Batch Distillation Pharmaceutical API Process Development and Design
Batch Distillation
Pharmaceutical API Process Development and Design
Module Structure
• Vapor Liquid Equilibrium Curves
• Rayleigh Distillation
• Column Configurations
• Column Operation
• Simulation
• Design of Batch Columns
Distillation
• Used for separating a mixture of two or more liquids
• Takes advantage of the differences in volatilities (vapor pressure)
• For a binary mixture,
0
0
j
iij P
P
αij – relative volatility,
Pi0 – vapor pressure of pure liquid i
VLE Curve and BP/DP Curves
y
xA
0
1
10
1
TSaturated Vapor
Saturated Liquid
Mixture of A and B
xA
Homogeneous AzeotropesFor non-ideal mixtures, the activity coefficients are different from unity:
S
1 1 1 1yP x P
S
2 2 2 2yP x P
s s
1 1 1 1 2 2P x P 1 x P( )
If the mixture has a minimumminimum-boiling azeotrope
i1
Phase diagrams for Isopropyl ether – Isopropyl Alcohol
Homogeneous AzeotropesFor non-ideal mixtures, the activity coefficients are different from unity:
S
1 1 1 1yP x P
S
2 2 2 2yP x P
s s
1 1 1 1 2 2P x P 1 x P( )
Phase diagrams for Acetone – Chloroform
If the mixture has a maximummaximum-boiling azeotrope
i1
Heterogeneous AzeotropesFor a minimum-boiling azeotrope with large deviation from Raoult’s law ( ), phase splitting may occur and a minimum-boiling heterogeneous azeotrope forms, having a vapor phase in equilibrium with two liquid phases.
i1
Homogeneous Azeotrope Heterogeneous Azeotrope
Thermo Properties Calculations• Important properties of pure components,
mixtures
Vapor liquid equilibria
Y-X diagrams, T-X, T-Y diagrams
Existence of multiple liquid phases
• Commercial packages
Part of process simulators
Activity++, PPDS etc
• Helps you identify distillation boundaries
Rayleigh DistillationVapor
Liquid ChargeHeat
i
io
x
x ii
i
xy
dx
L
L'0
'
ln
L’, xi – remaining liquid and mole fraction at any subsequent time
L’0, xi0 – initial liquid amount and mole fraction
Rayleigh Distillation (Contd)
• For binary mixture when ij is constant
i
i
ii
ii
ij x
x
xx
xx
L
L
1
1ln
)1(
)1(ln
1
1ln 0
0
0'0
'
jj
iiij xy
xy
/
/
iij
iiji x
xy
).1(1
.
Batch Evaporation
Qc
Qr
Accum 1 Accum 2
Batch Evaporation Example
Batch Distillation
• Preferred method for separation when
Feed quantities are small
Feed composition varies widely
Product purity specification change with time
High purity streams are required
Product tracking is important
Feed has solids
Batch Distillation Advantages
• Advantages
Flexible
Accurate implementation of recipe specific to a given mixture
Several components separated using one column
Requires least amount of capital
Conventional Batch Distillation Column
Qc
Qr
1
N
L D
Accum 1 Accum n
• •
Column Configurations
Qc
QrQr
F
F
Inverted BD
Accum 1 Accum n
Column Configurations
Qc
Qr
Qr
Qc
F
F
Middle Vessel BD
Accum 1 Accum n
Accum n+1 Accum m
Dual Column Configuration• Side stream from the
main column fed to a second column
• Can be used for mixtures with 3 or more components
• Take advantage of the build up of medium volatile component in the column
• Eliminate slop cut
• Reduce cycle time, energy consumption
Q1
C
Q2
A
262
260
270
232
228
240230
B
Q3
2
1
3
266
216
217
218
219
Side ColumnMain
Column
223
224
220
222
214
Column Operation• Start-up period
• Vapor boilup rate policy
Constant vapor boilup rate
Constant condenser vapor load
Constant distillate rate
Constant reboiler duty
• Product period: Reflux ratio policy
• Shutdown period
Column Operation• Operate under total reflux until the column reaches
steady state (L / V = 1, R = )
• Change reflux ratio to the desired value
• Collect distillate in accumulator
