Batch DistillationPharmaceutical API Process Development and Design

Module StructureVapor Liquid Equilibrium CurvesRayleigh DistillationColumn ConfigurationsColumn OperationSimulationDesign of Batch Columns

DistillationUsed for separating a mixture of two or more liquids Takes advantage of the differences in volatilities (vapor pressure)For a binary mixture,ij relative volatility, Pi0 vapor pressure of pure liquid i

VLE Curve and BP/DP CurvesyxA01TSaturated VaporSaturated LiquidMixture of A and BxA

Homogeneous AzeotropesFor non-ideal mixtures, the activity coefficients are different from unity: Phase diagrams for Isopropyl ether Isopropyl Alcohol

Homogeneous AzeotropesFor non-ideal mixtures, the activity coefficients are different from unity: Phase diagrams for Acetone Chloroform

Heterogeneous AzeotropesHomogeneous AzeotropeHeterogeneous Azeotrope

Thermo Properties CalculationsImportant properties of pure components, mixturesVapor liquid equilibriaY-X diagrams, T-X, T-Y diagramsExistence of multiple liquid phasesCommercial packagesPart of process simulatorsActivity++, PPDS etcHelps you identify distillation boundaries

Rayleigh DistillationVaporLiquid ChargeHeatL, xi remaining liquid and mole fraction at any subsequent timeL0, xi0 initial liquid amount and mole fraction

Rayleigh Distillation (Contd)For binary mixture when ij is constant

Batch EvaporationQcQrAccum 1Accum 2

Batch Evaporation Example

Batch DistillationPreferred method for separation whenFeed quantities are smallFeed composition varies widelyProduct purity specification change with timeHigh purity streams are requiredProduct tracking is importantFeed has solids

Batch Distillation AdvantagesAdvantagesFlexibleAccurate implementation of recipe specific to a given mixtureSeveral components separated using one columnRequires least amount of capital

Conventional Batch Distillation Column

Column ConfigurationsQcQrQrFFInverted BDAccum 1Accum n

Column ConfigurationsQcQrQrQcFFMiddle Vessel BDAccum 1Accum nAccum n+1Accum m

Dual Column ConfigurationSide stream from the main column fed to a second columnCan be used for mixtures with 3 or more componentsTake advantage of the build up of medium volatile component in the columnEliminate slop cutReduce cycle time, energy consumption

Column OperationStart-up periodVapor boilup rate policyConstant vapor boilup rateConstant condenser vapor loadConstant distillate rateConstant reboiler dutyProduct period: Reflux ratio policyShutdown period

Column OperationOperate under total reflux until the column reaches steady state (L / V = 1, R = )Change reflux ratio to the desired valueCollect distillate in accumulatorEnd the cut when certain criteria are satisfiedDurationCondenser compositionAccumulator composition, amountReboiler composition, amountQcQr1NLDAccum 1Accum n

Effect of Reflux RatioIncreasing reflux ratio Improves separationIncreases cycle timeIncreases energy consumptionProfile optimizationTrade-off between cycle time and value of recovered materialMaximize profit

Staged SeparationV1 vapor rate leaving plate 1 QcQr1NLDL / V Internal reflux ratioL / D Reflux ratioPlate jVj, yjVj+1, yj+1Lj-1, xj-1Lj, xjMj, xjV

Packed ColumnsHETP Height equivalent to one theoretical plateCharacteristic of packingNumber of plates = packed bed height/HETP

Simulation of Batch DistillationSimulation of startup periodSimulation of product periodColumn modelExamplesBenzenetolueneBenzenetolueneortho-xyleneAcetonechloroform

Simulation of Start-up PeriodDynamics of column during start-up are very difficult to modelRigorous model of tray hydraulicsRigorous model of heating column internalsTypical simulation of start-up periodRun column under total reflux until column reaches steady stateAt the beginning, assume that liquid compositions on plates and in the condenser are same as feed composition

Simulation of Product PeriodTotal condenser without sub-coolingPerfect mixing of liquid and vapor on platesNegligible heat lossesCondenser material balance

Column ModelMass balance equations on plate jConstant volume holdupVLE on each plateConstant molar holdupConstraint

Column Model (Contd)Enthalpy balance equations on plate jPhysical properties

Solution of Dynamic ModelVapor boilup rate from plate 1 is constantQuasi steady-state approximationDuring a small time interval, plate temperature, K values, vapor and liquid flowrates remain constantSolve the set of ODEs numerically up to the next update intervalAfter each update interval, recompute bubble point, K values, plate enthalpiesVapor compositionsReboiler composition from mass balanceLiquid and vapor flowrates from enthalpy derivatives

BenzeneToluene DistillationEquimolar mixture of Benzene and Toluene8000 liters chargeVapor boilup rate 20 kmol/hrNumber of plates = 20Plate holdup 4 litersCondenser holdup 180 litersRecover 99% mole fr Benzene and TolueneSimulated using BDIST-SimOptUses Activity++ physical properties package

BenzeneTolueneO-Xylene20 plates

AcetoneChloroformAzeotropic system

Use of Simulation in Batch DistillationSynthesis of operating recipe and rapid characterization of batch distillationsAccurate determination of operating and design parameters of a batch columnUse in column operation to determine cut amounts and switching policy for each batch

Role of Simulation in Column OperationSimulatorVerified ModelSimulatorModel DeveloperOperatorFeed AmountFeed CompositionDCSColumnComponentsCut SequenceFor each cut:Starting and stopping criteriaReflux ratio

Problems Related to Batch DistillationDesign of a batch columnOperating policy determination for individual column batchesDesign and operation issues are interdependent

Design of Batch ColumnsMain design parametersNumber of stagesVapor boilup rateDiameterStill capacity (batch size)Reboiler and condenser size heat transfer areasSingle separation dutyMultiple separation duties