📋 Case Study

Pharmaceutical Batch Hydrogenation Process Intensification

Poor mass transfer limiting reaction rate; inconsistent enantioselectivity above 50 L scale

🏗️ Project Overview

API manufacturing facility in Ireland scaling from 10 L to 200 L hydrogenation reactor

🎯 Challenge

Poor mass transfer limiting reaction rate; inconsistent enantioselectivity above 50 L scale

🔧 Design Approach

Combined kinetic + gas-liquid mass transfer modeling (k_La estimation); impeller redesign and H₂ partial pressure optimization

📐 Design Diagram

_La = 0.021 s⁻¹ HAI = 1.2 Large Scale (200 L) k_La = 0.008 s⁻¹ HAI = 0.6 Mass Transfer Limitation ↓ Enantioselectivity Intensification Strategy Impeller Redesign k_La Modeling H₂ P Optimization ∂(ee)/∂P_H₂ = 0.8 %ee/bar k_La modeling Impeller H₂ pressure Challenge

AI-generated project design illustration

📐 Key Calculations

Volumetric Mass Transfer Coefficient (k_La)

k_La = (1/V_L) * dC_L/dt

Result: 0.021 s⁻¹ @ 10 L, 0.008 s⁻¹ @ 200 L

Identified scale-dependent limitation

Hydrogen Availability Index (HAI)

HAI = (k_La * C*_H2) / (-r_H2)

Result: 1.2 @ small scale, 0.6 @ large scale

HAI < 1 indicates H₂ starvation

Enantiomeric Excess (ee) Sensitivity

∂(ee)/∂(H₂ pressure)

Result: 0.8 %ee/bar

Guided precise pressure control strategy

📊 Results

Reaction time reduced by 40%, ee maintained >99.5% across scales, eliminated off-spec batches

💡 Lessons Learned

•Kinetic selectivity is highly sensitive to local H₂ concentration gradients—not bulk pressure
•Impeller type (Rushton vs. A310) dominates k_La more than speed above critical power input
•In-line PAT (FTIR) enabled real-time endpoint detection and adaptive dosing

✅ Key Takeaways

1Kinetic selectivity is highly sensitive to local H₂ concentration gradients—not bulk pressure
2Impeller type (Rushton vs. A310) dominates k_La more than speed above critical power input
3In-line PAT (FTIR) enabled real-time endpoint detection and adaptive dosing