• End the ‘cut’ when certain criteria are satisfied
Duration
Condenser composition
Accumulator composition, amount
Reboiler composition, amount
Qc
Qr
1
N
L D
Accum 1 Accum n
• •
Effect of Reflux Ratio• Increasing reflux ratio
Improves separation
Increases cycle time
Increases energy consumption
• Profile optimization
Trade-off between cycle time and value of recovered material
Maximize profit
Staged Separation
V1 – vapor rate leaving plate 1
Qc
Qr
1
N
L D
L / V – Internal reflux ratio
L / D – Reflux ratio
Plate j
Vj, yj
Vj+1, yj+1
Lj-1, xj-1
Lj, xj
Mj, xj
V
Packed Columns
• HETP – Height equivalent to one theoretical plate Characteristic of packing
• Number of plates = packed bed height/HETP
Simulation of Batch Distillation
• Simulation of startup period
• Simulation of product period
• Column model
• Examples Benzene–toluene Benzene–toluene–ortho-xylene Acetone–chloroform
Simulation of Start-up Period• Dynamics of column during start-up are very
difficult to model
Rigorous model of tray hydraulics
Rigorous model of heating column internals
• Typical simulation of start-up period
Run column under total reflux until column reaches steady state
At the beginning, assume that liquid compositions on plates and in the condenser are same as feed composition
Simulation of Product Period• Total condenser without sub-cooling
• Perfect mixing of liquid and vapor on plates
• Negligible heat losses
• Condenser material balance
)/11(01 RLV
Column Model• Mass balance equations on plate j
jj AM
jjjjj LVLV
dt
dM 11
jijjijjijjijjij xLyVxLyVxMdt
d,,1,11,1, ....)(
• Constant volume holdup
jjj GM .
• VLE on each plate
jijiji xKy ,,, .
• Constant molar holdup
• Constraint
1, i
jiy
Column Model (Contd)• Enthalpy balance equations on plate j
Ljj
Vjj
Ljj
VJj
Ljj HLHVHLHVHM
dt
d....)( 1111
• Physical properties
),,,(
),,(
),,(
),,,(
PTyx
PTyHH
PTxHH
PTyxKK
jjjjj
jjVj
Vj
jjLj
Lj
jjjijij
Solution of Dynamic Model• Vapor boilup rate from plate 1 is constant
• Quasi steady-state approximation
During a small time interval, plate temperature, K values, vapor and liquid flowrates remain constant
• Solve the set of ODEs numerically up to the next update interval
• After each update interval, recompute
bubble point, K values, plate enthalpies
Vapor compositions
Reboiler composition from mass balance
Liquid and vapor flowrates from enthalpy derivatives
Benzene–Toluene Distillation• Equimolar mixture of Benzene and Toluene
• 8000 liters charge
• Vapor boilup rate 20 kmol/hr
• Number of plates = 20
• Plate holdup 4 liters
• Condenser holdup 180 liters
• Recover 99% mole fr Benzene and Toluene
• Simulated using BDIST-SimOpt
Uses Activity++ physical properties package
Benzene–Toluene–O-Xylene
20 plates
Acetone–ChloroformAzeotropic system
Use of Simulation in Batch Distillation
• Synthesis of operating recipe and rapid characterization of batch distillations
• Accurate determination of operating and design parameters of a batch column
• Use in column operation to determine cut amounts and switching policy for each batch
Role of Simulation in Column Operation
Simulator
Verified Model
Simulator
Model Developer
Operator
Feed AmountFeed Composition
DCS
Column
ComponentsCut SequenceFor each cut:
• Starting and stopping criteria• Reflux ratio
Problems Related to Batch Distillation
• Design of a batch column
• Operating policy determination for individual column batches
• Design and operation issues are interdependent
Design of Batch Columns• Main design parameters
Number of stages Vapor boilup rate Diameter Still capacity (batch size) Reboiler and condenser size heat transfer areas
• Single separation duty
• Multiple separation duties