/C₀) = −kt

Result: t = 4.2 h to reach 200 ppm

Validates drying cycle duration

📊 Results

Consistent Form II polymorph; acetone reduced to 180 ppm; 25% yield improvement over batch cooling

💡 Lessons Learned

• •Seeding strategy must match target polymorph
• •Residual solvent kinetics require real-time PAT monitoring

✅ Key Takeaways

• 1Seeding strategy must match target polymorph
• 2Residual solvent kinetics require real-time PAT monitoring