Applications of API Process Simulation Pharmaceutical API Process Development and Design

Module Structure Solvent replacement  Compare feed strategies

Solvent replacement Typical example Reaction carried out in solvent A Boil-off part of solvent A Replace with solvent B & carry-out second reaction step Solvent A & B Mix Evaporate A Add B Evaporate Mix Repeat Design Issues: How many steps & How much to boil off each step?

Solvent replacement (contd.) Reaction Product In Methanol Replace Methanol With Ethyl Acetate Required final Methanol mass Fraction ≤ 0.01 Optimal feed profile?

Solvent replacement (contd.) Temperature Profile of bulk Composition Profile of bulk Single stage Batch distillation

Example 3: Feed Profiles For Solvent Switching (see handout for detailed process description)

Balance Volumes 1.Bulk liquid 2.Heating fluid 3.Header tank 4.Vapor

Model Variables Transfer rate of solvent Mass transfer coerfficient Transfer area per unit volume Concentration of solvent in bulk phase Partition coefficient Vapor pressure of solvent Antoine equation constants for solvent Temperature of vapor phase

Mass Transfer Equations (Antoine Equation) (UNIFAC Method)

Feed Profile – Fed Batch Volume Time V min V max

Feed Profile – Put and Take Volume Time V min V max

DynoChem Model Summary Components  Activity coefficients calculated using group contribution method (UNIFAC)  new_solvent MW=60.096, groups=2CH 3 +1CH+1OH  old_solvent MW=103.13, groups=2CH 3 +1CH+1CH 3 COO

DynoChem Model Summary Process definition (statements)  Phase bulk liquid  Phase vapor  Mass transfer vapor with bulk liquid Vapor pressure calculated using Antoine equation Activity coefficients calculated using UNIFAC method  Remove off gas from vapor

DynoChem Model Summary Process definition (statements)  Heat bulk liquid with jacket  Phase header tank  Transfer to bulk liquid from header tank  Calculate feed rate Control algorithm for different feed strategies

DynoChem Model Summary Scenarios (initial values and parameters)  Bulk liquid: Initial temperature, old_solvent mass, density, specific heat  Feed tank: Temperature, new_solvent mass, density, specific heat  Jacket: Temperature difference, flow, specific heat, UA  Vapor: Pressure  Feed profile control algorithm parameters

Simulation Results